1.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.
2.Application of tracking methodology in investigation of contamination incidents of bronchoalveolar lavage fluid specimens from children
Shengmei LAN ; Wenting YIN ; Lili ZHAO ; Ling ZHANG ; Yanping SONG ; Lanxin LIU ; Juan LI
Chinese Journal of Nosocomiology 2025;35(18):2796-2799
OBJECTIVE To explore the effect of tracking methodology on investigation of contamination incidents of bronchoalveolar lavage fluid(BALF)specimens from the children.METHODS The onsite tracking was carried out for the contamination incidents of BALF specimens of the children through the tracking methodology,the quality control processes of cleaning and disinfection of bronchofiberscopes and the tracking routes were determined.The quality control process of cleaning and disinfection of bronchofiberscopes were evaluated,the existing risks were found out,and the specific improvement measures were formulated.RESULTS The onsite tracking was carried out for the incident of carbapenem-resistant Klebsiella pneumoniae(CRKP)that was caused by the contamination of 12 BALF specimens from pediatrics department wards before and after Nov.1,2021.No.2180014C bronchofiber-scope without biological surveillance was determined as the high-risk point of contamination of BALF specimens,the monitoring procedure of cleaning and disinfection of the bronchofiberscopes was revised.The BALF specimens that were submitted from Dec.1,2021 to Dec.31,2021 were tracked,and no CRKP was detected among the 23 submitted specimens.Totally 12 bronchofiberscope specimens were collected for biological surveillance,and the qualified rate was 100.00%.The treatment rooms of pediatrics department,hand disinfection effect of health care workers of cleaning and disinfection rooms and disinfection effect of object surfaces were monitored,and the quali-fied rate was increased from 98.39%to 100.00%.CONCLUSIONS The tracking methodology is an effective tool for quality management and can be used for evaluation of quality process of cleaning and disinfection of bronchofi-berscopes,which may find out the causes for adverse events in a timely manner and raise the medical safety.
3.Risk factors of thyroid nodules in patients with type 2 diabetes
Chong WANG ; Lanxin KONG ; Shuzhen WANG ; Xiumin ZHANG ; Junqi MA ; Jing KANG ; Qing LI ; Lihua JIANG ; Zheng SHEN ; Li AI
Chinese Journal of Endemiology 2025;44(10):851-853
Objective:To study the risk factors of thyroid nodules in patients with type 2 diabetes.Methods:Data of patients with type 2 diabetes with normal thyroid function admitted to the Department of Endocrinology of Heze Municipal Hospital from January to June 2024 were collected. Binary logistic regression was used to analyze the influencing factors of thyroid nodules in patients with type 2 diabetes, and the receiver operating characteristic curve (ROC curve) was used to evaluate the diagnostic efficacy of each influencing factor.Results:Among 162 patients with type 2 diabetes, 96 had thyroid nodules, accounting for 59.3%. The incidence of thyroid nodules in women was significantly higher than that in men (χ 2 = 4.56, P = 0.034). Multivariate logistic regression analysis showed that age (≥50 years old), overweight and obesity [body mass index (BMI)≥24.0 kg/m 2], high glycated hemoglobin (≥10%), and high total cholesterol ( > 6.5 mmol/L) were independent risk factors for thyroid nodules in patients with type 2 diabetes ( OR = 1.83, 1.67, 1.08, 3.65, P < 0.05), and men was an independent protective factor ( OR = 0.63, P = 0.039). The ROC curve results showed that total cholesterol and total cholesterol combined with glycated hemoglobin could distinguish patients with thyroid nodules from those without thyroid nodules, with AUC = 0.64 and 0.68, respectively, and the differences were statistically significant ( P < 0.05). Conclusions:The incidence of thyroid nodules in patients with type 2 diabetes is relatively high. Age, overweight and obesity, high glycated hemoglobin, and high total cholesterol are independent risk factors for thyroid nodules in patients with type 2 diabetes, and total cholesterol has the ability to distinguish patients with thyroid nodules.
4.Risk factors of thyroid nodules in patients with type 2 diabetes
Chong WANG ; Lanxin KONG ; Shuzhen WANG ; Xiumin ZHANG ; Junqi MA ; Jing KANG ; Qing LI ; Lihua JIANG ; Zheng SHEN ; Li AI
Chinese Journal of Endemiology 2025;44(10):851-853
Objective:To study the risk factors of thyroid nodules in patients with type 2 diabetes.Methods:Data of patients with type 2 diabetes with normal thyroid function admitted to the Department of Endocrinology of Heze Municipal Hospital from January to June 2024 were collected. Binary logistic regression was used to analyze the influencing factors of thyroid nodules in patients with type 2 diabetes, and the receiver operating characteristic curve (ROC curve) was used to evaluate the diagnostic efficacy of each influencing factor.Results:Among 162 patients with type 2 diabetes, 96 had thyroid nodules, accounting for 59.3%. The incidence of thyroid nodules in women was significantly higher than that in men (χ 2 = 4.56, P = 0.034). Multivariate logistic regression analysis showed that age (≥50 years old), overweight and obesity [body mass index (BMI)≥24.0 kg/m 2], high glycated hemoglobin (≥10%), and high total cholesterol ( > 6.5 mmol/L) were independent risk factors for thyroid nodules in patients with type 2 diabetes ( OR = 1.83, 1.67, 1.08, 3.65, P < 0.05), and men was an independent protective factor ( OR = 0.63, P = 0.039). The ROC curve results showed that total cholesterol and total cholesterol combined with glycated hemoglobin could distinguish patients with thyroid nodules from those without thyroid nodules, with AUC = 0.64 and 0.68, respectively, and the differences were statistically significant ( P < 0.05). Conclusions:The incidence of thyroid nodules in patients with type 2 diabetes is relatively high. Age, overweight and obesity, high glycated hemoglobin, and high total cholesterol are independent risk factors for thyroid nodules in patients with type 2 diabetes, and total cholesterol has the ability to distinguish patients with thyroid nodules.
5.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.
6.Application of tracking methodology in investigation of contamination incidents of bronchoalveolar lavage fluid specimens from children
Shengmei LAN ; Wenting YIN ; Lili ZHAO ; Ling ZHANG ; Yanping SONG ; Lanxin LIU ; Juan LI
Chinese Journal of Nosocomiology 2025;35(18):2796-2799
OBJECTIVE To explore the effect of tracking methodology on investigation of contamination incidents of bronchoalveolar lavage fluid(BALF)specimens from the children.METHODS The onsite tracking was carried out for the contamination incidents of BALF specimens of the children through the tracking methodology,the quality control processes of cleaning and disinfection of bronchofiberscopes and the tracking routes were determined.The quality control process of cleaning and disinfection of bronchofiberscopes were evaluated,the existing risks were found out,and the specific improvement measures were formulated.RESULTS The onsite tracking was carried out for the incident of carbapenem-resistant Klebsiella pneumoniae(CRKP)that was caused by the contamination of 12 BALF specimens from pediatrics department wards before and after Nov.1,2021.No.2180014C bronchofiber-scope without biological surveillance was determined as the high-risk point of contamination of BALF specimens,the monitoring procedure of cleaning and disinfection of the bronchofiberscopes was revised.The BALF specimens that were submitted from Dec.1,2021 to Dec.31,2021 were tracked,and no CRKP was detected among the 23 submitted specimens.Totally 12 bronchofiberscope specimens were collected for biological surveillance,and the qualified rate was 100.00%.The treatment rooms of pediatrics department,hand disinfection effect of health care workers of cleaning and disinfection rooms and disinfection effect of object surfaces were monitored,and the quali-fied rate was increased from 98.39%to 100.00%.CONCLUSIONS The tracking methodology is an effective tool for quality management and can be used for evaluation of quality process of cleaning and disinfection of bronchofi-berscopes,which may find out the causes for adverse events in a timely manner and raise the medical safety.
7.Effects of Erxian Decoction (二仙汤) on Choroid Plexus Folate Transport-Hippocampal Neurogenesis in Rat Brain Tissue of Late-Onset Depression Model
Lanxin LI ; Ningxi ZENG ; Tiange ZHANG ; Can YAN ; Lili WU
Journal of Traditional Chinese Medicine 2024;65(10):1046-1055
ObjectiveThis study aims to investigate the effectiveness and potential mechanism of Erxian Decoction (二仙汤) for late-onset depression (LOD). MethodsForty Wistar male rats of 7
8.Clinical analysis of invasive pulmonary aspergillosis combined with pulmonary infection
Jian HUANG ; Yuanyuan LI ; Chengcheng ZHANG ; Lanxin CAO ; Kai ZHANG ; Lihua HU ; Gensheng ZHANG
Chinese Journal of Emergency Medicine 2024;33(4):502-509
Objective:To analyze the clinical features, risk factors and prognosis of IPA combined with lung infection, aiming to further improve clinicians' understanding and diagnosis and treatment of it.Methods:Patients with IPA admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2013 to October 2021 were retrospectively enrolled, and their clinical data was collected from the electronic medical record, including demographic information, clinical characteristics, biochemical indicators, auxiliary examination, microbial data and prognostic indicators. Patients were divided into two groups of IPA with pulmonary infection and IPA alone, and the clinical features, risk factors and prognosis of IPA patients with pulmonary infection were compared and analyzed in comparison with IPA patients alone.Results:A total of 156 IPA patients were finally recruited, with an average age of (67.12±12.89) years old and a main male proportion of 69.20%. Among them, there were 86 cases (55.13%) with IPA with pulmonary infection and 70 cases (44.87%) with IPA alone. Half of the IPA patients with pulmonary infection were mixed with one pathogen. The main pathogen of mixed infection was bacteria (82.72%), whereas acinetobacter baumannii accounted for the most common pathogen(25.93%, 42/162). Multivariate logistic regression analysis found that mechanical ventilation ( OR 4.89, 95% CI 2.23-10.70) and prior neutropenia ( OR 6.41, 95% CI 1.33-30.93) were independent risk factors for the occurrence of IPA with pulmonary infection. Compared with IPA alone, IPA patients with pulmonary infection were more likely to develop septic shock(69.80% vs. 32.90%, P <0.05), and have longer lengthes of hospital stay [16.00(8.00,36.50) vs.13.50 (7.00,20.50)] and ICU stay[11.50(6.00,31.25) vs.8.50(1.75,11.00)], and mechanical ventilation days [12.00(6.75, 25.25) vs.8.00(2.00,10.00)], as well as a higher 28-day mortality (55.80% vs.35.70%) and in-hospital mortality (64.00% vs. 35.70%). Conclusions:IPA patients with pulmonary infection accounts for more than half of IPA patients. The main respiratory etiology of IPA with pulmonary infection is acinetobacter baumannii. The independent risk factors of IPA patients with pulmonary infection are mechanical ventilation and neutropenia. The prognosis of IPA patients with pulmonary infection is worse than patients with IPA alone, which is worthy for the attention of physicians.
9.Protective effect and mechanism of Ba Bao Dan on doxorubicin-induced myocardial injury in a zebrafish model
Xianmei LI ; Laifeng ZENG ; Bin HUANG ; Lanxin YU ; Jiumao LIN
Acta Laboratorium Animalis Scientia Sinica 2024;32(5):557-565
Objective To investigate the effect of Ba Bao Dan(BBD)on cardiac injury induced by doxorubicin in zebrafish.Methods We induced a zebrafish myocardial injury model using the chemotherapeutic drug,doxorubicin.We then examined the effects of different concentrations of BBD on pericardial edema and heart rate under an in vivo microscope.We also examined the inhibitory effects of BBD on neutrophil infiltration in the heart in Tg(mpx:EGFP)transgenic zebrafish.The impacts of BBD on superoxide dismutase,catalase,and malondialdehyde were observed.mRNA expression levels of ferroptosis-related factors,including glutathione peroxidase 4a(gpx4a),prostaglandin-endoperoxide synthase 2(ptgs2),arachidonate 5-lipoxygenase(alox5a),and acyl-CoA synthetase long-chain family member 4(acsl4)were determined by Real-time quantitative polymerase chain reaction.The accumulation of ferrous ions in zebrafish heart was assessed using a fluorescent probe for ferrous ions.Results BBD alleviated doxorubicin-induced pericardial edema and bradycardia in zebrafish,reduced neutrophil infiltration in the heart(P<0.05),decreased malondialdehyde concentration(P<0.05),and enhanced the activities of superoxide dismutase and catalase(P<0.05).BBD also significantly inhibited ferroptosis,reduced the accumulation of ferrous ions in the zebrafish heart,suppressed the expression of ptgs2,alox5a,and acsl4(P<0.05),and promoted the expression of gpx4a(P<0.05).Conclusions BBD can attenuate doxorubicin-induced zebrafish myocardial injury and improve cardiac function by inhibiting lipid peroxidation and regulating ferroptosis.
10.Exploring the Mechanism of Action of Shenfu Yixin Granules in the Treatment of Heart Failure Based on Network Pharmacology,Molecular Docking and Experimental Verification
Bin WANG ; Xinlu WANG ; Lanxin LI ; Ludan ZHANG ; Lijie QIAO ; Jingjing WEI ; Mingjun ZHU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1352-1363
Objective This study aims to examine the potential mechanism of Shenfu Yixin Granules on heart failure(HF)based on network pharmacology,molecular docking,and experimental verification.Methods(1)The active components of herbs in Shenfu Yixin Granules were screened and retrieved through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).PubChem database and Swiss Target Prediction platform were used to predict targets.GeneCards and OMIM databases were used to screen HF-related targets.The intersection of active ingredient targets of Shenfu Yixin Granules and HF-related targets was performed by using Venny 2.1.0 platform to obtain common targets,which were the potential targets for anti-HF effect of Shenfu Yixin Granules.The potential targets were imported into the STRING database to construct a protein-protein interaction(PPI)network and screen the core targets of Shenfu Yixin Granules for the treatment of HF.GO functional and KEGG pathway enrichment analysis of potential targets were carried out by using DAVID database.AutoDock Vina software was used for molecular docking validation of key active ingredients and core targets.(2)SD rats were randomly allocated into sham operation group,model group,Shenfu Yixin Granules(5.28 g·kg-1)group,and positive control group(sacubitril-valsartan,20.8 mg·kg-1),with eight rats in each group.A rat model of HF after myocardial infarction was established by ligating the left anterior descending coronary artery.The rats were subsequently administered orally with the corresponding drugs once daily for a period of four weeks.Cardiac function including left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)in rats was assessed by echocardiography.Additionally,the histopathological alterations in rat heart tissue were examined using hematoxylin-eosin(HE)staining and Masson staining.The serum levels of brain natriuretic peptide(BNP),artial natriuretic peptide(ANP),and aldosterone(ALD)were determined by enzyme-linked immunosorbent assay(ELISA).Furthermore,real-time quantitative PCR and Western Blot were employed to detect mRNA and protein expressions of CAV1、F2 and MAPK1 in heart tissue.Results(1)A total of 210 active ingredients and 1 196 targets of Shenfu Yixin Granules,as well as 801 HF-related targets were obtained.Venny 2.1.0 platform was used to acquire 97 potential targets(common targets)of Shenfu Yixin Granules for the treatment of HF.Key active ingredients,such as quercetin,luteolin,arachidonic acid,kaempferol,and tanshinaldehyde were screened by"drugs-active ingredients-disease-targets"network analysis.The core targets including MAPK1、F2、CAV1、EDN1 and GJA1 were identified through PPI network analysis.The potential targets are mainly concentrated in multiple biological processes,namely,the positive regulation of gene expression,cardiac development,and the positive regulation of MAPK cascade,and involve multi key pathways including MAPK signaling pathway,HIF-1 signaling pathway and PI3K/Akt signaling pathway etc.Good binding activities were observed between MAPK1,CAV1,EDN1,F2 and quercetin,luteolin,kaempferol,tanshinaldehyde,as well as MAPK1,F2 and arachidonic acid.(2)Compared with sham operation group,LVEF and LVFS of rats significantly reduced(P<0.01),heart mass index obviously increased(P<0.05)in the model group.Myocardial tissue appears obvious pathological damage,and the degree of interstitial fibrosis was serious.The collagen volume fraction of the heart significantly increased(P<0.01).The levels of serum BNP,ANP and ALD significantly increased(P<0.01).The mRNA and protein expressions of CAV1、F2 and MAPK1 in heart tissue significantly increased(P<0.05,P<0.01).Compared with the model group,LVEF and LVFS of rats obviously increased(P<0.01),but the decrease in heart mass index was not significant(P>0.05)in Shenfu Yixin Granules group and positive control group.The pathological damage in myocardial tissues was significantly improved,the degree of interstitial fibrosis was significantly reduced.The collagen volume fraction of the heart significantly decreased(P<0.01).The levels of serum BNP,ANP and ALD significantly decreased(P<0.01).The mRNA and protein expressions of CAV1、F2 and MAPK1 in heart tissue significantly decreased(P<0.05,P<0.01).Conclusion Shenfu Yixin Granules may improve heart function and myocardial fibrosis in heart failure rats through the interaction between the active ingredients(quercetin,luteolin,arachidonic acid,kaempferol,and tanshinaldehyde)and targets(MAPK1,F2,CAV-1,and EDN1),so as to regulate MAPK signaling pathway and PI3K/Akt signaling pathway.

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