Giving rituximab in patients with occult or resolved hepatitis B virus infection: are the current guidelines good enough?

Introduction: Hepatitis B virus (HBV) reactivation after ‘resolved’ infection can occur in the setting of immunosuppression, including iatrogenically induced by anti-CD20 antibodies. The presence of antibodies against the HBV core antigen (anti-HBc) is a marker of risk for this phenomenon. The risk of this occurring in patients with circulating HBV surface antigen (HBsAg) is well characterized, but is less well characterized in patients who are HBsAg negative.

Areas covered: This article reviews the literature regarding HBV reactivation in the context of rituximab therapy. We have limited our review to HBsAg-negative patients, and clinical outcomes following HBV reactivation.

Expert opinion: We have recommended prophylactic anti-viral therapy for all HBsAg-negative/anti-HBc-positive patients undergoing rituximab therapy in combination with other immunosuppressive therapy.     

Infection risk associated with anti-TNF-α agents: a review

Introduction: TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenesis of chronic immune-mediated diseases. TNF-α inhibitors can be administered either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs (DMARDs) to treat chronic immune-mediated diseases.

Areas covered: Patients receiving TNF-α inhibitors are at high risk of infections. Based on our experience, in this paper, we discuss the risk of infections associated with the administration of TNF-α inhibitors and the strategies for mitigating against the development of these serious adverse events.

Expert opinion: Infliximab more so than etanercept appears to be responsible for the increased risk of infections. Re-activation of latent tuberculosis (LTB) infection and the overall risk of opportunistic infections should be considered before beginning TNF-α inhibitor therapy. A careful medical history, Mantoux test and chest-x-ray should always be performed before prescribing TNF-α inhibitors. Particular attention should be paid to risk factors for Pneumocystis jirovecii infection. Hepatitis B and C virological follow-up should be considered during TNF-α inhibitor treatment. Finally, patients who are at high risk of herpes zoster (HZ) reactivation would benefit from a second vaccination in adulthood when receiving TNF-α inhibitors.     

An integrated pathway interaction network for the combination of four effective compounds from ShengMai preparations in the treatment of cardio-cerebral ischemic diseases

Aim:

SMXZF (a combination of ginsenoside Rb1, ginsenoside Rg1, schizandrin and DT-13) derived from Chinese traditional medicine formula ShengMai preparations) is capable of alleviating cerebral ischemia-reperfusion injury in mice. In this study we used network pharmacology approach to explore the mechanisms of SMXZF in the treatment of cardio-cerebral ischemic diseases.

Methods:

Based upon the chemical predictors, such as chemical structure, pharmacological information and systems biology functional data analysis, a target-pathway interaction network was constructed to identify potential pathways and targets of SMXZF in the treatment of cardio-cerebral ischemia. Furthermore, the most related pathways were verified in TNF-α-treated human vascular endothelial EA.hy926 cells and H2O2-treated rat PC12 cells.

Results:

Three signaling pathways including the NF-κB pathway, oxidative stress pathway and cytokine network pathway were demonstrated to be the main signaling pathways. The results from the gene ontology analysis were in accordance with these signaling pathways. The target proteins were found to be associated with other diseases such as vision, renal and metabolic diseases, although they exerted therapeutic actions on cardio-cerebral ischemic diseases. Furthermore, SMXZF not only dose-dependently inhibited the phosphorylation of NF-κB, p50, p65 and IKKα/β in TNF-α-treated EA.hy926 cells, but also regulated the Nrf2/HO-1 pathway in H2O2-treated PC12 cells.

Conclusion:

NF-κB signaling pathway, oxidative stress pathway and cytokine network pathway are mainly responsible for the therapeutic actions of SMXZF against cardio-cerebral ischemic diseases.     

Nutlin-3-induced redistribution of chromatin-bound IFI16 in human hepatocellular carcinoma cells in vitro is associated with p53 activation

Aim:

Interferon-γ inducible protein 16 (IFI16), a DNA sensor for DNA double-strand break (DSB), is expressed in most human hepatocellular carcinoma cell (HCC) lines. In this study we investigated the re-localization of chromatin-bound IFI16 by Nutlin-3, a DNA damage agent, in HCC cells in vitro, and the potential mechanisms.

Methods:

Human HCC SMMC-7721 (wild-type TP53), Huh-7 (mutant TP53), Hep3B (null TP53) and normal fetal liver L02 cell lines were examined. DSB damage in HCC cells was detected via γH2AX expression and foci formation assay. The expression of IFI16 and IFNB mRNA was measured using RT-PCR, and subcellular localization and expression of the IFI16 protein were detected using chromatin fractionation, Western blot analysis, and fluorescence microscopy.

Results:

Treatment of SMMC-7721 cells with Nutlin-3 (10 μmol/L) or etoposide (40 μmol/L) induced significant DSB damage. In SMMC-7721 cells, Nutlin-3 significantly increased the expression levels of IFI16 and IFNB mRNA, and partially redistributed chromatin-bound IFI16 protein to the cytoplasm. These effects were blocked by pretreatment with pifithrin-α, a p53 inhibitor. Furthermore, Nutlin-3 did not induce ectopic expression of IFI16 protein in Huh-7 and Hep3B cells. Moreover, the association of IFI16 with chromatin and Nutlin-3-induced changes in localization were not detected in L02 cells.

Conclusion:

Nutlin-3 regulates the subcellular localization of IFI16 in HCC cells in vitro in a p53-dependent manner.     

产妇血清表面抗原定量与乳汁中乙肝病毒载量的相关性分析

目的 探讨携带乙型肝炎病毒(HBV)的产妇血清表面抗原(HBsAg)含量与乳汁中HBV-DNA含量的相关性,并指导母乳喂养.方法 对140例产妇采用荧光定量PCR法测定乳汁中HBV-DNA和化学发光法测定表面抗原含量,并进行相关性分析.结果 A组乳汁HBV-DNA阳性组表面抗原含量为(58 183.2±39 147.8) IU/ml,B组HBV-DNA阴性组表面抗原含量为(1848.8±2458.3) IU/ml.A组血清中表面抗原含量比B组高,差异有统计学意义(P＜0.01),乳汁中HBV-DNA含量与血清中表面抗原含量呈正相关(r=0.799,P＜0.01).结论 慢性HBV感染孕产妇血清中乙肝表面抗原的定量的测定及检测其乳汁中HBV-DNA含量,对阻断母婴传播和预防家庭内水平传播及对HBV感染孕产妇的诊治和疗效评估有着重要意义,特别是为HBV感染产妇选择是否母乳喂养提供了指导依据.     

5334例住院患者HBsAg、抗-HCV、抗-HIV1/2和TP-Ab的检测结果分析

目的 检测5334例住院患者HBsAg、抗-HCV、抗-HIV1/2和TP-Ab并分析检测结果.方法 采用ELISA法检测5334例住院患者HBsAg、抗-HCV、抗-HIV1/2和TP-Ab阳性情况,并分析HBsAg、抗-HCV、抗-HIV1/2和TP-Ab检测阳性者性别和年龄分布.结果 5334例住院患者HBsAg阳性率最高(7.56％),抗-HIV1/2阳性率最低(0.52％);男性患者HBsAg、抗-HCV、TP-Ab检测阳性率与女性患者比较,差异无统计学意义(P＞0.05);男性患者抗-HIV1/2检测阳性率显著高于女性患者,差异具有统计学意义(P＜0.05);成年组患者HBsAg和抗-HCV阳性率均显著高于青少年组,差异具有统计学意义(P＜0.05);老年组患者HBsAg、抗-HCV和TP-Ab阳性率均显著高于青少年组,差异具有统计学意义(P＜0.05);老年组患者HBsAg、TP-Ab阳性率均显著高于成年组,差异具有统计学意义(P＜0.05);不同年龄组患者抗-HIV1/2阳性率比较,差异无统计学意义(P＞0.05).结论 住院患者乙型肝炎感染率较高,艾滋病感染存在性别分布差异,乙肝、丙肝和梅毒感染在年龄分布上存在差异.     

围产期孕妇生殖道B族链球菌感染和耐药性及不良妊娠结局的研究

目的 通过分析围产期孕妇生殖道B族链球菌(GBS)的感染和耐药性及不良妊娠结局,为临床医师制定有效的预防和治疗措施提供依据.方法 2013年1月至2015年2月,对795例围产期孕妇生殖道分泌物进行GBS培养鉴定与药敏试验,并观察临床症状及不良妊娠结局,对结果进行统计学分析.结果 795例孕妇中共检出GBS携带者256例,带菌率为32.2％.＜30岁组(28.9％)与≥30岁组(42.3％)的带菌率差异具有统计学意义(x2=19.095,P＜0.01).GBS阳性者与GBS阴性者的临床症状发生率(18.8％ vs 8.0％)差异具有统计学意义(x 2=39.514,P＜ 0.01).10种抗菌药物(万古霉素、利奈唑胺、青霉素、氨苄西林、头孢曲松、呋喃妥因、左氧氟沙星、克林霉素、红霉素及四环素)耐药率分别为:0％、0％、0.6％、3.1％、6.6％、9.6％、21.9％、23.8％、29.9％及58.1％.D-抑菌圈试验阳性率为23.9％.GBS阳性组与GBS阴性组比较,胎膜早破、早产、宫内感染及新生儿感染发生率的差异均有统计学意义(P＜0.01).结论 该区围产期孕妇GBS带菌率较高,且高龄者易于感染;围产期孕妇感染GBS可增加不良妊娠结局的发生,应据药敏试验结果选择敏感性抗生素予以临床干预.     

B超在小儿肠套叠诊断和临床辅助治疗中的应用价值分析

目的 探讨分析B超在小儿肠套叠诊断和临床辅助治疗中的应用价值分析.方法 将2009年4月1日至2013年4月1日我院收治的160例小儿肠套叠患儿按照抛硬币的方式随机分为两组,观察组和对照组,每组患儿80例.观察组采取B超对患儿进行小儿肠套叠诊断及临床辅助治疗,对照组采取腹部平片对患儿进行小儿肠套叠诊断及临床辅助治疗.比较两组患者的检出率和复位成功率.结果 通过两组比较,观察组的检出率(97.50％)显著高于对照组的检出率(57.50％),观察组的复位成功率(95.00％)显著高于对照组的复位成功率(62.50％),差异具有统计学意义(P＜0.05).结论 B超具有安全、精确等特点,在小儿肠套叠诊断及临床辅助治疗中具有很大的应用价值,深受临床的支持与关注,值得在临床上推广应用.     

盐酸普拉克索B晶型的制备和表征

目的 制备盐酸普拉克索的B晶型并优化制备工艺,同时进行结构表征和稳定性研究。方法 制备盐酸普拉克索的B晶型,采用热重法(TGA)、差示扫描量热法(DSC)、X射线粉末衍射(PXRD)、X射线单晶衍射(SXRD)等分析手段,对盐酸普拉克索B晶型进行表征研究。结果 制备得到了盐酸普拉克索B晶型,其晶型属正交晶系,空间群P2₁2₁2₁,结构中不含溶剂(包括水)。盐酸普拉克索B晶型热处理后晶型不发生转变。结论 盐酸普拉克索B晶型为无水晶型,热稳定性优于一水合物晶型,具有高温稳定性。     

血清S100B蛋白和神经元特异性烯醇化酶在新生儿缺氧缺血性脑病早期诊断中的应用价值

目的 探讨血清S100B蛋白和神经元特异性烯醇化酶(NSE)在新生儿缺氧缺血性脑病(HIE)早期诊断及判断预后的应用价值。方法 选取2010年1月至2014年12月深圳市儿童医院新生儿科住院的HIE的患儿和健康新生儿作为研究对象。健康对照组40例,HIE组97例,其中轻度组41例,中度组30例,重度组26例。入组的新生儿均于出生后的第1、3、7天晨起空腹时采集静脉血测定血清S100蛋白和NSE含量。结果 HIE组患儿各个时间点S100B蛋白和NSE含量均明显高于健康对照组(P均<0.05)。治疗前中、重度组血清S100B蛋白和NSE含量明显高于轻度组(P<0.05)经治疗后血清S100B蛋白和NSE含量均明显下降(P均<0.05)。血清S100B蛋白含量与NSE含量呈正相关(P<0.05)。结论 血清S100B蛋白和NSE在HIE的早期诊断、损伤程度及预后的判断有重要意义。