ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Polygonatum sibiricum， as a traditional Chinese medicine with both medicinal and edible properties， has attracted considerable attention due to its functions of nourishing Yin and moistening the lungs， tonifying the spleen and benefiting Qi， and nourishing the kidneys and filling essence. Recent studies have demonstrated that Polygonatum sibiricum plays a significant role in regulating the immune system， effectively enhancing and improving the morphology and function of immune organs， stimulating the proliferation and activation of immune cells， and regulating the secretion and release of immune factors， thereby enhancing the immune function of the body and improving various immune-related diseases. Although a large number of studies have explored the pharmacological effects and mechanisms of P. sibiricum， there has been no systematic review and summary of its immune regulatory activity and mechanisms. Therefore， this article comprehensively reviews the research achievements of P. sibiricum polysaccharides and saponins in the field of immune regulation in recent years， and further sorts out the immune regulatory mechanisms of P. sibiricum in multiple aspects： including increasing the organ index of the spleen and thymus， increasing the number and activity of tumor-suppressive bone marrow hematopoietic stem cells， improving intestinal flora imbalance， regulating the quantity and proportion of T lymphocyte subsets， increasing the level of immunoglobulin， promoting the proliferation of macrophages， enhancing the activity of natural killer cells， increasing the number of white blood cells， and promoting the maturation of dendritic cells， providing a solid theoretical basis and scientific evidence for the research and application of P. sibiricum， and promoting its development and application in traditional Chinese medicine immune enhancers and various functional products.

Objective To conduct a visual analysis of research hotspots and development trends in stress ulcer(SU)from 2004 to 2024 using CiteSpace software.Methods Relevant SU literature published between January 1,2004,and May 7,2024,was retrieved from the Web of Science data-base and analyzed visually using CiteSpace software.Results A total of 623 articles were included in this study.The number of publications followed a wavy increase trend from 2004 to 2024.The au-thor with the highest number of publications was MOLLER M H,the institution with the most publica-tions was Copenhagen University Hospital in Denmark,and the country with the most publications was China.Keyword analysis revealed that SU research primarily focused on exploring pathogenesis and developing prophylactic and therapeutic drugs.Conclusion The pathogenesis of SU needs further elucidation.Research on drugs and prevention tailored to different mechanisms inducing SU,the im-pact of enteral nutrition on patient prognosis,and the effectiveness of traditional Chinese medicine in prevention and treatment are hotspots and development trends in future research.

Objective:This study investigated the expression level of phosphatidylserine-specific phospholipase A1(PLA1A)in colorectal can-cer(CRC)and analyzed its correlations with clinicopathological features,prognosis,and immune infiltration.Methods:The expression level of PLA1A in CRC was screened,and the influence of this expression level on patient prognosis was analyzed using bioinformatics methods.A cohort of 192 patients diagnosed with CRC at Shanxi Province Cancer Hospital from January to December 2020 were selected.The PLA1A ex-pression level in those with CRC was determined using immunohistochemistry(IHC)and real-time quantitative reverse transcription PCR(RT-qPCR).The relationship between PLA1A level and the clinicopathological features of the patients with CRC was analyzed using the chi-square test.The expression levels of immune cell markers CD4 and CD8 as well as immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4 in CRC were detected via IHC,and their correlations with PLA1A level were analyzed using the chi-square test.Results:The results of bioinformatics analysis showed that the expression level of PLA1A in CRC tissue was higher than paracancerous tissue,which correlated with overall surviv-al(OS)(P<0.05).The IHC and RT-qPCR results showed that PLA1A expression level was significantly upregulated in CRC tissiue(P<0.05).High PLA1A level was closely associated with the TNM stage,degree of differentiation,and lymph node metastasis(P<0.05).The IHC results demonstrated that PLA1A positively correlated with the infiltrating CD8+T cell level(P<0.05).In addition,the elevated PLA1A levels upregu-lated the expressions of immunosuppressive checkpoints PD-1,TIM-3,and CTLA-4(P<0.05).Conclusions:PLA1A is highly expressed in CRC,which is closely related to immune infiltrating cells and immunosuppressive checkpoints,suggesting that PLA1A plays an important role in immune infiltration in CRC,a finding that provides guidance in the treatment of CRC.

Objective:To explore the expression of 7-dehydrocholesterol reductase (DHCR7) in gastric cancer using bioinformatics methods and its relationship with clinical pathological characteristics and prognosis of gastric cancer patients.Methods:DHCR7 expression in gastric cancer was analyzed using the UALCAN database; DHCR7 mRNA expression and its relationship with the prognosis of gastric cancer patients were analyzed using the Kaplan-Meier plotter database; The expression of DHCR7 and its correlation with tumor immune infiltration level were analyzed using Sangerbox 3.0 and TIMER database; Real-time fluorescence quantitative PCR was used to detect the expression of DHCR7 mRNA in gastric cancer tissues and adjacent tissues; immunohistochemical staining was conducted to detect the DHCR7 expression in gastric cancer tissues and adjacent tissues and its correlation with clinical pathological parameters; Receiver operator characteristic (ROC) curve was used to evaluate the efficacy of DHCR7 expression in the diagnosis of gastric cancer.Results:The analysis results of the UALCAN database showed that there were statistically significant differences in DHCR7 mRNA expression among gastric cancer patients of different genders ( χ2=18.15, P<0.001), grades ( χ2=16.32, P<0.001), and TP53 mutation status ( χ2=20.12, P<0.001). Survival analysis showed that the 10-year overall survival (OS) rate ( HR=1.55, 95% CI: 1.31-1.84, P<0.001), 10-year progression free survival (PFS) rate ( HR=1.67, 95% CI: 1.36-2.05, P<0.001), and 10-year post progression survival (PPS) rate ( HR=1.81, 95% CI: 1.43-2.28, P<0.001) of gastric cancer patients with high DHCR7 expression were significantly lower than those with low DHCR7 expression. Immune infiltration analysis showed the expression of DHCR7 was negatively correlated with the comprehensive score ( r=-0.51, P<0.001), stromal cell score ( r=-0.48, P<0.001), immune cell score ( r=-0.45, P<0.001), CD4 + T cells ( r=-3.01, P<0.001), macrophages ( r=-0.40, P<0.001), neutrophils ( r=-0.32, P<0.001), and dendritic cells ( r=-0.37, P<0.001) infiltration levels in gastric cancer, and positively correlated with the purity of gastric cancer cells ( r=0.15, P<0.001). The qRT-PCR results showed that compared with adjacent tissues (1.86±0.51), the expression of DHCR7 in gastric cancer tissues (3.43±0.13) was significantly upregulated, with a statistically significant difference ( t=42.89, P<0.001). The relative expression level of DHCR7 in normal gastric mucosal cells GES-1 was 1.06±0.19, and the relative expression levels in four types of gastric cancer cells (HGC-27, AGS, SNU-1, and SGC-7901) were 2.40±0.26, 1.88±0.11, 1.51±0.04, and 2.63±0.20, respectively, there were statistically significant differences in the expression of DHCR7 among the five types of cells ( F=38.34, P<0.001), and the relative expression level of DHCR7 in normal gastric mucosal cells was statistically significant different compared to the four types of gastric cancer cells mentioned above ( P=0.002; P=0.003; P=0.017; P<0.001) ; The immunohistochemical results showed that the high expression rate of DHCR7 in gastric cancer tissues was 80.0% (96/120), which was significantly higher than that in adjacent tissues (68.3%) (82/120) ( χ2=56.84, P<0.001). There were statistically significant differences in tumor maximum diameter ( χ2=40.17, P<0.001), histological grade ( χ2=16.20, P<0.001) and pTNM stage ( χ2=16.99, P<0.001) between patients with high and low DHCR7 expression. The ROC curve results showed that the area under the curve (AUC) of DHCR7 expression level for diagnosing gastric cancer were 0.76 (based on TCGA database, 95% CI: 0.68-0.83, P<0.001) and 0.97 (120 clinical samples of gastric cancer, 95% CI: 0.95-0.99, P<0.001), respectively. Conclusions:DHCR7 is highly expressed in gastric cancer and closely associated with poor prognosis in patients, which may be a novel biomarker for the diagnosis and prognosis of gastric cancer.

Objective To investigate the mechanisms of Danggui Shaoyao San(DSS)in treating adenomyosis(AM),endometriosis(EMs),and sequelae of pelvic inflammatory disease(SPID)through network pharmacology and molecular docking,guided by the traditional Chinese medicine(TCM)principle of"same treatment for different diseases".Methods Chemical components of DSS were retrieved from the TCMSP and SwissTargetPrediction databases,and their targets were identified.Disease targets for AM,EMs,and SPID were collected from DrugBank,OMIM,GeneCards,and DisGeNET.A Venn diagram was constructed using Venny 2.1 to identify common targets between DSS and the diseases.A"drug-active component-shared target"network was established via Cytoscape 3.7.2.Protein-protein interaction(PPI)networks were analyzed using STRING and Cytoscape 3.7.2 to explore molecular mechanisms.Key targets were localized to tissues using BioGPS.Functional enrichment analysis of GO terms and KEGG pathways was performed via DAVID,followed by molecular docking validation.Results Thirty-nine active components and 529 potential targets of DSS were identified,with 60 shared targets across the three diseases.Enrichment analysis revealed that DSS treats AM,EMs and SPID by modulating cancer-related pathways,the PI3K/Akt signaling pathway,HIF-1 signaling pathway,and TNF signaling pathway.Molecular docking demonstrated stable binding conformations between DSS's primary active components and core targets.Conclusion DSS treats AM,EMs and SPID through multiple compounds[e.g.,(+)-catechin,kaempferol,β-sitosterol]acting on key targets(TNF,EGFR,PTGS2,HIF1A)across various organs,modulating inflammation,immune response,angiogenesis,and cell signaling pathways,thereby exerting its"same treatment for different diseases"effect.

Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.

Traditional Chinese medicine(TCM)is an ancient medical system distinctive and effective in treating cancer,depression,coronavirus disease 2019(COVID-19),and other diseases.However,the relatively abstract diagnostic methods of TCM lack objective measurement,and the complex mechanisms of action are difficult to comprehend,which hinders the application and internationalization of TCM.Recently,while breakthroughs have been made in utilizing methods such as network pharmacology and virtual screening for TCM research,the rise of machine learning(ML)has significantly enhanced their inte-gration with TCM.This article introduces representative methodological cases in quality control,mechanism research,diagnosis,and treatment processes of TCM,revealing the potential applications of ML technology in TCM.Furthermore,the challenges faced by ML in TCM applications are summarized,and future directions are discussed.

Objective To explore the effects of Peiyuan Yishen Antai Decoction on cell senescence and decidualization of aged mice with recurrent spontaneous abortion(RSA)based on P53/P21 signaling pathway;To discuss its mechanism in the treatment of RSA.Methods 8-9 month old CBA/J female mice were randomly divided into aging model group(normal saline 0.3 mL/d),Chinese materia medica group(18.72 g/kg)and dydrogesterone group(2.6 mg/kg).6-8 week old CBA/J female mice were assigned to a reproductive age blank group(normal saline 0.3 mL/d),with five mice in each group.After administering the corresponding solutions by gavage for 2 weeks,the reproductive age blank group mice were housed in cages with BALB/c male mice,while the remaining groups were housed in cages with DBA/2 male mice.After confirming the presence of vaginal plug,gavage was continued until the 9th day of pregnancy for sampling.Mice embryo loss rate was observed,HE staining was used to observe the morphology of uterine decidua,immunohistochemistry was used to detect the localization and expression of aging related protein Pi6INK4a in decidua tissue,RT-PCR and Western blot were used to detect the mRNA and protein expressions of P53,P21,insulin-like growth factor binding protein 1(IGFBP-1)and prolactin(PRL)in decidual tissue.Results Compared with the reproductive age blank group,the embryo loss rate of the aging model group significantly increased(P＜0.05),the irregular endometrial cells were vacuolated,the number of glands and blood vessels was reduced,the expression of P16INK4a in decidual tissue significantly increased(P＜0.05),and the expressions of P53,P21 mRNA and protein significantly increased(P＜0.05),the mRNA and protein expressions of IGFBP-1 and PRL significantly decreased(P＜0.05).Compared with the aging model group,the Chinese materia medica group and the dydrogesterone group showed an decreasing trend in embryo loss rate in mice,the arrangement of cells in the decidua tissue was relatively neat,and the number of blood vessels and glands increased,the expression of P16INK4a in decidua tissue was significantly decreased(P＜0.05),the mRNA and protein expressions of P53 and P21 were significantly decreased(P＜0.05),while the mRNA and protein expressions of IGFBP-1 and PRL significantly increased(P＜0.05).Conclusion Peiyuan Yishen Antai Decoction can improve the aging status of endometrial stromal cells in aged RSA model mice by regulating the P53/P21 signaling pathway,promote decidualization process,and thus exert a protective effect on pregnancy.

Objective To simulate modern social stress using a pre-pregnancy chronic mild stress(CMS)model and to explore the mechanisms of emotional,behavioral,and neurodevelopmental changes in male offspring of pre-pregnancy liver qi stagnation female mice through corticosterone(CORT)-brain-derived neurotrophic factor(BDNF)extracellular signal-regulated kinase(ERK)1/2 signaling cascade-mediated hippocampal injury.This study aimed to elucidate the impact of negative life events on offspring and the interventional mechanism of Shuyu Capsules.Methods CMS stress was used to induce pre-pregnancy depression in female rats(liver qi stagnation state),followed by intervention with Shuyu and fluoxetine capsules.After screening,male rats were mated and 12 male offspring from each group were selected for behavioral testing and detection of serum CORT levels by enzyme-linked immunosorbent assay.BDNF,ERK1/2,phospho(p)-ERK1/2,cAMP-response element binding protein(CREB),and p-CREB protein levels in the hippocampus were detected by Western Blot,and BDNF,ERK1,ERK2,and CREB mRNA levels in the hippocampus were detected by reverse transcription-polymerase chain reaction(RT-PCR),to verify the effects of pre-pregnancy CMS on the BDNF-ERK1/2-CREB signaling pathway and to investigate the key micro-mechanisms of Shuyu Capsules on emotional and learning memory-related behaviors of male offspring of females with pre-pregnancy liver qi stagnation syndrome.Results The distance,number of entries,and duration of stay in the central area in open-field experiments were significantly reduced in offspring in the model group(all P＜0.05).The escape latency during the exploration period of the water-maze experiment was significantly prolonged(P＜0.05)and the swimming distance,duration of the target quadrant,and number of platform crossings were significantly reduced(P＜0.05,P＜0.05,P＜0.01),the suspension time and frequency in the forced-swimming experiment were increased(P＜0.05,P＜0.01),and the incubation period was shortened(P＜0.05)in offspring in the model group.Prophylactic treatment with Shuyu Capsules and fluoxetine improved the depression-like behavior and cognitive impairment in the offspring in the model group.Biochemical tests showed that CORT levels were increased in the CMS model group(P＜0.05),BDNF,p-ERK1/2,and p-CREB protein levels in the hippocampus were decreased(all P＜0.05),and BDNF,ERK1,ERK2,and CREB mRNA levels were significantly reduced(P＜0.01,P＜0.05,P＜0.01,P＜0.05).Treatment with Shuyu Capsules and fluoxetine increased the CORT content and BDNF,ERK1/2,and CREB protein and mRNA levels in male offspring to varying degrees.Conclusions High levels of CORT in offspring act selectively on the hippocampus,exerting adverse effects on the emotional and learning memory functions of rats by downregulating the BDNF-ERK1/2 signaling cascade.The Chinese medicine Shuyu Capsules can reduce the impact of an adverse intrauterine environment on offspring development by correcting abnormal levels and pathways of glucocorticoids.