大剂量胸腺肽联合干扰素治疗慢性乙型肝炎的临床疗效观察

本文选择慢性乙型肝炎90例,分大剂量胸腺肽联合干扰素组,大剂量胸腺肽组和干扰素组。结果表明,大剂量胸腺肽联合干扰素治疗可以促进ALT复常,促使HBeAg、HBcAg、HBV－DNA阴转率与对照大剂量的胸腺肽治疗及干扰素治疗组比较,疗效显著（P＜0．05）。故认为大剂量胸腺肽联合干扰素治疗慢性乙型肝炎（CHB）是阻断或抑制HBV复制且疗效显著的一种新疗法。     

中医药治疗慢性乙肝的几个关键性问题

围绕慢性乙肝这一严重影响人类公共卫生的重大社会问题,开展中医药治疗的研究与探索,首先应肯定中医药治疗CHB具有临床疗效及优势,使其成为治疗CHB的主要方法;继而采用健康教育与药物治疗相结合,运用正确的中医认识和思维方法,结合生物医学的最新研究进展,根据病证结合的方法进行分阶段治疗;并选择宏观症状的改善和微观检查指标的应答及生存质量的提高为观察指标,合理而有效的评价其临床疗效。     

CTLA-4 siRNA对慢性乙型肝炎患者外周血Th1/Th2细胞因子的影响

目的:观察化学合成的小干扰RNA(small interfering RNA,siRNA)对慢性乙型肝炎(chronic hepatitis B,CHB)患者外周血淋巴细胞细胞毒T淋巴细胞相关抗原4(cytotoxic T-lympho-cyte antigen 4,CTLA-4)表达的抑制作用及干扰后对细胞因子IFN-γ、IL-2和IL-4分泌的影响,探讨CTLA-4对慢性乙型肝炎的T细胞免疫调节作用。方法:检测CHB患者外周血淋巴细胞CTLA-4,观察其与HBV-DNA的相关性(P<0.05);根据人淋巴细胞CTLA-4的基因序列,设计合成CTLA-4 siRNA及阴性对照siRNA(siR-NA-co),电穿孔法转染CHB患者外周血淋巴细胞,采用实时荧光定量PCR(real-time Q-PCR)方法检测淋巴细胞CTLA-4 mRNA的表达,采用Western Blotting检测淋巴细胞CTLA-4蛋白表达,采用酶联免疫吸附试验(enzyme-linkedim-muno sorbent assay,ELISA)检测IFN-γ、IL-2和IL-4分泌。结果:CHB患者外周血淋巴细胞CTLA-4表达量与血清HBV-DNA载量有关;CTLA-4 siRNA转染CHB患者外周血淋巴细胞后,CTLA-4 mRNA及CTLA-4蛋白表达均受到抑制,IFN-γ、IL-2分泌增加,与阴性对照相比差异具有统计学意义(P<0.01)。而IL-4分泌没有变化,与阴性对照相比差异没有统计学意义(P>0.05)。结论:CHB患者外周血淋巴细胞CTLA-4表达一定程度抑制免疫反应,利于HBV-DNA的复制;利用siRNA在mRNA水平抑制CHB患者外周血淋巴细胞CTLA-4的表达,能够诱导Th1型细胞因子IL-2、IFN-γ分泌增加,对Th2型细胞因子IL-4无影响。说明抑制CTLA4有助于慢性乙型肝炎患者T细胞免疫的增强。     

聚乙二醇干扰素α-2a成功治疗1例乙型肝炎多重耐药患者

患者,男性,47岁,国家公务员,有乙型肝炎(乙肝)家族史。2003年首次发现乙肝病毒(HBV)阳性,当时肝功能正常。2006年初查丙氨酸氨基转移酶(ALT)152IU/L,曾用甘利欣等保肝治疗,ALT反复波动。2007年2月查ALT65IU/L,HBeAg(+),HBV DNA 6.8×107拷贝/ml,开始恩替卡韦(博路定)抗病毒治疗。治疗半年HBV DNA未转     

The Effect of Pore Structure on Impact Behavior of Concrete Hollow Brick,Autoclaved Aerated Concrete and Foamed Concrete

Porous concrete is an energy absorption material, which has been widely used in civil engineering, traffic engineering and disaster reduction engineering. However, the effect of pore structure on the impact behavior of the porous concrete is lacked. In this study, a series of drop-weight impact tests were carried out on three typical types of porous concrete, i.e., concrete hollow brick (CHB), autoclaved aerated concrete (AAC) and foamed concrete (FC), to investigate the effect of pore structures on their impact behavior. For comparison, static load tests were also conducted as references. According to the damage to the samples, the developments of impact force, strain, contact stress–strain relationship and absorbed energy during drop-weight during the impact test were measured and analyzed. The results show that the ratio between the peak impact stress and compressive strength of CHB was 0.44, while that of AAC and FC increased to about 0.6, indicating that the small and uniform pore structure in AAC and FC had a higher resistance against impact load than the hollow cavity of CHB. In addition, the elastic recovery strain in AAC increased by about 0.2% and its strain at peak contact stress increased by about 160% for a comparison of CHB, implying that a small open pore structure could enhance ductility. Besides, the peak contact stress of FC was close to that of AAC during impact loading, while the strain at peak contact stress of FC increased by about 36% compared with AAC, revealing that the closed-pore structure could further enhance the deformation potential. Correspondingly, the energy absorption rates of CHB, AAC and FC were 85.9 kJ/s, 54.4 kJ/s and 49.7 kJ/s, respectively, where AAC decreased by about 58% compared with CHB, and FC decreased by about 10% compared with AAC.     

Hemodynamic study about cortical hyperintensity belt sign after direct bypass surgery for moyamoya disease

Transient neurological events (TNEs) are observed after direct bypass surgery in patients with moyamoya disease (MMD). Although a correlation between cortical hyperintensity belt signs (CHBs) and TNEs has been reported, the pathophysiology of CHBs is still unknown. The purpose of this study was to reveal the pathophysiology of CHBs by using dynamic susceptibility contrast-magnetic resonance imaging. Thirty patients with MMD were included in this study. We provided scores (0–2) for the existence of CHBs on postoperative FLAIR images. We placed the ROI for the presented area of CHBs in the images of cerebral blood flow, CBV, and MTT. We calculated the change of the hemodynamic parameters (increase ratio, IR) and analyzed the relationship between IRs, CHB scores, and TNEs. TNEs were observed in 15 cases (50%) and CHBs were detected in 28 cases (93%). TNEs showed significantly higher CHB scores than those without (p < 0.05). The group of CHB score 2 showed a significantly higher CBV IR than the group with of score 0 (p < 0.05). Patients with TNEs showed a significantly higher CBV IR than those without (p < 0.05). As for the cut-off level to predict an appearance of TNEs, the CBV IR was 1.36 by the Receiver Operating Characteristic analysis, and the sensitivity and specificity were 80% respectively. We hypothesize that the pathophysiology of the CHBs are vasogenic edemas because the postoperative CBV increase correlated with the CHBs.     

慢加急性肝功能衰竭患者心理合并症的配对病例-对照研究

目的：探讨慢加急性肝功能衰竭（ACLF）患者心理状况及与其他慢性肝脏疾病患者心理症状差异。方法采用病例对照研究,纳入40例 HBV相关ACLF患者,以年龄、性别因素分别匹配40例 HBV相关肝硬化患者、40例慢性乙型肝炎（CHB）患者及40例健康对照,采用描述性分析方法分析不同组间患者心理症状差异。结果汉密顿抑郁量表评分结果提示,HBV 相关 ACLF 组、HBV 相关肝硬化组评分均高于 CHB 组与健康对照组。症状自评量表（SCL-90）评分显示除敌对和偏执2个维度评分无差异,其他8个维度差异均具有统计学意义。结论 HBV相关ACLF患者抑郁程度和精神神经状况较CHB和健康对照组更严重。     

Natural history of chronic hepatitis B: what exactly has REVEAL Revealed?

Chronic hepatitis B virus (HBV) infection is a serious public health problem because of its worldwide prevalence and potential to cause adverse consequences. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer‐Hepatitis B Virus (REVEAL‐HBV) study carried out in Taiwan was used to investigate the natural history of chronic hepatitis B. The REVEAL‐HBV study has established an HBV viral load paradigm in the natural history of chronic hepatitis B (CHB). Serum HBV DNA level has been shown to be significantly and independently associated with incidence of hepatocellular carcinoma (HCC) and cirrhosis and liver‐related mortality across a biological gradient. It is also a major predictor of HBsAg seroclearance. Genetic features including HBV genotype and basal core promoter A1762T/G1764A mutant, and precore G1896A mutant were documented as predictors of HCC risk. Inactive HBV carriers still had an increased risk on HCC development and liver‐related mortality compared with HBsAg ‐seronegatives. Nomograms focusing on facilitating risk communication between patients and clinicians were developed incorporating non‐invasive clinical parameters to predict long‐term HCC risk. These will hopefully contribute to evidence‐based decisions in the clinical management of CHB patients. A somewhat provocative and novel finding from the REVEAL‐HBV study is the association of chronic HBV infection in active replication with an increased pancreatic cancer risk especially in women less than 50 years old. This finding will hopefully spur further research in this area seeking confirmatory evidence. Finally, we hope that the REVEAL‐HBV study will continue to be a source of data to answer other important questions in chronic hepatitis B research going forward.     

Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B

Introduction and ObjectivesHepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB.Patients and MethodsPatients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models.ResultsSixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study.ConclusionAlthough it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.