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Inhibitory effect of specific small interference RNA targeted against transforming growth factor β1 in mice with hepatic fibrosis infected with Schistosoma japonicum 特异性小干扰RNA对日本血吸虫感染肝纤维化小鼠转化生长因子β1的抑制作用
Pub Date : 2019-09-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.09.008
Luwen Wang, Hui Chen, F. Jiao, Fan Yang, Xun Li, Haiyue Zhang
Objective To investigate the inhibitory effect of small interference RNA (siRNA) targeted against transforming growth factor β1 (TGFβ1) in mice with hepatic fibrosis infected with Schistosoma japonicum. Methods Three short hairpin RNAs (shRNA) targeting different positions of TGFβ1 and one unrelated control sequence (HK) were designed and cloned to a plasmid pGenesil-1 respectively to obtain four recombinant expression vectors. Thirty male BALB/c mice were randomly divided into six groups, including normal group, model group, control group (pGenesil-HK) and three treatment groups (pGenesil-TGFβ1-m1, pGenesil-TGFβ1-m2 and pGenesil-TGFβ1-m3) and each group had five mice. The hepatic fibrosis animal models infected with Schistosoma japonicum were constructed. The levels of hydroxyproline (HYP) in liver tissue were examined by biochemistry. Liver histopathology was examined by hematoxylin-eosin and Masson staining. The mRNA expression and protein expression levels of TGFβ1, mothers against decapentaplegic homolog (Smad) 3, Smad 7 and α-smooth muscle actin (α-SMA) in the livers were detected by quantitative real time polymerase chain reaction (RT-qPCR) and Western blot. Two independent samples t test was used to compare the measurement data between groups. Results The liver fibrogenesis was obviously improved in all treatment groups compared with model group.The levels of HYP of liver tissue in all treatment groups were significantly lower than that in model group (t=14.870, 7.097 and 10.741, respectively, all P<0.01). The mRNA expression levels of TGFβ1, Smad 3 and α-SMA(model group vs pGenesil-TGFβ1-m1 group, t=3.235, 5.141 and 10.026, respectively; model group vs pGenesil-TGFβ1-m2 group, t=3.396, 5.145 and 4.951, respectively; model group vs pGenesil-TGFβ1-m3 group, t=3.511, 5.429 and 6.485, respectively)and protein (model group vs pGenesil-TGFβ1-m1 group, t=8.847, 8.044 and 10.746, respectively; model group vs pGenesil-TGFβ1-m2 group, t=9.709, 7.484 and 10.847, respectively; model group vs pGenesil-TGFβ1-m3 group, t=9.672, 8.766 and 11.508, respectively) were significantly decreased in all treatment groups compared with model group (all P< 0.01), while the levels of Smad 7 mRNA and protein were significantly increased in all treatment groups compared with model group(t=11.742 and 11.211, respectively in pGenesil-TGFβ1-m1 group; t=14.446 and 13.736, respectively in pGenesil-TGFβ1-m2 group; t=10.892 and 10.908, respectively in pGenesil-TGFβ1-m3 group, all P< 0.01). Conclusions Specific siRNA targeting TGFβ1 could significantly inhibit the liver fibrogenesis in mice infected with Schistosoma japonicum. The anti-fibrosis mechanisms of the siRNA maybe associated with the down-regulation of TGFβ1, Smad 3 and α-SMA expressions and up-regulation of Smad 7 expression in liver tissue, which results in suppressing the activation of hepatic stellate cells. Key words: Transforming growth factor beta 1; RNA, small interfering; Schistoso
目的探讨小干扰RNA (siRNA)对日本血吸虫感染肝纤维化小鼠转化生长因子β1 (tgf - β1)的抑制作用。方法设计3个靶向tgf - β1不同位置的短发夹rna (short hairpin RNAs, shRNA)和1个不相关的对照序列(HK),分别克隆到质粒pGenesil-1上,获得4个重组表达载体。将30只雄性BALB/c小鼠随机分为正常组、模型组、对照组(pGenesil-HK)和治疗组(pGenesil-TGFβ1-m1、pGenesil-TGFβ1-m2和pGenesil-TGFβ1-m3) 6组,每组5只。建立了日本血吸虫感染肝纤维化动物模型。采用生化法检测大鼠肝组织中羟脯氨酸(HYP)水平。苏木精-伊红染色、马松染色检查肝脏组织病理学。采用定量实时聚合酶链式反应(RT-qPCR)和Western blot检测大鼠肝脏中tgf - β1、抗十肢瘫痪同源物(Smad) 3、Smad 7和α-平滑肌肌动蛋白(α-SMA) mRNA和蛋白表达水平。采用两独立样本t检验比较组间计量资料。结果与模型组比较,各治疗组肝纤维化明显改善。各给药组大鼠肝组织中HYP水平均显著低于模型组(t分别为14.870、7.097、10.741,P均<0.01)。tgf - β1、Smad 3、α-SMA mRNA表达量(模型组vs pgenesil - tgf - β1-m1组,t分别=3.235、5.141、10.026;模型组与pgenesil - tgf - β1-m2组比较,t=3.396、5.145、4.951;模型组vs pgenesil - tgf - β1-m3组,t分别为3.511、5.429、6.485)和蛋白组(模型组vs pgenesil - tgf - β1-m1组,t分别为8.847、8.044、10.746);模型组与pgenesil - tgf - β1-m2组比较,t=9.709、7.484、10.847;模型组与pgenesil - tgf - β1-m1组比较,t=9.672、8.766、11.508)均显著降低(P均< 0.01),各处理组与模型组比较,Smad 7 mRNA和蛋白水平均显著升高(t=11.742、11.211,P< 0.01);pgenesil - tgf - β1-m2组t=14.446、13.736;pgenesil - tgf - β1-m3组t=10.892、10.908,均P< 0.01)。结论靶向tgf - β1的siRNA可显著抑制日本血吸虫感染小鼠肝纤维化的发生。siRNA的抗纤维化机制可能与下调肝组织中tgf - β1、Smad 3和α-SMA的表达,上调Smad 7的表达,从而抑制肝星状细胞的活化有关。关键词:转化生长因子β 1;RNA,小干扰;日本血吸虫;肝纤维化
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引用次数: 0
Preventive effects of antifungal drugs in patients with acute-on-chronic liver failure treated with glucocorticoid 抗真菌药物对糖皮质激素治疗急慢性肝功能衰竭的预防作用
Pub Date : 2019-09-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.09.006
Tingting Yu, Lunli Zhang, S. Ge, Xiaopeng Li
Objective To explore the efficacy of glucocorticoid (GC) therapy on hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF), and the effectiveness and safety of voriconazole (VCZ) in preventing pulmonary Aspergillus infection in HBV-ACLF patients treated with GC. Methods Two hundred and thirty-two patients with HBV-ACLF were enrolled from January 2016 to December 2018 in the First Affiliated Hospital of Nanchang University. They were divided into non-GC group (104 cases), GC group (74 cases), and GC+ VCZ group (54 cases). The observation period was four months. The baseline liver function, the incidence of pulmonary Aspergillus infection, the survival rate during observation period, and the incidence of complications were compared among the three groups. The adverse reactions of VCZ were observed to identify the best dose for prevention. Quantitative data were analyzed by analysis of variance or rank sum test. Count data were analyzed by chi-square test or Fisher exact test. Results The baseline liver functions were not significantly different among the three groups (all P>0.05). The incidence of pulmonary Aspergillus infection in the GC group (22.97%(17/74)) was both higher than that in the non-GC group (5.77%(6/104)) and GC+ VCZ group (1.85%(1/54)), the differences were both statistically signifrcant (χ2=11.373 and 9.843, respectively, both P<0.01). The overall mortality rate of HBV-ACLF patients with pulmonary Aspergillus infection was 79.2%(19/24). The survival rate in non-GC group (37.5%(39/104)) showed no statistical difference with that in GC group (39.19%(29/74), χ2=0.052, P=0.819). The survival rate of GC+ VCZ group (66.67%(36/54)) was significantly higher than that in GC group and non-GC group (χ2 =12.126 and 9.431, respectively, both P<0.01). The blood concentrations of VCZ were randomly measured in 16 patients from the GC+ VCZ group, and the range was 0.82-5.38 mg/L, with no evident adverse reactions. Conclusions The GC treatment is effective in HBV-ACLF patients in early stage. The VCZ treatment effectively reduces the incidence of pulmonary Aspergillus infection in HBV-ACLF patients receiving GC treatment and increases the survival rate. Oral VCZ (200 mg/d) treatment has a stable blood concentration in HBV-ACLF patients, with rare adverse reactions and good safety. Key words: Hepatitis B virus; Glucocorticoid; Acute-on-chronic liver failure; Voriconazole
目的探讨糖皮质激素(GC)治疗乙型肝炎病毒(HBV)相关急慢性肝功能衰竭(ACLF)的疗效,以及伏立康唑(VCZ)预防GC治疗的HBV-ACLF患者肺曲霉菌感染的有效性和安全性。方法选择2016年1月至2018年12月在南昌大学第一附属医院就诊的232例HBV-ACLF患者。分为非GC组(104例)、GC组(74例)和GC+VCZ组(54例)。观察期为4个月。比较三组患者的基线肝功能、肺曲霉菌感染发生率、观察期生存率和并发症发生率。观察VCZ的不良反应,以确定预防的最佳剂量。定量数据通过方差分析或秩和检验进行分析。计数数据采用卡方检验或Fisher精确检验进行分析。结果三组基线肝功能差异无统计学意义(均P>0.05):GC组肺曲霉菌感染发生率(22.97%(17/74))均高于非GC组(5.77%(6/104))和GC+VCZ组(1.85%(1/54)),HBV-ACLF患者合并肺曲霉菌感染的总死亡率为79.2%(19/24),非GC组的生存率(37.5%(39/104))与GC组(39.19%(29/74),GC+VCZ组的生存率(66.67%(36/54))显著高于GC组和非GC组(χ2=12.126和9.431,均P<0.01)。结论GC治疗早期HBV-ACLF是有效的。VCZ治疗有效降低了接受GC治疗的HBV-ACLF患者的肺曲霉菌感染发生率,并提高了生存率。口服VCZ(200mg/d)治疗HBV-ACLF患者血药浓度稳定,不良反应少,安全性好。关键词:乙型肝炎病毒;糖皮质激素;急性或慢性肝功能衰竭;伏立康唑
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引用次数: 0
Effect of hepatitis B virus X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B patients complicated with hepatocellular carcinoma 乙型肝炎病毒X基因整合对慢性乙型肝炎合并肝癌患者锌指蛋白ZBTB20表达的影响
Pub Date : 2019-09-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.09.007
Zebao He, Qiuyue Chen, Jiansheng Zhu, Yang Lu, Hai-hong Zhao, Zheping Fang
Objective To investigate the effect of hepatitis B virus (HBV) X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B (CHB) patients complicated with hepatocellular carcinoma (HCC). Methods Eighteen CHB patients complicated with HCC who underwent surgical treatment in Taizhou Enze Medical Center Enze Hospital and Taizhou Central Hospital from July 2015 to June 2017 were enrolled. Samples of carcinoma tissue, para-carcinoma tissue and corresponding normal liver tissue were collected from each case. DNA was extracted from three kinds of tissue samples. HBV-Alu-polymerase chain reaction (PCR) was used to amplify the integrated HBVX fragments and their bilateral flanking sequences in human genomic DNA. The integrated HBV fragments were determined by PCR products sequencing. Protein was extracted from three kinds of tissue samples.The level of expression of ZBTB20 was detected by protein imprinting. Statistical analysis was performed using t test, analysis of variance, and χ2 test. Results Among the 18 CHB patients complicated with HCC, integration of HBVX gene was found in 13 carcinoma tissue samples, 16 para-carcinoma tissue samples and 9 corresponding normal liver tissue samples. The difference was statistically significant (χ2=6.353, P=0.037). Of the 18 patients, the protein expressions of ZBTB20 in carcinoma tissue, para-carcinoma tissue and corresponding normal tissue were (50.14±11.25)%, (40.71±7.17)% and (39.06±5.17)%, respectively, which was statistically different (F=9.420, P<0.01). HBVX gene integration was detected at ZBTB20 locus in five patients. The expression levels of ZBTB20 in patients with HBVX gene integration at this locus in carcinoma tissue, para-carcinoma tissue and corresponding, normal liver tissue were all significantly lower than those in patients without HBVX gene integration (carcinoma tissue (37.37±10.30)% vs (55.06±7.06)%, para-carcinoma tissue (32.06±2.61)% vs (44.04±5.24)%, corresponding normal tissue (34.66±5.59)% vs (40.76±4.04)%, t=4.205, 4.821 and 2.589, respectively, all P<0.05). Conclusions Incidence of HBVX integration in para-carcinoma tissue is higher than that in carcinoma tissue in CHB patients complicated with HCC.The expression level of ZBTB20 in carcinoma tissue is higher than that in para-carcinoma tissue. Integration of HBVX gene at ZBTB20 locus may decreases the expression of ZBTB20. Key words: Hepatitis B virus; Carcinoma, hepatocellular; Gene integration; Zinc finger protein ZBTB20
目的探讨乙型肝炎病毒(HBV) X基因整合对慢性乙型肝炎(CHB)合并肝细胞癌(HCC)患者锌指蛋白ZBTB20表达的影响。方法选取2015年7月至2017年6月在泰州市恩泽医疗中心恩泽医院和泰州市中心医院行手术治疗的18例CHB合并HCC患者。取癌组织、癌旁组织及相应的正常肝组织标本。从三种组织样本中提取DNA。采用hbv - alu聚合酶链式反应(PCR)扩增HBVX整合片段及其在人类基因组DNA中的双侧序列。聚合酶链反应产物测序检测HBV整合片段。从三种组织样本中提取蛋白质。采用蛋白印迹法检测ZBTB20的表达水平。采用t检验、方差分析和χ2检验进行统计学分析。结果在18例CHB合并HCC患者中,13例癌组织样本、16例癌旁组织样本和9例相应的正常肝组织样本中发现HBVX基因整合。差异有统计学意义(χ2=6.353, P=0.037)。18例患者癌组织、癌旁组织及相应正常组织中ZBTB20蛋白表达分别为(50.14±11.25)%、(40.71±7.17)%、(39.06±5.17)%,差异有统计学意义(F=9.420, P<0.01)。5例患者在ZBTB20位点检测到HBVX基因整合。在该位点整合HBVX基因的患者中,ZBTB20在癌组织、癌旁组织和相应的正常肝组织中的表达水平均显著低于未整合HBVX基因的患者(癌组织(37.37±10.30)% vs(55.06±7.06)%,癌旁组织(32.06±2.61)% vs(44.04±5.24)%,相应的正常组织(34.66±5.59)% vs(40.76±4.04)%,t分别=4.205、4.821和2.589,P均<0.05)。结论CHB合并HCC患者HBVX在癌旁组织的整合率高于癌组织。ZBTB20在癌组织中的表达水平高于癌旁组织。在ZBTB20位点整合HBVX基因可降低ZBTB20的表达。关键词:乙型肝炎病毒;癌,肝细胞;基因整合;锌指蛋白ZBTB20
{"title":"Effect of hepatitis B virus X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B patients complicated with hepatocellular carcinoma","authors":"Zebao He, Qiuyue Chen, Jiansheng Zhu, Yang Lu, Hai-hong Zhao, Zheping Fang","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.09.007","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.09.007","url":null,"abstract":"Objective \u0000To investigate the effect of hepatitis B virus (HBV) X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B (CHB) patients complicated with hepatocellular carcinoma (HCC). \u0000 \u0000 \u0000Methods \u0000Eighteen CHB patients complicated with HCC who underwent surgical treatment in Taizhou Enze Medical Center Enze Hospital and Taizhou Central Hospital from July 2015 to June 2017 were enrolled. Samples of carcinoma tissue, para-carcinoma tissue and corresponding normal liver tissue were collected from each case. DNA was extracted from three kinds of tissue samples. HBV-Alu-polymerase chain reaction (PCR) was used to amplify the integrated HBVX fragments and their bilateral flanking sequences in human genomic DNA. The integrated HBV fragments were determined by PCR products sequencing. Protein was extracted from three kinds of tissue samples.The level of expression of ZBTB20 was detected by protein imprinting. Statistical analysis was performed using t test, analysis of variance, and χ2 test. \u0000 \u0000 \u0000Results \u0000Among the 18 CHB patients complicated with HCC, integration of HBVX gene was found in 13 carcinoma tissue samples, 16 para-carcinoma tissue samples and 9 corresponding normal liver tissue samples. The difference was statistically significant (χ2=6.353, P=0.037). Of the 18 patients, the protein expressions of ZBTB20 in carcinoma tissue, para-carcinoma tissue and corresponding normal tissue were (50.14±11.25)%, (40.71±7.17)% and (39.06±5.17)%, respectively, which was statistically different (F=9.420, P<0.01). HBVX gene integration was detected at ZBTB20 locus in five patients. The expression levels of ZBTB20 in patients with HBVX gene integration at this locus in carcinoma tissue, para-carcinoma tissue and corresponding, normal liver tissue were all significantly lower than those in patients without HBVX gene integration (carcinoma tissue (37.37±10.30)% vs (55.06±7.06)%, para-carcinoma tissue (32.06±2.61)% vs (44.04±5.24)%, corresponding normal tissue (34.66±5.59)% vs (40.76±4.04)%, t=4.205, 4.821 and 2.589, respectively, all P<0.05). \u0000 \u0000 \u0000Conclusions \u0000Incidence of HBVX integration in para-carcinoma tissue is higher than that in carcinoma tissue in CHB patients complicated with HCC.The expression level of ZBTB20 in carcinoma tissue is higher than that in para-carcinoma tissue. Integration of HBVX gene at ZBTB20 locus may decreases the expression of ZBTB20. \u0000 \u0000 \u0000Key words: \u0000Hepatitis B virus; Carcinoma, hepatocellular; Gene integration; Zinc finger protein ZBTB20","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44411884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of highly active antiretroviral therapy on growth and development of infants and children 高效抗逆转录病毒疗法对婴幼儿生长发育的影响
Pub Date : 2019-08-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.08.004
Jin Li, Zhenyu Xu, Yan He, Pei Pi, Jie-min Li, Zhu-ren Zhou
Objective To investigate the effect of high active antiretroviral therapy (HAART) on growth and development of infants born to pregnant women infected with human immunodeficiency virus (HIV) and the effect on blocking mother to children transmission. Methods Totally 165 pregnant women diagnosed with HIV infection from May 2006 to May 2017 and their 169 infants, including four pairs of twins were enrolled, and 82 infants born to HIV negative pregnant women in the same period were enrolled as control. All of the pregnant women in the experimental group were administrated with HAART when HIV antibody test was positive. The delivery intervention and artificial feeding were carried out as well. The weight, height, hemoglobin (Hb), serum iron and serum calcium level of infants at birth, 12 months and six years old were monitored and compared between the two groups. Apgar scores of newborns and intelligence tests at six-year-old were also recorded. Statistical analysis was performed by t test. Results Pregnant women were generally in good conditions and well tolerated to the drugs. There were no significant differences in neonatal Apgar scores, body weight, body length, Hb, serum iron, serum calcium and CD4+ T lymphocyte count between HIV positive experimental group and control group (t =-1.27, -1.12, -3.41, -5.62, -0.89, -3.02 and-0.74, respectively, all P>0.05). At the age of 12 months, there were no significant differences in body weight, length, Hb, serum iron, serum calcium and CD4+ T lymphocyte count between the two groups (t = 1.02, 1.41, 1.32, 1.03, 0.89 and 1.06, respectively, all P > 0.05). At the age of six years, there were no significant differences in all indexes between the two groups (t= 1.02, 0.87, 1.58, 1.03, 0.92 and 2.07, respectively, all P > 0.05). Intelligence assessment was performed in 78 children of the experimental group and 45 children of the control group at the age of six years, and there was no significant difference between the two groups ((89.7±12.5) score vs (91.2±13.7) score, t=1.67, P=0.43). All the children in the experimental group were positive for HIV antibody at birth, and six cases were positive for HIV RNA who were diagnosed with neonatal HIV infection. HAART was initiated for the six cases, while HIV antibody tests were still positive until the age of 18 months after HAART. The rest of the children′s HIV antibody tests became negative with the mother to children tramsission rate of 3.55% (6/169). Conclusion HAART could not only block mother to children tramsission of HIV, but also has no effect on growth and intellectual development of children during the observation period. Key words: Antiretroviral therapy, highly active; Human immunodeficiency virus; Child; Growth and development
目的探讨高活性抗逆转录病毒疗法(HAART)对感染人类免疫缺陷病毒(HIV)孕妇所生婴儿生长发育的影响及阻断母婴传播的作用。方法选择2006年5月至2017年5月被诊断为HIV感染的165名孕妇及其169名婴儿,包括4对双胞胎,同期HIV阴性孕妇所生82名婴儿作为对照。实验组所有孕妇在HIV抗体检测呈阳性时均给予HAART治疗。此外,还进行了分娩干预和人工喂养。监测并比较两组婴儿出生时、12个月和6岁时的体重、身高、血红蛋白(Hb)、血清铁和血清钙水平。新生儿的Apgar评分和六岁时的智力测试也被记录下来。统计分析采用t检验。结果孕妇一般情况良好,对药物耐受性良好。HIV阳性实验组与对照组新生儿Apgar评分、体重、身长、Hb、血清铁、血清钙和CD4+T淋巴细胞计数无显著差异(T=-1.27、-1.12、-3.41、-5.62、-0.89、-3.02和-0.74,均P>0.05),两组间血清钙和CD4+T淋巴细胞计数(T=1.02、1.41、1.32、1.03、0.89和1.06,均P>0.05),两组各指标无显著性差异(t=1.02、0.87、1.58、1.03、0.92和2.07,均P>0.05)。实验组78名儿童和对照组45名儿童在6岁时进行了智力评估,两组之间无显著性差别((89.7±12.5)分与(91.2±13.7)分,t=1.67,P=0.43)。实验组所有儿童出生时HIV抗体均呈阳性,6例HIV RNA阳性,诊断为新生儿HIV感染。对这6例患者进行了HAART,而HIV抗体检测在HAART后18个月大之前仍然呈阳性。其余儿童HIV抗体检测均为阴性,母婴阻断率为3.55%(6/169)。结论HAART不仅能阻断HIV母婴传播,而且在观察期内对儿童生长发育和智力发育没有影响。关键词:抗逆转录病毒疗法,高活性;人体免疫缺陷病毒;儿童;增长与发展
{"title":"Effect of highly active antiretroviral therapy on growth and development of infants and children","authors":"Jin Li, Zhenyu Xu, Yan He, Pei Pi, Jie-min Li, Zhu-ren Zhou","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.08.004","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.08.004","url":null,"abstract":"Objective \u0000To investigate the effect of high active antiretroviral therapy (HAART) on growth and development of infants born to pregnant women infected with human immunodeficiency virus (HIV) and the effect on blocking mother to children transmission. \u0000 \u0000 \u0000Methods \u0000Totally 165 pregnant women diagnosed with HIV infection from May 2006 to May 2017 and their 169 infants, including four pairs of twins were enrolled, and 82 infants born to HIV negative pregnant women in the same period were enrolled as control. All of the pregnant women in the experimental group were administrated with HAART when HIV antibody test was positive. The delivery intervention and artificial feeding were carried out as well. The weight, height, hemoglobin (Hb), serum iron and serum calcium level of infants at birth, 12 months and six years old were monitored and compared between the two groups. Apgar scores of newborns and intelligence tests at six-year-old were also recorded. Statistical analysis was performed by t test. \u0000 \u0000 \u0000Results \u0000Pregnant women were generally in good conditions and well tolerated to the drugs. There were no significant differences in neonatal Apgar scores, body weight, body length, Hb, serum iron, serum calcium and CD4+ T lymphocyte count between HIV positive experimental group and control group (t =-1.27, -1.12, -3.41, -5.62, -0.89, -3.02 and-0.74, respectively, all P>0.05). At the age of 12 months, there were no significant differences in body weight, length, Hb, serum iron, serum calcium and CD4+ T lymphocyte count between the two groups (t = 1.02, 1.41, 1.32, 1.03, 0.89 and 1.06, respectively, all P > 0.05). At the age of six years, there were no significant differences in all indexes between the two groups (t= 1.02, 0.87, 1.58, 1.03, 0.92 and 2.07, respectively, all P > 0.05). Intelligence assessment was performed in 78 children of the experimental group and 45 children of the control group at the age of six years, and there was no significant difference between the two groups ((89.7±12.5) score vs (91.2±13.7) score, t=1.67, P=0.43). All the children in the experimental group were positive for HIV antibody at birth, and six cases were positive for HIV RNA who were diagnosed with neonatal HIV infection. HAART was initiated for the six cases, while HIV antibody tests were still positive until the age of 18 months after HAART. The rest of the children′s HIV antibody tests became negative with the mother to children tramsission rate of 3.55% (6/169). \u0000 \u0000 \u0000Conclusion \u0000HAART could not only block mother to children tramsission of HIV, but also has no effect on growth and intellectual development of children during the observation period. \u0000 \u0000 \u0000Key words: \u0000Antiretroviral therapy, highly active; Human immunodeficiency virus; Child; Growth and development","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48533696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Validation of D2AS model for prediction of early hepatitis B virus-related hepatocellular carcinoma D2AS模型预测早期乙型肝炎病毒相关肝细胞癌的验证
Pub Date : 2019-08-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.08.005
Shitian Yang, Wei Wang, Ya-dong Wang
Objective To validate the predictive value of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk score model D2AS in chronic HBV infection patients without antiviral therapy. Methods A total of 93 patients with chronic HBV infection were selected between January 2015 and July 2017 in the Third Affiliated Hospital of Hebei Medical University. Clinical data including age, gender, medical history, ultrasonography, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), hepatitis B e antibody (anti-HBe), hepatitis B core antibody (anti-HBc), HBV DNA and alanine aminotransferase levels were collected by information center. REACH-B score and D2AS score were used to predict the risk of HCC. Receiver operating characteristic curve (ROC) was used to evaluate the discrimination, and Hosmer-Lemeshow (H-L) goodness-of-fit test was used to evaluate the calibration of the model. Results REACH-B score and D2AS score for the 95 chronic HBV infection patients were 9 (8, 12) and 0.95 (0.57, 2.08), respectively. The area under the curve (AUC) for REACH-B score and D2AS score were 0.916 (95% confidence interval [CI] 0.834-0.998) and 0.784 (95%CI 0.587-0.981), respectively. The difference was not statistically significant (P=0.195). However, for HBeAg-negative patients with chronic HBV infection, the AUC for D2AS score and REACH-B score were 0.952 (95%CI 0.876-1.000) and 0.913 (95%CI 0.821-1.000), respectively (P=0.458). The H-L goodness-of-fit test was P>0.05. Conclusions The D2AS score can be used for HCC prediction among patients who do not meet antiviral criteria. The predictive value of the D2AS score for HCC is comparable to the REACH-B score in HBeAg-negative patients with chronic HBV infection. Key words: Carcinoma, hepatocellular; Hepatitis B; Prediction model
目的验证乙型肝炎病毒(HBV)相关肝细胞癌(HCC)风险评分模型D2AS对未经抗病毒治疗的慢性HBV感染患者的预测价值。方法选取2015年1月~ 2017年7月河北医科大学第三附属医院慢性HBV感染患者93例。临床资料包括年龄、性别、病史、超声、乙型肝炎表面抗原(HBsAg)、乙型肝炎表面抗体(anti-HBs)、乙型肝炎e抗原(HBeAg)、乙型肝炎e抗体(anti-HBe)、乙型肝炎核心抗体(anti-HBc)、HBV DNA和丙氨酸转氨酶水平。采用REACH-B评分和D2AS评分预测HCC的发生风险。采用受试者工作特征曲线(ROC)评价鉴别性,采用Hosmer-Lemeshow (H-L)拟合优度检验评价模型的校正性。结果95例慢性HBV感染患者的REACH-B评分为9 (8,12),D2AS评分为0.95(0.57,2.08)。REACH-B评分和D2AS评分的曲线下面积(AUC)分别为0.916(95%可信区间[CI] 0.834-0.998)和0.784(95%可信区间[CI] 0.587-0.981)。差异无统计学意义(P=0.195)。而对于hbeag阴性的慢性HBV感染患者,D2AS评分和REACH-B评分的AUC分别为0.952 (95%CI 0.876-1.000)和0.913 (95%CI 0.821-1.000) (P=0.458)。H-L拟合优度检验P < 0.05。结论D2AS评分可用于不符合抗病毒标准的患者的HCC预测。D2AS评分对HCC的预测价值与hbeag阴性慢性HBV感染患者的REACH-B评分相当。关键词:肝癌;肝细胞癌;乙型肝炎;预测模型
{"title":"Validation of D2AS model for prediction of early hepatitis B virus-related hepatocellular carcinoma","authors":"Shitian Yang, Wei Wang, Ya-dong Wang","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.08.005","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.08.005","url":null,"abstract":"Objective \u0000To validate the predictive value of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) risk score model D2AS in chronic HBV infection patients without antiviral therapy. \u0000 \u0000 \u0000Methods \u0000A total of 93 patients with chronic HBV infection were selected between January 2015 and July 2017 in the Third Affiliated Hospital of Hebei Medical University. Clinical data including age, gender, medical history, ultrasonography, hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), hepatitis B e antibody (anti-HBe), hepatitis B core antibody (anti-HBc), HBV DNA and alanine aminotransferase levels were collected by information center. REACH-B score and D2AS score were used to predict the risk of HCC. Receiver operating characteristic curve (ROC) was used to evaluate the discrimination, and Hosmer-Lemeshow (H-L) goodness-of-fit test was used to evaluate the calibration of the model. \u0000 \u0000 \u0000Results \u0000REACH-B score and D2AS score for the 95 chronic HBV infection patients were 9 (8, 12) and 0.95 (0.57, 2.08), respectively. The area under the curve (AUC) for REACH-B score and D2AS score were 0.916 (95% confidence interval [CI] 0.834-0.998) and 0.784 (95%CI 0.587-0.981), respectively. The difference was not statistically significant (P=0.195). However, for HBeAg-negative patients with chronic HBV infection, the AUC for D2AS score and REACH-B score were 0.952 (95%CI 0.876-1.000) and 0.913 (95%CI 0.821-1.000), respectively (P=0.458). The H-L goodness-of-fit test was P>0.05. \u0000 \u0000 \u0000Conclusions \u0000The D2AS score can be used for HCC prediction among patients who do not meet antiviral criteria. The predictive value of the D2AS score for HCC is comparable to the REACH-B score in HBeAg-negative patients with chronic HBV infection. \u0000 \u0000 \u0000Key words: \u0000Carcinoma, hepatocellular; Hepatitis B; Prediction model","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47945477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Distribution and transmission characteristics of thirty-five dual genotype vancomycin-resistant Enterococcus faecium carrying both vanA and vanM in an intensive care unit 重症监护病房中携带vanA和vanM的35株双基因型耐万古霉素粪肠球菌的分布和传播特征
Pub Date : 2019-08-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.08.006
Yiqun Yuan, Li Ding, Ying Zhou, Pei Li, Dongfang Lin, Liumei Ding, Xiaogang Xu
Objective To investigate the distribution and transmission characteristics of vancomycin-resistant Enterococcus faecium (VREF) carrying both vanA and vanM in the intensive care unit. Methods VREF strains were isolated from patients in the intensive care unit of Jinshan Hospital, Fudan University in Shanghai from 2013 to 2017. Antimicrobial susceptibilities of the VREF strains to nine antibiotics, including vancomycin, teicoplanin, linezolid and chloromycetin, were tested by broth microdilution method. Multiple polymerase chain reaction (PCR) was used for van genotyping and pulsed field gel electrophoresis (PFGE) was used for homology analysis. Results Thirty-five strains were mainly isolated from urine (16 strains), blood (11 strains), feces (five strains), bile (two strains) and pleural effusion (one strain). All the strains (100.00%) were resistant to vancomycin, ampicillin and levofloxacin, but only 40.00% were resistant to teicoplanin. All the strains were sensitive to linezolid. The results of van genotyping showed that 33 (94.3%) strains belonged to vanA and vanM dual genotype VREF, and the other two were vanA type VREF. PFGE results showed that 35 strains could be divided into 14 PFGE patterns, and seven out of 10 strains isolated in 2014 were identical and the other three belonged to three different PFGE patterns. Conclusions A dual genotype VREF carrying both vanA and vanM has been emerging and spreading in the intensive care unit of Jinshan Hospital, Fudan University in Shanghai. Key words: Enterococcus faecium; Vancomycin; Drug resistance; Genes; Genotype
目的探讨同时携带vanA和vanM的耐万古霉素粪肠球菌(VREF)在重症监护室的分布和传播特征。方法从2013年至2017年上海复旦大学金山医院重症监护室患者中分离VREF菌株。采用肉汤微量稀释法测定了VREF菌株对万古霉素、替考拉宁、利奈唑胺和氯霉素等9种抗生素的耐药性。多聚合酶链式反应(PCR)用于van基因分型,脉冲场凝胶电泳(PFGE)用于同源性分析。结果35株主要分离自尿液(16株)、血液(11株)、粪便(5株)、胆汁(2株)和胸腔积液(1株)。所有菌株(100.00%)对万古霉素、氨苄青霉素和左氧氟沙星均有耐药性,但对替考拉宁仅有40.00%的耐药性。所有菌株均对利奈唑胺敏感。van基因分型结果表明,33株(94.3%)属于vanA和vanM双基因型VREF,另外2株为vanA型VREF。PFGE结果显示,35株菌株可分为14种PFGE模式,2014年分离的10株菌株中有7株相同,其余3株属于3种不同的PFGE模式。结论携带vanA和vanM的双基因型VREF已在上海复旦大学金山医院重症监护室出现并传播。关键词:粪肠球菌;万古霉素;耐药性;基因;基因型
{"title":"Distribution and transmission characteristics of thirty-five dual genotype vancomycin-resistant Enterococcus faecium carrying both vanA and vanM in an intensive care unit","authors":"Yiqun Yuan, Li Ding, Ying Zhou, Pei Li, Dongfang Lin, Liumei Ding, Xiaogang Xu","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.08.006","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.08.006","url":null,"abstract":"Objective \u0000To investigate the distribution and transmission characteristics of vancomycin-resistant Enterococcus faecium (VREF) carrying both vanA and vanM in the intensive care unit. \u0000 \u0000 \u0000Methods \u0000VREF strains were isolated from patients in the intensive care unit of Jinshan Hospital, Fudan University in Shanghai from 2013 to 2017. Antimicrobial susceptibilities of the VREF strains to nine antibiotics, including vancomycin, teicoplanin, linezolid and chloromycetin, were tested by broth microdilution method. Multiple polymerase chain reaction (PCR) was used for van genotyping and pulsed field gel electrophoresis (PFGE) was used for homology analysis. \u0000 \u0000 \u0000Results \u0000Thirty-five strains were mainly isolated from urine (16 strains), blood (11 strains), feces (five strains), bile (two strains) and pleural effusion (one strain). All the strains (100.00%) were resistant to vancomycin, ampicillin and levofloxacin, but only 40.00% were resistant to teicoplanin. All the strains were sensitive to linezolid. The results of van genotyping showed that 33 (94.3%) strains belonged to vanA and vanM dual genotype VREF, and the other two were vanA type VREF. PFGE results showed that 35 strains could be divided into 14 PFGE patterns, and seven out of 10 strains isolated in 2014 were identical and the other three belonged to three different PFGE patterns. \u0000 \u0000 \u0000Conclusions \u0000A dual genotype VREF carrying both vanA and vanM has been emerging and spreading in the intensive care unit of Jinshan Hospital, Fudan University in Shanghai. \u0000 \u0000 \u0000Key words: \u0000Enterococcus faecium; Vancomycin; Drug resistance; Genes; Genotype","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48950833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection: a systematic review and meta-analysis 粘菌素单一疗法与联合疗法治疗碳青霉烯耐药革兰氏阴性菌感染的安全性和有效性:系统综述和荟萃分析
Pub Date : 2019-07-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.07.006
H. Meng, Ailing Zhang, Jingli Lu, Xiaoli Guo, Xiaojian Zhang
Objective To study the safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection. Methods CNKI, Wanfang database, PubMed, Embase and Cochrane library were systematically searched. Randomized controlled trials about colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection were enrolled. The Cochrane Reviewers′ Handbook 5.2 was employed to evaluate the quality of the enrolled studies.The primary outcome was all-cause mortality.The secondary outcomes included infection-related mortality, clinical response, bacterial clearance, nephrotoxicity and hepatotoxicity.Meta-analysis was conducted by RevMan 5.3 software. Results Seven articles containing 859 patients were finally included.There were no significantly statistical differences in all-cause mortality rate (relative risk [RR]=1.07, 95%CI: 0.93-1.24, P>0.05), infection-related mortality rate (RR=1.35, 95%CI: 0.98-1.87, P>0.05), bacterial clearance rate (RR=0.85, 95%CI: 0.71-1.02, P=0.08), hepatotoxicity development rate (RR=0.68, 95%CI: 0.41-1.13, P=0.14), and nephrotoxicity development rate (RR=1.01, 95%CI: 0.85-1.22, P>0.05) between colistin monotherapy and combination therapy. The clinical response rate was higher in combination therapy than that in colistin monotherapy (RR=0.81, 95%CI: 0.66-0.98, P=0.03). In the subgroup analysis, no statistical differences were found in all-cause mortality rate between colistin monotherapy and combination therapy for carbapenem-resistant Acinetobacter baumannii infection (RR=1.00, 95%CI: 0.86-1.12, P>0.05). The dosage of colistin with or without loading dose was not associated with the treatment response. Conclusions Although colistin-based combination therapy has a better clinical response against carbapenem-resistant bacteria infection, especially for Acinetobacter baumannii infection, the mortality rate dose not decline compared to colistin monotherapy.Large-scale randomized controlled trials are needed to evaluate the effect in the future. Key words: Colistin; Meta-analysis; Carbapenem-resistant gram-negative bacteria; Systematic review
目的研究粘菌素单药与联合治疗对碳青霉烯耐药革兰氏阴性菌感染的安全性和有效性。方法系统检索CNKI、万方数据库、PubMed、Embase和Cochrane数据库。关于粘菌素单药治疗与联合治疗对抗碳青霉烯耐药革兰氏阴性菌感染的随机对照试验被纳入。采用Cochrane评审员手册5.2来评估入选研究的质量。主要结果是全因死亡率。次要结果包括感染相关死亡率、临床反应、细菌清除率、肾毒性和肝毒性。采用RevMan 5.3软件进行荟萃分析。结果最终纳入7篇文章,859例患者。全因死亡率(相对危险度[RR]=1.07,95%CI:0.93-1.24,P>0.05)、感染相关死亡率(RR=1.35,95%CI:0.98-1.87,P>0.05),细菌清除率(RR=0.85,95%CI:0.71-1.02,P=0.08),肝毒性发展率(RR0.68,95%CI:0.41-1.13,P=0.014),粘菌素单药和联合用药的肾毒性发生率(RR=1.01,95%CI:0.85-1.22,P>0.05)。联合治疗的临床有效率高于粘菌素单药治疗(RR=0.81,95%CI:0.66~0.98,P=0.03),粘菌素单药治疗和联合治疗耐碳青霉烯鲍曼不动杆菌感染的全因死亡率无统计学差异(RR=1.00,95%CI:0.86-1.12,P>0.05)。结论尽管以粘菌素为基础的联合治疗对碳青霉烯耐药菌感染,特别是对鲍曼不动杆菌感染有更好的临床疗效,但与粘菌素单一治疗相比,死亡率并没有下降。未来需要进行大规模的随机对照试验来评估效果。关键词:粘菌素;荟萃分析;碳青霉烯耐药革兰氏阴性菌;系统审查
{"title":"Safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection: a systematic review and meta-analysis","authors":"H. Meng, Ailing Zhang, Jingli Lu, Xiaoli Guo, Xiaojian Zhang","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.07.006","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.07.006","url":null,"abstract":"Objective \u0000To study the safety and efficacy of colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection. \u0000 \u0000 \u0000Methods \u0000CNKI, Wanfang database, PubMed, Embase and Cochrane library were systematically searched. Randomized controlled trials about colistin monotherapy versus combination therapy against carbapenem-resistant gram-negative bacteria infection were enrolled. The Cochrane Reviewers′ Handbook 5.2 was employed to evaluate the quality of the enrolled studies.The primary outcome was all-cause mortality.The secondary outcomes included infection-related mortality, clinical response, bacterial clearance, nephrotoxicity and hepatotoxicity.Meta-analysis was conducted by RevMan 5.3 software. \u0000 \u0000 \u0000Results \u0000Seven articles containing 859 patients were finally included.There were no significantly statistical differences in all-cause mortality rate (relative risk [RR]=1.07, 95%CI: 0.93-1.24, P>0.05), infection-related mortality rate (RR=1.35, 95%CI: 0.98-1.87, P>0.05), bacterial clearance rate (RR=0.85, 95%CI: 0.71-1.02, P=0.08), hepatotoxicity development rate (RR=0.68, 95%CI: 0.41-1.13, P=0.14), and nephrotoxicity development rate (RR=1.01, 95%CI: 0.85-1.22, P>0.05) between colistin monotherapy and combination therapy. The clinical response rate was higher in combination therapy than that in colistin monotherapy (RR=0.81, 95%CI: 0.66-0.98, P=0.03). In the subgroup analysis, no statistical differences were found in all-cause mortality rate between colistin monotherapy and combination therapy for carbapenem-resistant Acinetobacter baumannii infection (RR=1.00, 95%CI: 0.86-1.12, P>0.05). The dosage of colistin with or without loading dose was not associated with the treatment response. \u0000 \u0000 \u0000Conclusions \u0000Although colistin-based combination therapy has a better clinical response against carbapenem-resistant bacteria infection, especially for Acinetobacter baumannii infection, the mortality rate dose not decline compared to colistin monotherapy.Large-scale randomized controlled trials are needed to evaluate the effect in the future. \u0000 \u0000 \u0000Key words: \u0000Colistin; Meta-analysis; Carbapenem-resistant gram-negative bacteria; Systematic review","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42105438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of yimitasvir phospha combined with sofosbuvir in patients with chronic hepatitis C virus infection 伊米他司韦-福沙联合索非司布韦治疗慢性丙型肝炎病毒感染的疗效和安全性
Pub Date : 2019-07-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.07.007
B. Luo, Jinglan Jin, H. Rao, Q. Ning, J. Hou, L. Bai, Yongfeng Yang, S. Zheng, X. Mao, Jun Quan, Dongliang Yang, Lunli Zhang, Caiyan Zhao, Z. Jia, Fuchun Zhang, Z. Gong, F. Lin, Guiqiang Wang, L. Luo, Liping Deng, Hongming Xie, Jing Li, Yingjun Zhang, Lai Wei
Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus (HCV) genotype 1 infection who were treatment-naive or had a virologic failure to prior interferon-based treatment. Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted. The patients were randomly assigned to yimitasvir phosphate 100 mg+ sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+ sofosbuvir 400 mg group (Group 200 mg) in a 1∶1 ratio with the stratified factors of "treatment-naive" or "treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment. During the clinical trial, HCV RNA was tested in all patients. Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored. Safety and tolerability were assessed by monitoring adverse events, physical examination, laboratory examination, electrocardiogram, and vital signs during the study. The primary end point was SVR12 after the end of therapy. Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables. Descriptive statistics were used and summarized according to HCV genotypes and treatment groups. Safety data were presented using descriptive statistics and summarized according to treatment groups. Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018. One hundred and twenty-nine patients were successfully enrolled and received treatment, and 127 completed the study. There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively. Among the 129 patients who underwent randomization and were treated, 18.6% were treatment-experienced and: 100% were HCV genotype 1b infection. The total SVR rate was 98.4% (127/129), with 98.4% (63/64, 95% confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50% (64/65, 95%CI: 91.72%-99.96%) in the Group 200 mg. There was no significant difference between the two groups (χ2=0.000 2, P=0.989 2). The SVR rates in treatment-naive group and treatment-experienced group were 98.10% (95%CI: 93.29%-99.77%) and 100.00% (24/24, 95%CI: 85.75%-100.00%), respectively. Virological failure during treatment (including breakthrough, rebound and poor efficacy) and relapse after treatment did not occur during the trial. By Sanger sequencing, 11.6% (15/129) patients had baseline NS5A Y93H/Y or Y93H resistance-associated substitutions (RAS), 1.6% (2/129) patients had baseline NS5A L31M RAS. No mutation was observed in NS5B S282 at baseline. There was no S282 mutation in HCV NS5B. A total of 100 (77.5%) subjects had adverse events. No adverse events ≥Grade 3 or severe adverse events related to the study treatment. No patient prematurely discontinued study treatment owing to an adverse event. No life-threatening adverse event was reported.
目的评价100mg或200mg伊米他司韦联合索非司布韦治疗非肝硬化慢性丙型肝炎病毒(HCV)基因型1感染的疗效和安全性,这些患者是治疗初期或之前干扰素治疗的病毒学失败患者。方法采用多中心、随机、开放标签的2期临床试验。将患者按1∶1的比例随机分为磷酸依米他韦100 mg+索非布韦400 mg组(100 mg组)和磷酸依米塔司韦200 mg+索非布韦400 g组(200 mg组),分层因素为“治疗初期”或“治疗经验”,共12周,治疗结束后随访24周。在临床试验期间,对所有患者进行了丙型肝炎病毒核糖核酸检测。对未达到持续病毒学应答(SVR)的患者的病毒耐药性进行监测。研究期间通过监测不良事件、体格检查、实验室检查、心电图和生命体征来评估安全性和耐受性。主要终点是治疗结束后的SVR12。分类变量采用描述性统计,连续变量采用8种描述性统计。根据HCV基因型和治疗组使用描述性统计并进行总结。安全性数据采用描述性统计,并根据治疗组进行总结。结果2017年7月31日至2018年9月26日,共筛查174名受试者。129名患者成功入选并接受治疗,127人完成了研究。有64名患者和65名患者分别被分为100 mg组和200 mg组。在129名接受随机分组并接受治疗的患者中,18.6%有治疗经验,100%为HCV基因型1b感染。总SVR率为98.4%(127/129),100mg组为98.4%,95%CI:91.60%-99.96%,200mg组为9.850%(64/65,95%CI:91.72%-99.96%),两组比较差异无统计学意义(χ2=0.0002,P=0.9892)。未接受治疗组和有治疗经验组的SVR率分别为98.10%(95%CI:93.29%-99.77%)和100.00%(24/24,95%CI:85.75%-100.00%)。试验期间未发生治疗期间的病毒学失败(包括突破、反弹和疗效差)和治疗后复发。通过Sanger测序,11.6%(15/129)的患者具有基线NS5A Y93H/Y或Y93H耐药性相关替代(RAS),1.6%(2/129)的患者有基线NS5A L31M RAS。在基线时,在NS5B S282中未观察到突变。HCV NS5B中未发现S282突变。共有100名(77.5%)受试者出现不良事件。无与研究治疗相关的≥3级不良事件或严重不良事件。没有患者因不良事件而提前停止研究治疗。未报告危及生命的不良事件。结论对于既往未接受过治疗或干扰素治疗后病毒学失败的非丙型肝炎病毒1b型感染肝硬化患者,12周磷酸伊米他司韦100mg或200mg联合索非司布韦400mg每日给药是一种高效、安全的治疗方案。关键词:丙型肝炎,慢性;Yimitasvir;索非司布韦;基因型1;病毒治疗;持续的病毒学反应;安全
{"title":"Efficacy and safety of yimitasvir phospha combined with sofosbuvir in patients with chronic hepatitis C virus infection","authors":"B. Luo, Jinglan Jin, H. Rao, Q. Ning, J. Hou, L. Bai, Yongfeng Yang, S. Zheng, X. Mao, Jun Quan, Dongliang Yang, Lunli Zhang, Caiyan Zhao, Z. Jia, Fuchun Zhang, Z. Gong, F. Lin, Guiqiang Wang, L. Luo, Liping Deng, Hongming Xie, Jing Li, Yingjun Zhang, Lai Wei","doi":"10.3760/CMA.J.ISSN.1000-6680.2019.07.007","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.1000-6680.2019.07.007","url":null,"abstract":"Objective \u0000To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus (HCV) genotype 1 infection who were treatment-naive or had a virologic failure to prior interferon-based treatment. \u0000 \u0000 \u0000Methods \u0000A multicenter, randomized, open-label, phase 2 clinical trial was conducted. The patients were randomly assigned to yimitasvir phosphate 100 mg+ sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+ sofosbuvir 400 mg group (Group 200 mg) in a 1∶1 ratio with the stratified factors of \"treatment-naive\" or \"treatment-experienced\" for 12 weeks and followed up for 24 weeks after the end of treatment. During the clinical trial, HCV RNA was tested in all patients. Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored. Safety and tolerability were assessed by monitoring adverse events, physical examination, laboratory examination, electrocardiogram, and vital signs during the study. The primary end point was SVR12 after the end of therapy. Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables. Descriptive statistics were used and summarized according to HCV genotypes and treatment groups. Safety data were presented using descriptive statistics and summarized according to treatment groups. \u0000 \u0000 \u0000Results \u0000A total of 174 subjects were screened from July 31, 2017 to September 26, 2018. One hundred and twenty-nine patients were successfully enrolled and received treatment, and 127 completed the study. There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively. Among the 129 patients who underwent randomization and were treated, 18.6% were treatment-experienced and: 100% were HCV genotype 1b infection. The total SVR rate was 98.4% (127/129), with 98.4% (63/64, 95% confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50% (64/65, 95%CI: 91.72%-99.96%) in the Group 200 mg. There was no significant difference between the two groups (χ2=0.000 2, P=0.989 2). The SVR rates in treatment-naive group and treatment-experienced group were 98.10% (95%CI: 93.29%-99.77%) and 100.00% (24/24, 95%CI: 85.75%-100.00%), respectively. Virological failure during treatment (including breakthrough, rebound and poor efficacy) and relapse after treatment did not occur during the trial. By Sanger sequencing, 11.6% (15/129) patients had baseline NS5A Y93H/Y or Y93H resistance-associated substitutions (RAS), 1.6% (2/129) patients had baseline NS5A L31M RAS. No mutation was observed in NS5B S282 at baseline. There was no S282 mutation in HCV NS5B. A total of 100 (77.5%) subjects had adverse events. No adverse events ≥Grade 3 or severe adverse events related to the study treatment. No patient prematurely discontinued study treatment owing to an adverse event. No life-threatening adverse event was reported. \u0000 \u0000 \u0000","PeriodicalId":10127,"journal":{"name":"Chinese Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48861280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Resistance genotype, capsular serotype and virulence gene of hypermucoviscous Klebsiella pneumoniae in Anhui Province 安徽省高粘肺炎克雷伯菌耐药性基因型、荚膜血清型及毒力基因
Pub Date : 2019-07-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.07.005
Kaili Sun, Zhou Liu, Haoran Chen, Dongmei Zhao, Yi Gu, Yanyan Liu, Yalong Zhang, Jiabin Li
Objective To investigate the resistance genotype, capsular serotype and virulence gene of hypermucoviscous Klebsiella pneumoniae (HMVKP). Methods A total of 698 strains of Klebsiella pneumoniae (non-repetitive strains) were collected from 35 hospitals of Anhui in September 2017. A total of 78 HMVKP strains were isolated and screened, and the phenotypes of hypermucoviscosity were identified by slime test. The minimum inhibitory concentrations (MIC) of 17 antibiotics drugs were determined by agar dilution method. The resistance related genes, serotype and virulence gene were determined by polymerase chain reaction (PCR). Molecular typing was performed with multi-locus sequence typing (MLST). The homology of major ST-sequence strains was analyzed by pulsed-field gel electrophoresis (PFGE). The carrying rate between HMVKP virulence gene rmpA positive group and the negative group were compared and analyzed. Chi-square test was used for rates comparison between two groups. Results The results showed that 66 strains among 78 strains of HMVKP were isolated from sputum samples. The HMVKP strains were sensitive to 17 antibiotics drugs but had slightly high resistance rates to chloramphenicol, ceftriaxone and ceftizoxime. Four strains produced extended-spectrum beta lactamase carried drug resistance genes including TEM (one strain), CTX-M1 (one strain) and CTX-M2 (two strains), and one strain was resistant to carbapenems, which carries the IMP resistance gene. K2 (30/78, 38.46%) and K1 (13/78, 16.67%) were the major capsular serotypes in 78 HMVKP. IroNB (71/78, 91.03%) and aerobactin (67/78, 85.90%) were the major virulence genes among the five tested virulence genes, and the highest detection rates of virulence gene were found in K2 serotype. A total of 28 ST-sequences were found in 78 strains of HMVKP, and the PFGE results indicated that the four major clones (ST23, ST65, ST86 and ST412) were divided into 16 types, and some of them had homology. In addition, statistical analysis found that the HMVKP virulence gene rmpA positive group (27/52, 51.92%) was more likely to carry the virulence gene kfu than the negative group (7/26, 26.92%). Conclusions The detection rate of drug resistance genotypes in HMVKP stains is not high. K2 and K1 are the major capsular serotypes in 78 HMVKP; iroNB and aerobactin have the highest carrying rate, and the highest detection rates of virulence genes are found in K2 serotype. Key words: Klebsiella pneumoniae; Drug resistance; Electrophoresis, gel, pulsed-field; Virulent gene; Hyper mucoviscous
目的探讨高粘肺炎克雷伯菌(HMVKP)的耐药基因型、荚膜血清型和毒力基因。方法2017年9月在安徽省35所医院共采集肺炎克雷伯菌698株(非重复株)。共分离和筛选了78株HMVKP菌株,并通过粘液试验鉴定了高粘粘度表型。采用琼脂稀释法测定17种抗生素的最低抑菌浓度。采用聚合酶链式反应(PCR)方法检测了抗性相关基因、血清型和毒力基因。分子分型采用多基因座序列分型(MLST)。采用脉冲场凝胶电泳(PFGE)技术对主要ST序列菌株进行同源性分析。比较分析HMVKP毒力基因rmpA阳性组与阴性组的携带率。采用卡方检验对两组患者的发生率进行比较。结果78株HMVKP菌株中有66株是从痰标本中分离得到的。HMVKP菌株对17种抗生素敏感,但对氯霉素、头孢曲松和头孢噻肟的耐药率略高。4株产超广谱β-内酰胺酶的菌株携带TEM(1株)、CTX-M1(1株和CTX-M2(2株)等耐药基因,1株对携带IMP耐药基因的碳青霉烯类药物产生耐药性。K2(30/78,38.46%)和K1(13/78,16.67%)是78个HMVKP的主要荚膜血清型。IroNB(71/78,91.03%)和好氧菌素(67/78,85.90%)是5个毒力基因中的主要毒力基因,K2血清型毒力基因检出率最高。在78株HMVKP中共发现28个ST序列,PFGE结果表明,四个主要克隆(ST23、ST65、ST86和ST412)分为16个类型,其中一些具有同源性。此外,统计分析发现,HMVKP毒力基因rmpA阳性组(27/52,51.92%)携带毒力基因kfu的可能性高于阴性组(7/26,26.92%)。K2和K1是78个HMVKP的主要荚膜血清型;iroNB和好氧菌素的携带率最高,K2血清型毒力基因检出率最高。关键词:肺炎克雷伯菌;耐药性;电泳、凝胶、脉冲场;毒力基因;高粘土质
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引用次数: 0
The dynamic characteristics and predictive value of hepatitis B core antibody titers in chronic hepatitis B patients treated with interferon 干扰素治疗慢性乙型肝炎患者乙型肝炎核心抗体滴度的动态特征及预测价值
Pub Date : 2019-06-15 DOI: 10.3760/CMA.J.ISSN.1000-6680.2019.06.004
T. Yan, Yuanyuan Li, Yuan Yang, Yingli He, Tianyan Chen, Ying‐ren Zhao, Jinfeng Liu
Objective To observe the dynamic characteristics of hepatitis B core antibody (anti-HBc) titers in chronic hepatitis B (CHB) patients treated with interferon and to explore the predictive value of anti-HBc for response to interferon. Methods The clinical information of the patients diagnosed with CHB in Department of Infectious Diseases, the First Affiliated Hospital of Xi′an Jiaotong University from October 2011 to October 2014 were collected. HBV DNA, liver function and HBV serological markers of CHB patients were tested dynamically during and after interferon treatment. The dynamic characteristics of anti-HBc titers in patients with different virological responses were analyzed. The predictive values of anti-HBc titer for the efficacy of interferon treatment of CHB patients were analyzed by binary logistic regression. Results Of the 42 CHB patients aging(30.8±10.1) years old, 34 patients were hepatitis B e antigen (HBeAg) positive and 8 were negative. All patients completed 48-week interferon treatment and 24-week follow-up after the end of treatment. Among them, 28.6% (12/42), 26.2% (11/42) and 45.2% (19/42) of patients achieved sustained virological response (SVR), virological relapse (VR) and non-response (NR), respectively. Patients with different virological response presented various characteristics of anti-HBc titers. Compared with NR group, the anti-HBc titers at baseline and week 12 were significantly higher in SVR group (at baseline: [4.93 ± 0.30] vs [4.70 ± 0.33] lg IU/mL, t=2.147, P=0.013; at week 12: [4.83 ± 0.23] vs [4.44 ± 0.41] lg IU/mL, t=3.032, P=0.007). The anti-HBc titers in SVR group at week 12 and week 24 were significantly higher than those in VR group (at week 12: [4.83 ± 0.23] vs [4.67 ± 0.51] lg IU/mL, t=2.400, P=0.039; at week 24: [4.73 ± 0.21] vs [4.55 ± 0.50] lg IU/mL, t=2.542, P=0.039). By multivariate logistic regression analysis, the anti-HBc titer at baseline was the independent predictive factor for SVR in CHB patients treated with interferon (OR=6.000, 95%CI: 1.118 - 20.486, P=0.037). The area under receiver operating characteristics curve was 0.753 and the optimal cutoff value of anti-HBc titer for the response to interferons in CHB patients was 5.03 lg IU/mL, with positive predictive value of 64.3% and negative predictive value of 89.3%. Conclusions Dynamic pattern of anti-HBc titers is correlated with different virological responses in CHB patients treated with interferon, and the baseline anti-HBc titer is the independent predictive factor for SVR. Key words: Interferon; Hepatitis B, chronic; Anti-HBc titer
目的观察干扰素治疗慢性乙型肝炎(CHB)患者乙型肝炎核心抗体(anti-HBc)滴度的动态特征,探讨抗- hbc对干扰素应答的预测价值。方法收集2011年10月至2014年10月西安交通大学第一附属医院感染性疾病科诊断为慢性乙型肝炎患者的临床资料。在干扰素治疗期间和治疗后动态检测CHB患者的HBV DNA、肝功能和HBV血清学标志物。分析不同病毒学反应患者抗hbc滴度的动态特征。采用二元logistic回归分析抗hbc滴度对慢性乙型肝炎患者干扰素治疗效果的预测价值。结果42例CHB患者(30.8±10.1)岁,HBeAg阳性34例,阴性8例。所有患者均完成48周干扰素治疗,治疗结束后随访24周。其中,28.6%(12/42)、26.2%(11/42)和45.2%(19/42)的患者达到持续病毒学应答(SVR)、病毒学复发(VR)和无应答(NR)。不同病毒学反应的患者抗hbc滴度表现出不同的特点。与NR组比较,SVR组基线和第12周抗hbc滴度显著升高(基线时:[4.93±0.30]vs[4.70±0.33]lg IU/mL, t=2.147, P=0.013;第12周:[4.83±0.23]vs[4.44±0.41]lg IU/mL, t=3.032, P=0.007)。SVR组第12、24周抗hbc滴度显著高于VR组(第12周:[4.83±0.23]vs[4.67±0.51]lg IU/mL, t=2.400, P=0.039;第24周:[4.73±0.21]vs[4.55±0.50]lg IU/mL, t=2.542, P=0.039)。多因素logistic回归分析显示,基线抗hbc滴度是干扰素治疗CHB患者SVR的独立预测因素(OR=6.000, 95%CI: 1.118 ~ 20.486, P=0.037)。受试者工作特征曲线下面积为0.753,CHB患者对干扰素反应的抗- hbc滴度最佳临界值为5.03 lg IU/mL,阳性预测值为64.3%,阴性预测值为89.3%。结论干扰素治疗CHB患者抗hbc滴度动态模式与不同病毒学反应相关,基线抗hbc滴度是SVR的独立预测因素。关键词:干扰素;慢性乙型肝炎;Anti-HBc效价
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引用次数: 0
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中华传染病杂志
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