Diabetes is associated with an increased risk of colon cancer (CC). Epidemiologic studies previously reported a higher risk for right-sided colon cancer (RCC) compare to left-sided colon cancer (LCC), although data are conflicting. We performed a meta-analysis to investigate this issue.We systematically searched the PubMed, EMBASE, Web of Science and Cochrane Library database for prospective cohort studies published up to June 2021. Studies were included if they reported site-specific estimates of the relative risk (RR) between diabetes and the risks of RCC and LCC. Random effects meta-analyses with inverse variance weighting were used to estimate the pooled site-specific RRs and the RCC-to-LCC ratio of RRs (RRRs).2 = 0%).Data from 10 prospective cohort studies, representing 1,642,823 individuals (mainly white) and 17,624 CC patients, were included in the analysis. Diabetes was associated with an increased risk of both RCC  and LCC . After adjusting for major risk factors, individuals with diabetes had a greater risk for RCC than for LCC , with no significant heterogeneity between studies (IThis meta-analysis indicates that diabetes is associated with a higher risk for RCC than for LCC. Our findings suggest that colonoscopic surveillance in diabetic patients with careful examination of the right colon is warranted. The relationship between diabetes and the risk of colon cancer (CC), two highly prevalent and major health problems worldwide, is well recognized. Most previous epidemiologic studies have provided evidence that individuals with diabetes have an increased risk of CC compared with their nondiabetic counterparts –4. An upAlthough extensive research has been performed on this topic, several features of the association between diabetes and the risk of CC remain unclear. For instance, it is not known whether diabetes is differentially associated with the risks of right-sided colon cancer (RCC) and left-sided colon cancer (LCC). A growing body of evidence suggests that LCC and RCC should be considered two distinct clinical and biological tumor entities. The left side of the colon originates from the midgut, whereas the right side originates from the hindgut. Differences also exist that correlate to physical function, artery supply, histology and biochemical features , 8. SubsUnderstanding whether diabetes is differentially associated with the risks of developing RCC and LCC may have important clinical and public health implications. Screening for colorectal cancer (CRC) in average-risk or high-risk patients using flexible sigmoidoscopy (FS) or colonoscopy is now common in many countries. However, FS screens only the distal colon . In 2005Given the rising prevalence of diabetes as a global health problem and the substantial clinical implications that any important subsite difference in the association between diabetes and CC risk would have, we undertook a meta-analysis of all available prospective cohort studies that reported the site-specific effects of diabetes on the subsequent risk of CC.This study was conducted according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines .A comprehensive, computerized literature search was performed using the PubMed, Embase, Web of Science and Cochrane Library database up until June, 2021. The following search key words were used: “diabetes”, “diabetes mellitus”, “colorectal”, “colorectal”, “colon”, “neoplasm”, “cancer”, “carcinoma” and “tumor”. Details on the search strategy are provided in the Studies included in our meta-analysis were required to meet the following inclusion criteria: 1) used a prospective cohort design; 2) reported the RR and the corresponding 95% confidence interval (CI); 3) classified CC into no more than two outcomes ; 4) defined the proximal or right-sided colon as including at least the cecum, the ascending colon, and the transverse colon, but no anatomical sites distal to the splenic flexure, and the distal or left-sided colon as including at least the descending and sigmoid colons, but not the rectosigmoid junction or the rectum, and no anatomical sites proximal to the splenic flexure; 5) included only the most recent publication when duplicate reports from the same study were identified; and 6) classified at least 80% of CRC cases or CC cases by subsite. Meeting abstracts, commentaries and letters were excluded.via email if a study reported insufficient data  to include in the meta-analysis. For studies that provided separate RRs for men and women, we pooled the RRs weighted by the inverse of the variance within each study.Data were extracted independently by two authors, and discrepancies were resolved by team consensus. The following information was extracted from each eligible study and entered into a structured database: study name, year of publication, country, age (mean and range), sample size, prevalence of diabetes, the numbers of RCC and LCC, year of baseline data collection, study duration, RRs reflecting the greatest degree of control for potential confounders were adopted in the meta-analysis. We also contacted the corresponding author The quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS) . This scFor each study, we extracted the site-specific RRs and 95% CIs for individuals with diabetes versus individuals without diabetes. Adjusted RRs were used for the analysis to account for confounding variables. If a study reported results for males and females separately, we estimated the pooled RRs. These RRs and 95% CIs were subsequently used to calculate the RCC-to-LCC ratio of RRs (RRRs) and 95% CIs, which compared the association between diabetes and the risk of RCC with the association between diabetes and the risk of LCC , 17.2 statistic; p ≤ 0.05 or I2 > 50% indicated significant heterogeneity  and level of adjustment. We use random effects meta-regression analyses to examine whether there was a significant difference between the subgroups and whether differences in the duration of the study follow-up and prevalence of diabetes contributed to heterogeneity between studies.We investigated publication bias by visual inspection of funnel plots, Begg’s rank correlation test and Egger’s regression test , 21. AllThe detailed steps of the systemic research are shown in The characteristics of these studies are shown in Rating of the quality of the included studies according to the NOS is presented in Relative Risk Between Diabetes and the Risks of Right-Sided Colon Cancer and Left-Sided Colon Cancer2 = 25.7%, p = 0.143) , with low heterogeneity between studies (I= 0.143) Figure 22 = 23.5%, p = 0.227) , with low heterogeneity between studies (I= 0.227) Figure 22 = 0%, p = 0.461) , with no heterogeneity between studies (I= 0.461) Figure 22 = 0%, p = 0.607) and no indication of publication bias  Figure 3In this pooled analysis of prospective cohort studies, with data from 1,642,823 individuals and 17,624 CC events, we examined the site-specific association between diabetes and the risk of CC. Our findings support a role for diabetes in the etiology of CC, including both RCC and LCC. After adjusting for major risk factors, individuals with diabetes showed a significant 13% increased risk of RCC compared with LCC.The main strength of this pooled analysis is that by including only prospective cohort studies, we were able to perform an objective meta-analysis based on a large population size over a long follow-up duration. The ten large prospective cohort studies included better resemble clinical practice, are of good quality and lack obvious selection bias compared with case-control studies and retrospective cohorts. Our findings were robust with no heterogeneity across studies and no obvious evidence of publications bias. Moreover, our results were consistent in a range of subgroup analyses.Diabetes and CC share similar risk factors, including obesity, physical activity and the Western diet. Thus, our results could be confounded by these risk factors. However, a previous meta-analysis found that BMI and meat consumption were associated with a more pronounced risk of LCC, while physical activity and other dietary risk factors did not differ between LCC and RCC –41. In oNevertheless, several limitations merit comment. First, there are racial/ethnic differences in the incidence of CRC. According to the 2014 Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics, CRC incidence rates were highest among blacks, followed by American Indians/Alaska Natives, non-Hispanic whites, Hispanics and Asian/Pacific Islanders . In our The hyperinsulinemia theory, which implies that elevated insulin and free IGF-1 levels are the two key components that promote the growth of colon tumors , may relIn 2014, the worldwide prevalence of type 2 diabetes was approximately 422 million, accounting for 8.4% of adults, and this rate is projected to increase rapidly. In 2019, diabetes was the direct cause of 1.5 million deaths . The preTo conclude, the results from this meta-analysis suggest that diabetes is associated with increased risks for both RCC and LCC and that the association between diabetes and the risk of RCC is significantly higher than the risk of LCC after adjusting for major risk factors. Our findings add to the increasing evidence for the distinct clinical and biological patterns between RCC and LCC and provide further support for public health efforts aiming to establish a more tailored approach to CRC screening strategies in diabetic patients.The original contributions presented in the study are included in the article/WX and BW contributed to the study concept and design, data analysis, interpretation of the data and editing the manuscript. WX and JH contributed to the data acquisition, statistical analysis and editing the manuscript. WX, JH, CZ and LD contributed to the statistical analysis. WX, JH and XW contributed to the interpretation of the data. All authors commented on drafts of the paper and have approved the final draft of the manuscript for submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The global ecological environment is facing increasingly severe challenges; therefore, it is crucial to implement sustainable development policies and promote corporate innovation. Based on imprinting theory, we examine the relationship between CEO financial background and corporate innovation within the Chinese context. The results confirm that CEOs with a financial background negatively impact corporate innovation, while managerial ownership mitigates this effect. Existing literature has considered the impact of CEO background on corporate innovation; however, it mainly takes up corporate innovation from the perspective of upper-echelon theory. In addition, the mechanism of CEO financial background on corporate innovation is ambiguous in the Chinese cultural context. This study enriches the literature on the relationship between the characteristics of CEO background and corporate behavior, thereby offering guidance for corporate innovation practices. Making Peace with Nature. In the report, climate change, natural degradation and biodiversity loss, and pollution and waste crisis are identified as the three major environmental crises that the world is currently facing. These crises pose a serious threat to human survival. For instance, air pollution causes 300,000 to 700,000 premature deaths each year, while 25 million cases of chronic laryngitis among children are reported yearly. Further, in 2022, major ecological events such as extremely high temperatures in Europe and volcanic eruptions in Japan occurred. As these ecological and environmental problems aggravate, humanity’s future is at risk; consequently, the idea of sustainable development is progressively becoming a worldwide objective. As the world’s largest carbon emitter and energy consumer , whereas data on corporate innovation were collected from the Chinese Research Data Service (CNRDS). We found that CEOs with FB had a negative impact on corporate innovation through cognitive imprinting and capability imprinting. Additionally, when CEOs have higher managerial ownership, the negative effect of their FB on corporate innovation will be mitigated. This study’s findings were found to be robust.The present study made the following contributions: First, the existing literature is extensive, remaining firmly rooted on upper-echelon theory and mainly paying attention to the statistical relationship between CEO experience or background and corporate innovation. However, prior studies have overlooked this relationship’s intrinsic mechanisms. Based on imprinting theory, we provide an in-depth interpretation of the mechanisms by which CEO characteristics influence corporate innovation. Second, prior research on CEO background has mainly considered their foreign , militarThe remainder of this paper is organized as follows. (Section “2. Literature review and hypothesis development”) summarizes the available research and presents the research hypothesis. (Section “3. Research design”) presents the research design, thereby introducing the data sources, sample selection, variable measurement, and establishment of the empirical model. The findings of the empirical analysis are presented in (Section “4. Results”), together with descriptive statistics, correlation analysis, main regression analysis, and the outcomes of the robustness test. The research findings and implications are presented in (Section “5. Conclusion and discussion”).Innovation is a prominent component affecting the economic development of the country and the firm . NumerouR&D innovation is a complex and risky investment decision. Simultaneously, CEOs are the most critical decision-makers in firms; accordingly, CEO characteristics have a significant impact on firms’ innovation decisions. Prior studies classify CEO characteristics into personality and background traits. In terms of personality traits, using data from the U.S., Business Week and discovered that corporate R&D investment is the same regardless of whether the firm employs CEOs with FB, thus demonstrating that CEOs with FB are not correlated with corporate R&D investment.Prior findings on the relationship between CEO FB and corporate innovation have been inconsistent and contradictory. As previously described, there are three main perspectives on the relationship between CEO FB and corporate innovation: positive, negative, and unrelated. Firstly, some scholars argue that CEO FB is beneficial to corporate innovation. In the context of European countries, by creating new information exchange channels with financial institutions, Although the relationship between CEO FB and corporate innovation has been discussed in the literature, further research is necessary. First of all, a large and growing body of literature has investigated the impact of CEO FB based on upper-echelon theory, focusing more on the statistical link between CEO background and its economic consequences, without opening the “black box” and lacking in-depth analysis of the mechanism of this relationship. Moreover, while prior studies have mentioned the association between CEO FB and corporate innovation, there is no consensus; thus, further research is required to provide new evidence. Finally, most prior studies have examined the Western context; however, culture is a significant factor, so the same background may have diverse effects on people’s cognition and behavior in different cultural contexts. Hence, it is essential to analyze in the Chinese cultural context.According to imprinting theory, during individuals’ formative professional years, work experience leaves an imprint on their psyche , which will have a continuous impact on their career . The finIn terms of cognition, the CEO preference for short-term investments is determined by their financial experience. Due to its brief history, compared with Western economies, China’s capital market may exhibit speculative traits . ExecutiIn terms of capability, CEOs’ financial investment ability and social connections in finance lead to a “crowding-out effect” on corporate physical assets investment. CEOs with FB have a deeper and more specialized understanding of decision-making in the financial field , and theIn summary, CEOs with an FB have a negative impact on corporate innovation in terms of both cognition and capabilities. Therefore, we propose hypothesis H1:H1: CEOs’ FB has a negative impact on corporate innovation.According to According to In sum, managerial ownership mitigates the negative impact of CEO FB on corporate innovation. Accordingly, we propose research hypothesis H2:H2: Managerial ownership mitigates the negative impact of CEOs’ FB on corporate innovation.This study examined data from Chinese A-share listed companies for the period between 2017 and 2021. CEO FB data were obtained from the CSMAR’s China Corporate Figure Characteristic Series. Missing data on CEO FB were supplemented by manually searching for the information, and we removed data that were still vacant. The data on corporate patents were collected from the CNRDS, which is widely used by Chinese scholars. The other data used in the model were all from the CSMAR.The sample selection criteria were as follows: (i) excluding the financial industry samples; (ii) excluding the ST and *ST companies; (iii) excluding missing and abnormal samples of relevant data; (iv) excluding the current year listed company sample; (v) we applied 1 and 99% tailing to all continuous variables in the model to reduce the impact of an extreme value on the research results. Our final sample included unbalanced panel data of 12,248 firm-year observations.Referring to Following previous studies e.g., , we measReferring to Referring to Dividing total liabilities by total assets results in LEV. SIZE is the natural logarithm of total assets. We used the natural logarithm to calculate FAGE by adding one to the gap between the year the data were collected and the year it was founded. By dividing the growth in sales from the current year by that of the previous year, SALEGRO was calculated. The proportion of current net income to total assets was used to calculate ROA. The market value of assets divided by the book value of all assets results in Tobin’s Q. We determined SOE according to the type of actual controller; we assigned state-owned enterprises a value of 1; other types of enterprises were given a value of 0. Using the shares held by institutional investors relative to all shares, INSHOLD was calculated. The percentage of independent directors to all directors was used to calculate IDRATIO. The total number of directors on the board was BSIZE. In order to control the differences between industries and years, IND and YEAR were selected as the control variables. The industrial dummy variables were divided into industries according to the 2012 industry classification standard of China Securities Regulatory Commission. The manufacturing industry was categorized into the secondary industry classification, and the other industries were categorized into the primary industry classification. 1 of FB is negative and significant, H1 is supported.H1 predicted that CEO FB would have a negative impact on corporate innovation. The model was set using the ordinary least squares method to test H1. If the regression coefficient β2 of FB*MO is positive and significant, H2 is supported.H2 predicted that managerial ownership mitigates the negative effect of CEO FB on firm innovation. To test H2, we added the interaction term FB*MO based on model 1 to form model 2. If the coefficient βt = −1.72), indicating that CEO FB has a negative impact on firm innovation, and the results of the regression analysis support the H1. Column (2) reports the moderating effect of managerial ownership on the relationship between CEO FB and corporate innovation, and the coefficient of FB*MO is the primary concern. The coefficient of FB*MO in column (2) is 1.407 significant at the 1% level (t = 3.48), indicating that managerial ownership mitigates the negative effect of CEO FB on firm innovation, supporting H2.The results of the main regression analysis are reported in We performed robustness tests using a modified corporate innovation measurement method. According to t = −5.13) and the coefficient of FB in column (3) is significantly negative at the 10% level (−0.087 with t = 1.74), revealing that CEO FB has a negative effect on corporate innovation after changing the dependent variable measurement. The coefficient of FB*MO in column (2) is positive and significant at the 5% level (0.011 with t = 2.18) and the coefficient of FB*MO in column (4) is positive and significant at the 1% level (1.101 with t = 3.04), indicating that managerial ownership mitigates the negative effect of CEO FB on firm innovation after replacing the dependent variable. The empirical results in We added CEO gender (GENDER), age (CEOAGE), and overseas background (OVERSEAS) to the control variables. t = −1.81), indicating that CEO FB still has a negative effect on corporate innovation after adding the control variables. The coefficient of FB*MO in column (2) is positive and significant at the 1% level (1.426 with t = 3.52), indicating that after increasing the control variables, managerial ownership mitigates CEO FB’s negative effect on firm innovation. The empirical results shown in In the model, CEO FB is not affected by corporate innovation; accordingly, there was no endogeneity problem due to reverse causality in the model. The measurement of CEO FB in the model is accurate, accordingly, there was no endogeneity problem caused by variable measurement bias. Enterprises must be non-random when hiring CEOs, thus there may be endogeneity problems due to sample selection bias. Therefore, we used propensity score matching to alleviate any potential endogeneity problems due to sample selection bias, as follows. First, a sample of firms with CEOs who a background in finance was selected as the treatment group, whereas a sample of firms without such CEOs is selected as the control group. Second, CEO FB was selected as the independent variable, whereas LEV, SIZE, FAGE, SALEGRO, ROA, Tobin’s Q, SOE, INSHOLD, IDRATIO, and BSIZE were selected as covariates. After performing a logit regression to determine the propensity score, we utilized the one-to-four nearest neighbor matching approach to determine the final propensity score and one-to-four matching to minimize the mean square error .The average effect on the treated (ATET) intervention group is reported in Sustainable development has become a key topic within the context of escalating global environmental issues. In this regard, studying how to foster corporate innovation is essential, from a practical standpoint, because it drives sustainable development. Based on imprinting theory, we analyzed data from Chinese A-share-listed companies for the period 2017–2021 to explore the relationship between CEO FB and corporate innovation. According to our research, CEOs with FB have a detrimental impact on the innovation of their enterprises. However, when CEOs have higher managerial ownership, this negative impact is mitigated. After a series of robustness tests, our findings remained valid. The mechanisms by which CEO background influences corporate micro behavior are analyzed in this study, thereby contributing to the literature on the variables influencing corporate innovation.First, while existing literature on the topic is relatively extensive, it is firmly rooted in upper-echelon theory and mainly attentive to the statistical relationship between CEO experience or background and corporate innovation. Notably, prior studies have overlooked this relationship’s intrinsic mechanisms. Based on imprinting theory, we provide an in-depth interpretation of the mechanisms by which CEO characteristics influence corporate innovation.Second, prior research on CEO background has primarily explored their foreign , militarThird, several studies  have exaBased on the finding that CEO FB inhibits corporate innovation, enterprises should fully consider the compatibility between CEO background and the backgrounds of other executives, control the weight of executives with a background in financials to reduce the negative impact on corporate innovation strategy, and build innovation-oriented executive teams. Second, imprinting theory reveals that executive experience forms the imprint that affects their cognition and capabilities, which in turn impacts their decision-making; thus, enterprises should introduce an executive rotation system that encourages executives to abandon the rigid thinking answerable to their FBs, re-examine innovation strategies from new perspectives, and enhance their cognitive and decision-making abilities. Third, the findings suggest that managerial ownership inhibits the adverse effects of CEO FB on corporate innovation; in response, enterprises should establish and improve equity incentive plans to create incentive compatibility, thus allowing CEOs to exert their initiative and promote corporate value creation.Regarding executives, first, they should be aware of how their background affects their behavior and decision-making, objectively perceive their own background imprinting and the limits of their reasoning, and fully take into account any background traits that could potentially influence their decision-making. Second, to establish the groundwork for scientific decision-making, executives should collaborate with team members from all backgrounds, gather information from various sources, and reduce their cognitive bias.This study had a few limitations. First, due to limitations in the availability of research data, this study only included listed companies. Future research should also collect data from non-listed companies to test whether the FBs of CEOs in non-listed companies also impact corporate innovation.Second, we mainly explored the impact of CEO FB on corporate innovation from the perspective of corporate technology innovation. However, in addition to technological innovation, corporate innovation also includes product innovation, process innovation, and other dimensions. Future studies should explore the relationship between CEO FB and product innovation or process innovation to specify the analytical framework of this topic.Third, the national culture model developed by The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.YT has collected the data. YG and YT wrote the first draft. YG and JZ analyzed the data, contributed to the research problem formulation, theory, analysis, and conclusion. All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.


The studies yielded a significant inverse association between childhood exposure to family violence and telomere length, with a small effect size . Furthermore, the strength of this association was stronger in studies examining the co-occurrence of multiple types of violence than in those examining just one type . These findings suggested that victims’ telomere length may be negatively influenced by childhood exposure to family violence and that such impairment appears to be stronger for those who are exposed to multiple types of violence. Future studies are necessary to examine the moderating and mediating factors underlying the association between childhood exposure to family violence and telomere length.The aims of this meta-analysis were to examine the association between childhood exposure to family violence and telomere length and the moderating variables that influence this association. Relevant works published on or before 1st September 2022 were identified through a search in five major databases in English and 19 articles  finally met the inclusion criteria. A meta-analysis was conducted to compute the pooled effect size (correlation;  Exposure to family violence during childhood is a significant public health and social welfare concern. Violence does not always involve tangible types, which is defined as the intentional use of physical force or power, threatened or actual, against others that may potentially result in injury, death, psychological harm, maldevelopment or deprivation . The twoIntriguingly, the growing field of research on biological markers, such as telomere length and telomere shortening, has opened a unique avenue for understanding the deleterious physical and mental effects of childhood exposure to family violence . TelomerSeveral meta-analyses and systematic reviews have summarized extant evidence for the influence of adversity on TL. Systematic reviews have reported inverse relationships between TL and adverse childhood experiences, such as child maltreatment and loss of a close family member ,13,14,15Previous studies focusing on the association between childhood exposure to family violence and TL have had mixed findings. A longitudinal study of 236 children found that exposure to two or more kinds of violence  was significantly associated with accelerated telomere erosion during a 5-year period . SimilarMany possible factors could explain the previous heterogeneity of findings on the association between childhood exposure to family violence and TL. For example, the extant studies differed in the length of time between exposure to adversity and TL assessment. Furthermore, many of them measured TL in adults ,27, whilThe objectives of this meta-analysis were to quantitatively summarize the association between childhood exposure to family violence and TL and to explore how the reported strength of that association was affected by moderators.Study selection was carried out in line with items for systematic reviews and meta-analyses (PRISMA) checklist. A description of the systematic review criteria is detailed below.We searched five major electronic databases  to identify studies published in English on or before 1st September 2022. Publications were systematically searched by their titles, keywords, and abstracts, and using the following three groups of keywords: (1) violence, victim, abuse, maltreat, neglect, trauma, adversity, adverse; (2) telomere, biomarker; and (3) infant, child, adolescent, newborn, youth. Additional relevant publications were identified by manually searching the reference lists of all of the retrieved articles. No additional articles were identified.We employed EndNote bibliographic management software to organize the studies. Of 21,867 titles, we first removed 7540 duplicates. Then, we screened the titles of the remaining 14,327 articles and eliminated 14,242 articles. After that, we examined the full text of the remaining 85 articles and 19 of them were included in this meta-analysis.Studies were included if they met the following criteria: (1) they were written in English; (2) they provided sufficient data to calculate effect sizes on the relationship between childhood exposure to family violence and TL in human subjects. Studies were excluded if they did not include an analysis of primary data .Data were extracted from all eligible studies by using a structured coding sheet that evaluated the following aspects: (1) publication information, including author(s), publication year, and country; (2) study characteristics, including sampling method, study design , and sample sizes; (3) participants’ demographic characteristics, including age, gender, and educational level; (4) violence-related information, including types of violence, the measurement types , and time frame of violence; (5) TL-related information, including TL cell type , the time frame of TL measurement , and TL assay type .Each included study was evaluated for quality, using a quality assessment checklist. This checklist was adapted from a previous study . Eight i2 statistics to calculate the proportions of observed variance of the included studies. Values of I2 up to 25% were considered to be low amounts of heterogeneity, from 25% to 50% were moderate, and from 50% to 75% were high [Comprehensive Meta-Analysis (CMA) software version 3.0  was used to conduct all statistical analyses. First, pooled correlations were used to examine the association between childhood exposure to family violence and TL. Data were derived from raw scores, for example, correlations, standard mean differences, and independent groups’ t-values. For studies with multiple correlation coefficients for the same variable, we averaged the multiple correlation coefficients, such that each study only involved one effect size for the final analysis. This method had been employed in a previous study . We consere high .Next, we performed subgroup analyses to explore the sources of heterogeneity. The studies were divided into subgroups according to gender , whether the violence was co-occurring, the types of measurement for the violence (self-report or by others), source of tissue , telomere measurement technique (qPCR or other techniques), timing of measuring telomeres (childhood or adulthood), whether the covariates were controlled, and sample sizes . Specifically, in the current study, the definition of co-occurrence of family violence (family polyvictimization) is two or more types of family violence rather than repeatedly occurring episodes of one single type of family violence ,40. A sep-value was less than 0.05. If there was publication bias, the trim and fill algorithm, a compensation technique for publication bias, was then used to impute the effect size estimates for missing studies in order to obtain an unbiased effect size, which was then compared with the original effect size [Finally, publication bias was visually examined by using a funnel plot delineating individual studies’ effect size against the standard error of the effect size and quantitatively tested by Egger’s regression and Begg–Mazumdar rank correlation ,42. The ect size .A flow chart of the study selection is shown in n = 13) and some used buccal swabs or saliva. 16 studies collected data on TL during adulthood, and 17 studies used qPCR to analyze TL.For the outcome measures, the majority of the studies assessed TL in blood cells  . The heterogeneity test was significant , suggesting the possibility of heterogeneity among the studies. The I2 statistic (I2 = 65.902) showed that more than 60% of the heterogeneity could be attributed to variation; thus, we continued to perform the subgroup analyses.r = −0.209) than for those examining a single type (r = −0.025) (Q = 8.143 p = 0.004). Larger effect sizes were found in smaller sample sizes (n < 100) (r = −0.132) than in medium (n >100 and <1000) (r = −0.036) and larger samples (n > 1000) (r = −0.023) . No significant moderating effects were found for gender , types of violence measurement , source of tissue , telomere measurement technique , or time of telomere measure , etc.The sensitivity analysis showed that removal of the studies did not alter the association.p > 0.05).As shown in r = −0.038, p = 0.025). Most previous systematic reviews and meta-analytic studies had found a significant association between widely defined adversity and TL [This meta-analysis identified 19 articles covering 18,977 individuals and found that childhood exposure to family violence had a significant negative effect on TL  axis, and especially its end product, cortisol. Vitro experiments have demonstrated a causal relationship between elevated cortisol exposure and telomere erosion , which mOne likely cause of the small overall effect size in this study is qPCR measurement error. TL is commonly measured using the qPCR-based method in the current study, mainly due to its cheapness, quickness, and the small quantities of DNA. However, one obvious limitation of qPCR is that it has higher measurement errors and thus reduces the statistical power to detect associations ,57. SomeOur moderator analyses of the moderating effect exerted by co-occurrence of childhood exposure to family violence showed that co-occurring violence had a significantly larger effect size than non-co-occurrence events did, which is consistent with previous findings that telomeres tend to be shorter among individuals reporting greater life adversity . MeanwhiWe did not find a significant difference between studies involving both genders and those involving females only. The literature has inconsistent findings on gender differences in TL in adults. Males may present with shorter telomeres than females, likely because of complex hormonal processes ,59. TestIn checking for a moderating effect from different sample sizes, we found that the studies with smaller sample sizes showed a larger effect size––data that should be interpreted with caution. A review found that findings of larger samples were less conclusive compared to findings of smaller samples . The larp = 0.002) [Studies grouped by the telomere measurement method (qPCR vs. other techniques) were not significantly different in the present study. The literature has conflicting results on the telomere measurement technique ,20,21: t= 0.002) . Thus, wThis meta-analysis has several strengths. As already mentioned, most previous review studies conceptualized childhood exposure to family violence within a broad definition of adversity, rendering them unable to provide information delineating the relationship between childhood exposure to family violence and TL. The present study offers quantitative findings on this association and on how the strength of this association is affected by moderators. We believe that this is the first meta-analytic study to examine the association between childhood exposure to family violence and TL.The findings of this meta-analysis advance knowledge about the association between childhood exposure to family violence and TL, but the study findings need to be interpreted with the following caveats. First, we only included cross-sectional data, making it impossible to investigate causality between childhood exposure to family violence and TL. Four articles provided longitudinal data of the effect of childhood exposure to family violence on TL over time, but we chose only to include their baseline data in the analysis because it was difficult to estimate accurately on the basis of only four sets of longitudinal data with different follow-up intervals. Second, our number of included studies was small. Although we tried hard to contact authors of the studies that did not provide sufficient data for calculating their effect sizes, we could not reach some of those authors and that omission limited our ability to fully assess the association. Third, we cannot separate the data of different types of violence to see the specific effects of various forms of family violence as no relative data were available. This is an important area for future studies with more comprehensive data to explore. Furthermore, most studies included in this analysis were from countries in North America and Europe, and the generalizability of those findings to other cultures is uncertain. Finally, this research was limited to studies published in English, thus opening the possibility of cultural bias.The reverse relationships between childhood exposure to family violence and TL make it highly important for practitioners and health professionals to screen for violence in the family, and especially to look for the co-occurrence of multiple types of violence and then to provide timely trauma-informed interventions. Policymakers should consider childhood exposure to family violence to be a risk factor for biological issues  and should prioritize prevention and intervention for individuals who are exposed to family violence during childhood.p = 0.02) [TL throughout life is determined by the interaction between endogenous (genetic) and external (nongenetic) factors . For the = 0.02)  A commun = 0.02) . At the  = 0.02)  and expe = 0.02)  may cont = 0.02) . Therefo = 0.02) . However = 0.02) .Because longitudinal studies are scarce, future research on childhood exposure to family violence and health should include well-designed longitudinal studies from diverse cultural backgrounds to further confirm the current findings. Furthermore, because the relationship between co-occurring types of childhood exposure to family violence and TL was found to be stronger than that between TL and a single type of violence, future studies should focus on the added negative impacts of family polyvictimization. To complete the picture, future studies should look closely at the mediating role of TL in the relationship between co-occurring childhood exposure to family violence and health-related consequences. Additional research is also needed on other potential moderators  and mediators of the association between childhood exposure to family violence and TL.This study contributes to the current knowledge by documenting that childhood exposure to family violence is negatively associated with TL, thus further indicating that such violence impairs victims’ biological health. In addition, the strength of this association was stronger in studies examining the co-occurrence of childhood exposure to family violence than in those examining one type.


Research productivity was positively correlated with population, gross domestic product (GDP), health expenditure, number of healthcare establishments, neurologists, and research personnel. The Philippine research landscape is dominated by articles of neurologists belonging to institutions in the NCR, which has the greatest number of neurologists, training institutions, and highest GDP. There is a need to address the disparity seen in other regions to bridge gaps in healthcare, health human resources, and health information through research.Philippine research productivity in neurology has not been fully characterized. We investigated the research output of adult and child neurologists in the Philippines and correlated this to the Philippine socioeconomic and healthcare indices among different regions. We used electronic databases to retrieve studies published by Filipino neurologists using the 2022 Philippine Neurological Association website as reference. We included all studies published until December 2021. Official government region-specific socioeconomic indices were used. Correlational analysis was completed on bibliometric indices and collected data. We retrieved 746 articles from 274 of 526 Filipino neurologists which were published in 245 publications over 45 years with 12,409 citations. The National Capital Region (NCR) had the most publications ( The Philippines is an archipelago comprised of 17 administrative regions in 3 major islands  consisting of various topographies, which gives rise to several geographically isolated and disadvantaged areas. Governance fragmented into local government units has caused stark socioeconomic disparity and health inequity in that the public sector providing for the underserved is under-resourced whereas the private sector catering to the wealthy is over-resourced [In Southeast Asia, the Philippines has shown the greatest increase in disability-adjusted life-years (DALYs) for neurological diseases over the last two decades . A compaThe Philippine Neurological Association (PNA), formed in 1972, is the local authority for the specialty which accredits neurology training programs for both adult and pediatric neurology and board-certifies graduates of these programs. At present, there are 11 accredited training programs for adult neurology residency and 3 for pediatric neurology fellowship. The official PNA website lists five hundred adult and pediatric neurologists in the country [In 2007, BRAIN Inc. compiled neuroscience research studies from 1985 to 2006 in the country in a compendium that included 610 abstracts, including 102 studies that have already been published locally . This, hResearch productivity is defined as the number of peer-reviewed articles published and the frequency of citations . PreviouThus, this study investigated the research output in terms of publications and citations of Filipino adult and child neurologists in the country and the correlation of these bibliometrics to socioeconomic and healthcare indices in the Philippines.International  and local  electronic medical databases were used to retrieve studies published by Filipino neurologists using the PNA official website as reference. An initial total of 1310 publications were retrieved and extracted from the electronic databases using the following criteria: (a) authored by a Filipino adult or child neurologist ; (b) published completed studies until December 2021 of any study design; (c) book chapters in published text; (d) available in full text; (e) published under at least one institution in the Philippines. Additional articles were included from perusing existing local publications and reference lists. An additional search was also completed for neurologists with hyphenated names using both maiden and married names. Deceased Filipino neurologists were sourced from the PNA website and directory and also included in the search. We excluded studies that were authored by PNA neurologists but did not have an affiliation in the Philippines at the time of publication, conference proceedings, letters to the editor or correspondence, editorials or commentaries, and guidelines.Duplicates were identified and excluded through juxtaposition of study titles, authors, and year of publication. Eligibility was assessed by two reviewers (ADOA and RDGJ) after duplicates were removed. Disagreements were resolved by discussion and consensus. Studies fulfilling the eligibility were included in the quantitative analysis.Extracted articles were encoded and archived into a Microsoft Excel file including: (a) year of publication, (b) authors, (c) affiliations, (d) journal of publication, (e) 2021 journal impact factor, (f) study design, (g) main topic of research. Citation count of articles on Scholar, CrossRef, Web of Science, Dimensions, and Scopus was manually collected, and the citation count was determined by the highest value. Journal impact factor was determined from SCImago Journal and Country Rank [A list of Filipino adult and child neurologists practicing in the Philippines was compiled using the PNA website. The list was further organized by region of practice and field of practice . Region-specific socioeconomic parameters (gross domestic product (GDP), population, health expenditure, number of health establishments, %GDP allocated for research and development (R&D), and number of R&D personnel) were sourced from official government reports under the Philippine Statistics Authority ,22 and tp-value was set at 0.05.Data syntheses were conducted in Microsoft Excel and R version 4.0.3  using deA total of 1232 articles were retrieved from an electronic database search and an additional 78 articles were identified from a manual review of locally published journals. We removed 38 duplicate records prior to screening. Screening of 1272 article titles and abstracts yielded 314 studies for exclusion. These included conference proceedings and guidelines. The full text could not be retrieved for 29 articles. The 929 remaining full-text articles were assessed for eligibility. A total of 746 studies were included for quantitative analysis. All retrieved studies were published in the English language .Neurology in 1984, garnering 511 citations [Muscle and Nerve in 1996 [The 746 studies were published in 245 journals and books from 1966 to 2021, amassing a total of 12,409 citations. Each cited article had an average of 17 and a median of 8 citations (range 0–511). Of the 746 studies, 302 (40.5%) were uncited. The most cited article was a cohort study about juvenile myoclonic epilepsy published in itations . The sec in 1996 . The yean = 662) of Philippine publications and 83.6%  of total citations , followed by Western Visayas (Region VI) . Davao Region (Region XI) had the second highest number of citations  closely followed by Western Visayas (Region VI) . NCR had the most inter-regional collaborations (n = 15), followed by Region IVA (n = 11) and CAR (n = 10). Regions XII, IVB, VIII, and XIII had the least.The majority of the research output and citations came from the National Capital Region (NCR). NCR publications comprised 88.7%  and child neurologists  have at least one publication. Adult neurologists have published 460 papers internationally and 210 locally. For pediatric neurologists, the number is 38 internationally and 53 locally , University of Santo Tomas , St. Luke’s Medical Center , Philippine Children’s Medical Center , Makati Medical Center , and Jose Reyes Memorial Medical Center . These institutions also had the most citations: University of Santo Tomas , followed by the Philippine General Hospital, University of the Philippines Manila , and St. Luke’s Medical Center . These top-cited institutions are all located in the NCR.The institutions with the most publications are the National University of Singapore , University of Luebeck, Germany , National Neuroscience Institute of Singapore , Seoul National University , Mahidol University of Thailand , and Massachusetts General Hospital . There were 88 affiliations from the United States, 43 from Germany, and 38 from Japan.The majority of studies were completed between at least two institutions. Of the 746 studies, 314 (42.1%) were single-institution studies, and 521 (69.8%) were initiated by a local institution. With international collaborators, the greatest number of articles were published with the n = 183, 24.5%) and movement disorders . Neurologic infections  were the next most common followed by neuro-immunology and autoimmune diseases , dementia , and epilepsy . There were 23 (3.1%) studies about nerve disorders and 21 (2.8%) studies about neurodevelopmental or genetic disorders and neuromuscular disorders, respectively. The remaining topics were neuro-oncology , neuropsychiatry , neurotoxicology , headache and pain , and congenital disorders   .n = 183, 24.5%) were the most common, followed by cohort studies (prospective and retrospective)  and cross-sectional studies . There were 59 reviews (7.9%), 51 systematic reviews and/or meta-analyses (6.8%), 48 clinical trials (6.4%), 33 case–control (4.4%), 32 animal or laboratory studies (4.3%), and 27 book chapters (3.6%) (Case reports and case series (s (3.6%) .n = 491, 65.8%) were published in international journals, accounting for the majority of citations . More than 1 out of every 10 articles was published locally in the Philippine Journal of Neurology . Nearly one-fourth of indexed articles were published in local journals including Acta Medica Philippina , the Philippine Journal of Internal Medicine , and the University of Santo Tomas Journal of Medicine . The top publishing international journals were Parkinsonism and Related Disorders , Neurology Asia , and Stroke .A total of 235 journals were identified, 24 of which were local journals. Most articles . The highest impact journals where Filipino neurologists published were Cell (IF 45), The Lancet (IF 22.23), Lancet Neurology (IF 15.9), Nature Communications (IF 15.41), and Science (IF 15.19). Only 34 articles were published in the top 10% of journals by IF, which was less than 5% of the total number of indexed articles.As of 2021, nearly half of the journals had an impact factor (IF) of more than 2 , which published 12 articles, Neurology , Annals of Neurology , Muscle & Nerve , and the Journal of Neural Transmission .The most cited journals were As of 2020, the most populated regions are Region IVA (CALABARZON), NCR, and Region III . Together these comprise 38.6% of the total Philippine population. The least populated regions are Region IVB (MIMAROPA), Region XIII (CARAGA), and the Cordillera Administrative Region (CAR). GDP was highest in NCR, Region IVA, and Region III and lowest in CAR, Region XIII, and the Autonomous Region in Muslim Mindanao (ARMM).n = 236, 46.0%), Region IVA , and Region III . Region IX (Zamboanga), Region XIII, and ARMM only have four, three, and two neurologists, respectively, which altogether is less than 2% of the total number of neurologists in the country. However, in terms of proportion of neurologists with at least one publication, Region IX (75.0%), XIII (66.7%), and CAR (66.7%) had more published neurologists compared to NCR (65.6%).According to the Philippine Statistics Authority, the number of healthcare establishments was greatest in NCR, Region IVA, and Region III; and the least in CAR, Region XIII, and ARMM. Health expenditure in 2020 was greatest in NCR, Region III, and Region VI (Western Visayas). It was lowest in Region XIII, ARMM, and Region IVB. As of 2022, there are 513 adult and child neurologists. Most neurologists are based in NCR , Region III (0.35%), and Region IVA (0.2%), and lowest in Region I (Ilocos Region) (0.05%), Region XII (SOCCSKSARGEN) (0.03%), and Region IVB (0.03%). In terms of overall personnel for research and development, NCR, Region IVA, Region III have the most and Region XIII, XII, ARMM have the least .p = 0.001 to p = 0.020), regional gross domestic product (p < 0.001 to p = 0.002), number of healthcare establishments (p < 0.001 to p = 0.005), healthcare expenditure (p = 0.007 to p = 0.039), number of personnel in research and development (p < 0.001 to p = 0.002), and the number of neurologists (p < 0.001 to p = 0.003). The ratio of published to unpublished neurologists was negatively associated with the population (p = 0.169), regional GDP (p = 0.322), number of healthcare establishments (p = 0.323), health expenditure (p = 0.155), and number of personnel in research and development (p = 0.351); however, these were not statistically significant. %GDP for research and development did not show a significant correlation with any of the variables (p = 0.313 to p = 0.799)  See .n = 38), systematic reviews and reviews (n = 20), cohort studies (n = 19), and cross-sectional studies (n = 13).Research activity in Southeast Asia has been shown to be predominated by countries with higher income such as Singapore, Thailand, and Malaysia . While tDespite the increase in the number of publications, 4 out of every 10 studies remain uncited. These studies were mostly local publications and recently published studies that would reasonably have fewer or no citations yet. Additionally, indices for local publications and the studies retrieved through printed text do not have embedded counters for citations, which may underestimate the total reach of these studies.n = 11) than there are institutions offering Pediatric Neurology fellowship training (n = 3). In general, more years are spent in residency (3 to 4 years) compared to fellowship (3 years) with more training slots offered for residency compared to fellowship. This creates a larger pool of trainees in total per year, which would evidently produce more graduates and also afford more opportunities for senior neurologists to collaborate and co-author research publications. Despite this, the percentage of published child neurologists was greater than that of adult neurologists.At least one in two Filipino neurologists has been published. There are disproportionately more adult neurologists in the Philippines than there are pediatric neurologists. This may be in part due to the number of years required to complete training and the number of training slots available. Any licensed physician may apply for Adult Neurology residency, but to be a pediatric neurologist, one must complete Pediatrics or Adult Neurology residency in order to be eligible for fellowship training. There are also more institutions offering Adult Neurology residency training  and the number of affiliated institutions  with the total number of publications regardless, if local or international  of research outputs in Southeast Asia about dystonia, ranking first in the region. This is a stark contrast to the country’s research contributions to motor neuron disease, headache, multiple sclerosis, neuro-oncology, and dementia, ranging from 1–6% of total publications [In the case of movement disorders, the Philippines contributed to 45.9% , yet almost half of the studies identified had authors belonging to only one institution . Leading collaborators based on the number of co-written articles were from Germany, Singapore, South Korea, Thailand, and the United States. Although foreign-led studies only comprised 29.8% of total publications, these studies were co-authored by institutions in countries belonging to a higher income stratum, which may guarantee greater funding and better success in international publication [Single-authored papers are a rare minority , and Western Pacific Region Index Medicus [Philippine Journal of Internal Medicine was previously indexed in Scopus from 1973–1995 and 1997 [In contrast, it was observed that local publications had comparatively lower citation counts. This may in part be due to the lack of online documentation and citation metrics embedded in these local journals, especially in their print form. Obtaining readership and research impact has been identified as a challenge, but this has been precluded in this age of digital media by setting up websites and allowing open access for articles under these journals . Additio Medicus . The Phiand 1997 ,36.The scarcity of indexed local journals may in part be due to the challenge in meeting international standards, which is grossly dependent on the number and quality of submissions. However, despite local policy changes offering incentives for improvement of local journal quality since 2009  the appePublication in high-impact journals is uncommon. Despite the majority of studies being published in international journals, only 5% of studies were accepted in journals with the top 10% highest impact factors. A survey evaluating determinants of publication in high-impact journals found a higher likelihood for doctorate holders compared to medical doctors; older authors; more time and resources devoted to research; and English as a first language . The PhiFor this study, in the absence of regionally distributed data on incidence, the burden of disease was grossly approximated by the number of neurologists and healthcare establishments  and the amount of healthcare expenditure . Analysis showed a positive correlation between the aforementioned factors and research productivity. Based on this, areas with a greater burden of disease will have a larger patient population, lending to more research opportunities for descriptive studies. These areas with more doctors and hospitals would also more likely belong to an urban area where general income would be higher, and income has already been shown to be correlated with research output.In summary, there were more publications and citations in more populated areas with higher income, better access to healthcare establishments, and more neurologists. At present, the bulk of training institutions and neurologists are concentrated in NCR . This stThis study has quantified 45 years of research output of Filipino adult and child neurologists. This is the second known aggregation of studies specific to Philippine neurosciences, and it has surpassed its predecessor in terms of scope and content. The year of inclusion is twice as long and contains more than seven times the original number of published articles. This study provides an updated and comprehensive glimpse of the trends in research in Philippine neurology.This study is limited in that only published studies were accounted. There are numerous studies completed each year in the country; however, only a percentage of which are published. Further research on the characteristics of unpublished completed studies may be pursued. In addition, neurologists were indexed according to their assigned region on the PNA website without redundancy between regions. In reality, there are neurologists based in other regions with visiting practices in NCR or nearby regions and vice-versa. The total number of neurologists also remains an approximation as a number of them are currently in training abroad and may not be contributing to the local health workforce. Identification of publications by female neurologists was doubly difficult as a thorough search using their maiden name, married name, and the hyphenated name was required. Likewise, conscientious screening of studies by neurologists with common surnames needed verification based on affiliation.Research productivity in Philippine neurology has shown steady growth in recent years. The research landscape is dominated by studies authored by neurologists belonging to institutions in the NCR, which has the greatest number of neurologists, training institutions, and GDP. Greater research productivity was associated with population, GDP, health expenditure, number of healthcare establishments, neurologists, and research personnel. There is a need to address the disparity seen in more distant regions in order to bridge gaps in healthcare, health human resources, and health information through research.


Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been widely employed to improve the outcome of gastric cancer patients. In the present study, the impact of posttreatment growth hormone (GH) levels on the treatment efficacy of ICIs for advanced gastric cancer (AGC) patients was assessed.χ2 test or Fisher’s exact test. Survival curves were drawn by the Kaplan–Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model.Seventy-five AGC patients treated with anti-PD-1 antibodies at The Fourth Hospital of Hebei Medical University were involved. We divided AGC patients into two groups as high-GH group and low-GH group based on the GH level. Immunotherapy efficacy was assessed in terms of objective response rate, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) based on the National Comprehensive Cancer Network Guidelines. The enumeration data were compared by P = 0.046). The subsequent univariate analysis showed that a high GH level was associated with both shorter PFS (P = 0.016) and shorter OS at the borderline statistical level (P = 0.052) in AGC patients treated with ICIs. Cox model analysis also proved that the GH level was an independent risk factor for the outcome of AGC patients .The higher GH levels were associated with a lower DCR of ICIs with a DCR of 30.0% in the high-GH group and 53.3% in the low-GH group (The post-treatment GH level might be a predictor for ICIs treatment in AGC patients. Helicobacter pylori infection, alcohol abuse, smoking, and pickled foods (Gastric cancer (GC) is a common lethal malignant tumor worldwide. According to latest data published by GLOBOCAN 2020, there were more than 1 million new cases of GC with 769,000 deaths, ranking the fifth for the incidence and the fourth for the mortality of malignant tumors around the world  is a protein hormone secreted by eosinophils in the anterior pituitary gland, which not only binds specifically to the growth hormone receptor (GHR) of the target tissue but also is involved in the regulation of cell proliferation and differentiation by inducing the release of insulin-like growth factor (IGF) as well as mediating signal transduction for Janus kinase 2 (JAK2), mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription (STAT) , 13. As d/or TME –19. In tAGC patients treated with anti-PD-1 antibody monotherapy or combination with chemotherapy or targeted therapy at The Fourth Hospital of Hebei Medical University from January 2019 to April 2022 were involved. Patients who were previously treated with other immunotherapies or had high GH-related underlying diseases were excluded. All clinical data including age, gender, Eastern Cooperative Oncology Group Performance Status (ECOG PS), human epidermal growth factor receptor 2 (HER2) status, MSI status, combined positive score (CPS), Epstein–Barr virus (EBV) status, surgical history, histological type, TNM stage, treatment lines, treatment regimen, disease status, immune-related adverse events (irAE), baseline GH level, and posttreatment GH level were collected for analysis. GH levels of fasting blood samples were measured using the electrochemiluminescence method on a Roche Cobas e602 analyzer with a supporting Elecsys hGH kit and calibrator , and all samples were analyzed twice in one assay. The baseline GH level was the GH test value of the first hospitalization before immunotherapy. If the result was abnormal, we repeated the measurement the following day and took the average. The posttreatment GH level was emphasized as the main research factor of this study and was defined as the mean of two hospitalization GH tests after the initial immunotherapy. A high posttreatment GH level means that the GH value exceeds the upper limit of the reference value and occurs twice or more on different days. Low and high GH levels were defined as <2.47 and ≥2.47 ng/ml, respectively, while the watershed is a normal threshold for a healthy person. All procedures were reviewed and approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University (No. 2021136). Informed consent was obtained for all participating patients.Patients received standard anti-PD-1 antibodies (monotherapy or combination with targeted/chemotherapy drugs) every 21 days until disease progression, clinical worsening, unacceptable toxicity, and patient refusal. χ2 test or Fisher’s exact test. Survival curves were drawn by the Kaplan–Meier method, and the association between clinical features and survival was analyzed by the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazard model, and P < 0.05 was considered statistically significant.Statistical analysis was carried out with SPSS 21.0 software . PFS was defined as the time interval from the first application of anti-PD-1 therapy to progression, death, or study cutoff. OS was defined as the time interval from commencement of ICI-based systemic therapy to death or study cutoff. The enumeration data were compared by the A total of 75 AGC patients treated with anti-PD-1 antibodies were identified as study subjects, among whom only one patient was treated with ICI monotherapy  and the other 74 were treated with combination therapies , but the DCR distribution was significantly different with 30.0% for the high-GH group and 53.3% for the low-GH group . In addition, the treatment lines , ECOG PS , and TNM stage  were associated with PFS in these AGC patients, whereas gender, age, HER2 status, MSI status, CPS, EBV status, surgical history, irAE, treatment regimen, and serum albumin had no significant effect on PFS (P > 0.05). In multivariate analysis, a high posttreatment GH level was independently associated with a poor PFS , TNM stage , surgery history , and treatment lines  were proved to be independently associated with PFS . Besides, ECOG PS , surgical history , and treatment lines  were also significantly correlated with the OS of AGC patients (P = 0.062) by univariate analysis. The multivariate analysis indicated that posttreatment GH levels , TNM stage , surgical history , and treatment lines  were independent factors for the OS of AGC patients  displayed prolonged survival time than that of the high group with a mean OS of 11.779 months (95% CI: 9.409 to 14.149 months) at the borderline statistical level /Akt, matrix metallopeptidase 2, and VEGF/VEHGR in gastric cancer, breast cancer, and melanoma , 20–22. via PI3K/Akt and MEK/ERK signaling pathways  were elevated, which might be related to the immune activation of ICIs, while the underlying mechanisms remain unknown. Kanie et al.  retrospeThis study also has some limitations that could be improved. Firstly, it is a single-center retrospective study, and data from multiple centers would be evaluated in further studies. Secondly, limited by our current condition, the sample size of this study was small, which might lead to large confidence intervals and affect the imprecision of the results. The larger sample size is valuable for stratified analysis to identify the effect of GH on ICI efficiency in different surgical history subgroups. Thirdly, there are some potential limitations in regarding ORR as an endpoint in the study of ICI efficacy, because it might miss AGC patients who continuously obtain stable results from immunotherapy and bring long-term survival, and it is not a comprehensive measure of clinical benefit. Therefore, this study not only applied ORR and DCR but also integrated OS and PFS results to evaluate the effect of GH level on treatment efficacy of ICIs in AGC patients, which makes the overall conclusion more comprehensive and reliable. Fourthly, the side effect of combined medicine was not completely excluded in this study, although the combination with medicines such as trastuzumab, lenvatinib, apatinib, and chemotherapeutic agents often displayed different side effects compared with ICIs for GC treatment and rarely showed endocrine toxicity. Endocrinopathies including hypophysitis, thyroid dysfunction, and adrenal insufficiency are among the most common irAEs associated with ICI treatment. However, to the best of our knowledge, this is the first study to reveal the relationship between GH and the ICI efficacy in the treatment of gastric cancer. The influence of GH on ICI treatment of tumor seems to be gastric cancer specific; we evaluated its effect on hepatocellular carcinoma and esophageal cancer patients with ICI treatment, but no association could be found Table S3In conclusion, GH might be used as a predictive marker for ICI therapy in AGC patients.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University (No. 2021136). The patients/participants provided their written informed consent to participate in this study.YZ and ZG contributed to the conceptualization and study design; ZJ, CW, and JL collected the patient data; YZ, ZJ, and JL performed the statistical analysis; YZ and SZ wrote the original draft of the manuscript; RZ and ZG administrated and supervised the project; all authors contributed to manuscript revision and read and approved the submitted version.This study was funded by a grant from the S&T Program of Hebei Province (number 20377726D).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.


Dear Editor,A 25-year-old man presented to the dermatology department with an 8-year history of yellowish-brown skin lesions on his right chest, axilla, and arm. The lesions first appeared on the right chest and increased in number and size gradually, showing a linear distribution, with no pain or itching. He was otherwise healthy with no other special medical history. Physical examination revealed a yellowish-brown firm, smooth papules and plaques on his right chest, axilla, and arm, ranging from 1 to 10 mm in diameter Figs.  . The diSyringoma is a benign neoplasm that derives from eccrine sweat gland ducts. The typical clinical manifestation is single or multiple skin-color or yellowish papules on the lower eyelid, 1 to 3 mm in size. Friedman and Butler classified syringoma into 4 clinical variants: generalized forms, localized forms, familial forms and variants associated with Down’s syndrome.Though syringoma is a common ailment, the pathogenesis remains unclear, some investigators have suggested that syringomas may be caused by hormonal factors.As we all know, syringoma rarely shows the unilateral or linear distribution. There have been only 4 reports of unilateral linear syringoma, all involving the upper trunk and limb.Medical Science and Technology Research Projects in Guangdong Province (A2021365) and Science and Technology Plan Projects of Zhuhai (ZH2202200003HJL).This work is supported by Danyi Huang took effective participation in research orientation and completed the preparation and writing of the manuscript. Yanqing Chen was in charge of the data collection, analysis and interpretation. Jianjian Li helped with data collection. Han Ma formed the study conception and planning and approved the final version of the manuscript.None declared.


The past four decades have seen the growing use of tissue or cell transplants in Parkinson’s disease (PD) treatment. Parkinson’s cell therapy is a promising new treatment; however, efficacy of cell transplantation for Parkinson’s disease are entirely unclear.To conduct a meta-analysis and a systematic review of the efficacy of cell therapy in patients with PD.2 index were applied to evaluate the quality of studies between-study heterogeneity, respectively.A systematic literature review and meta-analysis of 10 studies were performed to assess the efficacy of cell therapy in Parkinson’s patients. To achieve this, we compared the change in Unified Parkinson’s Disease Rating Scale (UPDRS) II and III scale scores to baseline and assessed the incidence of transplant-related adverse events. The MINORS score and the In = 120). The improvement in motor function based on the UPDRSIII assessment was −14.044  (p < 0.001), whereas improvement in daily living ability based on the UPDRSII assessment was −5.661  (p < 0.001).The literature search yielded 10 articles (The present findings demonstrate important clues on the therapeutic effect of cell therapy in alleviating motor impairment and daily living ability in PD patients. Parkinson’s disease (PD), the second most common neurodegenerative disease after Alzheimer’s disease, is characterized by prodromal symptoms, motor difficulties, and psychological or cognitive problems. The median age-standardized annual incidence rate of PD is 14 per 100,000 people, 160 per 100,000 people aged 65 years or older in high-income countries. For Asians, the incidence rate of PD is 11.3 per 100,000 people . Of noteAs a progressive neurodegenerative disease, PD causes focal degeneration of midbrain dopamine (MesDA) neurons. This reduces the release of the midbrain dopamine neuron cytosol of PD, localized in the ventral midbrain (Vm) in the substantia nigra densa, from associated axons and spiny neurons in the striatum . Aside fIn addition, surgical procedures such as pallidotomy or thalamotomy, or deep brain stimulation can be used to manage PD . UnfortuIn view of the above reports, cellular therapy presents more benefits compared to traditional treatment modalities as it improves the continuity of drug therapy, shortens the off-time, reduces the severity of movement disorders, and delay drug-related complications associated with oral medications .The present systemic review was performed following guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 and the PRISMA 2020 updated statement. The requirements of an Institutional Review Board approval or informed patient consent were waived for this review. A literature search was performed in English on PubMed (MEDLINE) and Web of Science databases with no time restrictions. The search string was built as follows: (Parkinson) AND (cell transplantation). A manual search of the reference lists supplemented the electronic database search. The reference list of all selected articles was screened independently to identify additional studies that may have been missed in the initial search.The study question was formulated according to the Population, Intervention, Comparison, Outcome, and Study design (PICOS) strategy. Studies that met the following inclusion criteria were analyzed: PD patients receiving stem cell therapy (Population), Stem cells with different cell types and different ways of administration (Intervention), Placebo control (Comparison), UPDRS II and III score staging changes from baseline (Outcome). All study designs were eligible for inclusion. However, animal experimental studies, letters, comments, and editorials were excluded. Care was taken to avoid data duplication. In the first screening phase, all studies were evaluated for eligibility based on a review of the title and the abstract. In the second screening phase, full-text articles were reviewed for eligibility criteria.Three investigators reviewed all articles independently. The investigators consulted amongst themselves in cases of differing opinions and if agreement could not be reached other experts were consulted. The data extracted from each study included the following: first author, publication year, study type, sample size, age, course of PD, dose, route of administration, type of administration, follow-up time, treatment-related complications, UPDRS score, UPDRS improvement rate, results, and conclusions. Cross-checking of the data was performed before analysis.One author evaluated the methodological quality of all studies. Two authors held discussions and verification to achieve consensus and establish an agreement with overall rating scores. Three investigators assessed the quality of the included studies independently with the Strengthening the Methodological Index for Non-randomized Studies (MINORS) method. Notably, items were scored 0 if not reported; 1 if the reporting was inadequate; 2 if the reporting was adequate. The global ideal score was 24 and 16 for comparative and non-comparative studies. The final assessment result was decided after the discussion. None of the included studies was a comparative in nature; therefore, the maximum score was 16.2 and Cochrane’s Q statistics were applied to evaluate the heterogeneity among studies. For I2 < 40%, a fixed-effects approach was employed. Otherwise, the between-study variance was determined by the random-effects method. The Begg test was used to test for publication bias. In case of publication bias, trim and fill analysis was performed to evaluate the number of missing studies, impute missing studies and recalculate the pooled risk estimate.Meta-analyses were performed by R software 4.1.1  with Meta package (version 4.18-2) and the R package “Meta” to establish changes in UPDRS scores before and after the intervention. Results were presented as proportions at 95% confidence intervals (CIs). Forest plots were applied to illustrate the improvement of dyskinesia in PD patients by cell therapy. IThe literature search yielded 1,082 articles after eliminating duplicates. In the first screening phase, 862 articles were excluded, leaving 220 articles that underwent full-text review. In the second screening phase, 206 articles were excluded. As a result, 10 articles reporting on cell therapy treatment in patients with PD were included for analysis. The study selection process is illustrated in a PRISM flowchart . The Resp < 0.001) for motor. I2 index and Cochrane’s Q test were employed to assess the heterogeneity between studies. I2 and Q statistics were 81.3% (95% CI: 66.7–89.5%) and 48.19 (P < 0.001) (p < 0.001) for ADL. I2 and Q statistics were 25% (95% CI: 0–64.6%) and 10.610 (P = 0.225), This result illustrates no significant heterogeneity  were included for analysis. The present meta-analysis aimed at assessing the efficacy and safety of cell transplantation for PD. Regarding efficacy, a significant improvement in all primary outcomes (UPDRSIII) was reported with a score improvement of −14.044  (< 0.001) . The stu< 0.001) . And a sogeneity .2 = 80.6%; duration mean > 10 years −18.611  I2 = 67.7%; (subgroup difference test: P = 0.115). Outcomes based on different follow-up times: Follow up = 6–12 months −18.061  I2 = 73.7%; Follow up > 18 months −2.912  I2 = 4.6%, (subgroup difference test: P < 0.001). Of note, the heterogeneity of the subgroups was reduced, suggesting that these factors are a potential heterogeneity source. More specifically, the best improvement is achieved at nearly 1 year postoperatively  and different follow-up time endpoints (6–12 months or ≥ 18 months) on the effectiveness of cell transplantation. Outcomes based on different mean durations: duration mean < 10 years −8.569  Iratively .The results of Begg’ test for the 10 studies was 0.325 indicating no significant publication bias. Further evaluation of potential publication bias was performed by sensitivity analysis. Similarly, results revealed no obvious bias among studies.P < 0.0001), −5.661  (P < 0.0001). Of note, the confidence intervals did not include 0, indicating that the results are statistically significant.The present meta-analysis of the safety and efficacy of cell transplantation for Parkinson’s disease demonstrated that cell transplantation therapy improves motor function and daily living ability of Parkinson’s patients. The meta-analysis focused on the improvement of UPDRS scores in Parkinson’s patients before and after cell transplantation, whereby the amount of improvement in UPDRSIII and UPDRSII was −14.044  , transplantation of embryo-derived dopaminergic neurons (DA neurons) into PD patients could replace endogenous degenerated DA neurons and improve clinical symptoms of PD . This apMesenchymal stem cells are adopted in PD therapy, probably for their neuroprotective potential driven by anti-inflammatory properties and paracrine factors. In the past few years, most researchers purposed to evaluate the positive impact of MSCs in reducing apoptosis and on neuronal cell survival . In addiIn the future, finished ESC induced iPSC and MSCs may be more superior options compared to previous approaches that used fetal cells .The most critical issue in cell therapy protocols is the scheme to determine the optimal dose of cells and the best administration route while considering efficacy and safety. At the same time, the main challenge in cell therapy is the mechanism for the safe and efficient delivery of stem cells to the lesion . ControvMoreover, intravenous administration is relatively safe but systemic injections of cells such as (MSC) are easily captured by cells in the lungs, arriving at the brain in very limited numbers.For successful intravascular drug delivery, cells must cross the hepatic and pulmonary capillary networks and the blood-brain barrier (BBB) , In thisCurrent evidence indicates that cell transplantation is yet to be applied fully in the clinical treatment of Parkinson’s disease. Therefore, more exploration is warranted to fully elucidate the potential mechanisms of cell therapy and provide reliable evidence for the clinical application of cell-based therapies. Accordingly, the present meta-analysis qualitatively and quantitatively evaluated the safety and efficacy of cell transplantation therapy for Parkinson’s disease. The findings suggest that cell transplantation is safe and effective, relative to conventional treatments and hold great application prospect at the forefront of Parkinson’s disease treatment. However, to substantiate the robustness of the findings, studies with larger sample sizes and longer follow-up periods are needed.Despite promising results regarding efficacy in various clinical trials and proven safety and feasibility, many questions remain unanswered. The cell type, administration route, dose and frequency vary widely between the individual studies. Even among studies for the same disease and using the same cell type, there is large variability between these parameters. all results should be interpreted with caution . In termA few limitations of this study should be considered. To begin with, some excellent clinical studies could not be included in the clinical analysis due to the lack of raw data. Secondly, limited by the experimental outcome data, the present work only used UPDRS and ADL scores as outcome indicators, which may not completely describe the experimental results. Furthermore, The sample size we used for subgroup analysis was small and there may be false-positive or false-negative results. And the inherent stability of single-arm meta-analysis is lower than that of 2-arm, which is one explanation for the high heterogeneity of this study.Differences in improvement rates between RCTs and open clinical trials: In studies of cellular therapy for Parkinson’s disease, it is difficult to design a double-blind, identical route of administration, placebo control group when the principle of no harm is to be considered in relation to the potential surgery-inflicted harm to the brain. Differences in improvement rates between RCTs and open clinical trials: According to the principle of no harm, it is difficult to design a double-blind, identical route of administration, placebo control group in studies of cell therapy for Parkinson’s disease that needs to take into account for potential surgery-inflicted harm to the brain. Comparing results of clinical trials to those of randomized controlled trials, the divergence in the efficacy of cell transplantation is wide. Explaining this discrepancy is difficult and can be partly related to differences in the heterogeneity of transplanted tissues, the application of immunosuppressive agents, and follow-up duration. Therefore, extensive research will have to be conducted in the future including elucidating the exact mechanism of action, possible immune rejection, functionality and the survival of the administered cells to draw adequate conclusions. In doing so, controlled or comparative and blinded studies with a large sample size and longer follow-up should be performed using the same cell type, administration route, dose and frequency. Also, for such studies with surgical procedures (including stereotactic surgery), more alert for highly relevant placebo reactions with patients and observers is required . An attevia an invasive surgical procedure, ideally a sham-surgical control would be preferred.Collectively, the use of a double-blind placebo-controlled design should be considered for future large multicenter studies whenever possible. In case the cell product has to be administered Cellular therapy in Parkinson’s patients is beneficial in improving the motor symptoms of Parkinson’s. However, the effectiveness of this approach warrants further exploration. Meanwhile, in the future, the focus should be to explore the mechanism for screening patients suitable for transplantation, identify cells that are most suitable for Parkinson’s patients, How to implant cells safely and efficiently. To solve this important issue, the development of adequate models reflecting, as accurately as possible, the pathological processes of Parkinson’s disease is required. The iPSCs was a real breakthrough along this path. Our results require additional long-term prospective clinical studies with large samples. With the establishment of best practice guidelines for stem cell therapies, it will be possible to develop more effective and Safety approaches to treating PD.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.JW and YT performed the data analyses and wrote the manuscript. XS contributed in literature review and quality assessment of included studies. ZF helped with data extraction and quality assessment of included studies. LJ contributed to the conception of the study, and the manuscript preparation. YH helped to perform the analysis with constructive discussions. 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.