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Background: Education, intelligence, and cognition are associated with hypertension, but which one plays the most prominent role in the pathogenesis of hypertension and which modifiable risk factors mediate the causal effects remains unknown. Methods: Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted 2-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, or cognition on hypertension (FinnGen study, 70 651 cases/223 663 controls; UK Biobank, 77 723 cases/330 366 controls) and blood pressure (International Consortium of Blood Pressure, 757 601 participants), and used 2-step Mendelian randomization to evaluate 25 potential mediators of the association and calculate the mediated proportions. Results: Meta-analysis of inverse variance weighted Mendelian randomization results from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.2 years) higher education was associated with 44% (95% CI: 0.40–0.79) decreased hypertension risk and 1.682 mm Hg lower systolic and 0.898 mm Hg lower diastolic blood pressure, independently of intelligence and cognition. While the causal effects of intelligence and cognition on hypertension were not independent of education; 6 out of 25 cardiometabolic risk factors were identified as mediators of the association between education and hypertension, ranked by mediated proportions, including body mass index (mediated proportion: 30.1%), waist-to-hip ratio (22.8%), body fat percentage (14.1%), major depression (7.0%), high-density lipoprotein cholesterol (4.7%), and triglycerides (3.4%). These results were robust to sensitivity analyses. Conclusions: Our findings illustrated the causal, independent impact of education on hypertension and blood pressure and outlined cardiometabolic mediators as priority targets for prevention of hypertension attributable to low education.

Evidence regarding the impact of education on diabetes risk is scarce in developing countries. We aimed to explore the association between education and diabetes within a large population in China and to identify the possible mediators between them.Information on educational level and lifestyle factors was collected through questionnaires. Diabetes was diagnosed from self-report and biochemical measurements. A structural equation model was constructed to quantify the mediation effect of each mediator.Compared with their least educated counterparts, men with college education had a higher risk of diabetes (odds ratio [OR] 1.19; 95% confidence interval [CI], 1.12-1.27), while college-educated women were less likely to have diabetes (OR 0.77; 95% CI, 0.73-0.82). Obesity was the strongest mediator in both genders (proportion of mediation: 11.6% in men and 23.9% in women), and its association with education was positive in men (β[SE] 0.0387 [0.0037]) and negative in women (β[SE] -0.0824 [0.0030]). Taken together, all behavioral factors explained 12.4% of the excess risk of diabetes in men and 33.3% in women.In a general Chinese population, the association between education level and diabetes was positive in men but negative in women. Obesity was the major mediator underlying the education disparities of diabetes risk, with a stronger mediation effect among women.目的: 在发展中国家，关于教育对糖尿病风险的影响的证据很少。我们的目的是在中国的一个大人群样本中探索教育和糖尿病之间的联系，并确定可能的中介因素。 材料和方法: 通过问卷调查，收集有关文化程度和生活方式因素的信息。糖尿病的诊断是通过自我报告和生化测量进行的。我们构建了结构方程模型量化了各变量的中介效应。 结果: 与受教育程度最低的男性相比，受过大学教育的男性患糖尿病风险较高(优势比OR:1.19, 95%可信区间(95%CI):1.12~1.27)，而受过大学教育的女性患糖尿病风险较低(OR:0.77, 95%CI:0.73~0.82)。肥胖在两性中均是最强的中介因素(中介比例:男性11.6%，女性23.9%)，肥胖与教育呈正相关(β[SE]0.0387[0.0037])，与女性中负相关(β[SE]-0.0824[0.0030])。所有行为因素加在一起，可以解释12.4%的男性和33.3%的女性患糖尿病的额外风险。 结论: 在中国普通人群中，男性受教育程度与糖尿病之间存在正相关，而女性则为负相关。肥胖是糖尿病风险教育差异的主要中介因素，在女性中的中介作用更强。.

The triglyceride glucose (TyG) index is closely associated with subclinical atherosclerosis. However, the association remains inconclusive among obese and nonobese individuals.This prospective study was conducted in 5751 adults with normal carotid intima-media thickness (CIMT) at baseline. We divided the population into four groups based on the TyG index, which was calculated by the following formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Information on CIMT was acquired by ultrasonography. Incident elevated CIMT was defined as IMT values greater than 0.9 mm at follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between TyG index and elevated CIMT were estimated using multivariable logistic regression models.After a median follow-up of 4.3 years, 722 (12.6%) individuals had progressed to elevated CIMT. Compared with the second quartile of the TyG index, the first and fourth quartile both conferred higher risks of elevated CIMT after adjusting for potential confounders. In the total population, the ORs for the first and fourth quartile were 1.29 (95% CI, 1.00-1.66) and 1.42 (95% CI, 1.11-1.83), respectively. Restricted cubic splines demonstrated an approximately U-shaped association between TyG index and elevated CIMT among the total and nonobese adults (P for nonlinearity.05), but not in those with general or abdominal obesity.A U-shaped association was observed between TyG index and elevated CIMT only among nonobese Chinese adults.背景: 甘油三酯血糖(TyG)指数与亚临床动脉粥样硬化密切相关。然而，肥胖者和非肥胖者之间的联系仍然没有定论。 方法: 这项前瞻性研究在5751名基线颈动脉内膜中层厚度(CIMT)正常的成年人中进行。根据TyG指数将人群分为四组，计算公式为:Ln(空腹甘油三酯[mg/dL]×空腹血糖[mg/dL]/2)。超声检查获得CIMT的相关信息。升高的CIMT定义为随访时IMT值大于0.9 mm。用多变量Logistic回归模型估计TyG指数与CIMT升高之间关联的优势比(OR)和95%置信区间(CI)。 结果: 经过平均4.3年 的随访，有722例(12.6%)患者进展为CIMT升高。与TyG指数的第二个四分位数相比，在校正了潜在的混杂因素后，第一和第四个四分位数都具有更高的CIMT升高风险。在总人口中，第一和第四个四分位数的OR值分别为1.29(95%CI，1.00~1.66)和1.42(95%CI，1.11~1.83)。限制立方样条法显示TyG指数与非肥胖者和非肥胖者的CIMT升高呈近似的U型相关(P0.05)，但在一般肥胖者或腹型肥胖者中不存在。 结论: 仅在非肥胖的中国成年人中，TyG指数与CIMT升高呈U型相关。.

The joint effect of famine exposure and adulthood obesity on risk of dyslipidemia remains unclear. Thus, we aim to explore the joint effect of famine exposure and adulthood obesity on the risk of dyslipidemia, and the potential effect of adult general or abdominal obesity on the association between famine exposure and dyslipidemia.We conducted a community-based cohort study in 8880 subjects aged 40 years or older. Participants were divided into nonexposed, fetal-exposed, childhood-exposed, adolescent-exposed according to birth date. General obesity and abdominal obesity were defined according to body mass index (BMI: overweight≥24.0 kg/mCoexistence of early-life undernutrition and adulthood obesity was associated with a higher risk of dyslipidemia in later life.

Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells.To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis.Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3.Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.

OBJECTIVE To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status. RESEARCH DESIGN AND METHODS We analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality. RESULTS In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82–1.30), 1.23 (1.07–1.42), and 1.61 (1.30–2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92–1.18), 1.12 (1.06–1.18), and 1.15 (1.09–1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2–34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15–17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44–77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters. CONCLUSIONS Glucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity.

The aim of this study was to investigate the associations of diabesity with incident cardiovascular disease (CVD) and subclinical atherosclerosis.The prospective cohort study included 8,006 participants without baseline CVD. Diabesity was categorized as (i) normal glucose tolerance (NGT) with nonobesity; (ii) NGT with obesity; (iii) prediabetes with nonobesity; (iv) prediabetes with obesity; (v) diabetes with nonobesity; and (vi) diabetes with obesity. The hazard ratios (HRs) for incident CVD and odds ratios (ORs) for subclinical atherosclerosis associated with diabesity categories were examined.Compared with the category of NGT with nonobesity, the categories of NGT with obesity (HR 1.68; 95% CI: 1.10-2.57), diabetes with nonobesity (HR 1.42; 95% CI: 1.08-1.88), and diabetes with obesity (HR 1.78; 95% CI: 1.24-2.55) were associated with higher risks of CVD. Prediabetes with or without obesity conferred no excess risk for CVD but higher risks for subclinical atherosclerosis. The diabetes with obesity category was associated with the highest risk for elevated pulse pressure (OR 3.07; 95% CI: 2.06-4.58) and albuminuria (OR 3.39; 95% CI: 2.31-4.99), and diabetes with or without obesity showed comparable ORs for elevated brachial-ankle pulse wave velocity.The association patterns between diabesity and CVD risks support the value of diabesity as a prevention target for CVD.

Hepatitis-associated aplastic anemia (HAAA), a rare subtype of aplastic anemia (AA), is defined as bone marrow failure occurring after acute hepatitis. Severe HAAA requires immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT) as lifesaving treatment. The outcomes of HAAA patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) have not been systematically evaluated. We retrospectively compared the characteristics of 15 patients with HAAA and 60 non-hepatitis-associated aplastic anemia (non-HAAA) patients, all 75 of whom underwent haplo-HSCT in our hospital between January 2006 and October 2021. The median ages of the patients were 18 years old (range, 3-36) for HAAA patients and 13 years (range, 2-45) for non-HAAA patients (p = 0.693). The median time for neutrophil engraftment was 14 days (range, 11-22) in the HAAA group and 12 days (range, 10-21) in the non-HAAA group (p = 0.363). At the time of analysis, 15 HAAA patients and 58 non-HAAA patients were alive, and their median follow-up times were 37 (range, 3-87) months and 31 (range, 2-110) months (p = 0.347), respectively. There were no significant differences in the three-year overall survival (OS) rates (100% vs. 96.7 ± 0.33%, P = 0.638) or liver event-free survival (LEFS) (80.0 ± 0.17% vs. 76.7 ± 0.19%, P = 0.747) between the two groups. Despite the small number of HAAA patients due to the rarity of the disease, these results, such as the similar incidence rates of 3-year OS and fewer liver events than expected, suggest that haplo-HSCT is a feasible treatment for HAAA a when there are no human leukocyte antigen (HLA)-matched donors available and has a low risk of transplant-related mortality and complications.

The Apolipoprotein A5 (APOA5) rs662799 was significantly associated with blood lipid level at genome-wide significance level. Whether dynamic changes of adiposity influence the effect of lipid loci on long-term blood lipid profile remains unclear. We assessed interactions of 5-year body mass index (BMI) change and rs662799 genotypes with risk of incident dyslipidemia and longitudinal changes in serum lipids in a prospective cohort.We included 4329 non-dyslipidemia participants aged ≥ 40 years at baseline from a well-defined community-based cohort and followed up for an average of 5 years. BMI and blood lipids were measured at baseline and follow-up.The association of each rs662799 A-allele with risk of incident dyslipidemia was stronger along with the increase in BMI change level, with the odds ratios (OR) increasing from 1.03 in the lowest tertile of BMI change (0.02 kg/mBMI changes significantly modulate rs662799 genetic contribution to dyslipidemia and long-term lipid profile, which provide new evidence for personalized clinical management of lipids according to individual genetic background.

Family history of diabetes, unhealthy lifestyles, and metabolic disorders are individually associated with higher risk of diabetes, but how different combinations of the three risk categories are associated with incident diabetes remains unclear. We aimed to estimate the associations of comprehensive risk profiles of family history and lifestyle and metabolic risk factors with diabetes risk.This study included 5290 participants without diabetes at baseline with a mean follow-up of 4.4 years. Five unhealthy lifestyles and five metabolic disorders were each allocated a score, resulting in an aggregated lifestyle and metabolic risk score ranging from 0 to 5. Eight risk profiles were constructed from combinations of three risk categories: family history of diabetes (yes, no), lifestyle risk (high, low), and metabolic risk (high, low).Compared with the profile without any risk category, other profiles exhibited incrementally higher risks of diabetes with increasing numbers of categories: the hazard ratio (HR, 95% confidence interval [CI]) for diabetes ranged from 1.34 (1.01-1.79) to 2.33 (1.60-3.39) for profiles with one risk category, ranged from 2.42 (1.45-4.04) to 4.18 (2.42-7.21) for profiles with two risk categories, and was 4.59 (2.85-7.39) for the profile with three risk categories. The associations between the numbers of risk categories and diabetes risk were more prominent in women (pThis study delineated associations between comprehensive risk profiles with diabetes risk, with stronger associations observed in women and slightly stronger associations in adults younger than 55 years.背景: 糖尿病家族史, 不健康的生活方式和代谢紊乱分别与较高的糖尿病风险相关, 但这三种风险类别的不同组合如何与糖尿病事件相关仍不清楚。我们旨在评估家族史, 生活方式以及代谢风险因素的综合风险概况与糖尿病风险的相关性。 方法: 这项研究包括5290名基线时无糖尿病的参与者, 平均随访时间为4.4年。对五种不健康的生活方式和五种代谢紊乱分别进行评分, 使生活方式和代谢风险综合评分从0到5不等。根据三个风险类别的组合构建了八个风险类别:糖尿病家族史(是, 否), 生活方式风险(高, 低)和代谢风险(高, 低)。 结果: 与无任何危险类别的相比, 随着危险类别的增加, 患糖尿病的风险逐渐增加:具有一个危险类别的风险比(HR, 95%可信区间[CI])为1.34(1.01~1.79)~2.33(1.60~3.39), 具有两个危险类别的为2.42(1.45~4.04)~4.18(2.42~7.21), 具有三个危险类别的HR为4.59(2.85~7.39)。风险类别的数量与糖尿病风险之间的关联在女性中更加显著(P

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

Polyetherketoneketone (PEKK) is considered to be a potential substitute material for metal bone implants because of its advantageous biocompatibility, chemical stability, and mechanical properties, but clinical application has been severely restricted due to PEKK's lack of antibacterial ability and biological activity. In this study, LL-37, a natural human antimicrobial peptide, was successfully modified on the PEKK surface with polydopamine as the intermediate layer and released continuously for more than 6 days. The results of the MTT assay, colony counts, and Live/Dead staining demonstrated that compared to unmodified PEKK, the LL-37-modified PEKK significantly inhibited the adhesion, vitality, and bacterial biofilm growth of

Serum electrolytes were found to associate with type 2 diabetes. Our study aimed to stratify nondiabetes by clusters based on multiple serum electrolytes and evaluate their associations with risk of developing diabetes and longitudinal changes in glucose and lipid metabolic traits.We performed a data-driven cluster analysis in 4937 nondiabetes individuals aged ≥40 years at baseline from a cohort follow-up for an average of 4.4 years. Cluster analysis was based on seven commonly measured serum electrolytes (iron, chlorine, magnesium, sodium, potassium, calcium, and phosphorus) by using the k-means method.A total of 4937 nondiabetes individuals were classified into three distinct clusters, with 1635 (33.1%) assigned to Cluster A, 1490 (30.2%) to Cluster B, and 1812 (36.7%) to Cluster C. Individuals in Cluster A had higher serum chlorine, were older, and more were women. Individuals in Cluster B had higher serum iron and body mass index (BMI). Individuals in Cluster C had higher serum phosphorus, were younger, and had lower BMI. Cluster B had 1.41-fold higher risk of developing diabetes and Cluster C's risk was 1.33-fold higher compared with Cluster A. Over an average follow-up of 4.4 years, Cluster A showed a moderate and stable BMI, Cluster B showed an accelerated deterioration in glucose metabolism, and Cluster C showed the most sharply increased serum low-density lipoprotein cholesterol level.Clusters based on seven common serum electrolytes differed in diabetes risk and progression of glucose and lipid metabolic traits. Serum electrolytes clusters could provide a powerful tool to differentiate individuals into different risk stratification for developing type 2 diabetes.背景: 既往研究发现血清电解质水平与2型糖尿病相关。本研究旨在综合考虑临床常用多种血清电解质, 并对其进行聚类分析, 研究不同血清电解质聚类人群(簇)的临床表型特点, 不同血清电解质簇人群的糖尿病发生风险及糖脂代谢纵向进展变化特征。 方法: 研究纳入4937名40岁及以上基线非糖尿病社区人群, 平均随访4.4年。采用k-means法对基线常规检测的7种血清电解质(铁, 氯, 镁, 钠, 钾, 钙和磷)进行数据驱动的聚类分析。 结果: 基于聚类分析的结果, 4937名基线非糖尿病人群被分为3个不同电解质簇, 1635人(33.1%)分配到簇A人群, 1490人(30.2%)分配到簇B, 1812人(36.7%)分配到簇C。簇A人群基线血清氯水平较高, 年龄较大且女性居多, 簇B人群血清铁及体重指数(body mass index, BMI)水平较高, 簇C人群血清磷水平较高, 年龄偏轻及BMI水平低。以簇A作为参照, 簇B的糖尿病发病风险增加41%(OR=1.41, 95%CI 1.09-1.82), 簇C的糖尿病发病风险增加33% (OR 1.33, 95%CI 1.03-1.71)。平均4.4年随访期间, 簇A人群保持稳定且中等水平的BMI(25 kg/m

Background Age has substantial influence on metabolic diseases patterns. Ethnic disparities of metabolic characteristics between Chinese and other populations also exist. Large-scale investigations of age-specific prevalence, subtypes and modifiable risk factors of metabolic disorders are essential to promote individualized strategies for the control and prevention of metabolic diseases in multi-ethnic populations. The study aims to address the age-specific prevalence, subtype characteristics and risk factor profiles of metabolic diseases among different races/ethnicities. Methods We analyzed data from the China Noncommunicable Disease Surveillance 2010 and the National Health and Nutrition Evaluation Survey (NHANES). We examined the prevalence and subtypes of hypertension, diabetes and hyperlipidemia across age groups in four ethnic populations. We also investigated the odds ratios (ORs) of metabolic diseases associated with 11 classical risk factors in the young and the elder Mainland Chinese. Results The sex and BMI standardized prevalence of hypertension in Chinese aged 18–40 years was 18.5% and was the highest among the four populations. The main pathophysiologic subtype of diabetes was characterized by insulin resistance, instead of β-cell dysfunction in Mainland Chinese, and this pattern was more evident in obese subjects. The major subtype of hyperlipidemia in Mainland Chinese was hypertriglyceridemia, while Non-Hispanic Whites and Blacks were more prone to high low-density lipoprotein cholesterol. For risk of hypertension, diabetes and hyperlipidemia, young Chinese adults were more prone to general and central obesity than older ones. The other factors showed similar effects on the young and the old. Conclusions The age-specific prevalence, subtypes and risk factors of metabolic diseases were substantially different in Chinese and other ethnic/racial populations.

Gestational hyperglycemia increases the risk of diabetes in later life. However, the risk of future cardiovascular diseases (CVD) related to gestational hyperglycemia remains inconclusive. The purpose of this study was to investigate the impact of gestational hyperglycemia on the subsequent risk of CVD and its modifying factors among elderly Chinese women.We conducted a case-control study of elderly women from the baseline survey of Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Women with gestational hyperglycemia (n = 82), and controls matched by age and study site (n = 410) were included. Information on CVD, including reported coronary heart disease, stroke, or myocardial infarction, was collected through an interviewer-assisted questionnaire.Women with gestational hyperglycemia were more likely to develop diabetes (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.18) and CVD (OR, 1.98; 95% CI, 1.05-3.74). Even without progressing to type 2 diabetes, gestational hyperglycemia was associated with an increased risk of CVD (OR, 2.88; 95% CI, 1.18-7.00). However, subgroup analysis indicated that compared with those without gestational hyperglycemia or hypertension, women with both gestational hyperglycemia and hypertension had higher risk of CVD (OR, 3.98; 95% CI, 1.65-9.58), whereas the risk estimate did not significantly change in women with gestational hyperglycemia alone (OR, 2.15; 95% CI, 0.71-6.57). Stratified analysis indicated that among those with overweight/obesity, inactive physical activity, or unhealthy dietary habits, gestational hyperglycemia increased the risk of CVD.In elderly Chinese women, gestational hyperglycemia was associated with an increased risk of CVD in later life. This association was independent of the progression to diabetes and might be modified by lifestyle factors and hypertension.背景: 妊娠高血糖会增加以后患糖尿病的风险。然而，与妊娠高血糖相关的未来心血管疾病(Cardiovascular diseases, CVD)的风险仍然不确定。本研究旨在探讨妊娠高血糖对中国老年女性后续心血管疾病风险的影响及其可能的影响因素。 方法: 我们在中国2型糖尿病患者恶性肿瘤发生风险的流行病学(REACTION)研究的老年妇女中开展了一项病例对照研究。研究纳入82名妊娠高血糖女性及410名按年龄和研究中心匹配的对照女性。心血管疾病信息(包括冠心病、中风和心肌梗死)通过调查员辅助的标准化问卷收集。 结果: 有妊娠高血糖的女性更容易发生糖尿病 [比值比(Odd ratio, OR)，2.51； 95%可信区间(Confidence interval, CI)，1.50-4.18] 和CVD(OR，1.98； 95%CI，1.05-3.74)。即使没有进展为 2 型糖尿病，妊娠高血糖也与 CVD 风险增加相关(OR，2.88；95%CI，1.18-7.00)。然而，亚组分析表明，与没有妊娠期高血糖或高血压的女性相比，同时有妊娠期高血糖和高血压的女性患心血管疾病的风险更高(OR，3.98；95%CI，1.65-9.58)，而CVD风险在单纯有妊娠高血糖的女性中没有显著变化(OR，2.15；95%CI，0.71-6.57)。分层分析表明，在超重/肥胖、缺乏体力活动或饮食不健康的人群中，妊娠高血糖会显著增加CVD风险。 结论: 在中国老年女性中，妊娠期高血糖与晚年 CVD 风险增加有关。这种关联与是否发展为糖尿病无关，而可能会受到生活方式和高血压的影响。.

Context Observational studies have been associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. Objective We aimed to investigate the causality of obesity with CKD and arterial stiffness using mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11 384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single-nucleotide variations (SNVs, formerly single-nucleotide polymorphisms [SNPs]) were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2. Arterial stiffness was defined as brachial-ankle pulse wave velocity greater than 1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-SD increment in BMI with CKD (odds ratio [OR]: 2.36; 95% CI, 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI, 1.22-2.39). Using the 14 SNVs individually as IVs, each 1-SD increment in BMI was casually associated with CKD (OR: 2.58; 95% CI, 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI, 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (both P for intercept ≥ .34). The causality between obesity and CKD was validated in 2-sample MR analysis among Europeans (681 275 of Genetic Investigation of ANthropometric Traits and 133 413 of CKD Genetics). Conclusion This study provided novel insights into the causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

Background: Many studies demonstrate a J-shaped association between blood pressure and cardiovascular diseases (CVDs), but the findings are plagued by confounding from other traditional cardiovascular risk factors (CVRFs). Our aims were to examine the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels with CVD in individuals without major CVRFs and whether there were thresholds for the association. Methods: In the 4C study (China Cardiometabolic Disease and Cancer Cohort), 36 042 CVRF-free participants without CVD, diabetes, dyslipidemia, hypertension, or smoking were identified during 2011 to 2012. Among CVRF-free participants, 17 476 CVRF-preferable individuals with better glycemic (fasting glucose, Results: We found that both baseline SBP and DBP presented significantly linear associations with CVD risks in CVRF-free and CVRF-preferable participants. There is significant increase in the CVD risk among CVRF-free participants with baseline SBP level of 110 to 119 mm Hg (hazard ratio, 1.79 [95% CI, 1.19–2.71]), 120 to 129 mm Hg (hazard ratio, 2.03 [95% CI, 1.36–3.03]), and 130 to 139 mm Hg (hazard ratio, 2.15 [95% CI, 1.40–3.28]) compared with SBP Conclusions: SBP and DBP with levels currently considered normal were significantly and linearly associated with incident CVD without thresholds above 110/70 mm Hg among Chinese adults without major CVRFs.

ObjectivesRecent studies found that secreted protein acidic and rich in cysteine-like protein 1 (Sparcl1) could inhibit lipid droplets accumulation by peroxisome proliferator-activated receptor-gamma (PPARγ) signal pathway. However, the associations of serum Sparcl1 level with lipids profiles and other metabolic phenotypes remain unknown in human population study.MethodsWe determined serum Sparcl1 using sandwich enzyme-linked immunosorbent assays among 1750 adults aged 40 years and older from a community in Shanghai, China. Generalized linear regression models were used to evaluate the association between Sparcl1 and metabolic measures. Multivariable-adjusted logistic regression analyses were performed to evaluate the relationship of serum Sparcl1 with prevalent dyslipidemia.ResultsWith the increment of serum Sparcl1, participants tended to have lower level of triglycerides, and higher level of high-density lipoprotein cholesterol (all P for trend < 0.01). No significant associations between serum Sparcl1 and glucose, blood pressure, or body size were observed. The generalized linear regression models suggested that per standard deviation (SD) increment of serum Sparcl1 was significantly inversely associated with triglycerides (β= -0.06, P=0.02). The prevalence of dyslipidemia decreased across the sparcl1 quartiles (P for trend 0.05).ConclusionSerum Sparcl1 was significantly associated with decreased risk of prevalent dyslipidemia in Chinese population. Further studies are warranted to confirm this association.

Previous studies reported that famine exposure had an effect on metabolic syndrome (MetS). However, there is an inadequacy of study regarding the association between famine exposure, adulthood general obesity, and the risk of MetS.A total of 8883 subjects aged ≥40 years from Jiading community in Shanghai were included. We defined famine exposure subgroups as nonexposed (1963-1974), fetal exposed (1959-1962), childhood exposed (1949-1958), and adolescence exposed (1941-1948). MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria.Compared with the nonexposed group, the risks of MetS were increased in the fetal-, childhood-, and adolescence-exposed groups with odds ratios (OR) and 95% confidence intervals (CI) of 1.48 (1.23-1.78), 1.89 (1.63-2.20), and 2.34 (1.99-2.74), respectively. After adjusting for sex, age, smoking status, drinking status, education, body mass index (BMI), and physical activity, the increased risk of MetS related to the fetal-exposed and childhood-exposed groups with OR and 95% CI of 1.42 (1.04-1.94) and 1.50 (1.02-2.21), respectively, were observed only in women. Famine exposure was significantly associated with MetS among individuals with a BMI 23 kg/mObesity in adulthood significantly further aggravated the risk of MetS in individuals who experienced early life undernutrition, especially in females.背景: 以前的研究报道了饥荒暴露对代谢综合征(MetS)有影响。然而, 关于饥荒暴露、成年期肥胖和 MetS 风险之间的关系则较少研究。 方法: 纳入上海市嘉定社区年龄40岁的8883名受试者。我们将饥荒暴露亚组定义为未暴露(1963-1974)、胎儿暴露(1959-1962)、儿童暴露(1949-1958)和青春期暴露(1941-1948)。 MetS根据 NCEP-ATP III标准定义。 结果: 与未暴露组相比, 胎儿、儿童和青春期暴露组的 MetS 风险增加, OR 和 95% CI 分别为 1.48 (1.23-1.78)、1.89 (1.632.20) 和 2.34 (1.99- 2.74)。在校正性别、年龄、吸烟状况、饮酒状况、教育程度、体重指数(BMI)和体力活动后, 女性中观察到胎儿暴露组和儿童暴露组发生 MetS 的风险增加, OR 和 95%CI 分别为 1.42( 1.04-1.94) 和 1.50 (1.02-2.21)。在 BMI23 kg/m

AimTo determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk.Methods35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes.ResultsAfter 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], P <0.0001 vs. 1.015 [0.975-1.056], P = 0.4643; PInteraction=0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all P < 0.0036).ConclusionsThe early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years.

Background Prediabetes is an important risk factor of cardiovascular disease (CVD) and is associated with subclinical atherosclerosis. However, the evidence of prediabetes as a cardiovascular risk factor is mainly derived from middle-aged adults. Recently, multiple studies supported that prediabetes in older adults would not lead to higher risk of CVD or mortality. We aimed to investigate the age-specific difference in the association between prediabetes and subclinical atherosclerosis in a Chinese prospective cohort study. Methods We included 4739 individuals aged ≥ 40 years and without diagnosed diabetes or CVD history, and divided them into middle-aged adults (age Results 1634 participants aged over 60 years, and 64.3% of them had prediabetes. 3105 participants aged 40–59 years, and 49.3% of them had prediabetes. We found that prediabetes was associated with increased risk of subclinical atherosclerosis in middle-aged adults, but the association attenuated substantially in older adults. Impaired glucose tolerance (IGT), compared to normal glucose tolerance, was associated with 39% lower risk of increased baPWV only in older adults. In accordance, the association between 2 h-PPG and risk of increased baPWV was “U-shaped” in older adults, while risk of elevated baPWV increased linearly with 2 h-PPG in middle-aged adults. In the cross-lagged analysis, increase in FPG and 2 h-PPG tended not to precede increase in baPWV in older adults, but appeared to increase simultaneously with baPWV in middle-aged ones. Conclusion Our results indicated that prediabetes might be less related to subclinical atherosclerosis in older adults than in middle-aged adults and suggested that age was important to consider in the care of adults with prediabetes.

Context Little is known about the link between nonalcoholic fatty liver disease (NAFLD) evolution and incident chronic kidney disease (CKD). Objective We aim to assess the associations of NALFD status changes and NAFLD fibrosis progression with the risk of incident CKD. Methods We conducted a community-based prospective study that included participants aged 40 years or older and free of CKD at baseline in 2010, with follow-up evaluations after a mean of 4.4 years. NAFLD was diagnosed by ultrasonography and NAFLD fibrosis score (NFS) was used to evaluate fibrosis stage and progression. CKD was defined by estimated glomerular filtration rate or urine albumin-to-creatinine ratio. All the measurements were performed at baseline and follow-up examination. Results Among 4042 participants with 4 NAFLD status change groups, incident NAFLD was associated with an increased risk of incident CKD (odds ratio [OR] = 1.44; 95% CI, 1.003-2.06; P = 0.048) compared with non-NAFLD after adjustments for the confounders, including evolution of diabetes, hypertension, and obesity, in addition to the baseline levels. However, the risk of incident CKD was not significantly different between NAFLD resolution and persistent NAFLD. Among 534 participants in the persistent NAFLD group, fibrosis progression from low NFS to intermediate or high NFS was associated with a significantly increased risk of incident CKD compared with stable fibrosis in low NFS (OR = 2.82; 95% CI, 1.22-6.56; P = 0.016). Conclusion NAFLD development and fibrosis progression are associated with increased risk of incident CKD.

Aims/Introduction To analyze the associations and interactions of the genetic susceptibility and family history of diabetes with lifestyle factors in relation to diabetes among Chinese adults. Materials and Methods We constructed a genetic risk score of 34 single‐nucleotide polymorphisms in 11,596 participants from Songnan and Youyi communities, Baoshan District, Shanghai, China. We determined a healthy lifestyle by a normal body mass index (1 year prior, sufficient physical activity (≥600 metabolic equivalent minutes per week), and a sleep duration of ≥6 to ≤8 h/day. Logistic regression models were used to examine the associations and interactions between heritability and lifestyle on diabetes. Results A healthier lifestyle was associated with a lower prevalence of diabetes within any heritable risk groups categorized by the genetic risk score and family history of diabetes. In the combined communities, the odds ratio (95% confidence interval) for diabetes associated with each additional healthy lifestyle factor was 0.83 (0.77–0.89) among participants with a low genetic risk score and 0.86 (0.81–0.91) among participants with a high genetic risk score (P interaction = 0.66). Similar interaction patterns of family history (P interaction = 0.15) and the combination of family history and the genetic risk score with healthy lifestyle (P interaction = 0.55) on diabetes were observed. Conclusions A healthier lifestyle was associated with a significantly lower prevalence of diabetes regardless of heritable risk groups, highlighting the importance of adhering to a healthy lifestyle for diabetes prevention among the entire population., In this study of 11,596 middle‐aged and elderly Chinese adults, a healthier lifestyle was associated with a substantially lower prevalence of diabetes regardless of heritable risk categories determined by the genetic risk score and family history of diabetes, highlighting the importance of adhering to a healthy lifestyle for diabetes prevention among the entire population.

Background Excessive adiposity in adulthood is positively associated with the risk of cardiovascular disease (CVD). However, it is less studied how the risk is separately explained by early adulthood weight and later weight change, especially in Asian ancestries. Methods This study included 121160 participants in a large population-based cohort in China. Body weight at 20 and 40 years of age wase self-reported. Information on CVD history was obtained through standard questionnaires. Results The odds ratios (ORs) were 1.20 (95% CI, 1.10–1.31) for coronary heart disease (CHD), 1.74 (95% CI, 1.36–2.22) for myocardial infarction (MI), 1.14 (95% CI, 0.99–1.32) for stroke and 1.21 (95% CI, 1.12–1.31) for total CVD among individuals with early overweight, and became more prominent for early obesity. Meanwhile, A moderate weight gain of 2.5 kg between early adulthood and midlife significantly increased the risk of CHD (OR: 1.18, 95% CI: 1.05–1.32), stroke (OR: 1.19, 95% CI: 1.03–1.38) and total CVD (OR: 1.15, 95% CI: 1.04–1.27), and the risk escalated with higher amounts of weight gain. Conversely, a weight loss of 2.5 kg conferred lower risk of CVD compared with a stable weight. In further cross-analysis, participants with early adulthood overweight or obesity and significant weight gain afterwards exhibited the greatest risk of CVD. Conclusions High early adulthood BMI and subsequent weight gain had both independent and combined effect on the risk of CVD after midlife. Therefore, weight management should start before early adulthood, and emphasized throughout adulthood for CVD prevention.

Purpose To investigate the etiologies and the clinical characteristics of angle-closure glaucoma (ACG) patients younger than 40 years old in Chinese. Methods Inpatients with diagnosis of ACG and diagnosed age younger than or equal to 40 years old, who were admitted in Eye, Ear, Nose, and Throat Hospital Fudan University from 2002 to 2017, were included in this retrospective non-comparative case series. The underlying causes and clinical features for all the patients were analyzed by comprehensive review of medical charts. Results A total of 298 patients (463 eyes) met the criteria, including 153 females (51.3%) and 145 males (48.7%); the mean age was 25.6 ± 13.0 years. Primary angle-closure glaucoma (PACG), uveitis, and anterior segment dysgenesis (ASD) were the top three etiologies in our patients, which accounted for 32.6%, 20.3%, and 15.1% of the total patients respectively. PACG mainly occurs after 30 years of age and ASD is the top reason of ACG in patients younger than 20 years old. Other known etiologies include iridocorneal endothelial syndrome, neovascular glaucoma, nanophthalmos, retinitis pigmentosa, spherophakia, bestrophinopathy, persistent fetal vasculature, iridociliary cysts, congenital retinoschisis, Marfan’s syndrome, retinopathy of prematurity, familial exudative vitreoretinopathy, congenital retinal folds, Coat’s disease, and neurofibromatosis. Conclusions We described the uncommon presentation of ACG in Chinese young patients. Although unusual, most of the etiologies could be identified. Therefore, more careful and comprehensive examinations are needed for early detection and timely treatment for young ACG patients.

Polyaryletherketone (PAEK) has good biocompatibility and mechanical properties and thus may have great potential in the fields of reparative medicine and bone intervention. In this study, the key representative PAEKs, polyetheretherketone (PEEK) and polyetherketoneketone (PEKK), were modified by UV grafting with sodium polystyrene sulfonate (polyNaSS) to improve their biocompatibility. Toluidine blue staining and Fourier transform infrared spectroscopic analyses showed that sulfonic acid groups were successfully introduced into PAEK, and the hydrophilicity and protein adsorption capacity of the materials were enhanced in a concentration-dependent manner. The effects of the grafted polyNaSS on osteoinduction and antibacterial properties of PAEK were analyzed in detail. We found that polyNaSS enhanced the viability, alkaline phosphatase activity, calcium mineral deposition, and levels of expression of osteoblast-related genes and proteins of adherent human umbilical cord Wharton's jelly-derived mesenchymal stem cells. In addition, wheniEscherichia coli/i,iStaphylococcus aureus/iandiPorphyromonas gingivalis/iwere incubated with the materials, bacterial colony counting revealed that grafting of polyNaSS onto PAEK led to more potent inhibition of bacterial adhesion, and polyNaSS-grafted PEKK had stronger antibacterial performance than did polyNaSS-grafted PEEK fabricated under the same grafting conditions. These data show that polyNaSS-grafted PAEK, and particularly polyNaSS-grafted PEKK, may be useful as orthopedic and dental implant materials.

The gut microbiota has been linked to many cancers, yet its role in acute myeloid leukaemia (AML) progression remains unclear. Here, we show decreased diversity in the gut microbiota of AML patients or murine models. Gut microbiota dysbiosis induced by antibiotic treatment accelerates murine AML progression while faecal microbiota transplantation reverses this process. Butyrate produced by the gut microbiota (especially Faecalibacterium) significantly decreases in faeces of AML patients, while gavage with butyrate or Faecalibacterium postpones murine AML progression. Furthermore, we find the intestinal barrier is damaged in mice with AML, which accelerates lipopolysaccharide (LPS) leakage into the blood. The increased LPS exacerbates leukaemia progression in vitro and in vivo. Butyrate can repair intestinal barrier damage and inhibit LPS absorption in AML mice. Collectively, we demonstrate that the gut microbiota promotes AML progression in a metabolite-dependent manner and that targeting the gut microbiota might provide a therapeutic option for AML.

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) provides an important alternative for children and adolescents with acquired severe aplastic anemia (SAA) lacking matched donors. To test whether pretransplant serum ferritin (SF) represents a candidate predictor for survival and a potential biomarker for graft-versus-host disease (GvHD) in pediatric haplo-HSCT, we retrospectively evaluated 147 eligible patients with SAA who underwent haplo-HSCT. The patients were divided into the low-SF group ( 1000 ng/mL) and the high-SF group (≥ 1000 ng/mL). We found that SF ≥1000 ng/mL independently increased the risk of grade II-IV aGvHD (HR = 2.596; 95% CI, 1.304-5.167, P = 0.007) and grade III-IV aGvHD (HR = 3.350; 95% CI, 1.162-9.658, P = 0.025). Similar probabilities of transplant-related mortality at 100 days were observed in the two groups (6.19 ± 2.45% vs 8.00 ± 3.84%, P = 0.168). The two-year overall survival (85.29 ± 3.89% vs 92.00% ± 3.84%, P = 0.746) and failure-free survival (83.23% ± 4.08% vs 83.37% ± 6.27%, P = 0.915) were comparable. GvHD-/failure-free survival were 60.06 ± 5.10% and 75.56 ± 6.87%, respectively (P = 0.056). In conclusion, elevated pretransplant SF level is associated with higher incidences of grade II-IV aGvHD and grade III-IV aGvHD. However, it is not associated with worse survival after haplo-HSCT for children and adolescent patients with SAA.

Elevated intraocular pressure (IOP) is the major risk factor for glaucoma. The molecular mechanism of elevated IOP is unclear, which impedes glaucoma therapy. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible Poly-ADP-ribose Polymerase (TIPARP), a member of the PARP family, catalyses mono-ADP-ribosylation. Here we showed that TIPARP was widely expressed in the cornea, trabecular meshwork, iris, retina, optic nerve, sclera, and choroid of human eyes. The expression of TIPARP was significantly upregulated in the blood and trabecular meshwork of patients with primary open angle glaucoma compared with that of healthy controls. Transcriptome analysis revealed that the expression of genes related to extracellular matrix deposition and cell adhesion was decreased in TIPARP-upregulated human trabecular meshwork (HTM) cells. Moreover, western blot analysis showed that collagen types I and IV, fibronectin, and α-SMA were increased in TIPARP-downregulated or TIPARP-inhibited HTM cells. In addition, cross-linked actin networks were produced, and vinculin was upregulated in these cells. Subconjunctival injection of the TIPARP inhibitor RBN-2397 increased the IOP in Sprague–Dawley rats. Therefore, we identified TIPARP as a regulator of IOP through modulation of extracellular matrix and cell cytoskeleton proteins in HTM cells. These results indicate that TIPARP is a potential therapeutic target for ocular hypertension and glaucoma.

ObjectiveThe purpose of this study was to investigate the key nursing factors associated with ventilator-associated pneumonia (VAP) in critical care patients.MethodsThrough the quality control platform of Hebei Province, questionnaires were sent to intensive care nurses in 32 tertiary hospitals in Hebei Province, China to collect data concerning the incidence of VAP and the status of the nursing staff. All the data were analyzed using an independent t-test and a one-way analysis of variance (ANOVA). The Pearson correlation coefficient was used to analyse the correlation between the nursing factors and the incidence of VAP. Multivariate logistic regression analysis was used to determine the risk factors affecting VAP.ResultsIn terms of nursing, the incidence of VAP was affected by the differential nursing strategies. Multivariate logistic regression analysis showed that the incidence of VAP was significantly associated with the following six variables: the ratio of nurses to beds (p = 0.000), the ratio of nurses with a bachelor's degree or higher (p = 0.000), the ratio of specialist nurses (p = 0.000), the proportion of nurses with work experience of 5–10 years (p = 0.04), the number of patients nurses were responsible for at night (p = 0.01) and the frequency of oral care (p = 0.000).ConclusionThe incidence of VAP is closely related to nursing factors. In terms of nursing human resources, even junior nurses (less experienced nurses) can play an essential role in reducing VAP. In addition, to reduce VAP, the number of patients that nurses are responsible for at night should be reduced as much as possible, and improving nursing qualifications.

Objective To examine the association between stage 1 hypertension defined by the 2017 American College of Cardiology and American Heart Association (ACC/AHA) guideline and risk of developing arterial stiffness. Methods During 2010-2015, 4595 adults aged ≥40 years without cardiovascular disease were followed up for a median of 4.3 years. BP levels at baseline were categorized into normal, elevated, stage 1 hypertension, and stage 2 hypertension. The development of arterial stiffness was defined as a normal brachial-ankle pulse wave velocity (ba-PWV) at baseline and an increased ba-PWV at follow-up. Results Compared with participants with normal BP, participants with stage 1 hypertension had a 1.48-fold increased risk of developing arterial stiffness [odds ratio (OR) =2.48; 95% confidence interval (CI) =1.59-3.85] after adjustment for cardiovascular risk factors. The association was more evident in adults aged 40-59 years (OR =4.08; 95% CI =2.06-8.08) than that in those aged ≥60 years (OR =1.47; 95% CI =0.81-2.67). A systolic BP 130~139 mmHg was significantly associated with arterial stiffness independent of diastolic BP (OR =2.90; 95% CI =1.86-4.52). Stage 1 hypertension either at baseline or at follow-up was associated with increased risks compared with normal BP at both baseline and follow-up. Conclusions The 2017 ACC/AHA stage 1 hypertension was significantly associated with higher risks of arterial stiffness.

Context The body mass index (BMI) and waist circumference (WC) as diagnostic tools of obesity do not reflect the same level of fat mass and whether obesity leads to various effects on cardiometabolic risk factors among different racial/ethnic population is unknown. Objective The study aims to address the multicollinearity between BMI and WC by using the residual model approach and to assess and compare the effects of obesity metrics on cardiometabolic risk factors among different races/ethnicities. Design, setting, and participants Data from a nationally representative sample of mainland Chinese adults collected in 2010 and data from the National Health and Nutrition Evaluation Survey 2005-2016 were used. By conducting a regression analysis between WC and BMI, the variation of BMI was removed from WC measures and residual of WC was obtained. The associations between obesity metrics and cardiometabolic risk factors were compared among different races/ethnicities by sex. Results The residual WC was significantly associated with all the cardiometabolic risk factors in mainland Chinese, and most of the factors in non-Hispanic white and non-Hispanic black adults, but not in the other races/ethnicities. The standardized regression coefficients of the associations between obesity metrics and cardiometabolic factors showed that the obesity metrics had greater impact on systolic blood pressure, diastolic blood pressure, and triglyceride in Chinese adults than those of other racial/ethnic groups. Conclusions Chinese adults are more susceptible to the effects of overall obesity and fat distribution on cardiometabolic risk factors than the other racial/ethnic population.

Purpose Whether the association between fruit and type 2 diabetes (T2D) is modified by the genetic predisposition of T2D was yet elucidated. The current study is meant to examine the gene–dietary fruit intake interactions in the risk of T2D and related glycemic traits. Methods We performed a cross-sectional study in 11,657 participants aged ≥ 40 years from a community-based population in Shanghai, China. Fruit intake information was collected by a validated food frequency questionnaire by asking the frequency of consumption of typical food items over the previous 12 months. T2D-genetic risk score (GRS) was constructed by 34 well established T2D common variants in East Asians. The risk of T2D, fasting, 2 h-postprandial plasma glucose, and glycated hemoglobin A1c associated with T2D-GRS and each individual single nucleotide polymorphisms (SNPs) were tested. Results The risk of T2D associated with each 1-point of T2D-GRS was gradually decreased from the lower fruit intake level ( 3 times/week) [the corresponding ORs and 95% CIs were 1.08 (1.05–1.10) and 1.07 (1.05–1.08); P for interaction = 0.04]. Analyses for associations with fasting, 2 h-postprandial plasma glucose and glycated hemoglobin A1c demonstrated consistent tendencies (all P for interaction ≤ 0.03). The inverse associations of fruit intake with risk of T2D and glucose traits were more prominent in the higher T2D-GRS tertile. Conclusions Fruit intakes interact with the genetic predisposition of T2D on the risk of diabetes and related glucose metabolic traits. Fruit intake alleviates the association between genetic predisposition of T2D and the risk of diabetes; the association of fruit intake with a lower risk of diabetes was more prominent in population with a stronger genetic predisposition of T2D.

Blood pressure (BP) variability may have its effect on the development of vascular disease. The authors aimed to examine the association between the visit‐to‐visit variability (VVV) of BP and arterial stiffness in Chinese adults. The authors included 1407 participants from a prospective cohort study of community residents who were ≥40 years, without a history of myocardial infarction or stroke, and with data at the baseline, the second and the third visits in 2008, 2009, and 2013. The VVV of BP was defined as the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV), and the variability independent of the mean (VIM) in BP levels at the 3 visits. Arterial stiffness was measured by brachial‐ankle pulse wave velocity (ba‐PWV) at the 2nd and the 3rd visits. Levels of ba‐PWV change and the occurrence of an elevated ba‐PWV increased significantly in the highest tertile of VVV measures of systolic BP (SBP) and pulse pressure (PP) compared with the lowest tertile, respectively. The multivariable regression analysis revealed that VVV measures of SBP and PP were significantly associated with levels of ba‐PWV change and the risks of developing an elevated ba‐PWV. The odds ratios (ORs) and 95% confidence intervals (CIs) for the risk were 2.12 (1.57–3.12) and 1.92 (1.38–2.68) in participants with the highest versus the lowest tertile of SBP‐SD and PP‐SD, respectively. No significant association was found for diastolic BP variability measures. The increased long‐term variabilities of SBP and PP were associated with an increased risk of arterial stiffness.

Retinoblastoma is the most common intraocular malignancy during childhood. Currently, there is no effective treatment for metastatic retinoblastoma. We investigated potential biomarkers of retinoblastoma by utilizing three datasets from a public database. Functional enrichment analysis, including gene ontology, Kyoto encyclopedia of genes and genomes, gene set enrichment analysis and variation analysis, suggested that differentially expressed genes in retinoblastoma were enriched in accelerated cell cycle events. Protein-protein interaction analysis constructed a network consisting of six hub genes, including benzimidazoles 1 (BUB1), cyclin dependent kinase 1 (CDK1), centromere protein E (CENPE), kinesin family member 20A (KIF20A), PDZ binding kinase (PBK), and targeting protein for xklp2 (TPX2). Drug sensitivity analysis showed that nelarabine was positively correlated with five hub genes. All six genes were expressed differently in six immune subtypes and were positively correlated with stemness indices in most human cancer types. Since CENPE is the least known hub gene in retinoblastoma, we further analyzed the potential non-coding RNAs and transcription factors that regulate CENPE and built interaction networks of competing endogenous RNA and transcription factors. Immune cell infiltration, especially by plasma and B cells, was enhanced in samples with high CENPE expression. Pan-cancer analysis illustrated that CENPE was highly expressed in a wide range of human tumors. In vitro validation revealed that CENPE was significantly upregulated at both the mRNA and protein levels in retinoblastoma cells. In conclusion, CENPE, along with other hub genes, could serve as a potential biomarker and intervention target for retinoblastoma.

Low-grade albuminuria, as an early marker of endothelial dysfunction and kidney damage, has been recognized as a risk factor for metabolic disorders. Epidemiological studies manifesting the association of low-grade albuminuria with the risk of incident NAFLD and fibrosis were not available. We aimed to investigate the association of low-grade albuminuria with incident NAFLD and fibrosis by glycaemia status.A prospective population-based study was performed in 3308 participants without NAFLD at recruitment. Baseline urinary albumin excretion was obtained by a first-voided early morning spot urine sample. At follow-up visit, incident NAFLD was diagnosed by hepatic ultrasound after excluding alcohol abuse and other cause of hepatic diseases. Fatty liver index (FLI) was employed to reflect liver fat content. Liver fibrosis was evaluated by NAFLD fibrosis score (NFS), fibrosis-4 score (FIB-4) and Hepamet fibrosis score (HFS) respectively.After 4.3 years of follow-up, 622 (18.8%) were detected as incident NAFLD. Participants with low-grade albuminuria imposed a 40.4% [1.404 (1.112-1.772)] greater risk on incident NAFLD, and 52.0% [1.520 (1.141-2.026)], 87.4% [1.874 (1.291-2.720)] and 40.4% [1.404 (1.038-1.898)] higher risks on newly onset higher values of FLI, NFS and FIB-4 respectively. The effect of low-grade albuminuria was stronger in the subgroup of non-diabetic population.Low-grade albuminuria was independently associated with incident NAFLD and a higher probability of fibrosis, especially among non-diabetic individuals.

Poly (rC)-binding protein 1 (PCBP1), an RNA- or DNA-binding protein with a relative molecular weight of 38 kDa, which is characterized by downregulation in many cancer types. Numerous cases have indicated that PCBP1 could be considered as a tumor suppressor to inhibit tumorigenesis, development, and metastasis. In the current review, we described the multilevel regulatory roles of PCBP1, including gene transcription, alternative splicing, and translation of many cancer-related genes. Additionally, we also provided a brief overview about the inhibitory effect of PCBP1 on most common tumors. More importantly, we summarized the current research status about PCBP1 in hypoxic microenvironment, autophagy, apoptosis, and chemotherapy of cancer cells, aiming to clarify the molecular mechanisms of PCBP1 in cancer. Taken together, in-depth study of PCBP1 in cancer may provide new ideas for cancer therapy.

Locally advanced rectal cancer (RC) is treated with neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery. Currently, organ-sparing approaches and/or "watch-and-wait" strategies other than unnecessary surgery have been suggested as the best option for patients who achieve complete regression after neoadjuvant treatment. However, patients respond differently to nCRT, hence the urgent need for effective methods to predict whether individual rectal cancer patients could benefit from this treatment. In this review, we summarize the biomarkers reported to be potential predictors of the therapeutic response of RC to nCRT. Biomarkers that are associated with genes, ribonucleic acid (RNA) and proteins are summarized and described first, followed by other types including immune and tumour microenvironment-related biomarkers, imaging biomarkers, microbiome-associated biomarkers, and blood-based biomarkers.

Secondary poor graft function (sPGF) increases the risk of life-threatening complications after hematopoietic stem cell transplantation (HSCT). The incidence, clinical outcomes, and risk factors of sPGF have not been elucidated in haploidentical (haplo-) HSCT for acquired aplastic anemia (AA) patients. We retrospectively reviewed 423 consecutive AA patients who underwent haplo-HSCT between January 2006 and December 2020 and report a 3-year cumulative incidence of 4.62% (95% confidence interval [CI]: 3.92%-10.23%) of sPGF. While no primary PGF occurred. The median time to sPGF was 121 days (range 30-626 days) after transplantation. To clarify the risk factors for sPGF, 17 sPGF cases and 382 without PGF were further analyzed. Compared to patients without PGF, the 2-year overall survival was significantly poorer for sPGF patients (67.7% vs 90.8%, p =.002). Twelve sPGF patients were alive until the last follow-up, and 7 achieved transfusion independency. The multivariable analyses revealed that later neutrophil engraftment (OR 2.819, p=.049) and a history of refractory cytomegalovirus viremia (OR=7.038, p=.002) post-transplantation were associated with sPGF. There was weak evidence that a history of grade 3-4 acute graft-versus-host disease increased the risk of sPGF (p=.063). We advocated better post-transplantation strategies to balance the risk of immunosuppression and viral reactivation for haplo-HSCT in AA patients.

Although previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with incident T2DM. Causal mediation analyses indicate 34 significant causal mediation linkages, with 88.2% through obesity and lipids. Variances explained in the serum metabolites are modestly limited in the comprehensive catalog of risk factor-metabolite-diabetes associations. These findings reveal that systematic AAs and MRMs change profile before T2DM onset and support a potential role of metabolic alterations in the pathogenesis of diabetes.

Purpose To provide the clinical and genetic characteristics of a large cohort of Chinese patients with vitelliform macular dystrophies. Design Cross-sectional study. Methods One hundred and thirty-four unrelated Chinese patients diagnosed with Best vitelliform macular dystrophy (BVMD), autosomal recessive bestrophinopathy (ARB), or adult vitelliform macular dystrophy (AVMD) were enrolled. Detailed ophthalmic examinations and genetic testing on vitelliform macular dystrophy–related genes were performed. Genotype and phenotype association were analyzed among different diagnostic groups. Results In total, 87 BVMD, 30 AVMD, and 17 ARB patients were enrolled in this study. Genetic analysis identified 37 BEST1 mutations in 53 patients with BVMD and ARB. Of these, 5 variants (c.254A>C, c.291C>G, c.722C>G, c.848_850del, c.1740-2A>C) were novel. The variant c.898G>A was a hotspot mutation, which was identified in 13 patients with BVMD and 1 patient with ARB. There were significant differences of ocular biometric parameters among patients with homozygous or compound heterozygous mutations, heterozygous mutations, and those without mutations of BEST1. Homozygous or compound heterozygous patients had shortest axial length (AL), shallowest anterior chamber depth (ACD), and highest intraocular pressure (IOP); patients without mutations had longest AL, deepest ACD, and lowest IOP; and heterozygous patients were in between. Moreover, 7 patients harboring heterozygous mutations in BEST1 and 3 patients without BEST1 mutations showed similar clinical appearance to ARB in our cohort. Conclusions This is the largest sample size study of Chinese vitelliform macular dystrophy patients. Our results indicated that assessment of angle-closure risk is a necessary consideration for all types of BEST1-related vitelliform macular dystrophies. The study expanded both the clinical and genetic findings of 3 common types of vitelliform macular dystrophies in a Chinese population.

Background Early life exposure to famine and adulthood obesity increased the risk of nonalcoholic fatty liver disease (NAFLD) in adulthood. However, the joint effects on adulthood NAFLD risk are not clear. Aim This study aimed to explore the joint effects of famine exposure and adulthood obesity on NAFLD risk in later life. Methods We included 7632 subjects aged ≥40 years from a community-dwelling population. Participants were divided into 4 famine exposure groups according to the birth year, including nonexposed (1963-1974), fetal-exposed (1959-1962), childhood-exposed (1949-1958) and adolescent-exposed (1941-1948). General obesity was assessed by body mass index (BMI: overweight ≥24.0 kg/m2 , obesity ≥28.0 kg/m2 ) and abdominal obesity assessed by waist-to-hip ratio (WHR, men/women: moderate ≥0.90/0.85, high ≥0.95/0.90). Results Compared with nonexposed, fetal- and childhood-exposed participants show an increased risk of NAFLD with multivariable-adjusted odds ratio (OR) and 95% confidence interval (CI) of 1.28 (1.02-1.61) and 1.40 (1.04-1.88) respectively. After further adjusting BMI and WHR, the increased risk was observed only in childhood-exposed participants (OR = 1.46, 95% CI = 1.04-2.05). Significant interaction between famine exposure and general obesity on the risk of NAFLD was observed in women (P for interaction = .02). No significant interactions were detected between famine exposure and abdominal obesity (all P for interaction >.05). Compared with normal-BMI and -WHR participants, those with both general and abdominal obesity in adulthood had 20.74 (95% CI: 12.00-35.96), 14.45 (8.76-23.86), 23.02 (16.28-32.57) and 13.04 (8.30-20.48)-fold higher risk in nonexposed, fetal-, childhood- and adolescent-exposed groups respectively. Conclusion Coexistence of early life famine exposure and adulthood obesity was associated with a higher risk of NAFLD.

Prostate cancer (PCa) is a malignancy with the highest morbidity rate in 105 countries worldwide and was a major cause of cancer‑associated death in men in 2018. Accumulating evidence suggests that microRNAs (miRNAs/miRs) have important functions in the carcinogenesis of PCa, and may provide novel treatment targets. Previous studies have indicated that miR‑16‑5p is associated with PCa. However, the relevance and importance of miR‑16‑5p in PCa carcinogenesis are still not completely understood. In the current study, we aimed to investigate the role and mechanism of miR‑16‑5p in PCa carcinogenesis. The results showed that miR‑16‑5p was markedly downregulated in PCa cells, and MTS assay, colony formation, flow cytometric analyses demonstrated that miR‑16‑5p inhibited PCa cell survival, regulated cell cycle distribution and induced apoptosis. Moreover, luciferase reporter assay and western blot analysis showed that miR‑16‑5p directly targets AKT3 (AKT serine/threonine kinase 3), which is associated with PCa carcinogenesis, and the effects of the downregulation of AKT3 were similar to the effects of upregulation of miR‑16‑5p in PC‑3 cells. In conclusion, our data clarify that miR‑16‑5p has anticancer functions in PCa cells, and our findings provide experimental evidence to highlight the potential value of miR‑targeting treatment strategies for PCa.

OBJECTIVE We aim to investigate the impact of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and adulthood diabetes risk. RESEARCH DESIGN AND METHODS This study included 77,925 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study who were born around the time of the Chinese Great Famine and free of diabetes at baseline. They were divided into three famine exposure groups according to the birth year, including nonexposed (1963–1974), fetal exposed (1959–1962), and childhood exposed (1949–1958). Relative risk regression was used to examine the associations between famine exposure and ICVHMs on diabetes. RESULTS During a mean follow-up of 3.6 years, the cumulative incidence of diabetes was 4.2%, 6.0%, and 7.5% in nonexposed, fetal-exposed, and childhood-exposed participants, respectively. Compared with nonexposed participants, fetal-exposed but not childhood-exposed participants had increased risks of diabetes, with multivariable-adjusted risk ratios (RRs) (95% CIs) of 1.17 (1.05–1.31) and 1.12 (0.96–1.30), respectively. Increased diabetes risks were observed in fetal-exposed individuals with nonideal dietary habits, nonideal physical activity, BMI ≥24.0 kg/m2, or blood pressure ≥120/80 mmHg, whereas significant interaction was detected only in BMI strata (P for interaction = 0.0018). Significant interactions have been detected between number of ICVHMs and famine exposure on the risk of diabetes (P for interaction = 0.0005). The increased risk was observed in fetal-exposed participants with one or fewer ICVHMs (RR 1.59 [95% CI 1.24–2.04]), but not in those with two or more ICVHMs. CONCLUSIONS The increased risk of diabetes associated with famine exposure appears to be modified by the presence of ICVHMs.

Background & aims Nonalcoholic fatty liver disease (NAFLD) has been considered as a risk factor of adverse cardiovascular prognosis, but the relationship between subclinical atherosclerosis and NAFLD remains controversial. We aimed to investigate the impact of subclinical atherosclerosis on incident NAFLD and liver fibrosis. Methods We included 3433 subjects aged ≥40 years and free of NAFLD. Brachial-ankle pulse wave velocity (ba-PWV) and carotid intima-media thickness (CIMT) were measured at baseline to assess subclinical atherosclerosis status. At follow-up visit, NAFLD was diagnosed by hepatic ultrasound and fibrosis was assessed by NAFLD fibrosis score (NFS), fibrosis-4 score (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI). Results A total of 654 (19.1%) subjects developed NAFLD during the follow-up period of 4.3 years. In the multivariate logistic regression models, each standard deviation (SD) increment of ba-PWV was associated with 20% (95% confidence interval [CI] 1.07-1.33), 22% (95% CI 1.08-1.39), 17% (95% CI 1.04-1.32) and 37% (95% CI 1.07-1.75) higher risk of incident NAFLD, higher NFS, FIB-4 and APRI respectively. Compared with the lowest quartile of ba-PWV, the highest quartile ba-PWV had 63% (95% CI 1.20-2.22), 112% (95% CI 1.42-3.17), 86% (95% CI 1.28-2.69) and 201% (95% CI 1.29-7.04) higher risk of incident NAFLD, higher NFS, FIB-4 and APRI respectively. Besides, per SD increase of CIMT was associated with a 12% (95% CI 1.01-1.24) higher risk of incident NAFLD. Conclusions Increased ba-PWV was independently associated with incident NAFLD and higher probability of fibrosis, whereas CIMT was associated with incident NAFLD but not with fibrosis.

This study aimed to evaluate the discriminative abilities of glycosylated hemoglobin (HbA1c) and to examine the optimal HbA1c cutoff values for diabetes and prediabetes in Chinese adults.Data of a population-based cohort of Chinese adults aged ≥40 years living in Jiading District in Shanghai were used. At baseline, 9389 and 7241 participants were included to identify the optimal HbA1c cutoff values for diabetes and prediabetes, respectively using the 1999 World Health Organization criteria as reference. In addition, the follow-up data on incident diabetes of 4538 participants were used to determine the HbA1c cutoff value for prediabetes using the development of diabetes as reference. The discriminative abilities of HbA1c were evaluated using receiver operating characteristic (ROC) curves, and the optimal cutoff values were determined by Youden's index.The areas under the ROC curves were 0.849 for diabetes, 0.614 for prediabetes using baseline data, and 0.648 for prediabetes using follow-up data. An HbA1c cutoff value of 6.0% had the largest Youden's index to diagnose diabetes with a sensitivity of 70.2% and a specificity of 87.4%. An HbA1c cutoff value of 5.6% was indicated for prediabetes using both baseline and follow-up data. However, the sensitivity and specificity were both low (55.4% and 61.1% using an oral glucose tolerance test as reference, 64.6% and 57.1% using incident diabetes as reference).An HbA1c value ≥6.0% could be used to detect diabetes in Chinese adults aged ≥40 years. However, although an HbA1c value of 5.6% to 5.9% was indicated in this study, the overall discrimination of HbA1c for prediabetes was poor.背景: 本研究旨在中国成年人群中, 评估糖化血红蛋白 (HbA1c) 诊断糖尿病和糖尿病前期的表现并寻找诊断的最佳HbA1c切点。 方法: 研究人群来自上海市嘉定区年龄≥40岁的社区居民。采用基线调查横断面数据, 以1999年世界卫生组织 (WHO) 糖尿病和糖尿病前期定义为参照标准, 分别纳入9389名和7241名研究对象来确定诊断糖尿病和糖尿病前期的最佳HbA1c切点。另外采用随访数据, 以糖尿病发病为参照标准, 纳入4538名研究对象来确定诊断糖尿病前期的最佳HbA1c切点。使用受试者工作特征曲线 (ROC) 评估HbA1c的诊断表现, 并根据约登指数确定最佳诊断切点。 结果: 采用基线数据, HbA1c诊断糖尿病的ROC曲线下面积(AUC)为0.849, HbA1c诊断糖尿病前期的AUC为0.614。采用随访数据, HbA1c诊断糖尿病前期的AUC为0.648。HbA1c切点取6.0%时, 诊断糖尿病的约登指数最大, 其敏感性为70.2%, 特异性为87.4%。基线和随访数据均显示, 诊断糖尿病前期的最佳HbA1c切点为5.6%, 但其敏感性和特异性均较低 (采用口服葡萄糖耐量试验为参照标准时,敏感性和特异性分别为55.4%和61.1%；采用随访过程中糖尿病发病作为参照标准时, 敏感性和特异性分别为64.6%和57.1%)。 结论: 在年龄≥40岁的中国成年人中, HbA1c≥6.0%可用于诊断糖尿病。然而, 尽管本研究得出糖尿病前期的HbA1c范围为5.6%-5.9%, 但HbA1c对诊断糖尿病前期的效果较差。.

The cardiometabolic risk associated with metabolically healthy obesity (MHO) remains the subject of debate. It is unclear whether MHO is a transient condition that affects subclinical atherosclerosis risk. In this study, we aimed to investigate the association of MHO and its transition over time with incident subclinical atherosclerosis. A prospective study was conducted with 6220 Chinese adults who were free of cardiovascular disease (CVD) at baseline. Obesity was defined as BMI ≥25.0 kg/m2. Metabolic health was defined as an individual having fewer than two of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) criteria for components of the metabolic syndrome (excluding waist circumference). Subclinical atherosclerosis was measured by brachial–ankle pulse wave velocity, pulse pressure and albuminuria, separately or combined. Participants were cross-classified by BMI categories and by metabolic health status and its transition during follow-up. Inverse probability weighted logistic regression models were used to estimate ORs and 95% CIs for subclinical atherosclerosis. The MHO phenotype accounted for 16.3% of the total population and 32.8% of the population with obesity at baseline. Baseline MHO was not significantly associated with incident subclinical atherosclerosis. During a follow-up period of 4.4 years, 46.8% of individuals with MHO developed a metabolically unhealthy status. Those with transient MHO had an increased risk of composite subclinical atherosclerosis compared with those in the metabolically healthy non-obesity reference group (OR 2.52 [95% CI 1.89, 3.36]). A transition from metabolically unhealthy to healthy status was shown to decrease the outcome risk. The relationship between BMI and subclinical atherosclerosis was partly mediated by BP and plasma glucose. MHO is not a stable condition and transient MHO conferred an increased risk of subclinical atherosclerosis, the early stage of CVD. Hence, individuals may benefit from early behavioural or medical management in order to avoid a deterioration of metabolic status and prevent atherosclerosis and CVD.

Monitoring and imaging glutathione (GSH) in living systems is an essential tool to determine the key roles of GSH in biological pathways, but most fluorescent sensors can only be used in vitro because of their potential biotoxicity. Here, a peptide-based fluorescent sensor, FP, has been successfully designed and synthesized based on the biocompatibility of the peptide backbone and low toxicity. The design strategy of FP contains a specific spatial structure of the peptide sequence which selectively binds to Cu2+, triggering fluorescence quenching. Interestingly, the fluorescence of FP can be fully restored by GSH, due to the strong binding between Cu2+ and the GSH sulfhydryl groups. Finally, the sensor is highly sensitive and selective for imaging GSH both in vitro and in vivo with low toxicity. Thus, FP with its strong "on-off-on" fluorescence changes is a powerful way to image GSH both in cells and zebrafish larvae to study the GSH pathway.

Epidemiological evidence on the association between elevated lipoprotein (a) (Lp (a)) with risk of stroke remains inconsistent. We aimed to investigate the association between serum Lp (a) level and the risk of stroke among middle-aged and elderly Chinese.A community-based prospective cohort study of 8500 participants aged 40 years or older was conducted in Jiading district, Shanghai, China, in 2010. The incident strokes were documented at follow-up visit during 2014-2015.During a mean follow-up of 5.1 years, 444 incident cases of stroke occurred. The incidences of stroke were 4.44%, 5.14% and 6.14% from the lowest to the highest serum Lp (a) tertile, respectively. A significant association between serum Lp (a) tertile and the risk of incident stroke was observed (p for trend0.05). Compared with individuals in the lowest tertile of serum Lp (a), the multivariable adjusted hazards ratio (HR) and 95% confidence interval (CI) for incident stroke in Lp (a) tertile 3 were 1.34 (1.06-1.70).Serum Lp (a) concentration was associated with increased risk of incident stroke in Chinese adults.

A bis-dimethylamine substituted xanthone (Xan-2) was obtained by cationic modification of the free C3 and C6 hydroxy groups of 1,3,6-trihydroxyxanthone (Xan-1) which was isolated from Polygala hongkongensis Hemsl.. The results of the spectroscopic analysis, melting profiles, electrophoretic migration, PCR assay and molecular docking indicated that the hydrophobic plane of Xan-1 and Xan-2 could intercalate into the DNA base pairs meanwhile the basic amine alkyl chain of Xan-2 could bind with DNA phosphate framework via electrostatic interaction. Thus, Xan-2 exhibited higher DNA binding affinity than Xan-1. Further study showed that Xan-2 could inhibit the proliferation of HeLa, SGC-7901 and A549 cells effectively by MTT assay and induce apoptosis of HeLa cells as detected by AO/EB staining and flow cytometry assay. Interestingly, Xan-2 exhibited selective cytotoxicity to cells, which was proved by its relatively low inhibitory effect on Raw 264.7 cell. What these studies mean is that disubstituted amine alkyl chains will play an important role in DNA binding property and cytotoxic activity, providing a direction for the development of novel potential antitumor agents.