Objective To investigate the protective effect of Vitamin D (VitD) on diabetic rats,and whether the protective mechanism is associated with the expression of nuclear factor kappa B (NF-κB) and insulin resistance (IR).Methods Diabetic Wistar rats were established by intraperitoneal injection of streptozotocin,and randomly divided into diabetic group,VitD treatment group (treatment group).Normal rats were served as normal control group.Treatment group was treated with VitD for 8 weeks.The levels of 24 h urinary protein (24 h UP),fasting plasma glucose (FPG),plasma insulin (p-Ins),plasma adiponectin (p-Adi),plasma glucagon (p-Gln) were measured.Tumor necrosis factor alpha (TNF-α),monocyte chemotactic protein 1 (MCP-1),interleukin-6 (IL-6) were determinated in renal cortical homogenate.The activity of NF-κB was evaluated by electrophoretic mobility shift assay.The mRNA expressions of glucose transporter protein 1 (GLUT1) and GLUT4 in renal cortex were detected by reverse transcriptase (RT)-PCR.Western blot analysis was performed to measure the phosphorylation of NF-κB and its inhibitor I kappa Balpha (IκBα),insulin receptor substrate protein 1 (IRS1),phosphatidylinositol 3 kinase (PI3K),p38 mitogen activated protein kinase (p38MAPK).Results Compared with the normal control group,24 h UP,FPG,p-Ins,p-Gln were significantly increased,and inflammatory markers and the expression of GLUT1 elevated in renal cortex in DM group,there were significant differences(all P ＜0.01).The activity of NF-κB (P ＜0.01) and the phosphorylation of NF-κB p65 and p38MAPK were elevated (all P ＜ 0.01),and phosphorylation of IκBα,IRS1,PI3K were decreased (all P ＜ 0.05,0.01) in diabetic group compared with those of normal control group.VitD treatment could ameliorate urine protein,increase p-Adi,reduce inflammatory markers and NF-κB activity (P ＜ 0.01),maintain GLUT1 expression,but had no effect on GLUT4 expression in renal cortical,attenuate NF-κB p65,p38MAPK phosphorylation (all P ＜ 0.05),partly restore IκBα,IRS1,PI3 K phosphorylation in diabetic rats (all P ＜ 0.05,0.01).Conclusions Protective role of VitD is associated with inhibiting the expression of NF-κB and reducing the insulin resistance in diabetes.

OBJECTIVE:To establish a method of simultaneous determination of inulicin and deacetylinulicin in Inulae Flos. METHODS:HPLC was performed on the column of Zorbax SB-C18 with mobile phase of acetonitrile-water(gradient elution)at a flow rate of 1.0 ml/min,the column temperature was 25 ℃,the detection wavelength was 210 nm,and the injection volume was 10 μl. RESULTS:The linear range was 0.000 2-0.005 μg/ml(r=0.999 8)for inulicin and 0.000 1-0.001 7 μg/ml(r=0.999 4)for deacetylinulicin;RSDs of precision,stability and reproducibility tests were lower than 2.0%;recoveries were 99.63%-103.56%(RSD=1.26%,n=9)and 95.98%-101.21%(RSD=1.84%,n=9),respectively. CONCLUSIONS:The method is simple,accurate and reliable,and can be used for the quality evaluation of Inulae Flos.

Objectives To study the protective effects of vitamin D (VitD) on podocyte insulin resistance and its mecha-nisms. Methods Immortalized mouse podocytes in vitro were randomly divided into 4 groups:podocytes+5 mmol/L glucose group (group A);podocytes+5 mmol/L glucose+1 nmol/L propylene glycol group (group B);podocytes+30 mmol/L glucose+1 nmol/L propylene glycol group (group C); podocytes+30 mmol/L glucose+1 nmol/L propylene glycol+1 nmol/L VitD group (group D). The percentage of podocyte apoptosis was determined after 48 h of incubation. Podocyte viability was assessed by MTT assay. The mRNA expressions of vitamin D receptor (VDR) and insulin receptor substrate protein 1 (IRS1) in podocyte were detected by RT-PCR. Western blot analysis was performed to measure the protein levels of p-IRS1/IRS, p-Akt/Akt and p-ERK1/2/ERK1/2. Results There were significant differences in apoptosis percentage, viability and the expression of VDR, IRS1, p-ERK1/2 of podoctyes(P<0.05)among 4 groups. There was no difference in p-Akt/Akt expression among 4 groups(P>0.05). Compared with group A, B , and D, the percentage of podocyte apoptosis in group C was significantly increased, the cell viabi-lity was decreased, the expressions of VDR and IRS1 mRNA and p-IRS1 and p-Akt proteins were down-regulated, whereas p-ERK1/2 was up-regulated in group C. The levels of p-IRS1/IRS1, p-Akt/Akt, p-ERK1/2/ERK1/2 had no statistical differences in group A, B, and D (P>0.05). Conclusions VitD-VDR system alleviates podocyte apoptosis induced by high glucose, and acti-vates insulin signaling pathway and counteracts insulin resistance signal to improve podocyte insulin resistance.

Aim To optimize the traditional method of right catheterization in rats and establish a rapid , stable and reliable method of the right heart catheter guided intubation to measure pulmonary artery pressure. Methods Nighty male wistar rats were used to optimize the method of detection of pulmonary arte-rial pressure. Three catheter namely PE50, PU I, and PU II were used for choosing the best intubation. The new technology of right catheterization was established and used for the research of pulmonary arterial hypertension. Results The PU I catheter was obviously better than PE50 and PU II catheter in the success rate and measurement time ( P <0. 05 ) . The method of right heart catheter guided intubation was significantly superior to the traditional right heart direct intubation (P<0. 05 or P<0. 01). After improving the right catheterization, the detection of hemo-dynamic indexes in PAH-model rat was successful with regular pressure curve and reliable experimental data. Conclusions The right heart catheter guided intubation method has a high suc-cess rate and it can detect the pulmonary artery pressure quick-ly, easily, and can help other researchers to complete experi-ment as efficiently as possible.

Objective To test the effects of Vitamin D (VitD) on endothelial nitric oxide(NO) production and to study the signal pathway leading to NO release.Methods In vitro cultured human umbilical vein endothelial cells (HUVEC) were treated with various concentrations of VitD(0 mmol/L,0.01 mmol/L,0.10 mmol/L,1.00 mmol/L,10.00 mmol/L) for 60 min,and VitD at concentration of 1.00 mmol/L at different time points (30 min,60 min,90 min,120 min).The effect of VitD on NO production in presence of VitD receptor(VDR) agonist(ZK191784) or antagonist(ZK159222) for 60 min were examined in cell culture supernatant with kit for the detection of nitric oxide fluorescent probe(DAF-FM DA).HUVEC was cultured with VitD in presence of VDR agonist or antagonist for 60 min,and the effect of VitD on NO production with DAF-FM DA and the protein expression and phosphorylation of Caveolin-1 and endothelial nitric oxide synthase(eNOS) were detected by Western blot,respectively.Results VitD caused a concentration-dependent increase in NO production.The maximum effect was observed at a concentration of 1.0 mmol/L and the optimal time of stimulation was 60 min.Effects induced by VitD were enhanced by VDR agonist,and abolished by antagonist.VitD and VDR agonist maintained the expression of Caveolin-1 at the same low phosphorylation level the same as normal,increased the phosphorylated level of eNOS.However,VDR antagonist increased the phosphorylation of caveolin-l,but reduced the level of eNOS phosphorylation,respectively.Conclusions VitD can induce a significant increase in endothelial NO production through VDR.VitD interaction with VDR causes the low phosphorylation of caveolin-1 leading to eNOS activation and NO production.

Intestinal microorganisms and their metabolites are involved in the pathogenesis and progression of various cardiovascular diseases,especially in the progression of heart failure.This paper mainly discussed the gut microbial metabolites trimethylamine oxide(TMAO)participated in the pathological process of heart failure,and application value of TMAO in heart failure patients.This paper introduced the change characteristics of intestinal flora and its metabolites in heart failure patients,illu-minated the TMAO-mediated inflammatory response,and the related signal pathways and mechanism of myocardial hypertrophy and heart failure.High levels of TMAO are associated with poor outcomes in patients with heart failure indicating a good predictive value for the prognosis of heart failure.Regulating TMAO levels through diet,probiotics and prebiotics,antibiotics,fecal transplan-tation,and other pathways is expected to be a potential treatment for heart failure.

Objective To analyze the current situation and characteristics of risk factors in antithrombotic therapy(in-cluding antiplatelet and anticoagulant treatments)at home and abroad,and to provide a theoretical basis for the prevention and treatment of thrombosis or bleeding associated with antithrombotic therapy.Methods The literature on risk factors of an-tithrombotic therapy published in Chinese databases(China Journal Full-text Data,Wanfang Database,VIP Database)and Eng-lish databases(PubMed,Web of Science,MEDLINE)from January 2011 to November 2021 was searched and bibliometric analy-sis was performed.The visualization analysis was performed using VOS viewer software.Results A total of 595 publications were included in the analysis.The top three countries for English publications were the USA,China,and Japan.The type of stud-ies were predominantly cohort studies,with sample sizes mostly being below 1 000.Risk factors for antithrombotic therapy are cat-egorized into those affecting antiplatelet drugs,warfarin,and new oral anticoagulants.Age,gender,renal function,and combination of antithrombotic drugs are common risk factors,and different risk factors of antithrombotic drugs also have their characteristics.Conclusion While there is substantial research on risk factors in antithrombotic therapy globally,the sample size needs to be improved.Pharmacists should provide individualized medication services based on different drugs and different groups to ensure medication safety for patients.