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Lin F.-S.,Nanjing Chest Hospital | Wu M.-Y.,The Fifth Peoples Hospital of Suzhou | Tu W.-J.,The Third Peoples Hospital of Changzhou | Pan H.-Q.,The Third Peoples Hospital of Zhenjiang | And 9 more authors.
Journal of Thoracic Disease | Year: 2015

Background: To investigate the prevalence of and risk factors for leukopenia in tuberculosis patients and the impact of anti-tuberculosis regimens on the occurrence of leukopenia in newly treated tuberculosis patients. Methods: A total of 1,904 tuberculosis patients were included in the study. A cross-sectional survey of the prevalence of leukopenia was initially conducted, and then factors influencing leukopenia were identified using Logistic regression analysis. Non-treatment factors influencing peripheral blood leukocyte counts were analyzed using univariate COX proportional hazards models. Covariate analysis was used to assess the independent effect of different anti-tuberculosis regimens on peripheral blood leukocyte counts. Results: Being female, advanced age and longer duration of previous anti-tuberculosis treatment (>6 month) were risk factors for leukopenia in tuberculosis patients, while secondary pulmonary tuberculosis, higher body mass index (BMI: 24-27.9 kg/m2), and higher degree of education (senior high school or above) were protective factors. Gender, vegetable consumption, drinking, pulmonary infection, other chronic diseases, and use of antibiotics were significantly associated with the development of leukopenia in patients on antituberculosis treatment. In tuberculosis patients treated with anti-tuberculosis regimens not containing antibiotics, peripheral blood leukocyte levels gradually declined with the prolongation of treatment duration. In tuberculosis patients treated with anti-tuberculosis regimens containing antibiotics, peripheral blood leukocyte levels showed a declining trend. Conclusions: Female patients, patients at advanced age and recurrent tuberculosis patients having longer previous anti-tuberculosis treatment are high-risk populations for leukopenia. Attention should be paid to the influence of vegetable consumption and drinking, co-morbidities and use of antibiotics during antituberculosis treatment. © Journal of Thoracic Disease.

Gu J.,Tongji University | Tang S.-J.,Capital Medical University | Tan S.-Y.,Guangzhou Chest Hospital | Wu Q.,Tianjin Haihe Hospital | And 10 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

Objective: To assess the clinical efficacy and safety of Silibinin in preventing drug-induced liver injury (DILI) in the general population (high-risk patients with non-drug induced liver injury). Method: A prospective, multi-center, randomized, open-label and controlled trial was conducted with 568 patients undergoing primary treatment of pulmonary tuberculosis. The study included 277 patients in experimental group and 291 patients in control group. The patients in the two group were treated with conventional 2HREZ (S)/4HR for tuberculosis (TB), and additional Silibinin capsules (oral administration of 70 mg/time, 3 times/day for 8 weeks in experimental group. Outcomes of liver function, interruption of anti-TB treatment and therapeutic results, as well as adverse reactions were observed and analyzed. Results: At 2, 4 and 8 weeks of treatment, the incidences of liver injury in experimental group were 3.97%, 1.44% and 2.17%, respectively; the incidences in control group were 4.12%, 4.12% and 2.41%, respectively. Statistical analysis showed that there was no difference in the incidence between the two groups at each treatment period (P>0.05). At 8 weeks, the numbers of patients diagnosed of DILI were 18 (7.22%) and 27 (9.28%) in experimental and control groups, respectively (P>0.05). 34.30% and 27.49% of the patients in experimental and control groups had transient abnormal liver function or symptoms, respectively; similar percentages (3.25% and 6.19%) of the patients in two groups have liver function injury and symptoms, and were suspended for anti-TB treatment (P>0.05). The incidence of anorexia and nausea symptoms was lower in experimental group than in control group, and the differences were significant at 4 and 8 weeks (P<0.05). 8 weeks after the treatment, 98.30% of the sputum smear culture were negative in experimental group, which was significantly higher (P<0.01) than that in control group (92.98%). Conclusion: Preventive hepatoprotective therapy in the general population may reduce drug discontinuation rate, improve patient’s compliance and outcomes of anti-TB treatment. © 2015, Int J Clin Exp Med. All rights reserved.

Zhou A.-P.,Shanghai JiaoTong University | Zhou A.-P.,Tibet University | Xu Z.-H.,Shanghai JiaoTong University | Sun Q.,Shanghai JiaoTong University | And 2 more authors.
Journal of Shanghai Jiaotong University (Medical Science) | Year: 2012

Objective: To analyse the 5 MIRU loci of Mycobacterium tuberculosis, and investigate the relationship between polymorphisms of MIRU loci and expression of downstream genes. Methods: Bioinformatics method was used to predict the downstream genes promoter regions of 5 MIRU loci (ETR-C, Mtub-30, Mtub-39, MIRU-27 and MIRU- 40). Promoter sequence was amplified by PCR, and was cloned into mycobacterial promoterless probe vector pMC210 to generate the recombinants. After confirmation by restriction endonuclease digestion and sequence analysis, the recombinant plasmids were transformed into mycobacterium smegmatis mc2155 by electroporation. The transcriptional level of reporter gene lacZ was evaluated by Real-Time PCR, and the influence of polymorphisms of MIRU loci on the expression of downstream genes was examined. Results: Mtub-39 locus core region contained the promoter of the downstream gene. The recombinant plasmids harboring Mtub-39 locus with 1, 3 or 5 copy numbers were constructed. Real-Time PCR revealed that Mtub-39 locus with polymorphisms (pMC210-Mtub-39-N158, pMC210-Mtub-39-N139 and pMC210-Mtub-39-N146) had significant differences in the transcriptions of reporter gene lacZ (P=0.0065). Conclusion: The polymorphisms of Mtub-39 can significantly affect the promotor activity of the downstream genes, and sequentially regulate the expression of the gene.

Qian F.,The Fifth Peoples Hospital of Suzhou | Li M.,The Fifth Peoples Hospital of Suzhou | Zhu C.-W.,The Fifth Peoples Hospital of Suzhou
World Chinese Journal of Digestology | Year: 2015

Chronic hepatitis caused by hepatitis B virus (HBV) infection remains an incurable disease at present, which is mainly because the approved antiviral agents, such as interferon-alpha and nucleos(t)ide analogues, cannot effectively eradicate intrahepatic hepatitis B virus covalently closed circular DNA (cccDNA). And thus a suboptimal efficacy of antiviral agents and relapse after therapy occur very commonly. Therefore, novel drugs and treatment strategies remain to be developed on the basis of further theoretical and clinical research of HBV infection to achieve the ultimate goal of eradication of HBV cccDNA in the future. In this paper, we discuss multiple agents and therapeutic regimens influencing cccDNA levels, in order to help clinicians comprehensively understand the present situation in the research of the clearance of HBV cccDNA. © 2015 Baishideng Publishing Group Inc. All rights Reserved.

Wang Z.R.,Soochow University of China | Wang J.H.,Soochow University of China | Hu C.L.,Soochow University of China | Cao W.G.,The Fifth Peoples Hospital of Suzhou | And 4 more authors.
Brazilian Journal of Medical and Biological Research | Year: 2011

Searching for effective Smad3 gene-based gene therapies for hepatic fibrosis, we constructed siRNA expression plasmids targeting the rat Smad3 gene and then delivered these plasmids into hepatic stellate cells (HSCs). The effect of siRNAs on the mRNA levels of Smad2, Smad3, Smad4, and collagens I-α1, III-α1 and IV-α1 (Col1α1, Col3α1, Col4α1, respectively) was determined by RT-PCR. Eighty adult male Sprague-Dawley rats were randomly divided into three groups. Twice a week for 8 weeks, the untreated hepatic fibrosis model (N = 30) and the treated group (N = 20) were injected subcutaneously with 40% (v/v) carbon tetrachloride (CCl 4)-olive oil (3 mL/kg), and the normal control group (N = 30) was injected with olive oil (3 mL/ kg). In the 4th week, the treated rats were injected subcutaneously with liposome-encapsulated plasmids (150 μg/kg) into the right liver lobe under general anesthesia once every 2 weeks, and the untreated rats were injected with the same volume of buffer. At the end of the 6th and 8th weeks, liver tissue and sera were collected. Pathological changes were assessed by a semi-quantitative scoring system (SSS), and a radioimmunoassay was used to establish a serum liver fibrosis index (type III procollagen, type IV collagen, laminin, and hyaluronic acid). The mRNA expression levels of the above cited genes were reduced in the HSCs transfected with the siRNA expression plasmids. Moreover, in the treated group, fibrosis evaluated by the SSS was significantly reduced (P < 0.05) and the serum indices were greatly improved (P < 0.01). These results suggest that Smad3 siRNA expression plasmids have an anti-fibrotic effect.

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