直接抗病毒药物治疗丙型肝炎合并透析患者的临床应用

丙型肝炎病毒（HCV）感染在慢性肾功能不全患者中较常见，尤其是在进行透析的患者中，HCV感染较普通患者的风险极大增加，同时还会导致肝细胞癌及肝硬化的发病率明显升高。近年来直接抗病毒药物（DAAs）在慢性丙型肝炎的治疗中取得了较好的疗效及安全性，本文通过总结DAAs在丙型肝炎合并透析患者中的应用进展，发现对于基因1~6型HCV合并透析患者，推荐使用G/P方案；由于索磷布韦（SOF）经肾脏代谢，在重度肾损害人群中的血药浓度较高，因此SOF组合方案并不推荐用于丙型肝炎合并透析患者的治疗。     

2‐deoxy D‐glucose treatment does not elicit a hair growth response in alopecia areata

2‐deoxy D‐glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T‐cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell‐mediated autoimmune mouse disease, alopecia areata.     

Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

Immunogenicity of the hepatitis A vaccine 20 years after infant immunization

To determine the duration of immunity provided by the Hepatitis A vaccination (HepA), we evaluated a cohort of participants in Alaska 20 years after being immunized as infants. At recruitment, participants received two doses of inactivated HepA vaccine on one of three schedules. We conducted hepatitis A antibody (anti-HAV) testing for participants at the 20-year time-point. Seventy-five of the original 183 participants (41%) were available for follow-up. The overall anti-HAV geometric mean concentration was 29.9 mIU/mL (95% CI 22.4 mIU/mL, 39.7 mIU/mL) and 50 participants (68%) remained seropositive (titer ≥ 20 mIU/mL). Using a fractional polynomial model, the predicted percent seropositive at 25 years was 55.3%, 49.8% at 30 years and 45.7% at 35 years, suggesting that the percent sero-positive could drop below 50% earlier than previously expected. Further research is necessary to understand if protection continues after seropositivity diminishes or if a HepA booster dose may become necessary.     

miRNA93和miRNA192在H3N2亚型SIV病毒复制及宿主抗病毒免疫中的作用

目的 探讨分离于广西猪流感病毒SW/Guangxi/NS2783/2010和SW/Guangxi/NS650/2012跨种属感染人肺腺癌A549细胞的miRNA93和miRNA192对病毒复制及宿主抗病毒免疫的影响。方法 通过测定不同稀释浓度的病毒感染细胞HA滴度值,确定病毒最佳稀释浓度。荧光定量PCR检测病毒感染细胞后miRNA93和miRNA192表达,Western blot检测病毒NP和HA蛋白表达水平;转染miRNA93和miRNA192抑制剂后,重新检测miRNA93、miRNA192、IFN-β及病毒NP、HA蛋白表达水平。结果 不同稀释度病毒感染人A549细胞后HA滴度的结果显示病毒SW2783的最佳稀释度为10^-3,而SW650的HA滴度无明显变化趋势,提示病毒SW2783对人A549细胞具有较好的适应性和感染能力。荧光定量PCR和Western blot结果提示两株病毒感染细胞后病毒NP和HA蛋白表达均先升高后降低,加入miRNA93抑制剂,两株病毒NP和HA蛋白的表达均上调;加入miRNA192抑制剂,病毒SW2783的HA蛋白表达下调（P=2.10×10^-4）,而SW650的HA蛋白表达上调（P=5.45×10^-5）,NP蛋白反而下调（P=0.034）;ELISA结果提示病毒SW2783和SW650感染细胞后炎症因子IFN-β表达水平随感染时间延长而升高。结论 研究表明miRNA93和miRNA192的表达与SIV病毒增殖及宿主抗病毒免疫有关,可作为干预猪流感病毒跨种属感染的新靶点。     

Epstein-Barr virus-related encephalitis in a young woman: A case report

Although infectious mononucleosis due to Epstein-Barr virus (EBV) is a common disease among young individuals, central nervous system (CNS) complications are rare. In this report, we describe a case of CNS complications caused by EBV in a previously healthy young woman. She presented to our hospital with a 9-day history of headache and sore throat, followed by the development of fever and facial edema 6 days prior to admission. On Day 2 of admission, she was confused (Glasgow Coma Scale score: 10 points) and had fever, muscle weakness in her right arm and leg, stiff neck, and roving eye movement. We detected EBV in a cerebrospinal fluid (CSF) sample using a polymerase chain reaction (PCR) test. The magnetic resonance imaging of her brain revealed dural enhancement and right parietal and temporal lobe lesions. She was treated with acyclovir and high-dose steroid therapy. She responded well to treatment, recovered without neurologic sequelae, and was discharged home on Day 12.Our experience suggests that PCR detection of EBV DNA in CSF may be useful in diagnosing EBV encephalitis and that prognosis may be associated with an area of the brain that is affected and the time from symptom onset to starting treatment.