Psychological symptoms and non-suicidal self-injury (NSSI) are independently associated with suicide attempts (SA). Yet, no study has tested the interaction effects between NSSI and psychological symptoms on SA in community adolescent populations, or examined whether the interaction varies by gender. We sought to examine the interaction effects of NSSI and psychological symptoms on SA in adolescents and explore gender differences.A school-based health survey in 3 provinces in China was conducted between 2013–2014. 14,820 students aged 10–20 years completed standard questionnaires, to record the details of various psychological symptoms, SA and NSSI.p < 0.001). Adolescents with psychological, conduct or social adaptation symptoms without concurrent NSSI, were twice as likely to report SA  than those who reported NSSI. Male adolescents with psychological, emotional, conduct or social adaptation symptoms had a higher risk of SA in the non-NSSI group than the NSSI group . While in girls, only adolescents with social adaptation symptoms had a higher risk of SA in the non-NSSI group than NSSI group . In the non-NSSI group, boys reporting psychological symptoms exhibited a higher likelihood of a SA than their female counterparts.Psychological symptoms and NSSI were independently associated with a higher likelihood of SA in both boys and girls (Psychological symptoms and NSSI are independently associated with an increased risk of SA in adolescents. However, to some extent, NSSI may reduce the risk of SA among individuals with psychological symptoms, especially in boys. Suicide is a major public health problem in adolescents as it constitutes the second leading cause of mortality in youth worldwide . It is eTo date, an array of risk and protective factors have been examined in relation to youth suicide –10. Of wA host of studies have also demonstrated a correlation between psychological symptoms and NSSI in adolescents , 18, witEarly evidence is conflicting in relation to the nature and underlying function of self-harm across genders with some studies suggesting that females more likely to use self-harm as a means of externalizing internal distress  while otThe main hypothesis tested in this study is that individuals with psychological symptoms or NSSI would be associated with a higher risk of engaging in SA, and the interaction effects between psychological symptoms and NSSI increase the occurrence of SA, as well as there may be gender differences. Therefore, the aim of this paper is to investigate the independent effects of psychological symptoms and NSSI on SA in a sample of general population adolescents, secondly examine the interaction effects between psychological symptoms and NSSI on SA, and thirdly ascertain whether the interaction effects differs by gender.n = 226), and (2) high levels of missing data or obviously fictitious or inconsistent responses (n = 232). Thus, a total sample of 14,820 participants were analyzed. And it has been reported in previous studies  in China. The survey was conducted from November 2013 to January 2014. We have weighed the economic development and population composition of each region. These three provinces are broadly representative of the average level in China, and are also where our adolescent health research network is located, which facilitates data collection. Eight schools  were selected from each city, all of which were general junior and senior schools. As four schools consisted of junior and senior parts, the total number of the schools was 20 for the survey. A total of 15,278 students from grades 7–12 were selected to participate in the study and asked to complete an anonymous questionnaire. Of all participants, 458 (3.0%) were excluded from the study because of (1) absence from school on the day of the survey or unwillingness to respond to the questionnaire . The research was performed in accordance with the Declaration of Helsinki.Demographic data for each participant was recorded, including age, gender, urban/rural residency, parents' education level , self-perceived economic status of the family .p < 0.01), an ordinal 'number of ACEs types' score was created by summing the dichotomous ACEs items (range 0 to 6), and analyses were conducted with 4 categories of summed score  (The model adjusted for the presence of adverse childhood experiences (ACEs) due to the correlation with psychological symptoms, NSSI and SA. ACEs were defined as having experienced childhood maltreatment and/or household dysfunction. Childhood maltreatment was assessed using the Child Trauma Questionnaire (CTQ) , a widel–4, 5–6) .Psychological symptoms in the past 12 months were examined by the psychological domain of the “Multidimensional Sub-health Questionnaire of Adolescents” (MSQA) , 34. BriYes or No?” A list of eight NSSI methods was then presented. The details of the questions were as follows: (1) hit yourself (2) pulled your own hair (3) banged your head or fist against something (4) pinched or scratched yourself (5) bitten yourself (6) cut or pierced yourself (7) burned yourself (8) Have you ever done some other things with the intention of hurting yourself (Yes or No) , which asked “In the past 12 months, have you ever harmed yourself in a way that was deliberate, but not intended to take your life? yourself . For thos or No) . The intSuicide attempt (SA) was defined by responses to the question “Have you ever tried to kill yourself in the past 12 months?” (Yes/No).Comparisons of sociodemographic risk factors, ACEs, psychological symptoms and SA between the NSSI and non-NSSI group were assessed using chi-squared test for categorical variables and one-way analysis of variance for continuous. Binomial logistic regression models were used to examine the associations between psychological symptoms and SA in the NSSI and non-NSSI groups. In the models, adjustment was made for age, gender, regional area, school, urban/rurality, mother's education level, economic status of the family and ACEs. In case collinearity problem, mother's educational level was adjusted for in the model, rather than father's educational level.p-value of <0.05 was considered statistically significant in the analyses.Gender differences in the associations between psychological symptoms and SA in the NSSI vs. non-NSSI were examined by calculating a ratio of two odds ratios (RORs) . All anaIn 14,820participants, the mean age was 15.4 years (SD = 1.8), with a range of 10 to 20 years. 50.2% of the sample were females and 58.7% were recorded as living in a rural area. A total of 649(4.4%) adolescents reported that they had engaged in SA in the past 12 months. The rate of psychological symptoms and NSSI was 24.1% (3572) and 26.1% (3872), respectively.p < 0.001). The details of differences between the NSSI and non-NSSI group can be seen in Compared to the non-NSSI group, individuals with NSSI were more likely to report psychological symptoms, emotional symptoms, conduct symptoms, social adaptation symptoms and SA (p < 0.001). Psychological symptoms and NSSI had independent effects on SA after controlling for age, regional areas, school, urban/rurality, mother's education level, economic status of family and ACEs in males and females  than those with NSSI. There was an interaction effect between psychological symptoms, conduct symptoms, social adaptation symptoms and NSSI on SA in the total sample (corresponding OR(95%CI) were 0.56(0.40–0.79), 0.59(0.42–0.82) and 0.47(0.33–0.65), respectively; p < 0.01), but no interaction effect was found for emotional symptoms and NSSI on SA .In the multivariate adjusted logistic regression models, as shown in p < 0.01). While in females, adolescents with social adaptation symptoms had a higher likelihood of SA in the non-NSSI group than NSSI group . There was an interaction effect of psychological symptoms, emotional symptoms, conduct symptoms, social adaptation symptoms and NSSI on SA in males (corresponding OR(95%CI) were 0.37(0.22–0.62), 0.45(0.27–0.76), 0.46(0.27–0.78) and 0.35(0.21–0.58), respectively; p < 0.01). While the only interaction effect was observed for social adaptation symptoms and NSSI on SA in females ; p = 0.011). In the non-NSSI group, males with symptoms of psychological, emotional and conduct problems were more likely to report SA than females , while in the NSSI group, no gender differences were found.Adjusted OR for SA by psychological symptoms and NSSI, in males and females are shown in The finding that psychological symptoms and NSSI represent independent risk factors for suicidal behaviors are akin to numerous prior studies –15. HoweThe results of the present suggest that the relationship between NSSI, psychological symptoms and risk of SA may manifest differently in males and females. Among those who did not self-harm but reported psychological symptoms, the risk of SA was higher for males than their female counterparts. Moreover, among those who reported self-harm, the risk of SA was reduced only among females with social adaption symptoms, whereas for males, the risk was reduced for those with multiple forms of psychological symptoms.These findings may in part, be explained by studies which have shown that females tend to make greater use of active coping skills and are more likely to seek social support than males , 40. It Furthermore, the results provide substantive support for the divergent function of self-harm in males and females. In previous Chinese cohort studies, adolescent male self-injurers were found to be more likely than their female counterparts to endorse functions which included increasing control and getting others' attention . As the The strengths of the current study include the following: First, we were able to examine the association between psychological symptoms, NSSI and SA among a large-scale school-based adolescent sample, covering urban and rural areas in China.Second, to our knowledge, the current study was the first study to identify the interaction effects between psychological symptoms and NSSI on SA. Third, the large sample, including many co-variables at data collection has provided enough statistical power to examine gender differences of the role.However, several limitations should be considered when interpreting these results. First, it is difficult to establish a temporal order between psychological symptoms, NSSI and SA, due to the cross-sectional design. Moreover, the replication of these findings using longitudinal data would also assist in establishing the chronological stability of the relationships as it is possible that the persistent use of this maladaptive coping strategy this may serve to increase the long term risk. We need therefore to identify if this is the first instance of self-harm or whether it represents a history of self-harm behaviors as repeated use of this strategy may serve to habituate the individual to pain and fear of death and ultimately increase the risk of suicide. Second, due to the reliance on self-reported questionnaires it is possible that recall bias may exist and that rates of NSSI and SA maybe under-reported because of the sensitive nature of the questions. Future studies may therefore seek to integrate more robust measures of NSSI and psychological symptoms. Third, the extent to which these findings can be generalized to adolescents in other countries or cultures is also unclear as all participants in this study were located in mainland China. Fourth, this study can not get the cut-off for NSSI to regulate emotions, whether it is possible in the short term, or at low frequency, NSSI may be helpful to emotion regulation, it also needs to be further explored in the future. Fifth, there are many other risk factors for suicide behavior , includiThe findings indicate that psychological symptoms and NSSI are independently associated with an increased risk for SA in school adolescents, which by extension, would imply that the combination of these factors may be particularly detrimental in increasing the likelihood of behavioral enactment. However, to the contrary, the current results suggest that in adolescent males at least, NSSI may play a functional role the buffering impact on the relationship between psychological symptoms and SA. So far, from a clinical and developmental perspective, many theories and related studies have linked NSSI to mood disorders , 45, 46.With these in mind, intervention and prevention programs for SA may utilize these findings to identify higher-risk individuals early and tailor programs. Clinical assessment and interventions may benefit from an understanding that problem solving is especially important in responding to psychological symptoms among males, and moreover, that NSSI among this population may be helpful rather than maladaptive under these circumstances in the short term. From this, clinicians should assist these individuals choose more adaptive solutions to problems instead of NSSI, in order to weaken the impact of psychological symptoms on risk for SA.Psychological symptoms and NSSI are associated with an increased the risk of SA in adolescents however in some instances, NSSI may help to temper the relationship between psychological symptoms and SA, especially in males. Further research is needed to better understand the function of NSSI in individuals with psychological problems and how this might help individuals avoid transitioning toward suicidal behaviors particularly in males.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Ethics Committee of Anhui Medical University (2012534). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.HX reviewed the topic related literature and drafted the first version of manuscript. RW involved in interpretation of the data and revision of the manuscript. YW and FT performed the study design, coordination, data collection, and the guarantors for the study. RL and ZJ worked on data analysis. All authors checked interpreted results and approved the final version.Funding for the project was provided by National Natural Science Foundation of China (81773453 and 81202223). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Previous studies have demonstrated that patients with a cancer diagnosis have an elevated risk of suicide and cardiovascular death. However, the effects of the diagnosis of multiple primary cancers (MPCs) on the risk of suicide and cardiovascular death remain unclear. This study aimed to identify the risk of suicide and cardiovascular death among patients with MPCs in the United States.Patients with a single or MPC(s) between 1975 and 2016 were selected from the Surveillance, Epidemiology, and End Results database in a retrospective cohort study. Mortality rates and standardized mortality ratios (SMRs) of suicides and cardiovascular diseases among patients with MPCs were estimated.p < 0.001). In patients with MPCs diagnosed asynchronously, the cumulative incidence rates of suicides and cardiovascular deaths were higher than those diagnosed synchronously. Among all MPCs, cancers of the pancreas and esophagus had the highest SMRs of suicide , while acute myeloid leukemia and brain cancer had the highest SMRs of cardiovascular diseases . The SMR of suicide was highest within 1 year after diagnosis, while that of cardiovascular diseases was highest 5 years after diagnosis.Of the 645,818 patients diagnosed with MPCs included in this analysis, 760 and 36,209 deaths from suicides and cardiovascular diseases were observed, respectively. The suicide and cardiovascular-disease mortality rates were 1.89-  and 1.65-times , respectively, that of the general population. The cumulative mortality rate from both suicides and cardiovascular diseases among patients with MPCs were significantly higher than those of patients with a single primary cancer (Both This study showed that the mortality rates from suicides and cardiovascular diseases among patients with MPCs were higher than those with a single primary cancer. Therefore, our results underscore the need for psychological assessment and targeted preventive interventions for suicides and cardiovascular diseases among patients with MPCs. As a consequence of improved cancer screening and treatments, there is a growing and aging population of cancer survivors. The amount of Americans living with cancer is predicted to reach 20.3 million people by 2026 , 2. HoweCancer patients had perpetually increased risks of suicide and serious cardiovascular death (CVD), either from shared lifestyles or from toxicities of cancer treatment –8. PreviIn this study, we conducted a population-based analysis to characterize the patterns and risk factors of deaths from suicides and cardiovascular events among patients with MPCs in the United States. Our findings will facilitate clinicians to screen patients with MPCs who are at high risk of suicide and cardiovascular death and provide personalized psychiatric care and better decision-making for cancer treatment.We used data from the Surveillance, Epidemiology, and End Results (SEER) program database to perform a retrospective cohort study. As a population-based cancer registry, the SEER database collects cancer data including demographics, incidence, anatomic site, morphology, stage, follow-up data, and treatment in the United States .*Stat software version 8.3.6 was applied to extract information on patients who were diagnosed with cancer between 1975 and 2016. We included patients with single or MPC(s) and excluded cancer patients diagnosed only by autopsy reports or death certificates. Patients without complete follow-up information, including age at diagnosis, follow-up duration, or race, were also excluded . The following variables were evaluated: age at diagnosis, sex, race, year of diagnosis, rural/urban status, median household income, cancer stage, surgical therapy, number of primary cancers, survival months, anatomic site, cause of death, and time from diagnosis. Notably, death from suicide or cardiovascular death was selected as the event of interest.Patients with the cause of death coded as “50220” were considered to have died due to suicide, and “50060,” “50070,” “50080,” “50090,” “50100,” and “50110” were considered to have died due to cardiovascular death . The cauAdditionally, because the shortest time interval was 1 month in the SEER database, patients whose survival duration was shorter than a month were recorded as 0 months. According to standard epidemiologic conventions, we changed records of “zero month” to “one-half month” .*Stat software, version 8.3.6  and R version 3.52  statistical software package were used for analysis.The mortality rates from suicides or cardiovascular deaths among patients with MPCs were calculated as the number of deaths due to suicide or cardiovascular death divided by person-years of follow-up, while the standardized mortality ratios (SMRs) and corresponding 95% CIs in non-cancer deaths were calculated in accordance with previous studies –19. SMRsOf the 645,818 cancer patients with MPCs included in the analysis , 760 deap < 0.001) (p < 0.001) (p < 0.001) and cerebrovascular diseases  (p < 0.001) and cardiovascular deaths  than that in those with an SPC  . It rema< 0.001) , both in< 0.001) . Univarih an SPC .p = 0.06). Male sex , older age at diagnosis , low income , distant stage , and not undergoing surgery  were positively related with suicide commitment.Multivariable Cox analysis further validated the above results . Diagnosp = 0.004). Other risk factors of cardiovascular death included older age , male sex , black race , low income , distant stage of cancer , and receiving no surgery .Moreover, the risk of cardiovascular death was also observed to be significantly higher in patients with MPCs, compared with those with SPC in the multivariable analyses  and cardiovascular deaths  between patients with MPCs and SPC, indicating the underlying impacts from confounding factors.We further performed multivariable Cox analysis adjusted by baseline characteristics of age, sex, race, and year of diagnosis . The resp = 0.003) and CVD (p < 0.001), including heart diseases (p < 0.001) and cerebrovascular diseases (p < 0.001), were significantly associated with synchronous MPCs , prostate (13.0%), colon and rectum (12.1%), urinary bladder (7.9%), and non-basal skin (7.6%), which accounted for more than half of the total suicidal deaths. Among all types of MPCs, the SMR for suicide was observed greatest in the cancers of the pancreas , followed by cancers of the esophagus , acute myeloid leukemia , larynx , and oral cavity and pharynx  .In the terms of CVD mortality risk , the pluWe further explored which combination of first primary cancer and second primary cancer was related with the highest risk of suicide and cardiovascular death , S4. ComOverall, the SMR of suicide and CVD among MPCs patients remained significantly elevated throughout all follow-up times despite fluctuations. Compared with the general population, the risk of suicide was immediately elevated within 1 year following diagnosis , which gradually subsided with a longer follow-up time. Similarly, the SMR of CVD prominently declined during 1–5 years after diagnosis, compared to that within the first year following diagnosis. However, this SMR peaked at over 5 years after diagnosis .We present a contemporary population-based analysis of the risk of suicide and CVD among over 640,000 MPCs patients and revealed that risks of suicide and CVD death varied as a function of age, gender, race, cancer type, time since initial cancer diagnosis, and follow-up time. The mortality rates from suicide and CVD in MPCs patients were significantly higher than those with SPC. Diagnosis with MPCs represents a great challenge not only in cancer management but also in the psychological construction of patients. The participants in healthcare should be aware of this underlying risk and implement timely targeted interventions for subpopulations at elevated risk.The relative risk of suicide among cancer patients was nearly 2-folds that of the general population, and MPCs patients exhibited apparently higher cumulative mortality of suicide than those with SPC. The results of the current work suggested that suicide-prevention strategies should be aimed at patients with the MPCs of the pancreas, esophagus, and larynx, as well as acute myeloid leukemia. Our finding was supported by the work by Henson et al., who reported that patients with primary cancer of the pancreas and esophagus have the highest risk of suicide in England . This waMPCs survivors, when compared to single cancer survivors, had a lower global quality of life, poorer emotional role function, greater and more frequent distress, and greater sub-clinical anxiety , 27, allWe observed that MPCs patients are perpetually at elevated risk of death from CVD compared to the general population, as well as comparison with SPC patients. Consistent with previous reports, younger age of diagnosis is associated with higher SMR , and theWhen stratified by cancer site, the relative risk of CVD was found higher in MPCs patients with acute myeloid leukemia, brain cancer, and chronic myeloid leukemia. Several pathways for increased risk of stroke in cancer patients have been proposed, and there are several cancer-specific types and causes of stroke in cancer patients , 39. FirThis study has several limitations. First, the risk of bias on reporting death certificates may exist, which may result in incorrect classification of the causes of death , 45. HowThis study demonstrated, for the first time, that the mortality rates from suicide and cardiovascular diseases among patients with MPCs were significantly higher than those of patients with SPC in the United States. The mortality rates from suicide and cardiovascular diseases among patients with MPCs were 1.89 times and 1.65 times those of the general population, respectively. In addition, patients with asynchronous MPCs had a higher risk of suicide and cardiovascular death than those with synchronous MPCs. The highest SMR of suicide was observed in MPCs of the pancreas and was within the first year after diagnosis of the MPCs, while the highest SMR of cardiovascular death was found in MPCs of acute myeloid leukemia and after 5 years after diagnosis of the MPCs. Diagnosis with MPCs represents a great challenge not only in cancer management but also in the psychological construction of patients. The participants in healthcare should be aware of this underlying risk and implement timely targeted interventions for subpopulations at elevated risk.https://seer.cancer.gov/.Publicly available datasets were analyzed in this study. This data can be found here: This study was reviewed and approved by the ethics committee of The First Affiliated Hospital, Sun Yat-sen University.JT had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis, concept and design, and funding. CS, YW, FW, and JT: acquisition, analysis, or interpretation of data. CS, YW, YQ, and JT: drafting of the manuscript. CS and JT: statistical analysis and supervision. CS, FW, and JT: administrative, technical, or material support. All authors: critical revision of the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.This work was supported by the National Nature Science Foundation of China (82000461) and Medical Scientific Research Foundation of Guangdong Province of China (C201903).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Telerehabilitation in neurological and cardiological diseases is an alternative rehabilitation that improves the quality of life and health conditions of patients and enhances the accessibility to health care. However, despite the reported benefits of telerehabilitation, it is necessary to study its impact on the healthcare system.The systematic review aims to investigate the costs and results of telerehabilitation in neurological and cardiological diseases. MEDLINE and EMBASE databases were searched from 2005 to 2021, for studies that assess the costs and results of telerehabilitation compared to traditional rehabilitation (center-based programs) in neurological and cardiological diseases. A narrative synthesis of results was carried out.p < 0.05). In contrast, most studies found differences in costs and clinical effects between the telerehabilitation performed and the rehabilitation performed at the clinic. Just one study found quality-adjusted life years (QALY) significant differences between groups , identifier [19619838].[ Telerehabilitation can be defined as “the delivery of rehabilitation services at a distance utilizing electronic information and communication technologies” . The useRehabilitation is prescribed to enhance the patient’s quality of life and reduce the impact of a health condition, focusing on the particular aspects based on the patient’s needs, goals, and preferences. For acute and chronic patients, with neurological and cardiological diseases, early access to rehabilitation is crucial for symptom recovery and long-term continuity of care in many cases , 5. SpecIn most countries, rehabilitation is not integrated as a standard of care in the public health system, and this situation worsens in low- and middle-income countries . The WorTelerehabilitation may overcome the lack of accessibility to rehabilitation programs for most patients in need, mostly in remote or rural areas without medical facilities. Moreover, the COVID-19 pandemic has reflected the significant contribution of telerehabilitation as a means of treatment accessibility, not only in isolated areas but also when physical attendance is impossible . TelerehDespite the reported benefits of telerehabilitation , 7, therIn total, four different modalities have been found in the literature when addressing telerehabilitation’s costs or effects: cost-effectiveness, cost-utility, cost-benefit, and cost-analysis.Cost-effectiveness analysis is a systematic method of comparing two or more interventions by measuring their costs and consequences , where the consequences of each are measured in the same standard units related to the clinical objective of the interventions  .Cost-utility analysis is similar to the cost-effectiveness analysis. However, instead of measuring its incremental effects in units related to its objective or commonly used in the clinic , effectiveness is measured in quality-adjusted life-years (QALYs). This encompasses life expectancy and quality of life. This measure of effectiveness makes it possible to compare different programs or interventions, as it is not specific to a specific intervention .Cost-benefit analysis measures and compares a healthcare intervention’s net costs with the benefits arising from the intervention, where both net costs and benefits are expressed in monetary units .Finally, cost minimization analysis or cost analysis can be performed when, regardless of the units in which health outcomes are measured, they are the same in the different options compared . TherefoTherefore, the present systematic review aimed to investigate the costs and effects  of telerehabilitation in neurological and cardiological diseases.This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist (PRISMA) refer to . This stThe study included all empirical studies that met the following inclusion criteria: (1) The study reported telerehabilitation vs. traditional center-based rehabilitation on neurological or cardiological diseases; (2) studies published from 2005 to 2021; (3) studies published in a peer-reviewed English or Spanish language journal; and (4) studies focused on the costs and effects of rehabilitation and virtual rehabilitation. No limits were set on the ages of participants. The exclusion criteria were as follows: (1) duplicated studies; (2) abstracts or conference papers; (3) study protocols or systematic reviews; (4) studies with inpatient participants; and (5) studies with participants with other diseases different from neurological or cardiological diseases. The protocol for this systematic review can be found in the public repository “FigShare.” The search was performed in MEDLINE and EMBASE databases in cooperation with a trained librarian and was finished in January 2021. Topics in The three reviewers used a preformatted Excel sheet to extract the data for the prespecified relevant data and outcomes for each included article: (1) neurological or cardiological disease; (2) total sample size; (3) percentages of males; (4) sample size included in the telerehabilitation or control group; (5) age of each group; (6) objective of the study; (7) methods ; and (8) results.Risk of bias assessment was performed using the Cochrane’s risk of bias tool , which dThe reporting quality of the economic evaluation studies was assessed with the updated Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) checklist  and perfThe literature search retrieved 430 records, which were reduced to 369 after removing the duplicated ones . A meticConcerning the variables included , 2, the The duration of the telerehabilitation ranged from 6 to 48 weeks , being 1Regarding the neurological studies, which included costs and effects of telerehabilitation , 2, we oThe sample size of the neurological studies included between 20 and 230 participants (56.6–95% were men). The mean age of the telerehabilitation group ranged between 55.9 ± 9.6 and 72.4 ± 9.4. Only one study performed a two-arm study with a randomized controlled trial . In otheRegarding the results , HousleyLloréns et al.  describeBendixen et al.  detectedRegarding the cardiological studies, five studies were selected . These sp < 0.001) of −1,590.00  in favor of the telerehabilitation group ; Maddison et al. (p < 0.021); Frederix et al.  (p = 0.001)   and $565= 0.001) . In cont= 0.001)  and Madd= 0.001)  found no= 0.001)  found thFinally, regarding QALY results, Frederix et al.  revealed2 max testing were blinded to treatment allocation at 12 weeks, and in the study by Kidholm et al.  , 27 and As part of the vCare project, the systematic review focused on neurological diseases in general and stroke and Parkinson’s disease in particular. However, only three studies included costs and clinical results of telerehabilitation in patients after stroke. None of these studies included QALY assessment, but cost, feedback questionnaires, clinical visits, and home stays. A study by Housley et al.  was the Regarding clinical results, patients gave positive feedback on the telerehabilitation performed after stroke and showed significant improvements in balance and gait. In contrast, Lloréns et al.  did not Telerehabilitation in cardiological diseases is also relevant since cardiac rehabilitation is an essential component of improving physical, psychological, and social functioning , 29, butThe telerehabilitation time ranged from 6 to 48 weeks in the studies reviewed . This difference could be a limitation in making a comparison between them. However, most of the cardiological studies reviewed performed telerehabilitation for 12 weeks.There is an increased interest in healthcare spending in Europe and worldwide, specifically in telerehabilitation and care for elders. Chronic illness contributes to disability, diminishes the quality of life, and decreases health and long-term care costs . TraditiOur systematic review showed that comparing costs and the cost-effectiveness of different interventions is crucial for making evidence-based decisions regarding telerehabilitation implementation in health systems. Telerehabilitation seems to be as effective as traditional rehabilitation and even less costly. Patients who performed telerehabilitation presented greater satisfaction and adherence to treatment and rehabilitation. However, few studies reported economic evaluation of the rehabilitation performed, and in those that included it, costs varied across different intervention designs. Future clinical trials should include cost-effectiveness analysis as a relevant measure to decide whether telerehabilitation is a good option to be implemented in public health systems. In addition, future research should also consider comparing different telerehabilitation and interventions to determine which are the ones that best meet the needs of each disease.The studies reviewed found several limitations that also should be taken into account. First, the small number of studies that met the inclusion criteria for this systematic review limits the generalization of the study’s conclusions. Moreover, the study design  and the lack of blinding during the patient allocation process restrict the effectiveness measurement. Finally, the duration of the treatment is variable among studies, and the sample  produces variability in the findings. Future studies should overcome these limitations to obtain more consistent and generalizable findings.In conclusion, telerehabilitation is a suitable alternative to traditional rehabilitation care in post-stroke patients and in cardiological diseases, especially in remote or underserved areas. More extensive economic evaluation studies are needed to evaluate the cost-effectiveness and the health-related quality of life of patients who perform telerehabilitation.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.RD and MD-C contributed equally to the conception, design of the study, and interpretation of the results. RD, MD-C, IU-A, and SG-L contributed to the acquisition and analysis of data. RD, MD-C, and IU-A contributed to initial and final manuscript. All authors contributed to the critical revision of the manuscript and final version approval.


OR) of HBcAb (+) increased with blood lead and the result was 1.09 . This study showed that older adults, men, people with a lower education level, a lower ratio of family income to poverty (PIR), a lower body mass index (BMI), or a history of blood transfusion, people who lived with a companion or with a total number of people in the family >3, people living in the United States for a longer time, U.S. citizens by birth or naturalization, and people not born in the United States were associated with higher blood lead exposure, and blood lead had a positive association with HBcAb (+).The objective of this project was to explore the distribution and related factors of blood lead and the association between blood lead and hepatitis B core antibody (HBcAb). All the data were from the U.S. National Health and Nutrition Examination Survey (NHANES). In total, 15,097 (aged 20–80 years) participants were included. Participants without a history of blood transfusion were more likely to be exposed to lower levels of blood lead [−2.30  for HBcAb (–) and −2.23  for HBcAb (+)]. The odds ratio ( Lead is a hazardous metal that is harmful to public health . PreviouThe most sensitive index of HBV infection history, hepatitis B core antibody (HBcAB), indicates that the clinical states of patients are naturally diversified . HoweverIn summary, this study analyzed the characteristics of blood lead distribution according to whether participants were seropositive for HBcAb or not in subgroups and explored the association between blood lead and HBcAb.The NHANES is a study designed to assess the health and nutrition status of adults and children in the United States. The data in NHANES are updated every 2 years as a cycle. We collected four consecutive 2-year cycles (2011–2018) in the study, as these cycles contain the most complete information on blood lead and HBcAb. We included all participants aged 20–80 years who contained information on blood lead and HBcAb.The data of serology HBcAb were collected from the laboratory examination items in NHANES. This item contained information related to Serology HBcAb, HBV surface antigen, and hepatitis D antibody, and extracted the data we wanted to obtain and merged the data of four consecutive cycles. Participants with missing serological HBcAb information were removed.https://www.cdc.gov/nchs/nhanes/index.htm. Blood lead data from 2011 to 2018 were merged with the data of HBcAb by respondent sequence number.In addition, blood lead data were obtained in the laboratory examination items from NHANES. Detailed information on laboratory quality assurance and monitoring is available at Based on previous studies , 26, thehttp://www.R-project.org) and EmpowerStats (http://www.empowerstats.com), and the statistical significance was set at p < 0.05. In the calculation for all estimates, we used 2-year sample weights following the analytical guideline edited by the National Center for Health Statistics (NCHS) to promise the data of NHANES could represent the civilian non-institutionalized U.S. population. The classified variables were expressed in percentage (%) and the value of p was calculated by the weighted chi-square test. Continuous variables were denoted by means ± standard deviation (SD) and the value of p was calculated by a weighted linear regression model. If any covariate information was missing, the classified data were grouped separately, and the continuous data were processed using the average replacement. We showed the standardized regression coefficients (β), odds ratios (ORs), and 95% confidence intervals (95% CIs) in regression models. A weighted generalized additive model and a smooth curve fitting were conducted to address a non-linearity relationship, and we found cut-off points for segmentation effects. At the same time, subgroup analysis was used to find specific populations.We performed all statistical analyses by using R (p < 0.01). Unexpectedly, participants who lived in the United States for more than 15 years and had a higher education level would tend to have a higher ratio of HBcAb (+) (p < 0.01). We show the demographic and laboratory data of the participants in A total of 15,097 participants were included in our study, of whom 1,323 (8.76%) had HBcAb (+). Grouping the data by HBcAb, we knew that there were statistical differences in all characteristics between the two groups except “total number of people in the family.” Based on the analysis results, participants with HBcAb (+) would have a higher blood lead, older age, lower BMI, and a lower PIR than participants with HBcAb (–) , missing information about ever being informed to have HBV, did not prescribe medicines to treat HBV, had a history of blood transfusion, born in other countries, citizen by birth or naturalization, unclear for the length of stay in the United States, under high school graduate, living with companion, and total number of people in the family ≤3 for HBcAb (+) participants, and male, other race , missing information about the HBV status, prescribed medicines to treat HBV, had a history of blood transfusion, born in all 50 states or Washington, D.C, citizenship in others, more than 15 years of stay in the United States, under high school graduate, living with a companion, and total number of people in the family ≤3 for HBcAb (–) participants. The blood lead tended to increase with the increase of age in three kinds of models, and we did the trend test for the phenomenon (p for trend < 0.01). In the analysis of the association between BMI with blood lead, we found participants who had higher BMI would have lower serum lead in all the models, and p for trend < 0.01. This trend was more obvious in HBcAb (+) participants. The standardized regression coefficient and 95% CI were −6.24  for BMI >23.9 when we adjusted “age, gender, and race.” Participants who had lower PIR would be harmed from higher blood lead in the non-adjusted model and adjusted “age, gender, and race” model, and p for trend < 0.05. Although there was no statistical difference for the trend test among HBcAb (+) in the all-adjusted model, the regression coefficient (−1.30) suggested that those participants with higher PIR had a lower blood lead potentially (p for trend = 0.55). In this part, we showed standardized regression coefficients and 95% 95% We used a weighted generalized additive model and a smooth curve fitting to address the non-linear relationship and select the corresponding model according to the result of the logarithmic likelihood ratio (LLR) for threshold effect analysis. The non-linear model was selected when the LLR <0.05. In the association between age and blood lead, we found a non-linear relationship and obvious cut-off points for all the participants, and the non-linear relationship and cut-off points also existed when the participants were grouped by HBcAb . Models OR and 95% CI were 1.09 . Additionally, we performed subgroup analysis based on population data. As blood lead levels increased, participants with the characteristics of female, age between 60 and 80 years, other Hispanic, PIR >3.5, BMI <18.5, born in 50 U.S. states or Washington, D.C, citizen by birth or naturalization, lived in the United States for more than 15 years, more than high school graduate, and living with a companion were more likely to be HBcAb (+). Results of subgroup analysis are shown in ORs and 95% CIs of participants who received antiviral treatment and those who did not were 2.55  and 1.34 , and this result was presented separately here because the 95% CIs were beyond the limit.In this part, we converted the unit of serological HBcAb into deciliters and multiplied all the data by 10 to explore the association between blood lead and HBcAb at a lower concentration. After multivariate adjustment for the above-mentioned covariates, an increased odds of HBcAb (+) was observed across the blood lead in all participants. The According to previous studies, the diversity of blood lead levels in different age groups was complex, with younger children and older adults tending to have higher blood lead levels , 15, 26.As depicted in previous studies, blood lead levels were higher in low-income, male, and non-Hispanic populations . At the 2, but such results still need to be confirmed by more studies. The mechanism of why participants with higher BMI had lower blood lead levels instead requires further explanation in subsequent studies.Studies have shown that single heavy metal level in urine was negatively correlated with BMI , but theOR with the increasing blood lead levels. The timely detection of HBV infection is related to many factors, one of which is the frequency of medical institution visits. Previous studies indicated that the management of HBV would increase a huge economic burden on both society and individuals  and HBcAb (–) groups. Among participants with previous HBV infection, there was a higher likelihood of higher blood lead levels among men of lower economical means and lower levels of education compared with other participants, and this risk had the potential to increase with age. Finally, we confirmed a positive relationship between blood lead and positive expression of HBcAb.https://wwwn.cdc.gov/nchs/nhanes/Default.aspx.Publicly available datasets were analyzed in this study. This data can be found here: Material preparation, data collection, and analysis were performed by KH, TH, WS, and YG. The first draft of the manuscript was written by KH and all authors commented on previous versions of the manuscript. All authors contributed to the study conception and design, read, and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Other factors associated with delayed DS management were: transfer mode, primary hospital type, site of large-vessel occlusion, and intravenous thrombolysis. Total transfer time was faster for distances <50 km by ambulance and for distances >71 km by helicopter. CONCLUSION: Assessment of DS processes and times throughout the patient pathway allows identification of potentially modifiable factors for improvement of the very time-critical workflow for stroke patients.BACKGROUND: We sought to identify factors for delayed drip-and-ship (DS) management in stroke patients transferred from primary hospitals to our comprehensive stroke center (CSC) for endovascular therapy (EVT). METHODS: We conducted a retrospective study of all patients transferred to our CSC for EVT between 2016 and 2020. We analyzed emergency and hospital records to assess DS process times and factors predictive of delays. We dichotomized the admission period to 2016–2017 and 2018–2020 according to the main process optimization, including the introduction of a prenotification call. RESULTS: We included 869 DS patients (median age 76 years (IQR 65–82), NIHSS 16 (IQR 11–21), 278 min (IQR 243–335) from onset to EVT); 566 were transferred in 2018–2020. Admission in 2016–2017, during on-call, longer tranfer distance, and general anesthesia were factors independently associated with delayed onset to EVT time  = 14.76,  Most patients with acute ischemic stroke due to anterior circulation large-vessel occlusion (LVO) benefit from endovascular therapy (EVT) . RecentlFor both paradigms, time to EVT is crucial as it is strongly associated with functional outcomes . RecentlWe assessed all processes and times throughout the patient pathway from the primary hospital to our CSC to identify potentially modifiable factors for continuous improvement of the very time-critical workflow for stroke patients.We conducted a retrospective analysis of our registry of consecutive patients with an acute ischemic stroke due to LVO who were screened for EVT at our CSC  between January 2016 and December 2020. We analyzed all DS patients, including baseline, emergency medical service, clinical characteristics, and process times. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement .2 [Our regional stroke network is an association of 24 hospitals that provides high quality stroke expertise for the eastern part of the state of Saxony and southern part of the state of Brandenburg in Germany . Approxi2 .The University Hospital Dresden is the main hub and coordinating CSC of the network, providing EVT and teleconsultation 24/7. The affiliated primary hospitals consist of 15 community hospitals (CH) without a dedicated neurology department/stroke unit and 8 primary stroke centers (PSC), i.e., hospitals with a neurology department and certified stroke unit. Two of them offered EVT during the study period. All hospitals in the network provided stroke imaging 24/7. A stroke fellow of the CSC supported the affiliated CHs via stroke telemedicine (telestroke) system .We included all patients (>18 years) who were secondarily transferred to the CSC from an affiliated primary hospital. We excluded patients who were admitted directly to the CSC or suffered an in-hospital stroke, and patients who were secondarily transferred to the CSC from a hospital not affiliated to our network. We recorded the following patient baseline characteristics: age, sex, National Institute of Health Stroke Scale (NIHSS) score, location of LVO, and extent of early ischemic changes as assessed with the Alberta Stroke Program Early CT Score (ASPECTS) if the middle cerebral artery territory was involved. Good outcome was assessed with the modified Rankin scale (mRS 0–2), which indicates functional independence at 90 days after treatment.We established standard operating procedures and quality assurance measures, including biannual meetings with interdisciplinary representatives from affiliated hospitals and the emergency medical service to optimize workflows, regular training of participating staff, morbidity and mortality conferences, and external certification during the study period.The emergency medical service decided on the primary transport destination depending on the location where the patient presented with stroke symptoms. Generally, patients were first transported to the nearest hospital in the network. If a hospital did not have admission capacity, the CSC or another network hospital was chosen as the primary destination.We used available clinical information and computed tomography (CT) imaging to select patients for IVT and EVT according to international recommendations ; CT-angiFor CHs, clinical and imaging findings were discussed via a telestroke platform with the stroke fellow of the CSC and patients eligible for EVT were secondarily transferred to the CSC. For PSCs, the primary indication for transfer to the CSC was made by the local neurologist. The mode of inter-hospital transfer (ambulance or helicopter) was selected by the primary hospital physicians and the emergency medical service coordinator based on transport distance and availability. At the end of 2017, we additionally offered special training to emergency medical service coordinators to increase the transport logistics of stroke patients.The standard procedure included repeated imaging with non-contrast CT (NCCT), CTA and optional CTP at the CSC. If LVO persisted and there were no contraindication to treatment , we performed EVT according to international guidelines. In collaboration with the anesthesiologist, we chose the type of anesthesia for each patient . After treatment, patients were monitored either in a stroke unit or in a neurological intensive care unit.Neuro-interventionalists were on-call on weekdays between 4:00 p.m. and 7:00 a.m., on weekends, and holidays. In June 2017, we implemented a team prenotification call, announcing the approximate arrival of the patient at the CSC to optimize workflow through the direct availability of stroke neurologists, neuro-interventionalists and anesthesiologists, as well as the CT scanner .We aimed to analyze factors associated with delayed onset to EVT times and to identify areas of improvement. Specifically, we analyzed the following factors: admission period , age, gender, baseline NIHSS score on arrival at CSC, affected vascular circulation, ASPECTS, admission time , type of primary hospital, IVT administration, transfer mode and distance, and type of anesthesia. We divided the onset to EVT time into (1) initial phase: symptom onset to arrival in primary hospital; (2) primary hospital phase: arrival to transfer request, including imaging and IVT admission times (if applicable); (3) transfer phase: transfer request to arrival CSC, including departure time; (4) CSC hospital phase: door of CSC to imaging and start of EVT (if applicable), Secondarily, we analyzed which transfer mode (ground ambulance or helicopter) was faster depending on the distance of ground transfer  between the primary hospital and the CSC. Distance categories were chosen based on the local network and infrastructure .t-test, Mann–Whitney U-test test or the chi-square test as appropriate. We used linear regression with stepwise selection  for multivariate analysis. For all statistical analyses, a p-value of < 0.05 was considered significant. We analyzed the data using SPSS Statistics .Continuous variables are presented as mean and standard deviation (SD) or median and interquartile range (IQR). Categorical variables are presented as absolute and relative frequencies. We used the Shapiro–Wilk tests to test for normal distribution. We compared variables between the groups using Student’s During the study period, 1369 patients were screened for EVT at our CSC of whom 869 (63.5%) were transferred secondarily to the CSC from an affiliated primary hospital, 303 in 2016–2017 and 566 in 2018–2020, The median age of DS patients was 76 years (IQR 65–82), 49.3% were male, 87.3% had an anterior circulation LVO, the median NIHSS score was 16 (IQR 11–21). More than half of the patients (57.3%) received IVT and 61.4% received EVT. The most common reasons for not performing EVT were large infarct size and recanalization of the LVO before EVT. The overall rate of functional independence at 3 months was 32.4%. In 2018–2020, patients presented with a lower NIHSS score and received IVT less frequently but EVT more frequently compared with 2016–2017. The rate of helicopter transfers and general anesthesia increased in 2018–2020. Patient characteristics are shown in p < 0.000, n = 358, adjusted(a) R2 = 0.162. In detail, onset to EVT was shorter for patients admitted in 2018–2020, during on-duty hours, and if the distance between the primary hospital and CSC was ≤10 km or 11–30 km. Onset to EVT was longer when patients received general anesthesia  = 14.76, esthesia . To optip < 0.000, n = 734, adjusted(a) R2 = 0.108. Primary hospital time was shorter for patients with anterior circulation LVO, when the hospital was a PSC and if the admission was on-duty. When patients reveived no IVT, the primary hospital phase was longer  = 23.28, s longer .p < 0.000, n = 841, adjusted(a) R2 = 0.458. Transfer time was longer for longer distance transport, transport via ambulance, and patients with posterior circulation LVO. Transfer was shorter for patients admitted in 2018–2020  = 89.85, 018–2020 .Times of onset to EVT and of the individual phases are shown in At distances ≤10 km, for ground transport, we transferred all patients by ambulance. At distances of 11–30 km and 31–50 km, the transfer time of the ambulance was faster than the helicopter transfer time, mainly due to the shorter time from requesting the transfer to departure from the primary hospital. At a distance of 51–70 km, the request time was significantly shorter but the door-to-door time from the primary hospital to CSC was significantly longer by ambulance than by helicopter, resulting in a comparable total time.At distances of 71–100 km and >100 km, ground ambulances were more promptly available, but the transfer time was significantly longer compared with a helicopter, resulting in significantly longer times for the transfer phase by ambulance, In this study, we found that admission in 2016–2017, during on-call time, CH without stroke unit, longer transfer distance, posterior circulation occlusions, no IVT administration, and general anesthesia were associated with delays in the processes of DS stroke patients who were transferred to our CSC for EVT.According to the admission period, the median time from onset to treatment was reduced from 300 min (IQR 255–360) in 2016–2017 to 270 min (IQR 234–318) in 2018–2020. We attribute this improvement to our quality assurance measures, including transport optimization and the introduction of a prenotification call in the CSC, because rates of admissions on-call, type of primary hospital, and affected vascular circulation were comparable in both admission periods. Interestingly, the rate of IVT administration actually declined in 2018–2020 and the rate of general anesthesia increased over the course.The advantages of the prenotification, announcing the approximate arrival of the patient at the CSC to optimize workflow through the direct availability of stroke neurologists, neuro-interventionalists and anesthesiologists, as well as the CT scanner, for the management in the CSC have been discussed in detail in a previous study . Based oIn patients who received general anesthesia for EVT, the delay compared with procedural sedation is not surprising because general anesthesia management, including intubation, is time-consuming . In addiOur transfer optimization resulted in shorter total transport times, i.e., from request of the transport to arrival at the CSC in 2018–2020. Interestingly, the median time from transport request to departure from the primary hospital increased slightly. Thus, the main factor for the improvement was higher travel speed. This is also consistent with the higher rate of helicopter transfers in 2018–2020. In our secondary analysis, we found that the selection of transfer mode could be further improved according to the distance between the primary hospital and CSC, i.e., for distances <51 km, ambulance and for >70 km, helicopter transfer. Our finding is in line with a previous study and highlights that the efficiency of transfer of stroke patients depends on the logistics prior to emergency medical service arrival as well as the speed of travel . It is wThe primary hospital phase was shorter in PSC than in CH, i.e., in hospitals without a neurology department. In CH, the attending physicians were mostly not trained neurologists, and patient assessment, imaging interpretation, as well as IVT administration and decision making towards EVT transfer, were coordinated with a stroke fellow of the CSC via telestroke service. This may indeed result in time delays. Though stroke neurologists have been found to reliably interpret the NCCT-scan of stroke patients in telemedicine , the intIt is unclear why patients who did not receive IVT specifically had a longer primary hospital time. One possible explanation could be that these patients were outside the IVT time window or were admitted with unknown stroke onset time. Due to the lack of a primary treatment indication, the decision making for EVT could have been delayed. It is essential that we further investigate this phenomenon and also the delay in patients with LVO in the posterior circulation. We need to intensively train all involved staff because there is clear evidence of the benefit of EVT in certain patients in the extended or unknown time window ,23, and Finally, the time to treatment could be further shortened by using the mothership instead of the DS approach . MothersThe rate of functional independence at three months was 32.4% in our study, which is lower compared to the EVT groups of the randomized trials assessing the benefit of EVT in anterior circulation (46%)  and postThis single-network study has all the limitations of a retrospective observational design. However, we prospectively recorded the data in our institutional stroke register and the study offers homogeneity in its processes. The generalizability of our results to other networks with DS management of stroke patients remains to be evaluated.The factors we identified may be relevant in other DS networks or in prospective studies comparing DS and mothership paradigms, and targeted evaluation and optimization should be considered. Shorter time to endovascular therapy is critical because it is strongly associated with favorable outcomes .A detailed assessment of all processes and times throughout the patient pathway from the primary hospital to the CSC, as performed in our stroke network, allows identification of potentially modifiable factors for continuous improvement of the very time-critical workflow for stroke patients.


P < 0.05), and the MOS significantly increased TAC level (P < 0.05). Furthermore, the DMH+MOS-exposed group exhibited a significantly lower expression of the PCNA, CEA, and PDGF proteins than those of the DMH group. Overall, the MOS showed that it can effectively prevent DMH-induced colon lesions. This mixture, as a strong antioxidant agent, can be clinically applied for preventing and treating colorectal cancer, the effectiveness of which is higher than that of vitamin E.Cancer is one of the leading causes of death worldwide, and natural agents have shown some promise in fighting it. Thus, the present study tried to evaluate the healing potential of an equal combination of olive and sesame extract (MOS) against the colorectal cancerous lesions that were induced by dimethylhydrazine (DMH) in male rats and also compare the anticarcinogenic potential of the MOS and vitamin E with each other. Therefore, the mixture of equal olive and sesame extract (MOS) was used as the main treatment, alongside vitamin E as a parallel treatment. This study examined the red blood cell (RBC) and white blood cell (WBC) levels, biochemical indices, lactate dehydrogenase (LDH), C-reactive protein (CRP), total protein (TP), creatine kinase (CPK), albumin, and the colon tissue pathology, as well as the level of protein expression of the adenomatous polyposis coli (APC), proliferating cell nuclear antigen (PCNA), carcinoembryonic antigen (CEA), and platelet-derived growth factor (PDGF). Also, the tissue stress markers including total antioxidant capacity (TAC), malondialdehyde (MDA), and superoxide dismutase (SOD) were analyzed. Overall, the results represented a significant reduction in the congestion, mitotic index, inflammation, and cell destruction in the MOS group compared to the DMH group. In terms of the oxidative stress level, a significant increase was observed in the DMH group in comparison with the DMH-MOS group ( Cancer is known among the major causes of mortality and morbidity worldwide . For exaThe severity and prognosis of colorectal cancer are determined by using the markers, the most specific one of which is the CEA. The serum CEA level is low, which enhances when adults develop cancer . FurtherThe critical aspect of using naturopathy has been reported consistently . These tOlive contains a high value of fatty acids and oleic acids, which are innately anticancer . The antThe results of the previous studies suggested the cancer therapeutic effects of sesame oil , 23 and This study aimed to evaluate the antioxidant and anticancer potentials of the mixture of these two compounds as a single therapeutic agent against colorectal cancer in rats, and compare them with vitamin E, which is a proven anticancer substance , 29.Olive and sesame were freshly obtained from northern Iran (52.35°E and 36.47°N). Sesames were sieved, and olives were separated from their leaves and branches, then were washed, and dried. Then, each compound was individually extracted through indirect aeration under high mechanical pressure, and the oil of which was stored in a refrigerator at 4°C until consumption , 31.A mixture of olive and sesame oil extracts with equal ratio (MOS) was analyzed by using the GC-MS method to detect its various components . In this regard, About 1 mL of the mixed extract was injected into the GC-MS using a microsyringe. After comparing the spectra of the constituents with those available in the Wiley and NIST/EPA/NIH34-44 libraries, they were sorted according to the ascending order of their retention time. The relative frequency of each component was reported by stating its maximum level. The values below 1% were removed from the table , 33.The present study was performed among 60 adult 8 weeks old male Wistar rats, weighing 200-220 g. They were obtained and kept in the animal house of the Pasteur Institute of Iran at 20-23°C in a 12 h light/dark cycle under the relative humidity of 60-70%. It should be noted that the ARRIVE guidelines 2.0 was followed throughout the whole study . Also, tVitamin E and dimethylhydrazine (DMH) were purchased by Merck. Initially, the animals were randomly classified into six groups (10 members).Group 1: the control rats received no treatment, but a normal saline gavage.Group 2: the MOS group received a 1 mL/kg/day dose of the MOS [ the MOS  via gavaGroup 3: the vitamin E group received a 180 mg/kg/week dose of vitamin E [itamin E  orally.Group 4: the DMH group received a 30 mg/kg dose of DMH subcutaneously once a week [e a week , 38.Group 5: the DMH+MOS group received the DMH and MOS simultaneously with the same dose.Group 6: the DMH+vitamin E group was administered the DMH and vitamin E at the same time with the same dose.After 13 weeks, all rats survived. At the end of the project, for the complete anesthesia, the cocktail of ketamine with10 mg/kg concentration  and xylazine with 80 mg/kg level  was applied intraperitoneally injection . Then, tThe blood samples were collected for examining the CBC  and measuring the related serum markers on a BIOLIS24i autoanalyzer (Tokyo Boeki Medisys Inc) .The colon tissue homogenates were utilized by a previously approved method . The homThe levels of MDA, SOD, and TAC in all homogenates were measured by employing the TebPazhouhan Razi, Nasdox, and Naxifer kits, respectively . Regardiβ-actin, which was the control protein. The membranes were rinsed with TBS for 10 minutes and subjected to a PNP-1000D electrophoresis power supply. Finally, the bar indices were analyzed by using the ImageJ software [Similar to the oxidative stress assessment, the homogenates were utilized by the method of a previous study . Furthersoftware , 43.For histopathological examination, the colon tissues were placed in a 10% formalin buffer. Then, they were rinsed with normal saline, fixated , dehydrated, and passaged to obtain paraffin blocks . The blocks were cooled , the five-micron sections of which  were stained with H&E and assessed on an Olympus CX23 optical microscope .P value less than 0.05 was considered a significant difference. Regarding the histological analysis, the groups were histopathologically scored and a mitotic index was obtained to compare their difference by employing Kruskal-Wallis and Mann–Whitney-U assays [SPSS 26 software, one-way ANOVA, and Duncan's post hoc tests were applied to analyze the data of CBC, serum tests, and stress and inflammatory markers as well as the ratios of western blot proteins. A U assays , 45.To expedite the review by the readers, a graphical abstract has been prepared that briefly depicts the project method and the significant data.The results of GC-MS indicated the presence of a great value of oleic acid, palmitic acid, stearic acid, and sesamin in the MOS .Despite the lower RBC, hemoglobin (Hb), RDW, MCHC, MCH, MCV, and hematocrit (HCT) levels in the DMH group had no significant difference observed between the groups .P < 0.05) and DMH+MOS-receiving (P < 0.05) group, respectively. In the DMH group, the neutrophil percentage was elevated, and the lymphocyte percentage decreased significantly (P < 0.05), in both of which the MOS improved the WBC ratio  and a rise in the CPK level. All three markers were declined by treating with the MOS significantly , which was diminished among the animals receiving DMH+MOS. Also, a lower level of MDA was seen in the vitamin E group  (As displayed in  < 0.01) .P < 0.05), which then was enhanced by consuming the MOS. The DMH group also showed a significant rise in the expression of CEA protein compared to the control group (P < 0.05). Although the CEA level was significantly diminished among the rats exposed to DMH+MOS (P < 0.05). In terms of the PCNA protein level, a significant increase was observed in the DMH group compared to the control group (P < 0.05), which was significantly decreased in both treatment groups (P < 0.05). In addition, a significantly better status was achieved in the animals that received the DMH+MOS than in those which were administrated the DMH+vitamin E (P < 0.05). Following the use of DMH, the PDGF protein was significantly more expressed compared to the control group, which was significantly reduced in both treatment groups (P < 0.05), while they were not significantly different from the control group  Figure.P > 0.05) difference between the control, MOS, and vitamin E-receiving groups regarding necrosis, inflammatory cell, and mitotic levels (P < 0.05). After scoring and staging, a significant decline was obtained in the necrosis, inflammatory cell infiltration, and mitosis of the DMH+MOS-exposed group compared to the DMH one (P < 0.05) (The results demonstrated an insignificant (c levels . However < 0.05) .P < 0.05) and influenced the blood and serum factors positively. The Wistar rats did not have pseudopoisoning effects because of administering the MOS. DMH is a poisonous substance with carcinogenic and methylation properties, which can lead to various levels of inflammation and precancerous and cancerous lesions [The results of the present study represented a diminution in the anti-inflammatory and anticancer activity in the DMH-exposed colorectal tissue during the carcinogenesis and tumorigenesis phases following the simultaneous administration of the DMH, as well as an equal combination of the sesame and olive oil extracts. The tissue stress and inflammation in the precancerous stage were reduced after using the MOS. This mixture resulted in expressing significantly lower CEA, PCNA, and PDGF proteins , which was reduced in the treatment groups. More CRP, as an inflammatory biomarker, after consuming the DMH reflects the body's acute phase. The rats receiving DMH+MOS had less level, reflecting a better status, and a diminution in the tissue inflammation. Regarding the LDH, as an enzyme that is available in the most alive cells, its higher level represents the extensive destructions at the cellular level, which was reduced in this study by utilizing the MOS. The increase in the CPK level can be attributed to skeletal muscle problems, heart damage, and myocardial microinfarction. In this study, the number was elevated due to the DMH-induced liver injury, followed by a decline in the treatment group [The results of the present study indicated a significant rise in the CRP and LDH levels after the administration of the DMH compared to the control group (nt group –75.P < 0.05). Moreover, the histological observations of colon revealed the necrotic and inflammatory lesions. The DMH group experienced a decline in the SOD content (an antioxidant enzyme) compared to the control group [P < 0.05), which is a tissue stress index. In addition to leading to oxidative stress, lipid peroxidation products also represent the necrotizing effects and increase the neoplasm rate [P < 0.05) and promoted the power of the body's antioxidant system against the free radicals and metabolites that were formed in the lipid peroxidation cycle. The TAC level and metabolites that are created during the oxidation process (MDA) can be used to calculate the level of tissue's oxidative stress [The three tissue stress markers were significantly increased in the DMH group compared to the control group , which reflected the cancerous status of that tissue. CEA content is often enhanced by the tumor cell secretions. In this study, the CEA level was risen in the colon tissue due to the effect of the DMH on this tissue, as well as disruption in its oxidant balance and the following methylation and mutation. The main reason for that rise in protein concentration was the probable presence of cancerous cells in the colon tissue. Compared to the control group, this content was significantly reduced in the DMH+MOS group because of the establishing oxidant balance in this tissue . The PCNA protein had more expression in all cancerous tissues following the use of DMH in comparison with the control group. The results indicated the antiproliferative properties of the MOS on cells, particularly cancer cells. It represented an anticancer effect by inhibiting the cells from proliferating. Regarding the APC level, the DMH group experienced a significant decrease compared to the control group (P < 0.05), and elevated unbridled cell divisions and tumorigenesis were observed due to the loss of chromosomal stability. After consuming the MOS, this protein's concentration was improved in cells because of the reexpression of the APC genes, and as a result, the chromosomal stability was enhanced, which caused a controlled cell reproduction cycle and a declined carcinogenesis rate. At last, a significantly greater PDGF level was observed in the DMH group than that of the control group (P < 0.05), which was significantly diminished among the rats that were exposed to the DMH+MOS. This result may be ascribed to the inhibition of the factor from production, which was clinically manifested as reduced congestion in histology and less PDGF content in the colon tissue [The expression levels of the APC, PCNA, CEA, and PDGE proteins in the tissue were assessed relative to the  protein . The resn tissue .P < 0.05). It could be seen that the results of this study are consistent with the results of the previous studies in terms of pathological changes [Finally, based on the results of the histopathological assessment, the different tissue lesions were generated in the Wistar rat colon after using the DMH, which was similar to the results of a previous study. . The les changes , 86, 87.Due to the high anti-inflammatory, anticancer, antitumor, and antioxidant activities of the mixture of an equal olive and sesame extract, it is suggested that the administration of this mixture with the 1 mL/kg/daily dose will decrease the oxidative stress by controlling the lipid peroxidation pathway. This mixture declines the free radicals by improving the body's antioxidant defense system substantially. Overall, it controls the cell division markers, which leads to a lower uncontrollable cell division and a diminution in the rate and extent of carcinogenesis and tumorigenesis.


Kaposi’s Sarcoma (KS) is a neoplasm derived from endothelial cells and is associated with human herpesvirus-8 (HHV-8) infection. It is mostly seen in patients suffering from AIDS and/or chronic immunosuppression. Currently, systemic chemotherapy is the primary treatment option for the advanced KS. However, there is no consensus on the treatment of KS. In this case, an 84-year-old man with a history of psoriasis developed multiple painful dark purple nodules on the trunk and extremities during the treatment of drug reaction with eosinophilia and systemic symptoms (DRESS). KS was confirmed by the skin biopsy, and the immunohistochemical staining demonstrated the positivity for HHV-8 while the anti-HIV test was negative. The patient then received anlotinib treatment, a tyrosine kinase inhibitor, for 5 months, and his skin lesions subsided. This case indicates that anlotinib may be a potential treatment option for KS. Kaposi’s Sarcoma (KS) is an HHV-8 associated angiogenic sarcoma that predominantly develops in lower extremities and was first described in 1872 by Kaposi , soft tiAn 84-year-old man presented with multiple dark purple and painful nodules on the trunk and extremities. He had a history of psoriasis for 3 years and was well-controlled by acitretin and topical corticosteroids. Body surface area (BSA) of the initial psoriasis was 13%, and the psoriasis area and severity index (PASI) score was 17.6. About 9 months ago, the patient was admitted to the hospital 3 weeks after taking traditional Chinese medicine. He presented with fever, mild facial edema, widespread erythema (BSA = 75%), and icteric sclera. The patient’s laboratory results were as follows: Eosinophil count of 2,640/μl; alanine aminotransferase, 283 U/L; aspartate aminotransferase, 173 U/L; serum lipase(Rate method) of 163 u/L; and hemoglobin of 89 g/L. The patient was assessed using a diagnostic score according to the RegiSCAR. The final score was six, suggesting probable DRESS syndrome. Methylprednisolone (1 mg/kg/day) and plasmapheresis were immediately administered. After 1 month of admission, the DRESS syndrome improved, but two localized purplish nodules were noticed in his lower limbs. The nodules were painful with a coarse texture and had a diameter of 2–3 cm . Then, tcis-retinoid acid can also be used , and iatrogenic subtypes observed in patients receiving immunosuppression, especially organ transplant recipients . DRESS i be used . PLD and be used . But PLD be used , 14.via targets VEGFR1, VEGFR3, VEGFR2/KDR, PDGFR-α, c-kit, and fibrogenic growth factor receptors(FGFR). It may inhibit more targets than other RTK inhibitors  and its receptor (VEGFR) expression to participate in the activation of angiogenesis, thereby inducing the formation of new blood vessels . An incrhibitors , 18. Thehibitors . This poThe underlying mechanism of action of anlotinib on KS is related to VEGFR and PDGFR pathways. However, its potential in the treatment of KS has not been reported. Therefore, anlotinib may be a new potential treatment for KS. With future studies and increased clinical experience, anlotinib is expected to be used for the treatment of other cancers.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of the First Affiliated Hospital of Fujian Medical University. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.ML, RL, and PZ conceptualized and designed the study and wrote the manuscript. TG and CJ critically revised the manuscript for important intellectual content. PZ and ZX collected clinical pictures and analyzed data. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Echinococcosis (E) is a zoonotic parasitic disease caused by the larval morphology of echinococcosis tapeworms. Among the recognized species, two are of medical importance—E. granulosus and E. multilocularis—causing cystic echinococcosis (CE) and alveolar echinococcosis (AE) in humans, respectively. Diagnosis of AE is based on clinical manifestation and epidemiological data, imaging techniques, histopathology and/or nucleic acid detection, and serology. At present, WHO guidelines suggest that benzimidazoles (BMZ) are mandatory in all AE patients, temporarily after complete resection of the lesions and for life in all other AE cases. Interventional procedures should be preferred to palliative surgery whenever possible, and radical surgery is the first choice in all cases suitable for total resection of the lesion. However, some research centers have proposed that local ablation (LA) including radiofrequency ablation (RFA) and microwave ablation (MWA) is no less effective than radical surgery or better than simple medication in the early stage hepatic AE (WHO-IWGE PNM classification of AE: P1N0M0). This study attempted to compare the real efficacy of the above treatment methods, so as to find the best treatment for this kind of patient.The data of patients with hepatic AE who underwent laparoscopic hepatectomy (LH), RFA, and MWA in Qinghai Provincial People's Hospital from January 2015 to January 2021 were collected. At the same time, the cases treated with Albendazole (ABZ) were collected together with the institution for disease control and prevention. According to the treatment methods, the above cases were divided into LH group, RFA group, MWA group, and medication group. The basic data and postoperative recovery indices of the four groups were compared, respectively.p > 0.05). The RFA group and MWA group were more advantageous than the LH group regarding operation time and incidence of postoperative complications (p < 0.05). But recurrence rate of the lesion in the LH group was significantly lower than the RFA group, MWA group, and medication group. However, there was no significant difference in recurrence-free survival time among the four groups (p >0.05).A total of 199 patients with hepatic AE were enrolled in this study, including 90 males and 109 females. The youngest was 5 years old and the oldest was 66 years old, with an average of 33.41±14.64 years old. 20.6% of the patients had hepatitis B (41/ 199). A total of 45 patients underwent ultrasound-guided RFA, 47 patients underwent ultrasound-guided MWA, 51 patients were treated with ABZ, and 56 patients underwent LH. There were no significant differences in baseline characteristics among the four groups (LH has a significant effect in the treatment of early-stage hepatic AE, especially in terms of recurrence which is significantly better than LA and medication alone. Follow-up and adherence to ABZ therapy are essential if conservative treatment is to achieve better outcomes. Alveolar Echinococcosis (AE) is a zoonotic parasitic disease caused by the larval morphology of echinococcus tapeworms. There are more than 16,000 new cases per year, approximately 60 million people are threatened, and the annual direct economic loss is RMB 3 billion. The prevalence of AE in some areas of the Qinghai, 96Tibet Plateau is as high as 6.0%. Its treatments mainly include radical resection and medication. Drugs are mandatory in all patients, while radical resection is the first choice in all cases suitable for total resection of the lesion and can significantly prolong the survival time of AE patients. With the popularization of the concept of minimally invasive, LA as an emerging interventional technology has been recognized by the medical community in the treatment of small lesions. However, LH also has many advantages compared with open surgery in the treatment of initial hepatic AE. So it is necessary to explore the efficacy difference of LH, LA, and medication in the early stage of hepatic AE. And we found that LA was more advantageous than LH regarding operation time and the incidence of postoperative complications. But recurrence rate of a lesion in LH was significantly lower than in LA and medication. However, there was no significant difference in recurrence-free survival time among these treatments.r <5 cm) and peripheral lesions without proximal vascular and/or biliary involvement, which are classified as P1 − 2N0M0 by WHO-IWGE PNM classification of AE and belonged to the early stage . (2) The diameter of a single AE lesion was <5.0 cm. (3) There was no cirrhosis and the patient's liver function was graded as A or B  before operation according to Child–Pugh classification. For the patients whose liver function was grade B, reevaluation was performed after treatment and if it was grade A, they were included in the study. (4) The patients underwent LH, RFA, or MWA. Exclusion criteria: (1) patients with extrahepatic AE and the diameter of a single AE lesion was more than 5.0 cm. (2) The patients underwent open hepatectomy. (3) Patients who could not complete follow-up due to refusal or inability to contact were excluded. After screening through the above criteria, 148 patients who met the requirements finally were enrolled in the group. Such as 45 patients underwent ultrasound-guided RFA, 47 patients underwent ultrasound-guided MWA and 56 patients underwent LH. At the same time, 51 patients treated with ABZ were collected together with the institution for disease control and prevention, the inclusion criteria of cases refer to the inclusion and exclusion criteria above. The general information, clinical data, and follow-up data of the enrolled patients were collected. Definition of early stage hepatic AE: The diameter of a single lesion was <5.0 cm and the lesion was far away from the hilum of the liver without bile duct or vascular invasion. Or the lesion is located deep in the liver but is limited to a segment or half of the liver and without invasion of important intrahepatic bile ducts and blood vessels. According to different treatment methods, the patients were divided into LH group, RFA group, MWA group, and medication group. There were no patients with liver cirrhosis and jaundice in the four groups. Informed consent was signed by patients and their families, and the disease was approved by the hospital ethics committee.As one of the designated treatment units for echinococcosis in Qinghai Province, Qinghai Provincial People's hospital treats about 400–500 cases of echinococcosis per year, and about 300 cases per year of hepatectomy, including more than 20 cases of LH and more than 80 cases of LA. The clinical data of 656 patients with hepatic AE who underwent surgical resection or LA in Qinghai Provincial People's Hospital from January 2015 to January 2021 were collected in this study. Inclusion criteria: (1) All patients met the WHO-TWGE PNM  diagnostDiagnosis of AE is based on clinical manifestation and epidemiological data, imaging techniques, histopathology, and/or nucleic acid detection and serology. All hospitalized patients with hepatic AE underwent enhanced CT of the head, chest and abdomen, portal vein and inferior vena cava angiography, liver and kidney function, coagulation function, enzyme-linked immunosorbent assay  for the AE, Hepatic AE was diagnosed preoperatively by the above examination. Metastasis of AE to the brain, lung, and other organs was excluded before surgery based on relevant imaging examinations. None of the enrolled patients had jaundice.1N0M0. RFA is suggested that the lesions are located in the liver and close to important pipelines and laparoscopic resection of the lesions is difficult or for those patients with P2N0M0. MWA is advised that intrahepatic lesions but far away from important ducts and mainly for those patients with P2N0M0. ABZ was given to patients who refused LH or LA.Analyze all preoperative clinical indexes, such as location, size, and number of a lesion, and the relationships between lesions and blood vessels or bile ducts were evaluated to formulate a reasonable treatment plan. LH is recommended for superficial lesions with good resectability or suitability for AE patients with PDuring intraoperative resection of the lesion, the liver tissue within 1.0 cm from the lesion should be removed as far as possible. If the AE was closed to the important intrahepatic ducts, the lesion should be completely removed along the edge of the lesion and the negative margin should be ensured .2, and the temperature of the puncture needle was routinely set at 60–100 °C , the ablation time was set at 10 min , two times after breakfast and dinner. Liposome dose was 1.0 ml/(mg. d), twice a day .In the MWA group or RFA group, patients were given intravenous inhalation combined with general anesthesia. They were able to drink water after waking up and we had no restrictions in their activities. Patients in the LH group drank water after waking up from anesthesia and were encouraged to get out of bed as soon as possible and liquid diet on the 1st day after surgery. They were given anti-infection, liver protection and nutritional support therapy, and the fluid volume was controlled to 2,000 ml. Postoperative analgesia in the LH group, RFA group and MWA group were treated with an intravenous self-controlled analgesic pump and subcutaneous injection of analgesic medications.Patients in the LH group, RFA group, and MWA group were treated with ABZ after liver function indices including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) returned to normal . ABZ was taken orally at a daily dose of 10–15 mg/kg. Stop taking ABZ for 2–3 weeks and reexamine the liver function indicators. If the liver function indicators are normal and continue taking ABZ 2–3 days later if the liver function indicators are obviously abnormal, it is recommended to stop taking medications for liver protection treatment, and start the next cycle of medication after the liver function indicators return to normal. The course of treatment with ABZ is at least 2 years after the operation (LH). After that, if the two kinds of imaging examinations show no recurrence of AE in the liver, and the two times results of the hydatid enzyme immunity tests are negative, the medication can be stopped. However, patients in the RFA group, MWA group, and ABZ group must take medication for life .The patients were followed up after discharge and the maximum follow-up time was 72 months. Follow-up visits were made every 6 months for the first 2 years after discharge and every 12 months after 2 years. The main contents of each follow-up visit include medical history collection, physical examination, hydatid enzyme-linked immunosorbent assay, liver and kidney function test, abdominal color ultrasound, and abdominal CT examination (every 12 months). Diagnosis of AE recurrence: imaging examination found new AE lesions in the liver, and echinococcosis enzyme-linked immunosorbent assay (ELISA) was positive. The treatments of AE recurrence, including drugs, reoperation, and comprehensive treatment, were based on the WHO guidelines for the diagnosis and treatment of echinococcosis . The treCure: AE lesions disappear or the lesions are completely calcified. Effective: The clinical symptoms and signs of AE are improved or the ultrasound examination has one of the following characteristics: Contrast-enhanced ultrasound examination shows a significant decrease in contrast agent perfusion in the peripheral area of the lesion or enhanced echo in the original lesions, it indicates that the active zone around the lesion has misfire or decreased focal activity. Invalid: no relief of clinical symptoms and signs, contrast-enhanced ultrasound examination revealed enhanced contrast agent perfusion in the surrounding area of the original lesion.The evaluation criteria for postoperative efficacy of LH are mainly recurrence and RFS. Diagnosis of postoperative recurrence: imaging examination revealed new lesions in the liver and the echinococcosis enzyme-linked immunosorbent test was positive. According to the location of the lesion, it is divided into margin recurrence and intrahepatic distant recurrence. Margin recurrence refers to the new lesion within 2.0 cm of the primary surgical margin. Intrahepatic distant recurrence refers to the new lesion 2.0 cm away from the primary surgical margin.Cure: AE lesions disappear or the lesions are completely calcified. Effective: The clinical symptoms and signs of hydatid disease are improved or the ultrasound examination has one of the following characteristics, such as the focus is reduced or the focus is not enlarged and the echo of the lesion is enhanced. Invalid: No relief of clinical symptoms and signs and ultrasound examination revealed no changes or progressive enlargement of the lesion.p < 0.05 was statistically significant.SPSS 22.0 software was used for data analysis. The non-normal measurement data were expressed by quartile [M ], and the rank sum test was used for analysis; The counting data were analyzed by chi-square test. The non-hydatid focus period was expressed by the survival curve and drawn by Kaplan–Meier method. The differences of different survival curves were compared and analyzed by log-rank test. A total case of 199 patients with hepatic AE was collected, including 90 males and 109 females, aged from 5 years old to 66 years old with an average age of 33.41±14.64 years old, 20.6% (41/199) of whom had hepatitis B. Forty-five cases of patients underwent RFA, 47 cases of patients underwent MWA, 51 cases of patients underwent medication and 56 cases of patients underwent LH. There were no significant differences in age, gender, lesion size, number of the lesion, preoperative ALT, AST, and hepatitis B infection among the four groups .in situ recurrences. In addition, after Clavien Dindo graded the severity of postoperative complications in the four groups, we found that two patients in the RFA group and 1 patient in the medication group were graded I, seven patients in the LH group were grade I and three patients were grade II, and no patients in the four groups had serious complications of grade III or higher  in the LH group was significantly lower than that in the other three groups. Among them, the recurrence cases in the LH group were considered to be a marginal recurrence, while the other three groups were all r higher .p < 0.05). But recurrence rate of the lesion in the LH group was significantly lower than the RFA group, MWA group, and medication group. However, there was no significant difference in RFS time among the four groups (p < 0.05)  analysis of all patients showed a median survival of 70 months . The RFS < 0.05) .in vivo experimental study showed that  and which may be the key factor for recurrence. Second, more than 95% of our research objects are Tibetan. Due to the limitation of the living environment and weak awareness of medical care, most patients did not take ABZ as prescribed by the doctor and there are few patients who could take regular review voluntarily. Third, although RFA or MWA is mature in the treatment of liver cancer, it is still in the initial stage for AE. Especially in the selection of indications, there are still many controversies. For example, the size, number, and location of lesions as well as the frequency of ablation should be further studied. Finally, it needs to be reviewed regularly to find out whether the lesion has recurrence at an early stage. If there were signs of recurrence, it should be treated as soon as possible. Besides, due to religious reasons, it is difficult to take blood samples from AE patients during the follow-up for drug concentration testing. As a result, we cannot accurately evaluate the efficacy of ABZ and most patients cannot achieve early diagnosis and early treatment of AE recurrence. Therefore, many factors contribute to the high postoperative recurrence rate of patients in the LA group and the drug therapy group. Similarly, the above reasons are also factors of recurrence after hepatectomy in AE patients. In recent years, due to the gradual increase in screening for echinococcosis, the diagnosis rate of early hepatic AE has increased significantly, especially since the prevalence rate of echinococcosis is still high in preschool children , 28. FurIn conclusion, we demonstrate that LH should be the first choice for early hepatic AE, and its long-term effect is much better than LA. However, this study is a single-center retrospective study limited by sample size and follow-up time. So, we also need multi-center data comparison and verification, and further study after prolonging the follow-up time.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.The studies involving human participants were reviewed and approved by the Ethics Committee of the Qinghai Provincial People's Hospital . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.JA, SZ, and HW conceived and designed the study. JA, JC, and XA collected the data. JA and ZS contributed to the data analysis, interpretation, and writing the article. JY approved the study and this submission. All authors contributed to the article and approved the submitted version.This work was supported by the Qinghai Province Talent Action Plan of Kunlun, Basic Research Project of Qinghai Province (No: 2020-wjzdx-27), Natural Science Foundation of Qinghai Province (No: 2017-ZJ-914), Natural Science Foundation of Qinghai Province (No: 2022-0301-ZJC-0114), Natural Science Foundation of Qinghai Province (No: 2022-0301-ZJC-0051), Qinghai Province 2022 Innovation Platform construction special project (No: 2022-ZJ-T01), and High-end Innovative Talent Project of Kunlun Talents of Qinghai Province in 2021.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.