人类免疫缺陷病毒1型耐药基因的监测

2001年12月在美国举行的第41届ICAAC年会上公布的研究结果显示,美国78％的成人人类免疫缺陷病毒1型(HIV-1)感染者中存在着对一种或多种抗反转录病毒(ARV)药物耐药的病毒株。其中,对核苷类反转录酶抑制剂(NRTI)的耐药率最高,为……     

2010年广州地区淋球菌耐药监测结果分析

目的了解广州地区淋球菌对抗生素耐药性的变化及PPNG和TRNG的流行趋势。方法用琼脂稀释法测定头孢曲松、大观霉素、环丙沙星、阿奇霉素和四环素的最低抑菌浓度（MIC）;用纸片碘量法检测β-内酰胺酶。结果83株淋球菌检出PPNG24株（28．9％）、TRNG50株（60．2％）、环丙沙星耐药率高达98．8％,高度耐药株（MIC≥16mg／L）43株（51．8％）,而76株淋球菌中阿奇霉素耐药株11株（14．5％）,均未出现对头孢曲松、大观霉素耐药的菌株,抗菌活性强。结论合理规范使用抗生素及动态监测淋球菌耐药性变迁是临床减少淋球菌耐药菌株出现的有效办法。     

2004～2010年武汉同济医院临床分离多重耐药菌株监测分析

目的了解武汉同济医院2004年至2010年临床分离多重耐药菌株的检出情况。方法对临床分离菌株,采用纸片扩散法按统一的方案进行药敏试验。按照CLSI 2009年标准进行判断。结果 2004年至2010年该院耐甲氧西林金葡菌（MRSA）和耐甲氧西林凝固酶阴性葡萄球菌（MRSCN）的检出率分别在35.6%～63.8%和21.5%～61.4%。2004年至2010年共检出36株耐万古霉素肠球菌（VRE）。大肠埃希菌产ESBLs株检出率在29.6%～81.7%,肺炎克雷伯菌产ESBLs株检出率在36.0%～56.6%,产酸克雷伯产ESBLs株检出率在35.3%～67.4%,奇异变形杆菌产ESBLs株检出率在0～26.2%。自2005年起每年均有泛耐药的铜绿假单胞菌和鲍曼不动杆菌的检出。结论该院2004年至2010年多重耐药菌株呈增多趋势,尤其是VRE和泛耐药的铜绿假单胞菌和鲍曼不动杆菌的出现,给临床治疗带来了严峻挑战。     

采用熔点曲线法研究乙肝病毒准种与拉米夫定临床耐药相关性

为了研究乙型肝炎病毒(HBV)准种与拉米夫定耐药的关系以指导临床用药,随机选取拉米夫定治疗后发生YMDD变异的慢性乙型肝炎(CHB)患者30例,以及停用拉米夫定后发生病毒反弹的CHB患者30例作为研究对象,同时以未经拉米夫定治疗的CHB患者30例为对照,采用聚合酶链反应(PCR)扩增这些病人体内HBV的P区,再用熔点曲线法分析3组患者体内的HBV准种情况。另外,采用相同方法对HBV C区、S区准种也进行了对比。结果显示,病毒变异组患者体内HBV P区准种数量为2.50±0.86个,病毒反弹组为5.30±0.95个,未治疗组为8.37±0.93个,3组间准种数量两两比较均有显著性差异(P<0.05)。HBV C区病毒变异组准种数量为6.10±1.86个,病毒反弹组为6.37±1.81个,未治疗组为6.33±1.64个,3组准种数量无显著性差异(P>0.05)。HBV S区病毒变异组准种数量为5.23±1.85个,病毒反弹组为6.17±1.93个,未治疗组为5.77±2.11个,3组准种数量无显著性差异(P>0.05)。HBV P区熔点曲线图显示,病毒变异组优势病毒群的熔点与病毒反弹组和未治疗组相比,已发生明显的偏移,而在HBV C区和S区熔点曲线图中,3组的波峰数和优势病毒群的熔点均没有明显变化。可见,在拉米夫定的作用下HBV P区准种数量减少,准种的性质也发生变化,发生变异后劣势耐药病毒株变为优势病毒株易被检测到。拉米夫定对HBV C区、S区作用不明显。     

内蒙古某医院2012—2021年念珠菌的临床分布及耐药变迁分析

目的 分析内蒙古自治区人民医院2012—2021年念珠菌的分布以及耐药情况,为临床管理念珠菌感染提供依据。方法 回顾性分析内蒙古自治区人民医院2012年1月到2021年12月念珠菌的菌株分布和药敏实验结果。结果 共分离出5472株念珠菌。标本主要来源于尿液、痰液、分泌物,分别占41.28%、31.69%和11.22%。临床科室分布主要来自保健病房、呼吸与危重症病房和ICU,分别占27.54%、18.29%和17.71%。主要念珠菌菌种有：白念珠菌、热带念珠菌、光滑念珠菌、近平滑念珠菌、无名念珠菌、克柔念珠菌和葡萄牙念珠菌,占比分别为63.96%、14.33%、5.40%、5.23%、3.42%、1.83%和1.70%。白念珠菌、热带念珠菌、近滑念珠菌、光滑念珠菌、无名念珠菌、克柔念珠菌和葡萄牙念珠菌对5-氟胞嘧啶、两性霉素B、伏立康唑、氟康唑和伊曲康唑5种抗真菌药物耐药率分别为0.14%～3.53%、0.39%～22.41%、0～2.82%、0～12.50%、0.53%～5.88%、1.05%～57.895和0～12.22%。白念珠菌的耐药变迁情况不明显。结论 2012—2021年期间...     

2015年至2019年辽宁省某医院血培养病原菌分布及耐药分析

分析2015年至2019年辽宁省人民医院血培养分离菌的科室分布及耐药情况,为临床提供数据参考.利用Whonet5.6软件对2015年至2019年辽宁省人民医院血培养临床数据进行分析.血培养阳性率为12.3％,共分离病原菌1266株,其中革兰阴性菌546株、革兰阳性菌649株、真菌71株;革兰阴性菌主要为大肠埃希菌(Es...     

2006-2010年舟山地区鲍曼不动杆菌感染动态观察

目的 了解舟山地区近5年鲍曼不动杆菌(Acinetobacter baumanii,Ab)的感染状况及对常见抗菌药物的耐药情况,为有效控制感染和治疗提供依据.方法 对2006年1月至2010年12月临床送检的血、尿及痰等各类标本进行细菌培养、分离与鉴定和药物敏感试验,细菌鉴定采用ATB-expression细菌鉴定仪,药敏试验采用其配套的PSE-5条.结果 2006-2010年共检出鲍曼不动杆菌696株.Ab主要分布于ICU (301,43.4％)和呼吸内科(132,19.0％)的送检标本.痰标本检出率最高,为524株(75.3％).Ab对除妥布霉素以外抗生素的耐药性呈逐年上升的趋势(P＜0.01).多重耐药鲍曼不动杆菌比例也逐渐增加.结论 鲍曼不动杆菌对临床常用抗菌药物的耐药性呈逐年上升趋势,多重耐药菌比例明显增加.碳青霉烯类抗生素仍是治疗Ab感染最敏感的药物.应加强鲍曼不动杆菌细菌耐药监测,进一步合理有效使用抗生素,以防止鲍曼不动杆菌的传播,降低多重耐药鲍曼不动杆菌交叉感染的发生.     

福建某基层医院CRE碳青霉烯类耐药基因分析

目的 对福建省南平市第二医院分离的碳青霉烯类耐药肠杆菌科细菌进行碳青霉烯类基因和其他β-内酰胺类耐药基因检测。方法 收集碳青霉烯类耐药肠杆菌科细菌,采用Vitek-2 Compact全自动细菌鉴定/药敏仪器进行细菌鉴定和药敏试验;采用改良Hodge试验对实验菌株进行表型检测;利用PCR及测序法对常见的碳青霉烯类和β-内酰胺类耐药基因进行检测;质粒接合试验检测碳青霉烯类耐药基因是否具有可转移性。结果 共收集到4株碳青霉烯类耐药肠杆菌科细菌,呈多重耐药性。2株改良Hodge试验阳性。试验菌株均检出碳青霉烯类耐药基因（NDM-1、IMP-8或VIM-2）,并同时携带有其他β-内酰胺类基因;4株细菌中有3株的碳青霉烯类耐药基因接合成功。结论 碳青霉烯类耐药肠杆菌科细菌已在福建基层医院出现,并具有一定传播性,应引起相关主管部门的注意,以防耐药菌的流行。     

HBV耐药变异及其与基因型的关系

目的:乙型肝炎病毒是乙性肝炎的病原体,极易引起慢性感染,其中部分可进展为肝硬化、肝功能衰竭或肝癌,严重危害人类健康。拉米夫定为新一代核苷类似物,能抑制病毒的复制,是当今较有效的抗病毒治疗药物。但长期用药可引起病毒基因突变,产生耐药变异株,特别易发生YMDD变异,影响疗     

2013年新疆17家三级医院细菌耐药性监测分析

目的:了解新疆地区17家三级医院2013年临床分离细菌的分布特征及对抗生素的耐药性。方法:采用最小抑菌浓度法(MIC)和纸片扩散法(K-B)对细菌进行药物敏感试验。结果:临床共分离出细菌44022株,其中革兰阳性菌占30.2%,革兰阴性菌占69.8%。1大肠埃希菌、肺炎克雷伯菌和奇异变形杆菌产ESBLs菌株检出率分别为66.2%、48.0%和52.0%。2鲍曼不动杆菌和铜绿假单胞菌对亚胺培南和美洛培南的耐药率分别为51.8%、30.4%和37.6%、22.9%。3耐甲氧西林金黄色葡萄球菌(MRSA)和耐甲氧西林凝固酶阴性葡萄球菌(MRSCN)的检出率分别为27.7%和79.8%。414岁以下儿童肺炎链球菌对青霉素的耐药率(4.2%)高于成人(2.1%)。泛耐药菌株(XDR)中,鲍曼不动杆菌381株(9.6%),铜绿假单胞菌57株(1.7%),大肠埃希菌6株(0.1%),肺炎克雷伯菌16株(0.3%)。结论:通过对细菌耐药数据分析情况来看,细菌耐药情况普遍存在,对于耐药克隆株的传播,应加以关注;此外,应加强细菌耐药监测,合理使用抗生素。     

慢性乙型肝炎病毒感染自然史中HBsAg和HBsAb共存血清学模式分析

目的分析慢性乙肝病毒感染者HBsAg和HBsAb共存模式中血清学指标、HBV-DNA和肝酶等指标与自然病程的关系,探讨其临床意义。方法回顾性分析2016年重庆医科大学附属第一医院HBsAg和HBsAb双阳性患者的血清学指标、HBV-DNA和ALT、GGT检测结果,并对其感染的自然病程进行分析。结果 2016年该院HBsAg和HBsAb双阳性患者共520例,占全部HBV感染者的2.80%,占总送检标本数的0.42%。可分期的184例双阳性患者中,免疫耐受期47例(25.54%),免疫清除期17例(9.24%),低复制期108例(58.70%),再活动期12例(6.52%),HBsAg、HBsAg/HBsAb比值、HBV-DNA、ALT和GGT水平差异均有统计学意义(P<0.05),低复制期患者HBsAg/HBsAb比值均低于其他患者(P<0.05)。不同分期患者HBsAb、年龄和性别比较差异无统计学意义(P>0.05),且HBsAb水平均较低。284例资料完整HBsAg和HBsAb共存病例中HBV-DNA阳性136例,占47.89%。HBsAg浓度与HBV-DNA载量成正相关(r=0.295,P<0.05),HBsAb浓度与HBV-DNA载量之间没有显著相关性(r=0.04,P>0.05)。结论 HBsAg和HBsAb共存患者并不少见,与性别无关,可发生在各个年龄阶段,以低复制期患者为最多。HBsAg和HBsAb共存患者中HBsAb多以低浓度形式存在,且浓度与自然病程无关。HBsAb的出现并非代表患者体内病毒复制停止,在诊断及治疗HBsAg和HBsAb共存模式的乙肝病毒感染者时仍需结合HBV-DNA载量来判断感染状态。     

microRNA在乙型肝炎病毒感染及相关疾病中的作用

乙型肝炎病毒(hepatitis B virus,HBV)是一种嗜肝性DNA病毒,感染后可导致急性和慢性肝炎,而慢性感染是导致肝硬化、肝癌和肝衰竭的主要病因。在乙型肝炎病毒复制、转录和相关疾病进程中,microRNA(miRNA)扮演着重要的角色。乙型肝炎病毒感染肝细胞后能引起细胞内microRNA表达谱的改变:一方面,microRNA能促进乙型肝炎病毒的转录和诱导宿主细胞向肿瘤细胞转化;另一方面,microRNA也能抑制乙型肝炎病毒包装和复制。重要的是,乙型肝炎病毒的感染能影响宿主血清microRNA的表达。因此,这类特殊的microRNA今后可成为乙型肝炎病毒相关疾病诊断的潜在生物标记物。将对乙型肝炎病毒与宿主microRNA之间相互作用及其相关生物学效应作一综述。     

Interference of hepatitis B virus with cellular signaling

The presence of hepatitis B virus (HBV) proteins leads to changes in the cellular gene expression. As a consequence, the cellular signaling processes are influenced by the actions of HBV proteins. It has been shown that HBV nucleocapsid protein and the amino-terminal part of polymerase termed as terminal protein (TP) could inhibit interferon signaling. Further, the global gene expression profiles differ in hepatoma cells with and without HBV gene expression and replication. The expression of interferon (IFN) stimulated genes (ISGs) was differently regulated in cells with HBV replication and could be modulated by antiviral treatments. The HBV TP has been found to modulate the ISG expression and enhance the HBV replication. The modulation of the cellular signaling processes by HBV may have significant implications for pathogenesis.     

不同年龄慢性乙肝病毒感染者的肝组织病理特点

目的探讨不同年龄阶段慢性乙肝病毒感染者的肝组织病理特点。方法 288例慢性HBV感染者行1 s肝穿刺,标本均送免疫组化双标记及HE染色、Masson染色、网状纤维染色,进一步分析其病理特点。结果不同年龄根据谷丙转氨酶（ALT）水平[≤1正常值上限（ULN）、1-2 ULN、≥2 ULN]有抗病毒治疗指征比例：≤20岁组为18.2%、66.7%、80.0%;21-30岁组为18.8%、22.7%、57.1%;31-40岁组为37.0%、47.1%、84.6%;≥41岁组为44.2%、51.6%、71.4%。结论对于年龄〈30岁的慢性乙肝病毒感染者,若ALT大于正常上限也应考虑抗病毒治疗,对于ALT正常但年龄大于30岁、ALT1-2ULN、有肝硬化肝癌家族史、合并肥胖或脂肪肝的慢性乙肝病毒感染者行肝穿刺可有效指导抗病毒治疗时机。     

The earliest steps in hepatitis B virus infection

The early steps in hepatitis B virus (HBV) infection, a human hepadnavirus, initiates from cell attachment followed by entry and delivery of the genetic information to the nucleus. Despite the fact that these steps determine the virus-related pathogenesis, their molecular basis is poorly understood. Cumulative data suggest that this process can be divided to cell attachment, endocytosis, membrane fusion and post-fusion consecutive steps. These steps are likely to be regulated by the viral envelope proteins and by the cellular membrane, receptors and extracellular matrix. In the absence of animal model for HBV, the duck hepadnavirus DHBV turned out to be a fruitful animal model. Therefore data concerning the early, post-attachment steps in hepadnaviral entry are largely based on studies performed with DHBV in primary duck liver hepatocytes. These studies are now starting to illuminate the mechanisms of hepadnavirus route of cell entry and to provide some new insights on the molecular basis of the strict species specificity of hepadnavirus infection.     

Comparison and significance of specific and non-specific cellular immunity in patients with chronic hepatitis B caused by infection with genotypes B or C of hepatitis B virus

The present study was designed to investigate possible relationships between the genotypes of hepa-titis B virus (HBV) and the HBV-specific cytotoxic T lymphocyte (CTL) responses. HBV genotypes, HBV specific CTL HBV DNA and other markers of HBV infection were determined in 138 patients with chronic hepatitis B. The results showed that the patients infected with genotype C (n=62) had a significantly lower HBV-specific CTL response than those who were infected with HBV genotype B (P<0.01). HBV DNA titer was higher in patients infected with HBV genotype C than in those infected with HBV geno-type B (P<0.01). Both alanine aminotransferase (ALT) and total bilirubin (TBIL) were higher in HBV genotype C infected patients than in those infected with genotype B (P<0.01 and <0.05, respectively). These results suggest that compared with CHB patients infected with HBV genotype B, the higher HBV DNA level and more severe liver damages in the patients infected with genotype C of HBV may be as-sociated with genotype C of the virus.     

Prevalence of hepatitis B virus infections in nonhuman primates

The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in nonhuman primates. Serum samples from Europe, Thailand and Vietnam were analyzed. Sera obtained from 262 apes and 454 monkeys were tested for HBV infection serologically and for HBV DNA using nested PCR (nPCR). A total number of 198 ape sera and all but one (Cercopithecus aethiops) of the 4543 monkey sera had no serological signs of HBV infection. Among the 64 of 262 (24.4%) seropositive ape sera, we found, as in humans, different stages of HBV infection: very early HBV infection, active infection with high level of infectivity, virus carriers with low infectivity, and passed HBV infection. In the cases with passed infection, 47.8% harbored HBV DNA in the presence of protective antibodies to the HBV surface antigen (HBsAb). This indicates HBV persistence in apes despite immune control. In contrast to apes, in monkeys HBV infection is a very rare event.     

Interaction of preS domains of hepatitis B virus with phospholipid vesicles

The role of preS domains of the hepatitis B virus (HBV) envelope proteins in the first steps of viral infection has been restricted to their implication in virus attachment to a putative hepatocyte receptor. In order to explore a fusion activity in these regions, we used recombinant preS domains to characterize their interaction with liposomes. Binding experiments carried out with NBD-labeled proteins indicated that preS were able to interact in a monomeric way with acidic phospholipid vesicles, being the partition coefficient similar to that described for peptides which can insert deeply into bilayers. Fluorescence depolarization of DPH-labeled vesicles confirmed the specificity for negative charged phospholipids. Upon interaction the proteins induced aggregation, lipid mixing and release of internal contents of acidic vesicles at both acid and neutral pH in a concentration-dependent manner. Taken together, all these data indicate that preS domains are able to insert into the hydrophobic core of the bilayer. Moreover, the insertion resulted in a protein conformational change which increased the helical content. Therefore all these results suggest that, besides their participation in the recognition of a cellular receptor, the preS domains could be involved in the fusion mechanism of HBV with the plasma membrane of target cells.     

Serum progranulin levels are elevated in patients with chronic hepatitis B virus infection,reflecting viral load

Progranulin (PGRN) is implicated in infection, immunity and host defense, but its role in the pathogenesis of HBV infection remains unknown. Here we investigated whether there is dysregulated production and the clinical significance of circulating PGRN in patients with chronic HBV infection. Serum concentrations of PGRN were analyzed by enzyme-linked immunosorbent assay. Serum PGRN levels were significantly higher in patients with chronic HBV infection than healthy subjects. PGRN levels were significantly associated with HBV-DNA levels, but did not correlate with the concentrations of alanine aminotransferase and aspartate aminotransferase. This study demonstrates increased circulating PGRN production and association between PGRN levels and viral loads in patients with chronic HBV infection, suggesting a functional role of PGRN in the pathogenesis of HBV infection.     

Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: A meta-analysis

Objective

The aim of this meta-analysis is to evaluate the associations between functional polymorphisms in the interleukin-4 (IL4) gene and individuals' responses to hepatitis B vaccine and their susceptibility to hepatitis B virus (HBV) infection.

Methods

A literature search on articles published before December 1st, 2012 was conducted in PubMed, Embase, Web of Science and China BioMedicine (CBM) databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistical analyses were performed using the STATA 12.0 software.

Results

Eight studies were eligible for inclusion in this meta-analysis, including five cross-sectional studies on individual's response to hepatitis B vaccine and three case–control studies on HBV infection risk. The meta-analysis results showed that the T allele of rs2243250, the T allele of rs2070874, and the C allele of rs2227284 in IL4 gene were associated with high responses to hepatitis B vaccine. Further subgroup analysis by ethnicity showed that there was a significant association between IL4 genetic polymorphisms and an individual's responses to hepatitis B vaccine among Asian populations, but similar association was not found among Caucasian populations. However, there was no evidence indicating a correlation between IL4 genetic polymorphism and susceptibility to HBV infection.

Conclusion

Our current meta-analysis suggests that rs2243250, rs2070874 and rs2227284 polymorphisms in IL4 gene may play an important role in determining the response to hepatitis B vaccine, especially among Asian populations. However, further studies are still needed to evaluate the associations between IL4 genetic polymorphisms and HBV infection risk.