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Background longitudinal evidence concerning frailty phenotype and the risk of cardiovascular disease (CVD) remained insufficient, and whether CVD preventive strategies exert low CVD risk on frail adults is unclear. Objectives we aimed to prospectively evaluate the association of frailty phenotype, adherence to ideal cardiovascular health (CVH) and their joint associations with the risk of CVD. Methods a total of 314,093 participants from the UK Biobank were included. Frailty phenotype was assessed according to the five criteria of Fried et al.: weight loss, exhaustion, low physical activity, slow gait speed and low grip strength. CVH included four core health behaviours (smoking, physical activity and diet) and three health factors (weight, cholesterol, blood pressure and glycaemic control). The outcome of interest was incident CVD, including coronary heart disease, heart failure and stroke. Results compared with the non-frail people whose incident rate of overall CVD was 6.54 per 1,000 person-years, the absolute rate difference per 1,000 person-years was 1.67 (95% confidence interval, CI: 1.33, 2.02) for pre-frail and 5.00 (95% CI: 4.03, 5.97) for frail. The ideal CVH was significantly associated with a lower risk of all CVD outcomes. For the joint association of frailty and CVH level with incident CVD, the highest risk was observed among frailty accompanied by poor CVH with an HR of 2.92 (95% CI: 2.68, 3.18). Conclusions our findings indicate that physical frailty is associated with CVD incidence. Improving CVH was significantly associated with a considerable decrease in CVD risk, and such cardiovascular benefits remain for the frailty population.

Mycobacterium tuberculosis (Mtb), a typical intracellular parasite that cause tuberculosis (TB), which rank the top infectious killer for human death. Pathogenic mycobacterium has evolved numerous strategies to favor their intracellular survival including a unique lipid-rich cell wall component and granuloma formation during early infection [1]. Phthiocerol dimycocerosate (PDIM) is a critical virulence factor of mycobacteria including Mycobacterium marinum (Mm), which manipulate host immune responses and granuloma induction and facilitate immune evasion [2-7], but the mechanisms are still remains questionable. We used an AACT/SILAC-based quantitative proteomic approach to determine PDIM-responded proteome profiles during Mm early infection. A major difference was the high abundance of galectin3 (Gal-3) in WT Mm-infected cells and not with PDIM-deficient. Gal-3 induction by PDIM-replete bacteria was primarily via Toll-like receptor 2, and also engaged TGF-β non-classical pathway. Elevated Gal-3 in macrophages prevented the turnover and translocation of NF-κB to effectively modulate the profile of inflammatory cytokines. Silencing of Gal-3 effectively relieved tissue damage induced in mice by PDIM-expressing Mm. We found upregulated Gal-3 in the serum and BALF of confirmed clinical tuberculosis cases, while decreased significantly after effective chemotherapy. Our findings demonstrated that upregulated Gal-3 not only plays an important role in regulating host immune response and granuloma formation in vivo, but also that target-Gal-3 therapy is a promising anti-tuberculosis strategy in the future. Funding Statement: This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 31772709 and 31572485 to D.W), the new faculty startup research fund of China Three Gorges University (KJ2014B023 to D.W), Health Commission of Hubei Province in China (WJ2019H528 to D.W; WJ2019F080 to D.L), and in part by the intramural research program of NIAID, NIH (Bethesda MD, USA). Z.L was supported by grants from the China’s 13th Five Year Programs for the prevention and cure of great infectious diseases (2017ZX10201301-005) and Open Fund of Shanghai Key Laboratory of Tuberculosis (2018kf03). XY.Fan is the recipient of National Natural Science Foundation of China (31771004). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: The case-control study of TB was reviewed and approved by the Ethics Committee of the Third People’s Hospital of Yichang (2017008H). Written informed consent was obtained from all participants. The animal experiments were reviewed and approved by the Animal Care and Use Committee of China Three Gorges University (2017010M).

Background: Chemoprevention of colorectal adenoma and cancer remains its importance in public health. The rate of adenoma recurrence in the first year after polypectomy is very high in East Asian populations. We aimed to investigate the clinical potential and safety of Berberine hydrochloride for colorectal adenoma recurrence. Methods: This double-blind, randomised, placebo-controlled clinical trial was done in seven hospital centers across six provinces in China. Patients with recently diagnosed adenomas and after complete polypectomy were recruited and randomized into a BBR group (Berberine hydrochloride 0.3g, twice daily) or a placebo group. They were anticipated for at least one follow-up colonoscopy until a diagnosis of CRA/CRC or the last enrolled patient reached the 2-year follow-up. The primary efficacy endpoint was the recurrence of adenomas at any follow-up colonoscopy. The secondary outcomes were the recurrences of polypoid lesions as well as advanced adenomas or CRC. Findings: Between Nov 14, 2014 and Dec 29, 2018, 1136 patients were screened for eligibility, and 1108 underwent randomization. 553 patients were assigned to receive Berberine hydrochloride and 555 to placebo. An unadjusted RR for recurrent adenomas and all polypoid lesions were 0.77 (95% CI, 0.66 to 0.91) and 0.77 (95% CI, 0.67 to 0.89), representing a decrease of 22.72% and 22.70%, respectively. No CRC occurred during the whole trial. Interaction test showed taking BBR was effective in female with unadjusted RR for recurrent adenomas of 0.58 (95% CI, 0.41 to 0.81); P=0.07 (Alpha = 0.10). No serious adverse events were reported. Interpretation: Although the mechanism has not been fully elucidated yet, Berberine hydrochloride was effective to reduce colorectal adenoma recurrence after polypectomy. Trial Registration: This trial is registered with ClinicalTrials.gov number NCT02226185. Funding Statement: This project was supported by grants from the National Natural Science Foundation of China (81421001, 81530072, 81830081 and 8177100232), the funds from Shanghai Shenkang Center (SHDC12018121), from Shanghai Municipal Key Clinical Specialty, and from Innovative research team of high-level local universities in Shanghai. The project was also partially supported by Top-Notch project of China and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant (20152514). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Approval for this study was obtained from the Ethics Committee of Renji Hospital, Shanghai Jiao-Tong University School of Medicine on 13th August 2014. The protocol and informed consent forms were also approved by the institutional ethics committees at each of the participating clinical centers.

Baicalin is a flavone glycoside that possess numerous pharmacological properties including anti-inflammatory, anti-cancer and anti-pruritic effects. Based on these properties, we investigated whether baicalin could be used to alleviate kidney fibrosis induced by diabetes mellitus. Using a streptozotocin (STZ)-induced diabetic mouse model, we found that baicalin treatment could suppress diabetes-enhanced water consumption, urine volume production, blood urea nitrogen (BUN), serum creatinine and urinary albumin/urinary creatinine (UACR). Correspondingly, baicalin treatment could significantly maintain the morphology of the glomerulus and renal tubules in diabetes-induced kidney lesions by repressing WT1 and Nephrin expressions in the glomeruli, as well as LTL, caspases-9 and Fas expressions in the renal tubules. We also determined that baicalin could suppress inflammation responses and reduced MDA activities that were enhnaced by diabetes while increasing SOD, CAT, GPX and Nrf2 expressions that were inversely lowered. We demonstrated the presence of interstitial fibrosis in the diabetic kidney but this could be alleviated by baicalin which downregulated ɑ-SMA and TGF-β1 expressiond (key pro-fibrotic markers). We investigated Klotho a transmembrane protein that is expressed by renal tubule epithelial cells. Secreted form of Klotho could bind to TGF-β1 receptors and block the TGFβ1 signaling pathway. We determined that hypermethylation of the Klotho promoter plays an important role in baicalin's ability to rescue renal fibrosis induced by diabetes mellitus. In sum, our results showed that baicalin could alleviate renal fibrosis-induced by diabetes through partly modulating Klotho promoter methylation. Funding Statement: This study was supported by NSFC grant (31771331, 81741016), Science and Technology Planning Project of Guangdong Province (2017A050506029, 2017A020214015, 2016B030229002), Science and Technology Program of Guangzhou (201710010054), Guangdong Natural Science Foundation (2016A030311044), Project of National University Students "Challenge Cup" (18112003). Declaration of Interests: The authors declare that there are no competing financial interests. Ethics Approval Statement: This study was carried out in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Animal Ethic Committee at Jinan University.

The effect of technology spillovers is widely considered as one of the main channels through which domestic firms benefit from FDI (Foreign Direct Investments), and plays an important role in economic development of host countries. FDI is expected to generate technology spillovers to indigenous firms in transition economies. This paper will analyse and try to figure out the development patterns of ASEAN (Association of Southeast Asian Nations) by utilizing time-series data between 1990 and 2008 in ASEAN countries. The empirical results render a support to the existence of technology spillovers in ASEAN, which have a positive effect on the economic development of ASEAN. The regression results also suggest that it is necessary to combine FDI technology spillovers with domestic human capital, that is, in the process of promoting economic development, factors such as skilled labour force and sophisticated infrastructure are crucial. China’s FDI in ASEAN requires lower education threshold, also has positive effect on economy growth in six countries of ASEAN.