Objective To investigate the causal relationship between hyperthyroidism and systemic lu-pus erythematosus(SLE).Methods According to the current summary data of genome-wide association studies(GWAS),the screened single nucleotide polymorphism(SNP)was selected as the instrumental varia-bles,hyperthyroidism served as the exposure factor and SLE as the outcome variable,and the Mendelian ran-domization analysis(MR)analysis method was used for conducting the study.Among them,the inverse vari-ance weighting(IVW)was the main MR analysis method,the MR-Egger regression method was used to the test for horizontal pleiotropy,and the sensitivity adopted the leave-one-method test,and the MR results con-ducted the visualized analysis by scatter plot,forest plot and funnel plot.Results Ten valid SNP were screened.In the MR analysis,IVW supported a causal relationship between hyperthyroidism and SLE(OR=1.838,95%CI:1.302-2.593,P<0.001);the MR-egger regression method supported the relationship be-tween hyperthyroidism and SLE(OR=4.070,95%CI:1.961-8.449,P=0.003);in addition,the weighted median method also supported the relationship between hyperthyroidism and SLE(OR=1.685,95%CI:1.238-2.294,P<0.001).Conclusion There appears to be a causal relationship between hyperthyroidism and SLE.

[Purpose]To analyze the diagnostic yield of quantitative fecal immunochemical test(FIT)at different cut-offs in colorectal cancer(CRC)screening.[Methods]The sequential screening method was adapted in Jiashan CRC screening program for local residents aged 40～74 years old,which included a quantitative FIT and high-risk factor questionnaire for primary screening and subsequent colonoscopy for the diagnostic screening.Subjects who participated in quantitative FIT were included in this study between September,2021 and August,2023.The positive predictive values(PPVs)for colorectal neoplasms were calculated at the cut-offs of 100,120,140,160,180 and 200 ng/mL of FIT.The Cochran-Armitage trend test was performed to compare the trend of PPVs at different cut-offs.The effects of different starting age and FIT cut-offs on requirement of colonoscopy and advanced neoplasia detection were assessed.[Results]A total of 58 256 individuals completed the quantitative FIT,and 3 106 had fecal hemoglobin concentrations＞100 ng/mL,among whom 2 186 underwent colonoscopic examination with a compliance rate of 70.38％.The colonoscopy detected 588 cases of non-advanced adenomas and 355 cases of advanced neoplasms(AN),in-cluding 30 cases of CRC and 325 cases of advanced adenomas.Progressively increasing the cut-off showed a decrease in PPVs of non-advanced adenomas and an increase of AN.The ratio of the rate of reduced requirement of colonoscopy to the missed rate of the progressive lesions was the smallest when the screening start age was 45 years old and the positive FIT threshold was set at 100 ng/mL.[Conclusion]There were significant differences in the diagnostic yield at different cut-offs of FIT.Increasing the cut-offs of FIT will elevate PPVs for the advanced neoplasms.

[Purpose]To analyze the diagnostic yield of quantitative fecal immunochemical test(FIT)at different cut-offs in colorectal cancer(CRC)screening.[Methods]The sequential screening method was adapted in Jiashan CRC screening program for local residents aged 40～74 years old,which included a quantitative FIT and high-risk factor questionnaire for primary screening and subsequent colonoscopy for the diagnostic screening.Subjects who participated in quantitative FIT were included in this study between September,2021 and August,2023.The positive predictive values(PPVs)for colorectal neoplasms were calculated at the cut-offs of 100,120,140,160,180 and 200 ng/mL of FIT.The Cochran-Armitage trend test was performed to compare the trend of PPVs at different cut-offs.The effects of different starting age and FIT cut-offs on requirement of colonoscopy and advanced neoplasia detection were assessed.[Results]A total of 58 256 individuals completed the quantitative FIT,and 3 106 had fecal hemoglobin concentrations＞100 ng/mL,among whom 2 186 underwent colonoscopic examination with a compliance rate of 70.38％.The colonoscopy detected 588 cases of non-advanced adenomas and 355 cases of advanced neoplasms(AN),in-cluding 30 cases of CRC and 325 cases of advanced adenomas.Progressively increasing the cut-off showed a decrease in PPVs of non-advanced adenomas and an increase of AN.The ratio of the rate of reduced requirement of colonoscopy to the missed rate of the progressive lesions was the smallest when the screening start age was 45 years old and the positive FIT threshold was set at 100 ng/mL.[Conclusion]There were significant differences in the diagnostic yield at different cut-offs of FIT.Increasing the cut-offs of FIT will elevate PPVs for the advanced neoplasms.

Objective To investigate the relationship between biological aging and the rate of cognitive decline in middle-aged and elderly populations.Methods Longitudinal tracking data of cognitive function were obtained from the China Health and Retirement Longitudinal Study(CHARLS).We employed the Klemera and Doubal method(KDM)to estimate biological age(BA),and calculate the biological aging index(BAI)and biological aging type(BAT).A multivariate linear regression model was employed to analyze the relationships between baseline BAI,BAT,and cognitive function scores.Based on the baseline analysis,a mixed-effects model was used to examine the longitudinal associations between baseline BAI,BAT,and cognitive function during follow-up.Results A total of 5 897 participants were included in the study.BAI was found to be negatively associated with baseline cognitive function scores,with the partial regression coefficient(β)(95％CI)being-0.185(—0.231,—0.139)(P＜0.001).Compared with the lagged aging group,the premature aging group had lower cognitive function scores(β[95％CI]:—0.741[—0.966,—0.516]).For age and sex,for each additional year of baseline BAI,cognitive function scores declined by an average of 0.012(95％CI:—0.019,—0.005)points per year after adjusting for age and sex,and declined by 0.011(95％CI:—0.018,—0.004)points per year after adjusting for other covariates.Compared with participants with lagged aging,those with premature aging experienced,on average,an additional decline of 0.042(95％CI:—0.075,0.009)points per year in cognitive function scores after adjusting for age and sex alone,and by 0.039(95％CI:—0.072,—0.007)points per year after adjusting for other covariates.Conclusion Biological aging affects the rate of cognitive decline in middle-aged and elderly populations.A higher BAI is associated with a faster decline in cognitive function.Compared with those with lagged aging,individuals with premature aging exhibit a more rapid rate of cognitive decline.

Objective By exploring changes of six degrees of freedom(6DOF)kinematics of the knee joint during extra weight bearing of the body trunk,the influence of extra weight on knee joint movement patterns was studied.Methods A total of 24 healthy subjects were recruited to walk/run on a treadmill at four speeds under two states:self-weight and wearing a 16 kg vest,and gait analysis was conducted.A three-dimensional(3D)portable knee kinematics analysis system based on infrared stereophotography was used to capture 6DOF movement trajectory data of the tibia relative to the femur.Results Compared to the self-weight state,when additional trunk weight was added,the knee external rotation angle was reduced at 3.6 km/h speed(1.4°-2.1°)and 5.4 km/h speed(2.2°-2.7°);the knee internal rotation angle was reduced at 10.8 km/h speed(2.1°-4.2°);the knee flexion angles was increased significantly at the speed of 3.6 km/h(1.5°-1.8°),9 km/h(1.6°-3.3°)和 10.8 km/h(1.9°-3.1°);the knee adduction angle increased at 5.4 km/h speed(0.5°-0.6°),and decreased at 10.8 km/h speed(0.9°-1.3°).At 10.8 km/h speed,the distal knee displacement(0.2-0.4 mm)was increased,and the lateral knee displacement(0.1-0.2 mm),and anterior knee displacement(0.2-0.3 mm)were significantly reduced.Conclusions The 6DOF kinematics of human knee is significantly affected by the extra trunk weight.Performance is also different at lower and higher speeds.It is suggested that there may exist a hidden injury in military training,and this study provides a kinematic basis for the occurrence of sports injury.

Objective By exploring changes of six degrees of freedom(6DOF)kinematics of the knee joint during extra weight bearing of the body trunk,the influence of extra weight on knee joint movement patterns was studied.Methods A total of 24 healthy subjects were recruited to walk/run on a treadmill at four speeds under two states:self-weight and wearing a 16 kg vest,and gait analysis was conducted.A three-dimensional(3D)portable knee kinematics analysis system based on infrared stereophotography was used to capture 6DOF movement trajectory data of the tibia relative to the femur.Results Compared to the self-weight state,when additional trunk weight was added,the knee external rotation angle was reduced at 3.6 km/h speed(1.4°-2.1°)and 5.4 km/h speed(2.2°-2.7°);the knee internal rotation angle was reduced at 10.8 km/h speed(2.1°-4.2°);the knee flexion angles was increased significantly at the speed of 3.6 km/h(1.5°-1.8°),9 km/h(1.6°-3.3°)和 10.8 km/h(1.9°-3.1°);the knee adduction angle increased at 5.4 km/h speed(0.5°-0.6°),and decreased at 10.8 km/h speed(0.9°-1.3°).At 10.8 km/h speed,the distal knee displacement(0.2-0.4 mm)was increased,and the lateral knee displacement(0.1-0.2 mm),and anterior knee displacement(0.2-0.3 mm)were significantly reduced.Conclusions The 6DOF kinematics of human knee is significantly affected by the extra trunk weight.Performance is also different at lower and higher speeds.It is suggested that there may exist a hidden injury in military training,and this study provides a kinematic basis for the occurrence of sports injury.

Objective To develop a model based on a graph convolutional network(GCN)to achieve ef-ficient classification of the cold and hot medicinal properties of Chinese herbal medicines(CHMs).Methods After screening the dataset provided in the published literature,this study includ-ed 495 CHMs and their 8 075 compounds.Three molecular descriptors were used to repre-sent the compounds:the molecular access system(MACCS),extended connectivity finger-print(ECFP),and two-dimensional(2D)molecular descriptors computed by the RDKit open-source toolkit(RDKit_2D).A homogeneous graph with CHMs as nodes was constructed and a classification model for the cold and hot medicinal properties of CHMs was developed based on a GCN using the molecular descriptor information of the compounds as node features.Fi-nally,using accuracy and F1 score to evaluate model performance,the GCN model was ex-perimentally compared with the traditional machine learning approaches,including decision tree(DT),random forest(RF),k-nearest neighbor(KNN),Na?ve Bayes classifier(NBC),and support vector machine(SVM).MACCS,ECFP,and RDKit_2D molecular descriptors were al-so adopted as features for comparison.Results The experimental results show that the GCN achieved better performance than the traditional machine learning approach when using MACCS as features,with the accuracy and F1 score reaching 0.836 4 and 0.845 3,respectively.The accuracy and F1 score have increased by 0.869 0 and 0.812 0,respectively,compared with the lowest performing feature combina-tion OMER(only the combination of MACCS,ECFP,and RDKit_2D).The accuracy and F1 score of DT,RF,KNN,NBC,and SVM are 0.505 1 and 0.501 8,0.616 2 and 0.601 5,0.676 8 and 0.624 3,0.616 2 and 0.607 1,0.636 4 and 0.622 5,respectively.Conclusion In this study,by introducing molecular descriptors as features,it is verified that molecular descriptors and fingerprints play a key role in classifying the cold and hot medici-nal properties of CHMs.Meanwhile,excellent classification performance was achieved using the GCN model,providing an important algorithmic basis for the in-depth study of the"struc-ture-property"relationship of CHMs.

Immune Checkpoint Inhibitors ; Transcriptome ; Immunotherapy ; Biomarkers, Tumor

Objective: To investigate the factors influencing the development of gastric cancer in Chinese populations, so as provide insights into creating a model for predicting gastric cancer incidence among Chinese populations. Methods: The case-control and cohort studies pertaining to factors affecting the development of gastric cancer were retrieved in electronic Chinese and English databases, including CNKI, Wanfang Data, VIP, PubMed, Web of Science and Embase from their inception until September 30, 2021. A meta-analysis was performed using R package version 4.1.0. Sensitivity analysis was performed using the “leave-one-out” evaluation procedure, and the publication bias was evaluated using the Egger regression test and the trim-and-fill procedure. Results: A total of 5 301 publications were screened and 116 eligible studies were included in the final analysis, including 103 case-control studies and 13 cohort studies, which covered approximately 3.23 million study subjects. A total of 45 factors affecting the development of gastric cancer were collected, and there were less than 4 publications reporting 7 factors, which were only qualitatively described. There were 38 factors included in the final meta-analysis. A total of 21 factors were identified as risk factors of gastric cancer, including a history of gastrointestinal diseases (pooled OR=4.85, 95%CI: 3.74-6.29), H. pylori infection (pooled OR=3.18, 95%CI: 2.35-4.32), binge eating and drinking (pooled OR=2.88, 95%CI: 2.09-3.97) and a family history of tumors (pooled OR=2.78, 95%CI: 2.17-3.56), and 10 factors as protective factors, including vegetable intake (pooled OR=0.48, 95%CI: 0.38-0.61), tea consumption (pooled OR=0.55, 95%CI: 0.47-0.64), administration of aspirin (pooled OR=0.53, 95%CI: 0.31-0.92) and administration of statins (pooled OR=0.59, 95%CI: 0.44-0.80). Sensitivity analyses of eating moldy food frequently, white meat intake, favoring spicy food and administration of sulfonylureas were not robust. Following correction with the trim-and-fill procedure, there was still a publication bias pertaining to high income, diabetes, administration of stains, alcohol consumption, tea consumption and white meat intake. Conclusions The development of gastric cancer is associated with a medical history of gastrointestinal disease, H. pylori infection, family history of tumors and poor dietary habits. Risk and protective factors of gastric cancer are recommended to be included in models used to predict gastric cancer incidence among Chinese populations.

Objective:To explore the association between lifestyle-related factors and colorectal adenoma.Methods:Based on the Screening Project of Early Diagnosis and Treatment of Colorectal Cancer in Jiashan county Zhejiang province, from August 2012 to March 2018, information gathered through records on questionnaire and colonoscopic diagnosis were collected from participants with positive results during the primary screening stage. According to the findings of colonoscopy, 11 232 controls without any colorectal diseases and 3 895 cases with colorectal adenoma were included in the study. Multivariate logistic regression models were used to analyze the association between lifestyle-related factors and colorectal adenoma.Results:After adjusting for possible confounding factors, results from multivariate logistic regression analysis showed that smoking, alcohol drinking and obesity were positively related to the risk of colorectal adenoma, with ORs (95 %CIs) as 1.38 (1.24-1.54), 1.37 (1.24-1.51) and 1.38 (1.20-1.59) respectively. However, regular aspirin intake was negatively related with the risk of colorectal adenoma ( OR=0.65, 95 %CI: 0.53-0.80). After stratified by sex and age, data showed that the associations between smoking, alcohol drinking and colorectal adenoma were statistically significant in males, and the association between regular aspirin intake and colorectal adenoma was also statistically significant in older participants (aged 60 years and older). Conclusion:Smoking, alcohol drinking, regular aspirin intake and obesity were associated with colorectal adenoma.