抗乙肝病毒药物研究新进展

慢性病毒性乙型肝炎的根治是完全清除肝脏乙肝病毒,但是目前一线治疗药物恩替卡韦(ETV)和替诺福韦酯(TDF)等不能达到根治的目的。乙肝病毒cccDNA持续潜伏在肝细胞核中,机体的免疫应答也不能将其清除。目前用于治疗乙肝的药物包括核苷(酸)类似物、非核苷(酸)类似物和免疫调节剂,但这些药物均有各自的局限性,因此寻找新的药物作用靶点和研发新型抗乙肝病毒药物显得极为迫切。鉴于近年来乙肝病毒cccDNA和宿主免疫治疗的研究有了突破性进展,本文总结了新型乙肝病毒药物研究和发展现状,并展望了未来靶向病毒和宿主免疫反应的治疗策略。     

慢性乙型肝炎抗病毒药物的选择

慢性乙型肝炎抗病毒治疗的研究有了明显的进展.1998年前,抗乙型肝炎病毒(HBV)注册药物只有标准α干扰素;1998年之后,核苷(酸)类似物拉米夫定、阿德福韦酯、恩替卡韦和替比夫定相继用于临床;2005年聚乙二醇化干扰素α-2a(PAGasys)批准上市用于慢性乙型肝炎治疗.这些研究的进展,一方面使临床医生在慢性乙型肝炎抗病毒治疗时有了更多的选择,另一方面也使临床医生在决定治疗方案时面临困难.     

胸腺肽α1联合恩替卡韦对乙肝肝硬化患者乙型肝炎e 抗原的影响*

目的:分析胸腺肽α1联合恩替卡韦治疗对于乙肝肝硬化患者的乙型肝炎e抗原(HBe Ag)的影响。方法:选取2013年4月至2016年4月于哈尔滨医科大学附属第二医院感染二科住院和门诊复查的患者50例,随机将患者分为两组,应用胸腺肽α1联合恩替卡韦治疗的患者为实验组,共25例,单一应用恩替卡韦治疗的患者为对照组,共25例。比较两组患者治疗前和治疗半年后的肝功能、乙肝病毒载量以及HBe Ag定量。结果:治疗半年后,实验组患者的肝功能和乙肝病毒载量与对照组比较无明显差异(P0.05),实验组的HBe Ag量明显低于对照组(P0.05)。结论:胸腺肽α1联合恩替卡韦可以有效的降低HBe Ag量,促进e抗原转阴,减少病毒复制。     

恩替卡韦改善了乙型肝炎病毒所致急性肝衰竭的预后

目的：阐明乙型肝炎相关急性肝衰竭的预后因素和恩替卡韦的疗效。方法：本研究回顾性选取了47名因感染乙型肝炎病毒而明确诊断急性肝衰竭的患者,其中5名短期内行肝移植手术被排除,其余42名患者的数据被总结分析。结果：42名患者中12名患者服用了恩替卡韦,在诊断之初,服用恩替卡韦组和未服用恩替卡韦组的一般情况基本相当。使用与未使用恩替卡韦者的生存率分别为67%和23%,此外,年龄〉45岁和没有服用恩替卡韦是不良预后的两个独立相关因素。在年龄〉45岁的患者中使用恩替卡韦和未使用恩替卡韦者的存活率分别为50%和8%。结论：本研究证实了恩替卡韦对乙肝相关急性肝衰竭的治疗作用,我们建议所有乙型肝炎病毒引起的急性肝衰竭患者均应尽早开始恩替卡韦抗病毒治疗。     

银杏叶提取物联合恩替卡韦对慢性乙肝致肝纤维化的干预研究

目的:探讨银杏叶提取物(EGb761)联合恩替卡韦对慢性乙型肝炎患者肝纤维化指标的影响.方法:将45例慢性乙型肝炎患者分为治疗组22例及对照组23例,治疗组应用EGb761及恩替卡韦治疗,对照组仅予恩替卡韦治疗,连续治疗2个月.治疗前后分别检测肝功能、Ⅲ型前胶原(PCⅢ)、Ⅳ型前胶原(PClⅣ)、透明质酸(HA)、层黏连蛋白(LN)水平.结果:治疗后治疗组肝纤雏化指标较对照组明显改善(P均＜0.001).结论:银杏叶提取物EGb761恩替卡韦联合应用对慢性乙肝有明显的抗肝纤维化作用.     

肝脏移植后乙肝复发的临床病理学研究

目的:探讨乙肝终末期肝移植术后乙肝复发的组织病理学特征.方法:回顾性研究分析18例移植术后乙肝复发病人的肝脏病理学和血清学检查资料.结果:14例病人在术后抗病毒治疗过程中乙肝病毒出现YMDD变异.4例病人肝癌复发行化疗后乙肝复发.14例病毒发生YMDD变异病人将恩替卡韦加阿德福韦替换拉米夫定治疗,4例肝癌复发者化疗后用恩替卡韦治疗.经治疗后,14例病人肝脏功能渐近恢复,乙肝病毒DNA拷贝数＜102 U/ml,4例肝癌复病人最终死亡.肝移植术乙肝复发后肝脏病理呈现出肝细胞坏死,纤维化增生和炎症反应.血清学检查呈现出乙肝病毒DNA复制增多.结论:乙肝终末期肝移植术后乙肝复发时肝组织坏死、炎症反应以及纤维化增生与乙肝病毒拷贝数相关.术后检测乙肝病毒以及有效及时的抗乙肝病毒治疗能明显改善病人的预后.     

恩替卡韦联合胸腺肽α1 治疗慢性乙型肝炎疗效研究

目的:观察和比较恩替卡韦联合胸腺肽α1治疗HBeAg阳性慢性乙型肝炎的疗效。方法:选取我院58例HBeAg阳性慢性乙型肝炎患者分成联合组和对照组。联合组28例,初始同时使用恩替卡韦及胸腺肽α124周,之后停胸腺肽α1继续用恩替卡韦至48周。对照组30例,单用恩替卡韦0.5mg/d,48周。定期检测ALT复常率,HBVDNA转阴率,HBeAg/抗HBe血清转换率,肝纤维化组合,Fibroscan评分两组在治疗结束时进行疗效评价。结果:24周时两组ALT复常率无差异显著性(P>0.05),联合组和对照组HBV DNA阴转率在24周、48周时均差异有显著性(P<0.05)。联合组与单用组HBeAg血清转换率在第24周、48周时,两组比较差异均有显著性(P<0.05)。肝纤维化组合各指标(HA,LN,PⅢP,Ⅳ型胶原),Fibroscan评分两组治疗48周后比较差异均有显著性(P<0.05),且两组治疗前后差异联合组更显著。治疗过程中,未发现明显副作用。结论:恩替卡韦联合胸腺肽α1治疗HBeAg阳性慢性乙型肝炎,安全性与耐受性良好,联合组在ALT复常率,HBeAg血清转换率和HBV DNA转阴率,抗肝纤维化的疗效上显著优于单用恩替卡韦组。     

恩替卡韦联合聚乙二醇干扰素α-2b治疗HBeAg阳性乙肝的临床研究

目的:探讨恩替卡韦联合聚乙二醇干扰素α-2b治疗乙型肝炎E抗原(HBeAg)阳性乙肝的临床疗效、安全性及对相关标志物的影响。方法:选取2015年10月至2017年10月我院收治的97例HBeAg阳性乙肝患者,采用随机数字表法将其分为对照组48例和观察组49例。对照组患者采用单纯皮下注射聚乙二醇干扰素α-2b注射剂治疗,观察组采用恩替卡韦联合聚乙二醇干扰素α-2b治疗。比较两组患者治疗后的临床疗效、谷草转氨酶(AST)、丙氨酸转氨酶(ALT)、乙肝病毒的脱氧核糖核酸(HBV-DNA)含量以及ALT复常率、HBeAg血清转换率、HBV-DNA转阴率及不良反应发生率。结果:观察组总治疗有效率为91.84%,明显高于对照组的77.55%(P0.05);治疗后,观察组的ALT、AST、HBV-DNA含量明显低于对照组(P0.05),观察组的ALT复常率、HBeAg血清学转换率、HBV-DNA转阴率明显高于对照组(P0.05);观察组治疗期间不良反应发生率为30.61%,与对照组的29.17%比较差异无统计学意义(P0.05)。结论:恩替卡韦联合聚乙二醇干扰素α-2b治疗HBeAg阳性乙肝较单用干扰素的抗病毒治疗疗效更高,可降低传染性,用药安全性较好。     

恩替卡韦治疗乙型肝炎相关急性肝衰竭疗效和安全性研究

目的:通过临床观察,研究乙型肝炎相关急性肝衰竭的综合治疗中恩替卡韦抗病毒治疗的有效性和安全性.方法:本研究前瞻性选取了近18个月住院的15例感染乙型肝炎病毒而明确诊断急性肝衰竭的患者,明确诊断后第一时间给予每日服用恩替卡韦0.5mg抗病毒治疗,定期观察生化及病毒学指标,并予以随访.结果:15名患者中除5例病情恶化死亡,2例行原位肝移植外,其余8例服用恩替卡韦患者痊愈出院并完整随访.所有病人在开始恩替卡韦抗病毒治疗后2个月内生化指标完全正常,HBVDNA低于检测下限,耐受性良好.6个月内有7位患者都发生了血清学转换,一位患者HBsAg始终阳性.结论:通过临床观察进一步证实,对乙肝相关急性肝衰竭患者尽早使用恩替卡韦抗病毒治疗,可以缩短病程,改善预后,甚至避免肝移植.     

无创肝纤维化检测在慢性乙型肝炎抗肝纤维化治疗中的应用价值

目的探讨无创肝纤维化检测在慢性乙型肝炎抗肝纤维化治疗中的应用价值。方法选择2016年10月~2017年10月在我院诊治的慢性乙型肝炎患者825例,按照随机数字法分为两组,治疗组412例患者采用恩替卡韦与扶正化瘀胶囊治疗,对照组413例患者单用恩替卡韦治疗,并采用无创肝纤维化检测,以观察两组治疗的临床效果。结果治疗前,两组患者的肝功能、肝脏硬度值、脂肪衰减数水平比较,差异无明显统计学意义(P0.05)。治疗后,两组患者的脂肪衰减数值无明显差异(P0.05),但治疗组的肝功能、肝脏硬度值均较对照组明显改善,差异均有统计学意义(P0.05)。结论慢性乙型肝炎患者采用恩替卡韦与扶正化瘀胶囊抗肝纤维化治疗的效果显著,同时采取无创肝纤维化检测动态评估抗肝纤维化治疗效果,为临床大样本、长期观察慢性乙型肝炎肝纤维化的转归提供了一种有着良好应用前景的检测方法。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.