Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objective To observe the effect of rat bone marrow mesenchymal stem cells(BMSCs)on the apoptosis of rat peritoneal mesothelium cells(PMCs)induced by high glucose peritoneal dialysis fluid(PDF),and to explore its possible molecular mechanism.Methods The primary BMSCs and PMCs were extracted and identified.Apoptosis of PMCs was induced by high glucose PDF.Cell supernatant from BMSCs after 24 h of culture was collected as the conditioned medium(BMSCs-CM).PMCs were co-cultured with BMSCs by conditioned media or Transwell chambers.PMCs were randomly divided into the control group,the PDF group and the PDF+BMSCs-CM group.The viability of PMCs was measured by CCK-8 in each group.The depolarization of mitochondrial membrane potential was measured by JC-1 method.TUNEL staining was used to detect cell apoptosis.Western blot assay was used to detect the expression levels of apoptosis related proteins B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),Cleaved cysteine aspartase-3(Cleaved Caspase-3)and pathway related protein serine/threonine protein kinase(Raf),mitogen-activated extracellular signal-regulated kinase(MEK),extracellular-signal regulated protein kinase(ERK)and their phosphorylated proteins in each group.Results Compared with the control group,the proliferative activity and mitochondrial membrane potential of PMCs were decreased in the PDF group,while the apoptosis rate and the ratio of Bax/Bcl-2,Cleaved Caspase-3/Caspase-3,p-Raf/Raf,p-MEK/MEK and p-ERK/ERK were increased(P＜0.05).Compared with the PDF group,the proliferative activity and mitochondrial membrane potential of PMCs were increased in the PDF+BMSCs-CM group,while the apoptosis rate and the ratio of Bax/Bcl-2,Cleaved Caspase-3/Caspase-3,p-Raf/Raf,p-MEK/MEK and p-ERK/ERK were decreased(P＜0.05).Conclusion BMSCs can reduce the apoptosis of PMCs induced by high glucose PDF,and its mechanism maybe related to inhibiting the activation of Raf/MEK/ERK signaling pathway.

Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.

Background Tear meniscus gained by OCT device is essential to the dry eye diagnosis.Currently,RTVue Fourier-domain optical coherence tomography (FD-OCT) is commercially available to image the tear menisci.However,there were few studies to report the repeatability and reproducibility of lower and upper tear meniscus parameters measured by RTVue FD-OCT.Objective The purpose of this study was to assess the repeatability and reproducibility of lower and upper tear meniscus parameters measured by RTVue FD-OCT in normal and dry eyes.Methods In this prospective study,20 dry eyes of 20 patients were finally recruited,and 20 normal eyes of 20 age-and gender-matched healthy subjects were included during the same period.Successive three-time scans were performed at a 3-minute interval with RTVue FD-OCT in optional eye by one well-trained examiner,and the other operator performed the same measurement 10-15 minutes later.Six parameters of tear meniscus were yielded by custom software,including upper meniscus curvature (UMC),upper meniscus height(UMH),upper meniscus area (UMA),lower meniscus curvature (LMC),lower meniscus height (LMH) and lower meniscus area (LMA).The between-image repeatability was assessed using mean coefficient of repeatability (MCOR),while between-operator reproducibility were evaluated using coefficient of repeatability (COR) and interclass correlation of coefficients (ICC).Results As for the between-image repeatability,the results of MCOR for UMH,UMA,LMH and LMA were 5.11％,3.58％,4.98％ and 4.82％ respectively in the normal eyes and 5.60％,5.80％,5.03％ and 5.74％ respectively in the dry eyes.As for the between-operator reproducibility,the results of COR and ICC for UMA were 5.38％ and O.975,the COR and ICC for LMA were 5.28％ and 0.961 respectively in the normal eyes,and the results of COR and ICC for LMA were 9.69％ and 0.964 in the dry eyes.Conclusions The UMA,LMH and LMA tear meniscus parameters obtained by RTvue FD-OCT show good between-image repeatability,and LMA also presents good between-operator reproducibility.Measurement of tear meniscus parameters with RTVue FD-OCT measuring is a potential diagnostic index for the diagnosis of dry eye.

15.6 ?mol/L. Group B, 55 cases, Hcy≤15.6 ?mol/L). The Hcy, FBG, TC, TG, HDL-C, LDL-C, LP(a) and UA of both groups were compared. Results The concentration of FBG,LP(a) and UA of group A was higher than that of group B (P

Objective To observe the effect of Astragalus Injection(AI) on aquaporin-1(AQP-1) expression of peritoneal mesothelial cells in rats with peritoneal dialysis.Methods Twenty-five male SD rats were divided into the normal control group(N =7),model group(N =9) and AI group(N =9).Except the normal control group,the model group was given intraperitoneal injection of peritoneal dialysate(containing glucose 42.5 g/L),and AI group was given intraperitoneal injection of peritoneal dialysate(containing glucose 42.5 g/L) plus AI(20 mg/mL),25mL/d for 10 continuous days.On the 11th day of experiment,the amount of dialysis ultrafiltration(UF) and net UF,and the concentration ratio of dialysate and plasma sodium(D/PNa) were measured,peritoneal pathological changes were observed with light microscope,and the expression of AQP-1 in peritoneal mesothelial cells was detected with immunohistochemical method.Results When the peritoneal dialysate was kept in the abdominal cavity for 60 min,the amount of UF and Net UF was increased in AI group(P