OBJECTIVE:The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients.METHODS:Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated.RESULTS:A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity.DISCUSSION:Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects.CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov number: NCT02430259.

目的 分析肺结核患者滤泡辅助T细胞表达及相关因子谱变化.方法 70例初治肺结核患者为本院2017年11月-2018年11月收治的患者,检测患者滤泡辅助性T细胞亚群及其相关因子IL-17、IL-21表达水平,根据肺结核治疗效果分为进展期20例(进展组)、好转期50例(好转组),同时以健康体检的30例患者作为对照组,对比不同病情肺结核患者血清中Tfh、IL-17、IL-21表达水平,以肺结核初治无效为终点事件采用Logistic回归分析探讨影响肺结核初治无效的独立危险因素.结果 进展组患者Tfh、IL-17、IL-21水平均明显高于好转组、对照组患者(P＜0.05);血清Tfh、IL-17、IL-21与患者胸腔积液呈正相关(P＜0.05),与初治效果、肺功能呈负相关(P＜0.05);Tfh(P =0.03)、IL-17(P =0.02)、IL-21(P =0.03)是肺结核初始治疗效果无效的独立危险因素.结论 肺结核患者Tfh、IL-17、IL-21是肺结核患者预后不良的独立危险因素.

To investigate the effect of high dose gamma globulin combined with naloxone in the treatment of severe viral encephalitis in children ,and its influence on nerve function and immune function.Methods From March 2012 to May 2017,103 children with viral encephalitis in the First People＇s Hospital of Wenling were randomly divided into observation group (53 cases) and control group (50 cases) according to the digital table.The control group was given routine treatment.The observation group was given naloxone combined with high dose gamma globulin on the basis of routine treatment.The therapeutic effect,clinical symptoms,serum neurological function and humoral immune function were compared between the two groups.Results The total effective rate of the observation group was significantly higher than that of the control group (92.45% vs.78.00%) (χ2 ＝4.319,P＜0.05).The clinical symptoms,signs disappearance time and hospitalization time of the observation group were significantly shorter than those of the control group [(2.17 ±0.56) d vs.(3.12 ±0.79) d;(2.25 ±0.31) d vs.( 3.87 ±0.93) d; (3.84 ±0.46)d vs.(5.31 ±0.69)d;(2.01 ±0.83)d vs.(3.86 ±1.21) d;(1.85 ±0.58) d vs.(2.79 ±0.77)d;(11.36 ±2.14)d vs.(13.05 ±1.85) d;(10.21 ±3.05) d vs.(13.85 ±3.72) d] ( t＝7.072,11.998,12.789, 9.093,7.024,4.276,5.444,all P＜0.05).After treatment,the serum NSE,S-100βand NGF levels of the two groups were significantly decreased [(12.64 ±1.22) ng／L vs.(18.95 ±2.15) ng／L, (0.85 ±0.24) ng／L vs. (1.69 ±0.35)ng／L,(0.17 ±0.05)ng／mL vs.(0.98 ±0.12)ng／mL,(16.38 ±1.38)ng／L vs.(19.04 ±2.78)ng／L, (1.22 ±0.30) ng／L vs.(1.70 ±0.41) ng／L,(0.33 ±0.10) ng／mL vs.(0.96 ±0.14) ng／mL] ( t ＝18.583, 14.010,45.361,6.239,6.878,25.58,all P＜0.05),and the serum neurological function indicators of the observation group were significantly lower than those of the control group ( t ＝14.592,6.931,10.358,all P ＜0.05).After treatment,the level of IgG in the two groups were significantly higher than those before treatment [(15.62 ±2.31)g／L vs.(9.12 ±1.74)g／L;(11.52 ±2.05)g／L vs.(8.97 ±1.56)g／L]( t＝16.363,6.999,all P＜0.05),and the IgG level in the observation group was significantly higher than that in the control group (P＜0.05).There were no signifi-cant changes in the levels of IgM in the two groups before and after treatment (all P＞0.05).Conclusion High-dose gamma globulin combined with naloxone can effectively improve the clinical efficacy of severe viral encephalitis

目的 探讨miRNA-155在重症肺炎大鼠肺组织中的表达及过表达miRNA-155对重症肺炎肺组织的保护作用及可能机制.方法 将45只大鼠根据随机数字表法分为对照组、肺炎组(肺炎模型)、miRNA-155组(肺炎模型+miRNA-155 mimics),每组15只.采用反转录-聚合酶链反应(RT-PCR)测定肺组织miR-NA-155水平,采用苏木精-伊红(HE)染色观察肺组织病理形态学变化,采用酶联免疫吸附测定(ELISA)法检测肺组织匀浆和血清中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子α(TNF-α)水平,采用Western blot测定肺组织pp65、p65、磷酸化IκB激酶α(p-IκBα)、IκBα蛋白水平.结果 HE染色显示对照组大鼠肺组织无渗出、出血和炎性细胞漫润;肺炎组大鼠肺组织见明显渗出、出血和炎性细胞浸润;miRNA-155组大鼠肺组织渗出、出血和炎性细胞浸润较肺炎组减轻.与对照组比较,肺炎组大鼠肺组织miRNA-155水平降低(P＜0.05),肺组织匀浆中1L-1β、IL-6、TNF-仅水平升高(P＜0.05),血清中IL-1β、IL-6、TNF-α水平升高(P＜0.05),肺组织pp65、p-IκBα蛋白水平升高(P＜0.05);与肺炎组比较,miRNA-155组大鼠肺组织miRNA-155水平升高(P＜0.05),肺组织匀浆中IL-1β、IL-6、TNF-α水平降低(P＜0.05),血清中IL-1β、IL-6、TNF-α水平降低(P＜0.05),肺组织pp65、p-IkBα蛋白水平降低(P＜0.05).3组大鼠肺组织p65、IkBα蛋白水平比较,差异无统计学意义(P＞0.05).结论 重症肺炎大鼠肺组织中miRNA-155水平降低,过表达miRNA-155通过抑制NF-κB信号通路可减轻肺组织炎性反应.

目的 探讨肝硬化并发自发性细菌性腹膜炎(Spontaneous bacterial peritonitis,SBP)患者血清中颗粒蛋白前体水平及其在疾病诊断和预后评估中的价值.方法 选择温岭市第一人民医院2016年1月-2017年12月肝硬化并发SBP患者96例作为肝硬化并发SBP组,肝硬化未并发SBP患者96例作为肝硬化组,同期96名健康体检者作为对照组.测定血清颗粒蛋白前体 、C-反应蛋白 、降钙素原水平.结果 肝硬化并发SBP组血清颗粒蛋白前体 、C-反应蛋白 、降钙素原水平[(72.15±7.58)μg/L、(14.86±2.65)mg/L、(1.42±0.08)ng/ml]均高于对照组和肝硬化组(P<0.05),肝硬化组C反应蛋白水平[(7.48±1.52)mg/L]高于对照组(P<0.05),肝硬化组和对照组颗粒蛋白前体和降钙素原水平比较差异无统计学意义.肝硬化并发SBP组患者血清颗粒蛋白前体水平与C-反应蛋白 、降钙素原呈正相关(r=0.597、0.653,P<0.05).血清颗粒蛋白前体诊断肝硬化并发SBP的截断值为63.28μg/L,ROC曲线下面积为0.817,灵敏度为88.92％,特异度为91.43％.肝硬化并发SBP存活者和死亡者不同时间血清颗粒蛋白前体水平比较差异有统计学意义(P<0.001),时间和分组之间血清颗粒蛋白前体水平有交互作用(P<0.001),两组之间血清颗粒蛋白前体水平比较差异有统计学意义(P<0.001).结论 肝硬化并发SBP患者血清颗粒蛋白前体水平升高,颗粒蛋白前体水平在肝硬化并发SBP患者的诊断及预后评估中具有潜在价值.

患者男性，49岁，1997年体检发现 HBsAg 阳性，ALT＜2 ULN。母亲患肝硬化早亡。2009年6月在上海某医院检查ALT 77 U／L，HBsAg 阳性、抗HBe阳性、抗HBc阳性，HBV DNA1.4×107拷贝／ml，诊断为HBeAg阴性慢性乙型肝炎，2009年6月作者给予替比夫定治疗。1个月后复查ALT 136 U／L， HBV DNA1.4×103拷贝／ml。

目的 探讨乙型肝炎病毒(HBV)感染患者外周血中特异性白细胞介素-21(IL-21) +CD4+T细胞及γ-干扰素(IFN-γ)+ CD8+T细胞表达差异,为阐明HBV感染后T细胞功能衰竭机制提供理论依据.方法 选取2013年4月-2015年4月医院收治的HBV感染患者127例,其中慢性乙型肝炎患者41例、非活动性HBsAg携带患者38例、急性乙型肝炎(AHB)患者31例、慢性HBV携带患者17例,再选择同期医院健康体检人员30名作为对照组,比较各组受试者外周血中特异性IL-21+CD4+T细胞及IFN-γ+ CD8+T细胞表达情况;采用SPSS22.0软件对数据进行统计分析.结果各组受试者特异性IL-21+ CD4+T细胞比例及非特异性IL-21+CD4+T细胞比例均显著高于阴性对照(P＜0.05),急性乙型肝炎患者特异性IL-21 +CD4+T细胞比例及非特异性IL-21+ CD4+T细胞比例较对照组、慢性乙型肝炎、非活动性HBsAg携带、慢性HBV携带显著升高(P＜0.05);各组受试者特异性IFN-γ+ CD8+T细胞比例及非特异性IFN-γ+ CD8+T细胞比例均显著高于阴性对照(P＜0.05),急性乙型肝炎特异性IFN-γ+ CD8+T细胞比例及非特异性IFN-γ+ CD8+T细胞比例显著高于对照组、慢性乙型肝炎、非活动性HBsAg携带以及慢性HBV携带患者(P＜0.05);特异性IL-21+ CD4+T细胞与IFN-γ+CD8+T细胞比例在对照组及各HBV感染组中均呈显著正相关关系(P＜0.05).结论 在急性乙型肝炎患者中,特异性及非特异性IL-21 +CD4+T细胞与IFN-γ+ CD8+T细胞水平较慢性HBV感染患者显著升高,且特异性IL-21+ CD4+T细胞与IFN-γ+ CD8+T细胞具有着明显的相关性,提示HBV慢性感染患者存在T细胞免疫功能的低下.

Objective To compare the lamivudine (LAM) combined with adefovir dipivoxil (ADV) therapy and switching to ADV monotherapy in LAM-resistant chronic hepatitis B patients with HBeAg-positive.Methods A total of 172 LAM-resistant patients were randomly divided into 2 groups,116 cases received ADV (10 mg/d) therapy (switching to ADV group),56 cases received LAM (100 mg/d) combined with ADV (10 mg/d) therapy (combined with ADV group),40 cases with poor efficacy in switching to ADV group received LAM (100 mg/d) combined with ADV (10 mg/ d) therapy(re-combination group).The liver function and the levels of HBeAg,anti-HBe,HBsAg,anti-HBs and HBV DNA were tested once every 3 months.Results The complete virologic response rate of combination group was 66.1％,switching group was 45.7％,re-combination was 60.0％,the difference between combinalion with ADV group and switching to ADV group was statistically significant (x2 =5.075,P ＜ 0.05),while there was no difference between recombination group and combination group(x2=0.371,P ＞ 0.05); the primary treatment failure rate of combination group was 7.1％,switching group was 22.4％,the difference between combinalion with ADV group and switching to ADV group was statistically significant (x2 =6.116,P ＜ 0.05),and there was no difference between re-combination and combination group(x2 =0.788,P ＞ 0.05).Conclusions Completely virological response rate of combination ADV group is significantly higher than switching to ADV group.When some patients in switching to ADV group get poor efficacy,re-LAM + ADV combination is also a method of salvage therapy.To optimize the treatment should be based on the early virological response.

替比夫定是口服L核苷类似物,是一种特异性的HBV DNA多聚酶的强效抑制剂[1].国内外临床试验结果显示,替比夫定比拉米夫定具有更强的病毒抑制作用,更高的HBeAg血清学转换率,且2年耐药率更低[2-4].本研究观察单用替比夫定与胸腺肽序贯替比夫定的抗HBV疗效,现将观察结果报道如下.

AIM:To investigate the clinical character of patients who had achieved complete or partial response relapsed after withdrawal with lamivudine therapy.METHODS:160 patients with complete response and 35 patients with partial response continue to be monitored after withdrawal with lamivudine therapy.The liver function was checked once a month,the levels of HBV DNA,HBsAg,anti-HBs,HBeAg,anti-HBe and anti-HBc were tested once every 3 months.And detailed record of the condition and re-treatment outcomes.RESULTS:The relapse rates of HBV-DNA were 30.6% in the complete response group and 85.7% in the partial response group.The difference was statistically significant(χ2=36.164,P0.001).ALT recurrence rate were 28.75%(46/160) and 82.9%(29/35),the difference was statistically significant(χ2=32.645,P0.001).In 6 months after withdrawal,the relapse rates of the patients were 80% in the complete response group and 53.1% in the partial response group.With a long course,the recurrence rate was relatively low.The relapsed patients who had achieved complete response were mild.Lamivudine withdrawal with the long-term follow-up,timely treatment,prognosis was good.CONCLUSION:The relapse rate of the patients who had achieved complete response is lower.The state of illness is better in the patients who had achieved complete response,whereas,the treatment of the patients who had achieved partial response with lamivudine should not be discontinue.