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1.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 225-232, 2022.
Article in Chinese | WPRIM | ID: wpr-940713

ABSTRACT

The present study explored the effective approaches to realize the leading role of traditional Chinese medicine (TCM) in preventing diseases, the synergistic role in treating serious diseases, the core role in the rehabilitation of diseases and summarized the experience to provide feasible plans for the evaluation of other dominant diseases of TCM. To evaluate the effectiveness, safety, and economy of TCM in the treatment of ischemic stroke, encephalopathy project team of the China Center for Evidence-based Traditional Chinese Medicine(CCEBTCM) established an evaluation group to determine the work plan and complete the evaluation work. The concepts of the evaluation involved high-quality evidence, expert opinion survey, expert interview, and drug catalog. Under the guidance of clinical experts and methodologists, the evaluation work was completed in accordance with four steps, i.e., plan making, data collection and data extraction, evidence synthesis and evaluation, and report writing with the rapid review method. Through the review of TCM and western medicine experts, the advantage of TCM in the treatment of ischemic stroke was positioned in the convalescence period with the predominant effects of improving the neurological function defect and improving the daily living ability. In the convalescence period of stroke, TCM treatment could improve post-stroke motor dysfunction, post-stroke cognitive impairment, consciousness disorder, swallowing disorder, aphasia, constipation, urinary function, diplopia, etc., and the advantages of acupuncture, Chinese medicine, and traditional exercise were more prominent. In terms of safety, TCM treatment of ischemic stroke showed lower incidence of adverse reactions, fewer adverse events, and a milder degree of related symptoms. In terms of economic performance, the combined treatment of TCM and western medicine played a synergistic role and made the treatment cost more reasonable. Compared with conventional intervention, the integrated TCM and western medicine rehabilitation program showed more economic and social benefits.

2.
China Journal of Chinese Materia Medica ; (24): 4644-4653, 2021.
Article in Chinese | WPRIM | ID: wpr-888168

ABSTRACT

To systematically review the efficacy and safety of acupuncture combined with minimally invasive surgery or basic the-rapy in treating hypertensive intracerebral hemorrhage(HICH) patients compared with minimally invasive surgery or basic treatment. In this study, the four Chinese databases, the four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, all above were systematically and comprehensively retrieved from the time of database establishment to September 10, 2020. Rando-mized controlled trials(RCTs) were screened out according to inclusion criteria and exclusion criteria established in advanced. The methodological quality of included studies was evaluated by the tool named "Cochrane bias risk assessment 6.1". Meta-analysis of the included studies was performed using RevMan 5.4, and the quality of outcome indicators was evaluated by the GRADE system. Finally, 17 studies were included, involving 1 852 patients with HICH, and the overall quality of the included studies was not high. According to Meta-analysis,(1)CSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-3.50,95%CI[-4.39,-2.61],P<0.000 01);(2)NIHSS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.78,95%CI[-5.55,-4.00],P<0.000 01);(3)the cerebral hematoma volume of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=-4.44,95%CI[-5.83,-3.04],P<0.000 01);(4)ADL score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=20.81,95%CI[17.25,24.37],P<0.000 01);(5)the GCS score of the group of acupuncture combined with minimally invasive surgery or basic therapy was superior to the group of minimally invasive surgery or basic therapy(MD=2.41,95%CI[1.90,2.91],P<0.000 01). The GRADE system showed an extremely low level of evidence for the above outcome indicators. Adverse reactions were mentioned only in two literatures, with no adverse reactions reported. The available evidence showed that acupuncture combined with minimally invasive surgery or basic therapy had a certain efficacy in patients of HICH compared with minimally invasive surgery or basic therapy. However, due to the high risk of bias in the included studies, its true efficacy needs to be verified by more high-quality studies in the future.


Subject(s)
Humans , Acupuncture Therapy , Intracranial Hemorrhage, Hypertensive/therapy , Treatment Outcome
3.
China Journal of Chinese Materia Medica ; (24): 4633-4643, 2021.
Article in Chinese | WPRIM | ID: wpr-888167

ABSTRACT

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.


Subject(s)
Humans , Cerebral Hemorrhage/drug therapy , Drugs, Chinese Herbal , Meta-Analysis as Topic , Reproducibility of Results , Systematic Reviews as Topic , United States
4.
China Journal of Chinese Materia Medica ; (24): 4601-4614, 2021.
Article in Chinese | WPRIM | ID: wpr-888164

ABSTRACT

The study aims to analyze the outcome indicators of randomized controlled trial(RCT) of traditional Chinese medicine(TCM) in the treatment of hypertensive intracerebral hemorrhage(HICH) in recent three years, and thus provide suggestions for the future studies in this field. Four English databases, four Chinese databases and two online registration websites of clinical trials were searched. The RCTs published between January 2018 and September 2020 were screened. The risk of bias was assessed and outcome measures were classified. A total of 151 839 articles were retrieved, of which 44 RCTs were included for analysis after screening. The outcome measures of the included RCTs were classified into 7 categories, among which the symptoms/signs category showed the highest reporting rate. National Institute of Health stroke scale(72.73%) was the most frequently reported outcome indicator, while the vo-lume of intracerebral hemorrhage determined by computerized tomography(36.36%) was the most frequently reported lab test outcome. Most studies collect the outcomes at the end of treatment, while 9 studies reported long-term outcomes 3 months or more after onset. Compared with those of international clinical trials, the application of some of the outcomes was reasonable, focusing on patients' symptoms, quality of life and objective outcomes. However, there were still several problems: unclear primary and secondary outcome measures, insufficient attention to long-term prognosis, insufficient attention to social function, few TCM outcomes, lack of measurement blindness and the use of unreasonable composite outcomes. It is recommended that researchers should rationally design the outcome indicators of clinical trials and develop the core outcome set.


Subject(s)
Humans , Drugs, Chinese Herbal/therapeutic use , Intracranial Hemorrhage, Hypertensive/drug therapy , Medicine, Chinese Traditional , Quality of Life , Randomized Controlled Trials as Topic
5.
China Journal of Chinese Materia Medica ; (24): 2984-2994, 2021.
Article in Chinese | WPRIM | ID: wpr-888036

ABSTRACT

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage, four Chinese databases, four English databases, clinical trials registration center(ClinicalTrials.gov) and Chinese clinical trial registry were retrieved. The retrieval time was from the establishment of each database to September 9, 2020. According to the set criteria, the randomized controlled trial(RCT) of Naoxueshu Oral Liquid combined with conventional Western medicine was selected. The "Cochrane bias risk assessment" tool was used to evaluate the quality of the included studies. RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators. Eleven studies were finally included, with a total sample size of 1 221 cases, 612 cases in the treatment group and 609 cases in the control group. Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS) after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10), but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI [-1.39,-0.94],P<0.000 01). Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05) and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.000 1), but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13). In terms of effective rate, studies using Guideline for clinical trials of new patent Chinese medicines, NHISS or Glasgow outcome scale(GOS) had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RR_(Guideline for clinical trials of new patent Chinese medicines)=1.27,95%CI[1.10,1.46],P=0.001;RR_(NHISS)=1.26,95%CI[1.13,1.40],P<0.000 1;RR_(GOS)=1.54,95%CI[1.22,1.93],P=0.000 2). In reduction of hematoma volume, Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD_(2 week)=-2.31,95%CI[-3.12,-1.49],P<0.000 01;MD_(4 week)=-2.04,95%CI[-2.41,-1.68],P<0.000 01). GRADE system showed that the evidence level of the above outcome indicators was low and extremely low. In terms of adverse reactions, two of the included studies reported mild adverse reactions, and the rest of studies were not mentioned, so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid. This study showed that compared with conventional Western medicine, combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage. However, due to the high bias risk in the included studies, more large-sample and high-quality RCTs are still needed in the future.


Subject(s)
Humans , Drugs, Chinese Herbal/adverse effects , Intracranial Hemorrhage, Hypertensive/drug therapy , Nonprescription Drugs , Stroke
6.
Chinese Journal of Contemporary Pediatrics ; (12): 353-358, 2012.
Article in Chinese | WPRIM | ID: wpr-320647

ABSTRACT

<p><b>OBJECTIVE</b>N-acetyltransferase 2 (NAT2) and cytochrome P450 2EI (CYP2E1) play a crucial role in the drug metabolic process. The aim of this study was to understand the genotype and phenotype polymorphisms of NAT2 and CYP2E1 in the Han Chinese pediatric population in order to provide a theoretical basis for individualized drug treatment.</p><p><b>METHODS</b>A total of 341 (211 males and 130 females) randomly sampled Han Chinese children, aged from 2 months to 14 years, were enrolled in this study. Genotyping was carried out by PCR method, and metabolic phenotypes were identified.</p><p><b>RESULTS</b>In this study population, wild genotype was found as a major genotype in seven SNPs of NAT2, rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208 and rs1799931. The frequency of NAT2 fast metabolism was highest (61.3%), followed by middle to slow metabolism (34.1%). Wild genotype also predominated in the four SNPs of CYP2E1 (rs2031920, rs3813867, rs6413432 and rs72559720) named as CYP2E1*5, *6 and *2, with a frequency of 61.3%, 60.1% and 99.4% respectively. As the relationship between CYP2E1 genotype and phenotype was unknown, phenotyping of CYP2E1 was not done.</p><p><b>CONCLUSIONS</b>The important SNPs of NAT2 and CYP2E1 are predominantly wild genotype in the Han Chinese pediatric population. Fast metabolic phenotype predominates in important SNPs of NAT2.</p>


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Arylamine N-Acetyltransferase , Genetics , China , Ethnology , Cytochrome P-450 CYP2E1 , Genetics , Genotype , Phenotype , Polymorphism, Single Nucleotide
7.
Chinese Medical Journal ; (24): 275-280, 2012.
Article in English | WPRIM | ID: wpr-333502

ABSTRACT

<p><b>BACKGROUND</b>Very few researchers have studied the changes in peripheral lymphocyte patterns in adult tuberculosis (TB) and even less researches have been conducted in pediatric TB. In this study, we obtained blood samples from 114 Chinese pediatric TB patients and 116 matched controls to study the association of phenotypic subsets of peripheral lymphocytes with different clinical phenotypes of TB.</p><p><b>METHODS</b>The subjects were classified as the control group and the TB patients group which were further divided into a pulmonary TB group and an extra-pulmonary TB group (more serious than the former). The distribution of lymphocyte subpopulations, including T lymphocytes, CD4(+) T lymphocytes, CD8(+) T lymphocytes, B lymphocytes, and natural killer (NK) cells, were quantitatively analyzed by flow cytometry.</p><p><b>RESULTS</b>Compared to the healthy controls, TB infection was associated with significantly higher B cell (P < 0.0001), and lower T cell (P = 0.029) and NK cell (P < 0.0001) percentages. Compared to pulmonary TB patients, extra-pulmonary TB was associated with relatively higher B cell (P = 0.073), and lower T cell percentages (P = 0.021), higher purified protein derivative (PPD) negative rate (P = 0.061), and poorer PPD response (P = 0.010). Most pulmonary TB cases were primary pulmonary TB (89.1%), and most extra-pulmonary TB cases had TB meningitis (72.1%).</p><p><b>CONCLUSIONS</b>This study demonstrates changes in the lymhocyte distribution in children suffering from different clinical phenotypes of TB; such as primary pulmonary TB, and TB meningitis. These patterns may have significance in understanding the pathogenesis and prognostic markers of the disease, and for developing immunomodulatory modalities of therapy.</p>


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Asian People , B-Lymphocytes , Allergy and Immunology , CD4-Positive T-Lymphocytes , Allergy and Immunology , CD8-Positive T-Lymphocytes , Allergy and Immunology , Flow Cytometry , Immunophenotyping , Methods , Killer Cells, Natural , Allergy and Immunology , Lymphocytes , Allergy and Immunology , T-Lymphocytes , Allergy and Immunology , Tuberculosis , Allergy and Immunology
8.
Chinese Medical Journal ; (24): 2786-2791, 2010.
Article in English | WPRIM | ID: wpr-237415

ABSTRACT

<p><b>BACKGROUND</b>Prompt diagnosis of Mycobacterium tuberculosis (MTB) infection is an essential step in tuberculosis control and elimination. However, it is often difficult to accurately diagnose pediatric tuberculosis (TB). The tuberculin test (TST) may have a low specificity because of cross-reactivity with antigens present in Mycobacterium bovis bacillus Calmette-Guerin (BCG) and other mycobacteria, especially in China with a predominantly BCG-vaccinated population. Early-secreted antigenic target 6-kDa protein (ESAT-6) and culture filtrate protein 10 (CFP-10), stand out as suitable antigens that induce an interferon-gamma (IFN-γ) secreting, T-cell-mediated immune response to infection. While, considered the higher costs and complexity of the IFN-γ release assay (TSPOT), we aimed to evaluate the TSPOT and TST test in the clinical diagnosis of pediatric tuberculosis and to establish a diagnostic process suitable for China.</p><p><b>METHODS</b>The sensitivity and specificity of the assay were evaluated in total seventy four children with active tuberculosis and fifty one nontuberculous children with other disease, and then the results were compared with TST. Logistic regression models were used to identify variables that were associated with positive results for each assay. The independent variables included sex, age, birth place, vaccination history, close contract with an active TB patient.</p><p><b>RESULTS</b>The sensitivity of TSPOT was higher than TST in active TB children with or without BCG vaccination, as well as in children with culture-confirmed TB. But the difference was not significant statistically. Combining results of the TSPOT and TST improved the sensitivity to 94.6%. Agreement of the TST and TSPOT was low (77.0%, κ = 0.203) in active TB patients. The difference in specificity between TSPOT and TST test was statistically significant (94.1% vs. 70.6%, P = 0.006). Specificity of the two tests in patients without prior BCG vaccination history was similar (80.0% vs. 60.0%). The concordance between the two tests results in BCG vaccinated subjects was low (71.7%, κ = 0.063). For TSPOT, none of the included risk factors was significantly associated with positive results. For TST, BCG vaccination (OR: 1.78; 95%CI: 1.30 - 2.00) was significantly associated with positive results.</p><p><b>CONCLUSIONS</b>Although IFN-γ release assay had relatively high sensitivity and specificity, we also should consider the higher costs and complexity of this test. Therefore, TSPOT could be used as the complementary tool of TST in circumstances when a suspected patient with negative TST results, or to exclude a positive TST result caused by BCG vaccination.</p>


Subject(s)
Child , Child, Preschool , Female , Humans , Male , BCG Vaccine , Allergy and Immunology , Interferon-gamma , Bodily Secretions , Logistic Models , Sensitivity and Specificity , Tuberculin Test , Methods , Tuberculosis , Diagnosis , Vaccination
9.
Chinese Journal of Preventive Medicine ; (12): 215-222, 2009.
Article in Chinese | WPRIM | ID: wpr-242664

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the application of different variable number tandem repeats (VNTR) locus in genotyping of Mycobacterium tuberculosis (M.tuberculosis) strains isolated from eight provinces in China, and to find the suitable locus-set of VNTR for epidemical strains in China.</p><p><b>METHODS</b>All 140 M.tuberculosis strains were randomly selected from 2800 M.tuberculosis strains isolated from eight provinces in China, 27 VNTR loci were used for typing all isolates. Discriminatory power (Hunter-Gaston Index, HGI) of every locus and different locus-set were analyzed by BioNumerics software. Meanwhile, Spoligotyping was used to identify Beijing family and non-Beijing family. Then the HGI of different locus-sets in two families was also evaluated.</p><p><b>RESULTS</b>All 140 isolates were clustered into Beijing kindred (112 strains, 80%) and non-Beijing kindred (28 strains, 20%) by Spoligotyping. The discriminatory power of Spoligotyping in 140 isolates was 0.4589. Every locus showed different polymorphism and HGI were from 0 to 0.809. The number of VNTR loci with HGI higher than 0.5 in all strains, Beijing family and non-Beijing family was 8, 7 and 14 respectively. 27 loci were combined into four groups which included 8, 12, 15 and 24 VNTR loci respectively. Four locus-sets showed different polymorphism, HGI of eight-locus, 12-locus, 15-locus, and 24-locus set in 140 strains was 0.9991, 0.9882, 0.9980 and 0.9986, and their discriminatory power were calculated in Beijing kindred (HGI: 0.9987, 0.9318, 0.9969 and 0.9975) and non-Beijing kindred (HGI: 1, 0.9894, 1 and 1).</p><p><b>CONCLUSION</b>Different VNTR locus and locus-set showed different discriminatory power in the selected M.tuberculosis strains isolated from China. Eight-locus set can be used in molecular epidemiological study of M.tuberculosis in China after standardization.</p>


Subject(s)
Bacterial Typing Techniques , DNA, Bacterial , Genetics , Mycobacterium tuberculosis , Classification , Genetics , Tandem Repeat Sequences
10.
Chinese Journal of Contemporary Pediatrics ; (12): 283-287, 2009.
Article in Chinese | WPRIM | ID: wpr-347936

ABSTRACT

<p><b>OBJECTIVE</b>Tuberculosis is still a public health problem. Host genetic factors, such as polymorphisms in NRAMP1 gene, may play a role in the development of tuberculosis. To clarify the effect of NRAMP1 gene polymorphisms on the development of childhood tuberculosis, the association of NRAMP1 gene polymorphisms with susceptibility to tuberculosis in the ethnic Han Chinese children was investigated.</p><p><b>METHODS</b>From January 2005 to March 2008, 130 ethnic Han children with tuberculosis (TB group) were enrolled. Three hundred and ninety hospitalized ethnic Han children for physical examination in the surgery department were used as the control group. The controls were matched with tuberculosis children by age, sex and area. PCR-RFLP analysis was performed on DNA samples to identify allele genotypes of INT4 and D543N in NRAMP1 gene. Genotype frequency differences between tuberculosis patients and controls were analyzed using x2 test.</p><p><b>RESULTS</b>No statistical difference was found in the genotype frequency of variants G/C and C/C at the INT4 locus between the TB and the control groups. At the D543N locus, the frequency of genotype variants (G/A and A/A) was significantly higher in the TB group (34/130) than that in the control group (66/390) (x2=5.349, P<0.05; OR=1.74, 95%CI=1.08-2.79). When stratified by sex, differences in the genotype distribution were observed only in females at the D543N locus, which the variant genotypes were higher in the TB group (16/52) than in the control group (21/155) (x2=7.866, P<0.05; OR=2.84, 95%CI=1.34-5.99). For males, there was no difference between the TB and the control groups. At the INT4 locus, no difference was observed between the two groups in boys and girls.</p><p><b>CONCLUSIONS</b>Genotypic variation at the D543N locus in NRAMP1 gene may be associated with susceptibility to tuberculosis in ethnic Han Chinese children. Variant genotypes in NRAMP1 gene (G/A and A/A) may be susceptible genotypes to tuberculosis in ethnic Han Chinese children. Girls with variant genotypes were more susceptible to tuberculosis.</p>


Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Cation Transport Proteins , Genetics , China , Ethnology , Gene Frequency , Genetic Predisposition to Disease , Genotype , Polymorphism, Genetic , Sex Factors , Tuberculosis , Ethnology , Genetics
11.
Chinese Medical Journal ; (24): 30-34, 2009.
Article in English | WPRIM | ID: wpr-265879

ABSTRACT

<p><b>BACKGROUND</b>Congenital heart disease is a diverse group of diseases determined by genetic and environmental factors. Considerable research has been done on genes associated with development of the heart. A recent focus is the role of transcription factor TBX5 in the development of atria, left ventricle and conduction system. As part of a larger study, high density, single nucleotide polymorphism (SNP) scanning was used to explore the relationship between TBX5 gene polymorphism and susceptibility to ventricular septal defect not associated with forelimb malformation in the Chinese Han population.</p><p><b>METHODS</b>One hundred and ninety two paediatric patients with congenital ventricular septal defect and 192 matched healthy control subjects were studied. The haplotype reconstructions were calculated by PHASE2.0 software. Haploview software was used to perform linkage disequilibrium assessment and defining of haplotype blocks. The algorithm used for defining of blocks was the confidence interval method.</p><p><b>RESULTS</b>The TBX5 gene region can be divided into 3 haplotype blocks of 27, 15 and 2 SNPs. Strong linkage disequilibrium exists within each block. SNP rs11067075 within the TBX5 gene had significant correlation with ventricular septal defect (P = 0.0037) by single marker association analysis. In addition, a 20 kb haplotype composed of 27 SNPs correlated with ventricular septal defect (P = 0.05, multiple loci regression analyses based on reconstructed haplotype blocks).</p><p><b>CONCLUSIONS</b>TBX5 is associated with the occurrence of ventricular septal defect and may be a predisposing gene to congenital heart disease in Han Chinese. This finding has set a direction for further genetic and functional studies.</p>


Subject(s)
Humans , Asian People , Genetics , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Haplotypes , Genetics , Heart Septal Defects, Ventricular , Genetics , Linkage Disequilibrium , Genetics , Polymorphism, Genetic , Genetics , Polymorphism, Single Nucleotide , T-Box Domain Proteins , Genetics
12.
Chinese Medical Journal ; (24): 814-819, 2007.
Article in English | WPRIM | ID: wpr-240325

ABSTRACT

<p><b>BACKGROUND</b>China is one of the high burden countries of Mycobacterium tuberculosis (TB) infection globally, with high incidence and mortality. We studied the molecular characteristics of rifampin (RIF) and isoniazid (INH) resistant Mycobacterium tuberculosis strains from Beijing, China, in order to find out the genetic marker for rapid detection of specific drug resistance.</p><p><b>METHODS</b>Forty pansusceptible and 81 resistant strains of Mycobacterium tuberculosis isolated from Beijing, China during 2002-2005 were analyzed. The modified rifampin oligonucleotide (RIFO) assay based on reverse line blot hybridization was used to detect mutations in the 81 bp hot-spot region of rpoB gene, which is associated with RIF resistance. The INH resistance associated genes, regulatory region mab-inhA (-15C/T) and structural gene katG S315T were detected by reverse line blot hybridization and PCR-restriction fragment length polymorphism (RFLP) method respectively. All the strains were typed by spoligotying and the Beijing genotype was further subdivided by NTF locus analysis. The distribution of drug resistance associated mutations in the above genes was compared in these groups.</p><p><b>RESULTS</b>Sixty-five (91.5%) of 71 RIF resistant and 52 (92.9%) of 56 multidrug-resistant (MDR, i.e. resistant to at least RIF and INH) strains were found to harbor mutations in the rpoB hot-spot region. No mutation was detected in RIF sensitive strains. The specificity and sensitivity of the modified RIFO assay were 100% and 91.5%, respectively. katG315 AGC>ACC and inhA-15C>T mutations were found in 40 (60.6%) and 10 (15.2%) of 66 INH resistant strains, respectively; 7.6% of INH-resistant strains had mutations in both of these genes. Therefore, a combined use of both katG315 and inhA-15 identified 68.2% of INH-resistant strains. The Beijing genotype accounted for 91.7% of total strains and was further subdivided into "modern" (76.6%) and "ancestral" (23.4%) group. There is no significant difference between "ancestral" and "modern" group in prevalance of drug resistance-associated gene mutations.</p><p><b>CONCLUSIONS</b>The hot-spot region of rpoB gene can be used as genetic marker for detection of RIF resistant strains; a combined use of both katG315 and inhA-15 can improve the detection rate of INH resistant strains; the Beijing genotype is prevalent in Beijing, China; the modified RIFO assay can be a practical tool for rapid detection of RIF resistant and MDR isolates in the routine diagnostic work.</p>


Subject(s)
Antitubercular Agents , Pharmacology , Bacterial Proteins , Genetics , Catalase , Genetics , DNA Transposable Elements , DNA, Bacterial , DNA-Directed RNA Polymerases , Drug Resistance, Bacterial , Isoniazid , Pharmacology , Microbial Sensitivity Tests , Mutation , Mycobacterium tuberculosis , Genetics , Rifampin , Pharmacology
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