Background: Sex hormones may influence the development of gastrointestinal cancer, but evidence is inconsistent. Methods: We systematically searched MEDLINE and Embase databases to identify prospective studies examining associations between prediagnostic circulating levels of sex hormones and risk of five gastrointestinal cancers: esophageal, gastric, liver, pancreatic, and colorectal cancer. Pooled ORs and 95% confidence intervals (95% CI) were calculated using random-effects models. Results: Among 16,879 identified studies, 29 were included (11 cohort, 15 nested case–control, and three case–cohort studies). Comparing the highest versus lowest tertiles, levels of most sex hormones were not associated with the studied tumors. Higher levels of sex hormone binding globulin (SHBG) were associated with increased risk of gastric cancer (OR = 1.35; 95% CI, 1.06–1.72), but such associations were restricted in men only (OR = 1.43; 95% CI, 1.10–1.85) when stratified by sex. Higher SHBG levels were associated with increased risk of liver cancer (OR = 2.07; 95% CI, 1.40–3.06). Higher testosterone levels were associated with increased risk of liver cancer overall (OR = 2.10; 95% CI, 1.48–2.96), particularly in men (OR = 2.63; 95% CI, 1.65–4.18), Asian populations (OR = 3.27; 95% CI, 1.57–6.83), and in hepatitis B surface antigen-positive individuals (OR = 3.90; 95% CI, 1.43–10.64). Higher levels of SHBG and testosterone were associated with decreased risk of colorectal cancer in men (OR = 0.89; 95% CI, 0.80–0.98 and OR = 0.88; 95% CI, 0.80–0.97, respectively) but not in women. Conclusions: Circulating levels of SHBG and testosterone may influence the risk of gastric, liver, and colorectal cancer. Impact: Further clarifying the role of sex hormones in the development of gastrointestinal cancer may unravel future novel targets for prevention and treatment.

Ischemic stroke is the most common type of stroke, with high mortality, disability and recurrence rate, which brings a heavy burden to individuals, families and the medical system. Therefore, the intervention and treatment of ischemic stroke are of great significance. Chinese herbal medicine is widely used in treating stroke, for example, Dengzhan shengmai (DZSM) capsule. The current systematic review aims to comprehensively evaluate the efficacy and safety of the DZSM capsule in treating ischemic stroke. Eligible randomized controlled trials (RCTs) were included to evaluate the efficacy and safety of Chinese herbal medicine DZSM capsule in treating ischemic stroke. Eight electronic databases were searched up to January 27, 2021. The risk ratio (RR), standardized mean difference (SMD), or weighted mean difference (WMD) with 95% confidence interval (CI) were used to assess DZSM capsule treatment outcomes. A total of 28 RCTs involving 6683 participants were included in the systematic review and meta-analysis. Compared with conventional therapy group, DZSM capsule plus conventional therapy improved Barthel Index scores (WMD: 8.97, 95%CI: 5.88-12.05) and reduced modified Rankin Scale (WMD: -0.75, 95%CI: -1.02∼ -0.48), reduced neurological functional deficit scores (WMD: -2.81, 95%CI: -4.17∼ -1.44), recurrence rate (RR: 0.57, 95%CI: 0.44-0.73) and mortality (RR: 0.54, 95%CI: 0.31-0.95), improved clinical effect (RR: 1.18, 95%CI: 1.12-1.24) and quality of life (WMD: 21.67, 95%CI: 6.74-36.61), exhibited a beneficial effect on hemorheology such as elevated levels of APTT (SMD: 1.17, 95%CI: 0.87-1.47) and INR (SMD: 1.12, 95%CI: 0.82-1.42), and on lipid metabolism such as levels of TC (SMD: -0.62, 95%CI: -1.04 ∼ -0.20), TG (SMD: -0.72, 95%CI: -1.18∼ -0.26), LDL (SMD: -1.14, 95%CI: -1.57∼ -0.71) and HDL (SMD: 0.93, 95%CI: 0.36-1.50). No trials reported severe adverse events. DZSM capsule appears to be safe and effective in clinical applications for ischemic stroke. Based on conventional therapy, adding the DZSM capsule could reduce the mortality, recurrence rate, and neurological functional deficit scores, improve clinical effect and quality of life. In addition, compared with conventional therapy, the addition of the DZSM capsule played a beneficial role in hemorheology and lipid metabolism, which may attribute to the potential mechanism.

Background. Some studies showed that microRNA-497 (miR-497) might act as a prognostic biomarker of cancer. However, the conclusion was not consistent. The aim of this study was to investigate the prognostic role of miR-497 in various carcinomas. Methods. We systematically searched the databases of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data to identify relevant studies. Two independent reviewers performed the data extraction and assessed the study quality. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for overall survival (OS) and disease-free survival/relapse-free survival (DFS/RFS) were used to assess the associations between miR-497 expression and cancer prognosis. Results. A total of 15 studies involving 1760 participants fulfilled the inclusion criteria. The lower level of miR-497 expression was significantly associated with shorter overall survival (HR=2.19, 95% CI: 1.84-2.60). No significant association was found between miR-497 expression and DFS/RFS in various carcinomas (HR=1.17, 95% CI: 0.53-2.57). Subgroup analyses by ethnicity and cancer type showed the consistent results. Conclusion. Our studies suggested that miR-497 might be a prognostic biomarker in cancers. However, further multicenter prospective clinical researches are needed to confirm the association between miR-497 expression and cancer prognosis.

Background: The AJCC 8th edition post-neoadjuvant pathologic stage (ypStage) shows limited prognostic discrimination in esophageal squamous cell carcinoma (ESCC). Alternative strategies have been proposed, but most were limited by small samples and lack of inclusion of patients treated with immunotherapy. This study aimed to validate the AJCC 8th edition ypStage and develop a refined ypStage system with improved prognostic performance for ESCC. Methods: This was a large retrospective cohort study including 1848 consecutive ESCC patients treated with neoadjuvant therapy followed by esophagectomy between June 2018 and September 2023. Patients were randomly assigned to training ( n = 1108) and validation ( n = 740) cohorts. A refined ypStage was developed using recursive partitioning analysis (RPA). Survival outcomes were evaluated using Kaplan-Meier curves and log-rank tests, and multivariable Cox proportional hazards regression was used to confirm independent prognostic value. Prognostic performance of the RPA and AJCC 8th edition ypStage systems was compared using the Groome criteria: hazard consistency, hazard discrimination, sample balance, outcome prediction, and overall score. Subgroup analyses were performed by neoadjuvant therapy type. Results: The AJCC 8th edition ypStage showed a reversal of the expected survival hierarchy between ypStage II and IIIA [3-year overall survival (OS): II, 80.1%; IIIA, 90.7%]. RPA identified three groups: ypStage I (ypT0-2N0-1), II (ypT0-2N2-3 or ypT3-4bN0-1), and III (ypT3-4bN2-3). In the validation cohort, RPA ypStage demonstrated clear survival separation (3-year OS: I, 91.2%; II, 79.1%; III, 60.5%; pairwise P < 0.01). Multivariable analysis confirmed its independent prognostic value [II vs I: Hazard Ratio (HR) = 2.44, 95% Confidence Interval (CI): 1.68–3.52; III vs I: HR = 3.67, 95% CI: 2.28–5.90; both P < 0.001]. RPA ypStage outperformed AJCC ypStage across all evaluation metrics. Subgroup analyses further supported its robustness, particularly in patients receiving chemotherapy or chemo-immunotherapy. Conclusion: The RPA-derived ypStage provides improved prognostic stratification compared with the AJCC 8th edition in ESCC patients following neoadjuvant therapy. Further external validation is warranted for potential incorporation into future staging guidelines.

Background: Men with esophageal squamous cell carcinoma (ESCC) have worse survival than women, a disparity in which sex hormones may play a role. Yet, whether circulating sex hormone levels are associated with survival in ESCC remains largely unexplored. Methods: This prospective cohort study included 402 men with ESCC who underwent curative surgery in 2013–2020, with follow‐up until May 1, 2023. Associations between preoperative levels of 11 sex hormone measures and all‐cause mortality were assessed using multivariable Cox regression, reporting hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for age, calendar year of surgery, education, smoking, alcohol consumption, pathologic tumor stage, postoperative complications, and chemo(radio)therapy. Sex hormone measures were analyzed both as quartiles and continuously. Continuous analyses were conducted using z‐scores of ln‐transformed hormone levels, with HRs interpreted per one standard deviation (SD) increase. Results: In the overall cohort, no clear associations were observed after adjustment. In tumor stage‐stratified analyses, higher free testosterone index was associated with lower mortality in stage 0–II disease (HR per 1‐SD increase, 0.78; 95% CI, 0.62–0.97), whereas higher progesterone levels were associated with higher mortality in stage III–IV disease (HR per 1‐SD increase, 1.21; 95% CI, 1.01–1.44), with evidence of effect modification by tumor stage for progesterone ( p for interaction = 0.011). Conclusions: Preoperative sex hormone measures showed possible stage‐dependent associations with survival in men with ESCC, with higher free testosterone index associated with better survival in stage 0–II disease and higher progesterone levels associated with worse survival in stage III–IV disease.

Supplementary Table S1 shows characteristics of studies included in the meta-analysis.