1.Mechanism of active ingredient compatibility of Dimocarpus longan Lour. leaves in improving glucose and lipid metabolism disorders in type 2 diabetic mellitus rats
Yanli LIANG ; Shijia AN ; Fengsheng LI ; Jiani MAI ; Anqi HUO ; Jiali WEI ; Zejuan ZHANG ; Shuyan QIN ; Wenqing HUANG ; Jie LIANG
China Pharmacy 2026;37(13):1697-1703
OBJECTIVE To explore the mechanism of the active ingredient compatibility(quercetin, quercitrin and kaempferol at a mass ratio of 2∶9∶3)of Dimocarpus longan Lour. leaves(abbreviated as CDL) on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus (T2DM) rats. METHODS SD rats were randomly divided into blank control group, model group, metformin hydrochloride group (100 mg/kg), and CDL high-, medium- and low-dose groups (280, 140, 75 mg/kg), with 10 rats in each group. Rats in the blank control group were fed with standard chow, while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling, rats in each administration group were given corresponding drug solution, and rats in the blank control group and model group were intragastrically administered with equal volume of pure water, once a day, for consecutive 4 weeks. Fasting blood glucose (FBG) was detected at fixed time every week. The curves of oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were plotted, and the area under curve (AUC) was calculated. The pancreatic islet function indexes [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISI)],blood lipid indexes [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group, the FBG, AUC of IPITT curve, AUC of OGTT curve, HOMA-IR, the levels of FINS, TC, TG and LDL-C, as well as the protein and mRNA expression of phosphatase and tensin homolog, forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group ( P <0.05). ISI, the levels of HDL-C and hepatic glycogen content, along with the protein and mRNA expression of PI3K, insulin receptor substrate-1, Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased ( P <0.05). In model group rats, the arrangement of hepatocytes was irregular, the overall structure of pancreatic lobules was disordered, and a large number of inflammatory cell infiltration was observed. Compared with the model group, most of the above quantitative indexes were significantly reversed in the CDL high-dose group ( P <0.05), and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders, elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.
2.Mechanism of active ingredient compatibility of Dimocarpus longan Lour. leaves in improving glucose and lipid metabolism disorders in type 2 diabetic mellitus rats
Yanli LIANG ; Shijia AN ; Fengsheng LI ; Jiani MAI ; Anqi HUO ; Jiali WEI ; Zejuan ZHANG ; Shuyan QIN ; Wenqing HUANG ; Jie LIANG
China Pharmacy 2026;37(13):1697-1703
OBJECTIVE To explore the mechanism of the active ingredient compatibility(quercetin, quercitrin and kaempferol at a mass ratio of 2∶9∶3)of Dimocarpus longan Lour. leaves(abbreviated as CDL) on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus (T2DM) rats. METHODS SD rats were randomly divided into blank control group, model group, metformin hydrochloride group (100 mg/kg), and CDL high-, medium- and low-dose groups (280, 140, 75 mg/kg), with 10 rats in each group. Rats in the blank control group were fed with standard chow, while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling, rats in each administration group were given corresponding drug solution, and rats in the blank control group and model group were intragastrically administered with equal volume of pure water, once a day, for consecutive 4 weeks. Fasting blood glucose (FBG) was detected at fixed time every week. The curves of oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were plotted, and the area under curve (AUC) was calculated. The pancreatic islet function indexes [fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISI)],blood lipid indexes [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group, the FBG, AUC of IPITT curve, AUC of OGTT curve, HOMA-IR, the levels of FINS, TC, TG and LDL-C, as well as the protein and mRNA expression of phosphatase and tensin homolog, forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group ( P <0.05). ISI, the levels of HDL-C and hepatic glycogen content, along with the protein and mRNA expression of PI3K, insulin receptor substrate-1, Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased ( P <0.05). In model group rats, the arrangement of hepatocytes was irregular, the overall structure of pancreatic lobules was disordered, and a large number of inflammatory cell infiltration was observed. Compared with the model group, most of the above quantitative indexes were significantly reversed in the CDL high-dose group ( P <0.05), and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders, elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.
3.Factors influencing daily blood donation attendance and their spatial heterogeneity at fixed donation sites in Nanjing
Zhanghui LI ; Wenbiao LIANG ; Wenjia HU ; Xian CHEN ; Wenqing YUAN ; Nizhen JIANG
Chinese Journal of Blood Transfusion 2026;39(7):908-916
Objective: To analyze the time-related factors influencing daily blood donation attendance at fixed donation sites in Nanjing and the heterogeneity among sites, and to provide evidence for optimizing site layout and operational management. Methods: Based on daily attendance data from 17 fixed donation sites in Nanjing for the full year of 2025, matched with contemporaneous meteorological and air quality data, a two-stage negative binomial generalized linear mixed model (NB-GLMM) was constructed. In the second stage, site-level static characteristics (number of scenic spots, daily operating hours, number of shopping malls, public transport stops, hospitals, universities, and residential buildings) were additionally incorporated. Model comparison was performed using Akaike information criterion (AIC). Significance of random effects was tested by likelihood ratio test, and site-specific random effects were extracted using empirical Bayes estimation. Robustness of the results was verified through residual diagnostics and multiple sensitivity analyses. Results: The first-stage model showed that rainfall was associated with lower attendance (IRR=0.943, P<0.001); holidays were associated with higher attendance (IRR=1.162, P<0.001); Saturdays and Sundays showed higher attendance than Mondays, with the strongest association on Sundays (IRR=1.195, P<0.001). Temperature exhibited a non-linear relationship (linear term P=0.051, quadratic term P=0.036). The joint results of the linear and quadratic terms for temperature suggested a nonlinear relationship between attendance and temperature. After introducing static characteristics in the second stage, the number of scenic spots (IRR=1.372, P=0.008) and daily operating hours (IRR=1.823, P<0.001) were found to be positively associated with attendance, while the numbers of shopping malls, public transport stops, hospitals, universities, and residential buildings showed no significant effects. Conclusion: Daily blood donation attendance at fixed sites in Nanjing is influenced by multiple factors including weather, day of the week, holidays, and site surroundings. Substantial heterogeneity exists among different sites; extended operating hours and more nearby scenic spots are associated with increased attendance.
4.Preoperative prediction of lymphovascular invasion in breast cancer with digital breast tomosynthesis-based intratumoral and peritumoral radiomics
Suxin ZHANG ; Haiyan LI ; Yiqun ZHENG ; Wenqing CHEN ; Sheng HE ; Caixian YANG ; Gang LIANG ; Jianding LI ; Zengyu JIANG
Journal of Practical Radiology 2025;41(1):46-51
Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.
5.Distribution characteristics of food intolerance in children with autism spectrum disorders
Xiaoshuang ZHANG ; Jiajia ZHANG ; Hongfei DU ; Guohui LI ; Wenqing ZHANG ; Jing SU
Chinese Journal of Clinical Laboratory Science 2025;43(5):369-373
Objective To investigate the distribution of serum specific IgG antibodies against food in children with autism spectrum disorders(ASD),and provide experimental evidence for improving gastrointestinal symptoms of ASD children.Methods A retrospec-tive study was conducted on 411 children with ASD visited the Department of Psychology and Behavior of Hebei Children's Hospital from January 2021 to December 2022.Additionally,631 healthy children who underwent physical examination during the same period were collected as the healthy control group.Their venous blood samples were collected,and ELISA was used to detect the levels of 14 kinds of serum specific IgG antibodies against food.The distribution characteristics of food intolerance in children with different genders and ages were investigated.Results The total positive rate of specific IgG antibodies against food in children with ASD reached 91.84%(405/441).The top 3 positive rates of specific IgG antibodies were against egg(71.89%),milk(56.70%),and wheat(56.02%),respectively,which were significantly higher than those in the healthy control group(χ2=42.81,27.48,and 26.88,re-spectively,P<0.05).The comparative results of gender composition showed that the positive rate of specific IgG antibody against rice in female ASD children(15.96%)was significantly higher than that in male ASD children(4.90%,χ2=11.84,P<0.05).The posi-tive rates of specific IgG antibodies against egg and wheat in male and female ASD children were significantly higher than those in the healthy control group(χ2=19.44 and 4.42 for males,χ2=4.66 and 10.93 for females,P<0.05).The positive rate of specific IgG anti-body against milk in male ASD children was significantly higher than that in the healthy control group(χ2=12.62,P<0.05),while those against soybean and rice in female ASD children were also significantly higher than that in the healthy control group(χ2=7.00 and 5.42,P<0.05).There were significant differences in the positive rates of food intolerance to milk and soybean in ASD children with different ages(χ2=13.74 and 9.70,P<0.05)and they decreased with age.The positive rates of specific IgG antibody against wheat in ASD children aged 2-3 and 4-6 years were significantly higher than those in the healthy control group(χ2=5.78 and 4.55,P<0.05).The positive rate of specific IgG antibody against milk in ASD children aged 4-6 years was significantly higher than that in the healthy control group(χ2=7.57,P<0.05).Conclusion The highest positive rate of specific IgG antibodies against food in ASD chil-dren is against egg,which is not related to the patient's gender.Next are milk and wheat.The gastrointestinal issues and related food intolerance should be taken into account in the management of patients with ASD.
6.Analysis of the current status and influencing factors of frailty in patients aged 75 and above after percutaneous coronary intervention
Yang CHEN ; Shiyu WANG ; Chuan GAO ; Wenqing CAI ; Yajing SU ; Yumeng ZHANG ; Qingyin LI
Chinese Journal of Nursing 2025;60(13):1588-1595
Objective To evaluate the frailty status and risk factors among hospitalized elderly patients after percutaneous coronary intervention(PCI),and to provide a reference for improving and delaying their frailty.Methods From March to August 2024,using convenience sampling,patients aged over 75 years who underwent PCI in a tertiary cardiovascular disease specialist hospital in Beijing were selected as the survey participants.Patient-related informations were collected through a self-designed general information questionnaire.The Fried Phenotype Frailty Scale,the Katz Activities of Daily Living,Lawton Instrumental Activities of Daily Living(IADL)scale,the Charlson Comorbidity Index,the Morse Fall Scale,the Mini Nutritional Assessment-Short Form(MNA-SF),and the 15-item Geriatric Depression Scale(GDS-15)were evaluated postoperatively until discharge.Univariate and multivariate logistic analyses were conducted to identify factors associated with frailty among patients after PCI.Results A total of 278 patients were included.The incidence of frailty after PCI was 52.16%.Based on Fried Phenotype scores,patients were divided into a non-frail group and a frail group.Univariate analysis showed statistically significant differences between the 2 groups in terms of age,gender,hemoglobin,NT-ProBNP,LVEF,IADL scores,living alone status,nutrition status,falls risk,and depression level(P<0.05).Multivariate logistic regression analysis revealed that age,Lawton IADL scores,falls risk,nutrition status,depression level were factors influencing frailty,with odds ratios of 1.167,0.575,1.597,0.399,and 3.610,respectively(P<0.05).Conclusion The incidence of frailty is high among patients aged over 75 years after PCI,and there are multiple risk factors affecting their frailty status.Clinical healthcare providers should prioritize long-term management of these patients and implement comprehensive interventions with the consideration of their physiological,psychological,and social conditions.
7.POEMS syndrome with hepatosplenomegaly as the initial manifestation: A report of two cases
Ye ZHANG ; Wenqing WANG ; Jing LI ; Qianrong BAI ; Jiayu LI ; Yan CHENG ; Miaomiao FANG ; Nana GAO ; Changxing HUANG
Journal of Clinical Hepatology 2025;41(1):127-132
POEMS syndrome is a rare condition associated with plasma cell disorders, and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease, the patients presented with lower limb weakness, hepatosplenomegaly, lymph node enlargement, ascites, hypothyroidism, positive M protein, and skin hyperpigmentation, and 18F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome, and the symptoms were relieved after immunomodulatory treatment.
8.Clinical study on Qigong Pills combined with IVF-ET technique in the treatment of PCOS infertility with phlegm-dampness type
Meiwei ZHANG ; Wenqing YIN ; Xiaoxia LI ; Yan ZHAO ; Lei WANG
International Journal of Traditional Chinese Medicine 2025;47(5):601-606
Objective:To explore the effects and safety of Qigong Pills in IVF-ET outcome of PCOS infertility patients with phlegm-dampness type.Methods:A randomized controlled trial study was carried out. In the Reproductive and Genetic Medicine Center of Dalian Women and Children Medical Center (Group) from January 2021 to December 2023, 60 patients with sputum and damp-induced PCOS infertility assisted by in-vitro fertilization and embryo transfer (IVF-ET) were enrolled and randomly divided into 2 groups by block randomization method, with 30 cases in each group. Patients in both groups took ethinylestradiol cyproterone tablets orally on the 2nd to 5th day of the 1st menstrual cycle before IVF-ET cycle, and received down-regulation treatment on the 18th to 20th day of menstruation. After confirming that the down-regulation standard was reached, Qigong Pills was added to the treatment group, and placebo was taken orally until the trigger day. Two groups of patients underwent transvaginal ultrasound-guided ovarian aspiration after injection of chorionic gonadotropin (hCG) for 24-36 h. The total amount of Gn, the days of Gn, the endometrial thickness of HCG, the number of eggs obtained, the rate of diprokaryotic (2PN) fertilization, the number of transferable embryos, the number of high-quality embryos, the rate of high-quality embryos, the incidence of OHSS and the clinical pregnancy rate were compared between the two groups.Results:Among the 60 patients, 28 cases in the final treatment group and 27 cases in the control group were included in the outcome index evaluation. During controlled hyperstimulation (COH), the total Gn [2 025 (1 575, 2 325) U vs. 2 700 (2 025, 3 150) U, Z=-3.67] and the number of Gn days of the treatment group [10 (8,11) d vs. 11 (9,13) d, Z=-2.31] were lower than those in control group ( P<0.001 or P<0.05). There was no statistical significance in endometrial thickness between 2 groups on HCG day ( P>0.05); the number of high-quality embryos [3 (3, 4) vs. 2 (2, 3), Z=0.11] and the rate of high-quality embryos [46.28% (87/188) vs. 35.19% (57/162), Z=4.42] in the treatment group were higher than those in the control group ( P<0.05). There was no statistical significance in the number of eggs obtained, the fertilization rate of 2PN and the number of transferable embryos between the two groups ( P>0.05). The incidence of OHSS was 3.6% (1/28) in the treatment group and 11.1% (3/27) in the control group, without statistical significance ( P=0.352). The clinical pregnancy rate was 53.6% (15/28) in the treatment group and 37.0% (10/27) in the control group, without statistical significance ( P=0.218). There was no significant difference in the safety indexes of liver and kidney function between 2 groups ( P>0.05). Conclusion:Qigong Pills combined with IVF-ET can effectively reduce the total amount of Gn and the number of days of treatment in PCOS infertility patients with phlegm-dampness type, increase the number and rate of high-quality embryos, and improve the outcome of IVF-ET, and it is safe and effective.
9.Depression Syndrome Typing and Medication Pattern Analysis Through Unsupervised Clustering Combined With Latent Structure Dual Analysis
Huanxi ZHU ; Cheng YU ; Xuejun LI ; Ruixue WANG ; Yongjun CHEN ; Taiyi WANG ; Wenqing WU ; Lin YAO
Journal of Sichuan University (Medical Sciences) 2025;56(3):656-664
Objective Depression,a most common psychiatric disease,is defined in Traditional Chinese Medicine(TCM)as Yu Syndrome,i.e.,depression disorder,or Baihe Disease,i.e.,lily bulb disease,a category of emotional disorders treated with lily-based TCM preparations.In TCM,depression is managed through syndrome differentiation and treatment,which is characterized by high efficacy and safety.However,there is no unified standard for the classification of depression syndromes,which leads to a disconnection between the analysis of patients'medication patterns and their actual syndromes and hinders the study of medication patterns specific to particular syndromes.Therefore,this study is focused on investigating the medication patterns of different sub-types of depression patients based on an objective classification system of depression.Methods We searched for and retrieved clinical literature on TCM formulas for depression from relevant databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP Database,Sinomed,Web of Science,and PubMed.Information on patient symptoms and medication was standardized.Then,the symptoms and the medication frequency of depression patients were statistically analyzed.We used the K-means clustering method combined with implicit structural analysis to objectively categorize depression patients into sub-types.In addition,the main symptoms and core TCM formulas of each sub-type of depression patients were identified.On the basis of objective classification system,we also statistically analyzed the characteristics of herbs used on depression patients,including the 4 basic properties,the 5 flavors,the attributes,the therapeutic efficacy,and the co-occurrence patterns,which may help reveal the medication patterns.Results A total of 3 537 publications and 4 434 prescriptions were included in the analysis.By using the K-means algorithm and latent structure analysis methods,patients with depression were categorized into 9 sub-types,with Cluster 6 accounting for the largest proportion.The most common symptoms among depression patients were insomnia and a depressed mood.Medication frequency analysis showed that Radix Bupleuri(Chai Hu),Radix Paeoniae Alba(Bai Shao),Poria(Fu Ling),Rhizoma Chuanxiong(Chuan Xiong),and Radix Curcumae(Yu Jin)were the most commonly used TCM herbs.For the depression sub-types of Clusters 1,2,and 6,blood-activating and stasis-dissolving herbs were used most often.The depression sub-types of Clusters 3,4,5,8,and 9 were mainly treated with qi-regulating herbs,while the depression sub-type of Cluster 7 was treated with qi-supplementing herbs.Depression patients were mostly treated with herbs that were cold or warm in nature and had sweet,bitter,and pungent flavors.Moreover,treatments for Cluster 1 and Cluster 6 mainly targeted the spleen meridian,while those for Cluster 2,Cluster 3,Cluster 4 and Cluster 5 mainly targeted the heart meridian.The treatments for the other sub-types mainly targeted the liver meridian.The core TCM formulas for the 9 depression sub-types included Zishui Qinggan Decoction,Danzhi Xiaoyao Powder,Huanglian Wendan Tang,Chaihu Guizhi Tang,Modified Xiaoyao Powder,Qinggan Jieyu Tang,Xiaoyao Powder,Xuefu Zhuyu Decoction,and Bazhen Decoction.The most commonly used Chinese herbal medicinal formulas were Gan Cao-Chai Hu,Bai Shao-Chai Hu,and Chen Pi-Chai Hu.Conclusion Based on machine learning,this study reveals the scientific aspects of TCM typing and syndrome-based treatment.It clarifies the rationale for targeting different symptoms in depression treatment and provides theoretical support for clinicians to make medication prescriptions.It also presents a new perspective for investigating TCM medication patterns.
10.Tissue and plasma proteomic signatures associated with the risk of gastric cancer
Lanxin YANG ; Kaosaier AINIWAER ; Xue LI ; Hengmin XU ; Tong ZHOU ; Yang ZHANG ; Jingying ZHANG ; Weicheng YOU ; Kaifeng PAN ; Wenqing LI
Chinese Journal of Preventive Medicine 2025;59(3):302-308
Objective:To identify proteins associated with the risk of gastric cancer (GC) and build a protein risk score for risk prediction of GC based on proteomic analysis.Methods:Gastric mucosal proteomics data were used to construct Dataset One, comprising 94 GC cases and 230 individuals with different stages of gastric mucosal lesions. The GC cases were recruited from the National Upper Gastrointestinal Cancer Early Detection (UGCED) Program in Linqu, Shandong Province, as well as clinical patients from the Fifth Medical Center, General Hospital of PLA, and Peking University Cancer Hospital. Non-cancer individuals were enrolled from the National UGCED Program in Linqu and community screening programs at the Dongfang Hospital. All participants were pathologically confirmed. Multivariate logistic regression analysis was employed to identify gastric mucosal proteins significantly associated with GC risk. Subsequently, plasma proteomics data from the UK Biobank Pharma Proteomics Project (UKB-PPP) were used to construct Dataset Two, including 40 baseline GC cases and 47 933 non-cancer individuals, and Dataset Three, comprising 138 incident GC cases and 47 933 non-cancer individuals during a prospective follow-up period. In Dataset Two, multivariate logistic regression analysis was conducted to assess associations between plasma protein levels and baseline GC risk. In Dataset Three, multivariate Cox regression analysis was used to examine associations with the risk of incident GC. A poly-protein risk score (PRS) was developed using a weighted summation method based on protein effect sizes from Dataset Two. Its associations with GC risk and the progression of gastric mucosal lesions were evaluated using linear regression trend tests.Results:A total of 324, 47 973 and 48 071 participants were included in Datasets One, Two, and Three, respectively. Across the three datasets, the proportions of males and individuals aged>60 years were higher in the GC group than in the non-GC group (all P values<0.05). The follow-up period in Dataset Three had a M ( P 25, P 75) of 14.47 (13.7, 15.2) years, with a median of 7.4 (4.6, 11.3) years for those who progressed to GC. Based on Dataset One, 2 524 tissue-differential proteins associated with GC risk were identified through multivariate logistic regression analysis adjusted for age and sex. Among these, seven proteins were consistently associated with GC risk across tissue and plasma levels in Datasets Two and Three, with consistent directions of association. Five proteins (MRC1, APOL1, BST2, PON2, and GGH) were positively associated with GC risk, while two (GSN and CLEC3B) were negatively associated. Analysis of the PRS based on these seven proteins showed that for each standard deviation increase in the tissue-derived PRS, the risk of GC increased by 6.26 times (95% CI: 4.02-9.75). In Dataset Two, each standard deviation increase in the plasma-derived PRS was associated with a 2.13-fold increase in GC risk (95% CI: 1.68-2.69). In the prospective cohort of Dataset Three, individuals in the high PRS group had a 2.27-fold higher risk of GC compared to the low PRS group (95% CI: 1.50-3.45). Moreover, each standard deviation increase in the plasma PRS was associated with a 57% higher risk of GC ( HR=1.57, 95% CI: 1.34-1.84). Additionally, the tissue-derived PRS showed an increasing trend with the progression of gastric mucosal lesions. Conclusion:The tissue and plasma proteomics identified seven individual proteins that may indicate the risk of developing gastric cancer, showing the potential as biomarkers for aiding in the screening of gastric cancer.

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