OBJECTIVE To explore the effects of leonurine on growth arrest-specific protein-6 （GAS6）/Axl signaling pathway， and clarify its mechanism of alleviating myocardial injury in rats with coronary heart disease. METHODS The rat model of coronary heart disease was constructed； successfully modeled rats were randomly separated into model group， leonurine low- dose and high-dose groups （intragastric administration of leonurine 25， 100 mg/kg+intraperitoneal injection of normal saline 75 mg/kg）， and leonurine high-dose+GAS6/Axl signaling pathway inhibitor group （intragastric administration of leonurine 100 mg/kg+ intraperitoneal injection of R428 75 mg/kg）， with 12 rats in each group. Additional 12 normal rats were selected as control group. Each administration group was given relevant medicine； control group and model group were given a constant volume of normal saline intragastrically and intraperitoneally， once a day， for 48 consecutive days. After administration， the heart function of rats， and serum levels of inflammatory factors and myocardial injury markers were detected； the pathological morphology of myocardial tissue was observed； the myocardial cell apoptosis rate， the expressions of apoptosis and GAS6/Axl signaling pathway-related proteins were determined. RESULTS Compared with control group， model group showed disorders in the arrangement of myocardial cells and myocardial fibers， hypertrophy of myocardial cells， and nuclear condensation； left ventricular ejection fraction， left ventricular fractional shortening， ratio of early-diastolic and late-diastolic motion velocity of the mitral ring， the protein expression of GAS6， B-cell lymphoma 2/B-cell lymphoma 2 associated X protein and phosphorylated Axl/Axl ratios were decreased significantly （P＜0.05）. The levels of tumor necrosis factor-α， interleukin-1β， interleukin-6， creatine kinase isoenzyme， troponin Ⅰ and myoglobin， the cell apoptosis rate， and cleaved caspase-3/caspase-3 ratio were increased significantly （P＜0.05）. Leonurine could obviously improve the above pathological conditions and detection indicators （P＜0.05）， and the effect of leonurine high-dose group was more significant than that of leonurine low-dose group （P＜0.05）； R428 treatment could reverse the ameliorating effect of high-dose of leonurine on myocardial injury in rats with coronary heart disease （P＜0.05）. CONCLUSIONS Leonurine can alleviate myocardial injury in rats with coronary heart disease， and its mechanism of action is related to the activation of the GAS6/Axl signaling pathway.

BACKGROUND: China bears the biggest atrial fibrillation (AF) burden in the world. However, little is known about the incidence and predictors of AF. This study aimed to investigate the current incidence of AF and its electrocardiographic (ECG) predictors in general community individuals aged over 60 years in China. METHODS: This was a prospective cohort study, recruiting subjects who were aged over 60 years and underwent annual health checkups from April to July 2015 in four community health centers in Songjiang District, Shanghai, China. The subjects were then followed up from 2015 to 2019 annually. Data on sociodemographic characteristics, medical history, and the resting 12-lead ECG were collected. Kaplan-Meier curve was used for showing the trends in AF incidence and calculating the predictors of AF. Associations of ECG abnormalities and AF incidence were examined using Cox proportional hazard models. RESULTS: This study recruited 18,738 subjects, and 351 (1.87%) developed AF. The overall incidence rate of AF was 5.2/1000 person-years during an observation period of 67,704 person-years. Multivariable Cox regression analysis indicated age (hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.06-1.09; P < 0.001), male (HR, 1.30; 95% CI: 1.05-1.62; P = 0.018), a history of hypertension (HR, 1.55; 95% CI: 1.23-1.95; P < 0.001), a history of cardiac diseases (HR, 3.23; 95% CI: 2.34-4.45; P < 0.001), atrial premature complex (APC) (HR, 2.82; 95% CI: 2.17-3.68; P < 0.001), atrial flutter (HR, 18.68; 95% CI: 7.37-47.31; P < 0.001), junctional premature complex (JPC) (HR, 3.57; 95% CI: 1.59-8.02; P = 0.002), junctional rhythm (HR, 18.24; 95% CI: 5.83-57.07; P < 0.001), ventricular premature complex (VPC) (HR, 1.76; 95% CI: 1.13-2.75, P = 0.012), short PR interval (HR, 5.49; 95% CI: 1.36-22.19; P = 0.017), right atrial enlargement (HR, 6.22; 95% CI: 1.54-25.14; P = 0.010), and pacing rhythm (HR, 3.99; 95% CI: 1.57-10.14; P = 0.004) were independently associated with the incidence of AF. CONCLUSIONS The present incidence of AF was 5.2/1000 person-years in the studied population aged over 60 years in China. Among various ECG abnormalities, only APC, atrial flutter, JPC, junctional rhythm, short PR interval, VPC, right atrial enlargement, and pacing rhythm were independently associated with AF incidence.
Humans ; Male ; Middle Aged ; Aged ; Atrial Fibrillation/epidemiology* ; Prospective Studies ; Incidence ; Atrial Flutter/complications* ; Risk Factors ; China/epidemiology* ; Electrocardiography

Objective: To examine the effects of obesity and central obesity on hypertension, so as to provide insights into the prevention and control measures of hypertension. Methods: From September to December 2018, residents at ages of 35 to 75 years were sampled using the multi-stage random sampling method in Baiyin District, Baiyin City, Gansu Province, and subjected to questionnaire surveys and physical examinations. The interaction between obesity/central obesity and hypertension was evaluated using logistic regression analysis. The synergy index ( SI ), relative excess risk due to interaction ( RERI ) and attributable proportion due to interaction ( AP ) were calculated using Excel compiled by Andersson et al. Results: A total of 6 246 questionnaires were allocated and 6 169 valid questionnaires were recovered, with an effective recovery rate of 98.77%. The respondents included 3 038 men ( 49.25% ) and 3 131 women (50.75%), with a mean age of ( 52.05±8.78 ) years. There were 832 respondents with obesity ( 13.49% ) and 2 278 with central obesity ( 36.93% ). The crude and standardized prevalence rates of hypertension were 35.89% and 33.05%, respectively. Multivariable logistic regression analysis showed that obesity ( OR=2.020, 95%CI: 1.705-2.393 ) and central obesity ( OR=1.622, 95%CI: 1.433-1.836 ) were statistically associated with hypertension. There was no multiplicative interaction between obesity or central obesity and hypertension ( OR=1.011, 95%CI: 0.655-1.560 ), and no additive interaction was detected between obesity or central obesityand hypertension ( SI=1.405, 95%CI: 0.815-2.424; RERI=0.658, 95%CI: -0.298 to 1.614; AP=0.201, 95%CI: -0.075 to 0.476 ). Conclusions Obesity and central obesity increase the risk of hypertension; however, no interaction is detected between obesity or central obesity and hypertension.

Objective: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with its genetic evidence widely explored. This study explored the potential the parent-of-origin (PoO) effect of WNT pathway on the risks of NSCL/P, using a case-parent trio design. Methods: Data on the single nucleotide polymorphism (SNP) of WNT genes were selected from a genome-wide association study (GWAS). A total of 806 Chinese non-syndromic cleft lip patients, with or without cleft palate (NSCL/P) case-parent trios, were gathered from an international consortium. PoO effect of WNT pathway genes and its haplotypes were explored by log-linear models. Additional Wald tests were performed to assess: a) the heterogeneity of PoO effect between different maternal exposures, b) the interaction between PoO effect, c) maternal exposure to environmental tobacco smoke (ETS), and d) multivitamin supplementation during pregnancy. The threshold for statistical significance was adjusted as 3.47×10^-4, according to Bonferroni correction. Results: After quality control, a total of 144 SNPs within seven genes were included for analyses, among which 8 SNPs were of potential PoO effect (P<0.05). However, none of them achieved the statistical significance after Bonferroni correction. The haplotype rs4074668-rs12725747 (T-A) on WNT9A showed significant PoO effect, based on the haplotype test for PoO (P=2.74×10^-4). In addition, no statistically significant interaction was found in further exploration of this haplotype under environmental exposures as ETS or multivitamin supplementation. Conclusions Genes in the WNT pathway may influence the NSCL/P risks through the potential PoO effect. Particularly, the haplotype rs4074668-rs12725747 (T-A) on WNT9A presented significant PoO effect on NSCL/P, statistically. From this current study, findings on WNT pathway related risks among the NSCL/P, need to be further validated by independent samples in the future.

Objective To evaluate the role of autophagy in hydrogen-induced inhibition of apoptosis in hippocampal neurons in a rat model of orthotopic liver transplantation (OLT).Methods Fifty-six pathogen-free healthy adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 220-250 g,were used in the study.Thirty-two rats were selected and assigned into 4 groups (n =8 each) using a random number table:sham operation group (group S),OLT group,hydrogen-rich saline group (group HS) and chloroquine group (group CQ).The other 24 rats severed as the donors.In group S,laparotomy was performed,and the related blood vessels were isolated.The model of OLT was established in OLT,HS and CQ groups.In group OLT,normal saline 6 ml/kg was slowly injected via the inferior vena cava at 5 min before anhepatic phase.In group HS,hydrogen-rich saline 6 ml/kg was slowly injected via the inferior vena cava at 5 min before anhepatic phase.In group CQ,autophagy inhibitor chloroquine 60 mg/kg was injected intraperitoneally at 1 h before establishment of the model,and the other treatments were similar to those previously described in group HS.At 6 h of reperfusion,the rats were sacrificed and hippocampi were isolated for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity,for pathological examination (with light microscope),and for detection of cell apoptosis (by TUNEL staining) and expression of autophagy-and apoptosis-related proteins caspase-3,cytochrome c (Cyt c),microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ),Beclin-1 and p53 in hippocampal tissues (by Western blot analysis).Apoptosis index (AI) was calculated.Results Compared with group S,the MDA content and AI were significantly increased,the SOD activity was decreased,and the expression of caspase-3,Cyt c,LC3 Ⅱ,Beclin-1 and p53 was up-regulated in OLT,HS and CQ groups (P＜0.05).Compared with group OLT,the MDA content and AI were significantly decreased,the SOD activity was increased,the expression of caspase-3 and Cyt c was down-regulated,and the expression of LC3 Ⅱ,Beclin-1 and p53 was up-regulated in group HS (P＜0.05).Compared with group HS,the MDA content and AI were significantly increased,the SOD activity was decreased,and the expression of caspase-3 and Cyt c was up-regulated,and the expression of LC3 Ⅱ,Beclin-1 and p53 was down-regulated in group CQ (P＜0.05).Conclusion The mechanism by which hydrogen inhibits apoptosis in hippocampal neurons is related to promotion of autophagy in a rat model of OLT.

Objective:To explore the association and gene-environment interaction between single nu-cleotide polymorphisms (SNPs)involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate (NSCL/P)among Chinese population.Methods:A total of 806 NSCL/P trios were drawn by an international consortium,which conducted a genome-wide association study (GWAS)using a case-parent trio design to investigate genes affecting risks to NSCL/P.The transmission disequilibrium test (TDT)was used to explore the association between cell-cell adhesion genes,including CDH1,CT-NNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P.Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children.Four common maternal exposures including maternal smoking,environmental tobacco smoke,alcohol consumption and multivita-min supplementation during pregnancy were included in this study.Results:A total of 226 SNP markers were tested after quality control in this study.Although 23 SNPs in three genes (CTNNB1,CDH1, ACTN1)showed nominal significant association with NSCL/P in the TDT (P <0.05).There were no sig-nificant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction(P >0.000 2).Tests for gene-environment interaction yielded significant results be-tween rs7431 27 in ACTN1 and environmental tobacco smoke (P =0.000 1 )with an estimated OR (case |G and E)=2.00(95%CI:1 .23 -3.26)and OR (case |G no E)=0.59 (95%CI:0.38 -0.90).Among the lower P value results in gene-environment tests,there were no significant results be-tween rs1 475034,rs370535,rs227341 9 in ACTN1,rs1 06871 in CTNNB1 and environmental tobacco smoke interaction.There were also no significant results between rs7634000,rs2971 366,rs2634553, rs1 489032,rs762481 2 in PVRL3 and multivitamin supplementation during pregnancy in gene-environ-ment tests(P >0.000 2).Conclusion:There is no association between cell-cell adhesion genes,inclu-ding CDH1,CTNNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P when the genes are considered alone.But our results suggest that SNPs in ACTN1 may influence the risk to NSCL/P through gene-environment interaction.

Objective To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) / heme oxygenase-1 (HO-1) signaling pathway in reduction of acute kidney injury following orthotopic liver transplantation (OLT) by hydrogen-rich saline in rats.Methods Thirty-two healthy adult male SpragueDawley rats,weighing 220-250 g,were randomly assigned into 4 groups (n =8 each) using a random number table:sham operation group (S group),OLT group,hydrogen-rich saline group (HS group),and all-trans retinoic acid (ATRA) group.Laparotomy was performed,and the related blood vessels were isolated in group S.The model of orthotopic autologous liver transplantation was established in OLT,HS and ATRA groups.Normal saline and hydrogen-rich saline 6 ml/kg were injected through the inferior vena cava at 5 min before the portal vein was clamped in OLT and HS groups,respectively.In group ATRA,Nrf2 inhibitor ATRA 7 mg/kg was injected intraperitoneally once a day for 2 consecutive days,the model of orthotopic autologous liver transplantation was established at 16 h after the last injection of ATRA,and the other treatments were similar to those previously described in group HS.At 6 h of reperfusion,blood samples were collected for determination of serum blood urea nitrogen (BUN),creatinine (Cr),interleukin10 (1L-10) and tumor necrosis factor-alpha (TNF-α) concentrations.After blood sampling,the lungs were removed for determination of malondialdehyde (MDA) content,superoxide dismutase (SOD) activity,expression of HO-1,Bcl-2 and Bax mRNA (by using real-time reverse transcriptase polymerase chain reaction),and HO-1 protein expression in lung tissues (by Western blot) and for microscopic examination.The damage to the renal tubules was scored.Results Compared with group S,the serum BUN,Cr and TNF-α concentrations were significantly increased,the serum IL-10 concentrations were decreased,the MDA content and renal tubular damage score were increased,the SOD activity was decreased,and the expression of HO-1 protein and mRNA,and Bcl-2 and Bax mRNA was up-regulated in group OLT (P＜ 0.05).Compared with group OLT,the serum BUN,Cr and TNF-α concentrations were significantly decreased,the serum IL-10 concentrations were increased,the MDA content and renal tubular damage score were decreased,the SOD activity was increased,the expression of HO-1 protein and mRNA and Bcl-2 mR-NA was up-regulated,and the expression of Bax mRNA was down-regulated in group HS (P＜0.05).Compared with group HS,the serum BUN,Cr and TNF-α concentrations were significantly increased,the serum IL-10 concentrations were decreased,the MDA content and renal tubular damage score were increased,the SOD activity was decreased,the expression of HO-1 protein and mRNA and Bcl-2 mRNA was down-regulated,and the expression of Bax mRNA was up-regulated in group ATRA (P＜0.05).Conclusion The mechanism by which hydrogen-rich saline reduces acute kidney injury following OLT is probably associated with activation of Nrf2/HO-1 signaling pathway in rats.

Chronic obstructive pulmonary disease (COPD) refers to a common complex disease characterized by progressive and incomplete reversible airflow limitation.COPD is one of the leading causes on morbidity and mortality in China.Genetic risk factors play important roles on the occurrence of COPD.However,the genetic risk factors of COPD remain unknown,to some extent.The aim of this review is to provide a comprehensive overview on literature concerning the most promising findings related to genetic risk factors of COPD.

Objective To evaluate the role of autophagy on acute kidney injury after liver transplantation.Method Fifty-six healthy male Sprague-Dawley rats were randomly assigned into 4 groups:sham group,orthotopic liver transplantation (OLT) group,sirolimus pretreated (SRL) group and 3-methyladenine pretreated(3-MA) group.OLT model was established.Then the rats were sacrificed at 6 h after reperfusion.The renal function and the extent of oxidative stress relative proteins malondialdehyde (MDA) and superoxide dismutase (SOD) were observed.The levels of apoptosis relative genes caspase-3 and cyt c and the expression of autophagy relative proteins were detected.The pathological changes were microscopically examined in renal tissues.TUNEL staining was used to observe the apoptosis of tubular epithelial cells.Transmission electron microscopy was applied to observe the ultrastructure changes of tubular epithelial cells.Result As compared with sham group,OLT and 3-MA groups showed a serious renal injury including cellular vacuolization,loss of brush borders,and a significant rise in BUN,Cr and MDA,while a decrease in SOD activity.The levels of caspase-3 mRNA and cyt c rnRNA were increased significantly.Whereas compared to OLT and 3-MA groups,renal function and oxidative stress levels in SRL group ameliorated,and histopathologic damage and apoptosis alleviated after OLT.Simultaneously,the levels of caspase-3 mRNA and cyt c mRNA were decreased.The expression of beclin-1 and LC3-]Ⅱ was effectively upregulated.Conclusion Autophagy could alleviate acute kidney injury after liver transplantation through inhibiting oxidative stress and apoptosis.