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Background Although a U-shaped association between sleep duration and all-cause mortality has been found in general population, its association in the elderly adults, especially in the oldest-old, is rarely explored. Methods In present cohort study, we prospectively explore the association between sleep duration and all-cause mortality among 15,092 participants enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2005 to 2019. Sleep duration and death information was collected by using structured questionnaires. Cox regression model with sleep duration as a time-varying exposure was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). The dose-response association between them was explored via a restricted cubic spline function. Results During an average follow-up of 4.51 (standard deviation, SD: 3.62) years, 10,768 participants died during the follow-up period. The mean (SD) age of the participants was 89.26 (11.56) years old. Compared to individuals with moderate sleep duration (7–8 hours), individuals with long sleep duration (> 8 hours) had a significantly higher risk of all-cause mortality (HR: 1.13, 95%CI: 1.09–1.18), but not among individuals with short sleep duration (≤ 6 hours) (HR: 1.02, 95%CI: 0.96–1.09). Similar results were observed in subgroup analyses based on age and gender. In the dose-response analysis, a J-shaped association was observed. Conclusions Sleep duration was associated with all-cause mortality in a J-shaped pattern in the elderly population in China.

Brain metastasis (BM) is one of the common ways of tumor metastasis and has a poor prognosis. This study aims to identify potential biomarkers from the perspective of somatic mutations, providing a basis for the prognosis evaluation and immunogenicity prediction of BM patients. This study collected the somatic mutation profiles and clinical information of a total of 421 patients with BM in Memorial Sloan Kettering Cancer Center (MSKCC). Non-negative matrix factorization was employed to extract the mutational process signatures operating in the genome. Consensus clustering analysis was utilized to identify mutation-related molecular subtypes. Through a comprehensive analysis of genomic mutations and copy number variations (CNV), biomarkers associated with outcomes and tumor immunogenicity were screened. Non-small cell lung cancer, melanoma, and breast cancer were common primary tumors of BM, and these three tumor types exhibited better prognosis compared to other types. This study found that a higher tumor mutation burden (TMB) was significantly associated with a better prognosis of BM. A total of four mutational process signatures were extracted, and among them, a signature featured by C > T mutations and related to DNA damage repair was proven to be linked with an inferior outcome and a lower TMB. Through integrated genomic mutation analysis, mutation was determined to associate with improved prognosis of BM. More importantly, patients carrying this mutation also harbored a better response to immunotherapy. CNV analysis indicated that deletion and deletion were respectively associated with poorer and better outcomes in patients with BM. By integrating the somatic mutation data of patients with BM, this study identified molecular biomarkers related to outcomes and immunogenicity from three perspectives: mutational process signatures, molecular subtypes, and genomic variations. Our findings provide clues for prognosis evaluation in BM patients. They also establish a theoretical basis for predicting immunotherapy efficacy.

Objective Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are persistent pollutants and have endocrine disruptive and neurotoxic effects. The association between maternal PFAS concentrations and neuropsychological development in children is inconclusive. The present study aimed to examine the effect of maternal PFAS concentrations on neuropsychological development in 4-years-old children. Methods We used data from Shanghai-Minhang Birth Cohort, which recruited pregnant women at 12–16 gestational weeks. Among 981 women having PFAS measurement, 533 mother-child pairs were included in the study. A total of eight PFASs were measured, including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), and perfluorotridecanoic acid (PFTrDA). When infants turned 4 years old, mothers were asked to complete the Ages and Stages Questionnaires® (ASQ) to assess neuropsychological development of their children. Poisson regression model with robust variance estimates was used to examine the association between maternal PFAS concentrations and each developmental subscale of the ASQ. Results Prenatal plasma concentrations of most PFASs tended to be associated with increased risk of development problem in personal-social skills, including PFHxS, PFOS, PFOA, PFNA, PFDA, and PDUdA, and the associations for PFNA and PFDA were significant (per natural log unit increase: RR PFNA  = 1.92, 95% CI: 1.21, 3.05; RR PFDA  = 1.66, 95% CI: 1.17, 2.37). In stratified analyses by child’ sex, the consistent pattern of higher risk of developmental problems in personal-social skills associated with most PFASs was mainly observed among girls (RR PFOS  = 2.56, 95% CI: 1.20, 5.45; RR PFOA  = 9.00, 95% CI: 3.82, 21.21; RR PFNA  = 3.11, 95% CI: 1.36, 7.13; RR PFDA  = 2.20, 95% CI: 1.21, 4.00; RR PFUdA  = 2.44, 95% CI: 1.14, 5.20; RR PFDoA  = 1.62, 95% CI: 1.04, 2.54). Boys with higher maternal PFOA concentrations had a decreased risk of developmental problems in gross motor skills (RR = 0.47, 95% CI: 0.25, 0.89). Conclusion Prenatal plasma PFAS concentrations were associated with neuropsychological development in girls at 4 years of age, mainly in the subset of personal-social skills.

Small cell lung cancer (SCLC) is a highly malignant lung cancer subtype with a dismal prognosis and limited treatment options. This study aimed to identify new prognostic molecular biomarkers for SCLC and explore their immune-related implications for treatment strategies. We analyzed 200 SCLC samples via whole-exome sequencing (WES) and 313 samples by targeted sequencing. A smoking-related SBS4 mutational signature was linked to poorer prognosis and lower tumor mutational burden (TMB), while the APOBEC-mediated SBS13 signature was associated with better prognosis and higher TMB. We identified a molecular subtype with the worst outcomes and lowest TMB in both cohorts. Among 38 high-frequency mutated genes associated with SCLC prognosis, only UNC13A mutations were beneficial. Patients with UNC13A mutations had favorable immune infiltration and tumor immunogenicity. Additionally, TP53 splice site mutations were related to the worst survival outcomes. In conclusion, we discovered new molecular biomarkers for SCLC prognosis. Our findings on their immunological characteristics offer insights for developing novel SCLC treatment strategies.

Currently developed molecular markers can predict the effectiveness of cancer immunotherapy and screen beneficiaries to some extent, but they are not stable enough. Therefore, there is an urgent need for discovering novel biomarkers. At the same time, sex factor plays a vital role in the response to immunotherapy, so it is particularly important to identify sex-related molecular indicators. We integrated a pan-cancer cohort consisting of 2348 cancer patients who received immune checkpoint inhibitors and targeted sequencing. Using somatic mutation profiles, we identified mutational signatures, molecular subtypes, and frequently mutated genes, and analyzed their relationships with immunotherapeutic outcomes. We also explored sex disparities of determined biomarkers in response to treatments. We found that male patients exhibited better immunotherapy outcomes and higher tumor mutational burden. A total of seven mutational signatures were identified, among which signatures 1 and 3 were associated with worse immunotherapy outcomes, while signatures 2 and 6 correlated with better outcomes. Gender-based analysis revealed that mutational signature 1 continued to show a worse immunotherapy outcome in female patients, whereas signature 6 demonstrated a better outcome in male patients. Based on mutational activities, we identified four potential molecular subtypes with gender differences and relevance to treatment outcomes. PI3K-AKT, RAS signaling pathways, and 68 significantly mutated genes were identified to be associated with immunotherapy outcomes, with nine genes (i.e., ATM, ATRX, DOT1L, EP300, EPHB1, NOTCH1, PBRM1, RBM10, and SETD2) exhibiting gender differences. Finally, we discovered co-mutated gene pairs and TP53 p.R282W mutations related to treatment outcomes, highlighting their gender-specific differences. This study identified several molecular biomarkers related to cancer immunotherapy outcomes in terms of mutational signatures, molecular subtypes, and mutated genes, and explored their gender-relatedness in order to provide clues and basis for clinical treatment efficacy evaluation and patient selection.

Background China is one of the crucial countries with a significant number of diabetes patients, but only a limited number of studies on diabetes mellitus (DM) mortality rates have been reported among the Chinese population. This study examined trends in diabetes mortality in China from 2008 to 2021 and projected future rates from 2022 to 2030, providing evidence to guide prevention and control strategies. Methods Annual diabetes mortality data were obtained from the China Death Surveillance Dataset (2008–2021). Age-standardized mortality rate (ASMR) was calculated using the direct method, referencing the Sixth National Census population. Trends in diabetes mortality were analyzed via joinpoint regression to derive the annual percentage change (APC) and average annual percentage change (AAPC), and to assess the trends. Finally, a GM(1,1) model was constructed to predict the crude mortality rate (CMR) and ASMR of diabetes until 2030. Results From 2008 to 2021, the diabetes mortality rates in China rose from 9.72 to 18.88 per 100,000, while the ASMR rose from 10.59 to 12.37 per 100,000 (AAPC: 1.198%; 95% CI: 0.182%, 2.224%). A rising trend was observed in males (AAPC: 1.874%; 95% CI: 0.591%, 3.118%), in rural areas (AAPC: 1.992%; 95% CI: 1.108%, 2.884%), in the western region (AAPC: 3.857%; 95% CI: 2.249%, 5.491%), and in the 65-and-over age group (AAPC: 1.938%; 95% CI: 0.537%, 3.358%) from 2008 to 2021. By 2030, the CMR and ASMR for diabetes are projected to reach 31.26 and 14.44 per 100,000, respectively. Conclusion From 2008 to 2021, diabetes mortality rates in China showed an increasing trend, with disparities observed across sex, residence, region, and age groups. The increasing trend of diabetes mortality will continue in the future. Healthcare organizations and policymakers need to focus on male groups, rural areas, the western region and the population aged 65 and above, while implementing robust diabetes prevention strategies targeting younger cohorts.

Aims This study aimed to explore differences in preferences between Chinese patients with type 2 diabetes mellitus (T2D) and physicians when selecting anti‐hyperglycemic medications. Materials and Methods We conducted a discrete choice experiment (DCE) involving 1784 patients (face‐to‐face surveys) and 168 physicians (online questionnaires) across eastern, central, and western China. Seven treatment attributes were assessed: HbA1c reduction, hypoglycemia risk, cardiovascular benefits, gastrointestinal adverse events, weight change, mode of administration, and monthly out‐of‐pocket cost. Preference heterogeneity was explored using latent class model. Results Patients placed the greatest importance on monthly out‐of‐pocket cost, treatment efficacy, and hypoglycemia risk, whereas physicians prioritized hypoglycemia risk, cardiovascular benefits, and treatment efficacy. Notably, physicians tended to overestimate patients' willingness to pay for treatment benefits. Specifically, patients were willing to pay 277 CNY (39 USD) for cardiovascular benefits, whereas physicians estimated that patients would be willing to pay 864 CNY (121 USD). Latent class analysis identified substantial heterogeneity in both groups. In particular, the largest patient subgroup was strongly cost‐sensitive, with preferences driven primarily by financial burden, whereas no directly corresponding physician subgroup was observed. Conclusion Patients and physicians differ in how they prioritize diabetes medication attributes, especially regarding efficacy, cardiovascular benefit, and cost. Shared decision‐making should account for these differences to support value‐concordant, patient‐centered diabetes care. Highlights This study reveals substantial differences in anti‐hyperglycemic medication preferences between Chinese patients with T2D and physicians. Patients prioritized out‐of‐pocket cost and treatment efficacy, while physicians emphasized hypoglycemia risk and cardiovascular benefits. These discrepancies highlight the need for enhanced shared decision‐making to align treatment choices with patient values and improve adherence. Differences in patient and physician preferences for anti‐hyperglycemic medication attributes in China.

Background Evidence on the association between exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) and blood glucose concentrations in pregnant women is inconsistent. This study aimed to examine the association between PFAS exposure and the concentrations of fasting plasma glucose (FPG) and one-hour plasma glucose (1 h-PG) after a 50-g oral glucose tolerance test in pregnant women. Methods The study was based on the Shanghai-Minhang Birth Cohort, in which 1292 pregnant women were recruited. Among them, 981 women provided blood samples (at 12–16 gestational weeks) for PFAS measurement. FPG data collected from 856 women at 12–20 GW and 1 h-PG data collected from 705 women at 20–28 GW were obtained through medical records from the routine prenatal care system. High FPG or 1 h-PG was defined as ≥90th percentile of FPG or 1 h-PG. The analysis of eight PFASs was conducted in this study: perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), and perfluorotridecanoic acid (PFTrDA). The odds ratios (ORs) and associated 95% confidence intervals (CIs) were estimated to determine the associations of each PFAS compound with high FPG and 1 h-PG from a logistic regression model. Results After adjustment for potential confounders, most PFASs were positively associated with high 1 h-PG concentrations. The OR for high 1 h-PG concentrations was 1.87 (95% CI: 1.15–3.05) with a one log unit increase of PFOS; similar associations were observed for PFNA (OR: 2.15, 95% CI: 1.24–3.74), PFDA (OR: 1.61, 95% CI: 1.10–2.44), PFUdA (OR: 1.71, 95% CI: 1.12–2.62), and PFDoA (OR: 1.34, 95% CI: 1.00–1.81). When the PFAS concentrations were categorized into three groups by tertiles, the highest tertiles of PFOS, PFOA, PFNA, PFDA, PFDoA, and PFTrDA had a statistically significant increase in the risk of high 1 h-PG concentrations compared with the lowest tertiles. No statistically significant association was observed between PFAS exposure and high FPG. Conclusion PFAS exposure was associated with an increased risk of high 1 h-PG among pregnant women, but no such association was observed for FPG.

ObjectiveThis study aimed to investigate the preferences regarding risks, benefits and other treatment attributes of patients with type 2 diabetes mellitus (T2DM) in China when selecting a second-line anti-hyperglycaemic medicine.MethodsA discrete choice experiment with hypothetical anti-hyperglycaemic medication profiles was performed using a face-to-face survey administered to patients with T2DM. The medication profile was described using seven attributes: treatment efficacy, hypoglycaemia risk, cardiovascular benefits, gastrointestinal (GI) adverse events, weight change, mode of administration and out-of-pocket cost. Participants chose between medication profiles by comparing attributes. Data were analysed using a mixed logit model with marginal willingness to pay (mWTP) and maximum acceptable risk (MAR) calculated. The preference heterogeneity within the sample was explored using a latent class model (LCM).ResultsA total of 3327 respondents from five major geographical regions completed the survey. Treatment efficacy, hypoglycaemia risk, cardiovascular benefits and GI adverse events were major concerns among the seven attributes measured. Weight change and mode of administration were of lesser concern. Regarding mWTP, respondents would pay ¥236.1 (US$36.6) for an anti-hyperglycaemic medication with an efficacy of 2.5% points reduction in HbA1c, while they were willing to accept a weight gain of 3 kg only if they received a compensation of ¥56.7 (US$8.8). Respondents were willing to accept a relatively large increase in hypoglycaemia risk (MAR=15.9%) to improve treatment efficacy from intermediate (1.0% points) to high (1.5% points). LCM identified the following four unobserved subgroups: trypanophobia, cardiovascular-benefits-focused, safety-focused and efficacy-focused and cost-sensitive.ConclusionPatients with T2DM prioritised free out-of-pocket costs, highest efficacy, no hypoglycaemia risk and cardiovascular benefits over weight change and mode of administration. There exists great preference heterogeneity among patients, which should be taken into account in healthcare decision-making processes.