Status quo and influencing factors of drug resistance of tuberculosis in Inner Mongolia / 安徽医科大学学报

Objective @#To investigate the status quo of drug resistance and influencing factors of tuberculosis in Inner Mongolia , and to provide reference for accurate prevention and control of drug - resistant tuberculosis .@*Methods @#Random sampling was used in this study . TB patients from Tuberculosis designated hospital in Inner Mongolia were included , according to the rules and drug - resistant strains were identified and tested according to relevant norms . Composition ratio or rate was calculated for statistical description , and Logistic regression model was used to analyze the influencing factors of drug resistance in TB patients .@*Results @#Among 1321 patients, there were 936 males and 385 females, with an average age of (52.65 ±18 .09) years . The rates of mono - resistant , multidrug - resistant (MDR) , extensively drug - resistant (XDR) and total drug resistance were 19.00% , 11.58% , 11.66% and 42.24% , respectively . The highest resistance rates were ob served for streptomycin ( 7.27% ) , isoniazid (4.69% ) , and isoniazid + streptomycin (4.47% ) . The drug resistance spectrum presented diversity and com plexity . Compared to females , males had a higher proportion of drug resistance , and the difference was statistically significant (P < 0.001) . The proportion of patients who were sensitive to anti - tuberculosis drugs increased with age (P < 0.05) . Among different age groups , the proportion of drug - resistant patients was higher in the 20 - 40 age group , 40 - 60 age group , and 60 and above age group compared to the 0 - 20 age group (P < 0.05) . Addi tionally , the proportion of drug - resistant patients was higher in the 20 - 40 age group and 40 - 60 age group com pared to the 60 and above age group (P < 0.05) . Moreover , the proportion of drug - resistant and multi - drug resistant patients was higher among patients undergoing retreatment compared to those undergoing initial treatment (P < 0.001) . Multivariate Logistic regression analysis showed that male gender (OR = 1.48 , 95% CI: 1.02 - 2.14) , age 20 - 40 years (OR = 2.64 , 95% CI: 1.05 - 6.60) , retreatment (OR = 2.34 , 95% CI: 1.70 - 3.22) , and outpatient follow-up (OR = 1.56 , 95% CI: 1.05 - 2.33) were independent risk factors for drug - resistant tuber culosis .@*Conclusion @#Inner Mongolia has a high prevalence of MDR and overall drug - resistant tuberculosis among patients . The drug resistance profile exhibits diversity and complexity . Risk factors that contribute to drug resistance include being male , aged between 20 and 40 , undergoing retreatment , and receiving outpatient follow - up . Therefore , it is necessary to further improve clinical diagnosis and treatment , promote rational use of first - line anti - tuberculosis drugs , prioritize individualized treatment , enhance health education , improve the medical insurance system , and optimize patient management approaches in order to enhance patient compliance .

Factors influencing malnutrition in tuberculosis patients based on analysis of nutritional status in different populations / 安徽医科大学学报

Objective @#To investigate the nutritional status and dietary structure of tuberculosis patients among different populations , analyze the factors influencing the nutritional status of tuberculosis patients , and provide theoretical basis for improving clinical nutrition and related issues in tuberculosis patients.@*Methods @#Tuberculosis patients , non⁃tuberculosis patients , and healthy individuals were randomly selected for a questionnaire survey. Descriptive analysis was conducted using SPSS 20. 0 software. Statistical description was performed using rates and composition ratios , and qualitative data were described using relative numbers. Chi⁃square test was used to compare overall rates and composition ratios among different health conditions groups , with a significance level of α = 0. 05. Independent factors analysis of nutritional status body mass index (BMI) was conducted using multiple Logistic regression analysis for variables with statistically significant differences in the univariate analysis. @*Results @#There were differences in the nutritional status (χ2 = 62. 184 , P < 0. 05) and dietary diversity score (χ2 = 64. 049 , P < 0. 05 ) among tuberculosis patients , non⁃tuberculosis patients , and healthy individuals. Univariate analysis of nutritional status BMI showed statistically significant differences in gender, smoking , meat⁃based diet , vegetable⁃based diet , moderate diet diversity score , and 6 other variables for tuberculosis patients ( P < 0. 05 ) , and in gender, age , ethnicity , marital status , occupation , education level , smoking , drinking white wine , drinking beer, meatcally significant differences in the univariate analysis were included in the multiple ordinal logistic regression analysis model for both tuberculosis patients and healthy individuals. The results showed that the level of education , vegetable intake , moderate food diversity score (DDS) of 4 - 6 were independent influencing factors of nutritional status BMI among tuberculosis patients (P < 0. 05) ; marital status was an independent influencing factor of nutritional status BMI among non⁃tuberculosis patients (P < 0. 05) ; while gender and occupation were independent influencing factors of nutritional status BMI among healthy individuals (P < 0. 05) . @*Conclusion @#The dietary nutritional status of the three population groups varied. Targeted health education should be conducted , especially for tuberculosis patients , to address the issue of uneven dietary intake and promote good dietary habits among local tuberculosis patients.

NADH alleviates anti-tuberculosis drug-induced liver injury and apoptosis in mice through SIRT1/Nrf2 pathway / 安徽医科大学学报

Objective To investigate the mechanism by which Nicotinamide adenine dinucleotide(NADH)regu-lates anti-tuberculosis drug-induced liver injury and apoptosis in mice through SIRT1/Nrf2 pathway.Methods Twenty-four six-week-old SPF male mice were randomly divided into four groups according to body weight,ADLI group[90 mg/(kg·d)Isoniazid,135 mg/(kg·d)Rifampicin,315 mg/(kg·d)Pyrazinamide were given by gavage],control group[thesame volume of saline was given by gavage as antituberculosis drug-induced liver injury(ADLI)group],NADH group(30 mg/kg NADH wasgiven by gavage on the basis of control group)and NADH intervention group(30 mg/kg NADH wasgiven by gavage on the basis of ADLI group),with sixmice in each group.They were gavaged continuously for seven days,and their seruand liver tissues were collected.The mRNA and protein expression of silence information regulator 1(SIRT1),nuclear factor erythroid 2-related factor 2(Nrf2)in SIRT1/Nrf2 pathway,apoptosis indicators B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-3 were detected by qRT-PCR and Western blot,respectively.HE staining was performed to observe the morphology of liver tissue.The liver was weighedandthe liver index was obtained by dividingweight by body weight.The levels of glutamate aminotransferase(ALT),aspartate aminotransferase(AST)and lactate dehydrogenase(LDH),which are indicators of liver injury,were detected by microplate method.Results Compared with control group,the protein and mRNA expression of SIRT1,Nrf2decreased significantly in ADLI group.Liver tissue struc-ture wasdisturbed,hepatocytes were obviously swollen,and their boundary was unclear.The weight of mice de-creased,but liver index increased.The mRNA and protein expression level of anti-apoptotic factor Bcl-2 decreased,while that of Bax and caspase-3 was raised.The level of ALT,AST and LDH were also elevated.The differences a-bove were statistically significant(P＜0.05).Compared with ADLI group,the protein and mRNA expression of SIRT1,Nrf2 were higher after NADH intervention.Liver tissue structure became clear,and hepatocytes were po-lygonal.The protein and mRNA expression of anti-apoptosis factor Bcl-2 was elevated and while that of Bax and caspase-3 was lower.The weight of mice increased and liver index decreased.The expression of ALT,AST and LDH decreased.The differences above were statistically significant(P＜0.05).Conclusion NADH may allevi-ate anti-tuberculosis drug-induced liver injury and apoptosis in mice by regulating SIRT1/Nrf2 pathway.

Meta-analysis of the relationship between snoring and risk of cardiovascular and cerebrovascular diseases / 中国综合临床

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.

Relationship between long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 and IL-6/STAT3 signaling pathway in isoniazid-induced rats liver injury / 国际药学研究杂志

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.

MicroRNA-122 expression during isoniazid anti-tuberculosis drug-induced liver injury in mice / 中国药理学与毒理学杂志

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.

Antituberculosis drugs induce mitochondrial oxidative damage of hepatocytes / 中华传染病杂志

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.

Study of the relationship between polymorphisms of cytochrome P450 2E1 and antituberculosis druginduced hepatic injury / 中华传染病杂志

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.

The relationship between polymorphisms of N-acetyltransferase 2 genes and anti-tuberculosis drug induced hepatic-injury / 中华传染病杂志

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.

Research Progress of Small Non-coding RNA in Bacteria / 微生物学通报

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.

Immunogenicity and safety of a new inactivated hepatitis A vaccine in young adults: a comparative study / 中华医学杂志(英文版)

<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>