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Objective:To investigate the relationship between snoring and the risk of cardiovascular and cerebrovascular events.Methods:By searching PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructur, Wanfang Database, VIP Chinese journal database and Chinese biomedicine databases from the establishment to June 10, 2019, relevant domestic and foreign literature, extract data and apply Newcastle-Ottawa Quality Assessment Scale (NOS)method to quality evaluation, and finally integrate the data and analyze with Stata12.0 software.Results:A total of 11 articles and 145 267 participants met the inclusion criteria.Meta-analysis results showed that the correlation strength and 95% CI of snoring with cardiovascular and cerebrovascular events and stroke risk were 1.10 (1.03-1.17) and 1.26 (1.11-1.43)respectively , and all of them had statistical significance.Conclusion:Snoring is an independent risk factor for the risk of cardiovascular events and is more closely linked to stroke.
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Objective To explore the link between the expression of long non-coding RNA(lncRNA)metastasis associated lung adenocarcinoma transcript 1(MALAT1)and IL-6/signal trans ducers and activators of transcription 3(STAT3)signaling pathway in isoniazid induced rats liver injury. Methods Fifty-six specific pathogen-free(SPF)SD rats were randomly divided into experimen?tal group(48 rats)and control group(8 rats),each with half females and half males. The rats in experimental group were given isonia?zid of 63 mg/(kg·d)for 3,7,10,14,21 and 28 d,with 8 rats at the same time point of each day. The rats in control group were giv?en distilled water by intragastric administration. Serum levels of ALT and AST were measured by automatic biochemical analyzer;SYBR green real-time polymerase chain reaction was used to test the expression level of lncRNA MALAT1 and IL-6/STAT3 mRNA in the liver. Results Liver tissue injury occurred after 7 days and worsened with the extention of administration time. Compared with the rats in the control group,the expression level of lncRNA MALAT1 and IL-6/STAT3 mRNA as well as ALT and AST showed a trend of increase(P<0.01). The expression of ALT,AST and lncRNA MALAT1 declined at different degrees on 28(P<0.05). LncRNA MALAT1 and IL-6/STAT3 mRNA expression levels were positively correlated(P<0.01). LncRNA MALAT1 and IL-6/STAT3 mRNA expression levels had a positive correlation with the contents of ALT and AST(P<0.01). Conclusion The expression level of lncRNA MALAT1 in isoniazid induced liver injury rat models showed an abnormal rising trend,and the positive detection time preceded that of ALT and AST. The mechanism may be related to the activation of IL-6/STAT3 signaling pathway.
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OBJECTlVE To study the reIationship between microRNA(miRNA)-122 and Iiver injury in-duced by anti-tubercuIosis drugs,and to discover the new biomarkers for earIy diagnosis of this type of Iiver injury. METHODS mice were given 2 mL isoniazid oraIIy at 90 mg·kg-1 . BIood and Iiver tissue sampIes were coIIected at 1,3,5,7,14,21 and 28 d after administration of isoniazid. Serum gIutamic-pyruvic transaminase( GPT)and gIutamic-oxaIoacetic transaminase( GOT)IeveIs were determined using an automatic biochemicaI anaIyzer. Cu/ Zn-superoxide dismutase( Cu/ Zn-SOD ) activity and maIondiaIdehyde( mDA)content were detected by biochemicaI method. ReaI-time qPCR was used to measure the expression of miRNA-122. RESULTS GPT and GOT IeveIs were significantIy higher at 14 and 21 d(P﹤0.05)than in the controI. Cu/ Zn-SOD began to decIine whiIe mDA began to increase after 5 d(P﹤0.05). miRNA-122,which progressiveIy decreased after administration,was reduced to the mini-mum 0.58 ±0.02 at 14 d. There were good correIations between miRNA-122 and GPT,Cu/ Zn-SOD, mDA(the correIation coefficients were -0.370,0.268,and -0.298,respectiveIy),but no correIation with GOT was observed. CONCLUSlON The tissue miRNA-122 profiIe can be used as a sensitive marker for anti-tubercuIosis drug-induced Iiver injury,which couId contribute to the earIy diagnosis of Iiver injury.
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ObjectiveTo study the influence of anti-tuberculosis drugs on mitochondrial function in mice hepatocytes and to explore the mechanism of the anti-tuberculosis drugs induced liver injury.Methods A total of 150 mice were randomized into five groups:control group (C group),rifampin (RFP) group,isoniazid (INH) group,pyrazinamide (PZA) group and three antituberculosis drug combination group (MIX).The mice were administered intragastrically with 0.9 ％ NaC1 solution or RFP 135 mg · kg-1 · d-1 or INH 90 mg · kg-1 · d-1 or PZA 315 mg · kg-1 · d-1 or RFP+INH+ PZA (135±90+315) mg · kg-1 · d-1 once a day.Ten mice in each group were sacrificed at day 3,7 and 15 of administration,respectively.The following parameters in each group were monitored.the concentration of malondialdehyde (MDA),the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) in mitochondrion of hepatocytes and the concentration of 8-hydroxydeoxyguanosine (8-OH-dG) in mitochondrial DNA (mtDNA).The data were analyzed by one-way ANOVA or rank sum test.Results Along with the prolonged medication duration,the concentrations of MDA all gradually increased in RFP group (Z=6.020,P=0.049),IN H group (Z=10.220,P=0.006) and MIX group (Z=7.460,P=0.024),whereas the activity of SOD significantly decreased in RFP group (F=6.751,P =0.011 ) and MIX groups (F=4.891,P =0.041 ) compared with control group and PZA group.Meanwhile,the activity of GSH-PX was significantly lower in RFP group compared to the other groups (F=32.445,P＜0.01).The changes of other parameters didn't show meaningful trend.The concentrations of 8-OH-dG in mtDNA also increased in all treated groups,and those were all significantly increased in RPF group (F=6.602,P＜0.01 ),PZA group (F=5.927,P＜0.01) and MIX groups (F=7.974,P＜0.01).Conclusions Antituberculosis drugs can induce higher MDA concentration in mitochondrion and higher 8-OH-dG concentration in mtDNA,while result in lower activities of SOD and GSH-PX.The liver damage tends to become more severe along with the prolonged medication duration.The combination of three antituberculosis drugs could aggravate the damage of mitochondrion in mice hepatocytes.
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Objective To investigate the relationship between polymorphisms of N-acetyltransferase 2(NAT2)genes and anti-tuberculosis drug induced hepatic-injury(ADIH).Methods A 1:1 matched case-control study was conducted.One hundred and six cases fulfilling the criteria of ADIH were selected as ADIH group from the patients who received anti-tuberculosis therapy.whereas those patients without any hepatic inj ury related elinical symptoms during three months of follow-up period were selected as control.The genetic polymorphisms of the loci,NAT2481C/T,NAT2-590G/A and NAT2-857G/A,were determined by polymerase chain reaction and restriction fragment length polymorphism technique(PCR-RFLP)in patients who received antituberculosis therapy.The major environmental factors and genotypes were analyzed by univariate and multivariate conditional Logistic analyses.Results The T,AA allele frequencies of NAT2-481C/T,NAT2-590G/A and NAT2-857G/A were 7.5%,28.8%and 17.9%respectively in ADIH group,and 6.6%,18.9%and 17.5%,respectively in the control group.Univariate analysis demonstrated that the frequency of NAT2 slow acetylation genotype in ADIH group was significantly higher than that in control group with a crude OR(95%CI)of 2.250(1.140-4.441).Among 6 potential risk factors,i.e.education level,occupation,body mass index(BMI),smoking,drinking and the type of tuberculosis,the low BMI and drinking were two risk factors for ADIH.In multivariate analysis,ADIH remained associated with acetylation genotype after adjusting for BMI and drinking status.The adjusted OR(95%CI)was 2.246(1.086-4.644).Conclusion NAT2 slow acetylation genotype may be associated with the occurrence of ADIH.
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Objective To investigate whether the gene polymorphisms of cytochrome P450(CYP) 2E1 are associated with the risk of anti-tuberculosis drug induced hepatotoxity (ADIH).Methods In this case control study, 339 patients who matched the diagnosis criteria of tuberculosis were included. The gcneral healthy status and liver biochemical parameters were checked in all these patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) technique was used to determine CYP 2Et polymorphisms. The statistic analysis were performed by using both univariate and multivariate Logistic regression analysis. Results The allele frequencies of CYP 2E1 7632T/A, 1019C/T and 1259G/C in 103 tuberculosis patients of ADIH group were 17.5%, 26.2%and 27.2 % respectively, while those in 236 tuberculosis patients of control group were 29.7 % ,39.4 %and 40.7%, respectively (x2 =5.539, P＜0.05; x2 =5.458, P＜0.05; x2 =5.628, P＜0.05). The results of univariate analysis demonstrated that the risk of concurrent ADIH was significantly higher in patients with wild genotypes of CYP 2E1-7632T/A, CYP 2E1-1259G/C, CYP 2E1-1019C/T than in patients with other genotypes. After adjusted for sex, occupation and alcohol consumption status, the results of multivariate Logistic regression analysis also showed that wild genotypes of CYP 2E1-7632T/A, CYP 2El-1259G/C, CYP 2E1-1019C/T were significantly associated with higher risk of ADIH. The results of interaction analysis indicated that the wild genotypes of CYP 2E1-7632T/A and CYP 2E1-1259G/C or CYP 2E1-1019C/T had synergetic effects on the development of ADIH.Conclusions The risk of concurrent ADIH is significantly higher in patients with wild genotypes of CYP 2E1-7632T/A, CYP 2E1-1259G/C, CYP 2E1-1019C/T compared to patients with othergenotypes. Wild genotypes of CYP 2E1-7632T/A and CYP 2E1-1259G/C or CYP 2El-1019C/T have synergetic effects on the development of ADIH.
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Small non-coding RNA (sRNA) is a kind of newly discovered 50 nt~500 nt small RNAs that do not encode proteins. To date, more than 150 sRNA have been found in bacteria. The small RNA acting by base-pairing with target mRNAs, resulting in post-transcriptionally regulating gene expression, is important regulators in the bacterial response to stress, virulence and metabolism. At present, researches of sRNA mainly based on bioinformatical prediction and molecular biological experiments. The sRNA that obtained through these methods needs confirmation in laboratory, and then study of its functions through a variety of experimental methods.
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<p><b>OBJECTIVE</b>To evaluate the immunogenicity, safety, and dosage of a new inactivated hepatitis A vaccine administered to young adults.</p><p><b>METHODS</b>One hundred and four normal adult volunteers, seronegative for hepatitis A virus and hepatitis B surface antigen, were randomly assigned to one of three groups. The high-dose group received a primary dose of 1000 units of the new vaccine, the low-dose group received a primary dose of 500 units of the same vaccine, and the Havrix group received a primary dose of 1440 enzyme-linked immunosorbent assay units of Havrix, a licensed inactivated hepatitis A vaccine. All groups received a booster dose of the same vaccine 6 months after the primary dose. Local and systemic adverse reactions, seroconversion rates, and geometric mean titers of hepatitis A virus antibodies were measured in all three groups.</p><p><b>RESULTS</b>Local and systemic reaction types and rates were similar in all three groups after primary and booster doses, although local reactions were more frequent in the Havrix group following the primary dose. No serious adverse reactions occurred. One month after the primary dose, the seroconversion rate was 87.5% in the high-dose group, 70.0% in the low-dose group, and 50.0% in the Havrix group (P = 0.001, versus the high-dose group). At month 6 (before administration of the booster dose), seroconversion rates were 96.9% in the high-dose group, 65.0% in the low-dose group (P = 0.0029), and 68.8% in the Havrix group (P = 0.007). All subjects in all groups seroconverted by one month after receipt of the booster dose. Geometric mean titers were similar in all three groups at month 1, but were higher in the high-dose group (264 mIU/ml) than those in the Havrix group (135 mIU/ml) at month 6 (P = 0.0013). One month after the booster dose, geometric mean titers in the high-dose group (2747 mIU/ml) were higher than those in the low-dose group (1657 mIU/ml) (P = 0.0223) or in the Havrix group (1316 mIU/ml) (P = 0.01).</p><p><b>CONCLUSIONS</b>This new inactivated hepatitis A vaccine is immunogenic and safe; two doses of either 500 or 1000 units can induce hepatitis A virus antibodies well above the protection level.</p>