BackgroundBladder cancer is a common malignant tumor of the urinary system. The progression of the condition is associated with a poor prognosis, so it is necessary to identify new biomarkers to improve the diagnostic rate of bladder cancer.MethodsIn this study, 338 urine samples (144 bladder cancer, 123 healthy control, 32 cystitis, and 39 upper urinary tract cancer samples) were collected, among which 238 samples (discovery group) were analyzed by LC−MS. The urinary proteome characteristics of each group were compared with those of bladder cancer, and the differential proteins were defined by bioinformatics analysis. The pathways and functional enrichments were annotated. The selected proteins with the highest AUC score were used to construct a diagnostic panel. One hundred samples (validation group) were used to test the effect of the panel by ELISA.ResultsCompared with the healthy control, cystitis and upper urinary tract cancer samples, the number of differential proteins in the bladder cancer samples was 325, 158 and 473, respectively. The differentially expressed proteins were mainly related to lipid metabolism and iron metabolism and were involved in the proliferation, metabolism and necrosis of bladder cancer cells. The AUC of the panel of APOL1 and ITIH3 was 0.96 in the discovery group. ELISA detection showed an AUC of 0.92 in the validation group.ConclusionThis study showed that urinary proteins can reflect the pathophysiological changes in bladder cancer and that important molecules can be used as biomarkers for bladder cancer screening. These findings will benefit the application of the urine proteome in clinical research.

PurposeThe debate over the causal and longitudinal association between cystatin C and stroke in older adults persists. Our aim was to assess the link between cystatin C levels, both measured and genetically predicted, and stroke risk.MethodsThis study employed a retrospective cohort design using samples of the China Health and Retirement Longitudinal Study (CHARLS), which is a nationally representative cohort recruiting individuals aged 45 years or above. A multivariate logistic model and the two-sample Mendelian randomization framework were used to investigate the longitudinal and genetically predicted effect of serum cystatin C on stroke.ResultsThe study population had a mean age of 59.6 (SD ±9.5), with 2,996 (46.1%) women. After adjusting for confounding factors, compared to those in the first quartile of cystatin C, those in the last quartile had the greatest risk of stroke incidence [odds ratio (OR), 1.380; 95% confidence interval (CI), 1.046–1.825]. The Mendelian randomization analysis showed that a genetically predicted cystatin C level was positively associated with total stroke (OR by inverse variance-weighted method, 1.114; 95% CI, 1.041–1.192).ConclusionsThis national cohort study suggests that higher serum cystatin C is associated with an increased risk of total stroke, which is further supported by Mendelian randomization.

Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.

Triglyceride and glucose (TyG) index, a surrogate marker of insulin resistance, has been validated as a predictor of cardiovascular disease. However, effects of TyG-related indices combined with obesity markers on cardiovascular diseases remained unknown. We aimed to investigate the associations between TyG index and modified TyG indices with new-onset cardiovascular disease and the time-dependent predictive capacity using a national representative cohort. This study is a retrospective observational cohort study using data from China Health and Retirement Longitudinal Study (CHARLS) of 7 115 participants. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. The modified TyG indices were developed combining TyG with body mass index (BMI), waist circumference (WC) and waist-to‐height ratio (WHtR). We used adjusted Cox proportional hazards regression to analyze the association and predictive capacity based on hazard ratio (HR) and Harrell’s C‐index. Over a 7-year follow‐up period, 2136 participants developed cardiovascular disease, including 1633 cases of coronary heart disease and 719 cases of stroke. Compared with the lowest tertile group, the adjusted HR (95

结直肠癌是全球第三大癌症死因，每年有超过185万病例被发现，85万人死亡 [1] 。结直肠癌初期起病隐匿，发展缓慢，多数病例是在癌症晚期才被确诊，有效的诊断及发病机制的研究对肿瘤的预后有重要意义 [2] 。本研究通过二维色谱质谱联用技术、免疫印迹实验、免疫组化实验来探究ATP5B蛋白在结直肠癌组织与癌旁组织的表达及意义，为结直肠癌的临床诊断及发病机制的研究提供新的方向。1 材料与方法

Abstract Objectives Iron metabolism-related genes (IMRGs) play important roles in the prognostic assessment of many tumours. However, IMRGs have not been reported as prognostic biomarkers in bladder urothelial carcinoma (BLCA). Methods Gene expression profiles and clinical data from BLCA patients were obtained from The Cancer Genome Atlas (TCGA) database. We used the DESeq2 package to screen for differentially expressed genes (DEGs). The predictive values of the differentially expressed IMRGs in BLCA patients were further evaluated using univariate Cox regression analysis. The risk-scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm. The performance of this model for predicting the prognosis of BLCA patients in TCGA-BLCA cohort was assessed using Kaplan–Meier (K–M) and receiver operating characteristic (ROC) curves. This risk-scoring model was combined with the clinicopathological characteristics of BLCA patients in a multiple regression analysis, and a nomogram was constructed using the independent predictors identified. ROC analysis and calibration curves were adapted to test the predictive ability of the nomogram. Gene set enrichment analysis (GSEA) was used to identify potential molecular pathways and processes enriched by differential expression genes between risk groups. Finally, we explored the ability of the risk-scoring model to assess immune cell infiltration levels through a correlation analysis. Results Fourteen identified IMRGs with prognostic value were incorporated into the risk-scoring model. The ROC and K–M survival curves indicated that the model could effectively predict the overall survival (OS) outcomes of BLCA patients. The multiple regression analysis revealed that the risk-scoring model could be used as an independent prognostic factor for BLCA patients, and the associated nomogram could effectively predict the OS outcomes of BLCA patients. GSEA revealed that the DEGs between the risk groups were mainly involved in biological processes such as developmental process, cell cycle, mitosis, RHO GTPase reaction, DNA repair, and extracellular matrix regulation. The immune infiltration analysis showed that the infiltration levels of immune cells such as natural killer cells, memory T cells, effector T cells, Th2 cells, and macrophages differed significantly between the risk groups. Conclusions IMRGs screening revealed prognosis-associated genes. The prognostic model constructed could effectively predict the prognosis of BLCA patients, and the identified genes represent potential targets for BLCA treatment.

Arterial stiffness is a major contributor to morbidity and mortality worldwide. Although several metabolic markers associated with arterial stiffness have been developed, there is limited data regarding whether glycemic control modifies the association between diabetes and arterial stiffness. For these reasons, identification of traits around diabetes will directly contribute to arterial stiffness and atherosclerosis management in the context of predictive, preventive, and personalized medicine (PPPM). Thus, this study aimed to explore the relationship of diabetes and glycemic control status with arterial stiffness in a real-world setting. Data of participants from Beijing Xiaotangshan Examination Center (BXEC) with at least two surveys between 2008 and 2019 were used. Cumulative hazards were presented by inverse probability of treatment weighted (IPTW) Kaplan-Meier curves. Cox models were used to estimate the hazard ratio (HR) and 95

Background The triglyceride-glucose (TyG) index is a predictor of cardiovascular diseases; however, to what extent the TyG index is associated with cardiovascular diseases through renal function is unclear. This study aimed to evaluate the complex association of the TyG index and renal function with cardiovascular diseases using a cohort design. Methods This study included participants from the China Health and Retirement Longitudinal Study (CHARLS) free of cardiovascular diseases at baseline. We performed adjusted regression analyses and mediation analyses using Cox models. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Renal function was defined by the estimated glomerular filtration rate (eGFR). Results A total of 6 496 participants were included in this study. The mean age of the participants was 59.6 ± 9.5 years, and 2996 (46.1%) were females. During a maximum follow-up of 7.0 years, 1 996 (30.7%) people developed cardiovascular diseases, including 1 541 (23.7%) cases of heart diseases and 651 (10.0%) cases of stroke. Both the TyG index and eGFR level were significantly associated with cardiovascular diseases. Compared with people with a lower TyG index (median level) and eGFR ≥ 60 ml/minute/1.73 m 2 , those with a higher TyG index and decreased eGFR had the highest risk of cardiovascular diseases (HR, 1.870; 95% CI 1.131–3.069). Decreased eGFR significantly mediated 29.6% of the associations between the TyG index and cardiovascular diseases. Conclusions The combination of a higher TyG index and lower eGFR level was associated with the highest risk of cardiovascular diseases. Renal function could mediate the association between the TyG index and cardiovascular risk.

Background and aims: Visceral adiposity index (VAI), an indicator of visceral fat, is associated with metabolic health and arterial stiffness. However, studies correlating VAI and stroke are limited. This study aimed to explore the association between VAI and incident stroke in the Chinese population. Methods and results: We retrospectively analysed the data of 9127 individuals enrolled in the China Health and Retirement Longitudinal Study. The first survey of the study was conducted during 2011e2012 and the individuals were followed up until Survey 4 ( 2017-2018). Multivariable-adjusted Cox regression models were used to evaluate the association between VAI and stroke. The mean age of the study population was 59.3 +/- 9.5 years and 4938 (54.1%) participants were women. During the median follow-up of 5.2 [1.0-7.0] years, 833 (9.1%) participants developed stroke, and the cumulative incidence of stroke increased with increasing quartiles of VAI (8.6%, 8.7%, 9.2%, and 10.0%). Compared to those in the first quartile of VAI, individuals in the fourth quartile had an increased risk of stroke (adjusted hazard ratio, 1.45; 95% CI, 1.15-1.75). The results were stable in several sensitivity analyses. Conclusion: Our findings suggest a positive association between VAI and incident stroke in the Chinese population. (C) 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

结直肠癌（Colorectal Carcinoma,CRC）病因很多，不仅有基因水平因素，而且有蛋白水平和遗传等因素 [1] 。随着现代诊疗技术的进步，结直肠肿瘤的死亡率下降明显。但肿瘤复发和转移带来的问题仍然不容忽视 [2-3] 。研究针对该情况本研究设计并应用质谱色谱技术 [4-5] 寻找结直肠癌肿瘤蛋白新的标志物，留取组织标本采用二维液相色谱质谱联用技术鉴定出结直肠癌上调分泌性CypA蛋白，同时研究其在血清中表达情况。

Background and aims: Psychological symptoms are prevalent among individuals with non-communicable diseases, while the longitudinal association between triglyceride glucose (TyG) index, an indicator of metabolic health, and depression progression remains unclear yet. This study aims to investigate the association of baseline TyG index and depression progression in middle-aged and elder adults. Methods and results: This retrospective cohort study enrolled 8287 participants aged 45 years or above from national China Health and Retirement Longitudinal Study in visit 1 (2011-2012), which were biennially followed for depression score until visit 4 (2017-2018). Multivariateadjusted regression models were used to evaluate the association of baseline TyG index with the individual level change rate and slope of depression score. The mean age (+/- SD) of participants was 58.25 +/- 9.10 years, and 3806 (45.9%) were men. There was no significant difference of depression score at baseline across TyG quartile groups (P Z 0.228). Participants in the highest quartile of TyG index had a 0.124 (95% CI: 0.018-0.230) higher change rate of depression score, and a 0.127 (95% CI: 0.019-0.235) higher change slope, compared to those in the lowest. The observed associations were consistent in multiple sensitivity analyses, and stable in men, the elder, and overweight people. Conclusion: TyG index is positively associated with depression progression especially in men, the elder and overweight people, which provides new insights for the primary prevention of depression disorder. (c) 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

结直肠癌的发病率在发达国家位列第三，死亡人数在男性排行中最多的是肺癌、前列腺癌和结直肠癌，女性为肺癌、乳腺癌和结直肠癌 [1] 。生活方式导致年轻化趋势且患病率不断增加 [2] ，超过90%的胃肠道癌症是由饮食习惯引起的。我们实验室运用液相色谱-质谱联用技术，通过对10名结直肠癌患者的肿瘤组织与癌旁正常组织进行蛋白质组学分析，实验结果显示出差异表达的蛋白质，