Identification of novel therapeutic targets for chronic kidney disease and kidney function by integrating multi-omics proteome with transcriptome.

BACKGROUND: Chronic kidney disease (CKD) is a progressive disease for which there is no effective cure. We aimed to identify potential drug targets for CKD and kidney function by integrating plasma proteome and transcriptome. METHODS: We designed a comprehensive analysis pipeline involving two-sample Mendelian randomization (MR) (for proteins), summary-based MR (SMR) (for mRNA), and colocalization (for coding genes) to identify potential multi-omics biomarkers for CKD and combined the protein-protein interaction, Gene Ontology (GO), and single-cell annotation to explore the potential biological roles. The outcomes included CKD, extensive kidney function phenotypes, and different CKD clinical types (IgA nephropathy, chronic glomerulonephritis, chronic tubulointerstitial nephritis, membranous nephropathy, nephrotic syndrome, and diabetic nephropathy). RESULTS: Leveraging pQTLs of 3032 proteins from 3 large-scale GWASs and corresponding blood- and tissue-specific eQTLs, we identified 32 proteins associated with CKD, which were validated across diverse CKD datasets, kidney function indicators, and clinical types. Notably, 12 proteins with prior MR support, including fibroblast growth factor 5 (FGF5), isopentenyl-diphosphate delta-isomerase 2 (IDI2), inhibin beta C chain (INHBC), butyrophilin subfamily 3 member A2 (BTN3A2), BTN3A3, uromodulin (UMOD), complement component 4A (C4a), C4b, centrosomal protein of 170 kDa (CEP170), serologically defined colon cancer antigen 8 (SDCCAG8), MHC class I polypeptide-related sequence B (MICB), and liver-expressed antimicrobial peptide 2 (LEAP2), were confirmed. To our knowledge, 20 novel causal proteins have not been previously reported. Five novel proteins, namely, GCKR (OR 1.17, 95% CI 1.10-1.24), IGFBP-5 (OR 0.43, 95% CI 0.29-0.62), sRAGE (OR 1.14, 95% CI 1.07-1.22), GNPTG (OR 0.90, 95% CI 0.86-0.95), and YOD1 (OR 1.39, 95% CI 1.18-1.64,) passed the MR, SMR, and colocalization analysis. The other 15 proteins were also candidate targets (GATM, AIF1L, DQA2, PFKFB2, NFATC1, activin AC, Apo A-IV, MFAP4, DJC10, C2CD2L, TCEA2, HLA-E, PLD3, AIF1, and GMPR1). These proteins interact with each other, and their coding genes were mainly enrichment in immunity-related pathways or presented specificity across tissues, kidney-related tissue cells, and kidney single cells. CONCLUSIONS: Our integrated analysis of plasma proteome and transcriptome data identifies 32 potential therapeutic targets for CKD, kidney function, and specific CKD clinical types, offering potential targets for the development of novel immunotherapies, combination therapies, or targeted interventions.

Development of a prediction model for predicting the prevalence of nonalcoholic fatty liver disease in Chinese nurses: the first-year follow data of a web-based ambispective cohort study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is gradually becoming a huge threat to public health. With complex working characteristics, female nurses had been found with high risk of NAFLD. To develop and validate a prediction model to predict the prevalence of NAFLD based on demographic characteristics, work situation, daily lifestyle and laboratory tests in female nurses. METHODS: This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), and data were extracted from the first-year follow data collected from 1st June to 1st September 2021 by questionnaires and physical examination records in a comprehensive tertiary hospital. The questionnaires included demographic characteristics, work situation and daily lifestyle. Logistic regression and a nomogram were used to develop and validate the prediction model. RESULTS: A total of 824 female nurses were included in this study. Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, HDL-C, UA, BMI, TBil and Ca were independent risk factors for NAFLD occurance. A prediction model for predicting the prevalence of NAFLD among female nurses was developed and verified in this study. CONCLUSION: Living situation, smoking history, monthly night shift, daily sleep time, ALT/AST, FBG, TG, UA, BMI and Ca were independent predictors, while HDL-C and Tbil were independent protective indicators of NAFLD occurance. The prediction model and nomogram could be applied to predict the prevalence of NAFLD among female nurses, which could be used in health improvement. TRIAL REGISTRATION: This study was a part of the Chinese Nurse Cohort Study (The National Nurse Health Study, NNHS), which was a ambispective cohort study contained past data and registered at Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT04572347 ) and the China Cohort Consortium ( http://chinacohort.bjmu.edu.cn/project/102/ ).

MOnitoring human papillomavirus Vaccine effect on Infection and cErvical diseases (MOVIE): Protocol for a cohort study using electronic health records from Yinzhou, China.

Cervical cancer is the fourth most common cancer in women, with a high disease burden worldwide. Human papillomavirus (HPV) vaccination reduces HPV-related infection and associated cervical lesions and cancers. Few studies have explored HPV vaccination impact in real-world settings in China. This study aims to monitor HPV vaccine uptake and its effects on HPV-related diseases, evaluating vaccine effectiveness in a real-world context and complementing clinical trial results. Electronic health records (EHRs) from 2010 to 2020 from the Yinzhou Regional Health Information Platform (YRHIP) will be queried/extracted to identify and monitor HPV vaccine uptake in females aged 9-45 years, and HPV-related screening and prevalence (i.e., cervical HPV infection, cervical intraepithelial neoplasia [CIN] grades 1-3, and cervical cancer) in a cohort of females aged 9-70 years. Cervical cancer screening guidelines and expert consultation will be used for intra-database validation, to determine the best algorithm for identifying HPV-related disease. Pre-launch (2010-2016) and post-launch (2018-2020) periods are predefined. A time trend analysis will be performed to describe the vaccination impact on disease prevalence and, if prerequisite conditions are met, vaccine effectiveness will be computed using logistic regression, adjusting for age, calendar year, history of screening and HPV infection. Cohort study design, outcomes validation, data linkage, and multi-step statistical analyses could provide valuable experience for designing other real-world studies in the future. The study outcomes can help inform policy-makers about uptake and HPV vaccination policy in girls and women in Yinzhou District, and provide insights on progress toward achieving goals set by the World Health Organization.

Incidence of Inflammatory Bowel Disease in Urban China: A Nationwide Population-based Study.

BACKGROUND & AIMS: Limited studies have evaluated the burden of inflammatory bowel disease (IBD) in China. We aimed to estimate the incidence of IBD including ulcerative colitis (UC) and Crohn's disease (CD) in urban China. METHODS: The national urban incidence in 2016 was calculated based on urban basic medical insurance from 2012 to 2016 in China by using a 4-year washout period. The incidence in Yinzhou District estimated from the Yinzhou electronic health care record database was used to test the accuracy of the results from insurance data. RESULTS: A total of 95,555 patients with IBD were identified. The incidence in 2016 was 10.04 (95% confidence interval, 6.95-13.71) per 100,000 person-years. The incidence rates of both UC and CD were higher among males than among females. There was a sharp increase in UC incidence before the age of 30 years and stabilization in later years (50-79 years old), whereas CD incidence peaked at 30 to 34 years old and experienced decline subsequently. The incidence of UC was much greater than that of CD, with a UC-to-CD incidence ratio of 12.61. The results from the Yinzhou database confirmed these results. CONCLUSIONS: This study is the first to draw a portrait of the distribution of IBD in urban China. The difference in IBD incidence between urban China and other countries suggests an association between the IBD burden and industrialization process. The accelerating urbanization and industrialization process in China, a country with a population of 1.4 billion people, will likely increase the burden of IBD.

Incidence and cost of dermatofibrosarcoma protuberans in mainland urban China: a nationwide retrospective study 2014-2016.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma. Limited population-based epidemiological studies on DFSP have been conducted. OBJECTIVES: We aimed to estimate the incidence and disease burden of DFSP in China. MATERIALS & METHODS: We conducted a cross-sectional study using data from the national databases of the Urban Basic Medical Insurance scheme. Cases were identified by ICD code and Chinese language diagnostic terms. National incidence from 2014 to 2016 was estimated by gender and age, and associated medical costs were calculated. RESULTS: A total of 175 patients were confirmed with DFSP from 2014 to 2016. Crude incidence varied from 0.353 per 100,000 (95% CI: 0.203-0.503) in 2014 to 0.367 per 100,000 (95% CI: 0.279-0.455) in 2016. Incidence was higher in males than in females. The first incidence peak was observed between the ages of 20 and 39 years and the highest incidence rates were in those aged over 60 years. Average medical costs of DFSP were higher than the per capita disposable income of residents. CONCLUSION: Incidence of DFSP in mainland urban China is lower than in most developed countries and has remained relatively stable from 2014 to 2016. Further research is expected to clarify the potential pathophysiological mechanisms of DFSP.

Post-marketing surveillance for the safety of the 9-valent human papillomavirus vaccine: a retrospective real-world study in China.

BACKGROUND: The 9-valent human papillomavirus (9vHPV) vaccine was introduced in China in 2018. This study was conducted to monitor the occurrence of new-onset autoimmune diseases (AIs) in Chinese women vaccinated with the 9vHPV vaccine and adverse pregnancy outcomes in infants born to mothers with inadvertent pregnancy exposure. RESEARCH DESIGN AND METHODS: Women who received the first dose of the 9vHPV vaccine at age 16-26 years in Ningbo between January 2019 and March 2021 were monitored in the Ningbo Regional Health Information Platform. New-onset cases of seven pre-specified AIs diagnosed within six months after vaccination were collected. Cases of stillbirth and 23 major congenital anomalies diagnosed within three months of birth in target infants were collected. RESULTS: A total of 102,670 doses of the 9vHPV vaccine were administered to 41,609 women who had received no other HPV vaccine. New-onset AIs were diagnosed in 36 women, comprising 21 Hashimoto's, 11 Graves', and 4 uveitis disease cases. Among 50 women with maternal vaccination exposure, no stillbirths were observed. One case of microtia was observed. CONCLUSIONS: In this first post-marketing surveillance of the 9vHPV vaccine in China, no safety signals were identified when putting the results in context to published data.

Metabolic Disease and Risk of Thyroid Disease: Evidence from the National Nurse Health Cohort in China.

BACKGROUND: Previous studies have shown that metabolic diseases are risk factors for thyroid disease; most studies are cross-sectional design. We aimed to evaluate the causal relationship between thyroid and metabolic diseases in a cohort of Chinese nurses. METHODS: We conducted an ambispective cohort study of the National Nurses' Health Study. Thyroid disease data based on ultrasonography from 2017 to 2021 were collected. We described thyroid disease incidence and the risk factors associated with a cluster of metabolic factors. We used the Mann‒Whitney U test, repeated-measures ANOVA and multivariable Cox proportional hazard regression to analyze the data. RESULTS: A total of 1529 female nurses without thyroid disease were enrolled in 2017, of which, complete data were available for 1269 nurses. In 2018-2020, thyroid nodule incidence ranged from 32.8%-46.3%, thyroiditis incidence was 13.4%-14.3%, and goiter incidence was 4.1%-29.1%, thyroid adenoma and thyroid tumors incidence were 0.1%-0.5% and 1%-1.5%. We also found that NAFLAD was an independent risk factor for thyroid adenoma (p = .003). The age at diagnosis was an independent risk factor for goiter (p <. 001) and thyroid nodules (p < .001). Fasting blood glucose was an independent risk factor for thyroid tumors (p = .004). The age at diagnosis (p = .003), Body Mass Index (p = .006) and menopause (p = .031) were risk factors for thyroiditis. CONCLUSION: Thyroid disease incidence among nurses is increasing. Age at diagnosis, BMI, fasting blood glucose, and nonalcoholic fatty liver disease are independent risk factors for different types of thyroid disease. This study provides evidence for future studies to further explore the pathogenesis and prevention of thyroid diseases.

Incidence and cost of vertebral fracture in urban China: a 5-year population-based cohort study.

BACKGROUND: Osteoporotic vertebral fractures cause pain and disability, which result in a heavy socioeconomic burden. However, the incidence and cost of vertebral fractures in China are unknown. We aimed to assess the incidence and cost of clinically recognized vertebral fractures among people aged 50 years and older in China from 2013 to 2017. MATERIALS AND METHODS: This population-based cohort study was conducted by using Urban Employee Basic Medical Insurance (UEBMI) and Urban Resident Basic Medical Insurance (URBMI) data in China from 2013 to 2017, which covered more than 95% of the Chinese population in urban areas. Vertebral fractures were identified by the primary diagnosis (i.e. International Classification of Diseases code or text of diagnosis) in UEBMI and URBMI. The incidence and medical cost of these clinically recognized vertebral fractures in urban China were calculated. RESULTS: A total of 271 981 vertebral fractures (186 428, 68.5% females and 85 553, 31.5% males) were identified, with a mean age of 70.26 years. The incidence of vertebral fractures among patients aged 50 years and over in China increased ~1.79-fold during the 5 years, from 85.21 per 100 000 person-years in 2013 to 152.13 per 100 000 person-years in 2017. Medical costs for vertebral fractures increased from US$92.74 million in 2013 to US$505.3 million in 2017. Annual costs per vertebral fracture case increased from US$3.54 thousand in 2013 to US$5.35 thousand in 2017. CONCLUSION: The dramatic increase in the incidence and cost of clinically recognized vertebral fractures among patients aged 50 and over in urban China implies that more attention should be given to the management of osteoporosis to prevent osteoporotic fractures.

Integrated database-based Screening Cohort for Asian Nomadic descendants in China (Scan-China): Insights on prospective ethnicity-focused cancer screening.

Established in 2017, the Screening Cohort for Asian Nomadic descendants in China (Scan-China) has benefited over 180,000 members of a multi-ethnic population, particularly individuals of Mongolian descent compared with the general population (Han ethnicity), in the Inner Mongolia Autonomous Region, China. This cohort study aims to evaluate the effectiveness of cancer screening and serve as a real-world data platform for cancer studies. The 6 most prevalent cancers in China are considered-namely, breast, lung, colorectal, gastric, liver and esophageal cancer. After baseline cancer risk assessments and screening tests, both active and passive follow-up (based on the healthcare insurance database, cancer registry, the front page of hospital medical records, and death certificates) will be conducted to trace participants' onset and progression of cancers and other prevalent chronic diseases. Scan-China has preliminarily found a disproportionately lower screening participation rate and higher incidence/mortality rates of esophageal and breast cancer among the Mongolian population than among their Han counterparts. Further research will explore the cancer burden, natural history, treatment patterns, and risk factors of the target cancers.

Inflammatory Bowel Disease and Long-term Risk of Cancer: A Prospective Cohort Study Among Half a Million Adults in UK Biobank.

BACKGROUND: This study aims to examine the prospective association of inflammatory bowel disease (IBD) with long-term risk of overall, site-specific cancer and cancer-specific mortality in middle-aged and older people. METHODS: The study included participants free of any cancer at baseline from the UK Biobank, with IBD patients as an exposure group and non-IBD patients as a reference group. Primary outcome was the incidence of overall cancer and cancer-specific mortality. Secondary outcomes included site-specific cancers and types of digestive cancers. Cox proportional hazard model was used to investigate the associated risk of incident malignancies and related mortality. RESULTS: Among 455 927 participants, 5142 were diagnosed with IBD (3258 ulcerative colitis [UC]; 1449 Crohn's disease [CD]; others unspecified). During a median of 12.2-year follow-up, 890 cases of incident cancer were identified in IBD patients (15.74 per 1000 person years) compared with 63 675 cases in reference individuals (12.46 per 1000 person years). Of these cases, 220 and 12 838 cancer-specific deaths occurred in IBD and non-IBD groups. Compared with non-IBD participants, the adjusted hazard ratio (AHR) for overall cancer and cancer-specific mortality was 1.17 (95% CI, 1.09-1.25) and 1.26 (95% CI, 1.18-1.35) among IBD patients, with an AHR of 1.15 (95% CI, 1.02-1.31) and 1.38 (95% CI, 1.08-1.75) in UC and 1.15 (95% CI, 1.06-1.25) and 1.25 (95% CI, 1.06-1.49) in CD, respectively. Specifically, increased risk of digestive (1.33; 95% CI, 1.12-1.57), nonmelanoma (1.25; 95% CI, 1.11-1.41), and male genital (1.29; 95% CI, 1.09-1.52) cancers was observed in IBD patients. CONCLUSIONS: Compared with non-IBD, IBD may be associated with an increased risk of overall cancer and cancer-specific mortality, particularly digestive cancers, nonmelanoma and male genital cancers.

Regardless of IBD subtype, IBD may be associated with a 17% excess risk of incident overall cancer and a 26% higher risk of death due to cancer compared with non-IBD participants­and the risk seemed even higher in UC patients.

Associations between pulmonary function and cognitive decline in the middle-aged and older adults: evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND: Studies observing the relationship between pulmonary function and the risk of cognitive impairment in middle-aged and older adults was increasing, but the results were inconsistent. To date, evidence from longitudinal data is scarce and further research is urgently needed. METHODS: We used data from the China Health and Retirement Longitudinal Study. Participants were enrolled in 2011/2013 and followed up in 2013, 2015 and 2018. Pulmonary function was assessed via peak expiratory flow (PEF). Cognitive function, measured by episodic memory and mental status, was assessed through a face-to-face interview in each survey. RESULTS: A total of 8,274 participants (52.86% males; mean age, 56.44 years) were included. The scores of global cognition (12.46 versus 11.51, P < 0.001) of men were significantly higher than women at baseline, with a total of 5096 participants (61.59%) declining during the follow-up. Higher baseline PEF was associated with lower absolute decline in global cognition (OR per 1-SD difference 0.921; P = 0.031) and mental status (OR per 1-SD difference 0.9889; P = 0.002) during follow-up in men, and significant associations between higher baseline PEF and a lower absolute decline in the episodic memory were both found in men (OR per 1-SD difference 0.907; P = 0.006) and women (OR per 1-SD difference 0.915; P = 0.022). Second analysis showed that the significant associations between positive PEF variation and a lower rate of 4-year decline in global cognition, mental status and episodic memory were all only found in men. In subgroup analyses, higher PEF at baseline was significantly associated with a lower absolute decline of global cognition among male individuals >60 years. Significant associations between higher PEF at baseline and lower absolute decline in global cognition and episodic memory during follow-up were only found in never-smokers, while higher PEF was related to lower absolute decline in mental status among non-smoking and smoking males. CONCLUSIONS: Pulmonary function correlates with cognitive functions in middle-aged and older people, especially males. Additional studies characterizing early and long-term PEF changes are needed.

Impact of HPV vaccination on HPV infection and cervical related disease burden in real-world settings (HPV-RWS): protocol of a prospective cohort.

BACKGROUND: Cervical cancer is one of the most common cancers in women and could be prevented by human papilloma virus (HPV) vaccination. Cervarix, the first available HPV vaccine, has been widely administrated to Chinese women, while little was known about its effect on the prevention and control for HPV related diseases in China. The study aims to assess the impact of Cervarix on HPV infection and cervical related diseases in real world. METHODS: This is a prospective, multi-age birth cohort study to investigate the incidence and continuous status of HPV infection, and relevant cervical diseases by exposure status (with Cervarix vaccination history or without any HPV vaccination history). It is planned to recruit 12,118 eligible women at age of 9 to 45 years from vaccination clinics or hospital outpatient clinics, and then follow up them for three years. The standard questionnaire will be used to collect information such as demographic characteristics, menstruation and obstetrical histories, history of sexual behavior, personal behavior history, history of disease and pathogen infection, medication history, and family history at baseline. After three years, the changes of these behaviors will be investigated again, and other related health status information will be retrieved from the electronic health records during the follow-up period. If available physically and legally, the cervical cancer screening will be performed, including type-specific HPV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing and contingent thinprep cytologic test (TCT) and colposcopy. The free cervical cancer screening will be captured and uploaded timely to the Yinzhou Regional Health Information Platform (YRHIP); therefore, the long-term outcomes of participants will be monitored. DISCUSSION: This prospective cohort study will assess the impact of HPV vaccine on HPV infection and related cervical diseases in women aged 9-45 years, which makes up for the lack of evidence in Chinese women. The results of this study will provide support for understanding the impact of HPV vaccination in China, and make a contribution to increasing HPV vaccination and cervical cancer screening coverage in China. TRIAL REGISTRATION: This study has been retrospectively registered on clinicaltrials.gov (NCT05341284) on April 22, 2022.

Cost-Effectiveness of COVID-19 Sequential Vaccination Strategies in Inactivated Vaccinated Individuals in China.

To effectively prevent and control the COVID-19 pandemic, countries have adopted a booster vaccination strategy. This study aimed to estimate the cost-effectiveness of sequential booster COVID-19 vaccination compared to two-dose inactivated vaccination in China from a societal perspective. A Markov model was developed to estimate the cost-effectiveness of sequential vaccination, including two doses of an inactivated vaccine followed by a booster shot of an inactivated vaccine, adenovirus vectored vaccine, protein subunit vaccine, or mRNA vaccine. The incremental effects of a booster shot with an inactivated vaccine, protein subunit vaccine, adenovirus vectored vaccine, and mRNA vaccine were 0.0075, 0.0110, 0.0208, and 0.0249 QALYs and saved costs of US$163.96, US$261.73, US$583.21, and US$724.49, respectively. Under the Omicron virus pandemic, the sequential vaccination among adults and the elderly (aged 60-69, 70-79, over 80) was consistently cost-saving, and a booster shot of the mRNA vaccine was more cost-saving. The results indicate that the sequential vaccination strategy is cost-effective in addressing the COVID-19 pandemic, and improving vaccination coverage among the elderly is of great importance in avoiding severe cases and deaths.

Comparative Performance of 14 HCC Prediction Models in CHB: A Dynamic Validation at Serial On-Treatment Timepoints.

INTRODUCTION: To assess comparative performance of 14 hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B (CHB) patients using on-treatment values at different timepoints. METHODS: Based on a nationwide prospective cohort of 986 treatment-naive CHB patients undergoing entecavir therapy with every 26-week follow-up, 14 HCC risk scores were calculated using on-treatment values at week 26, 52, 78, and 104, respectively. Model performance predicting 3-year HCC was assessed using time-dependent area under the receiver operating characteristic curve (AUC) and calibration index. Model cutoffs were validated through common diagnostic accuracy measures. RESULTS: During median 4.7-year follow-up, 56 (7.5%) developed HCC. Discrimination using on-treatment values within first 2 years was generally acceptable for most models (AUCs ranging from 0.68 to 0.81), except for REACH-B, NGM-HCC, and PAGE-B, although AUCs slightly decreased from week 26 to 104. Of these, REAL-B, CAMD, GAG-HCC, AASL-HCC, LSM-HCC, mPAGE-B, and mREACH-BII showed highest discrimination with AUCs ranging from 0.76 to 0.81, 0.72 to 0.76, 0.70 to 0.76, and 0.71 to 0.74 when reassessment at week 26, 52, 78, and 104, respectively. With reassessment within first 2 years, both REAL-B and CAMD calibrated well (Brier score ranging from 0.037 to 0.052). Of 9 models reporting cutoffs, REAL-B, AASL-HCC, and mPAGE-B using on-treatment values could identify 30%-40% of patients as low risk with minimal HCC incidence in the low-risk group (0.40% [REAL-B]-1.56% [mPAGE-B]). DISCUSSION: In this undergoing antiviral treatment CHB cohort, most HCC prediction models performed well even using on-treatment values during first 2 years, particularly REAL-B, AASL-HCC, CAMD, and mPAGE-B model.

Sulfonylurea and Cancer Risk Among Patients With Type 2 Diabetes: A Population-Based Cohort Study.

Background: Current evidence of the association between the use of sulfonylurea and cancer risk is highly conflicting and little evidence of this association is from the mainland Chinese population. This study aimed to evaluate the potential effects of sulfonylurea use on cancer risk among patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study of T2DM patients who were new users of sulfonylurea or metformin was conducted using the Yinzhou Regional Health Care Database. A marginal structural Cox model was used to estimate the hazard ratio (HR) of cancer associated with the use of sulfonylurea compared with metformin, with time-varying confounders controlled by inverse probability weighting. Secondary analyses using different glucose-lowering drugs (GLDs) as comparator and sensitivity analyses for potential bias due to latency period, model misspecification, missing data, analyses strategy (intention-to-treat and per-protocol), and diagnosis validation were performed to examine the robustness of the results. Results: After fully controlling for time-varying confounding, baseline confounding, and competing risk, the use of sulfonylurea was not associated with the risk of any cancer (HR 1.09; 95% CI, 0.93-1.27), compared with the use of metformin. In the secondary analyses, compared with α - glucosidase inhibitors, thiazolidinediones, glinides, other GLDs except sulfonylure and insulin, and T2DM patients not treated with sulfonylureas, the HRs of the association between sulfonylurea use and cancer risk were 0.92 (95% CI; 0.78-1.08), 0.89 (95% CI; 0.66-1.19), 0.85 (95% CI; 0.71-1.02), 1.04 (95% CI; 0.89-1.22), and 1.07 (95% CI; 0.99-1.16), respectively. The results of analyses for various subgroups, risk of site-specific cancers, cumulative duration, dose-response relationship, and sensitivity analyses of different latency periods and missing data were generally consistent with the findings of the primary analyses. Conclusion: No association between sulfonylurea use and cancer risk was found in this study after properly controlling biases due to time-varying confounders and other sources. Further studies on the association between sulfonylurea use and the risk of cancer by using data from a Chinese population with higher representativeness are needed.

Differences in the Association Between Modifiable Lifestyle Factors and Gastric Precancerous Lesions Among Mongolians and Han Chinese.

Background: There has been a paucity of evidence examining whether preventable behavioral risk factors led to ethnic differences of gastric precancerous lesions (GPL). We aimed to investigate the ethnic disparity of associations between GPL and lifestyle factors in Mongolian and Han Chinese populations. Methods: The study included participants aged 36-75 years enrolled in the Cancer Screening Program during 2016-2017 in Hohhot and Tongliao City, Inner Mongolia. GPL was defined as the gross cascading events (i.e., gastric ulcer, atrophic gastritis, intestinal metaplasia, and dysplasia) that preceded gastric cancer. Results: A total of 61638 participants were included, of whom 6863(11·1%) were Mongolians. Alcohol consumption was positively associated with GPL risk in both ethnic groups, but the magnitude was greater in Mongolians (odds ratio (OR) 6·91, 95%CI 5·82-8·28) than in Han Chinese (OR 5·64, 95%CI 5·27-6·04), corresponding to a higher population attributable fraction (PAF) for Mongolians (53·18% vs 43·71%). Besides, the strength of the positive association between physical inactivity and GPL risk was greater among Mongolians (OR 2·02, 95%CI 1·70-2·41; OR 1·09, 95%CI 1·02-1·17 among Han Chinese) with a higher PAF. Smoking was strongly associated with GPL risk in both ethnic groups as well, but the association was more prominent among Han Chinese (OR 5·24 (1·70-2·41) for <10 cigarettes/d, 8·19 (7·48-8·97) for 11-20 cigarettes/d, 7·07 (6·40-7·81) for ≥21 cigarettes/d; the corresponding ORs were 2·96 (2·19-4·00), 6·22 (5·04-7·68), and 7·03 (5·45-9·08) among Mongolians). Lastly, our findings revealed that a significant correlation between insufficient fruits and vegetable consumption and GPL risk was only found among Mongolians (OR 1·27, 95%CI 1·04-1·56). Conclusions: Our result suggested that high-risk lifestyle factors should be reduced, particularly in Mongolians. Further studies are needed to elucidate the underlying mechanisms and to reduce health disparities in underserved ethnic groups.

Prevalence and incidence of pseudomyxoma peritonei in urban China: A nationwide retrospective cohort study.

BACKGROUND: Pseudomyxoma peritonei (PMP) is an extremely rare condition. Information regarding the disease burden of PMP in developing countries is limited. This study aimed to determine the epidemiology of PMP in China. METHODS: PMP data were extracted from the national databases of Urban Basic Medical Insurance. All cases were identified using the International Classification of Diseases (ICD) codes and Chinese diagnostic terms. The national prevalence from 2012 to 2016 and incidence in 2016 were estimated. RESULTS: In total, 153 patients with PMP were identified. The crude prevalence of PMP in 2016 was 2.47 (95% confidence interval [CI] 1.71 to 3.23) per million person-year, with a higher prevalence in females than males. Prevalence increased with age, with the first peak in those aged 15-29 years and the highest in those aged >80 years. The crude incidence of PMP in 2016 was 1.19 (95% CI 0.59 to 1.78) per million person-years. Similar to the prevalence, the rates were higher in women than in men. The incidence also increased with age, with the highest prevalence in those aged >80 years. Besides, the most frequent comorbidities before and after the first diagnosis of PMP were unspecified secondary malignancies and malignancies of unspecified sites, followed by abdominal malignant tumours. CONCLUSIONS: The rate of PMP was lower in mainland China than in European countries and increased with advancing age. Women were more likely to have PMP than men. Furthermore, an insufficient understanding of this rare disease presents a major challenge in accurately evaluating the disease burden.

Increasing prevalence and burden of bronchiectasis in urban Chinese adults, 2013-2017: a nationwide population-based cohort study.

BACKGROUND: While the prevalence and disease burden of bronchiectasis are increasing, data in the world's largest population are lacking. We aimed to investigate the prevalence and disease burden of bronchiectasis in Chinese adults. METHODS: We conducted a population-based study using data between 2013 and 2017 from the national databases of Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance in China. Data from over 380 million patients aged 18 years and older during the study period were analyzed, and a total of 383,926 bronchiectasis patients were identified. Primary outcomes included the age- and sex-specific prevalence of bronchiectasis. Annual visits and hospitalizations, as well as annual costs were also calculated. RESULTS: The prevalence of bronchiectasis in Chinese adults increased 2.31-fold, from 75.48 (62.26, 88.69) per 100,000 in 2013 to 174.45 (137.02, 211.88) per 100,000 in 2017. The increase was more remarkable for patients aged over 50 years in both genders. The per-capita total cost and hospitalization cost of patients with bronchiectasis increased 2.18-fold and 1.83-fold from 2013 to 2017, respectively, mostly driven by non-bronchiectasis costs. The average annual hospitalization ranged from 1.20 to 1.24 times during the 5 years. CONCLUSION: The prevalence and disease burden of bronchiectasis in Chinese urban adults ≥ 18 years had increased significantly between 2013 and 2017.

A Partially Randomized Patient Preference Trial to Assess the Quality of Life and Patency Rate After Minimally Invasive Cardiac Surgery-Coronary Artery Bypass Grafting: Design and Rationale of the MICS-CABG PRPP Trial.

Background: Minimally invasive cardiac surgery-coronary artery bypass grafting (MICS-CABG) has emerged as a safe alternative to standard cardiac surgery. However, treatment preferences can decrease the generalizability of RCT results to the clinical population (i.e., reduce external validity) and influence adherence to the treatment protocol and study outcomes (i.e., reduce internal validity). However, this has not yet been properly investigated in randomized trials with consideration of treatment preferences. Study Design: In this study, patients with a preference will be allocated to treatment strategies accordingly, whereas only those patients without a distinct preference will be randomized. The randomized trial is a 248-patient controlled, randomized, investigator-blinded trial. It is designed to compare whether treatment with MICS-CABG is beneficial in comparison to CABG. This study is aimed to establish the superiority hypothesis for the physical component summary (PCS) accompanied by the non-inferiority hypothesis for overall graft patency. Patients with no treatment preference will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoints are the PCS score at 30 days after surgery and the overall patency rate of the grafts within 14 days after surgery. Secondary outcome measures include the PCS score and patency rate at different time points. Safety endpoints include major adverse cardiac and cerebrovascular events, complications, bleeding, wound infection, death, etc. Conclusions: This trial will address essential questions of the efficacy and safety of MICS-CABG. The study will also address the impact of patients' preferences on external validity and internal validity.