Radiotherapy for rectal cancer has received increasing research attention in recent years; however, no bibliometric assessment has been conducted on the progress of research in this field. This study aimed to visualize the research evolution and emerging research hotspots in the field of rectal cancer radiotherapy using bibliometric methods. Data were collected from the Web of Science Core Collection database, including countries, institutions, authors, keywords, and co-citations of references, and the CiteSpace software was used for bibliometric analysis. A total of 5,372 publications on radiotherapy for rectal cancer, published between January 2000 and January 2022, were included. An increasing trend in the number of published articles was observed. There is an overall upward trend in the number of publications published, with the US publishing the most in this field, followed by China and the Netherlands. Italian writer Vincenzo Valentini and German writer R. Sauer ranked first in terms of published articles and co-cited authors, respectively. Literature co-citation and keyword co-occurrence analyses showed that early studies focused on topics such as preoperative radiotherapy, combined radiotherapy and chemotherapy, and total mesorectal excision. In recent years, gradually increasing attention has been paid to short-course radiotherapy, x-ray brachytherapy, and stereotactic systemic radiotherapy. Burst analysis suggested that magnetic resonance (MR)-guided neoadjuvant radiotherapy studies, mechanistic studies, and clinical trials may emerge as new research hotspots. Rectal cancer radiotherapy has been widely studied and the research hotspots have considerably changed in recent years. Future research hotspots may include MR-guided neoadjuvant radiotherapy studies, mechanistic studies, and clinical trials. Colorectal cancer is the third most commonly diagnosed cancer and the second major cause of cancer deaths worldwide. In 2021, colorectal cancer was diagnosed in 1,931,590 patients and caused the death of 935,173 people worldwide  database for the period from 1 January 2000 to 1 January 2022. Science Citation Index Expanded, Conference Proceedings Citation Index-Science, Conference Proceedings Citation Index-Social Science & Humanities, Book Citation Index-Science, and Book Citation Index-Social Sciences & Humanities were used as data sources, and the type of publication was limited to “article”. The main search terms were “rectal neoplasm”, “rectal tumor”, “rectal cancer” or “rectum cancer”, “colorectal cancer”, “colorectal carcinoma”, “colorectal tumor”, “radiotherapy”, and “radiation”. The detailed search strategies are described in the The CiteSpace software (version 5.8. R3) was selected as the main tool for the comprehensive analysis of the literature on radiotherapy for rectal cancer. The CiteSpace software is a Java-based visualization program developed by Professor Chen Chaomei of Dexrel University in the United States. The data sources of Citespace software are mainly from Web of Science database and PubMed database . The impTo predict the number of articles that will be published in 2022, Microsoft Office Excel 2016  was used to process the data and to construct a polynomial regression model: f(x) = p0x n + p1x n-1 + p2x n-2 + p3x n-3 + … + pn.n = 90, 1.68%) and that with the highest number of published articles was 2021 , with an average of 244 articles published per year. A statistically significant correlation between the year and number of publications was observed by fitting the data (R2 = 0.9823). On the basis of the fitted curve, we predicted that approximately 511 articles on radiotherapy for rectal cancer will be published in 2022.The search of the WoSCC database yielded a total of 5,372 articles on radiotherapy for rectal cancer published between 2000 and 2021. As shown in n = 1,314, 19.58%), China , and the Netherlands   . Accordi, 6.56%) , radioth, 6.56%) .n = 137, 6.87%), Memorial Sloan Kettering Cancer Center , and Catharina Hospital . Leiden University had the largest number of publications; however, the average publication year was in the early period. The institutions with more recent publications were Fudan University  and Sun Yat Sen University  in China, indicating a gradual increase in research activity related to radiotherapy for rectal cancer in China in recent years , Bengt Glimelius (n = 34), and Cornelis J.H. Van De Velde (n = 33) (n = 1398) ranked first, followed by E. Kapiteijn (n = 971) and J.F. Bosset (n = 849)  . Among t(n = 33) , R. Sauen = 849) . Figure n = 849) . He alson = 849) .When two articles are cited together in other articles, they are considered to be in a co-citation relationship, and the frequency of co-citations is a measure of the degree of the relationship between the two articles . For staBurst analysis can identify articles that have attracted the attention of peer researchers and can help in the timely discovery of articles with a strong influence on future research . The colAccording to the year of the citation burst, an article titled “Improved survival with preoperative radiotherapy in resectable rectal cancer” began to be associated with a surge of citations in 2000. This study concluded that a short-term regimen of high-dose preoperative radiotherapy may reduce local recurrence rates and improve survival in patients with resectable rectal cancer . The topNotably, among the top 15 articles with citation bursts, 5 articles were related to short-course radiotherapy –24, 30. In the cluster analysis, we found that the clustering themes of articles with citation bursts have considerably changed during the last 22 years. In The constructed co-citation network graph is presented based on the time nodes to obtain a timeline map . The sizThe largest cluster in the title clusters was “advanced rectal cancer”, reflecting its importance in research on radiotherapy for rectal cancer. The clusters with the largest silhouette coefficients were “ii study” and “study protocol”, indicating that these two clusters had the most explicit themes. The studies in these two clusters were mainly related to radiotherapy combined with chemotherapy and recurrent rectal cancer, reflecting the focus of research on this topic . In addiKeyword co-occurrence analysis can reflect the hotspots of research in a field. This analysis was performed on the 5,372 articles published between January 2000 and January 2022. The time slice was set to 1 year, and the top 30 keywords that appeared most frequently in each slice were selected. After merging similar keywords  and using a Pathfinder network for tailoring (PFNET pathfinding network), a keyword co-occurrence map was generated . The nodKeyword burst analysis not only can reflect the changes in research hotspots in a certain field but can also predict future research trends. As shown in The remaining 10 keywords that have received more attention from after 2015 to the present time are the focus of current studies in the field of rectal cancer radiotherapy. Among them, “multicenter” and “open label” had the highest burst strength, indicating that the research activity was more concentrated on clinical trials. Clinical trials have guiding significance in the formulation of clinical treatment strategies. Another research hotspot emerged related to preoperative and postoperative radiotherapy, with bursts beginning in 2015 and 2016, respectively, and continuing to the present time. On the basis of numerous clinical trials, total mesorectal resection after preoperative 5-fluorouracil-based neoadjuvant radiotherapy has become the standard treatment for locally progressive rectal cancer, significantly reducing the rate of local recurrence but not the risk of metastatic recurrence , 39. PosIn this study, a systematic literature search of the WoSCC database was conducted for articles on radiotherapy for rectal cancer published between 2000 and 2022. After excluding studies that did not meet the screening criteria, the scientometric analysis included 5,372 English-language papers from 130 countries. The research results and progress in this field were quantitatively and visually assessed using the CiteSpace econometric analysis software.Articles associated with research on rectal cancer chemotherapy over the last 22 years were analyzed from different dimensions and perspectives. With respect to the volume of publications, the number of articles in the field of rectal cancer has increased every year, indicating that increasing attention has been paid to research related to rectal cancer radiotherapy. In terms of countries of publication, European countries, Japan, Korea, Australia conducted the earlier studies on rectal cancer radiotherapy, and the United States has the highest number of publications in this field. The analysis of institutional bursts showed that foreign institutions have ushered the development of this field in the past. However, of the five institutions that emerged recently, three are in China. Although research in this field started late in China, rapid developments have been achieved. The analysis of authors and co-cited authors showed that the Italian author Vincenzo Valentini ranked first in terms of the number of published articles, reflecting his extensive research in the field, whereas the German author R. Sauer ranked first in terms of co-citations, indicating his significant influence in the field of radiotherapy for rectal cancer. In the co-citation analysis, R. Sauer's article published in the New England Journal of Medicine, which established the importance of neoadjuvant radiotherapy in the treatment of locally progressive rectal cancer, was the most frequently cited article .Through a literature clustering analysis, we found that the clustering topics of burst literature have considerably changed in recent years, which is mainly reflected in three aspects of rectal cancer radiotherapy: objects, types, and methods. In the past, the study participants included patients with resectable rectal cancer and some patients with advanced rectal cancer. More recently, studies gradually included patients with unresectable rectal cancer, patients with metastatic rectal cancer, patients with recurrent rectal cancer, and young patients with rectal cancer. Radiotherapy types have changed from postoperative radiotherapy to preoperative radiotherapy and now to preoperative radiotherapy combined with chemotherapy. Radiotherapy methods for rectal cancer has changed from conventional radiotherapy to brachytherapy and to the current stereotactic radiotherapy and MR-guided neoadjuvant radiotherapy. Notably, among these, the radiotherapy approach was the fastest evolving method. SBRT uses stereotactic technology for radiation therapy to improve positioning and positional accuracy , whereasKeyword co-occurrence and burst analyses have enabled the evaluation of hot research topics and emerging research areas in the field of rectal cancer radiotherapy over the past 22 years. Early researchers focused more on total mesorectal resection, combined radiotherapy and chemotherapy, local recurrence, sphincter preservation, and treatment with 5-fluorouracil. Later, researchers gradually explored a system of rectal cancer treatments based on surgery and supplemented by radiotherapy to reduce postoperative complications and improve prognosis. In recent years, the keywords of interest included “p53”, “expression”, “multicenter”, “open trial”, “preoperative radiotherapy”, and “postoperative radiotherapy”, which indicate that mechanistic studies, clinical trials, and neoadjuvant/adjuvant radiotherapy studies may be the recent hotspots in the field of rectal cancer. Currently, an increasing number of clinical trials are exploring the outstanding issues in the field of rectal cancer radiotherapy, such as the dose of radiotherapy, the optimal indications, and the timing of adjuvant therapeutic interventions, to guide the clinical development of a more rational individualized treatment strategy.Clinical trials related to rectal cancer radiotherapy are of great significance for promoting the development of clinical treatment. Previous clinical trials discussed the toxicity and survival outcomes of neoadjuvant radiotherapy, the choice of short- and long-course radiotherapy. Whether preoperative radiotherapy can increase patient survival remains controversial. Early studies have shown survival benefit of preoperative radiotherapy , 52, butTo our knowledge, this study is the first bibliometric analysis focusing on research in the field of rectal cancer radiotherapy. The data downloaded from the WoSCC database covered the vast majority of articles in the field of rectal cancer radiotherapy. Moreover, our data analysis was relatively objective and comprehensive, clearly demonstrating the current state of research in this field. However, this study had some limitations. First, this study included original articles published between 2000 and 2022 and indexed in the WoSCC database. The literature included in our study may not be exhaustive, as books, conference abstracts, and other types of publications were excluded from the document screening process. Second, only articles written in English were included in our analysis, which might have introduced some language bias. Third, recently published high-quality articles may not have received due attention because of low citation rates, which indicates the importance of future research updates. Therefore, the articles included in our analysis may not adequately reflect all studies on radiotherapy treatment for rectal cancer; however, our analysis covered the vast majority of articles in the field of rectal cancer radiotherapy, which is sufficient for the analysis of research trends and hotspots.Starting from the radiotherapy of rectal cancer, we use bibliometrics to visualize the research progress and emerging research hotspots in the field of rectal cancer radiotherapy, and provide researchers with a comprehensive landscape. In the past 20 years, a large number of high-quality studies on rectal cancer radiotherapy have emerged, which has promoted the development of clinical rectal cancer treatment. Through bibliometric analysis, we believe that rectal cancer radiotherapy will remain a hot research topic in the future and cooperations between countries and institutions will be closer. Research will continue to be mainly in the form of clinical trials, and basic research on mechanisms related to radiotherapy for rectal cancer will also expand. The research participants will be more diversified in the future, including patients with metastatic rectal cancer, patients with recurrent rectal cancer, and young patients with rectal cancer. The research themes will also keep pace with the times, whereas new treatment modalities, such as radiotherapy combined with different chemotherapeutic agents, SBRT, and MR-guided neoadjuvant radiotherapy, will continue to be explored. In conclusion, we hope this article can provide some inspiration for relevant researchers and clinicians.The original contributions presented in the study are included in the article/CQ contributed to the conception and design of this paper. YX, MQ, and WH downloaded and organized related papers. YX, MQ, WH, and SH contributed to all tables and figures and the main manuscript. CT, FN, XJ, DW, ML, and QL revised and supplemented the manuscript. All authors read and approved the final manuscript.This study was supported by the National Natural Science Foundation of China (NSFC-U1504818), Science and Technology Foundation of Henan Province , Natural Science Foundation of Henan Province (182300410359), Henan Provincial Education Fund (19A320020), Postgraduate Cultivating Innovation and Quality Improvement Action Plan of Henan University .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.


It is well known that children with autism spectrum disorder (ASD) had executive functions deficit. However, it is still unclear whether the poor dietary quality is related to the impairment of executive functions. The current study aimed to explore the association between dietary quality and executive functions in children with ASD.A total of 106 children with ASD (7.7 ± 1.3 years) and 207 typically developing (TD) children (7.8 ± 1.3 years) were enrolled from Guangzhou, China. The Chinese version of Behavior Rating Scale of Executive function (BRIEF), the working memory subscales of the Chinese version of Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), and the Stroop Color-Word Test (SCWT) were used to measure the participant's executive functions. The food frequency questionnaire (FFQ) was used to collect the dietary intake information, and the Chinese Diet Balance Index (DBI_16) was used to evaluate the dietary quality. Generalized linear models were used to estimate the association between dietary quality and executive functions.P < 0.05), while High Bound Score (HBS) and LBS were positively correlated with the organizable subscale score of BRIEF . Compared to TD children, children with ASD had a higher proportion of moderate and high levels of insufficient dietary intake  and moderate level of unbalanced dietary intake (36.8% vs.21.3%), higher scores on all subscales of BRIEF (P < 0.01), and lower score on the working memory , while there was no difference on the SCWT.In children with ASD, Low Bound Score (LBS) was positively correlated with the working memory subscale score of BRIEF (β = 0.23, 95% CI: 0.02–0.44, Poor dietary quality was associated with the impairment of working memory and organizational capacity in children with ASD. This study emphasized the importance of dietary quality in executive functions among children with ASD, and attention should be paid to improving their dietary quality. Autism spectrum disorder (ASD) is a developmental disorder characterized by social communication deficits and repetitive/unusual sensory-motor behaviors , with a Although there were many studies on dietary problems in children with ASD, the traditional dietary evaluation was based on specific foods or nutrient intake, with inconsistent results. Evans et al.  comparedUp to now, there are many studies exploring the relationship between dietary quality and executive functions in TD children see . Riggs evia appropriate inhibitory control. MI indicates the child's ability to initiate, plan, organize, and sustain future-oriented problem-solving in working memory. Corresponding to the two indices, the face-to-face experimental tasks used in the current study included working memory subscales of the Chinese version of Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and the Stroop Color-Word Test (SCWT), a classic inhibitory control task.Notably, comparatively little is known about the association between dietary quality and executive functions among children with ASD. Firstly, few studies have focused on children with ASD. Secondly, the dietary assessment methods used in previous studies cannot accurately reflect the complexity of dietary quality. Thirdly, there was a lack of overall assessment of the executive functions in children. To address these gaps, we used the revised Chinese Diet Balance Index (DBI_16) to comprehensively evaluate the dietary quality of Children with ASD, including indices of insufficient, excessive, or imbalanced dietary intake. We also used the parent-reported questionnaire of BRIEF and face-to-face experimental tasks to comprehensive evaluate the executive functions. BRIEF included 2 indices: the Behavioral Regulation Index (BRI) and the Metacognition Index (MI). BRI reflects the ability of the child to shift cognitive set and modulate emotions and behaviors In short, the purpose of the study was to explore the relationship between dietary quality and executive function in children with ASD.We used the baseline data of the ongoing cohort of “the Guangzhou Study of Children with ASD” in Guangzhou, China. We selected a subsample of 107 children with ASD and 209 TD children from Jan, 2021 to Sep, 2021. One child with ASD missed data from subscales of BRIEF and 2 TD children with Intelligence Quotient (IQ) below 80 were excluded. Finally, 106 children with ASD (89 boys and 17 girls) and 207 TD children (113 boys and 94 girls) were included in the final analysis. All the 313 participants took part in SCWT. But only 76 children with ASD and 173 TD children finished SCWT, because it was based on literacy. We obtained working memory index and a full-scale intelligence quotient (FSIQ) of 99 children with ASD and 207 TD children, who completed WISC-IV. All the children with ASD were diagnosed by a combination of the Childhood Autism Rating Scale (CARS) and an expert clinician. Their diagnosis was further confirmed by two professional child psychiatrists using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Revision (DSM-5) criteria. Detailed inclusion criteria for both groups were as follows: (1) chronological age between 6 years 0 months and 12 years 0 months; (2) voluntary participation of the children's parents. Exclusion criteria included: (1) dyslexia, seizures, head trauma, cerebral palsy, severe visual or auditory impairment, other movement disorders; (2) genetic or chromosomal abnormalities.Children underwent face-to-face measures performed by trained psychometrists or research assistants at the research center. Information on demographic, physical activity, executive functions, and dietary intake status was obtained through in-person interviews with primary caregivers or validated tools/questionnaires. All the parents of the participants signed informed consent forms. The study was approved by the Ethical Review Committee for Biomedical Research, Sun Yat-Sen University (2015-No.29).We assessed executive functions by parent-reported questionnaire and face-to-face experimental tasks. The rating scale we used was the Chinese version of BRIEF for children aged 6 to 18 years. The BRIEF is a validated 86-item questionnaire with the Cronbach α coefficient ranging from 0.74 to 0.96 . It inclChildren's executive functions were also assessed by face-to-face experimental tasks including working memory subscales of the Chinese version of WISC-IV, and the classical inhibitory control tasks . The WISC-IV's working memory index is a commonly index to test working memory of executive functions. Working memory subscales include Digit Span and Letter-Number Sequencing subtests; Digit Span assesses short-term working memory by asking the child to repeat a series of increasingly long number sequences forward and then backward; Letter-Number Sequencing is a well-validated measure of manipulation working memory. The tester read a series of numbers and letters, then asked the child to recall the numbers in ascending order and the letters in alphabetical order. The SCWT is a classical test of inhibition , which wThe dietary intake information of children was collected by a parent-reported Food Frequency Questionnaire (FFQ). The FFQ contains 20 kinds of food such as cereal, vegetables, fruit, animal food, condiments. The questionnaire had been validated before the study , the aveWe assessed dietary quality by the DBI_16 revised by He et al. , which cvia questionnaire.The children's age, gender, maternal age and education level, paternal age and education level, and per capita monthly household income were reported by parents 2 (m2). The definitions of overweight and obesity were using the screening thresholds for overweight and obesity in Chinese school-age children and adolescents released by the National Health and Family Planning Commission in 2018  was estimated by dividing weight (kg) by height in 2018 .Physical activity was assessed by the International Physical Activity Questionnaire short format which included vigorous physical activity, moderate physical activity, and walking. For the above activities, respondents were asked to review the activities of at least 10 min each time in the past 7 days and answer the number of days of activities and the average daily duration. Based on the total metabolic equivalent (MET), physical activity status was classified into three categories: low, moderate, and high .via the Chinese Version of WISC-IV, which provides a full-scale intelligence quotient (FSIQ) based on the sum of scores from the 10 core subtests . The results were presented as coefficient estimates (β) with a 95% confidence interval (CI). For all analyses, the statistical significance was set at P-value < 0.05 (two-sided). We conducted all statistical analyses with R 4.0.3 statistical software , a higher proportion of the low and moderate levels of physical activity , and lower maternal education level  and family economic situation . There were no differences between groups in children's age, category of BMI, or paternal education level.The demographic characteristics of the included children are shown in P < 0.05). HBS and LBS had positive associations with the organizable subscale score of BRIEF  in the adjusted model, while other indicators had no association with other components of executive functions.In addition, there was a null association between DBI_16 indicators and all executive function scores in the adjusted models in TD children see .P < 0.01), dairy  and dietary variety  categories than TD children.As shown in P < 0.01), dimensions scores  and all subscale scores, lower working memory score . There was no difference in reaction time and correct rate of SCWT between the two groups.The current study showed that higher HBS was associated with worse organizable ability, while higher LBS was associated with worse organizable ability and working memory in children with ASD. Children with ASD had more problems of insufficient and unbalanced dietary intake compared to TD children. Children with ASD also had lower scores of BRIEF and working memory than TD children, while there was no significant difference in SCWT. To our knowledge, it was the first study using the DBI_16 scores to evaluate the dietary quality of Chinese children with ASD and explore the association of dietary quality with executive functions in children with ASD.Chanyi approach in 1 month had positive effects on improving mental flexibility, response inhibition, and planning in children with ASD  to comprehensively reflect children's reality-based executive functions. Third, the dietary quality was assessed by DBI_16 rather than single food intake, which can represent the overall dietary information of children with ASD. However, some limitations should be considered. First, the current study was a cross-sectional design, thus it was impossible to determine the causal nature of the association between dietary quality and executive function in children with ASD. Further longitudinal studies or interventional studies are needed to confirm the relationship. Second, ASD represents a heterogeneity group of disorders, and most of the children with ASD in the current study were without ID, so the results couldn't reflect the association in autistic children with ID directly. Third, the study did not explore the relationship between dietary quality and cognitive flexibility which was an important component of executive function, and more studies were needed. Fourth, the dietary assessment in the current study was subjective reported, which could not accurately calculate the specific amounts of macronutrients and determine the intrinsic nutrient levels. Furthermore, the self-reported investigation might be influenced by parents' recall bias and personal expectations. Therefore, more objective investigations are needed to comprehensively collect children's dietary intake information.Poor dietary quality was associated with the impairment of working memory and organizational capacity in children with ASD. Compared to TD children, children with ASD had poorer dietary quality and executive functions. This study emphasized the importance of dietary quality in executive functions among children with ASD, and attention should be paid to improving their dietary quality.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 was approved by the Ethical Review Committee for Biomedical Research, Sun Yat-Sen University (2015-No.29). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.JJ and XL: conceptualization, supervision, project administration, and funding acquisition. XW and XS: methodology, formal analysis, and writing-original draft preparation. XW: study design, manuscript revise, and data curation. XW, XS, YJ, XZ, MC, XG, SL, XO, and TG: data collection. XS, XW, LC, and XL: writing - review and editing. All authors read and revised the manuscript, and approved the final manuscript.This work was supported by the Key-Area Research and Development Program of Guangdong Province (2019B030335001), the National Natural Science Foundation of China (81872639), and Guangdong Basic and Applied Basic Research Foundation (2021A1515011757).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.


Quinolones, broad-spectrum antibiotics, are frequently prescribed by urologists for many urological disorders. The mechanism of their bactericidal activity is based on the inhibition of topoisomerase II or IV complex with DNA, which consequently leads to cell death. It has been observed that these antibiotics also act against the analogous enzymes present in eukaryotic cells. Due to their higher accumulation in urine and prostate tissue than in serum, these drugs seem to be ideal candidates for application in genitourinary cancer treatment. In this study, an extensive literature review has been performed to collect information about concentrations achievable in urine and prostate tissue together with information about anticancer properties of 15 quinolones. Special attention was paid to the application of cytotoxic properties of quinolones for bladder and prostate cancer cell lines. Data available in the literature showed promising properties of quinolones, especially in the case of urinary bladder cancer treatment. In the case of prostate cancer, due to low concentrations of quinolones achievable in prostate tissue, combination therapy with other chemotherapeutics or another method of drug administration is necessary. Quinolones are chemotherapeutics discovered in 1962 by Lescher et al. who have synthetized nalidixic acid . It has in vitro, indicating their potential usage for cancer patients. Induction of apoptosis, cell cycle arrest, and disruption of mitochondrial membrane potential are examples of quinolones’ mechanism of action against cancer cells  is the most frequent type of cancer among men in Europe and second around the globe. According to the recent incidences in 2020, almost 1,400,000 new PCa patients with 375,000 deaths were noticed . Over thBladder cancer (BCa) is a much less common type of cancer than PCa. Worldwide, it is the 10th most common type of cancer, with 573,000 new cases and 213,000 deaths. It is more common in men than in women (4-times) . The incE. coli has dramatically emerged due to fluoroquinolone overuse and has become a challenge in the medical therapy of patients with urinary tract infection (UTI) (Escherichia coli (ESBL-EC)  . FluoroqESBL-EC) .Escherichia coli. However, in light of rising resistance, current prescribing guidelines recommend fluoroquinolones as second-line drugs  for normal and cancer cells other than those originating from the genitourinary system were also included. Additionally, the PubMed database was searched for information about concentrations achievable in urine and prostate tissue after oral or intravenous administration of different quinolones. The databases were reviewed until the end of June 2021.Extracted data included the following elements: type of quinolones and their derivatives, quinolone concentrations, type of tested cells, incubation time, influence on cell viability, changes induced in cells, measurement results, the way of assessing results, and the effectiveness of tested compounds. Among the 17 quinolones described, antitumor activity was examined for 15 of them, and no cytotoxic effects of grepafloxacin and finafloxacin have been analyzed so far in the literature. For other compounds, 54 full-text articles were included for the analysis of anticancer properties of quinolones. Detailed data extraction for each quinolone is presented in Most of the analyzed quinolones reach high concentrations in the urine Table 1.50 presented in 50 value after 72 h of incubation. Ciprofloxacin has a stronger activity than levofloxacin, ofloxacin, and fleroxacin due to the lower IC50 values obtained for three  or one (T24) tested cell line, respectively. Levofloxacin has better cytotoxic properties against the T24 cell line and similar to the BOY cell line compared to ofloxacin. The calculated IC50 values of ciprofloxacin, norfloxacin, enoxacin, and levofloxacin are achievable in the urine  show a stronger cytotoxic effect in acidic pH, and such conditions are present in urine. The results discussed above indicate that all quinolones presented in 50 values calculated for all tested cell lines. Low IC50 values were also calculated for norfloxacin, levofloxacin, and enoxacin, but compared to ciprofloxacin, a small number of data available in literature do not allow to draw reliable conclusions about their effectiveness. In our recent study, we additionally, for the first time, analyzed the influence of ciprofloxacin and levofloxacin on bladder cancer cells in 3D culture (spheroids). We showed that IC50 values calculated after drug incubation with cells in standard 2D culture were not effective in 3D culture. Only the concentration reducing 90% of cell viability was effective in cell viability reduction and caspase 3/7 activation in 3D culture. These concentrations were 1,500 and 245 µg/ml for ciprofloxacin and 4,670 and 730 µg/ml for levofloxacin, respectively, after 24 and 48 h of incubation with drugs. The concentration obtained after 48 h of incubation with ciprofloxacin is achievable in urine, which suggests the potential of this drug in clinical application. Additionally, we tested both drugs on a non-malignant uroepithelial cell line. Our results showed that both tested drugs were more effective against cancer cell lines which were more pronounced in 3D culture ; however, the majority of the compounds mentioned above (except enoxacin and norfloxacin) were tested only on the T24 cell line Table 3. culture .There is a lack of data in the literature about the concentration of some quinolones in prostate tissue. This concentration has not been determined for nalidixic and pipemidic acids, grepafloxacin, sparfloxacin, gemifloxacin, and finafloxacin. The use of other quinolones, in most cases, allows reaching a higher concentration in the prostate tissue than in the serum Table 2.50 values  can be obtained  have been so far studied on prostate cancer cell lines . In six studies, the use of ciprofloxacin was especially focused on prostate cancer, and the other two studies analyzed modified quinolones on the panel of various cell lines; therefore, information about prostate cancer is very limited Table 3.0 values , 76. In obtained . Ninety his drug , 72. In o et al. . Levofloo et al. . In the e tissue . In the e tissue . The IC5TOP2A and TOP2B genes, two isomers of topoisomerase II, were observed after ciprofloxacin and levofloxacin treatment . Three quinolones have been tested on an animal model so far. After oral administration of fleroxacin, a reduction in chemically induced bladder cancer was observed only when tested fluoroquinolone was used together with 5-FU  reach very high concentrations in urine both after oral or intravenous administration. Additionally, long-time administration of quinolones in high doses is safe, and if the risk of drug resistance is not taken into account, such therapy doses do not cause side effects. That is why quinolones are frequently used by urologists . AnotherTK: study design, data analysis, data collection, writing; SF: data collection, writing; JA: writing; KS: writing; MR: writing; TD: review and editing, supervision; MP: review and editing, supervision. All authors contributed to the article and approved the submitted version.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.


Implant survival was calculated using the Kaplan–Meier method. Results: Both groups showed statistically significant improvements at each follow-up compared with the preoperative values (p < 0.05). The CR group showed a higher flexion degree at T1 than the PS group . No differences were found between the two groups regarding survival rate . Three failures were noted in the CR group, while there were four in the PS group. Conclusions: This prospective clinical study demonstrates that CR and PS TKA had similar clinical outcomes in octogenarians with regard to knee function, postoperative knee pain, and other complications. Prosthesis survivorship for CR and PS TKA were both satisfactory, and in selected octogenarian patients, CR TKA should always be considered because of the reduced surgical time.Purpose: The primary goal of this study was to compare survivorship and functional results in individuals aged 80 and over who underwent total knee arthroplasty (TKA) with cruciate-retaining (CR) or posterior-stabilized (PS) implants. Methods: We prospectively analyzed the clinical records of two consecutive cohorts for a total of 96 implants in patients aged 80 years or over. The first cohort consisted of 59 consecutive cemented PS cases, while the second cohort comprised 37 consecutive cemented CR cases. The decision to either perform a PS or CR arthroplasty was taken based on preoperative magnetic resonance imaging and intraoperative findings. The clinical evaluation entailed evaluating each patient’s visual analogue scale for pain (VAS), range of motion (flexion and extension), Knee Society Score (KSS), and Oxford Knee Score (OKS). Each patient was clinically evaluated the day before surgery (T Osteoarthritis (OA) is the world’s most common joint ailment and one of the leading causes of pain and impairment in the aged. Age appears to be the single largest risk factor for the development of primary OA in vulnerable joints, according to accumulating research .People live longer across the world. Between 2020 and 2050, the number of people aged 80 and over is predicted to treble, reaching 426 million. Thus, managing the huge burden of osteoarthritis in this alarmingly aging population can prove to be a real challenge for healthcare professionals across the globe [In the end, it is the substantial burden of pain that patients with OA bear that is of paramount concern. This burden can be fundamentally classified into pain and functional impairment, which when combined have a significant negative impact on an individual’s quality of life (QOL) .Osteoarthritis predominantly affects the weight-bearing knee joints, and total knee arthroplasty (TKA) remains the standard-of-care treatment for advanced arthritis in patients in whom conservative measures have failed. Conventional primary TKA uses two designs: one in which the posterior cruciate ligament (PCL) is preserved and the other in which the PCL is sacrificed. The former is termed cruciate-retaining (CR) prosthesis, and the latter is known as a posterior-stabilized (PS) design. In PS designs, the PCL is excised, and the implant design used incorporates an intercondylar tibial prominence that can act as a substitute for serving the function of the PCL. In flexion, this part articulates with the femur, leading to a femoral roll-back. The possible advantage of the above mechanism is that it provides longer lever arm in the quadriceps mechanism, thereby providing a slightly greater range of motion. Various studies have supported the slight increase in the range of motion at the terminal flexion. Additionally, the femoral roll-back mechanism reduces shearing stress on the polyethylene liner. Cruciate-retaining implant designs, on the other hand, have a clear advantage in terms of knee stability and proprioception. In light of the retained PCL, studies on the cruciate-retaining group have suggested that this design has near-normal knee kinematics ,5,6.There is a paucity of reasearch on the long-term functional outcomes comparing both designs. However, a number of studies have compared the short- and medium-term functional results, and they have not demonstrated any significant difference in early functional outcomes. These studies have focused on patients aged 60–80 years old, with a small fraction of patients aged 80 and over. According to Swedish Knee Arthroplasty Register, the incidence of knee arthroplasty in patients aged 75 to 84 years old was 665.2/100,000 inhabitants for women and 546.4/100,000 for men [There are few studies comparing functional outcomes in the exclusive 80+ age group, which is growing swiftly. As a result, we believe it is critical to examine the results in the 80+ age range ,8,9The primary goal of this study was to compare survivorship and functional results in individuals aged 80 and over who underwent TKA surgery with CR or PS implants.All the procedures in this study involving human participants followed the ethical standards of the institutional and/or national research committee as well as the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was conducted following the STROBE guidelines . InformeThe inclusion criteria were as follows: 24-month minimum follow-up; TKA performed by a single surgeon; severe knee pain and disability requiring primary unilateral TKA based on physical exam and medical and radiographic history; ability to cooperate in the required postoperative therapy; ability to complete scheduled follow-up evaluations as described in the informed consent form.The exclusion criteria were as follows: follow-up < 24 months; multiple comorbidities and neurological illnesses ; revision surgery; previous surgery to the affected knee (except arthroscopy for meniscectomy or anterior cruciate ligament (ACL) reconstruction).The indication for TKA was either primary or secondary grade IV osteoarthritis of the knee. All preoperative radiographs were assessed using the Kellgren and Lawrence classification system .® Bone Cement R  [Each patients underwent plain radiographies and magnetic resonance imaging (MRI) preoperatively. Patients were allocated to receive PS or CR implants. The allocation followed the anatomopathological features of PCL at imaging, clinical, and intraoperative findings. If the PCL was intact and effective, a CR TKA was implanted, while in case of the lack of or a deficient PCL, a PS TKA was implanted. A standard medial para-patellar approach was used in all patients. No tourniquet was used. All patients received a cemented Vanguard Knee System  following the manufacturer’s instructions. Both tibial and femoral components were cemented using RefobacinIN, USA) .All arthroplasties were performed with a medial para-patellar approach without the use of a tourniquet, and the cementation of both tibia and femur was performed in all patients.Both patient groups followed the same rehabilitation protocol, which involved passive mobilization for both types of surgery; from day one, an active progressive mobilization of the joint and assisted walking with two crutches were started. Gradually and according to each patient, it was, therefore, recommended to increase the load during walking, continuing with isometric muscle-toning exercises until the total abandonment of walking aids.0) and at two consecutive follow-ups at least 1 (T1) and 2 (T2) years after surgery [All clinical assessments were performed by two independent clinicians who were not involved in the index surgery. The clinical evaluation entailed assessing each patient’s visual analogue scale for pain (VAS), range of motion (flexion and extension), Knee Society Score (KSS), and Oxford Knee Score (OKS). Each patient was clinically evaluated the day before surgery  or death of the patient .t-test, assuming a mean difference of 1, a standard deviation of 1.5 for both groups, 5% alpha, and 80% power. Given the same parameters, this sample also had 99% power to detect pre–post differences using a paired t-test, assuming a mean difference of 1, a standard deviation of 1.5, a correlation of 0.25 between measurements, and 5% alpha. Additional subjects were recruited to ensure statistical significance in case of adverse events.An estimated sample of 74 subjects, 37 for each group, was required to compare the VAS values between CR and PS groups with a two-sided t-test or, for categorical variables, a chi-squared test was performed to assess preoperative and clinical differences between CR and PS groups.Summary statistics are presented as means and standard deviations (SDs) or absolute frequencies and percentages. After having tested the distribution of continuous variables, a t-test was used to evaluate inter-group differences at each follow-up. Second, to assess differences based on time intervals in each group for each score, a mixed model analysis was performed, since it allowed us to consider correlations among repeated measures and to test the covariance structure. Compound symmetry, autoregressive models with both homogeneous and heterogeneous variances, and unstructured covariance structures were tested, and the unstructured covariance was evaluated as the best covariance structure using the likelihood ratio test and Akaike information criterion. Bonferroni adjustment was applied for multiple comparisons. Survival curves were estimated to assess differences in the failure rate between CR and PS groups. A Cox regression model was also performed using failure as the independent variable and group as a covariate. Lastly, according to the variable distribution, Pearson or Spearman correlations among the scores and the demographic and clinical variables, i.e., age, sex, and side, were estimated. All tests were two-sided, and p-values less than 0.05 were considered statistically significant. Statistical analyses were conducted in R version 4.1.1 .To examine the score differences between groups, first, a p > 0.05). The only statistically significant difference pertained to surgical time, which was significantly lower in the CR group . All data are reported in The two groups resulted homogeneous regarding all demographic and preoperative values (p < 0.05). The CR group showed a higher flexion degree at T1 than the PS group . Detailed results are reported in Both groups exhibited statistically significant improvements at each follow-up compared with the preoperative values . Three failures were noted in the CR group, while there were four in the PS group. Details on failures and risk survival are reported in No differences were found between the two groups regarding survival rate , which is well supported by the literature.Preoperative scores were assessed in terms of the VAS score, flexion/extension of knee joint, and two outcome scores, the KSS and Oxford Knee Society scores. The two groups were homogeneous regarding all preoperative values.The clinical evaluation of our patients included the visual analogue scale for pain (VAS), range of motion (flexion and extension), KSS, and OKS. The CR group showed a higher flexion degree than the PS group (at the one-year follow-up) even though the improvements in flexion movement became marginal at the two-year follow-up. This is a striking finding that we did not come across in any of the major studies highlighted below.In a multi-centric prospective randomized clinical trial, Harato et al. performed a mid-term comparison of CR vs. PS knees in a cohort of 222 patients from seven major surgical centers around the world. At the 5-year follow-up, the CR group had a flexion of 113.7°, while the PS group had a flexion of 117.0°, with a statistically significant difference. This study, with the longest follow-up and comparable cohorts with respect to age, is in stark contrast with our finding that the CR group had a higher flexion at the short-term follow-up. The author highlighted the postoperative stiffness of knees; in total, 7 out of 99 CR knees and 1 out of 93 PS knee were found to be stiff, and this was attributed to the difference in kinematics in the two designs involved as the possible explanation .Tanzer et al., in their study, found no differences in the range of motion between the CR and PS groups preoperatively or at any time postoperatively. However, in their study, the CR group had a mean age of 68 years, and the PS group had a mean age of 66 years, making it difficult to compare it with our study, where both the CR and PS groups had only patients in the over-80-year age group (35). In contrast to the above study, Maruyama et al. identified significant improvements in knee flexion after surgery only in PS knees, and the mean age of the study group was around 74.3 years (36). Wang et al. in their prospective clinical trial on 267 knees with an average participant age of 55 years found that PS knees had a higher flexion than CR knees at an average follow-up of 42 months .All the above studies had patients in the age group 44–89 years, and they categorically stated that PS knees demonstrated a higher postoperative knee flexion than CR knees at short- and medium-term follow-ups. Only patients aged 80 years and over were included in our study, and our short-term results very clearly indicate a higher postoperative knee flexion in the CR group.The postoperative gain in extension was the same with regard to CR and PS knees, which holds true with regard to the patients in the other studies here highlighted.Previous studies have suggested that surgeons should prefer the PS design for TKA, especially to achieve a higher postoperative range of motion in patients with high functional demands, but in our cohort, all patients were octogenarians, so they were supposed to have a sedentary lifestyle .Due to the lower physiological activity and lowered life expectancy, fears of revision surgery (and associated risks and complications) are minimized. The morbidity and complications associated with CR TKA, such as surgical time, and results in the form of pain relief and simpler rehabilitation provide high satisfaction levels . The retMost authors have found that there is an increase in the risk of complications in patients aged over 80 years undergoing TKA. Kuperman , in his This article categorically states an increase in mortality in terms of myocardial infarction, pulmonary embolism and deep-vein thrombosis. A few papers have quoted a statistically significant trend of mortality ,29, but Our study had a few limitations. Only age-matched cohorts were considered in this study, and other variables were not considered. We only considered a short-term follow-up of two years, which we believe is a serious limitation. Anteroposterior and mediolateral laxity measurements were not considered in our study. A large majority of the studies we reviewed only had elderly populations aged 75 years and under.This prospective clinical study demonstrates that CR and PS have similar clinical outcomes in octogenarians with regard to knee function, postoperative knee pain, and the other complications. Prosthesis survivorship for CR and PS are both satisfactory, and in selected octogenarian patients, CR should always be considered, taking into the reduced surgical time as well.


Pregnancy is associated with substantial stressful experiences. There are controversies concerning the positive and negative roles of social support during pregnancy. This research aimed to study the association of social support with the pregnancy-related stress.In the current cross-sectional research, 200 pregnant women were recruited through convenience sampling from two teaching hospitals affiliated with Babol University of Medical Sciences and a private obstetric clinic. The women completed two self-reported questionnaires during prenatal care appointments. The questionnaires included the Revised Prenatal Distress Questionnaire (NuPDQ) and Social Support Questionnaire (SSQ).P<0.001), as well as the scores of its four subscales, namely medical problems (P<0.001), parenting (P=0.25), infant health stress (P=0.006), and pregnancy symptoms (P=0.001). Based on the linear regression models, the social support of neighbors was significantly related to the medical problem-associated stress in pregnant women , pregnancy symptom , and fear of childbirth . Furthermore, the neighbors’ social support  and the total score of social support  were significantly associated with the total score of pregnancy stress.A significantly positive association was observed between the social support of neighbors and the total score of pregnancy stress (Neighbors’ support, as a component of social support, was found to be significantly related to pregnancy stress. This study recommends that healthcare providers consider the positive and negative impacts of social support during the pregnancy period. Social support is a multi-dimensional concept classified into emotional support, network, esteem, material resources, and informational support . Social Pregnancy is associated with substantial physiological and psychological changes as well as stressful experiences . PregnanThere are controversies about the positive and negative roles of social support during pregnancy. Negative social support refers to negative social interactions, including discouraging emotional expression, invading privacy, criticizing, and not offering assured help . Most avWe carried out a cross-sectional investigation at two teaching hospitals affiliated with Babol University of Medical Sciences in addition to a private obstetric clinic, from September 2018 to April 2019. The inclusion criteria were pregnant women aged above 18 years and with a minimum of five years of education. Women with a high-risk pregnancy, including hypertension, diabetes, maternal bleeding, and preterm labor, on top of those with a history of serious medical conditions, psychiatric problems, and drug abuse /alcohol addiction were excluded.P =0.6). The sample size was thus assessed as 188 with respect to α=0.05, P=0.6, and d=0.07. The researchers increased the number to 200 to compensate for the incomplete and missing data In order to recruit the subjects, we used convenience sampling method. Prior to starting the research, we calculated the ratio of pregnancy stress in a pilot study  so that the rural and low-income women could also be sampled. Furthermore, a private practice was randomly selected to include women with a high level of socio-economic status in the sampling. Thus, 100 rural women were selected equally from both hospitals  in addition to 100 urban women from private offices, to control both socio-economic status and place of residence.A total of 245 pregnant women were asked to participate in the study via convenient sampling. They were recruited by a member of the research team (first author) and two midwives, who interviewed the women and gathered their medical and obstetric histories, as well as demographic information, in order to determine their obstetric risks and appropriateness based on the inclusion criteria. Furthermore, the midwives gave the ladies a brief explanation about the study’s objective and how to fill out the surveys. The midwives entered every eligible women in the study. Eventually, 200 eligible women (100 women living in village and 100 in city) provided written informed consent. Accordingly, the response rate was 81.6%.All the 200 participants completed two self-reported questionnaires in their prenatal care appointments. These questionnaires included the Social Support Questionnaire (SSQ) and Revised Prenatal Distress Questionnaire (NuPDQ) (15-17).The Medical Ethics Committee of Babol University of Medical Sciences approved this study (IR.MUBABOL.HRI.REC.1397.108).Cronbach’s alpha for the subscales’ internal consistency ranged from 0.86 to 0.95.Fleming et al. (1982) developed this questionnaire which comprises 25 items with five subscales . The responders would reply to each item as yes/no. The range of the total score was between 0 and 25 . The valCronbach’s alpha for internal consistency of the scale was 0.91. We used the NuPDQ’s validated Persian version with five aspects, namely medical problem, parenting, infant healthy, pregnancy symptom, and fear of childbirth [This questionnaire is a modified version of the PDQ, with both tools being frequently employed for assessing pregnancy stress , 18. NuPildbirth .t tests. The correlations between social support and pregnancy-associated stress were measured with Pearson’s test. In order to explore the associations between the five subscales of pregnancy stress, social support was embedded into two linear regression analyses with adjusted and non-adjusted models. Based on each subscale of social support , a number of simple linear regression models were developed. Five variables, including age, place of living, level of education, job, gestational age, and duration of marriage, were considered as covariates in the adjusted models. The Statistical Package for the Social Sciences (SPSS) software (version 18.0 ) was used to analyze the data. A significant level was defined as a P-value of <0.05.The descriptive analysis of all the variables  was presented as percentages, means, and standard deviation. Since the quantitative variables of the study, such as self-care, depression, and fear of COVID-19, followed a normal distribution, we used parametric tests to compare the means. The mean comparison of pregnancy stress and social support between the village residents and city residents was performed utilizing student Table P=0.007) as well as neighbor’s support (P=0.005). Furthermore, a significantly negative association was seen between the working women and pregnancy stress. There was a significantly negative association between the place of residence and belief in social support (P=0.020). On the other hand, a significantly positive association was found between the gestational age of the women and pregnancy stress (P=0.025), as well as neighbors’ support (P=0.013). However, there was no significant correlation between their age, age of marriage, or the total scores of both social support and pregnancy stress.As shown in Table P<0.001), as well as of the four subscales of medical problems (P=<0.001), parenting (P=0.025), infant healthy stress (P=0.006), and pregnancy symptoms (P=0.001). The belief in social support was significantly and negatively correlated with the total pregnancy stress and stress concerning the infant’s health (P=0.033) on top of pregnancy symptoms (P=0.006). A significantly positive association was observed between the total score of social support and pregnancy stress (P=0.011) as well as stress concerning the infant’s health (P=0.034). Nevertheless, there was no significant association between the subscales of friends’ and family support and pregnancy stress along with its subscales, including medical problems (P<0.001), parenting (P=0.025), infant health stress (P=0.006), and pregnancy symptoms (P=0.001).Table Table β = 0.147, P = 0.047). The social support of neighbors  as well as family support  were significantly related to parenting stress in the non-adjusted model. The social support of neighbors  and general support were significantly and positively related to the infant’s health. However, the social support belief  was negatively related to the stress in pregnant women. Furthermore, the neighbors’ social support  was positively related to pregnancy stress symptoms in the subjects. The neighbors’ social support  and general support  were positively and significantly related to the fear of childbirth for pregnant women. Finally, in the adjusted model, the neighbors’ social support  and total social support score  were positively and significantly related to the total score of pregnancy stress.The support of neighbors was the independent variable related to the stress caused by medical problems in the pregnant women regression  examined the impact of neighborhood-related stressors and stress-relieving strategies on mental health. This research looked at the link between local stressors, stress coping techniques, and risk of adults’ mental health issues. The study found that a lower likelihood of mental illness in neighboring areas was associated with further stress-buffering mechanisms. People with low levels of social support in neighborhoods were also at a higher risk of elevated levels of social isolation (low average household occupancy) and mental illness [In order to answer the question of how social support is positively associated with women’s stress, we assessed the relationship between the subscales of social support and pregnancy stress. It was revealed that only one of these subscales, namely that of neighbors, was significantly and positively correlated with the total score as well as all the subscales of pregnancy stress. The results of regression analysis also confirmed that the neighbors’ support was significantly associated with the total score of social support in pregnancy stress. A few studies have reported the association between neighbors’ support and stress in pregnant women. Inconsistent with our results, a study in USA reported that lower neighborhood quality based on four measures  was related to a higher level of mental stress during pregnancy . Vinikoo illness .The reason behind the discrepancy between our study results and those of other works, especially regarding the neighbors’ support, is not clear. We could suggest that this be addressed in future research. Nevertheless, it could be associated with certain probable methodological differences between the investigations regarding the difference in the inclusion criteria, different scales, different social cultures, and socioeconomic situation of the participants.The findings herein can have clinical implications. The current research can suggest researchers to consider all the subgroups of social support, not only the total scores in data analysis, as well as interpretations of social support and stress. Certainly, further research is needed to develop assessment systems that include both merits and downsides of social interactions. In addition, future research should concentrate on developing a theoretical framework for understanding how neighbors’ support influences pregnant stress.One of the study’s strengths was that it looked at the association between social support and all its components with pregnancy stress. It also highlighted how one of the subcomponents of social support (neighbor support) was independently and significantly related to pregnancy stress. Meanwhile, a limitation of the study was that it was cross-sectional; therefore, in this work, the association between social support and pregnancy stress did not mean causal. Longitudinal investigations are also required to obtain a better understanding of the effect of social capital, particularly neighbors’ support, on pregnancy stress. Another limitation was the use of self-reporting tools for the participants rather than observation of the interactions with neighbors, which may have caused bias in the results. It could be recommended that further research collect information by directly observing the neighbors’ interactions with pregnant women. The small sample size, low number of employed women, and the use of convenient sampling methods were some other limitations of the study. Ultimately, the women may not represent the general population since our sample was selected from two obstetrics clinics in a referral hospital and a private practice.The findings demonstrated that social support does not always result in positive experiences for pregnant women. The study highlighted the negative effects of neighbors’ support on stress in this population. Healthcare providers are recommended to pay further attention to the positive and negative effects of social support during the pregnancy period. More research, such as interventional planning, would be conducive to reducing the effect of negative interactions of pregnant women during prenatal care.


Cancer-induced bone pain (CIBP) is a special type of cancer pain and lacks safe and effective treatments. Acupuncture is a potentially valuable treatment for CIBP, studies evaluating the effect of acupuncture on CIBP have increased significantly, but the safety and efficacy of acupuncture to control CIBP remains controversial.To provide the first meta-analysis to evaluate the safety and efficacy of acupuncture in CIBP management.CNKI, CBM, Wanfang, VIP Database, PubMed, Embase, and Cochrane Library were searched from their inception until 1 June 2022.RCTs with primary bone tumor patients or other types of primary cancer companied by bone metastases as the research subjects and to evaluate the efficacy of acupuncture treatment alone or combined with the control treatment were included. Meanwhile, RCTs should choose the pain score as the primary outcome and pain relief rate, frequency of breakthrough pain, analgesic onset time, analgesia duration, quality of life, and adverse events as reference outcomes.We designed a data-extraction form that was used to extract key information from the articles. Data extraction study evaluation was conducted independently by two reviewers, and a third reviewer would resolve any disagreements. The risk of bias was assessed by the Cochrane Collaboration's tool for assessing the risk bias. The quality of the evidence for main outcomes was evaluated by the GRADE system. Mean differences (MD), relative risk (RR), and 95% confidence intervals (CIs) were calculated. The forest plots were performed using the Review Manager Software (5.3 version). Subgroup analysis was used to investigate the possible sources of potential heterogeneity. Descriptive analysis was performed in case of unacceptable clinical heterogeneity.I2 = 98%, P < 0.01). Subgroup analyses based on acupoints type partly explain the potential heterogeneity. The results also showed that acupuncture plus control treatment (compared with control treatment) was connected with relieving pain intensity, increasing the pain relief rate, reducing the frequency of breakthrough pain, shortening analgesic onset time, extending the analgesic duration, and improving the quality of life. We have no sufficient evidence to prove the effectiveness of acupuncture alone. Four RCTs reported only adverse events related to opioids' side effects. Evidence was qualified as “very low” because of low methodological quality, considerable heterogeneity, or a low number of included studies.Thirteen RCTs  were included, and all studies were at high risk of bias owing to lack of blinding or other bias. Eleven studies evaluated the effectiveness of acupuncture as a complementary therapy, and showed that acupuncture plus control treatment (compared with control treatment) was connected with reduced pain intensity (MD = −1.34, 95% CI −1.74 to −0.94; Q < 0.1; Acupuncture has a certain effect as a complementary therapy on pain management of CIBP, which not only mitigates the pain intensity but also improves the quality of life and reduces the incidence of opioids' side effects, although the evidence level was very low. In future, a larger sample size and rigorously designed RCTs are needed to provide sufficient evidence to identify the efficacy and safety of acupuncture as a treatment for CIBP. Cancer pain is highly prevalent in patients with cancer . UncontrAcupuncture is an ancient traditional Chinese medical practice involving stimulating specific acupoints and meridian channels to control pain and other symptoms . A varieFour Chinese-language databases and three English-language databases were searched from their inception through 1 June 2022: China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang, VIP Database for Chinese Technical Periodicals, PubMed, Embase, and Cochrane Library. The restriction was set for the language (English and Chinese) but not for investigation regions. Reviewers independently searched the articles using the following search terms: (cancer-induced bone pain OR bone cancer pain OR bone metastasis pain OR bone cancer OR bone metastasis OR Bone neoplasm OR cancer of the bone) AND . The equivalent search words were used in the Chinese databases. Please refer to The inclusion criteria were (1) study design: only randomized controlled trials (RCTs) were eligible, and (2) participants: patients were diagnosed with primary bone cancer or other types of primary cancer companied by bone metastases. CIBP patients were diagnosed by imaging or biopsy. There was well-defined localized pain in CIBP patients, and (3) the number of subjects in each group of one RCT should be greater than or equal to 20, and (4) intervention and control: the intervention group received at least one of the following acupuncture treatments: manual acupuncture, auricular point acupressure, moxibustion, catgut-embedding therapy, thumb-tack acupuncture, wrist-ankle acupuncture, transcutaneous electrical acupoint stimulation, warm acupuncture, and electroacupuncture with or without the combination of the control treatment, regardless of acupoints, frequency, and sessions. Treatments in the control group can be oral morphine, morphine injection, fentanyl, parenteral morphine, zoledronic acid, nerve block, sham acupuncture, placebo, or usual care, and (5) outcome measures: pain intensity was described as the primary outcome, which should be reported in each included study. Pain intensity can be measured by a pain measurement, such as the Visual Analog Scale for Pain (VAS Pain), the Numeric Rating Scale for Pain (NRS Pain), or the item of “the current pain item” in the Brief Pain Inventory (BPI). We determined pain relief rate, frequency of breakthrough pain, analgesic onset time, analgesia duration, quality of life, and adverse events as reference outcomes.The exclusion criteria were (1) studies related to qualitative studies, animal studies, case reports, or other topics not related to RCTs, (2) the same study, which was republished, (3) studies with incomplete original data, or data that could not be extracted and still unavailable after contacting the authors, and (4) there are obvious errors in the outcome, and the statistical methods are inappropriate, and (5) when experimental group applies a pain relief method which is different from the control group.Two reviewers (Zhao-bo Yan and Zhi-miao MuRong) examined all studies independently according to the inclusion criteria. We designed a data-extraction form using Microsoft Excel 2016 that was used to extract key information from the articles. The key information will be extracted from studies that meet the inclusion criteria for data analysis. The extracted data mainly included the first author, publication year, country, sample size, age, cancer type, therapy types, control group types, outcomes, duration of intervention, and acupoints. If the above information was unclear, the report's corresponding authors were contacted to provide clarification or additional detail. The extracted data were cross-checked and discrepancies were resolved by discussion and mediated by a third reviewer (Mai-lan Liu).First, included studies' quality was appraised with the Cochrane collaboration tool  in sevenI2 test and quantified by the I2 statistic , a fixed-effects model was used for meta-analysis. When the heterogeneity was significant , a random-effects model was used for meta-analysis. Subgroup analyses would be performed to analyze the source of heterogeneity. Descriptive analysis should be selected instead of a meta-analysis if P < 0.1 and the sources of diversity are unknown. Pooled effects were calculated, and a two-sided P-value < 0.05 was considered to indicate statistical significance.The meta-analysis was performed using the Review Manager Software (5.3 version). The effect size of dichotomous and continuous data was presented as relative risk (RR) and mean difference (MD); both were reported with a 95% confidence interval. The heterogeneity among trials was identified by the tatistic . When thThrough database searching, 582 papers were screened, from which 261 duplicate papers were removed. Further titles and abstracts reviewed excluded 290 records as they were animal studies, qualitative studies, case reports, or other topics unrelated to the present study. After a cautious reading of the full-text versions of the remaining 31 studies, 18 studies were excluded for not satisfying the inclusion criteria. Therefore, 13 studies were included, of which 12 –45 were We included 13 studies –46 in thvia the use of sealed envelopes and were low risk of allocation concealment. However, allocation concealment was unclear in the remaining studies. Acupuncture research is difficult to implement a blinding design in clinical practice owing to the special nature of acupuncture. Only two studies   see . Given t.01) see . The resI2 = 95%, P = 0.09)  see .I2 = 43%, Q = 0.09) was observed among included studies. Hence, a fixed-effect meta-analysis was used to pool the data from different trials. The meta-analysis showed a statistical difference in pain relief rate between the two groups [RR: 1.23 ]. The date are shown in Eight studies –43, 45 pP-value of Z-test < 0.01).Only one study  by Du exI2 = 89%, P = 0.10), so a random-effects model was used. The pooled data revealed that the experimental group could effectively shorten the analgesic onset time compared to the control group [MD: −11.27 ]. The date were shown in Two studies , 39 provI2 = 93%, P < 0.1) was signed between the two studies, and the study by Liu et al. . In the study by Ni et al. . The date are shown in The reporting on the analgesia duration was provided in two studies , 39. We u et al.  showed tI2 = 72%, P = 0.004). PROSQOL scale was used in the study by Huang et al.  compared with the control group (19.4%). The study by Gou et al. (P < 0.05) compared with the control group (22.50%). The details of adverse events are shown in Four , 39, 44 u et al.  reportedThe GRADE system was used to assess the quality of evidence for the outcomes in this review. In the present study, every outcome was qualified as “very low.” From the perspective of methodological quality criteria, most included studies failed to perform effective blinding or allocation concealment, which may result in a risk of bias. Inconsistency might exist because different methods measured the outcomes, and several acupuncture techniques were used across included studies. Some meta-analyses included a low number of studies which added the imprecision of evidence. Considerable heterogeneity existing in most meta-analyses was associated with the increase in inconsistency. The details are shown in n = 2) and the effect of acupuncture as adjunctive therapy may have been overestimated, and the overall quality of evidence was rated as very low. We believe these metrics are important in evaluating the effectiveness of acupuncture in CIBP and should obtain more attention in future RCTs. There was considerable heterogeneity among included studies, and subgroup analysis based on acupoints type partly explained the sources of heterogeneity. Notably, seven kinds of acupuncture treatments have been used across 13 included studies, complicating this system review's analyses. The change in the acupuncture technique brings a corresponding change in the treatment frequency, duration of treatment, needle retention time, number of sessions, and needling depth, all of which might have been potential biasing factors. Given that studies concerning acupuncture's effectiveness on CIBP are less common, we had to use less restricted inclusion criteria to retrieve relevant RCT studies. In the future, more RCTs focusing on this matter should be carried out to confirm the effectiveness of acupuncture on CIBP.As far as we know, this is the first systematic review and meta-analysis to evaluate acupuncture's effectiveness in treating CIBP. Clinically, CIBP patients not only experienced background chronic pain but also suffer from acute pain termed breakthrough pain ; therefoIn recent years, many researchers or institutions have been appealing to pay more attention to the quality of life in cancer patients than just killing cancer itself . PreviouP=0.04, CI−3.88 to−0.10). Auricular point acupressure is the method of stimulating specific points on the ear by applying pressure to them , which was likely to reduce the outcomes' precision and produce misleading results. Based on the analysis above, future RCTs should include greater numbers of participants, be registered on relevant online platforms, disclose necessary information to improve the transparency and authenticity of clinical trials, and facilitate the provision of reference information for scientific researchers.This study has several limitations. First of all, there is a certain inclusion bias in this study. On the one hand, the literature search was limited to articles published in Chinese or English, excluding studies published in other languages such as Japanese, Korean, and German; on the other hand, in most cases, positive trials are published rather than negative ones; however, negative findings had important implications for our research. We had not retrieved studies with negative results. More avenues should be tried in the future, looking for negative reports. Second, CIBP is the most common type of cancer pain. The subjects included in the current review were all cancer patients with bone metastases, which always indicates that patients presented an advanced tumor stage. Primary cancer may also be a source of cancer pain at this stage. Cancer pain other than CIBP may have significantly influenced study outcomes. However, some studies , 45, 46 Acupuncture has a certain effect as a complementary therapy on pain management of CIBP, which not only mitigates the pain intensity but also improves the quality of life, and reduces the incidence of opioid side effects. Due to the poor quality of methodology and strong heterogeneity in the included studies, the results of this meta-analysis should be interpreted with caution. Regarding acupoint selection, the systemic therapeutic effect of acupuncture obtains more attention, and ear points, wrist-ankle acupoints, ST36, BL23, BL11, and KI3 are essential for the acupoint selection. In addition, whether Ashi Point is suitable for treating CIBP still needs further exploration. In future, a large sample size and rigorously designed RCTs are needed to provide sufficient evidence to identify the effectiveness and safety of acupuncture as a treatment for CIBP. Meanwhile, researchers should gradually explore the law of acupuncture treatment for CIBP, including the choice of acupuncture techniques, acupoints, needle retention time, and sessions, in hopes of promoting the application of acupuncture in the pain management of CIBP.The original contributions presented in this study are included in the article/MaL and MiL conceived and designed the research. HZ contributed to the design of a research strategy. ZY, ZM, and MaL contributed to the literature search, data extraction, and assessment of risks of bias. CY and HZ performed the statistical analysis, interpreted the data, and discussed the format and content of the article and contributed to the review and editing of the final manuscript. ZY and ZM wrote the first draft of the manuscript. MiL and CY revised the manuscript for intellectual content. All authors revised the manuscript for important intellectual content and read and approved the final manuscript.This study was supported by the National Natural Science Foundation of China (Grant No. 82074559), Key Scientific Research Foundation of Education Bureau of Hunan Province, China (Grant No. 21A0235), Scientific and Technological Personnel lift project in Hunan Province (Grant No. 2019TJ-Q04), Furong Scholars Award Program in Hunan Province (Xiang Jiao Tong [2020] 58.), and Training Program for Excellent Young Innovators of Changsha (Grant No. kq1905036).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.


Adult depression is a common consequence of adverse childhood experiences. There is also a higher likelihood of being affected by economic burdens after having experienced a traumatic event in childhood. As depression has been associated with economic burden, these long-term sequelae of childhood adversity are likely to interact.We investigated depression and economic consequences, such as unemployment, lower level of education, lower income as long-term sequelae of adverse childhood experiences in adulthood and their interaction.Childhood Maltreatment was measured by the German version of the Adverse Childhood Experience (ACE) questionnaire. Depression was measured by the Patient Health Questionnaire (PHQ-2). Logistic regressions were applied to investigate the risks of suffering economic burdens, with depression as a moderator.Depressive symptoms increased with the number of ACEs and were highest in those reporting four or more ACEs, especially amongst those who experienced sexual and emotional abuse, as well as neglect. Moderation analysis showed a significant effect of depression increasing almost all economic burdens. Migration background additionally increased the risk of unemployment and working in a blue-collar job. Female gender decreased the risk of unemployment and working in a blue-collar job, but increased the risk of low income and part-time employment.The moderation effect of depression increased the negative impact of exposure to multiple ACEs on economic life in adulthood. Prevention of ACEs and early intervention are needed to prevent the mental health and economic consequences. Adverse Childhood Experiences (ACEs) are a common phenomenon. In representative studies up to 43.7% of respondents of the German population reported having experienced at least one adverse childhood experience, which includes emotional, physical and sexual abuse, as well as neglect and household dysfunction, such as domestic violence and drug abuse . Most reAdditionally, studies have also found strong associations between the occurrence of ACEs and negative psychological, emotional, social, health and economic outcomes , 4–8. AdAccording to stress sensitization theory, having experienced adversity in childhood can reduce a person's coping ability in stressful times, leading to greater reactivity and more depressive reactions compared to people who did not experience such events . This maIn addition to these personal economic consequences following the experience of childhood maltreatment, researchers also began to evaluate the overall average economic lifetime costs of nonfatal childhood trauma and maltreatment in terms of medical costs, productivity losses and even in criminal justice costs. Fang et al. , for exaAs most of the current research is on non-German samples, this study aims to add to the growing research on the association between adverse childhood experiences and negative economic (as well as academic) outcomes in later life for Germany to understand better this complex interplay and to potentially aid in finding solutions to this big social, mental health and economic issue for a considerable part of the German population. We hypothesize, based on existing research, that ACEs negatively affect a person's mental health, increasing the risk of depression. We further hypothesize, that there is also an association between ACEs and economic burdens, such as lower levels of education and unemployment. Finally, due to the abovementioned “ripple effect” ACEs have on depression and depression on economic outcomes, we hypothesize that the associations between ACEs and economic burdens are moderated by depression. Finally, we assume gender effects regarding the negative psychological and economic outcomes.A nationwide representative survey conducted by the independent institute for polling and social research (USUMA Berlin) was performed between December 2020 and February 2021. In total, 2,519 participants were included. However, we excluded all participants under the age of 25 since, by this time, they have finished their early adulthood stage and typically have become economically independent. This left us with a sample of 2,288 respondents .not at all to 4 = almost every day. The subscale of PHQ-4 (PHQ-2) exhibits sufficient reliability . In order to estimate the prevalence of depression, we used the validated cut-off value of ≥3  . Adverseue of ≥3 .First, we examine if we find a cumulative effect among the ACEs on depression by correlating the frequencies of ACEs  with depression (PHQ-2), and with economic burdens  using oAll calculations were performed using the statistical program R .p < 0.001). Furthermore, they had graduated less from secondary school  and were less likely to hold a university degree . Regarding their current occupational status, respondents with ACEs were less likely employed full-time  but rather part-time employed  or currently unemployed  than their counterparts. Additionally, they were also more likely to have been unemployed at least twice . Participants with ACEs more frequently reported to be working blue collar jobs than participants without ACEs  and their mean household income was significantly lower . Respondents with ACEs were more likely to have a migration background . And finally, they also exhibited significantly more likely symptoms of depression .One thousand ninety-one (47.7%) of the respondents were male with a mean age of 53.3 years (SD = 16.1). The full description of the sample can be found in A total of 262 (11.5%) reported to have experienced one ACE, 138 (6.0%) two, 119 (5.2%) three, and 240 (10.5%) four or more ACEs. Emotional abuse was cited the most , followed by parental separation or divorce , physical abuse , substance abuse in the home , and emotional neglect . Incarceration of a family member  and sexual abuse  were mentioned least frequently.For individual ACEs, as well as multiple ACEs, we found significant moderate to strong associations with depression, income, level of education, current unemployment, blue collar education and higher risk of unemployment see . The assLooking at the economic burdens, we found a higher risk of unemployment within the high-risk group of 4+ ACEs (OR = 3.99). Having reported four or more ACEs was also highly associated with having an equivalized income of under 1,126€ and current unemployment (OR = 3.19 and OR = 3.75). For individual ACEs, the ratios ranged between OR = 1.70  and OR = 3.45 (incarceration of family member) for the equivalized income of under 1,126€ and between OR = 1.98  and OR = 3.73 (incarceration of family member) for current unemployment. Working a part-time job was associated with the incarceration of a family member (OR = 2.01), parental separation or divorce (OR = 1.75) and drug or alcohol abuse in household (OR = 1.84).B = 0.017  for working a blue-collar job to B = 0.034  for having a low income. Furthermore, both reporting 3 and 4+ ACEs was significantly associated with reporting any economic burden, with an increased effect of 4+ ACEs compared to 3 ACEs. The largest coefficients amongst participants who reported three ACEs were found for low income  and low level of education . Working a blue collar or part-time job and experiencing a higher risk of unemployment or being currently unemployed were not significantly associated with reporting three ACEs. The largest coefficients amongst participants who reported four or more ACEs were found for low level of education , low income , and higher risk of unemployment . Only part-time working was not significantly associated with reporting four or more ACEs, but was associated with reporting 2 ACEs .When put in linear structural equation models, we find significant associations between depression and all economic burdens, except for low level of education and part-time working see , 4. The B = 0.044 . Additionally, we also found gender effects as well as effects of having a migration background for almost all economic burdens when including gender and migration as control variables. Being a woman decreased the risk of being unemployed ] and working in a blue-collar job , but increased the risk of working part-time . Having a migration background increased the risk of being currently unemployed  and being at greater risk of unemployment in general , as well as having a lower income .The interaction terms between depression and number of ACEs were mostly significant, except for the cases of low level of education and part-time working. We found the largest moderation effects amongst those who reported four or more ACEs, indicating that demonstrating signs of depression amongst this population increased the total effect of number of ACEs by up to In this study, we investigated the (co-)occurrence of ACEs and their correlations to negative economic outcomes, such as lower income, lower level of education, type of occupation and unemployment, as well as depression. In total, 33.2% reported at least one ACE, including 10.5% reporting four or more. The most common ACE was emotional abuse, followed by parental separation or divorce. Least common were incarceration of a family member and sexual abuse. These findings were largely in line with other findings of representative studies in Germany, in which the prevalence of child maltreatment ranged from 31.0%  to 43.7%We found that each individual ACE showed a strong association to depression with odds ratios ranging from OR = 2.80  to OR = 6.35 . These findings were significantly higher than those of, for example, Witt et al. , who fouWe found that having experienced 3 or 4+ ACEs increased the risk for depressive symptoms. This result is in accordance with previous studies indicating an association between cumulative ACEs and negative psychological outcomes , 23, 39.As for economic burdens and the occurrence of ACEs, we found a generally higher risk of occurrence of economic burdens in one's life the more ACEs the person has experienced, except for people who worked part-time. Respondents who suffered four or more ACEs, for example, were more likely to be at risk of poverty with an equivalized income of under 1,126€ and a blue-collar job. Furthermore, they were also more likely to be currently unemployed and to be at greater risk of unemployment, in general. This mirrors results from previous studies –22, 42. Finally, the role of gender needs to be addressed. We found a lower likelihood for women to be affected by current unemployment or working a blue-collar job compared to men. Instead, we found that women were more likely to live at risk of poverty with an equivalized income of under 1,126€ and to work part-time jobs. This might be due to gender roles in traditional family constellations where women typically work part-time jobs in addition to caring for children while their husband is typically working full-time. This might also explain the lower income and the insignificant results for part-time working in the structural equation models for ACEs.Additionally, we have to consider migration background as an important factor when investigating economic burdens. Our analysis showed a significant association between having a migration background and an increased risk of being unemployed or being at risk of poverty. As this analysis showed by the increasing moderation effect of depression, this association might be due to the increased risks of depressive symptoms in those with migration background compared to non-migrants –46. HoweA strength of this study is the large and representative sample size of 2,288 participants. To measure adverse childhood experiences, we used the well-established ACE questionnaire. This measure has been discussed because of its reliability (since it's a retrospective self-reporting measure) and bias . HoweverElmar.Braehler@medizin.uni-leipzig.de.The data analyzed in this study is subject to the following licenses/restrictions. The dataset is not publicly available. Requests to access these datasets should be directed at: EB, The studies involving human participants were reviewed and approved by the Ethics Committee of the Medical Department of the University of Leipzig (Ref. No. 474/20-ek). Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.EB, JF, CS, and MB were involved in the study design. JP performed the statistical analysis and wrote the manuscript. A-CS, EB, MB, JF, and CS provided ideas as well as guidance and critical feedback to the final version of the manuscript. All authors contributed to the article and approved the submitted version.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.