Concentrations of perfluoroalkyl and polyfluoroalkyl substances and blood glucose in pregnant women.

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.

Sleep duration and all-cause mortality in the elderly in China: a population-based cohort study.

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.

Prenatal exposure to extremely low frequency magnetic field and its impact on fetal growth.

OBJECTIVE: Studies on the effect of prenatal exposure to magnetic field (MF) on fetal growth is inconclusive and subject to some methodological limitations, particularly in measurement of MF exposure. The present study aimed to examine the association between maternal extremely low frequency MF (ELF-MF) exposure during pregnancy and fetal growth in offspring. METHODS: A total of 128 pregnant women were recruited at their 3rd trimester and asked to wear an EMDEX Lite meter for 24 h to capture daily ELF-MF exposure. Time-weighted average (TWA), P50, and P75 of personal 24-h measurements were used to evaluate prenatal ELF-MF exposure. The medians of these measurements were used as cut-off points of high and low prenatal ELF-MF exposure. Fetal growth was measured by infant's birth weight, skinfold thickness of triceps, abdomen, and back, and circumference of head, upper arm, and abdomen. These measures were conducted within 24-h after birth. Generalized Linear Model was used to examine the association between maternal ELF-MF level and fetal growth indices after potential confounders were adjusted for. RESULTS: Compared with girls with lower prenatal ELF-MF exposure, girls with higher exposure had a lower birth weight, thinner skinfold of triceps, abdomen and back, and smaller circumference of head, upper arm and abdomen in all three ELF-MF matrices. The differences were statistically significant for birth weight and most other growth measurements (P < 0.05). These measures had no significant difference between higher and lower prenatal ELF-MF exposure in boys except back skinfold thickness. CONCLUSION: Prenatal exposure to higher ELF-MF levels was associated with decreased fetal growth in girls, but not in boys.

Prenatal plasma concentrations of Perfluoroalkyl and polyfluoroalkyl substances and neuropsychological development in children at four years of age.

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: RRPFNA = 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 (RRPFOS = 2.56, 95% CI: 1.20, 5.45; RRPFOA = 9.00, 95% CI: 3.82, 21.21; RRPFNA = 3.11, 95% CI: 1.36, 7.13; RRPFDA = 2.20, 95% CI: 1.21, 4.00; RRPFUdA = 2.44, 95% CI: 1.14, 5.20; RRPFDoA = 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.

Low triglyceride as a marker for increased risk of cardiovascular diseases in patients with long-term type 2 diabetes: A cross-sectional survey in China.

BACKGROUND: There are inconsistent findings regarding associations between triglyceride levels and cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). This study aimed to test whether the association between triglycerides and CVD depends upon duration of diabetes. METHODS: From April 1, 2012, to June 30, 2012, we conducted a cross-sectional survey of 223 612 patients with T2DM from 630 hospitals in China. Cardiovascular disease was defined as having either prior coronary heart disease or stroke, or diabetic foot. Binary logistic regression was used to estimate odds ratios of triglyceride for CVD. Relative excess risk due to interaction, attributable proportion due to interaction, and synergy index were used to estimate effect size of additive interaction between low triglyceride, ie, <1.7 mmol/L, and duration of diabetes, ie, ≥15 years. RESULTS: Among 223 612 T2DM patients, 31 898 (14.27%) suffered from CVD. A low level of triglyceride was associated with decreased risk of CVD (univariable OR, 0.91, 95% CI, 0.88-0.93; multivariable OR, 0.94, 95% CI, 0.92-0.97) among patients with <15 years of duration of diabetes but increased risk of CVD (univariable OR, 1.12, 95% CI, 1.04-1.21; multivariable OR, 1.18, 95% CI, 1.09-1.27) among those patients with 15 and more years of duration of diabetes with significant additive interactions (relative excess risk due to interaction, 0.39, 95% CI, 0.25-0.52; attributable proportion due to interaction, 0.20, 95% CI, 0.14-0.27; and synergy index, 1.80, 95% CI, 1.43-2.28). CONCLUSIONS: Whereas a high triglyceride level was associated with increased risk of CVD in short-term T2DM, low triglyceride was associated with increased CVD risk in long-term T2DM. Low triglyceride may be a marker of CVD risk in Chinese patients with long-term T2DM.

Uric acid, renal function and risk of hypoglycaemia in Chinese type 2 diabetes patients.

BACKGROUND: This study aimed to explore independent associations between serum uric acid and hypoglycaemia, and whether mildly increased serum uric acid exacerbated the association between mild decline in estimated glomerular filtration rate (eGFR) and hypoglycaemia. METHODS: A cross-sectional survey of 6713 inpatients with type 2 diabetes and eGFR ≥60 mL/min/1.73 m2 and admitted to 81 tertiary care hospitals in China was conducted. Self-reported asymptotic hypoglycaemia with plasma glucose ≤3.9 mmol/L, hypoglycaemia episodes with symptoms in 1 month or hypoglycaemia that needed assistance from other people in 3 months before hospitalization was used to define hypoglycaemia. Binary logistic regression was used to estimate odds ratios of serum uric acid for hypoglycaemia. Three measures, that is, relative excess risk due to interaction (RERI), attributable proportion due to interaction and synergy index (S) were used to estimate the effect of mildly decreased eGFR on the association of serum uric acid with hypoglycaemia. RESULTS: Serum uric acid was associated with hypoglycaemia in an ordinal manner (P for trend <0.01) with an odds ratio of top quartile versus the lowest quartile up to 3.03 (95% confidence interval: 2.13-4.32). The odds ratio of serum uric acid levels ≥ versus <283 µmol/L (i.e. the median) was 1.98 (95% confidence interval:1.58-2.48). Serum uric acid levels ≥ versus <283 µmol/L greatly enhanced the association between mild decline in eGFR (eGFR < 90 mL/min/1.73 m2 ) and hypoglycaemia from 0.94 (0.36-2.43) to 3.90 (2.55-5.95), with a significant additive interaction (P < 0.05 for RERI, AP and S). CONCLUSIONS: Mildly increased serum uric acid was associated with increased risk of hypoglycaemia and enhanced the association between mildly decreased eGFR and hypoglycaemia in type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

A bibliometric study on trends in chiropractic research from 1920 to 2023.

OBJECTIVE: An increasing body of evidence suggests a positive role of chiropractic in the treatment of neuro-musculoskeletal disorders. This study aims to explore current research hotspots and trends, providing insights into the broad prospects of this field. METHODS: A bibliometric review was conducted on all chiropractic articles included in the Web of Science Core Collection before December 31, 2023. RESULTS: Over the past century, the volume of research in the field of chiropractic has been fluctuating annually, with four peaks observed in total. The United States, Canada, Australia, and the United Kingdom are leading countries. Chu, Eric Chun-Pu is the author with the most publications, while Bronfort, Gert has the highest total citation count. The University of Southern Denmark has produced the most publications, while Queens University - Canada is the most central institution. The Journal of Manipulative and Physiological Therapeutics is the journal with the most publications and citations, while the Journal of the American Medical Association is the most central journal. The two most-cited articles were both authored by Eisenberg DM. Emerging keywords include "chronic pain" and "skills". The theoretical mechanisms and scientific basis of chiropractic, its clinical practice and safety, education and training, integration with other disciplines, and patient experiences and satisfaction are the frontiers and hotspots of research. CONCLUSION: This study integrates bibliometric analysis to summarize the current state of research and global network centers in the field of chiropractic, further highlighting the hotspots and trends in this field. However, Individual and national rankings should be interpreted with caution due to our focus on Web of Science rather than PubMed.

[Feasibility of the aging males' symptoms scale for the male population of Shanghai].

OBJECTIVE: To assess the reliability and validity of the Aging Males' Symptoms (AMS) scale in the male population of Shanghai. METHODS: We enrolled 973 males aged 40 years and over in a community of Shanghai, China. Using the AMS scale, we calculated the split-half reliability coefficient and Cronbach's alpha coefficient, assessed the validity through confirmatory factor analysis and correlation analysis, and obtained the domain scores of different people by analysis of variance and independent sample test. RESULTS: The split-half reliability was > 0.78 (P < 0.01) and Cronbach's alpha coefficients of all the dimensions > 0.82 (P < 0.01). Confirmatory factor analysis showed 3 domains in the AMS scale, Pearson correlation coefficients of all the items to their domains were > 0.49 (P < 0.01), and the total testosterone level was not correlated with AMS scores, with Pearson correlation coefficient of -0.04 (P > 0.05). Statistically significant differences were found in AMS scores among different age groups as well as among those with different chronic disease histories, but not in the psychological domain among different age groups. CONCLUSION: The reliability and validity of the AMS scale are acceptable in assessing aging males'symptoms among the male population of Shanghai, but further studies are needed to determine whether it could be used as a tool for screening late-onset hypogonadism (LOH) in males.

Patient preferences and shared decision making for the traditional Chinese medicine treatment of lung cancer: A discrete choice experiment study.

Background: Traditional Chinese Medicine (TCM), integrating patient preferences into decision-making process, has been widely used in the multimodality therapy of lung cancer. This study aimed to estimate patient preferences for treatment and shared decision-making (SDM) modes concerning inpatient TCM treatment of lung cancer in Shanghai in order to provide a basis for clinical decision-making process on TCM therapy for lung cancer. Methods: This study was conducted among patients (n = 347) from nine tertiary hospitals in Shanghai by discrete-choice experiment (DCE) survey and Shared Decision-Making Questionnaire-patient version (SDM-Q-9) survey. The DCE was developed with the inclusion of the most relevant attributes at appropriate levels for the TCM treatment of lung cancer. The empirical data analyses of patients were performed using mixed logit models. Additionally, subgroup analysis was conducted. Results: In total, 347 respondents completed the questionnaire. All attributes' coefficients were statistically significant for patients' preferences. Patients showed strong preferences for increasing disease control rate, relieving nausea and vomiting, reducing the risk of side effects, and were concerned about monthly out-of-pocket costs. Subgroup analysis indicated that patients with a lower SDM-Q-9 score and those who were satisfied with medical services emphasized more importance of higher disease control rate. Furthermore, most of the patients (90.20%) self-reported a high willingness to use SDM during the decision-making process. Conclusion: In Shanghai, patients mainly preferred SDM and considered disease control rate as the most essential attribute in the TCM treatment of lung cancer. The study findings could underscore the importance of considering patients' preferences and promote SDM.

Patient preferences for anti-hyperglycaemic medication for type 2 diabetes mellitus in China: findings from a national survey.

OBJECTIVE: This 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. METHODS: A 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). RESULTS: A 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. CONCLUSION: Patients 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.

Physician Preferences and Shared-Decision Making for the Traditional Chinese Medicine Treatment of Lung Cancer: A Discrete-Choice Experiment Study in China.

Background: With progress being made in the treatment of cancer, various clinical and treatment options are being pursued. In China, Traditional Chinese Medicine (TCM) is used widely in the treatment of cancer. Objective: To estimate TCM treatment preferences and SDM mode of physicians in China. Methods: This study was conducted among physicians (n=185) from nine tertiary hospitals in China by discrete-choice experiment (DCE) survey and Shared Decision-Making Questionnaire-physician version (SDM-Q-Doc) survey. The DCE was developed with the inclusion of the most relevant attributes at appropriate levels for the TCM treatment of lung cancer. The empirical data analyses of physicians were performed using mixed logit models. Additionally, subgroup analysis was conducted. Results: In total, 185 respondents completed the questionnaire. All attributes were statistically significant except out-of-pocket costs. Physicians showed the strongest preferences for increasing disease control rate, relieving nausea and vomiting, and reducing the risk of side effects. Most of the physicians (78.38%) self-reported a high willingness to use SDM during the decision-making process. The physicians with a higher SDM-Q-Doc score had more preference for improving all three attributes than those with a lower score. Little variation was found in preferences among the physicians with other sociodemographic characteristics. Conclusion: In China, physicians considered disease control rate as the most essential attribute in the TCM treatment of lung cancer. The physicians in China mainly preferred SDM, and the preference was different according to SDM mode when involving the TCM therapy for patients with lung cancer. The study findings could inform future TCM therapy for lung cancer and promote SDM.

The Causes of Death and Their Influence in Life Expectancy of Children Aged 5-14 Years in Low- and Middle-Income Countries From 1990 to 2019.

Introduction: Although child and adolescent health is the core of the global health agenda, the cause of death and its expected contribution to life expectancy (LE) among those aged 5-14 are under-researched across countries, especially in low- and middle-income countries (LMICs). Methods: Death rates per 10 years age group including a 5-14-year-old group were calculated by the formula, which used the population and the number of deaths segmented by the cause of death and gender from the 2019 Global Burden of Disease (GBD) study. LE and cause-eliminated LE in 10-year intervals were calculated by using life tables. Results: In 2019, the global mortality rate for children and adolescents aged 5-14 years was 0.522 (0.476-0.575) per 1,000, and its LF was 71.377 years. In different-income regions, considerable heterogeneity remains in the ranking of cause of death aged 5-14 years. The top three causes of death in low-income countries (LICs) are enteric infections [0.141 (0.098-0.201) per 1,000], other infectious diseases [0.103 (0.073-0.148) per 1,000], and neglected tropical diseases and malaria [0.102 (0.054-0.172) per 1,000]. Eliminating these mortality rates can increase the life expectancy of the 5-14 age group by 0.085, 0.062, and 0.061 years, respectively. The top three causes of death in upper-middle income countries (upper MICs) are unintentional injuries [0.066 (0.061-0.072) per 1,000], neoplasm [0.046 (0.041-0.050) per 1,000], and transport injuries [0.045 (0.041-0.049) per 1,000]. Eliminating these mortality rates can increase the life expectancy of the 5-14 age group by 0.045, 0.031, and 0.030 years, respectively. Conclusion: The mortality rate for children and adolescents aged 5-14 years among LMICs remains high. Considerable heterogeneity was observed in the main causes of death among regions. According to the main causes of death at 5-14 years old in different regions and countries at different economic levels, governments should put their priority in tailoring their own strategies to decrease preventable mortality.

Fatty Acid Synthase Mutations Predict Favorable Immune Checkpoint Inhibitor Outcome and Response in Melanoma and Non-Small Cell Lung Cancer Patients.

Fatty acid synthase (FASN) acts as the central member in fatty acid synthesis and metabolism processes, which regulate oncogenic signals and tumor immunogenicity. To date, no studies have reported the connection of FASN mutations with ICI efficacy. In this study, from 631 melanoma and 109 NSCLC patients who received ICI treatments, we retrospectively curated multiomics profiles and ICI treatment data. We also explored the potential molecular biological mechanisms behind FASN alterations. In melanoma patients, FASN mutations were observed to associate with a preferable immunotherapeutic prognosis and response rate (both p < 0.01). These connections were further corroborated by the NSCLC patients (both p < 0.01). Further analyses showed that a favorable tumor immunogenicity and immune microenvironment were involved in FASN mutations. This work confirms the clinical immunotherapy implications of FASN mutation-mediated fatty acid metabolism and provides a possible indicator for immunotherapy prognosis prediction.

HSPG2 Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) markedly promote the survival outcome of advanced melanoma and non-small cell lung cancer (NSCLC). Clinically, favorable ICI treatment efficacy is noticed only in a smaller proportion of patients. Heparan sulfate proteoglycan 2 (HSPG2) frequently mutates in both tumors. Herein, we aim to investigate the immunotherapeutic and immunological roles of HSPG2 mutations in melanoma and NSCLC. A total of 631 melanoma samples and 109 NSCLC samples with both somatic mutational profiles and clinical immunotherapy data were curated. In addition, by using The Cancer Genome Atlas data, genomic and immunological traits behind HSPG2 mutations were elucidated. Melanoma patients with HSPG2 mutations had a markedly extended ICI outcome than other patients. An association between HSPG2 mutations and the improved outcome was further confirmed in NSCLC. In addition, an elevated ICI response rate was presented in HSPG2-mutated NSCLC patients (81.8% vs. 29.7%, p = 0.002). Subsequent analyses revealed that HSPG2-mutated patients had a favorable abundance of response immunocytes, an inferior abundance of suppression immunocytes, enhanced mutational burden, and interferon response-relevant signaling pathways. We uncovered that HSPG2 mutations were predictive of a better ICI response and associated with preferable immunogenicity, which may be considered as a genomic determinant to customize biotherapy strategies.

Immunological and clinical immunotherapy implications of NLRP3 mutations in melanoma.

Recent studies have demonstrated the role of Nod-like receptor protein 3 (NLRP3) inflammasome in promoting melanoma progression. Immune checkpoint inhibitors (ICI) treatment dramatically extended the survival outcomes for advanced melanoma patients. Nevertheless, immunologic and immunotherapy implications of NLRP3 mutations in melanoma were obscure. Herein, we utilized publicly genomic data of 750 melanoma patients to explore the association of NLRP3 mutations with immunologic and genomic features. In addition, we curated 336 advanced/metastatic melanoma patients treated with ICI agents from 6 published studies to analyze the response rate and survival outcome in relation to NLRP3 mutations. We observed that patients with NLRP3 mutations had a significantly higher tumor mutation burden (P < 0.001) and neoantigen burden (P < 0.001). Moreover, significantly lower tumor heterogeneity (P = 0.048) and purity (P = 0.022) were also observed in this mutated subgroup. Elevated infiltration of immune-response cells, decreased enrichment of immune-suppressive cells, and immune response-related circuits were markedly enriched in patients with NLRP3 mutations. In the pooled ICI-treated cohort, NLRP3 mutations were linked with the higher response rate (P = 0.031) and preferable survival outcome (P = 0.006). NLRP3 mutations were identified to associate with the elevated mutational burden, favorable immune infiltration, and preferable ICI efficacy. Findings derived from our study suggest that NLRP3 mutations may serve as a potential biomarker for evaluating melanoma immunotherapy response.

Effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on the second to fourth digit ratio in children aged 4 years.

BACKGROUND: The second to fourth digit ratio (2D:4D) is assumed to be a biomarker of prenatal sex steroid exposure, correlating negatively with prenatal testosterone and positively with prenatal estrogen. The ratio has been suggested to be influenced by endocrine disrupting chemicals (EDCs). However, evidence regarding effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on 2D:4D of children was sparse. OBJECTIVES: We investigated the associations between prenatal exposure to PBDEs and 2D:4D of children aged 4 years. METHODS: Participants were mother-child pairs from the Shanghai-Minhang Birth Cohort Study (S-MBCS) which enrolled pregnant women at 12-16 weeks of gestation from April to December 2012. Nine PBDE congeners in venous umbilical cord plasma of 340 children were measured. Digit lengths were measured using a vernier caliper in children aged 4 years and 2D:4D for left and right hands and average 2D:4D value of both hands were calculated. A total of 281 children (160 boys and 121 girls) who had data on both 2D:4D and PBDE concentrations were included in the final analysis. Associations between prenatal PBDE exposures and 2D:4D were investigated using multiple linear regression models. RESULTS: Among the nine congeners, BDE-47 had the highest detection rate of 86.12% with the highest median concentration of 0.20 ng/ml lipid. Five PBDE congeners with detection rates greater than or close to 50% (BDE-28, -47, -99, -100 and -153) and Σ5PBDEs (the sum of them) were included in final analysis. For girls, a consistent pattern for the positive associations between prenatal PBDE exposures and 2D:4D of children was observed mainly for the left hand, where those in the highest exposure groups had higher 2D:4D compared to the lowest exposure groups (a feminizing effect), with statistically significant associations observed for BDE-47 (ß = 0.0247, 95% confidence interval (CI): 0.0017, 0.0477), -100 (ß = 0.0264, 95% CI: 0.0087, 0.0441) and Σ5PBDEs (ß = 0.0201, 95% CI: 0.0027, 0.0374). For boys, compared with the lowest exposure groups, statistically significantly higher (feminized) 2D:4D for both hands was observed in those with the highest exposure levels of BDE-100 (ß = 0.0147, 95% CI: 0.0005, 0.0289 for the left hand; ß = 0.0182, 95% CI: 0.0046, 0.0318 for the right hand) and those with the middle and the highest exposure levels of BDE-153 (middle vs. undetected, ß = 0.0215, 95% CI: 0.0072, 0.0358 for the left hand; ß = 0.0155, 95% CI: 0.0015, 0.0295 for the right hand; highest vs. undetected, ß = 0.0162, 95% CI: 0.0017, 0.0307 for the left hand; ß = 0.0152, 95% CI: 0.0011, 0.0294 for the right hand). CONCLUSIONS: Our study provides preliminary evidence that prenatal exposure to PBDEs might be associated with higher 2D:4D in boys and girls.

Association of Obstructive Sleep Apnea With the Risk of Repeat Adverse Cardiovascular Events in Patients With Newly Diagnosed Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: The impact of obstructive sleep apnea (OSA) on subsequent cardiovascular events in patients with acute coronary syndrome (ACS) remains inconclusive. AIM: Our aim was to systematically assess the relationship between preexisting OSA and adverse cardiovascular events in patients with newly diagnosed ACS by conducting a systematic review and meta-analysis. METHODS: We systematically searched PubMed, EMBASE, and Cochrane library for studies published up to May 1, 2020, that reported any association between OSA and cardiovascular events in patients with newly diagnosed ACS. The main outcomes were a composite of all-cause or cardiovascular death, recurrent myocardial infarction, stroke, repeat revascularization, or heart failure. We conducted a pooled analysis using the random-effects model. We also performed subgroup, sensitivity, heterogeneity analysis, and the assessment of publication bias. RESULTS: We identified 10 studies encompassing 3350 participants. The presence of OSA was associated with increased risk of adverse cardiovascular events in newly prognosed ACS (risk ratio [RR] 2.18, 95% confidence interval [CI]: 1.45-3.26, P < .001, I2 = 64%). Between-study heterogeneity was partially explained by a multicenter study (9 single-center studies, RR 2.33 95% CI 1.69-3.19, I2 =18%), and I2 remarkably decreased from 64% to 18%. Moreover, OSA significantly increased the incidence of repeat revascularization (8 studies) and heart failure (6 studies) in patients with newly diagnosed ACS. CONCLUSION: Patients with preexisting OSA are at greater risk of subsequent cardiovascular events after onset of ACS. Further studies should investigate the treatment of OSA in patient with ACS.

Interactive effect of serum uric acid and total bilirubin for micro-vascular disease of type 2 diabetes in China.

AIMS: Serum uric acid (SUA) and bilirubin at high levels had both pro-oxidant and anti-oxidant properties. The present study aimed to examine additive interactions between SUA and total bilirubin (TBIL) for the risk of micro-vascular disease (MVD) in type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional survey of 6713 inpatients with T2DM was conducted in 81 tertiary care hospitals in China. MVD was defined as having either prior diabetic retinopathy (DR) or diabetic nephropathy (DN). Binary logistic regression was used to estimate odds ratios of SUA and TBIL for MVD. Additive interaction was measured by three indices, i.e., relative excess risk due to interaction, attributable proportion due to interaction and synergy index. RESULTS: Among 6713 inpatients, 408 (6.08%) suffered from MVD. SUA ≥ 283 µmol/l (i.e., its media) was defined as high SUA, and TBIL <11.5 µmol/l (n = 2290 or 34.11%) was defined as low TBIL. Overall, 621 patients were exposed to co-presence of high SUA and low TBIL. The co-presence of both factors greatly increased the effect sizes from 1.03(95%CI: 0.72-1.46) (high SUA alone) or 0.70(95%CI: 0.48-1.05) (low TBIL alone) to 1.90 (95%CI: 1.26-2.87) for MVD in multivariable analysis. The additive interaction of both factors was significant for MVD in both univariable analysis and multivariable analysis. CONCLUSIONS: Co-presence of both high SUA and low TBIL indentified a group of patients at a markedly increased risk of MVD in high-risk Chinese patients with T2DM.

Long exposure to type 2 diabetes and risk of non-fatal coronary heart disease in Chinese females and males: Findings from a China national cross-sectional study.

AIMS: To investigate the risk of Chinese females versus males for non-fatal coronary heart disease (CHD) due to long exposure to type 2 diabetes mellitus (T2DM). METHODS: 223,612 Chinese patients with T2DM were recruited from China in 2012. Binary logistic regression analysis was performed to obtain odds ratios (OR) of females versus males for non-fatal CHD. Additive interaction was used to test whether female gender and long exposure to T2DM (≥15 years) had a synergistic effect for non-fatal CHD. Significant relative excess risk due to interaction (RERI > 0), attributable proportion due to interaction (AP > 0) or synergy index (SI > 1) suggest a significant additive interaction. RESULTS: More females than males with T2DM had non-fatal CHD (11.3% versus 10.6%, P < .0001). Females had slightly higher risk of non-fatal CHD since 5-10 years of diabetic duration and the effect size became larger since 15 years and onwards. Overall effect of females versus males for non-fatal CHD was 1.04 (95% CI: 1.01-1.08) among patients with <15 years of duration while the effect size increased to 1.17 (95% CI: 1.07-1.28) among patients with ≥15 years of duration. Using males with <15 years of duration as the reference, females with ≥15 years of duration were at 1.82-fold (95% CI: 1.70-1.95) non-fatal CHD risk while males with ≥15 years of duration were only at 1.56 (95% CI: 1.45-1.68) fold non-fatal CHD risk, with significant additive interaction (all three measures < 0.05). CONCLUSIONS: Long exposure to T2DM imparted a larger risk of non-fatal CHD to Chinese females than to Chinese males.

Interactions between general and central obesity in predicting gestational diabetes mellitus in Chinese pregnant women: A prospective population-based study in Tianjin, China.

BACKGROUND: The aim of the present study was to define cut-off points of body mass index (BMI) and waist circumference (WC) for gestational diabetes mellitus (GDM) and to investigate any interactions between high BMI and high WC on the risk of GDM in pregnant Chinese women. METHODS: From 2010 to 2012, 17 803 women in Tianjin, China, who were at 4-12 weeks gestation were recruited to the study. Gestational diabetes mellitus was diagnosed according to the criteria of the International Association of Diabetes and Pregnancy Study Group at 24-28 weeks gestation. Binary logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) while controlling for the confounding effects of traditional risk factors. Restricted cubic spline was used to identify cut-off points of WC and BMI, if any, for GDM. RESULTS: Gestational diabetes mellitus developed in 1383 (7.8%) women. The risk of GDM increased steeply with increasing WC from ≥78.5 cm and BMI ≥22.5 kg/m2 . If BMI <22.5 kg/m2 and WC <78.5 cm were used as the reference, BMI between ≥22.5 and <24.0 kg/m2 (multivariable OR 1.76; 95%CI 1.47-2.10) and WC between ≥78.5 and <85.0 cm (multivariable OR 1.53; 95%CI 1.31-1.78) were independently associated with increased risks of GDM. In addition, the presence of both BMI ≥22.5 kg/m2 and WC ≥78.5 cm further increased the OR to 2.83 (95% CI 2.44-3.28), with significant additive interaction. CONCLUSIONS: Body mass index ≥22.5 kg/m2 and WC ≥78.5 cm measured up to 12 weeks of gestation were independently and synergistically associated with increased risks of GDM in Chinese pregnant women.