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Background We prospectively examined the association between serum uric acid (SUA) levels and chronic kidney disease (CKD) in China and updated the evidence through a comprehensive meta-analysis of prospective studies worldwide. Methods Our original analyses were based on data from the China Health and Retirement Longitudinal Study. The primary exposure of interest was SUA at baseline, and the main outcome was incident CKD. Logistic regression models were used to examine the association between SUA levels and incident CKD. A meta-analysis was performed to pool our effect estimate and those from other cohort studies. Results During a 4-year follow-up, 180 participants developed incident CKD. Participants in the highest SUA quartile were 2.73 times as likely to develop incident CKD compared to those in the lowest quartile (multivariable-adjusted OR, 2.73; 95% CI, 1.65–4.50). Each 1 mg/dL increment in the SUA levels was associated with a 49% increased risk of incident CKD (multivariable-adjusted OR, 1.49; 95% CI, 1.28–1.74). In the meta-analysis of 30 cohort studies (including the current study), pooled relative risks (95% CIs) of incident CKD were 1.15 (1.10–1.21) for SUA each 1 mg/dL increment, 1.22 (1.14–1.30) for the highest versus lowest SUA group, and 1.17 (1.12–1.23) for hyperuricemia versus no hyperuricemia. Conclusions Baseline SUA levels were associated with higher risk of incident CKD in middle-aged and elderly Chinese adults, and this positive association was confirmed in the meta-analysis of multiple cohort studies. Our findings may imply that SUA levels need to be routinely monitored for future CKD risk.

Viruses can be transmitted from animals to humans (and vice versa) and across animal species. As such, host-virus interactions and transmission have attracted considerable attention. Non-human primates (NHPs), our closest evolutionary relatives, are susceptible to human viruses and certain pathogens are known to circulate between humans and NHPs. Here, we generated global statistics on virus infections in NHPs (VI-NHPs) based on a literature search and public data mining. In total, 140 NHP species from 12 families are reported to be infected by 186 DNA and RNA virus species, 68.8% of which are also found in humans, indicating high potential for crossing species boundaries. The top 10 NHP species with high centrality in the NHP-virus network include two great apes (Pan troglodytes, Pongo pygmaeus) and eight Old World monkeys (Macaca mulatta, M. fascicularis, M. leonina, Papio cynocephalus, Cercopithecus ascanius, C. erythrotis, Chlorocebus aethiops, and Allochrocebus lhoesti). Given the wide distribution of Old World monkeys and their frequent contact with humans, there is a high risk of virus circulation between humans and such species. Thus, we suggest recurring epidemiological surveillance of NHPs, specifically Old World monkeys that are in frequent contact with humans, and other effective measures to prevent potential circulation and transmission of viruses. Avoidance of false positives and sampling bias should also be a focus in future work.

Context While the associations between thyroid markers and gestational diabetes mellitus (GDM) have been extensively studied, the results are inconclusive and the mechanisms remain unclear. Objective We aimed to investigate the prospective associations of thyroid markers in early gestation with GDM risk, and examine the mediating effects through lipid species. Methods This study included 6068 pregnant women from the Tongji-Shuangliu Birth Cohort. Maternal serum thyroid markers (free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody) were measured before 15 weeks. Deiodinase activity was assessed by fT3/fT4 ratio. Plasma lipidome were quantified in a subset of 883 participants. Results Mean age of the participants was 26.6 ± 3.7 years, and mean gestational age was 10.3 ± 2.0 weeks. Higher levels of fT4 were associated with a decreased risk of GDM (OR = 0.73 comparing the extreme quartiles; 95% CI 0.54, 0.98, Ptrend = .043), while higher fT3/fT4 ratio was associated with an increased risk of GDM (OR = 1.43 comparing the extreme quartiles; 95% CI 1.06, 1.93, Ptrend = .010) after adjusting for potential confounders. Multiple linear regression suggested that fT3/fT4 ratio was positively associated with alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, sphingomyelin 34:1, and phosphatidylcholine 40:7 (false discovery rate [FDR] adjusted P < .05). Mediation analysis indicated 67.9% of the association between fT3/fT4 ratio and GDM might be mediated through the composite effect of these lipids. Conclusion Lower concentration of serum fT4 or higher fT3/fT4 ratio in early pregnancy was associated with an increased risk of GDM. The association of fT3/fT4 ratio with GDM was largely mediated by specific lipid species.

China has one of the largest populations with obesity in the world, and obesity has become a major challenge for the country's health-care system. Current guidelines for obesity management are not adequately supported by evidence from clinical studies in Chinese populations. Effective lifestyle interventions suitable for Chinese populations are scarce, insufficient weight-loss medications have been approved by regulatory bodies, and there is low acceptance of non-lifestyle interventions (ie, medications and surgery) among both health-care providers and the general public. Large, well designed, and well implemented clinical trials are needed to strengthen the evidence base for the clinical management of obesity in China. Obesity management can be improved through use of a tiered system involving health management centres, integrated lifestyle interventions and medical treatments, strengthened obesity education and training, and use of advanced electronic health technologies. Resource mobilisation, support from major stakeholders for people with overweight or obesity, and education and changes to social norms among the wider public are also needed. National health policies should prioritise both obesity prevention and improvement of the treatment and management of obesity.

Aims We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. Methods Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24 to 28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced. Results In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp., and Veillonellaceae were overrepresented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia, and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-hour and 2-hour postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P < 0.001) from 0.69 to 0.75. Conclusions Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.

Background The aim of the study was to examine the relations of individual lifestyle factors and its composite score with healthy ageing among Chinese adults. Method We included 14 159 participants aged 45–74 years at baseline from the Singapore Chinese Health Study, a population-based prospective cohort. A protective lifestyle score (0–5 scale) was calculated at baseline (1993–1998) and updated at the second follow-up visit (2006–2010) on the basis of optimal body mass index (18.5–22.9 kg/m2), healthy diet (upper 40% of the Alternative Healthy Eating Index score), being physically active (≥2 h/wk of moderate activity or ≥0.5 h/wk of strenuous activity), nonsmoking (never smoking), and low-to-moderate alcohol drinking (>0 to ≤14 drinks/wk for men and >0 to ≤7 drinks/wk for women). Healthy ageing was assessed at the third follow-up visit (2014–2016) and was defined as absence of specific chronic diseases, absence of cognitive impairment and limitations in instrumental activities of daily living, good mental and overall self-perceived health, good physical functioning, and no function-limiting pain. Results About 20.0% (2834) of the participants met the criteria of healthy ageing after a median follow-up of 20 years. Each 1-point increase in the protective lifestyle score computed at baseline and second follow-up visits was associated with higher likelihood of healthy ageing by 25% (95% CI: 20%–30%) and 24% (18%–29%), respectively. The population-attributable risk percent of adherence to 4–5 protective lifestyle factors was 34.3% (95% CI: 25.3%–42.3%) at baseline and 31.3% (23.0%–38.7%) at second follow-up visits for healthy ageing. In addition, positive increase in lifestyle scores from baseline to second follow-up visits was also significantly associated with a higher likelihood of healthy ageing with an odds ratio of 1.18 (95% CI: 1.12%–1.24%) for each increment in protective lifestyle score. Conclusions Our findings confirmed that adopting healthy lifestyle factors, even after midlife, was associated with healthy ageing at old age.

As a functional bowel disorder, irritable bowel syndrome (IBS), especially IBS-diarrhea (IBS-D), affects approximately 9-20% of the population worldwide. Classical treatments for IBS usually result in some side effects and intestinal microbial disorders, which inhibit the clinical effects. Natural edible medicines with beneficial effects and few side effects have received more attention in recent years. Puerarin is the main active ingredient in pueraria and has been used in China to treat splenasthenic diarrhea and as a natural food in folk medicine for hundreds of years. However, there have been no reports of using puerarin in the treatment of IBS-D, and the underlying mechanism is also still unclear. In this study, a comprehensive model that could reflect the symptoms of IBS-D was established by combining neonatal maternal separation (NMS) and adult colonic acetic acid stimulation (ACAAS) in rats. The results showed that puerarin could reverse the abdominal pain and diarrhea in IBS-D rats. The therapeutic effect was realized by regulating the richness of the gut microbiota to maintain the stabilization of the intestinal micro-ecology. Furthermore, the possible mechanism might be related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis by the suppressed expression of corticotropin-releasing hormone receptor (CRF) 1. At the same time, intestinal function was improved by enhancing the proliferation of colonic epithelial cells by upregulating the expression of p-ERK/ERK and by repairing the colonic mucus barrier by upregulating occludin expression. All these results suggest that puerarin could exert excellent therapeutic effects on IBS-D.

Accurate surveillance of diabetes is crucial for establishing relevant policies of diabetes prevention and control. Previous studies estimated the trends in diabetes among adults in the U.S.; however, many did not consider results of the oral glucose tolerance test (OGTT) (1), and those studies that included the OGTT results reported a higher prevalence of undiagnosed diabetes (2). Capitalizing on the OGTT data since 2005–2006 in the National Health and Nutrition Examination Survey (NHANES), we assessed the trends in diagnosed and undiagnosed diabetes among adults in the U.S. from 2005 to 2016. NHANES is a cross-sectional survey with a stratified, multistage probability design to assess the health status of the noninstitutionalized civilian population in the U.S. (3). A household interview was conducted to collect health-related information including demographic characteristics and medical history. A subset of participants was randomly selected to provide a fasting blood sample and take an OGTT at the mobile examination center. Sample weights were constructed to account for nonresponse and oversampling. The survey was approved by the research ethics review board of the National Center for Health Statistics. Written informed consent was obtained from each participant. This investigation included nonpregnant participants aged 20 years or older, recruited from 2005–2006 to 2015–2016 cycles, who had information on self-reported diagnosed diabetes or laboratory results of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and 2-h plasma glucose (2-h PG). We calibrated plasma glucose measurements to …

To propose a novel definition for hydrocephalus growth and to further describe the association between hydrocephalus growth and poor outcome among patients with intracerebral hemorrhage (ICH). We analyzed consecutive patients who presented within 6 h after ICH ictus between July 2011 and June 2017. Follow-up CT scans were performed within 36 h after initial CT scans. The degree of hydrocephalus were evaluated by the hydrocephalus score of Diringer et al. The optimal increase of the hydrocephalus scores between initial and follow-up CT scan was estimated to define hydrocephalus growth. Poor long-term outcome was defined as a modified Rankin Scale of 4–6 at 3 months. Multivariate logistic regression analysis was performed to investigate the hydrocephalus growth for predicting 30-day mortality, 90-day mortality, and poor long-term outcome. A total of 321 patients with ICH were included in the study. Of 64 patients with hydrocephalus growth, 34 (53.1%) patients presented with both concurrent hematoma expansion and intraventricular hemorrhage (IVH) growth. After adjusting for potential confounding factors, hydrocephalus growth independently predicted 30-day mortality, 90-day mortality, and 90-day poor long-term outcome in multivariate logistic regression analysis. Hydrocephalus growth showed higher accuracy for predicting 30-day mortality, 90-day mortality, and poor long-term outcome than IVH growth or hematoma expansion, respectively. Hydrocephalus growth is defined by strongly predictive of short- or long-term mortality and poor outcome at 90 days, and might be a potential indicator for assisting clinicians for clinical decision-making.

Background and aims Obesity often initiates or coexists with certain metabolic abnormalities. This study sought to examine the independent and joint relations of weight and metabolic syndrome (MetS) with incident chronic kidney disease (CKD) among Chinese elderly people. Methods and Results A total of 15 229 participants (mean age: 62.8 years) from the Dongfeng-Tongji Cohort with complete baseline questionnaire and medical examination data were followed from 2008-2010 to 2013. All participants were categorized into four phenotypes: metabolically healthy non-overweight/obesity (MHNO), metabolically healthy overweight/obesity (MHO), metabolically unhealthy non-overweight/obesity (MUNO), metabolically unhealthy overweight/obesity (MUO). Multivariable-adjusted logistic regression models were applied to estimate the odds ratios (ORs) and confidence intervals (CIs) of four phenotypes with the risk of incident CKD, which was defined as estimated glomerular filtration rate (eGFR) 60 years or with baseline diabetes. Conclusion Both overweight/obesity and MetS were associated with an increased risk of CKD. It's worth noting that MHO and MUNO also have an elevated risk. Maintaining both normal weight and healthy metabolic profile is recommended.

Objective Our research aimed to prospectively evaluate the association between arthritis and depression among middle-aged and elderly Chinese and confirmed this association in other populations. Methods Data from the China Health and Retirement Longitudinal Study were analyzed. Participants were enrolled in this study in 2011-2012 (Wave 1) and followed up in 2013-2014 (Wave 2) and 2015-2016 (Wave 3). Depression was defined as having a score equal to over 10 using the Chinese version of 10-item Center for Epidemiological Studies Depression scale. Arthritis was assessed by self-reported physician diagnosis in Wave 1. Cox proportional hazards regression models were fitted to evaluate prospective associations between baseline arthritis status and incident and persistent depression. Summary effect estimates were pooled from our findings and those reported in literature by applying random effects models. Results The study included 7,386 participants aged 58.48 years (standard deviation, 9.59) for final analyses. Individuals with arthritis had a 35% higher risk (multivariable-adjusted hazard ratio [HR]: 1.35; 95% confidence interval [CI]: 1.23, 1.49) and 50% higher risk (HR: 1.50; 95% CI: 1.22, 1.84) of developing incident and persistent depression compared with those without arthritis. The meta-analysis of prospective studies confirmed increased risk of depression in individuals with arthritis (summary HR: 1.42, 95% CI, 1.34, 1.52). Limitations Depression was assessed by a screening tool and arthritis was assessed by self-reported physician diagnosis. Conclusions A positive relationship between arthritis and depression was noted in the middle-aged and elderly Chinese adults and other populations.

Changes in gut motility and visceral hypersensitivity are two major features of irritable bowel syndrome (IBS). Current drug treatments are often poorly efficacious, with many side effects for patients with IBS. Complementary therapies, such as acupuncture or abdominal massage, have received more attention in recent years. In this study, a rat model of IBS with diarrhea (IBS-D) was established by instillation of acetic acid from the colon. The effects of abdominal massage on changes in gut motility, visceral hypersensitivity, and the possible mechanism were investigated. Continuous abdominal massage could decrease the stool consistency score and increase the efflux time of glass beads compared with model groups, while also decreasing mast cell counts in IBS-D rats. The mRNA and protein expressions of neuronal nitric oxide synthase (nNOS), choline acetyl transferase (CHAT), and protein gene product 9.5 (PGP9.5) were significantly upregulated by continuous abdominal massage compared with model groups. Continuous abdominal massage also improved the ultrastructure of enteric glial cells (EGCs) by decreasing the number of mitochondria and increasing the level of the heterochromatin. Meanwhile, continuous abdominal massage could upregulate the expression of glial cell line-derived neurotrophic factor (GDNF) and P-Akt/Akt. Furthermore, it could reduce visceral hypersensitivity and improve the IBS-D symptoms by regulating the phosphoinositide 3-kinase (PI3K)-Akt pathway, which would provide a novel method for the treatment of IBS-D in the clinical setting.

Cruciferous vegetables contain high levels of glucosinolates (GSL) and isothiocyanates (ITC). ITC are known to induce glutathione S-transferases (GST) and thus exert their anticarcinogenic effects. This study explored the combined effects of cruciferous vegetable, GSL and ITC intake and GST polymorphisms on breast cancer risk. A total of 737 breast cancer cases and 756 controls were recruited into this case–control study. OR and 95 % CI were assessed by multivariable logistic regression. Higher cruciferous vegetable, GSL and ITC intakes were inversely associated with breast cancer risk, with adjusted OR of 0·48 (95 % CI 0·35, 0·65), 0·54 (95 % CI 0·40, 0·74) and 0·62 (95 % CI 0·45, 0·84), respectively. Compared with women carrying the GSTP1 rs1695 wild AA genotype and high cruciferous vegetable, GSL or ITC intake, carriers of the AA genotype with low cruciferous vegetable, GSL and ITC intake had greater risk of breast cancer, with adjusted OR of 1·43 (95 % CI 1·01, 1·87), 1·34 (95 % CI 1·02, 1·75) and 1·37 (95 % CI 1·05, 1·80), respectively. Persons with the GSTM1-null genotype and lower intake of cruciferous vegetables, GSL and ITC had higher risk of breast cancer than those with the GSTM1-present genotype and higher intake, with OR of 1·42 (95 % CI 1·04, 1·95), 1·43 (95 % CI 1·05, 1·96) and 1·45 (95 % CI 1·06, 1·98), respectively. Among women possessing the GSTT1-present genotype, low intake of cruciferous vegetables, GSL or ITC was associated with higher risk of breast cancer. But these interactions were non-significant. This study indicated that there were no significant interactions between cruciferous vegetable, GSL or ITC intake and GST polymorphisms on breast cancer risk.

BackgroundCancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality.MethodsEMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted.ResultsThe HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66–0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42–0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses.ConclusionsAdopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention.

Anti-tumor effect of dietary flavonoids has been sustained by laboratory experiments, but epidemiological studies with breast cancer risk remained inconsistent and insufficient. This study aimed to investigate the associations between total and subclasses of flavonoid and breast cancer risk among Chinese population. This case-control study recruited 1522 eligible breast cancer cases and 1547 frequency-matched control subjects from June 2007 to July 2018 in Guangdong, China. Dietary intake was obtained by face-to-face interview using a validated food frequency questionnaire. Odds ratios and 95% confidence intervals were calculated by multivariable logistic regression models. After adjusting for potential confounders, inverse associations were observed between total flavonoids, anthocyanidins, proanthocyanidins, flavanones, flavones, flavonols and isoflavones and overall breast cancer risk. Comparing the highest versus the lowest quartile, odds ratio (95% confidence interval) was 0.66 (0.54-0.82) for total flavonoids, 0.61 (0.49-0.75) for anthocyanidins, 0.67 (0.54-0.83) for proanthocyanidins, 0.71 (0.57-0.88) for flavanones, 0.48 (0.39-0.60) for flavones, 0.51 (0.41-0.63) for flavonols and 0.67 (0.54-0.83) for isoflavones, respectively. No significant association was found between flavanols, flavan-3-ol monomers, theaflavins and breast cancer risk. Stratified analysis by menopausal status and estrogen receptor/progesterone receptor status showed that the associations of total flavonoids, most flavonoid subclasses with breast cancer risk were generally not modified by menopausal or estrogen receptor/progesterone receptor status. This study indicates that total flavonoids and most flavonoid subclasses intakes were inversely associated with breast cancer risk.

Purpose: To evaluate the treatment solutions and effectiveness of intravitreal ranibizumab (RBZ) or conbercept in patients with wet age-related macular degeneration (wAMD) in a real-life setting in China.Methods: The medical records of 368 patients with wAMD who started RBZ or conbercept treatment between 1 May 2014 and 30 April 2018 were evaluated. All patients were defined on fundus angiography at baseline to determine the subtype of AMD (PCV or CNV). We report visual acuity (VA) and central retinal thickness (CRT) measurements at baseline and 12 months.Results: The average number of anti-VEGF injections was 2.1 ± 1.2. The BCVA improvement of these two groups was similar with a difference of 1.00 letter (95% CI: −1.4~3.4, p = 0.8505). At the end of the study, a BCVA increase of at least 5 letters was determined to be a satisfactory efficacy endpoint. Several factors were related to the possible improvement in the satisfactory efficacy endpoint, including female sex (OR 2.07, 95% CI 1.22~3.51), number of injections (OR 1.40, 95% CI 1.12~1.75) and VA change at the first month (OR 13.75, 95% CI 7.41~25.51). Additionally, some factors were related to the possible reduction in the satisfactory efficacy endpoint, including diabetes (OR 0.27, 95% CI 0.10~0.73) and disease history (OR 0.75, 95% CI 0.57~0.98).Conclusion: Our study demonstrates that anti-VEGF drugs can effectively improve BCVA and reduce CRT in AMD patients. Sex, number of injections, VA change at the first month, diabetes and disease history are the most important factors affecting visual acuity.

Background: Assessing the relation between arthritis and cognitive impairment could expand the understanding of health consequences of arthritis. The aim was to prospectively examine the association between arthritis and cognitive functions among middle-aged and elderly Chinese.Methods: Our analyses were based on data from the nationwide China Health and Retirement Longitudinal Study (2011–2016). Arthritis was ascertained by self-reported doctor diagnosis during the baseline survey. Cognitive functions were evaluated in three domains including episodic memory, mental status, and global cognition. Linear mixed models were employed to assess the association between baseline arthritis and cognition functions.Results: Of 7,529 Chinese adults, 49.79% were men, and mean age was 57.53 years. During a follow-up of 4 years, participants with baseline arthritis showed lower scores of episodic memory [β = −0.08; 95% confidence interval (CI): −0.14, −0.03], mental status (β = −0.14; 95% CI: −0.22, −0.05), and global cognition (β = −0.22; 95% CI: −0.34, −0.11), compared to those without arthritis. In addition, participants with arthritis showed increased rates of decline in mental status and global cognition by 0.04 (95% CI: 0.01, 0.08) and 0.05 (95% CI: 0.01, 0.09) units per year, respectively.Conclusion: Arthritis was associated with subsequent risk of poorer cognitive functions and slightly faster declines in cognitive functions among Chinese middle-aged and elderly adults. Our findings should be confirmed in future large prospective studies in Chinese and other populations.

Pancreatic cancer is a highly aggressive and lethal digestive system malignancy. Our previous studies revealed the correlation of high levels of lncRNA SOX2OT expression with patients’ poor survival outcomes, the promoting role of SOX2OT in proliferation and cycle progression of pancreatic cancer cells, and the in vivo binding of SOX2OT to RNA binding protein FUS, which destabilized the protein expression of FUS. However, the mechanism of SOX2OT binding and inhibiting FUS protein stability remains unclear. In this study, we performed RNA pull-down, cycloheximide-chase, and ubiquitination assays to determine the effect of SOX2OT on FUS ubiquitination, and explored the specific regulatory mechanism of SOX2OT–FUS axis in pancreatic cancer cell migration, invasion, in vivo tumor growth, and metastasis through RNA sequencing. We found that SOX2OT binds to FUS through its 5′ and 3′ regions, resulting in FUS ubiquitination and degradation. The SOX2OT–FUS regulatory axis promotes migration, invasion, tumor growth, and metastasis ability of pancreatic cancer cells. The in-depth elaboration of the SOX2OT–FUS regulatory axis in pancreatic cancer may clarify the mechanism of action of SOX2OT and provide new ideas for pancreatic cancer treatment.

Aims To prospectively examine the association between arthritis and type 2 diabetes (T2D) in the Chinese population and confirm this association through a comprehensive meta-analysis of cohort studies. Meterials and methods Data were from the China Health and Retirement Longitudinal Study which was started in 2011-2013 and followed up in 2013-2014 and 2015-2016. Arthritis was defined as self-reported physician diagnosis at baseline, and incident T2D was determined by self-reported physician diagnosis, fasting blood glucose ≥7.0 mmol/L or glycosylated haemoglobin ≥6.5% during the follow-ups. Cox proportional hazards regression models were used to assess the association between arthritis and risk for T2D. A meta-analysis was conducted to pool our effect estimate and those from other cohort studies using a random-effects model. Results Eleven thousand four hundred and eight participants (47.9% men; mean age: 59.3 years) were included in final analyses. During a 4-year follow-up, 981 participants reported incident T2D. Compared with individuals without arthritis, those with arthritis at baseline had an 18% higher risk for incident T2D (multivariable-adjusted hazard ratio: 1.18; 95% confidence interval: 1.04, 1.34). In the meta-analysis of 13 cohort studies including ours, a total of 2,473,514 participants were included with 121,851 incident diabetes. The pooling HR was 1.32 (95% CI: 1.21, 1.44) for the association between arthritis and diabetes. Conclusion Arthritis was associated with an increased risk of incident diabetes in Chinese adults, and the positive association was confirmed in the meta-analysis of cohort studies. Our work can inform clinical trials to assess the effectiveness of arthritis treatments in reducing risk of diabetes.

AIMS We prospectively evaluated the association of circulating retinol-binding protein 4 (RBP4) levels in early pregnancy and risk of incident gestational diabetes mellitus (GDM) in pregnant women. METHODS A nested case-control study was conducted among 332 women who developed GDM and 664 matched controls based on the Tongji-Shuangliu Birth Cohort. GDM was diagnosed during 24-28 weeks of gestation according to the International Association of Diabetes and Pregnancy Study Group criteria. Serum RBP4 levels in early pregnancy (6-15 weeks of gestation) were determined by ELISA assay. Multivariable conditional logistic regression models were used to analyse the association and generated the odds ratio (OR) and 95% confidence interval (CI). EMBASE and PubMed were searched up to 30 November 2020 to identify studies investigating the association between blood RBP4 levels in early pregnancy and incident GDM. RESULTS In the multivariable model with adjustment of potential risk factors, the OR comparing the extreme quartiles of serum RBP4 levels was 2.26 (95% CI: 1.34, 3.81; p for trend

Background Gestational diabetes (GDM) is a global problem affecting millions of pregnant women, including in mainland China. These women are at high risk of Type II diabetes (T2DM). Cost-effective and clinically effective interventions are needed. We aimed to explore Chinese women’s perspectives, concerns and motivations towards participation in early postpartum interventions and/or research to prevent the development of T2DM after a GDM-affected pregnancy. Methods We conducted a qualitative study in two hospitals in Chengdu, Southwest China. Face-to-face semi-structured interviews were conducted with 20 women with recent experience of GDM: 16 postpartum women and 4 pregnant women. Women were asked about their attitudes towards postpartum screening for type 2 diabetes, lifestyle interventions, mHealth delivered interventions and pharmacologic interventions (specifically metformin). An inductive approach to analysis was used. Interviews were recorded, transcribed, and coded using NVivo 12 Pro. Results Most women held positive attitudes towards participating in T2DM screening, and were willing to participate in postpartum interventions to prevent T2DM through lifestyle change or mHealth interventions. Women were less likely to agree to pharmacological intervention, unless they had family members with diabetes or needed medication themselves during pregnancy. We identified seven domains influencing women’s attitudes towards future interventions: (1) experiences with the health system during pregnancy; (2) living in an enabling environment; (3) the experience of T2DM in family members; (4) knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions, and (7) lifestyle constraints. Those with more severe GDM, an enabling environment and health knowledge, and with experience of T2DM in family members expressed more favourable views of postpartum interventions and research participation to prevent T2DM after GDM. Those who perceived themselves as having mild GDM and those with time/lifestyle constraints were less likely to participate. Conclusions Women with experiences of GDM in Chengdu are generally willing to participate in early postpartum interventions and/or research to reduce their risk of T2DM, with a preference for non-drug, mHealth based interventions, integrating lifestyle change strategies, blood glucose monitoring, postpartum recovery and mental health. Supplementary Information The online version contains supplementary material available at 10.1186/s12978-021-01180-1., Plain language summary Gestational diabetes mellitus (GDM) is a common pregnancy complication affecting up to 1 in 6 pregnant women worldwide. Whilst the condition usually resolves soon after delivery, women are at high risk of developing type 2 diabetes mellitus (T2DM). In this study, we asked women living in Chengdu, a city in western China, about what they knew about their risk of diabetes and how they felt about participating in interventions after birth to prevent T2DM. After listening to the views of 20 women, we concluded that in this setting most women are happy to attend T2DM screening programs after birth, and would be willing to consider participating in interventions and research after birth to prevent T2DM. The interventions most preferred were those that aimed at lifestyle changes, and many women said would like to receive this information through their smartphone, for example through an app or social media channel. Women were reluctant to take medications to prevent T2DM. The main factors that influenced how women felt towards interventions to prevent T2DM were: (1) their experiences with the health system during pregnancy; (2) whether the home environment was supportive to make changes to diet and lifestyle; (3) any experiences of T2DM in family members; (4) their knowledge of diabetes and perception of risk; (5) concerns about personal and baby health; (6) feelings and emotions in the postnatal period, and (7) lifestyle constraints making it difficult to make dietary changes. Supplementary Information The online version contains supplementary material available at 10.1186/s12978-021-01180-1.

The mechanisms linking overall/central obesity with type 2 diabetes are not fully understood. In a nested case-control study of 1039 incident cases and 1039 matched controls from two prospective cohorts of Chinese adults, we measured 142 plasma metabolites using LCMS platforms. We identified and validated 28 metabolites associated with body mass index (BMI) and 34 metabolites with waist circumference (WC) in multivariable-adjusted linear models at false discovery rate Disclosure X. Pan: None. Z. Chen: None. T. Wang: None. W. Zheng: None. R. E. Gerszten: None. X. Shu: None. D. Yu: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK108159 to T.W., X-O.S., R.E.G.), (R01DK126721 to D.Y.); National Cancer Institute (UM1CA173640 to X-O.S.), (UM1CA182910 to W.Z.)

Objectives: The original intracerebral hemorrhage (oICH) score is the severity score most commonly used in clinical intracerebral hemorrhage (ICH) research but may be influenced by hematoma expansion or intraventricular hemorrhage (IVH) growth in acute ICH. Here, we aimed to develop new clinical scores to improve the prediction of functional outcomes in patients with ICH.Methods: Patients admitted to the First Affiliated Hospital of Chongqing Medical University with primary ICH were prospectively enrolled in this study. Hematoma volume was measured using a semiautomated, computer-assisted technique. The dynamic ICH (dICH) score was developed by incorporating hematoma expansion and IVH growth into the oICH score. The ultra-early ICH (uICH) score was developed by adding the independent non-contrast CT markers to the oICH score. Receiver operating characteristic curve analysis was used to compare performance among the oICH score, dICH score, and uICH score.Results: There were 310 patients in this study which included 72 patients (23.2%) with hematoma expansion and 58 patients (18.7%) with IVH growth. Of 31 patients with two or more non-contrast computed tomography markers, 61.3% died, and 96.8% had poor outcomes at 90 days. After adjustment for potential confounding variables, we found that age, baseline Glasgow Coma Scale score, presence of IVH on initial CT, baseline ICH volume, infratentorial hemorrhage, hematoma expansion, IVH growth, blend sign, black hole sign, and island sign could independently predict poor outcomes in multivariate analysis. In comparison with the oICH score, the dICH score and uICH score exhibited better performance in the prediction of poor functional outcomes.Conclusions: The dICH score and uICH score were useful clinical assessment tools that could be used for risk stratification concerning functional outcomes and provide guidance in clinical decision-making in acute ICH.

Background To prospectively examine the associations of baseline serum uric acid (SUA) and SUA changes with incident metabolic syndrome (MetS) and update the evidence through a meta-analysis. Methods Our analyses were based on the China Health and Retirement Longitudinal Study from 2011–2012 to 2015–2016. The exposures were baseline SUA and SUA changes, and the outcome was incident MetS assessed in 2015–2016. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). A meta-analysis was conducted to synthesize evidence from all cohort studies on the same topic. Results Of 3779 participants (47.2% men; mean age: 59.5 years) without MetS, 452 participants developed MetS after a follow-up of 4 years. Compared to the lowest quartiles, the adjusted ORs (95% CIs) for MetS were 1.08 (0.77–1.50), 1.32 (0.95–1.82), and 1.55 (1.12–2.16) for three higher quartiles of baseline SUA, and 1.23 (0.89–1.71), 1.39 (1.00–1.93), and 1.89 (1.38–2.58) for three higher quartiles of SUA changes. Each increment of 1 mg/dL of baseline SUA level was associated with 19% higher odds of MetS (adjusted OR 1.19; 95% CI 1.07–1.33). In the meta-analysis of 24 cohort studies among 140,913 participants, the pooled relative risk (95% CI) was 1.32 (1.25–1.40) for the highest versus lowest SUA category, and 1.15 (1.09–1.21) for each 1 mg/dL increase in the SUA level. Conclusions Both baseline SUA and longitudinal SUA changes were positively associated with risk of MetS among middle-aged and elderly Chinese, which was supported by findings from a comprehensive meta-analysis across multiple populations. SUA levels might need to be monitored closely for subsequent risk of MetS in clinical practice.

A healthy lifestyle has been widely recommended for the prevention and management of type 2 diabetes. However, no systematic review has summarised the relationship between combined lifestyle factors (including, but not limited to, smoking, alcohol drinking, physical activity, diet and being overweight or obese) and incident type 2 diabetes and risk of health outcomes among diabetic individuals. EMBASE and PubMed were searched up to April 2019 without language restrictions. References included in articles in relevant publications were also screened. Cohort studies investigating the combined associations of at least three lifestyle factors with incident type 2 diabetes and health outcomes among diabetic individuals were included. Reviewers were paired and independently screened studies, extracted data and evaluated study quality. Random-effects models were used to calculate summary HRs. Heterogeneity and publication bias tests were also conducted. Compared with participants considered to have the least-healthy lifestyle, those with the healthiest lifestyle had a 75% lower risk of incident diabetes (HR 0.25 [95% CI 0.18, 0.35]; 14 studies with approximately 1 million participants). The associations were largely consistent and significant among individuals from different socioeconomic backgrounds and baseline characteristics. Among individuals with type 2 diabetes (10 studies with 34,385 participants), the HRs (95% CIs) were 0.44 (0.33, 0.60) for all-cause death, 0.51 (0.30, 0.86) for cardiovascular death, 0.69 (0.47, 1.00) for cancer death and 0.48 (0.37, 0.63) for incident cardiovascular disease when comparing the healthiest lifestyle with the least-healthy lifestyle. Adoption of a healthy lifestyle is associated with substantial risk reduction in type 2 diabetes and long-term adverse outcomes among diabetic individuals. Tackling multiple risk factors, instead of concentrating on one certain lifestyle factor, should be the cornerstone for reducing the global burden of type 2 diabetes.

Objective Satellite sign (SS) and island sign (IS) are novel noncontrast computed tomography (CT) predictors of hematoma growth. The aim of this study was to compare diagnostic performance of IS and SS in predicting hematoma growth and functional outcome in patients with intracerebral hemorrhage (ICH). Methods The study included patients with ICH who underwent baseline CT scan within 6 hours of symptom onset and follow-up CT scan within 36 hours after initial CT between July 2012 and April 2017. Sensitivity, specificity, positive predictive value, and negative predictive value of IS and SS in predicting hematoma growth and functional outcome were assessed. Accuracy of the 2 signs in predicting hematoma growth and functional outcome was analyzed using receiver operating characteristic analysis. Association between the presence of IS and SS and ICH growth was assessed using multivariate logistic regression. Results Of 307 patients with ICH, IS was observed in 46 patients (15.0%), and SS was observed in 151 patients (49.2%). Rates of hematoma growth were 40.4% in SS+ patients, 91.3% in IS+ patients, 18.4% in SS−IS− patients, 21.1% in SS+IS− patients, 100% in SS−IS+ patients, and 90.5% in SS+IS+ patients. After adjusting for potential confounders, IS remained an independent predictor for hematoma growth and poor functional outcome. The area under the curve of IS was significantly larger than the area under the curve of SS in predicting hematoma growth (P = 0.001). Conclusions IS seems to be an optimal shape irregularity imaging marker for predicting hematoma growth and functional outcome in patients with ICH.

Gestational diabetes mellitus (GDM) can lead to adverse birth outcomes, but its effect on postnatal depression has not been thoroughly investigated, especially in Asian populations.To determine the prospective association between GDM and postnatal depressive symptoms in Western China.A prospective cohort study of 1449 mothers was conducted in Chengdu, capital city of Sichuan Province. GDM was diagnosed during pregnancy using oral glucose tolerance tests. Maternal depressive symptoms were measured at 32-37weeks of gestation, then at one and three months after giving birth using a validated Chinese version of the Edinburgh Postnatal Depression Scale (EPDS). Associations between the postnatal EPDS scores, GDM status and blood glucose levels were assessed by multivariable mixed-effects regression models, accounting for baseline EPDS scores of the cohort and other confounding factors.Compared to the non-GDM group (n=1220), women with GDM (n=229, 15.8%) reported significantly higher mean EPDS scores at both 1-month (p=0.02) and 3-month (p0.01) postpartum. Similarly, high levels of fasting, 1-h and 2-h blood glucose levels during pregnancy were associated with increased EPDS scores. Mixed-effects models further confirmed the positive association between GDM status and postnatal depressive symptoms, even though the mean EPDS scores decreased substantially over the three time points.Chinese women with GDM were more susceptible to postnatal depression than others without the condition, despite their depressive symptoms reducing over time after childbirth. It is thus important to raise awareness of postnatal depression amongst healthcare professionals who care for women with GDM.

This study aimed to explore the effect of dietary magnesium intake on breast cancer risk both directly and indirectly via its effect on inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). This case-control study recruited 1050 case patients and 1229 control subjects. Inflammatory marker levels of 322 cases and 322 controls, randomly selected, were measured using ELISA, and data on dietary magnesium intake were collected using a food frequency questionnaire. Multivariable logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI), and path analysis was used to investigate the mediating effect. A higher magnesium intake was associated with a lower breast cancer risk (adjusted OR = 0.80, 95% CI = 0.65, 0.99). A positive association was found between the CRP level and breast cancer risk (adjusted OR = 1.43, 95% CI = 1.02–2.01). However, IL-6 was not found to be associated with breast cancer risk. Path analysis revealed that dietary magnesium affected breast cancer risk both directly and indirectly by influencing the CRP level. The results indicate that a direct negative association and an indirect association through influencing the CRP level were observed between dietary magnesium intake and breast cancer risk.

Background Despite the known health benefits of physical activity, its impact on depression during pregnancy remains inconclusive, especially in Asian populations. A large prospective cohort study was conducted to ascertain the association between total and domain-specific physical activity during early pregnancy and antenatal depression in Chinese women. Methods Information was collected prospectively from a cohort of 1440 pregnant women in Chengdu, Western China. Habitual physical activities (total, domain-specific and intensity level) were measured by the validated Chinese version of the Pregnancy Physical Activity Questionnaire during the first trimester. Antenatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) at 32–37 weeks of gestation. Multivariable linear and logistic regression analyses were undertaken, modelling EPDS as both continuous score and binary variable, respectively. Results Overall, the mean EPDS score was 9.3 (SD 3.7) and the prevalence of antenatal depression (EPDS ≥13) was 17.5% (n = 252). The mean total physical activity was 149.1 (SD 84.2) MET-hours/week. A high level of occupational activity (>73 MET-hours/week) was associated with a reduced risk of antenatal depression (odds ratio 0.57; 95% CI 0.37 to 0.94). A similar inverse association was evident for the continuous EPDS score. However, no apparent associations with EPDS were observed for total, other domains and intensities of physical activity exposures. Limitations Lack of information on history of major depression. Use of self-reported questionnaires instead of objective measures of physical activity and clinical diagnosis of antenatal depression. Conclusions Being active at work during early pregnancy may reduce antenatal depressive symptoms for Chinese women.

Fetal macrosomia, defined as birth weight equal or over 4000 g, is a major concern for both neonatal and maternal health. A rapid increasing trend in fetal macrosomia is observed in different regions of China. We aimed to examine the association between fetal macrosomia and risk of childhood obesity in Western China. All macrosomic live singletons (≥ 4000 g), and a random sample of singletons with normal birth weight (2500–3999 g) born in four districts of Chengdu, Western China, in 2011 were included in the cohort study. Maternal demographics, obstetric factors, labor and delivery summary at baseline were extracted from the Chengdu Maternal and Child Health Management System. Anthropometric measurements before 3 years and infant feeding information at around 6 months were also collected. Childhood obesity under 3 years was primarily defined as a weight-for-length/height z score ≥ 1.645 using the WHO growth reference. Secondary definitions were based on weight-for-age and body mass index (BMI)-for-age over the same cut-offs. A total of 1767 infants were included in the analyses, of whom 714 were macrosomic. After controlling for maternal age, parity, gestational age and anemia at the first antenatal visit, pre-pregnancy BMI, gestational weight gain, gestational age at birth, baby age and sex, and breastfeeding practices at 6 months, the risk of childhood obesity defined according to weight-for-length/height among macrosomic babies was 1.90 (95% confidence interval 1.04–3.49) times that of babies with normal birth weight. The risk of childhood obesity for macrosomic babies was 3.74 (1.96–7.14) and 1.64 (0.89–3.00) times higher based on weight-for-age and BMI-for-age, respectively. Fetal macrosomia is associated with increased risk of obesity in children under 3 years in Western China.

Endothelial damage and blood brain barrier disruption contribute to ischemic stroke and brain injury. Gliptins are a novel class of treatment agents for diabetes, and recent studies have linked the use of gliptins to neuroprotection. Alogliptin is a type of orally available gliptin that was approved for clinical use by the FDA in 2013. In this study, we investigated the neurovascular protective effects of alogliptin both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, administration of alogliptin ameliorated cerebral infarction and disruption of brain vascular permeability, and restored expression of the endothelial tight junction proteins occludin and zona occludens 1 (ZO-1). In brain vascular endothelial cells exposed to oxygen and glucose deprivation/reperfusion (OGD/R), alogliptin prevented OGD/R-induced high permeability of the endothelial monolayer. Alogliptin treatment recovered the reduction in occludin and ZO-1 induced by OGD/R. Moreover, alogliptin treatment prevented OGD/R-induced induction of metalloproteinase (MMP)-2 and MMP-9, and restored expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Collectively, our data indicate that alogliptin can improve neurovascular integrity and exerts neuroprotective effects.

Objective:The current study evaluated the associations between different forms and sources of Fe and breast cancer risk in Southern Chinese women.Design:Case–control study. We collected data on the consumption of Fe from different forms and food sources by using a validated FFQ. Multivariable logistic regression and restricted cubic spline (RCS) analysis was used to reveal potential associations between Fe intake and breast cancer risk.Setting:A case-control study of women at three major hospitals in Guangzhou, China.Participants:From June 2007 to March 2019, 1591 breast cancer cases and 1622 age-matched controls were recruited.Results:In quartile analyses, Fe from plants and Fe from white meat intake were inversely associated with breast cancer risk, with OR of 0·65 (95 % CI 0·47, 0·89, Ptrend = 0·006) and 0·76 (95 % CI 0·61, 0·96, Ptrend = 0·014), respectively, comparing the highest with the lowest quartile. No associations were observed between total dietary Fe, heme or non-heme Fe, Fe from meat or red meat and breast cancer risk. RCS analysis demonstrated J-shaped associations between total dietary Fe, non-heme Fe and breast cancer, and reverse L-shaped associations between heme Fe, Fe from meat and Fe from red meat and breast cancer.Conclusion:Fe from plants and white meat were inversely associated with breast cancer risk. Significant non-linear J-shaped associations were found between total dietary Fe, non-heme Fe and breast cancer risk, and reverse L-shaped associations were found between heme Fe, Fe from meat or red meat and breast cancer risk.

Background Lipid metabolism plays an important role in the pathogenesis of diabetes. There is little evidence regarding the prospective association of the maternal lipidome with gestational diabetes mellitus (GDM), especially in Chinese populations. Objectives We aimed to identify novel lipid species associated with GDM risk in Chinese women, and assess the incremental predictive capacity of the lipids for GDM. Methods We conducted a nested case-control study using the Tongji-Shuangliu Birth Cohort with 336 GDM cases and 672 controls, 1:2 matched on age and week of gestation. Maternal blood samples were collected at 6-15 wk, and lipidomes were profiled by targeted ultra-HPLC-tandem MS. GDM was diagnosed by oral-glucose-tolerance test at 24-28 wk. The least absolute shrinkage and selection operator is a regression analysis method that was used to select novel biomarkers. Multivariable conditional logistic regression was used to estimate the associations. Results Of 366 detected lipids, 10 were selected and found to be significantly associated with GDM independently of confounders: there were positive associations with phosphatidylinositol 40:6, alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, and alkylphosphatidylethanolamine 40:5 (adjusted ORs per 1 log-SD increment range: 1.34-2.86), whereas there were inverse associations with sphingomyelin 34:1, dihexosyl ceramide 24:0, mono hexosyl ceramide 18:0, dihexosyl ceramide 24:1, and phosphatidylcholine 40:7 (adjusted ORs range: 0.48-0.68). Addition of these novel lipids to the classical GDM prediction model resulted in a significant improvement in the C-statistic (discriminatory power of the model) to 0.801 (95% CI: 0.772, 0.829). For every 1-point increase in the lipid risk score of the 10 lipids, the OR of GDM was 1.66 (95% CI: 1.50, 1.85). Mediation analysis suggested the associations between specific lipid species and GDM were partially explained by glycemic and insulin-related indicators. Conclusions Specific plasma lipid biomarkers in early pregnancy were associated with GDM in Chinese women, and significantly improved the prediction for GDM.

AIMS We prospectively examined the relationship between metabolic syndrome (MetS) and incident chronic kidney disease (CKD) among middle-aged and elderly Chinese, and conducted a systematic review and meta-analysis of all cohort studies on this topic. MATERIALS AND METHODS Our research data were derived from the China Health and Retirement Longitudinal Study. Participants (n=5752, age ≥45 years) without CKD (defined as estimated glomerular filtration rate

Background Noncontrast computed tomography (NCCT) markers are the emerging predictors of hematoma expansion in intracerebral hemorrhage. However, the relationship between NCCT markers and the dynamic change of hematoma in parenchymal tissues and the ventricular system remains unclear. Methods and Results We included 314 consecutive patients with intracerebral hemorrhage admitted to our hospital from July 2011 to May 2017. The intracerebral hemorrhage volumes and intraventricular hemorrhage (IVH) volumes were measured using a semiautomated, computer‐assisted technique. Revised hematoma expansion (RHE) was defined by incorporating the original definition of hematoma expansion into IVH growth. Receiver operating characteristic curve analysis was used to compare the performance of the NCCT markers in predicting the IVH growth and RHE. Of 314 patients in our study, 61 (19.4%) had IVH growth and 93 (23.9%) had RHE. After adjustment for potential confounding variables, blend sign, black hole sign, island sign, and expansion‐prone hematoma could independently predict IVH growth and RHE in the multivariate logistic regression analysis. Expansion‐prone hematoma had a higher predictive performance of RHE than any single marker. The diagnostic accuracy of RHE in predicting poor prognosis was significantly higher than that of hematoma expansion. Conclusions The NCCT markers are independently associated with IVH growth and RHE. Furthermore, the expansion‐prone hematoma has a higher predictive accuracy for prediction of RHE and poor outcome than any single NCCT marker. These findings may assist in risk stratification of NCCT signs for predicting active bleeding.

Objective Isoflavones and lignans are phytoestrogens present in plant-based foods, which have a potential preventive effect on breast carcinogenesis. The effects of phytoestrogens on breast cancer may differ according to the hormonal environment. This case-control study aimed to investigate the association between serum phytoestrogens and odds of breast cancer among Chinese pre- and postmenopausal women. Methods A total of 792 cases and 813 age-matched controls were included. Serum isoflavone (daidzein, genistein, glycitein, equol, and formononetin) and lignan (enterodiol and enterolactone) concentrations were measured using a liquid chromatography-tandem mass spectrometry method. Results Significant inverse associations were found between serum total soy isoflavone precursors, daidzein, genistein, formononetin, total lignans, enterodiol, enterolactone, and the odds of breast cancer in premenopausal but not postmenopausal women. For premenopausal women, the adjusted odds ratios (95% confidence intervals) for the highest versus the lowest serum concentration groups were 0.60 (0.41-0.87) for total soy isoflavones precursors, 0.64 (0.44-0.93) for daidzein, 0.62 (0.43-0.90) for genistein, 0.49 (0.35-0.68) for formononetin, 0.38 (0.25-0.57) for total lignans, 0.49 (0.33-0.73) for enterodiol, and 0.49 (0.33-0.74) for enterolactone. However, the interaction between serum phytoestrogens and menopausal status on odds of breast cancer was statistically significant only for daidzein. No significant association was found between serum equol or gycitein and the odds of breast cancer among either pre- or postmenopausal women. Conclusions Higher levels of certain serum isoflavones and lignans were associated with reduced odds of breast cancer in premenopausal women, but the interaction was statistically significant only for daidzein.

Objective We aimed to examine prospective associations between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods Analyses were based on two prospective nested case-control studies conducted in western China (336 GDM cases and 672 matched controls) and central China (305 cases and 305 matched controls). Fasting plasma fatty acids in early pregnancy (gestational age at enrollment: 10.4 weeks(s.d., 2.0)) and 13.2 weeks (1.0), respectively) were determined by gas chromatography-mass spectrometry, and GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Groups criteria during 24–28 weeks of gestation. Multiple metabolic biomarkers (HOMA-IR (homeostatic model assessment for insulin resistance), HbA1c, c-peptide, high-sensitivity C-reactive protein, adiponectin, leptin, and blood lipids) were additionally measured among 672 non-GDM controls at enrollment. Results Higher levels of saturated fatty acids (SFAs) 14:0 (pooled odds ratio, 1.41 for each 1-s.d. increase; 95% CI: 1.25, 1.59) and 16:0 (1.19; 1.05, 1.35) were associated with higher odds of GDM. Higher levels of n-6 polyunsaturated fatty acid (PUFA) 18:2n-6 were strongly associated with lower odds of GDM (0.69; 0.60, 0.80). In non-GDM pregnant women, higher SFAs 14:0 and 16:0 but lower n-6 PUFA 18:2n-6 were generally correlated with unfavorable metabolic profiles. Conclusions We documented adverse associations of 14:0 and 16:0 but a protective association of 18:2n-6 with GDM among Chinese pregnant women. Our findings highlight the distinct roles of specific fatty acids in the onset of GDM.

Objective. To investigate the association between early perihematomal edema (PHE) expansion and functional outcome in patients with intracerebral hemorrhage (ICH). Methods. Patients with ICH who underwent initial computed tomography (CT) scans within 6 hours after the onset of symptoms and follow-up CT scans within 24 ± 12 hours were included. Absolute PHE increase was defined as the absolute increase in PHE volume from baseline to 24 hours. A receiver-operating characteristic (ROC) curve was generated to determine the cutoff value for early PHE expansion, which was operationally defined as an absolute increase in PHE volume of >6 mL. The outcome of interest was 3-month poor outcome defined as modified Rankin scale score of ≥4. A multivariable logistic regression procedure was used to assess the association between early PHE expansion and outcome after ICH. Results. In 233 patients with ICH, 89 (38.2%) patients had poor outcome at 3-month follow-up. Early PHE expansion was observed in 56 of 233 (24.0%) patients. Patients with early PHE expansion were more likely to have poor functional outcome than those without (43.8% vs. 11.8%, p < 0.001 ). After adjusting for age, admission systolic blood pressure, admission Glasgow Coma Scale score, baseline ICH volume and the presence of intraventricular hemorrhage, and time from onset to CT, early PHE expansion was associated with poor outcome (adjusted odds ratio, 4.25; 95% confidence interval, 1.70–10.60; p = 0.002 ). Conclusions. The early PHE expansion was not uncommon in patients with ICH and was correlated with poor outcome following ICH.

Objective Pyrethroids-containing products are widely used as commercial and household insecticides. While animal studies and clinical case reports have shown acute cardiovascular outcomes of pyrethroids exposure, little has been known on the effect of chronic pyrethroid exposure on cardiovascular disease (CVD). We aimed to examine the associations between chronic pyrethroid exposure and CVD in the US adults. Methods Cross-sectional data from the National Health and Nutrition Examination Survey 1999–2002 and 2007–2012 were analyzed. The exposure to pyrethroids was determined as the urinary level of 3-phenoxybenzoic acid (3-PBA), and CVD was ascertained based on self-reported physician diagnoses. Multivariable logistic regression models were fitted to evaluate associations of pyrethroid exposure with CVD, coronary heart disease (CHD), and stroke. Results Included were 6,471 participants with a mean age of 44.77 years (standard error, 0.39) for final analyses. The weighted prevalence of CVD, CHD, and stroke was 6.85%, 4.57% and 2.27%, respectively. With adjustments for major confounders, participants in the highest tertile of urinary 3-PBA had higher odds of CVD (odds ratio, 1.58; 95% confidence interval: 1.12, 2.23) and CHD (OR, 1.75; 95% CI: 1.17, 2.61) compared to those in the lowest tertile. There were linear associations for CVD (P for trend = 0.04) and CHD (P for trend = 0.02). However, no significant association was noted for stroke (1.29; 0.78, 2.16) in the main analyses. Conclusions 3-PBA was adversely associated with CVD and CHD in the US adults. Our findings highlight potential cardiovascular risk of chronic exposure to pyrethroids, and should be validated in large prospective studies in different populations in future.

Background The Health Star Rating (HSR) is the government-endorsed front-of-pack labeling system in Australia and New Zealand. Objectives We aimed to examine prospective associations of a dietary index (DI) based on the HSR, as an indicator of overall diet quality, with all-cause and cardiovascular disease (CVD) mortality. Methods We utilized data from the national population-based Australian Diabetes, Obesity and Lifestyle Study. The HSR-DI at baseline (1999–2000) was constructed by 1) calculation of the HSR points for individual foods in the baseline FFQ, and 2) calculation of the HSR-DI for each participant based on pooled HSR points across foods, weighted by the proportion of energy contributed by each food. Vital status was ascertained by linkage to the Australian National Death Index. Associations of HSR-DI with mortality risk were assessed by Cox proportional hazards regression. Results Among 10,025 eligible participants [baseline age: 51.6 ± 14.3 y (mean ± standard deviation)] at entry, higher HSR-DI (healthier) was associated with higher consumption of healthy foods such as fruits, vegetables, and nuts, and lower consumption of discretionary foods such as processed meats and confectionery (P-trend, Better diet quality as defined by an Australian government–endorsed nutrient profiling system was associated with lower risk of all-cause and CVD mortality among Australian adults.

Objective The associations between statins use and incidence or recurrence of venous thromboembolism (VTE) are controversial. We aimed to conduct a meta-analysis to reconcile the conflicting results. Methods We searched PubMed, Embase and Cochrane Library for studies published from database inception until May 31, 2021. Cohort studies and Randomized Controlled Trials that reported incidence or recurrence of VTE using statins compared with placebo or non-statins were included for meta-analysis. Results A total of 43 studies comprising over 8.6 million participants were included for analysis. The median follow-up duration was 38.1 months. Compared with no statins treatment, statins appeared to have a protective effect in primary prevention of VTE (RR 0.78, 95% CI 0.72–0.85), but significant heterogeneity was found among included studies (I2 = 81%). Statins was also associated with a 26% reduced risk of recurrent VTE (RR 0.74, 95% CI 0.70–0.78), even in patients receiving anticoagulant therapy (RR 0.77, 95% CI 0.65–0.92). In patients with a history of VTE, statins was associated with a reduced risk of bleeding and all cause mortality. The NNT of statins to prevent one case of VTE in the cancer population, and one case of recurrent VTE in patients with a history of VTE was 103.1 and 90.7 person-years respectively. Conclusion In high-risk patients, statins treatment may reduce the incidence of VTE. Statins can also reduce the risk of recurrent VTE and all-cause mortality in patients with a history of VTE.

Background: This study will explore the effectiveness and safety of respiratory muscle training therapy (RMTT) for the treatment of patients with obstructive sleep apnea syndrome (OSAS) after stroke. Methods: In this study, we will systematically and comprehensively search Cochrane Library, PubMed, EMBASE, WANGFANG, VIP, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure for relevant literature from their inception to March 1, 2020 without any limitations to language and publication status. We will consider any randomized controlled trials focusing on the effectiveness and safety of RMTT for the treatment of patients with OSAS after stroke. The study quality will be checked using Cochrane risk of bias tool, and statistical analysis will be performed utilizing RevMan 5.3 software. Results: This study will summarize and synthesize the current evidence of RMTT for the treatment of patients with OSAS following stroke. Conclusion: The findings of this study will assess the present evidence for the benefits and harms of RMTT for treating OSAS after stroke, and will inform clinical practice and future research. PROSPERO registration number: PROSPERO CRD42020170355.

In vitro and in vivo studies suggested that flavonols, flavones, flavanones and flavan-3-ols have preventive effects on breast carcinogenesis. Epidemiological evidence about the associations between these flavonoid biomarkers and breast cancer risk is limited. This study aimed to investigate the association between serum concentration of these flavonoids and breast cancer risk among Chinese women. This hospital-based case–control study recruited 792 breast cancer cases and 813 age frequency-matched (5-year interval) controls who provided eligible blood samples in Guangdong Province, China. Ultra-high-performance liquid chromatography–tandem mass spectrometry was used to measure flavonoids. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI). Higher concentrations of serum flavonols, isorhamnetin, kaempferol, flavanones and naringenin were significantly associated with lower breast cancer risk, with adjusted ORs (95% CIs) for the highest versus the lowest group of 0.66 (0.49–0.89) for flavonols, 0.52 (0.38–0.70) for isorhamnetin, 0.60 (0.45–0.80) for kaempferol, 0.65 (0.49–0.87) for flavanones and 0.45 (0.34–0.60) for naringenin, respectively. Significant positive associations were observed between serum flavan-3-ols, epigallocatechin, epigallocatechin-3-gallate and breast cancer risk. No significant associations were observed for serum quercetin, flavones, apigenin, luteolin, hesperetin, catechin, epicatechin and epicatechin-3-gallate with overall breast cancer risk. This study suggested that serum flavonols and flavanones were inversely associated with breast cancer risk and serum flavan-3-ols were positively associated with breast cancer risk. Serum flavones were not associated with overall breast cancer risk. These findings warrant further confirmation in prospective studies.

ObjectiveTo evaluate the prognosis of unrecognised myocardial infarction determined by electrocardiography (UMI-ECG) or cardiac magnetic resonance imaging (UMI-CMR).DesignSystematic review and meta-analysis of prospective studies.Data sourcesElectronic databases, including PubMed, Embase, and Google Scholar.Study selectionProspective cohort studies were included if they reported adjusted relative risks, odds ratios, or hazard ratios and 95% confidence intervals for all cause mortality or cardiovascular outcomes in participants with unrecognised myocardial infarction compared with those without myocardial infarction.Data extraction and synthesisThe primary outcomes were composite major adverse cardiac events, all cause mortality, and cardiovascular mortality associated with UMI-ECG and UMI-CMR. The secondary outcomes were the risks of recurrent coronary heart disease or myocardial infarction, stroke, heart failure, and atrial fibrillation. Pooled hazard ratios and 95% confidence intervals were reported. The heterogeneity of outcomes was compared in clinically recognised and unrecognised myocardial infarction.ResultsThe meta-analysis included 30 studies with 253 425 participants and 1 621 920 person years of follow-up. UMI-ECG was associated with increased risks of all cause mortality (hazard ratio 1.50, 95% confidence interval 1.30 to 1.73), cardiovascular mortality (2.33, 1.66 to 3.27), and major adverse cardiac events (1.61, 1.38 to 1.89) compared with the absence of myocardial infarction. UMI-CMR was also associated with increased risks of all cause mortality (3.21, 1.43 to 7.23), cardiovascular mortality (10.79, 4.09 to 28.42), and major adverse cardiac events (3.23, 2.10 to 4.95). No major heterogeneity was observed for any primary outcomes between recognised myocardial infarction and UMI-ECG or UMI-CMR. The absolute risk differences were 7.50 (95% confidence interval 4.50 to 10.95) per 1000 person years for all cause mortality, 11.04 (5.48 to 18.84) for cardiovascular mortality, and 27.45 (17.1 to 40.05) for major adverse cardiac events in participants with UMI-ECG compared with those without myocardial infarction. The corresponding data for UMI-CMR were 32.49 (6.32 to 91.58), 37.2 (11.7 to 104.20), and 51.96 (25.63 to 92.04), respectively.ConclusionsUMI-ECG or UMI-CMR is associated with an adverse long term prognosis similar to that of recognised myocardial infarction. Screening for unrecognised myocardial infarction could be useful for risk stratification among patients with a high risk of cardiovascular disease.

Background The aim of this study was to identify associations between dietary intakes of eggs and cholesterol and all‐cause and heart disease mortality in a US population. Methods and Results Data from the National Health and Nutrition Examination Survey 1999–2014 were used in this study, which included 37 121 participants ≥20 years of age. Dietary information was assessed via 24‐hour dietary recalls at baseline. Mortality status was documented until December 31, 2015. Cox proportional hazards models were used to examine the associations between dietary intakes of eggs and cholesterol and all‐cause and heart disease mortality. During a median follow‐up of 7.8 years, 4991 deaths were documented, including 870 deaths from heart disease. No significant association was observed between additional daily consumption of half an egg and all‐cause mortality (multivariable‐adjusted hazard ratio, 1.04; 95% CI, 0.96–1.13), or heart disease mortality (0.96; 0.80–1.14). Each 50‐mg/day increase of cholesterol intake was inversely associated with all‐cause mortality among participants with daily intake Conclusions No significant association was found between egg consumption and mortality in US adults. The association between dietary cholesterol intake and all‐cause mortality depended on the baseline intake levels, with an inverse association in those with lower intake levels (

Objectives To quantify extent of intraventricular hemorrhage (IVH) following intracerebral hemorrhage (ICH) with a novel, simple IVH severity score, and to explore and compare its performance in predicting worse outcomes. Patients and Methods A new scoring system for IVH severity was proposed and termed Slice score. The Slice score features non-septum pellucidum section, internal capsule section, third ventricle occipital horn section, three standardized scans for scoring the lateral ventricles. 652 scans from 326 subjects were retrospectively analyzed. The correlations between measured IVH volume and Slice score, original Graeb, LeRoux, and IVH score (IVHS) were compared. The association between these scores and clinical outcomes were evaluated using logistic regression. We then identified clinical thresholds of Slice score by balancing the probability of prediction and accuracy. Primary outcome was defined as 90-day poor outcome (modified Rankin Scale score ≥ 4) and secondary outcome was 90-day mortality. Results Of 326 ICH patients, 122 (37.4%) had poor outcome and 59 (18.1%) died at 3 months. The Slice score showed the highest correlation with measured IVH volume (R = 0.73, R2 = 0.54, p 1.07, all p Conclusions The Slice score correlated highly with the IVH volume, was a reliable volumetric scale for measuring IVH severity, and could be an easy-to-use tool for predicting 90-day poor outcome and mortality in ICH.

Obesity has become a major public health issue in China. Overweight and obesity have increased rapidly in the past four decades, and the latest national prevalence estimates for 2015-19, based on Chinese criteria, were 6·8% for overweight and 3·6% for obesity in children younger than 6 years, 11·1% for overweight and 7·9% for obesity in children and adolescents aged 6-17 years, and 34·3% for overweight and 16·4% for obesity in adults (≥18 years). Prevalence differed by sex, age group, and geographical location, but was substantial in all subpopulations. Strong evidence from prospective cohort studies has linked overweight and obesity to increased risks of major non-communicable diseases and premature mortality in Chinese populations. The growing burden of overweight and obesity could be driven by economic developments, sociocultural norms, and policies that have shaped individual-level risk factors for obesity through urbanisation, urban planning and built environments, and food systems and environments. Substantial changes in dietary patterns have occurred in China, with increased consumption of animal-source foods, refined grains, and highly processed, high-sugar, and high-fat foods, while physical activity levels in all major domains have decreased with increasing sedentary behaviours. The effects of dietary factors and physical inactivity intersect with other individual-level risk factors such as genetic susceptibility, psychosocial factors, obesogens, and in-utero and early-life exposures. In view of the scarcity of research around the individual and collective roles of these upstream and downstream factors, multidisciplinary and transdisciplinary studies are urgently needed to identify systemic approaches that target both the population-level determinants and individual-level risk factors for obesity in China.

AimsTo evaluate the type 2 diabetes mellitus (T2DM) risk of individuals with different types of dyslipidaemia and compare the predictive value of distinct lipid parameters in predicting T2DM.MethodsWe conducted a secondary analysis of data from the China Health and Retirement Longitudinal Study (CHARLS). 17 708 individuals over 45 years old were interviewed, and 11 847 blood samples were collected at the baseline survey (2011–2012). Outcome of T2DM was confirmed during two follow-up surveys (2013–2014 and 2015–2016). The HRs and 95% CI of T2DM associated with dyslipidaemia were estimated by Cox proportional hazards regressions model. The discriminatory value of eight lipid parameters were compared by the area under the receiver operating characteristic (ROC) curve (AUC).ResultsA total of 7329 participants were enrolled in our analysis; during the mean follow-up time of 3.4 years, 387 (5.28%) participants developed new-onset diabetes. Compared with participants in normal lipid levels, the T2DM risk of those with hypercholesterolaemia, hypertriglyceridaemia and low high-density lipoprotein cholesterol (HDL-C) were significantly increased (HRs (95% CI) were 1.48 (1.11 to 1.96), 1.92 (1.49 to 2.46) and 1.67 (1.35 to 2.07), respectively). The AUCs of non-HDL-C (0.685, 95% CI 0.659 to 0.711), triglyceride (TG) (0.684, 95% CI 0.658 to 0.710), total cholesterol (TC)/HDL-C (0.685, 95% CI 0.659 to 0.712) and TG/HDL-C (0.680, 95% CI 0.654 to 0.706) were significantly (pConclusionMiddle-aged and elderly adults with hypertriglyceridaemia, hypercholesterolaemia and low HDL-C were at higher risk for developing diabetes. Non-HDL-C, TG, TC/HDL and TG/HDL have greater performance than other lipid parameters in predicting T2DM incidence.

The goal of this investigation was to evaluate the inhibiting effect of high proportion polyethyleneglycol of long-circulating homoharringtonine liposomes on RPMI8226 multiple myeloma cancer stem cells. The CD138−CD34− multiple myeloma cancer stem cells isolated from RPMI8226 cell line using magnetic activated cell sorting system were, respectively, incubated with the optimized formulation of polyethyleneglycol of long-circulating homoharringtonine liposomes and the homoharringtonine in vitro, and the multiple myeloma cancer stem cell proliferation, colony formation, and cell cycle were analyzed. The inhibition of the multiple myeloma CD138−CD34− cancer stem cell growth was investigated in non-obese-diabetic/severe-combined-immunodeficiency mice that were implanted with multiple myeloma RPMI 8226 cancer stem cells and treated with the LCL-HHT-H-PEG. The results showed that the polyethyleneglycol of long-circulating homoharringtonine liposomes significantly inhibited MM cancer stem cell proliferation, colony formation, and induced cancer stem cell apoptosis in vitro as well as MM cancer stem cell growth in non-obese-diabetic/severe-combined-immunodeficiency mice compared with the homoharringtonine. In addition, the mouse bone mineral density and the red blood cell count were significantly increased in polyethyleneglycol of long-circulating homoharringtonine liposomes group. In conclusion, the data demonstrated that the developed polyethyleneglycol of long-circulating homoharringtonine liposomes formulation may serve as an efficient therapeutic drug for suppressing CD138−CD34− multiple myeloma cancer stem cell growth by inducing cancer stem cell apoptosis in non-obese-diabetic/severe-combined-immunodeficiency mouse model. Impact statement Multiple myeloma (MM) remains largely incurable until now. One of the main reasons is that there are cancer stem cells (CSCs) in MM, which are responsible for MM’s drug resistance and relapse. In this study, we wanted to extend our previous investigation22 that whether we developed the LCL-HHT-H-PEG formulation have an inhibitory effect on MM CD138−CD34−CSCs in MM CSC engrafted NOD/SCID mouse model. Our data from the present study have demonstrated the therapeutic effect of LCL-HHT-H-PEG on MM-bearing mouse model. The study represents the first attempt to demonstrate that the LCL-HHT-H-PEG formulation is available for treatment MM patients in clinic. Therefore, this finding is important and deserves publication in Experimental Biology and Medicine.

Background. We undertake a systematic review and meta-analysis to evaluate the effect of preoperative hypertension and preoperative antihypertensive medication to postoperative atrial fibrillation (POAF) in patients undergoing cardiac surgery. Methods. We searched PubMed, Embase, and Cochrane Library (from inception to March 2016) for eligible studies. The outcomes were the effects of preoperative hypertension, preoperative calcium antagonists regimen, preoperative ACE inhibitors regimen, and preoperative beta blocking agents regimen with POAF. We calculated pooled risk ratios (OR) and 95% CIs using random- or fixed-effects models. Results. Twenty-five trials involving 130087 patients were listed. Meta-analysis showed that the number of preoperative hypertension patients in POAF group was significantly higher (P<0.05), while we found that there are no significant differences between two groups in Asia patients by subgroup analysis, which is in contrast to other outcomes. Compared with the Non-POAF group, the number of patients who used calcium antagonists and ACE inhibitors preoperatively in POAF group was significantly higher (P<0.05). And we found that there were no significant differences between two groups of preoperative beta blocking agents used (P=0.08). Conclusions. Preoperative hypertension and preoperative antihypertensive medication in patients undergoing cardiac operations seem to be associated with higher risk of POAF.