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To examine associations between metabolically obese phenotypes or their changes and increased carotid intima-media thickness (CIMT).This prospective cohort included 13,681 Chinese adults aged 20-80 years who completed follow-up health examination with carotid ultrasound and were divided according to metabolic and weight status: metabolically healthy and normal weight (MHNW); metabolically obese but normal weight (MONW); metabolically healthy but obese (MHO); metabolically abnormal and obese (MAO). Cox and logistic regression were used to evaluate the associations of the phenotypes or their changes with increased CIMT. During a mean follow-up of 33 months, 1927 participants developed increased CIMT. After adjusting for age, sex and potential biochemical confounders, MAO was significantly associated with increased CIMT (HR 1.22, 95% CI [1.07, 1.4]); the association remained significant in those 40 years or older. Compared with stable MHNW, increased CIMT risk was higher for stable MAO (OR 1.35 [1.16, 1.57]), transitional MAO from MONW (OR 1.44 [1.04, 1.97]), and transitional MHO from MHNW (OR 1.59 [1.10, 2.26]) in demographic adjusted models; only stable MAO remained significant in the multivariate adjusted model (OR 1.23 [1.05, 1.45]).MAO significantly elevated the risk of increased CIMT. Stable MAO and obese transitions also promoted CIMT progression.

The purpose of this study is to explore the relationship between Chinese visceral adipose index (CVAI) and the risk of coronary heart disease (CHD) in Chinese through a large cohort study.This study included 42,165 adults who were without CHD at baseline and who completed at least one annual follow-up between 2009 and 2016. We used the Cox proportional hazards model to estimate Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) for the association between CVAI and risk of CHD. During the median follow-up of 3.36 years (154,808 person years), 520 participants developed CHD, including 374 males and 146 females. Compared with the first quartile of CVAI, the risk of CHD was significantly increased in the fourth quartile of CVAI in multivariate model (HR [95% CI]: 9.92 [5.45, 18.04], P 0.001). Sensitivity analysis by excluding incident CHD developed in the first two years of follow-up reinforced our results. Gender stratification analyses showed that the relationship between CVAI and CHD risk was higher in males than that in females. The restricted cubic spline showed a non-linear dose-response relationship between CVAI and CHD risk. In addition, CVAI was associated with CHD risk in the subgroups of participants without T2DM, without hypertension, and without fatty liver.CVAI was significantly associated with the risk of CHD. Individuals should keep CVAI at normal level to prevent CHD.

ABCB11 encodes the bile salt export pump (BSEP), a key regulator in maintaining bile acid (BA) homeostasis. Although inherited ABCB11 mutations have previously been linked to primary liver cancer, whether ABCB11 deficiency leads to liver cancer remains unknown. Here, we analyzed ABCB11 mRNA expression levels in liver tumor specimens [29 with hepatocellular carcinoma (HCC), one with intrahepatic cholangiocarcinoma (ICC), and one with mixed HCC/ICC] with adjacent normal specimens and published human datasets. Liver tissues obtained from Abcb11-deficient (Abcb11-/- ) mice and wild-type mice at different ages were compared by histologic, RNA-sequencing, and BA analyses. ABCB11 was significantly downregulated in human liver tumors compared with normal controls. Abcb11-/- mice demonstrated progressive intrahepatic cholestasis and liver fibrosis, and spontaneously developed HCC and ICC over 12 months of age. Abcb11 deficiency increased BAs in the liver and serum in mice, most of which are farnesoid X receptor (FXR) antagonists/non-agonists. Accordingly, the hepatic expression and transcriptional activity of FXR were downregulated in Abcb11-/- mouse livers. Administration of the FXR agonist obeticholic acid reduced liver injury and tumor incidence in Abcb11-/- mice. In conclusion, ABCB11 is aberrantly downregulated and plays a vital role in liver carcinogenesis. The cholestatic liver injury and liver tumors developed in Abcb11-/- mice are associated with increased FXR antagonist BAs and thereby decreased activation of FXR. FXR activation might be a therapeutic strategy in ABCB11 deficiency diseases. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

This study aimed at investigating the relationships between Platelet-Lymphocyte ratio (PLR) and Neutrophil-Lymphocyte ratio (NLR) and their dynamic changes (∆PLR, ∆NLR) with type 2 diabetes mellitus (T2DM) in a Chinese cohort study.This study recruited 41,439 individuals who were diagnosed without T2DM at first health examination and completed at least one follow-up. The relationships between NLR, PLR, ∆PLR, ∆NLR and T2DM risk were analyzed using the Cox regression model with corresponding Hazard Ratios (HRs) and 95% Confidence Intervals (CIs).PLR exhibited significant correlation with T2DM risk in a linear reverse dose-response pattern, the corresponding HRs and 95% CIs were 0.81 (0.72, 0.90), 0.71 (0.63, 0.80) and 0.56 (0.49, 0.64) respectively (Higher PLR could reduce the risk of T2DM. Larger increase of NLR could increase T2DM risk.

Background It is indicated that Low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C ratio) has greater predictive value for thickened carotid intima-media thickness (CIMT) comparing with classic lipid parameters. However, there have been few reports about their association in general Chinese population. Method We included a total of 1220 CIMT participants and 2440 matched controls, who had ultrasonography of carotid artery during 2009 and 2016. Univariate and multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for thickened CIMT risk associated with LDL-C/HDL-C ratio. Result In the univariate logistic regression model, there was significant association between LDL-C/HDL-C ratio and thickened CIMT (Q4 vs. Q1, OR = 1.94, 95% CI: 1.60–2.36; ptrend < 0.05). After adjusting for potential covariates, LDL-C/HDL-C ratio remained significantly associated with thickened CIMT (Q4 vs. Q1, OR = 1.81, 95% CI: 1.41–2.34, ptrend < 0.001; ≥3.05 v.s. trend 2) (OR = 2.22; 95% CI = 1.63-3.03; Ptrend < 0.05) and BMI ≥25 (kg/m2) (OR = 2.50, 95% CI: 1.76–3.54; Ptrend < 0.05), dyslipidemia (OR = 3.28, 95% CI: 1.83–5,85; Ptrend < 0.001), and without periodontitis (OR = 2.08, 95% CI: 1.54–2.81 ; Ptrend < 0.05) comparing Q4 to Q1. Similar results were observed in the subgroup analyses for LDL-C/HDL-C ratio ≥3.05 v.s. Conclusion High LDL-C/HDL-C ratio could significantly increase the risk of thickened CIMT independent of gender, IFG, hypertension, and fatty liver disease in general Chinese population.

Plumula nelumbinis has great medicinal potential as a herbal tea and traditional drug in China. This study was aimed to evaluate the anticardiac fibrosis of the total alkaloids of P. nelumbinis (TAP). TAP at 50 mg/kg/day significantly ameliorated isoproterenol-induced cardiac fibrosis in mice (p .05). The circulating lipidomics study revealed that TAP improved the lipid metabolism dysfunction in cardiac fibrosis. Meanwhile, TAP suppressed the lipid accumulation, decreased MDA level (p .01) in heart, and increased FFA level (p .01). Furthermore, integrating lipidomics, chemical profiles and pharmacology network analysis found that AMPK and PI3K/Akt signaling pathways were the potential targeted pathway by TAP to regulate lipid metabolism dysfunction including glycerophospholipid metabolism. Above all, TAP provided a potential anticardiac fibrosis effect partly through regulation of lipid profiles. PRACTICAL APPLICATIONS: The total alkaloids of Plumula nelumbinis (TAP) suppressed ISO-induced cardiac fibrosis in mice. Network pharmacology analysis and experiments revealed that TAP-regulated AMPK and PI3K/Akt signaling pathway to improve lipid metabolism disorder in cardiac fibrosis. This study provides evidence to the therapeutic potential of TAP in the treatment of ISO-induced cardiac fibrosis and could be a drug candidate for prevention and treatment of cardiac fibrosis.

Worldwide, colorectal cancer (CRC) is one of the most common malignant tumors, leading to immense social and economic burdens. Currently, the main treatments for CRC include surgery, chemotherapy, radiotherapy and immunotherapy. Despite advances in the diagnosis and treatment of CRC, the prognosis for CRC patients remains poor. Furthermore, the occurrence of side effects and toxicities severely limits the clinical use of these therapies. Therefore, alternative medications with high efficacy but few side effects are needed. An increasing number of modern pharmacological studies and clinical trials have supported the effectiveness of Chinese herbal medicines (CHMs) for the prevention and treatment of CRC. CHMs may be able to effectively reduce the risk of CRC, alleviate the adverse reactions caused by chemotherapy, and prolong the survival time of patients with advanced CRC. Studies of molecular mechanisms have provided deeper insight into the roles of molecules from CHMs in treating CRC. This paper summarizes the current understanding of the use of CHMs for the prevention and treatment of CRC, the main molecular mechanisms involved in these processes, the role of CHMs in modulating chemotherapy-induced adverse reactions, and CHM's potential role in epigenetic regulation of CRC. The current study provides beneficial information on the use of CHMs for the prevention and treatment of CRC in the clinic, and suggests novel directions for new drug discovery against CRC.

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio may carry additional information and has been suggested as a better predictor for atherosclerosis progression and cardiovascular disease (CVD) than LDL-C and HDL-C alone. Therefore, we aim to explore the association between LDL-C/HDL-C ratio and high carotid intima-media thickness (CIMT) risk in a large Cohort in Beijing, China. This cohort study included 13,612 adults without high CIMT at first entry and who attended the baseline examination and at least one follow-up annual examination between 2009 and 2016. We used multivariable Cox regression to estimate hazard ratios (HR) with their 95% confidence intervals (CI) for the association between LDL-C/HDL-C ratio and risk of high CIMT. During 37,912 person-years of follow-up, 1996 (1268 men and 728 women) developed high CIMT. Compared with the first quartile of LDL-C/HDL-C ratio, the risk of high CIMT was significantly increased for the fourth quartile of LDL-C/HDL-C ratio (HR = 1.51, 95% CI: 1.29-1.78). We observed a significant association between LDL-C/HDL-C ratio and high CIMT risk comparing LDL-C/HDL-C ratio >2.78 with LDL-C/HDL-C ratio ≤2.78 and significant dose-response relationship between LDL-C/HDL-C ratio and risk of high CIMT. The restricted cubic spline showed a significant nonlinear association between LDL-C/HDL-C ratio and the risk of high CIMT (pnon-linearity = 0.009). We identify a significant association between LDL-C/HDL-C ratio and the risk of high CIMT in the Chinese Cohort study. Future studies are needed to evaluate the effectiveness of reducing LDL-C/HDL-C ratio treatment on the development of high CIMT.

Ethnopharmacological relevance Astragali radix (Huang Qi, HQ), a well-known Chinese herbal medicine, is widely coadministered with many other drugs for treating diseases. The potential herb–drug interactions (HDIs) possibly occur during the combination therapy. P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are the crucial targets that mediate the production of HDIs. We previously observed that HQ and its three main bioactive compounds, including Astragaloside IV (AS-IV), calycosin (CS) and formononetin (FMNT), could significantly induce the expression of P-gp and BCRP in HepG2 cells in vitro. However, their modulations on the function of P-gp and BCRP remain unknown; their impact on these two proteins expression in vivo is not clear; the exact regulatory mechanism has also not yet been explored. Aim of the study This study aimed to investigate the impact of HQ, AS-IV, CS and FMNT on P-gp and BCRP in vivo, and the exact regulatory mechanism involved. The effects of HQ and these compounds on the function of P-gp and BCRP were also studied. Materials and methods Wild-type C57BL/6 mice and nuclear factor E2-related factor-2 knockout (Nrf2−/−) C57BL/6 mice were orally treated with HQ, AS-IV, CS or FMNT. The protein levels of P-gp and BCRP in the liver of mice were measured by using Western blot and immunohistochemistry. The mRNA levels were measured by using real-time PCR. The activation of the drugs on the antioxidant response element (ARE)–luciferin activity was studied by using reporter assay in a stably transfected HepG2-C8 cells. The efflux activity of P-gp and BCRP in HepG2 cells were tested by using flow cytometer with typical probes. Results HQ, AS-IV, CS and FMNT significantly upregulated the P-gp and BCRP expression in the liver of wild-type mice. The induction was significantly reversed in the Nrf2−/− mice. HQ and these compounds significantly increased the Nrf2 expression in wild-type mice. HQ and these compounds also markedly enhanced the ARE-luciferin activity and promoted the nuclear translocation of Nrf2 in cells. Besides, HQ and these compounds significantly enhanced the efflux activity of P-gp and BCRP, and increased the intracellular ATP levels. Conclusions Our results proved that HQ and its main bioactive compounds could induce the P-gp and BCRP expression through the activation of the Nrf2-mediated signaling pathway. HQ and these compounds also significantly enhanced the efflux activity of P-gp and BCRP, and the increased intracellular ATP levels were likely involved in the increased P-gp and BCRP function. These results suggested that potentially HDIs likely occurred when HQ was used concomitantly with other drugs that are substrates of P-gp and BCRP.

To examine the association between blood urea nitrogen (BUN) and risk of type 2 diabetes (T2DM) among Chinese adults, we performed an ongoing cohort study of 38578 Chinese adults (56.3% males; average age, 41.6 y) who underwent repeated health check-up examinations between 2009 and 2016 and without T2DM at baseline. During follow-up, incident T2DM cases were identified based on self-report, medication use, measurements of fasting plasma glucose, 2 h post oral glucose, or haemoglobinA1c. 2009 (5.2%) cases confirmed with incident T2DM were identified during median follow-up of 3.1 years. With increasing quartiles of BUN levels, the incidences of T2DM gradually increased with 0.69%, 1.11%, 1.53%, and 1.87% for quartile 1 to quartile 4 (p trend

Hepatic fibrosis (HF) represents the excessive wound healing where an excess amount of connective tissues is formed within the liver, finally resulting in cirrhosis or even hepatocellular carcinoma (HCC). Therefore, it is significant to discover the efficient agents and components to treat HF, thus restraining the further progression of hepatopathy. Astragalus membranaceus (Fisch.) Bunge [also called Astragali Radix (AR)] is a famous herb in traditional Chinese medicine (TCM), which possesses a variety of biological activities and exerts good therapeutic effects in the treatment of HF. Flavonoids account for the major active ingredients related to the AR pharmacological effects. Total AR flavonoids have been proved to exert inhibitory effects on hepatic fibrosis. This study aimed to further undertake network pharmacology analysis coupled with experimental validation and molecular docking to investigate the effects and mechanism of multiple flavonoid components from AR against liver fibrosis. The results of the network pharmacology analysis showed that the flavonoids from AR exerted their pharmacological effects against liver fibrosis by modulating multiple targets and pathways. The experimental validation data showed that the flavonoids from AR were able to suppress transforming growth factor beta 1 (TGF-β1)-mediated activation of hepatic stellate cells (HSCs) and reduce extracellular matrix deposition in HSC-T6 cells via regulating the nuclear factor kappa B (NF-κB) signal transduction pathway. The results of the molecular docking study further showed that the flavonoids had a strong binding affinity for IκB kinase (IKKβ) after docking into the crystal structure. The above results indicated that, flavonoids possibly exerted the anti-inflammatory effect on treating HF by mediating inflammatory signaling pathways. The potential mechanism of these flavonoids against liver fibrosis may be related to suppression of the NF-κB pathway through effective inhibition of IKKβ. This study not only provides a scientific basis for clarifying the effects and mechanism of AR flavonoids against liver fibrosis but also suggests a novel promising therapeutic strategy for the treatment of liver fibrosis.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insulin deficiency due to pancreatic β-cell damage and leads to hyperglycemia. The precise molecular mechanisms of the etiology of T1DM are not completely understood. Oxidative stress and the antioxidant status of pancreatic β-cells play a vital role in the pathogenesis and progression of T1DM. The Keap1/Nrf2 signaling pathway plays a critical role in cellular resistance to oxidative stress. This study is aimed at investigating the role of the Keap1/Nrf2 signaling pathway in the progression of T1DM. An alloxan- (ALX-) stimulated T1DM animal model in wild-type (WT) and Nrf2 knockout (Nrf2-/-) C57BL/6J mice and a mouse pancreatic β-cell line (MIN6) were established. Compared with the tolerant (ALX exposure, nondiabetic) WT mice, the sensitive (ALX exposure, diabetic) WT mice exhibited higher blood glucose levels and lower plasma insulin levels. The Keap1/Nrf2 signaling pathway was significantly inhibited in the sensitive WT mice, which was reflected by overexpression of Keap1 and low expression of Nrf2, accompanied by a marked decrease in the expression of the antioxidative enzymes. Compared with WT mice, the Nrf2-/- mice had an increased incidence of T1DM and exhibited more severe pancreatic β-cell damage. The results of in vitro experiments showed that ALX significantly inhibited the viability and proliferation and promoted the apoptosis of MIN6 cells. ALX also markedly increased intracellular ROS production and caused DNA damage in MIN6 cells. In addition, the Keap1/Nrf2 signaling pathway was significantly inhibited in the damaged MIN6 cells. Moreover, Nrf2 silencing by transfection with Nrf2 siRNA markedly exacerbated ALX-induced MIN6 cell injury. Conclusively, this study demonstrates that inhibition of the Keap1/Nrf2 signaling pathway could significantly promote the incidence of T1DM. This study indicates that activation of Keap1/Nrf2 signaling in pancreatic β-cells may be a useful pharmacological strategy for the clinical prevention and treatment of T1DM.

Aim The aim of this study is to investigate the sex-specific association between the ZJU index and risk of fatty liver disease in a large Chinese cohort. Methods A total of 28 729 adults without fatty liver disease at baseline and who completed at least one follow-up of annual examinations between 2009 and 2016 were included in this study. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for fatty liver disease risk associated with the ZJU index. Results During a median follow-up of 3.01 years, 7373 developed fatty liver disease. There were significant associations between the ZJU index and fatty liver disease for women and men with increasing HRs as the quartiles increase across Q2-Q4, corresponding HRs (95% CIs) in M3 were 2.28 (1.98-2.64), 3.52 (3.07-4.04), and 4.87 (4.24-5.59) for women and 2.44 (2.17-2.75), 4.18 (3.73-4.68), and 6.23 (5.56-6.98) for men. The association between the ZJU index and fatty liver disease risk remained significant in all the subgroups except that of T2DM and abdominal obesity subgroups for men. However, the association became nonsignificant when comparing Q3 and Q2 of the ZJU index with reference in the subgroups of T2DM for men, and nonsignificant when comparing Q3 of the ZJU index with reference in the subgroups of participants with T2DM and abdominal obesity for women. Conclusion The ZJU index was significantly associated with the risk of fatty liver disease in Chinese population. It will be better to keep body mass index, alanine aminotransferase, aspartate aminotransferase, triglyceride, and fasting plasma glucose at a normal level for preventing fatty liver disease.

BACKGROUND The association of ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C ratio) change trajectory with risk of type 2 diabetes mellitus (T2DM) remains unknown. The aim of this study was to evaluate the association between risk of T2DM and TG/HDL-C ratio change trajectory. METHODS A total of 18 444 participants aged 18-80 years old were included in this cohort study. Linear regression and quadratic regression models were used to determine the TG/HDL-C ratio change trajectory. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TG/HDL-C ratio change trajectory and probability of T2DM. RESULTS T2DM developed in 714 participants during a median follow-up of 5.74 years (92 076.23 person-years of follow-up). After adjusting for baseline potential confounders, odds of T2DM were greater for participants with the increasing, U-shape, bell-shape, and other shape change vs decreasing change (adjusted OR [aOR] 2.01, 95% CI 1.42-2.81; 1.56, 1.15-2.13; 1.60, 1.17-2.20; and 1.49, 1.13-2.00, respectively). The results were robust in the sensitivity analyses on excluding baseline participants with T2DM. Moreover, the associations remained significant with male sex, age

Background The discordance of the low-density lipoprotein cholesterol-to-high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with alterative lipid parameters may explain the inconsistent association of CIMT with the LDL-C/HDL-C ratio. Therefore, this study aimed to explore the associations between LDL-C/HDL-C ratio discordance with alternative lipid parameters and elevated carotid intima-media thickness (CIMT) risk in a large cohort in Beijing, China. Methods In total, 13,612 adults who didn’t have elevated CIMT at baseline and who participated in at least one follow-up of annual examination between 2009 and 2016 were included in this cohort study. A multivariable Cox regression model was utilized to evaluate the associations of discordance of the LDL-C/HDL-C ratio with TC, TGs, LDL-C and HDL-C with elevated CIMT risk. Results During 37,999 person-years of follow-up, 2004 individuals (1274 men and 730 women) developed elevated CIMT. Among individuals with normal TC and TGs, 16.6 and 15.2% individuals had a discordantly high LDL-C/HDL-C ratio, respectively, and the risk of elevated CIMT increased by 1.54 (95% CI 1.33, 1.77) and 1.53 (95% CI 1.33, 1.76), respectively, comparing to individuals with a concordantly low LDL-C/HDL-C ratio. A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with LDL-C and HDL-C (P Conclusions A high LDL-C/HDL-C ratio could significantly increase elevated CIMT risk regardless of discordance/concordance with TC, TGs, LDL-C and HDL-C Even a low LDL-C/HDL-C ratio with discordantly high LDL-C and normal HDL-C could also significantly increase CIMT risk. Individuals should maintain both the LDL-C/HDL-C ratio and LDL-C at normal levels to prevent elevated CIMT.

BACKGROUND The study aimed to investigate the associations of baseline serum albumin level and its dynamic change with type 2 diabetes mellitus (T2DM) risk in a large Chinese cohort study. METHODS This cohort study included 30 442 adults without T2DM at first entry, who completed at least one follow-up of annual examinations between 2009 and 2016. Serum albumin level was measured at baseline and at every annual check-up. The dynamic change in serum albumin level (∆ALB) was calculated by subtracting serum albumin level at baseline from that at the last follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox regression models. RESULTS During 7 years of follow-up, we identified 1634 T2DM events. From the lowest to the highest quartile of serum albumin level, adjusted HRs (95% CI) were 1.00 (reference), 0.96 (0.94, 1.01), 0.98 (0.95, 1.02) and 0.88 (0.85, 0.98), respectively. As compared with stable change in serum albumin (-0.2 ≤ ∆ALB

Additional file 1: Supplementary Table 1. Association between LDL-C/HDL-C ratio concordance with TC and CIMT risk in the subgroup analyses. Supplementary Table 2 Association between LDL-C/HDL-C ratio concordance with TG and CIMT risk in the subgroup analyses. Supplementary Table 3 Association between LDL-C/HDL-C ratio concordance with LDL-C, HDL-C and CIMT risk in the subgroup analyses.

Background. Conflicting findings have been reported regarding the sex-specific association between serum uric acid (SUA) level and type 2 diabetes mellitus (T2DM) risk, and no study has explored the association between the change in hyperuricemia status and T2DM risk. The study was aimed at exploring the sex-specific association of baseline SUA and changes in hyperuricemia status with T2DM risk. Methods. We included 37,296 eligible adults without T2DM at the first examination who attended the baseline examination and at least one follow-up annual examination. Cox and logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) for T2DM risk associated with baseline SUA and the change in hyperuricemia status, respectively. Results. During a median follow-up of 3.09 years, of 37,296 eligible adults, 2,263 developed T2DM. Compared with the first SUA quartile, higher quartiles were associated with an increased risk of T2DM in women (HR 1.78, 95% CI 1.17-2.71 for Q3 and 1.93, 1.27-2.93 for Q4; Ptrend<0.001) but not in men. Compared with women with a persistent normal SUA level at baseline and the last follow-up, T2DM risk increased significantly among those whose SUA status changed from normal at baseline to hyperuricemia at the last follow-up (OR 1.71, 95% CI 1.12-2.55) and those with persistent hyperuricemia at baseline and the last follow-up (OR 2.37, 95% CI 1.60-3.46). However, for men, a nonsignificant association was found between the change in hyperuricemia status and T2DM risk. Conclusions. Baseline SUA and the change in hyperuricemia status were associated with T2DM risk only among women. The findings suggest the importance of monitoring SUA levels and maintaining them within a normal range for preventing or reducing incident T2DM in Chinese women.

This study aims to investigate the association between serum creatinine and risk of type 2 diabetes mellitus (T2DM) based on a cohort analysis and meta-analysis of cohort studies.We enrolled 41 439 participants aged ≥18 years without T2DM at baseline, who had ≥2 health examinations based on an ongoing prospective cohort in Beijing. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% CIs. For the meta-analysis, cohort studies reporting risk estimates for the serum creatinine-T2DM association were included. A random-effects model was used to calculate summary relative risks (RRs) and restricted cubic splines to model the dose-response association.During a mean follow-up of 3.54 years, 1867 developed T2DM. Low serum creatinine was associated with increased risk of T2DM; adjusted HRs (95% CIs) across sex-specific quartiles were 1.45 (1.24, 1.71), 1.19 (1.02, 1.39), 1.07 (0.92, 1.24), and 1.00 (reference). The association was significant for both sexes and individuals with overweight or obesity. In the meta-analysis of six cohort studies (including the current study) involving 115 767 participants and 5370 T2DM events, the pooled RR was 1.61 (95% CI 1.35, 1.92), comparing the lowest with the highest category of serum creatinine. We found a linear association between serum creatinine and T2DM risk (PThe cohort study and meta-analysis provide further evidence supporting the negative association between serum creatinine and T2DM risk in a linear dose-response pattern.背景: 本研究旨在通过队列研究和纳入队列研究的meta分析, 探讨血肌酐与2型糖尿病(Type 2 diabetes mellitus, T2DM)风险之间的关联。 方法: 本研究纳入了41439名年龄≥18岁, 在基线时未患有T2DM, 且进行了2次以上健康体检在北京的参与者。采用Cox比例风险回归来估计风险比(hazard ratios, HRs)和95%置信区间(confidence intervals, CIs)。Meta分析纳入的研究为报道血肌酐与T2DM关联的风险估计的队列研究。采用随机效应模型估计相对危险度(Relative risk, RR), 限制性立方样图拟合剂量-反应关系。 结果: 在平均3.54年的随访中, 有1867例T2DM新发病例。血肌酐过低明显增加了患T2DM的风险；性别特定的四分位数(Q1-Q4)的校正HR(95% CI)为1.45(1.24, 1.71), 1.19(1.02, 1.39), 1.07(0.92, 1.24)和1.00(参照组)。该关联在不同性别和超重/肥胖者中均显着相关。Meta分析共纳入6项队列研究(包括本研究), 共包含115,767名参与者和5,370例T2DM病例。将最低与最高的血肌酐水平进行比较, RR为1.61(95% CI 1.35, 1.92)。血肌酐和T2DM风险之间呈线性关联(P

Background Lung cancer remains the most common cause of cancer-related deaths, with a high incidence and mortality in both sexes worldwide. Chemoprevention has been the most effective strategy for lung cancer prevention. Thus, exploring novel and effective candidate agents with low toxicity for chemoprevention is essential and urgent. Houttuynia cordata Thunb. (Saururaceae) (H. cordata), which is a widely used herbal medicine and is also popularly consumed as a healthy vegetable, exhibits anti-inflammatory, antioxidant and antitumor activity. However, the chemopreventive effect of H. cordata against benzo(a)pyrene (B[a]P)-initiated lung tumorigenesis and the underlying mechanism remain unclear. Methods A B[a]P-stimulated lung adenocarcinoma animal model in A/J mice in vivo and a normal lung cell model (BEAS.2B) in vitro were established to investigate the chemopreventive effects of H. cordata and its bioactive compound 2-undecanone against lung tumorigenesis and to clarify the underlying mechanisms. Results H. cordata and 2-undecanone significantly suppressed B[a]P-induced lung tumorigenesis without causing obvious systemic toxicity in mice in vivo. Moreover, H. cordata and 2-undecanone effectively decreased B[a]P-induced intracellular reactive oxygen species (ROS) overproduction and further notably protected BEAS.2B cells from B[a]P-induced DNA damage and inflammation by significantly inhibiting phosphorylated H2A.X overexpression and interleukin-1β secretion. In addition, H. cordata and 2-undecanone markedly activated the Nrf2 pathway to induce the expression of the antioxidative enzymes heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Nrf2 silencing by transfection with Nrf2 siRNA markedly decreased the expression of HO-1 and NQO-1 to diminish the reductions in B[a]P-induced ROS overproduction, DNA damage and inflammation mediated by H. cordata and 2-undecanone. Conclusions H. cordata and 2-undecanone could effectively activate the Nrf2-HO-1/NQO-1 signaling pathway to counteract intracellular ROS generation, thereby attenuating DNA damage and inflammation induced by B[a]P stimulation and playing a role in the chemoprevention of B[a]P-induced lung tumorigenesis. These findings provide new insight into the pharmacological action of H. cordata and indicate that H. cordata is a novel candidate agent for the chemoprevention of lung cancer. Electronic supplementary material The online version of this article (10.1186/s13046-019-1255-3) contains supplementary material, which is available to authorized users.

Figure S1. The GC-FID chromatogram of standard compound 2-undecanone (A) and H.cordata water extract (B). Figure S2. Representative images showing haematoxylin and eosin staining of lung samples from the different groups. Figure S3. Effects of B[a]P on viability of BEAS-2B cells. Cell viability was examined using the MTT assay. The data represent the mean ± SD (n = 3). #p < 0.05 and ###p < 0.001 compared with the control cells (given water). Figure S4. Pairwise correlation between reduction in B[a]P-induced ROS over production and decreased p-H2A.X protein levels ratio in BEAS-2B cells by H. cordata (A) and 2-undecanone (B). The correlations were analyzed by using Person analysis. Figure S5. Pairwise correlation between reduction in B[a]P-induced ROS over production and decreased protein levels of pro-IL-1β or IL-1β in BEAS-2B cells by H. cordata (A) and 2-undecanone (B). The correlations were analyzed by using Person analysis. Figure S6. The efficiency of Nrf2 silencing. Nrf2 expression was silenced in BEAS-2B cells by transfection of three Nrf2-specific siRNA (siNrf2-1, siNrf2-2 or siNrf2-3), respectively. The protein levels of Nrf2 were evaluated by using Western blot analysis. Data shown represent the mean ± SD (n = 3). ***p < 0.001 compared with the cells transfected with the control siRNA (siCtrl). siNrf2-1 and siNrf2-2 were selected for subsequent assays according to the efficiency of Nrf2 silencing. (DOCX 7901 kb)

IntroductionBrachial-ankle pulse wave velocity (ba-PWV), as a simple and easily measured marker of arterial stiffness, has not been prospectively explored for its role in type 2 diabetes mellitus (T2DM) risk among the general population. This study aimed to explore the association between baseline ba-PWV value and new-onset T2DM among Chinese adults.Research design and methodsUsing data from Xiaotangshan Hospital, we conducted a prospective cohort study among those who underwent annual or biennial health check-up examinations and who had their ba-PWV measured from 2009 to 2016. We explored the risk of new-onset T2DM across ba-PWV tertiles using Cox proportional-hazards regression analysis.ResultsOf 6122 adults (68.9% male; mean age: 51.0 (SD 13.0) years) without T2DM and with ba-PWV measured at baseline, 599 participants developed T2DM during an average of 3.8 (SD 2.3) years of follow-up. After multivariable adjustment, ba-PWV was positively related to T2DM risk (p for trend=0.008). Compared with the lowest ba-PWV tertile, the HRs and their 95% CIs were 1.57 (1.18 to 2.10) for the second and 1.66 (1.24 to 2.22) for the third tertile. The risk across ba-PWV tertiles increased steadily from 1000 cm/s to 1400 cm/s and then reached a plateau. Subgroup analyses indicated a significantly higher risk among those aged ConclusionsOur findings suggest that ba-PWV might be a useful and independent predictor of new-onset T2DM with ba-PWV ranging between 1000 cm/s and 1400 cm/s, especially among younger individuals and current smokers.

Background High prevalence of metabolic diseases among young professional athletes with large body sizes has raised growing attention. However, few studies specifically examined whether additional aerobic exercise provides cardiometabolic beneficial effect among these young athletes under regularly intensive strength training. Objective We conducted a pilot trial to evaluate the effects of aerobic exercise on overall metabolic syndrome (MetS), individual MetS components, and aerobic capacity among metabolically unhealthy athletes in the heaviest-weight class. Methods Forty-nine professional athletes aged 15–30 years had large body weights (mean weight of 131 ± 15.5 kg and 108 ± 15.8 kg and mean BMI of 39.4 ± 4.7 kg/m2 and 36.4 ± 5.1 kg/m2 for 26 men and 23 women, respectively). They completed a supervised moderate intensity (maximal heart rate: 140–170 beats/min for 30–70 min/day) aerobic exercise training for 12 weeks. We collected and measured metabolic parameters and aerobic capacity for all participants before and after 12 weeks of aerobic exercise training. Results At baseline, 42 (86 %) of all 49 metabolically abnormal athletes were diagnosed as MetS according to the NCEP ATP III criteria (≥3 MetS components). After aerobic exercise training, 30 % (13/42) of MetS individuals tended to become free of MetS (