Currently, few studies have examined the mental states of Women methamphetamine patients, and the influence of impulsivity and perceived social support on substance misuse-induced mental disorders is unclear. We want to examine the mental state of women with methamphetamine use disorder and compare it to the Chinese norm value of healthy women. Investigate the connection between impulsivity, perceived social support and mental state of women with methamphetamine use disorder.t-test, Pearson correlation analysis, multivariable linear regression, stepwise regression models, moderating effect analysis were used to analyze the statistics.Two hundred thirty women subjects with a history of methamphetamine usage were recruited. The Chinese version of the SCL-90-R, (SCL-90) was used to evaluate psychological health problems, while the Multidimensional Scale of Perceived Social Support (MSPSS) and Barratt Impulsiveness Seale-11 (BIS-11) were utilized to evaluate perceived social support and impulsivity, respectively. The t = 24.34, p < 0.001), Anxiety , Phobic anxiety , and Psychoticism . In addition, perceived social support levels and impulsivity levels are independently predictive of SCL-90 scores. Lastly, the impact of Impulsivity on SCL-90 can be modulated by perceived social support.There was a noticeable difference between the Chinese norm and all participants’ SCL-90 ratings, especially for Somatization (According to this study, women with methamphetamine use disorder have worse mental health conditions compared to healthy subjects. Furthermore, certain psychological symptoms associated with methamphetamine use in women can be aggravated by impulsivity, while perceived social support acts as a protective factor for methamphetamine-related psychiatric symptoms. Specifically, perceived social support weakens the impact of impulsivity on psychiatric symptoms in women with methamphetamine use disorder. In receMethamphetamine intoxication affects nearly all systems of the body, causing certain pathological symptoms, including tremors, chest discomfort, nausea, vomiting, hypothermia or hyperthermia, and increased heart rate –6. Some Through numerous psychological questionnaire surveys and biological experiments, previous psychological research has shown that impulsivity is positively associated with several personality disorders, such as borderline personality disorder and antisocial personality disorder, as well as some clinical psychiatric symptoms, such as depression and anxiety –15. RegaOn the other hand, PSS refers to the extent to which an individual feels that their needs for support, information, and feedback are met , 26. SocA study by Joiner suggested that social support reduces the negative impact of impulsivity on irrational acts, such as suicide and mental illnesses . Some reThis study aimed to: (1) investigate the mental status of Chinese women with methamphetamine use disorder and compare it with healthy controls; (2) investigate whether PSS and impulsivity predict the occurrence of MAP in the remission period of MA and the impact of each dimension of PSS on MAP; and (3) investigate whether PSS moderates the relationship between impulsivity and MAP.2.2.1.A total of 230 women participants with MA were recruited from a drug rehabilitation center in Tianjin, China. Staff at the drug rehabilitation center organized a group test for the Meth patients, each group involving 46 patients. The inclusion criteria for participants were: (1) adults between 18 and 50 years; (2) using methamphetamine alone or in combination with alcohol or cigarettes, or in combination with both alcohol and cigarettes and diagnosed with amphetamine-type substance use disorder, according to the DSM-5; (3) a total of 3–20 months from the restricted phase(in this phase they were restricted from leaving the drug rehabilitation center); (4) with no history of brain injury or other mental illness diagnoses; (5) were not suffering from severe neurological and physical diseases; (6) subjects have both biological and sociological attributes of femininity. All subjects had received compulsory treatment in the hospital before the restricted phase. In the restricted phase, every subject was managed inpatient, without using medication or addictive substances. In addition, the patients were not allowed to leave the drug rehabilitation center alone in the restricted phase. The survey was conducted anonymously, and each subject answered the questionnaires independently. In this study, all subjects volunteered to participate and the informed consent form was signed by every participant. As compensation, we provided every patient with 2 weeks of group psychological counseling after the study had ended.Before the test, the authenticity and confidentiality of the test were emphasized by the Institutional Ethical Review Board of Tianjin Medical University.2.2.This study assessed the mental health of Meth patients using the Chinese version of the SCL-90-R (SCL-90). The SCL-90 is a self-report symptom inventory established by Derogatis . with stThe perceived social support among methamphetamine patients was evaluated using the Multidimensional Scale of Perceived Social Support (MSPSS), with 12 items and three subscale scores for Friends, Family, and Significant Others , 26. EacThe impulsiveness of Meth patients was evaluated using the Barratt Impulsiveness Scale-11 (BIS-11) Chinese edition. Zhou  altered 2.3.The questionnaires were filled out anonymously, without mentioning any personal information, to avoid potential bias. Moreover, the questionnaires were completed independently by subjects and were handed out and returned by trained investigators with the permission of the drug rehabilitation centers. Lastly, we eliminated the questionnaires with poor results, such as the answers to all questions being identical or unanswered questionnaires.2.4.2 test. Differences in SCL-90 scores between respondents with various demographic features were investigated. Differences in SCL-90 average scores, across the nine dimensions, between the healthy controls , while non-normally distributed data were analyzed using the χcontrols  and wome3.A total of 230 questionnaires were presented to women Meth patients in the drug rehabilitation center in Tianjin, China. Of these, 228 questionnaires were enrolled for data analysis after eliminating two due to poor quality.3.1.t-tests, one-way analysis of variance, and χ2 test revealed no significant differences in SCL-90 in all these Sociodemographic Characteristics.3.2.t = 24.34, p < 0.001), Anxiety , Phobic anxiety , and Psychoticism .The scores of subjects in nine SCL-90 factors are shown in . All par3.3.This study found a significant correlation between PSS and each dimension of SCL-90, except for Somatization and Hostility. In the subscales of MSPSS, “friends” only correlated with Phobic anxiety; “family” significantly correlated with each dimension of SCL-90, except for Somatization and Hostility; “others” significantly correlated with each dimension of the SCL-90, except for Somatization. There was a significant correlation between impulsivity and each dimension of SCL-90  illustraThe results of multivariable linear regression models of BIS-11, MSPSS, and each dimension of SCL-90 are shown in . The resp = 0.0101). Thus, PSS can regulate the influence of Impulsivity on SCL-90. However, the moderating effects are relatively weak. The results for combining PSS, Impulsivity, and SCL-90 are shown in In moderating effect analysis, the interaction item Impulsivity × PSS coefficient was −0.0003, while the value of p was 0.0101, indicating a significant interaction between PSS and Impulsivity (4.Previous studies have shown that: (1) people with substance use disorder have poorer mental status and a higher prevalence of psychiatric disorders than the norm , 12, 55 Herein, we examined the mental health status of 228 MA women and that of healthy women using the SCL-90 scale. We then measured the impulsivity and social support levels of the subjects using the BIS-11 and MSPSS scales, respectively. In addition, we analyzed the relationship between impulsivity, social support, and various psychiatric symptoms.Our results found that Chinese women with Meth use disorder had significantly higher SCL-90 scores than the healthy controls. In addition, impulsivity and PSS, especially “others,” were significantly associated with most SCL-90 dimensions and had a positive and negative predictive influence on SCL-90, respectively. Moreover, PSS could moderate impulsivity to lessen its effects on MAP. This study found that female methamphetamine patients had more psychiatric symptoms than healthy controls, consistent with the findings of Zhao on male methamphetamine patients . In addiNotably, to the best of our knowledge, this is the first study evaluating the psychiatric conditions and the level of PSS and impulsivity among Chinese women meth patients during the remission period of Meth use. We also discovered that, unlike individuals who live in open communities, Meth patients in restricted communities are more likely to receive social support from strangers and others. The social support from this part has a more significant influence on MAP than family and friends. Lastly, we found that PSS moderates the relationship between impulsivity and MAP.Our study found that Meth may influence the mental health of women with Meth misuse disorder. In addition, impulsivity may aggravate MAP, whereas PSS may prevent MAP and buffer the influence of impulsivity on the MAP process.However, this study had some limitations. First, although PSS and impulsivity are substantially associated with MAP, several reasons lead to MAP. Therefore, there is a need to investigate the factors that cause MAP further exhaustively. Second, this was a cross-sectional study. Consequently, we did not investigate the psychiatric health of the subjects before to Meth use. As a result, we cannot assume that all of the psychiatric symptoms of the subjects were caused by MA. Thirdly, we were unable to identify whether there was a correlation between the impulsivity of the subjects and the acute phase of MA at the time of the study, although they had been in withdrawal for at least 3 months. Fourth, it has been reported that the BIS-11 may have some limitations: (1) the subscale scores of the BIS-11 may be related to the affective state of the subjects, such as depression and manic  (2) the In conclusion, our results indicate that women Meth patients have poorer mental health conditions than healthy subjects. There was a significant association between impulsivity, PSS, and MAP. In addition, impulsivity positively predicted MAP, while PSS (particularly “other”) negatively predicted MAP. Finally, PSS can moderate impulsivity, reducing its impact on mental symptoms.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 Institutional Ethical Review Board of Tianjin Medical University. The patients/participants provided their written informed consent to participate in this study.JL and YBL, were in charge of the survey and data collecting, while YWX, and YG were responsible for data analysis. SZW was responsible for the experimental design and drafting of the paper. All the writers agreed to the publishing of the final paper. All authors contributed to the article and approved the submitted version.The work was supported by the Predominant Education and Treatment Project of the Tianjin Drug Detoxification Bureau funded this research. This research was supported by a second-class key project of the China Judicial Administration Association for Drug Rehabilitation.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.


The healthcare system is critical to the country’s overall growth, which involves the healthy development of individuals, families, and society everywhere. This systematic review focuses on providing an overall assessment of the quality of healthcare delivery during COVID-19.The literature search was conducted from March 2020 till April 2023 utilising the databases “PubMed,“ “Google Scholar,“ and “Embase.“ A total of nine articles were included. Descriptive statistics was performed using Microsoft Excel. PROSPERO registration ID- CRD42022356285.According to the geographic location of the studies included, four studies were conducted in Asia , three in Europe  and two in Africa . Overall patient satisfaction was found highest among studies conducted in Saudi Arabia (98.1%) followed by India (Madhya Pradesh) (90.6%) and the U.K. (90%).This review concluded five different aspects of patients satisfaction level i.e. reliability, responsiveness, assurance, empathy, and tangibility. It was found that the empathy aspect had the greatest value of the five factors, i.e., 3.52 followed by Assurance with a value of 3.51. Improving health is the main aim of every healthcare system. According to the World Health Organization (WHO), each national health system aims to achieve overall three goals which are good health, responsiveness to the expectation of people, and fairness to financial contribution. The objective of achieving good health includes attaining goodness along with health equity for every citizen. These goals could be successfully achieved only when each health system performs four vital functions that are quality service provision, resource generation, financing, and stewardship .Progress towards achieving United Nations Millennial Development Goals or any national health program depends entirely on the health care system of that nation and the quality of care provided therein . QualityThe COVID-19 pandemic has posed a huge challenge for all healthcare systems and governments globally. In 2020 alone, there were an estimated 2.0 million lives lost to COVID-19. Moreover, indirect health loss due to lapses in the provision of essential health services such as vaccination, and emergency care were also major concern. The unprecedented situation has severely impacted the availability and the ability of the health system to provide undisrupted health services. In countries where health services were widely accessible and affordable, governments were finding it difficultto respond to the sudden growing needs of the population and increased cost of health services . WHO andService excellence revolves around three factors that is doctor, patient, and organization. Patient satisfaction is also one of the important and commonly used indicators to measure the quality of healthcare. It indicates how much a health care provider and health care institution are effective in rendering health services . MeasuriThis systematic literature review followed the Preferred Reporting Items for Systematic literature reviews and Meta-Analyses (PRISMA) 2020 guideline and has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) (Registration ID- CRD42022356285).PRISMA 2020 guidelines were used to design the methodology for this systematic review . The PRIThe PICO was defined as follows:Population (P)- COVID-19 survivors who were hospitalized.Intervention (I)- Quality Assessment.Comparison/Control group (C)- Pre-COVID era.Outcome (O)- Quality assessment of the global health care system.The studies were selected on the basis of the inclusion and exclusion criteria as shown in Table (n = 750) or on specific departments like ENT, Cardiology, etc. (n = 546), focusing on other aspects such as tele genetics, telemedicine, artificial intelligence (n = 480), articles only focusing on patient satisfaction and not on quality assessment (n = 12) were also excluded. After the final screening and evaluation, 9 articles that met the inclusion criteria were finally included as shown in Fig. Two independent researchers selected the relevant studies in a two-step process. In the first step, we reviewed the title and abstracts of the studies for potential eligibility. For the second step, the full texts of these were obtained for in-depth evaluation. Only cross-sectional studies that had reported the patient satisfaction level for the quality assessment of health care were included. The initial data base search yielded 27,365 published articles matching the keywords over the last 3 years. After eliminating 2050 duplicate articles, 14,357 studies were excluded as they were not assessing the patient satisfaction level for quality of health. Furthermore, 1290 articles were also removed because of non-English publications or ineligible articles. The remaining 9668 articles were screened, and 7621 articles were excluded after the researcher read the abstract. For full text evaluation, 2047 articles were sought for retrieval of which 250 articles were not retrieved and 1797 articles were assessed for full text evaluation. Studies focusing on specific diseases like ophthalmology, neurological disorder, etc. The data were extracted and collated into Microsoft Excel spreadsheets and the following domains of data were extracted from each study: study design, sampling techniques, study population, sample size, type of health care, type of scale used, etc. Studies were categorized based on service quality and patient’s satisfaction. Given the nature of the review question, a meta-analysis was not undertaken and instead, a descriptive synthesis and thematic analysis were done.A total of nine studies were included in the analysis. An overview of each article was provided in Table Three out of nine studies, that were conducted in Indonesia (Surabaya), Malaysia and Albania used the SERVQUAL tool to assess the quality of care and patient’s satisfaction level. This tool focusses on assessing five components: reliability, responsiveness, tangibles, assurance, and empathy. Another study conducted in Saudi Arabia used the Hospital Consumer Assessment of Health Care Providers and System (HCAHPS) questionnaire, which was the first national, standardized, publicly reported survey for assessing the patient’s perception of hospitalcare and the remaining five studies used different collection tools such as mixed method questionnaire, interviews, and self-structured questionnaires. The studies were conducted in different types of institutions, with two studies in private hospitals/clinics, one in a tertiary hospital and six in public hospitals.Overall patient satisfaction was found highest amongst studies conducted in Saudi Arabia (98.1%) followed by India (Madhya Pradesh) (90.6%), U.K. (90%), Indonesia (71.8%), Poland (71.1%), Albania (67%), Tunisia (59.1%), Malaysia (54.5%) and Ethiopia (44.6%) as depicted in Fig. The nine studies collectively suggest that patient satisfaction during the COVID-19 pandemic varies depending on factors such as quality of care, communication, safety measures, and availability of personal protective equipment (PPE). Despite the challenges posed by the pandemic, overall satisfaction levels remained high in most cases. The review found that patient satisfaction varied across countries, with Saudi Arabia, India, and the U.K. reporting the highest levels of satisfaction, while Ethiopia reported the lowest level –12. SeveOverall, the studies suggest that healthcare providers should focus on providing high-quality care, effective communication, safety measures, and ensuring the availability of PPE to improve patient satisfaction during the COVID-19 pandemic. According to a service quality model developed by Parasuraman, Zeithaml, and Berry, there are five factors that determine quality, and they are listed in order of relevance to the patients/consumer. The five factors are Reliability, Responsiveness, Assurance, Empathy, and Tangibility Fig.  16]..16].Based on the above-mentioned quality determinants, this systematic review attempts to discuss the included studies for thematic evaluation based on the five factors listed above.Reliability can be defined as the ability to perform the services which are promised in a reliable and accurate manner . This inThe reliability aspect, which considered all the points, was found to be 3.5 on a 4- point Likert Scale and occupied the lowest score out of all five aspects . It was Responsiveness is the willingness to help consumers and provide services quickly . This inThe responsiveness aspect was rated at a value of 3.47 . ApproxiAssurance is the knowledge and courtesy of providers and their ability to generate trust and confidence among consumers. The provision of readily available information to the patients and a clear explanation of the drugs that have been prescribed to them constitutes the assurance aspect.With a rating of 3.51 on a 4-point Likert Scale, the assurance component held the position with the second-highest value . 93% of Empathy can be defined as a willingness to care and providing personal attention to customers . This woThe empathy aspect had the greatest value of the five factors, i.e., 3.52 . 77.6% oTangibility is the appearance of physical facilities, equipment, personnel, and communication materials , which wThe tangibility aspect had a value of 3.48 . 89.2% oThis Systematic review has certain limitations. One of the main limitations is the presence of significant heterogeneity found in the various regimens such as durations, center settings, and participant characteristics across the studies included in the review; which may affect the generalizability of the findings and thus creating a roadblock in conducting the meta-analysis. Additionally, many of the studies suffer from sources of bias, which could impact the validity and reliability of the results but still had to be included due to the limited number of studies available that met the inclusion criteria. Inclusion of fewer studies also led to a skewed effect while performing thematic evaluation.This systematic review concluded that patient satisfaction level with respect to the quality of health care provided was highest in Saudi Arabia (98.1%) followed by India (Madhya Pradesh) (90.6%) and U.K. (90%). We have discussed Patient satisfaction levels across five different aspects: - Reliability, Responsiveness, Assurance, Empathy, and Tangibility. It was found that the aspect of empathy had the greatest value of the five factors, i.e., 3.52 followed by Assurance with a value of 3.51. Given the multifactorial nature of different aspects influencing patient satisfaction with the quality of health care, further research is needed to identify additional factors especially from the patient’s perspective and explore context-specific strategies in order to increase the quality of health care. Thus, it can be concluded that a patient satisfaction survey is an effective, affordable, reliable, and quick method to assess the quality of health care and should be conducted periodically in order to evaluate and monitor ongoing health care delivery system. In light of this review, future research focusing on identifying factors that contribute to high patient satisfaction and positive outcomes in healthcare facilities during the pandemic is the need of the hour. This will aid in exploring whether these factors are consistent across different countries and healthcare systems globally. Additionally, incorporating comparison groups and non-self-reported data in future studies could provide more robust evidence regarding the effects of the pandemic on patient satisfaction and outcomes.


Total laparoscopic anterior resection (tLAR) has been gradually applied in the treatment of rectal cancer (RC). This study aims to develop a scoring system to predict the surgical difficulty of tLAR.RC patients treated with tLAR were collected. The blood loss and duration of excision (BLADE) scoring system was built to assess the surgical difficulty by using restricted cubic spline regression. Multivariate logistic regression was used to evaluate the effect of the BLADE score on postoperative complications. The random forest (RF) algorithm was used to establish a preoperative predictive model for the BLADE score.A total of 1,994 RC patients were randomly selected for the training set and the test set, and 325 RC patients were identified as the external validation set. The BLADE score, which was built based on the thresholds of blood loss (60 ml) and duration of surgical excision (165 min), was the most important risk factor for postoperative complications. The areas under the curve of the predictive RF model were 0.786 in the training set, 0.640 in the test set, and 0.665 in the external validation set.This preoperative predictive model for the BLADE score presents clinical feasibility and reliability in identifying the candidates to receive tLAR and in making surgical plans for RC patients. The fast development of laparoscopic surgery indicated great progress in the treatment of colorectal disease in past decades. Substantial evidence suggests that laparoscopic anterior resection (LAR) benefits rectal cancer (RC) patients through a high-definition surgical field, bleeding reduction, early recovery of bowel function, and short hospital stay –3. HowevScoring systems of surgical difficulty not only help to identify patients with a high risk of postoperative complication and poor prognosis but also help surgeons to select appropriate cases and make surgical plans. Although the predictors of the difficulty of anterior resection have been identified –22, no shttp://chinanoses.yiducloud.com.cn) and stored in a uniform format. This study was reviewed and approved by the institutional review board of China National Cancer Center and was exempt from patient consent given the retrospective nature of the study. All included patients were pathologically diagnosed with adenocarcinoma located within 15 cm from the anal verge. The exclusion criteria for tLAR were as follows: patient with multiple lesions, tumor spreading to other distant organs or invading adjacent organs, the patient underwent conversion to conventional laparoscopic surgery or open surgery, surgery performed with a robotic platform, and patient with incomplete data. The flowchart is presented in A total of 3,485 RC patients treated with tLAR between August 2008 and July 2021 were collected from the China national database of tLAR and NOSE for colorectal cancer. The data were collected by a secure online platform , and comorbidity], tumor characteristics , surgical information , and 30-day postoperative complications .All surgical procedures of tLAR were performed by experienced colorectal surgeons for laparoscopic surgery. The tLAR was performed as described previously . BrieflyThe surgical difficulty grading of the BLADE scoring system was built by two surgical variables including duration of surgery and estimated blood loss. Operative time was defined as the time from skin incision to final cutaneous closure. Anesthesiologists carefully evaluated blood loss during the operation and recorded it at the end of the operation. Restricted cubic spline (RCS) regression plots were performed to examine the full-range associations between the duration of surgery and the estimated blood loss with the odd ratios (ORs) for overall complication within 30 days to ascertain the optimal cutoff point to classify the operative time and total intraoperative blood loss into binary variables with a certain degree of objectivity. Each of the two intraoperative factors was assigned 1 point when it was at or above the threshold value. Therefore, the BLADE score ranged from 0 to 2, and patients scoring 0, 1, and 2 were classified as low, middle, and high difficulty of tLAR, respectively.Of included patients from the national database, 80%  were randomly selected for the training set, and the remaining 20% (n = 398) were used as the test set. Furthermore, 325 RC patients who underwent tLAR between January 2015 and August 2018 at Cancer Hospital Chinese Academy of Medical Sciences and the Second Affiliated Hospital of Harbin Medical University were identified as the external validation set according to the inclusion and exclusion criteria. The preoperative models for the BLADE score were developed based on the training cohort by using machine learning algorithms and then were tested in both the test set and the external validation cohort. Nine preoperative variables associated with surgical difficulty were obtained, including gender, age at diagnosis, BMI, history of previous diseases, receipt of neoadjuvant chemoradiotherapy, tumor location, tumor size, AJCC T stage, and AJCC N stage. The algorithms included logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), artificial neural network (ANN), generalized boosting machines (GBMs), and random forest (RF). The details of each model are described in p-value of less than 0.05 after univariate analysis were included in the multivariate analysis. Statistically significant results were defined as p < 0.05, and all p-values were two-sided. Data analyses were performed using IBM SPSS Statistics version 23.0 (IBM Corp.) and R software version 3.5.3 . The study was reported in line with the STROCSS criteria (The data were presented as the mean with standard deviation (SD) for continuous variables and proportions (%) for categorical variables. The association between surgical difficulty and overall postoperative complications was evaluated through uni- and multivariate binary logistic regression analyses by calculating ORs and 95% confidence intervals (CIs). The variables with a criteria .2 (SD = 2.96). A total of 617 (30.9%) patients had comorbidities, and 101 patients (5.1%) had received neoadjuvant therapy. The mean duration of surgery was 188.59 (range 75–669) min, and the mean intraoperative blood loss was 75.85 (range 40–600) ml. The overall complication rate was 17.9% . The details of patient information are shown in A total of 1,994 patients who underwent tLAR were identified, including 1,030 (51.7%) male and 964 (48.3%) female patients, with a median age of 60.20 (SD = 11.43) years and a mean BMI of 22.84 kg/mp-values were 0.001)   Table 2.p = 0.003), patients with comorbidity , lower tumor location , and the BLADE scoring system  were considered as the independent risk factors to postoperative complication for patients treated with tLAR. Similar findings of the association between the surgical difficulty of the BLADE score and complication were also presented in the external validation set (The multivariate logistic analysis was used to identify the association between the BLADE score and postoperative complication. In the derivation set, we found that male patients (OR, 1.438; 95% CI, 1.132–1.826, tion set Table 3.In order to identify the high-difficulty group, we combined patients in the low-difficulty group and patients in the middle-difficulty into one group. For logistic regression, we found that tumor location, comorbidity, and neoadjuvant therapy were considered predictors for the surgical difficulty of tLAR for RC patients Figure 3Individualized treatment has been gradually emphasized in current clinical practice, and a useful and easy scoring system of surgical difficulty could help to identify patients with a high risk of having postoperative complications and patients with poor prognoses. Here, our study is the first report to develop an easy-to-use BLADE scoring system to evaluate the surgical difficulty for tLAR and validate the performance in an independent external cohort to evaluate the ability of true replication, which could reflect the generalizability of this scoring system in the clinical setting. Then, we used preoperative variables to establish the predictive model for the BLADE score based on machine learning algorithms.The assessment of surgical difficulty is challenged by multiple factors that depend on the surgeon’s experiences, the cooperation of the surgical team, and the surgical platform . TherefoIn addition, a previous study has established a surgical difficulty scoring system for TME surgery based on preoperative variables. Baek et al. have established a scoring system to assess the surgical difficulty of robotic surgery for RC according to MRI-based pelvimetry, including large tumor size, narrow intertuberous distance, shallow sacral angle, and long sacral length . Then, tIn light of recent developments in machine learning and the accessibility of computing power, the application of the technique in the data mining and model development field has yielded promising results . CurrentThere are several limitations in this study. First, because a retrospective analysis was used, there are relatively heterogeneous data regarding the determination of tumor location based on different imaging protocols, surgical technique selection of tLAR, and the skills and experiences of surgeons. Second, pelvimetry in pelvic MRI plays an important role in determining the surgical difficulties of anterior resection. However, the information with regard to MRI was missing in the database, which could not be analyzed in this study. Third, the surgeon’s experiences have been considered a key influencing factor for surgical difficulty, but we cannot calculate the influence of the surgeon’s experience on this scoring system due to the lack of relevant information in this database. Fourth, the establishment and evaluation of the surgical difficulty grading system in anterior resection varied obviously between studies, which are unavailable for the comparison of our grading score with the others. Fifth, the subjectivity of the definition of surgical difficulty remains largely unaddressed, which likely leads to potential bias and makes the relationship between surgical difficulty and clinical outcomes difficult to explain. Despite the retrospective nature and limitations in the present study, the advantages of this study include that the surgical difficulty score grading of tLAR is established based on a large sample size of RC patients, and further investigations of the current scoring system should be performed with internal cohort and independent external cohort to validate the outcomes.The easy-to-use BLADE score appears to be effective in predicting the short-term outcome for patients who are candidates to receive tLAR, convenient in making surgical plans for RC patients, and significant in promoting more studies for tLAR in both multicenter studies and randomized clinical trials in the near future.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the institutional review board of China National Cancer Center. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.JFL: methodology, software, data curation, and writing—original draft preparation. XG: conceptualization, writing—original draft preparation, and data curation. RW: software. YFY: data curation. ERL: software. ZXZ: visualization. HPC: investigation. ZL: resources. ZJ: resources. XSW: supervision. All authors contributed to the article and approved the submitted version.


The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut–brain–cognition interaction remains largely unknown.One hundred and twenty-seven participants, including 35 normal controls (NCs), 62 with subjective cognitive decline (SCD), and 30 with cognitive impairment (CI), were included in this study. The participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Structural MRI data were analyzed for cortical anatomical features, including thickness, sulcus depth, fractal dimension, and Toro's gyrification index using the SBM method. The association of altered gut microbiota among the three groups with structural MRI metrics and cognitive function was evaluated. Furthermore, co-expression network analysis was conducted to investigate the gut–brain–cognition interactions.Lachnospiraceae, Lachnospiracea_incertae_sedis, Fusicatenibacter, and Anaerobutyricum decreased with cognitive ability. Rikenellaceae, Odoribacteraceae, and Alistipes were specifically enriched in the CI group. Mediterraneibacter abundance was correlated with changes in brain gray matter and cerebrospinal fluid volume  and significantly with changes in cortical structures in brain regions, such as the internal olfactory area and the parahippocampal gyrus. The three colonies enriched in the CI group were positively correlated with cognitive function and significantly associated with changes in cortical structure related to cognitive function, such as the precuneus and syrinx gyrus.The abundance of This study provided evidence that there was an inner relationship among the altered gut microbiota, brain atrophy, and cognitive decline. Targeting the gut microbiota may be a novel therapeutic strategy for early AD. Alzheimer's disease (AD) is the most common form of dementia, imposing a heavy economic and social burden worldwide. Currently, the pathogenesis of AD remains unclear. Due to the lack of effective treatments in the stage of AD dementia, exploring new mechanisms of AD may be vital for providing successful therapeutic strategies  and amyloid-β (Aβ) positive cognitively normal individuals  homeostasis through these substances or influence neural messages carried by the vagal and spinal afferent neurons, further leading to the development of AD   explore the characteristics of intestinal microbiota in the spectrum of AD in the Hainan cohort; (2) investigate the correlation between gut microbiota and brain atrophy; and (3) elucidate the interrelationship between gut microbiota, brain structure, and cognitive function using co-expression network analysis.n = 35), individuals with SCD (n = 62), and patients with cognitive impairment (CI) . The criteria for individuals with NC were as follows: (1) objective neuropsychological assessments within the normal range, adjusted for age, gender, and years of education; and (2) without complaints of cognitive decline or concerns about cognitive decline. Individuals with SCD were diagnosed according to the criteria proposed by Jessen et al.   those with left-handedness or double-handedness; (2) those suffered from cerebrovascular or psychiatric disorders or other neurological disorders that may lead to cognitive impairment or congenital intellectual disability; (3) those with an experience of traumatic brain injury that may lead to cognitive impairment; (4) those with severe sensory impairment or infectious disease that cannot complete the examination; (5) those who cannot undergo MRI scan, such as having metal implants or claustrophobia; (6) those with a history of taking probiotics, prebiotics, synbiotics, antibiotics, or medications to regulate gut microbiota within the last 3 months; (7) those with a history of long-term use of corticosteroids, immunosuppressants, or immunostimulatory drugs; and (8) those suffered from severe gastrointestinal disorders, such as irritable bowel syndrome, inflammatory bowel disease, and severe digestive and absorption abnormalities.All clinical information was collected according to standard procedures as experienced neurologists and memory clinic specialists prescribed. Research activities in this study were conducted following the ethical standards of the Declaration of Helsinki. The Medical Research Ethics Committee and Institutional Review Board of Xuanwu Hospital at Capital Medical University approved them. Written informed consent was obtained at the time when participants were recruited.Demographic information was collected on age, gender, and years of education. An experienced neurologist interviewed each participant and their informant about their essential physical condition, recorded the assessment of their self-perceived abilities, and sought confirmation from their informants.All participants carried on the following neuropsychological tests: (1) memory domain: Auditory Verbal Learning Test—Huashan version (AVLT-H) .In this study, fecal sample collection and preservation operations were carried out by the standardized fecal procedure proposed by the International Human Microbiome Standard (IHMS) and the Human Microbiome Project (HMP)  was used to extract DNA from the fecal samples in a Class II biosafety laboratory. After extraction, the DNA concentration was quantified using the UV microspectrophotometer Thermo Nano-Drop 2000 . The total DNA was checked for quality by 1% agarose gel electrophoresis. Finally, after assessing the DNA integrity and fragment size, the qualified DNA extracts were suspended in HThe 16S rRNA amplification region selected for this study is the V3-V4, using universal primers (341F and 806R) linked with indices and sequencing adaptors. The forward primer (5′-3′) was CCTAC GGGRSGCAGCAG (341F), and the reverse primer (5′-3′) was GGACTACVVGGGTATCTAATC (806R). The 5′ end of the universal primers was added to fit the Illumina NovaSeq PE250 sequencing of the splice and index sequences. The diluted genomic DNA was used as a template for PCR amplification using the KAPA HiFi Hotstart Ready Mix PCR kit high-fidelity enzyme. The 2% agarose gel electrophoresis was used to examine PCR products, and then the PCR product recovery was completed using the AxyPrep DNA Gel Extraction kit (AXYGEN). Amplified samples were subjected to library quality control using a Thermo Nano-Drop 2000 UV microspectrophotometer and 2% agarose gel electrophoresis. Qualified samples were subjected to library quantification using Qubit and homogenized according to the data available for each sample.The completed amplified DNA samples were sequenced using the Illumina NovaSeq PE250 platform, resulting in paired-end sequencing (PE250) data. Paired-end reads from the double-end sequencing were spliced into a single sequence using PANDAseq software-long reads with a high variation region. The final clean reads were selected to be in the range of 250–500 nt.http://rdp.cme.msu.edu/index.jsp) , each considered as a species representative Edgar, . For cleThe alpha and beta diversity in this study was assessed using QIIME software. The alpha diversity indices were used to assess the alpha diversity, and five alpha diversity indices  were selected for analysis in our study. Beta diversity was assessed by calculating the phylogenetic distance of the UniFrac values, which were divided into Weighted UniFrac concerning sequence abundance and Unweighted UniFrac without reference to sequence abundance.https://nmdc.cn/analyze/detailsid=600676b70b38496ee0c90921), as the processing platform, to estimate the influence of each species' abundance on the differences among groups and analyze the microbiota information and enrichment that had a significant response to the sample grouping information. Then, the significant difference information of the distribution of bacteria between different groups was screened using the rank sum test method, and the microbiota with the significant difference in relative abundance value between groups was obtained. The threshold value was p < 0.05 and was corrected by a false discovery rate (FDR).This study uses the Kruskal.test function in R studio's stats tool package to analyze the inter-group differences in microbiota structure. First, the linear discriminant analysis (LDA) typical method was used by LEfSe, a cloud tool of the National Microbial Science Data Center 3. The participants were asked to close their eyes and enter a quiet state without falling asleep and to keep their torsos as motionless as possible until the scan was completed.The MRI data acquisition equipment involved in this study was a 3-T MR imager  at the Radiology Department of Hainan General Hospital, using a magnetization-prepared rapid acquisition gradient-echo sequence to acquire three-dimensional T1-weighted images at the sagittal plane. T1-weighted imaging (T1W1) acquisition parameters: matrix = 256 × 256, FOV = 256 × 256 mmhttp://www.brain-development.org), and smoothed  using SPM 12 and the CAT 12 toolkit, including origin and bias field inhomogeneity correction. It segments the images into different gray matter, white matter, and cerebrospinal fluid volume (CSF) data files by CAT 12′s AMAP method. The images were normalized by the DARTEL algorithm function in the toolkit, aligned sample by sample image to a template of 555 healthy subjects in the IXI database . For all intra-group statistical and inter-group comparison work on grouped data, the Shapiro–Wilk test  and Levene's test (chi-square test) were performed before selecting the appropriate parametric or non-parametric test, respectively. A one-way ANOVA test was used for analyses of inter-group variance for continuous, normally distributed data, and the Kruskal–Wallis test for continuous, non-normally distributed data. The Pearson chi-square test was used to analyze inter-group variability for categorical variables.When calculating correlations among the altered gut microbiota abundance, the structural index, and the neuropsychological assessments, biased correlation analysis was used through a linear mixed-effects model with age, years of education, and TIV as covariates, the aim of which was to exclude the influence of other confounding factors on the results. GraphPad Prism  was used to describe the correlation.p < 0.05), the results were tested by FDR to estimate the relationship between the pathways represented by the above feature values as a Network diagram for overall representation.Using Cytoscape to perform Spearman correlation analysis on the abundance of the screened gut microbiota, cortical index, volumetric index, and cognitive-related neuropsychological assessments and reflect significant interrelationships (p > 0.05). There were also no statistical differences among the three groups in PSQI, RBDSQ, and ESS (p > 0.05). In the results of the three scales assessing mood , the differences among the three groups were statistically significant , and the SCD group had the highest scores in both HAMD and HAMA. There were extreme statistically significant differences (p < 0.001) in MMSE, MoCA-B, and FAQ scales, and the CI group had the most severe cognitive impairment on each of the scales.The results of demographic information and neuropsychological assessments of the NC, SCD, and CI participants are shown in A total of 1,227 OTUs were analyzed from the fecal samples collected from all the participants, of which 198 OTUs were shared between the NC and SCD groups, 44 OTUs were shared between the SCD and CI groups, and 608 OTUs were shared between the three groups . A totalp = 0.76, p = 0.49, p = 0.15, p = 0.15; p > 0.05)  . In this > 0.05) , and no  > 0.05) .Firmicutes was enriched in the NC group. In contrast, the abundance of the phylum Firmicutes was significantly lower, and the abundance of the phylum Bacteroidetes was significantly higher in the CI group compared with the NC group. At the genus level, the beneficial intestinal bacteria such as Faecalibacterium and Lachnospiracea were enriched in the NC group compared with the CI group. The abundance of these groups was reduced in comparison with the CI group.In this study, all samples detected were analyzed for species annotation and abundance, and the distribution of the dominant phylum and the composition of the dominant genus were consistent with the results of previous studies on the ecological structure of human-derived intestinal microbiota, as observed in the overall sample microbiota ecological structure . The stuFirmicutes, class Clostridia, order Clostridiales, family Lachnospiraceae, genus Fusicatenibacter, genus Lachnospiracea_incertae_sedis, and Anaerobutyricum showed a progressively decreased prevalence from NC to SCD and CI; compared with both CI and SCD subjects, the NC population demonstrated a significant decrease in the abundance of phylum Bacteroidetes, class Bacteroidia, and order Bacteroidales.In this study, to accurately know the information about the groups that were significantly different among the three groups, LEfSe analysis was used to assess the magnitude of the effect of the abundance of different species on the effect of group differences, to identify the groups or species that had a significant differential effect on the group information. As shown in Lachnospiraceae (LDA = 4.64), Lachnospiracea_incertae_sedis (LDA = 3.40), Fusicatenibacter (LDA = 3.29), and Anaerobutyricum (LDA = 2.69) had decreasing abundance with cognitive ability and a decreasing trend between groups; the abundance of family Rikenellaceae (LDA = 3.65) and Odoribacteraceae (LDA = 3.06), and genus Mediterraneibacter (LDA = 3.18) and Alistipes (LDA = 3.65) in individuals with SCD were significantly reduced compared with others and enriched in the CI group.Based on the results of the analysis of the differences between the three groups and the biological background of the screened groups, it was decided to retain nine distinct groups for the study. Among them, p = 0.013); TSA displayed a significantly inter-group difference (p = 0.004); WM_abs, GM_abs, CSF_rel, WM_rel, and GM_rel were shown extremely statistically inter-group difference (p < 0.001); there was no statistically significant difference among the groups in TIV (p = 0.093). There are consistent with previous relevant studies.In this study, sMRI image data from 100 participants acquired using a 3.0 T MRI machine were analyzed by the VBM method to obtain eight volume metrics, including the actual volume of each group of TIV, TSA, gray matter, white matter, and CSF  and the relative volume of comparison individual TIV . As shown in Participants' cortical morphology was analyzed using SBM, during which four participants' data that could not be aligned with the DK40 template were censored. Four cortical indices  were calculated for the 72 brain regions delineated. Due to the plethora of results, Mediterraneibacter's abundance was positively correlated with CSF_rel  and negatively correlated with GM_rel ; the Mediterraneibacter's abundance was negatively correlated with GM_abs ; and the Odoribacteraceae's abundance was negatively correlated with GM_abs .Correlations between sMRI brain volume metrics and characteristic microbiota abundance were performed using partial correlation analysis, adjusted for age, years of education, and TIV. As shown in Rikenellaceae's abundance was negatively correlated with thickness of the lateral orbitofrontal cortex in both right and left brain ; the Odoribacteraceae's abundance was negatively correlated with sulcus depth of the left parahippocampal gyrus , with Toro's gyrification index of the left precuneus , with Toro's gyrification index of the superior parietal cortex in both right and left brain , and with Toro's gyrification index of the left supramarginal cortex ; the Lachnospiraceae's abundance was positively correlated with thickness of the entorhinal cortex in both right and left brain , with Toro's gyrification index of the left precuneus , and with Toro's gyrification index of the superior parietal cortex in both right and left brain ; the Lachnospiracea_ incertae_sedis's abundance was negatively correlated with fractal dimension of the left fusiform gyrus ; the Fusicatenibacter's abundance was negatively correlated with fractal dimension of the left lateral orbitofrontal cortex ; the Anaerobutyricum's abundance was negatively correlated with thickness of the temporal pole in both right and left brain ; the Alistipes's abundance was negatively correlated with thickness of the left lateral orbitofrontal cortex ; and the Mediterraneibacter's abundance was negatively correlated with thickness of the left entorhinal cortex , with the thickness of temporal pole in both right and left brain , and positively correlated with Toro's gyrification index in the left parahippocampal gyrus .The correlation between characteristic microbiota and brain cortex structure is shown in Mediterraneibacter and Alistipes all correlated with the results of the different tables. The abundance of Rikenellaceae indicated a positive correlation with the FAQ results  and negative correlations with the results of MMSE, MES, AVLT-H N5, BNT, and MoCA-B . The abundance of Odoribacteraceae indicated positive correlations with STT-A and STT-B results  and negative correlations with BNT, MES, MoCA-B, and MMSE results . The abundance of Lachnospiraceae indicated a positive correlation with MES  and a negative correlation with the FAQ results . The abundance of Alistipes indicated a positive correlation with the FAQ results  and negative correlations with the MMSE, MES, AVLT-H N5, BNT, and MoCA-B results . The abundance of Mediterraneibacter performed a positive correlation with Ecog  and negative correlations with MMSE, MES, AVLT-H N5, BNT, VFT, and MoCA-B results .Using a linear mixed-effects model, we analyzed the correlations between the nine abundance values of distinct groups and the results of the eleven neuropsychological scales after excluding the effects of age and education . The abur > 0, p < 0.05) and negative correlations with STT, FAQ, and Ecog results . The fractal dimension of the fusiform and lateral orbitofrontal showed positive correlations with STT, FAQ, and Ecog results  and negative correlations with MMSE, AVLT-H, VFT, BNT, MES, and MoCA-B results .After implementing a linear mixed-effects model and regressing the effects of age and years of education, the results of the correlation analysis between 43 cortical indicators and the results of 11 neuropsychological scales were obtained. As shown in The results of the screened nine characteristic microbiota abundances, 43 cortical indicators, seven volumetric indicators, and neuropsychological assessment scales were subjected to an interaction network correlation analysis using Cytoscape to understand the interaction of colony characteristics and further explain the mechanism of formation of differences between characteristic colony groups. There was a tight correlation between the three feature values, forming a complete network of mechanisms .Mediterraneibacter abundance was positively correlated to CSF and negatively correlated to gray matter volume. Moreover, we found a significant correlation between specific gut microbiota abundance and changes in cortical structure in brain regions related to cognitive function, such as entorhinal, fusiform, parahippocampal, precuneus, and superior parietal.In this study, we found nine specific gut microbiota that possibly related to the development of AD, of which four were negatively correlated with cognitive function, and one was positively correlated with cognitive function. In addition, three specificities were enriched in the cognitively impaired population. The joint analysis of the abundance of nine specific microbiota and individual brain structure sMRI image biomarkers found a significant correlation. Firmicutes enriched in the NC group and the phylum Bacteroides enriched in the CI group at the phylum level. In the study of Vogt et al.  can inhibit Aβ deposition by interfering with the assembly of Aβ40 and Aβ42 polypeptides into soluble and neurotoxic Aβ aggregates r et al.  the sever et al.  found thr et al. .Rikenellaceae, Odoribacteraceae, and Alistipes were specifically enriched in the intestines of individuals with CI in our study. The abundance was significantly correlated with the degree of cognitive impairment. In their correlation studies with individual cortical indicators, the primary brain areas affected were the frontal pole, fusiform, lingua, parahippocampal, precuneus, superior parietal, and supramarginal gyrus. However, there are few studies involving the impact of the abovementioned bacteria on brain structural alterations and cognitive impairment.Several microbiotas associated with gastrointestinal and psychiatric disorders have been reported to colonize the gut specifically in AD patients, and this condition affects cognitive function in individuals with AD , and the results showed that there were complex connections between various indicators, which further confirmed the existence of gut microbiota changes in early AD risk groups. In summary, it is suggested that these three microbiotas are related to the decline of individual cognitive function. Their increased abundance may affect the stable structure of specific brain regions, thereby impairing cognitive function. However, further experiments are needed to study the mediator substances and pathways of this effect.There are several limitations to this study: (1) It is a single-center cross-sectional study of an elderly population in Hainan with a relatively small sample size; however, a larger sample size from multiple centers would be useful and necessary to provide more evidence. The results of this study will require a longitudinal study and randomized controlled trial of participants to determine whether the effect of the specific microbiota on disease progression is confounded by other factors. (2) The 16S rRNA high-throughput assay technique used in the current study achieves low resolution, is sensitive to the specific primers selected and the number of PCR cycles, and may be followed up with a macro-genome sequencing approach that extends taxonomic resolution to the species or strain level, as well as analyses potential functional information. (3) We have only confirmed that alterations in gut microbiota show effects on cognitive performance and brain structure, but the causal nature of the interaction between gut microbiota and cognitive function remains unclear. Subsequent inclusion of biomarkers such as gut microbiota metabolites and intra-blood cytokines will provide more comprehensive insights into the potential mechanisms that form a closed-loop study of gut–brain interactions in AD progression.The present study characterized the gut microbiota and brain structure in the spectrum of AD. It confirmed the possible interactions of gut microbiota alterations on brain structure and cognitive function, providing a new perspective on the pathogenesis of AD and a potential target for AD treatments.https://www.ncbi.nlm.nih.gov/bioproject/PRJNA984461.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Xuanwu Hospital, Capital Medical University, Beijing, China. 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.BH and CS contributed to the conception and design of the study. BH organized the database, performed the statistical analysis, and wrote the first draft of the manuscript. CS wrote sections of the manuscript and contributed to manuscript revision. XY and LZ contributed to the manuscript revision. YH and FC contributed to the manuscript revision, read, and approved the submitted version. All authors contributed to the article and approved the submitted version.


In cerebral palsy (CP), spasticity is the dominant symptom and hip pain is one of the most common secondary conditions. Aetiology is not clear. Musculoskeletal ultrasound (MSUS) is a low-cost, non-invasive imaging technique that allows assessment of structural status, dynamic imaging, and quick contralateral comparison.A retrospective case-matched-control study. To investigate associated factors with painful spastic hip and to compare ultrasound findings (focusing on muscle thickness) in children with CP vs. typically developing (TD) peers.Paediatric Rehabilitation Hospital in Mexico City, from August to November 2018.21 children  with CP, in Gross Motor Function Classification System (GMFCS) levels IV to V, with spastic hip diagnosis (cases) and 21 children age- and sex-matched (7 + 4.28 years) TD peers (controls).Sociodemographic data, CP topography, degree of spasticity, mobility arch, contractures, Visual Analog Scale (VAS), GMFCS, measurements of the volumes of eight major muscles of the hip joint and MSUS findings of both hips.All children with CP group reported chronic hip pain. Associated factors for hip pain (high VAS hip pain score) were degree of hip displacement (percentage of migration), Ashworth Level, GMFCS level V. No synovitis, bursitis or tendinopathy was found. Significant differences (p < 0.05) were found in muscle volumes in all hip muscles (right and left) except in the right and left adductor longus.Though possibly the most important issue with diminished muscle growth in CP children is the influence on their long-term function, it is likely that training routines that build muscle size may also increase muscle strength and improve function in this population. To improve the choice of treatments in this group and maintain muscle mass, longitudinal investigations of the natural history of muscular deficits in CP as well as the impact of intervention are needed. Cerebral palsy (CP) is one of the most common physical and developmental disabilities, consisting of a heterogeneous group of permanent movement and posture disorders usually attributed to nonprogressive disturbances that occurred in the developing child’s brain. They are attributed to non-progressive brain lesions at different stages of development: prenatal, neonatal, and early post neonatal (before 5 years old), 2.The sustained contraction of anti-gravitational muscle groups and the accompanying weakness of their antagonists creates a biomechanical imbalance, which results in a longitudinal retraction of the muscle. For this reason, patients with spastic-type CP, by maintaining a sustained contraction of the adductor hamstrings, and flexor muscles of the hip, present a high risk of dislocation. Most children with severely displaced or dislocated hips experience pain –5. The iThe aetiology of pain sensations in the group with CP does not provide any clear indication why pain, associated with hip joint dislocation of spastic origin, occurs in some patients only. Pain is related to multiple factors and associated with functional limitations that make it difficult to sit, stand, or walk, and a lower quality of life in all domains , 8–13. ADue to the depth of the hip joint and the limited number of examination manoeuvres, clinical evaluation of the hip is frequently limited. In children and the elderly, musculoskeletal ultrasound (MSUS) is used to diagnose, monitor, and treat musculoskeletal pathologies –17. BecaNo previous studies were found that measured normal thickness in the hip muscles in children without pathology. The aim of the present study was to investigate the factors associated with hip pain in painful spastic hip (dislocated or subluxated) among children with CP and to compare the ultrasound findings with typically developing children.A retrospective case-matched-control study was conducted at the Hospital de Pediatria del Centro Médico Nacional Siglo XXI (CMN S.XXI) in the period from August to November 2018, using a consecutive sampling method to form the two groups.Group 1 consisted of children with spastic CP. The inclusion criteria were: (a) verified CP diagnosis by a physician specializing in paediatric rehabilitation medicine, (b) with a spastic variant of cerebral palsy  (c) with levels 4 or 5 (GMFCS), (e) with a previous X-ray (for no longer than one week), where migration percentage was measured digitally in both hips by one of the authors (CGS) and (f) without previous treatment (chemo denervation or application of botulinum toxin injections to the lower limbs within the previous year). The exclusion criteria were: (a) children older than 15 years, (b) presence of hip deformity caused by trauma, infection, tumour, etc., (c) presence of neuromuscular disease other than CP; and 4) inadequately taken hip radiographs. Typically developing group consisted of children younger than 15 years without neurological- musculoskeletal disabilities and had no previous surgery to their lower limbs, who were recruited from the outpatient clinic of the same hospital and were included as a TD group. CP and TD groups were matched based on age and sex.This study was performed in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by Comité de Bioética del Hospital de Pediatría Dr Silvestre Frenk Freund Centro Médico Nacional Siglo XXI IMSS, IRB number: F/2018/3603/82). Informed consent was obtained from parents and / or guardians before inclusion in the study. In the same way, the researchers ensured that all minors, capable of understanding enough to participate in decision-making, gave their consent to participate in the research.Both groups were recruited at the same time for both measurements . First, they went to their ultrasonographic assessment, and then, to their assessment with the rehabilitation physician  to carry out their clinical measurements. With a total time of one hour and 30 minuties for each patient in a period of August to November 2018.We made clinical record sheet for the children with CP, that includes:Age and gender.Topography of the CP: Diparesis (affection of 4 extremities predominantly pelvic limbs),.Degree of spasticity: Degree of resistance of as muscle to fast-passive movement. According to this scale, the first assessment is a slow-passive (›1.5 seg) movement (this manoeuvre helps us to identify a contracture in a specific joint), then the second assessment is a fast- passive (≤ 1 seg) movement . Moderate to high inter and intra-rater reliabilities were reported in a recent meta-analysis, with higher reliability for upper than lower extremities. The scale is as follows: 0 (no increase in muscle tone), 1 , 1+ , 2  and 4 (rigid in flexion or extension). DegreesMobility arch: analysed according to the range of motion (ROM) measured by goniometry. Patient in supine position, five measures were taken: hip flexion, hip abduction, adduction, internal rotation, and external rotation. And lateral position for de hip extension.Degree of contracture (measured by goniometry). Patient in supine position, three measures were taken: hip flexors, hip adductors, and hamstrings: considering 0–30 degrees physiological and > 30 degrees inability to walk.The intensity of pain at the moment of move de hip in their different range of motion, according to age and cognitive development, using the Visual Analog Scale (0–10) if the child can answer, where 0 is no pain and 10 is the most intense pain that you have felt in your life or, through the Wong-Baker FACES® Visual Analog Scale (VAS), composed of six drawn faces  with scores ranging from 0 to 10, in the case of the child do not have de capacity for answer, so the parents and physician take a score according at the face of the child at the time of move the hip. For the present study, we categorized hip pain scores 1 to 3 as mild, 4 to 7 as moderate, and 8 to 10 as severe hip pain.Gross motor function measured using GMFCS, a 5-level classification system based on their self-initiated movement with particular emphasis on sitting, walking, and wheeled mobility: level IV children and youths are more likely to be transported in a manual wheelchair or use powered mobility and level V, individuals have severe limitations in head and trunk control and require extensive assisted technology and physical assistance .The degree of hip displacement, measured with the percentage of migration in both hips using Reimers’ method, which varies from 0 to 100%, previously diagnosed by a hip x-ray. Percentage of femoral head coverage  in relation to acetabulum was calculated using ultrasound .The MSUS findings of both hips were carried out using an Esaote MyLab 25® Equipment, with a 7.5–12 MHz multi-frequency linear transducer, gain between 50 and 70%. Ultrasound examination was performed in two orthogonal planes: a longitudinal view in the standard plane at rest  and a transverse view of the flexed hip with and without stress . The thiThe clinical record sheet for the children with TD, includes: age, gender, mobility arch, degree of contracture, normal hip x-ray, MSUS findings of both hips.Interobserver analysis was estimated using interclass correlation coefficients (ICC), with one-way random effect. The reliability is regarded as excellent if ICC 0.90, fair to good between 0.5 and 0.75, and poor if less than 0.5 .Observer agreement. Interobserver agreement between ultrasound investigators showed a good to excellent correlation .Shapiro–Wilks tests of normality found that the measured volume data was normally distributed for all muscles (p < 0.05) and required parametric statistics. Demographic and clinical data between CP and TD groups were compared with Pearson chi-square tests  and independent t-test, (for continuous outcome variables). Associated factors for hip pain  on CP group were compared with Pearson chi-square tests  and one way ANOVA, (for continuous outcome variables). Left and right hip muscle measurements on moderate and severe pain were compared with independent t-test.All tests were 2-sided. A significance level of 0.05 was chosen. Statistical analysis was performed with IBM® SPSS® Statistics .A total of 42 subjects (84 hips) were included. 61.9% were male (n = 26) and 38.1% female (n = 16), with a mean age of 7.02 (SD = 4.22) years (range 1–15 years). Case group consisted of 21 children with spastic CP   degree of hip displacement (migration percentage) in both hips , (2) Ashworth Level (p = 0.021) (3) Degree of contracture (Left hip flexion contracture (p = 0.047) and (4) GMFCS level V (p < 0.001)  Degree of hip displacement (percentage of migration): At a mean age of seven years, the average of children with CP have subluxated hips, increasing the risk for luxation. This is likely to occur, in children that are unable to walk. If hip displacement progresses to dislocation, the child may develop early onset arthritis and chronic pain.Otherwise, we had children with CP with normal percentage of migration and mild hip pain; and other group of patients, with a similar migration percentage, they show moderate-severe pain. In those cases, we wonder what was the reason of pain, an what structures were implicated.2) Degree of function (GMF V): as functional deterioration and physically impaired are more severe, perception of pain and risk of luxation increases 70–80%. Similar results have been shown from the Victorian Cerebral Palsy register,3) Restriction in all hip range of motion in patients with CP, compared with typically developed children, cause musculoskeletal disorders, contractures and chronic pain.4) Spasticity in the muscles around the hip joint, and 5) patients with moderate vs. severe hip pain had significant increase in left long adductor and right ischium on MSUS measured, which correlates with muscles that intervene on the adduction of de hip.Pain in children with CP has wide-ranging consequences, so early recognition is essential. This significantly reduces quality of life, affects mental health, impaired sleep and causes less participation in activities of daily living (e.g. relationships and recreation) , 33.In childhood pain is a predictor of restricted participation. Motor disorders of CP are often associated with musculoskeletal abnormalities, hip displacement is the second most common. Hip pain is a frequent phenomenon with a reported prevalence of 27 to 77% in patients with CP, this variation depends on the research criteria, time period, age, CP type and GMF level , 34, 35.Hip displacement can lead to pain, reduced function, and quality of life; this displacement is due to spasticity and contraction of the hip adductors and flexors, as well as the medial hamstrings, with atrophy of the hip extensor and abductor muscles, resulting in muscle imbalance and bony deformity .Hip muscle thickness has not been clarified on individuals with CP vs. TD. Having measurements of muscle thickness is valuable because it may, in the future, allow doctors to rule out other causes of pain, that are not previously considered in the literature. In our study, no data of joint inflammation or soft tissue injuries were found.In this study we assessed the thickness of eight hip muscles and we find out that all of them were significantly smaller in the group of children with CP than in the group of TD children of comparable age and sex, except the right and left adductor longus. We found studies with measurements of some lower extremity muscles and their relationship with gait, but not with pain , 36, 37.Some studies report changes in muscle thickness associated with spasticity and stiffness, that may be due to the musculoskeletal alterations in CP , 24, 28.The force-generating capacity of a muscle is mainly due to its morphological and architectural characteristics , 38. TheOne of the weakness of the study was the assessment of pain, which was based on self-report with a numerical or visual analogue scale (pain is understood as a participatory experience), using self-report as the standard criterion . We recrThis study is cross –sectional, so it cannot infer causality. On the other hand, the vision of the ultra-sonographer is modificated because of the operator-dependent bias, but we can still find the muscle structures despite the patient spasticity and difficulties to access and measure some studied areas.The clinical implications of the study, related to the modification of muscle thickness in patients with CP and painful spastic hip, are the initial step to find the causes of these changes and early detection of them through the MSUS; and even to determine if these changes occur before or after hip subluxation or dislocation.Currently, the effectiveness of the different treatments in painful spastic hips are carried out using qualitative self-applied or hetero-applied instruments, and there is no quantitative measurement of pain improvement. It is important to carry out prospective, randomized, controlled, double-blind studies with methods of imaging with additional technology such as elastography, muscle mapping with other techniques; and evaluation of treatment, by assessing it effects at the structural and functional level. This study opens new opportunities to improve the early diagnosis of musculoskeletal injuries, the quality of life of children with CP and spastic hip, start early treatment, and improve prognosis in the medium and long term. To choose properly treatments in this group and maintain muscle mass, longitudinal investigations of the natural history of muscular deficits in CP as well as the impact of intervention are needed.Though possibly, the diminished muscle growth in PC children, influence their long-term function. It is likely that training routines, building up muscle size, increasing muscle strength will improve function in this population. The low muscle reserves could expose individuals to harmful consequences of muscle aging.It’s a common complain that pain in CP people is underdiagnosed and undertreated; the approach of pain is complex and a challenge, due to the existence of many pain causes and difficulties in communication. In this study, the causes of pain, were related to the degree of hip dislocation, spasticity, and structural changes by MSUS, which showed a direct association with structural muscle architecture (decrease in its thickness). More studies are required to identify risk groups, standardize hip muscle imaging and measurement techniques, to enhance an early treatment and avoid or delay quality of life deterioration.In order to prevent painful musculoskeletal complications of CP, in patients with spastic hips, prior to subluxation, periodic muscle evaluations should be done. It is possible that the MSUS can provide surveillance of musculoskeletal findings to prevent complications in the medium and long term.Hip surveillance is defined as the process of monitoring and identifying early critical indicators of hip displacement. In addition to identification, early intervention in these types of hips can reduce the number of reconstructive surgeries, and reduce negative effects on their daily activities, participation, quality of life, and mental health.


The objective of this study is to conduct a comprehensive bibliometric analysis to identify and evaluate global trends in diabetic retinopathy (DR) research and visualize the focus and frontiers of this field.Diabetic retinopathy-related publications from the establishment of the Web of Science (WOS) through 1 November 2022 were retrieved for qualitative and quantitative analyses. This study analyzed annual publication counts, prolific countries, institutions, journals, and the top 10 most cited literature. The findings were presented through descriptive statistics. VOSviewer 1.6.17 was used to exhibit keywords with high frequency and national cooperation networks, while CiteSpace 5.5.R2 displayed the timeline and burst keywords for each term.A total of 10,709 references were analyzed, and the number of publications continuously increased over the investigated period. America had the highest h-index and citation frequency, contributing to the most influence. China was the most prolific country, producing 3,168 articles. The University of London had the highest productivity. The top three productive journals were from America, and Investigative Ophthalmology Visual Science had the highest number of publications. The article from Gulshan et al.  served as the representative and symbolic reference. The main research topics in this area were incidence, pathogenesis, treatment, and artificial intelligence (AI). Deep learning, models, biomarkers, and optical coherence tomography angiography (OCTA) of DR were frontier hotspots.Bibliometric analysis in this study provided valuable insights into global trends in DR research frontiers. Four key study directions and three research frontiers were extracted from the extensive DR-related literature. As the incidence of DR continues to increase, DR prevention and treatment have become a pressing public health concern and a significant area of research interest. In addition, the development of AI technologies and telemedicine has emerged as promising research frontiers for balancing the number of doctors and patients. AccordiDiabetic retinopathy is the subject of extensive research, with vast literature making it difficult to identify the research emphasis and frontier. Therefore, a comprehensive retrospective analysis is crucial to understanding the development state, research hotspots, and future development trends of DR.To achieve this, we used VOSviewer, a program that excels at constructing any type of text map, for literature-based cooperative network analysis, co-occurrence analysis, citation analysis, literature coupling analysis, and co-citation analysis . We also2.2.1.We obtained all literature from the Web of Science (WOS), a leading global database of scholarly information founded in 1985. WOS includes authoritative and influential journals across a wide range of disciplines. We used the WOS core collection to ensure that high-quality academic journals were selected and searched the database from its establishment until 1 November 2022. To maximize precision while maintaining search sensitivity, we merged the title and abstract and excluded interference from the “early treatment of diabetic retinopathy study.” Our retrieval formula was as follows: {[TI = (“diabetic retinopathy”) OR AB = (“diabetic retinopathy”)] NOT [AB = (“early treatment of diabetic retinopathy study”) OR AB = (“early treatment diabetic retinopathy study”)]} OR {[TI = (diabet*) OR TI = (mellitu*)] AND [AB = (“early treatment of diabetic retinopathy study”) OR AB = (“early treatment diabetic retinopathy study”)]}. We limited the document types to articles, the language to English, and excluded retracted publications.2.2.We downloaded literature information in batches and recorded “Full Records and References Cited.” To integrate the downloaded bibliographic data into CiteSpace 5.5.R2 and VOSviewer 1.6.17, we named the downloaded file “download X.” We collected publication counts, citation frequency, and h-index of countries, institutions, and journals, along with primary information on the top 10 most cited articles from the WOS analysis results and citation reports. We also evaluated the impact factors (IFs) of important journals derived from the 2022 Journal Citation Reports (JCRs).2.3.N = 50. The node type was set as the keyword. We used Pathfinder, pruning networks, and pruning the merged networks to simplify minor wiring, while the remaining parameters were set to default settings.We imported the findings of the WOS analysis results and citation reports into Microsoft Excel to provide annual publication counts, major nations, institutions, and journals in charts. We condensed the most significant data from frequently referenced articles and presented the findings in a tabular format. We used VOSviewer to display collaboration networks of countries and high-frequency keywords, setting the node type successively as countries and all keywords, and different thresholds to display only the top 37 countries and top 60 keywords. National node weights were selected based on total link strength, and keywords node weights on documents. Both figures used network visualization as the image type. We visualized keyword timelines and burst keywords using CiteSpace, setting the period of analysis from 1996 to 2022 since the first relevant literature was published in 1996. The time-slicing was set to 1 year and the threshold to 3.3.1.A total of 10,709 records met the search criteria. Jirousek MR et al. released the first record on the subject of DR in 1996. They proposed the idea of inhibiting overactive PKC isoenzyme to treat DR . In 20113.2.According to the articles retrieved, relevant material was published in 127 countries. 3.3.The top 10 institutions in terms of the number of publications were from four distinct nations: England, America, China, and Singapore . The Uni3.4.Half of the top 10 most commonly circulated DR publications  were fro3.5.3.6.Keywords can refine literature and help identify the field’s hotspots based on their frequency. The VOSviewer node was set to all keywords, and synonyms such as diabetes and mellitus, vegf and vascular endothelial growth factor were combined. Eventually, we identified the top 20 keywords , and the3.7.3.8.Keyword bursts, which illustrate terms that abruptly and often emerge within a certain period, can be used to forecast hotspot changes. 4.Bibliometric analysis is a prominent method to identify active research hotspots and future trends. It can visualize the relationships between the literature as a scientific knowledge map and is widely recognized as a valuable tool for mining useful information from the complex network structure of literature data . In this4.1.The trend changes in the number of publications reflect the updating of knowledge about a subject. Before 2011, DR had not received sufficient attention, as fewer articles were published. However, with the increasing number of diabetics in the world, the incidence of DR is also significantly increasing. The increasing incidence of DR and the advancement and promotion of fundus examination equipment have both contributed to the expansion of DR research. Since 2011, the research on DR has been in a rapid development stage, as reflected by the number of published articles. Based on the posting trend, it is predicted that the number of publications will reach a new peak this year. In addition, the citation frequency in 2017 is the highest, indicating that the research results have gained widespread attention.4.2.According to the h-index and citation frequency, America is the leading country in DR research with the most impact, accounting for 23.795% of the total publications. China ranks second, with the largest number of publications but lesser influence. As research deepens, global cooperation is becoming closer. Based on the connections between the various nodes, America places great importance on communication and collaboration in academia, which explains why America has both high productivity and high-quality research. The top three prolific journals were all from America, with Investigative Ophthalmology and Visual Science (IOVS) being the most productive and cited journal in DR research. Among the top 10 prolific institutions, six were located in Europe and America, which is consistent with the increasing prevalence of DR in developed countries.4.3.The keyword analysis results from VOSviewer revealed four clusters in the DR field. Based on the findings of the bibliometric analysis, we discuss the following four main research fields of DR research:4.3.1.In recent years, the prevalence of diabetes has been steadily increasing, leading to an increase in the incidence of DR, a serious worldwide public health concern. DR is the leading cause of blindness among individuals of working age (20–74 years old) in many countries . AccordiMultiple factors influence the occurrence and progression of DR. The incidence rates of DR vary depending on the region and the type or duration of diabetes . In addi4.3.2.Advances in research have improved our understanding of the pathophysiological processes that lead to the development of DR. Hyperglycemia, along with other pathological risk factors such as hypertension, sets off a cascade of metabolic pathways that eventually cause microvascular damage and retinal malfunction.circRNA-CZNF532  through neovascularization  effectively regulate blood glucose levels and inhibit the manifestation of SGLT2 within the retina, thus mitigating the probability of DR . In addiFor individuals with a confirmed diagnosis of proliferative diabetic retinopathy (PDR), the main therapeutic options are retinal laser photocoagulation and intravitreal anti-vascular endothelial growth factor (VEGF) injection. Laser photocoagulation reduces VEGF production and the risk of vision loss by destroying the ischemic retinal area. Anti-VEGF treatment, on the other hand, improves retinal edema and patients’ vision by suppressing vascular permeability. Common anti-VEGF drugs include conbercept, aflibercept, ranibizumab, and bevacizumab. Intravitreal anti-VEGF injection has been found to significantly reduce peripheral vision impairment and decrease the incidence of macular edema in DR patients, making it the preferred option for treating diabetic macular edema. A meta-analysis has also shown that anti-VEGF pretreatment 6–14 days prior to vitrectomy in DR patients can reduce operation time, improve postoperative best-corrected visual acuity (BCVA), and decrease the recurrence rate of vitreous hemorrhage .When anti-VEGF therapy is not successful, corticosteroids may be considered due to the involvement of multiple inflammatory mediators in the pathological processes in the retina . Common 4.3.4.Diabetic retinopathy has different fundus manifestations in different stages. In the non-proliferative diabetic retinopathy (NPDR) stage, fundus manifestations include arteriolar hemangiomas, punctate retinal hemorrhage, hard exudation, cotton-wool spots, retinal edema, and beaded venous dilatation. Angiogenesis is the main feature of the fundus in the PDR stage. Fundus images can be used to detect and diagnose macular edema and vitreous hemorrhage, which are the main complications of DR. If the fundus image shows vitreous membranes with retinal eminence, it suggests that DR has developed tractional retinal detachment. Currently, fundus images of DR are not only used for clinical diagnosis but also for deep learning, to improve the detection rate and accuracy of DR.4.4.Keyword burst analysis provides a useful tool to forecast research frontiers and predict fundamental and clinical research trends. The current research frontiers of DR can be summarized as follows:4.4.1.The development and validation of deep learning algorithms for DR is the most commonly cited article . The imp4.4.2.Biomarkers can be objectively measured and used as indicators to assess normal biologic status, pathogenic processes, or response to interventions. Abnormal results of the fundus, blood markers, cytokines, etc. can all be used as the biomarkers of DR. Identifying these biomarkers can assist doctors in diagnosis and timely intervention to avoid the aggravation of the patient’s condition. Furthermore, DR biomarkers, abnormal gene expression , 71, andIn addition to biomarkers, OCTA, a non-invasive fundus imaging technique, can be utilized to classify DR objectively. OCTA is commonly used in conjunction with DR biomarker identification because it can provide a layered view of the retinal and choroidal vasculature in living tissue , 74. In In conclusion, OCTA is extensively utilized in clinical and research applications. It may be used for clinical assessment, to track changes in fundus conditions, and to evaluate the efficacy of therapy. Therefore, developing DR screening programs and discovering more specific and sensitive biomarkers is vital to assist early identification of DR to minimize the incidence of visual impairment and blindness.4.5.This study utilized bibliometrics to evaluate publishing trends, leading research countries, institutes, and journals in the area of DR. The use of VOSviewer allowed for the identification of national collaborations and keywords with high frequency. CiteSpace illustrated changes in research hotspots and predicted future research trends. However, the limitation of this study is that it only included literature from a single database, which may have omitted relevant DR-related literature and introduced bias.5.The results of this bibliometric analysis demonstrate that DR is a critical research field that has been expanding rapidly. The United States has had a significant academic impact on DR research, and international collaborations are increasingly important for the field’s development. OCTA screening and the identification of specific biomarkers are crucial for early DR detection and the prevention of visual impairment and blindness. With the increasing prevalence of DR, the development of AI technologies and telemedicine to address the shortage of ophthalmologists is a potential research hotspot and an urgent issue. These findings can provide valuable references for future DR research.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.HX and JT conducted the bibliometric analysis and drafted the manuscript. JD and FZ reviewed the manuscript. LL developed the search strategy. ML, MC, JZ, XW, and YN contributed to the data analysis. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted without any commercial or financial relationships that could potentially create a 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.