慢性乙肝给予干扰素及拉米夫定的干预疗效观察

目的:观察慢性乙肝给予干扰素及拉米夫定的干预疗效。方法:对照组1单用拉米夫定,对照组2单用干扰素α-2b,研究组联合应用干扰素α-2b及拉米夫定,对比3组治疗后ALT恢复正常患者比率、HBV-DNA转阴率、HBeAg/抗HBe血清转换率,研究组和对照组1治疗后YMDD变异率。结果:3组治疗后各时段ALT复常率、HBV-DNA转阴率、HBeAg/抗HBe血清转换率均显著上升,3组间ALT复常率无显著差异;研究组各阶段HBV-DNA转阴率及HBeAg/抗HBe血清转换率显著高于对照组1和对照组2,研究组YMDD变异率显著低于对照组1。结论:慢性乙肝给予干扰素及拉米夫定疗效确切。     

恩替卡韦与替比夫定治疗HBeAg阳性慢性乙型肝炎的Meta分析

目的系统评价恩替卡韦与替比夫定治疗HBeAg阳性慢性乙型肝炎的效果。方法检索2005～2012年中国期刊全文数据库、万方医学数据库及中文科技期刊全文数据库,纳入恩替卡韦与替比夫定治疗HBeAg阳性慢性乙型肝炎的随机对照试验(RCT)文献,手工检索其他相关文献,对纳入的研究进行质量评价,采用RevMan5.1软件进行Meta分析。结果共有11篇RCT文献符合纳入标准。Meta分析结果显示:治疗12周时,恩替卡韦和替比夫定在丙氨酸氨基转移酶(ALT)复常率、HBeAg阴转率、HBeAg/抗HBe血清学转换率、HBV DNA阴转率方面差异均无统计学意义(P>0.05);治疗24周和48/52周时,在HBeAg阴转率、HBeAg/抗HBe血清学转换率方面,替比夫定显著优于恩替卡韦(RR=0.69,95%CI为0.53～0.89;RR=0.61,95%CI为0.45～0.84;RR=0.66,95%CI为0.51～0.86;RR=0.54,95%CI为0.41～0.71),差异有统计学意义(P<0.01)。结论恩替卡韦与替比夫定在ALT复常率、HBV DNA阴转率方面疗效差异无统计学意义;在HBeAg阴转率、HBeAg/抗HBe血清学转换率方面疗效替比夫定优于恩替卡韦。但该系统评价纳入的研究质量较低,尚需高质量的临床试验加以验证。     

单用阿德福韦酯与联合α干扰素治疗HBeAg阳性慢性乙型肝炎的疗效观察

目的观察和对比单用阿德福韦酯与阿德福韦酯联合α干扰素治疗HBeAg阳性慢性乙型肝炎的疗效.方法对2003-2004年舟山市人民医院74例HBeAg(+)的慢性乙型肝炎患者随机分成治疗组(联合组)和对照组(单用组),联合组31例,同时使用α干扰素及阿德福韦酯26周,随后继续单用阿德福韦酯78周,总疗程104周;单用组43例,单用阿德福韦酯10 mg·d-1,疗程104周,定期检测丙氨酸转氨酶(ALT)复常率,HBVDNA转阴率,HBeAg/抗HBe血清转换率,两组在治疗结束时进行疗效评价.结果两组ALT复常率在12周时差异有显著性(P＜0.05),在以后各阶段差异无显著性(P＞0.05),联合组HBVDNA阴转率在12周时为19.35%,单用组为11.63%,两组相比较差异无显著性(P＞0.05),而在第26,52,78,104周时,两组比较差异有显著性(P＜0.05),联合组与单用组HBeAg/抗HBe血清转换率12周时无显著差异,在26,52,78,104周时,两组相比较差异显著(P＜0.05).结论阿德福韦酯和干扰素联合治疗HBeAg阳性慢性乙型肝炎,安全性与耐受性良好,联合组在HBeAg/抗HBe血清转换率和HBVDNA转阴率的疗效上显著优于单用组.     

恩替卡韦和阿德福韦酯治疗HBeAg阳性慢性乙型肝炎疗效和安全性的Meta分析

目的评价恩替卡韦(ETV)和阿德福韦酯(ADV)对核苷初治的乙型肝炎e抗原(HBe Ag)阳性慢性乙型肝炎(CHB)患者的疗效和安全性。方法计算机检索Pub Med、Ovid(SP)、中国期刊全文数据库(CNKI)、中文科技期刊数据库(VIP)、中国生物医学文献数据库(CBM)(建库至2013年12月)公开发表的有关ETV和ADV对核苷初治的HBe Ag阳性CHB患者疗效的随机对照试验(RCTs),并追查已获文献的参考文献。由两名研究者独立筛选文献,提取数据,按照改良后的Jadad评分标准进行质量评价。采用Rev Man 5.2软件进行Meta分析。结果最终纳入12个RCTs,共922例患者。采用固定效应模型,Meta分析结果显示,治疗48周时,ETV组在血清乙型肝炎病毒(HBV)DNA转阴率(RR=1.62,95%CI 1.41~1.87,P<0.000 01),血清丙氨酸转氨酶(ALT)复常率(RR=1.14,95%CI 1.06~1.21,P=0.000 2),HBe Ag转阴率(RR=1.35,95%CI 1.08~1.69,P=0.01)和HBe Ag血清学转换率(RR=1.67,95%CI 1.02~2.76,P=0.04)方面均显著高于ADV组。ETV组和ADV组在不良反应发生率方面无显著差异(P>0.05)。结论核苷初治的HBe Ag阳性CHB患者治疗48周时,ETV在降低血清HBV DNA、促使ALT复常、清除HBe Ag和促进HBe Ag血清学转换方面的疗效均优于ADV。ETV和ADV在安全性方面相似。     

恩替卡韦与阿德福韦酯对核苷初治HBeAg阳性慢性乙型肝炎48周疗效比较

目的比较恩替卡韦(ETV)与阿德福韦酯(ADV)对核苷初治HBeAg阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者48周时的疗效。方法 117例CHB患者随机分为ETV组和ADV组,分别给予0.5 mg/d ETV和10 mg/d ADV治疗,疗效的主要观测指标有:血清HBV-DNA、HbeAg转阴及ALT复常。结果 48周时,ETV与ADV组血清HBV-DNA转阴率分别为66.1%和18.2%,差异有统计学意义(P<0.05);两组ALT复常率分别为82.3%和56.4%,差异也有统计学意义(P<0.05);两组HBeAg转阴率(24.2%和16.4%)、抗-HBe转换率(8.06%和5.45%)及不良反应发生率(3.23%和3.64%),差异无统计学意义(P>0.05)。结论 ETV在促使CHB患者HBV-DNA转阴及ALT恢复正常方面显著优于ADV,在血清HBeAg转阴率、抗-HBe转换率及不良反应发生率方面二者相近。     

疏血通联合依达拉奉治疗急性脑梗死的系统评价

目的:系统评价疏血通联合依达拉奉治疗急性脑梗死(ACI)的安全性和有效性。方法:检索中国生物医学文献数据库(1978～2009)、中文科技期刊全文数据库(1979～2009)纳入疏血通联合依达拉奉治疗ACI的随机对照试验(RCT),手工检索其他的相关文献,对纳入研究进行方法学质量评价,并采用RevMan 5.0.0软件对其进行Meta分析。结果:共纳入11个RCT,967例患者;疏血通联合依达拉奉对比常规方法治疗ACI患者,痊愈率和总有效率联合组优于常规组,分别为[RR1.75,95%CI(1.30,2.35)]和[RR1.38,95%CI(1.22,1.55)]。疏血通联合依达拉奉对比单用依达拉奉治疗ACI的基本痊愈率和总有效率,联合组均优于单用组,且差异有统计学意义,其RR和95%CI分别为[:RR1.43,95%CI(1.03,1.97])和[RR1.16,95%CI(1.06,1.27)]。结论:疏血通联合依达拉奉能明显提高ACI患者治疗后的总有效率和痊愈率,疗效显著,未见明显不良反应。     

拉米夫定耐药的慢性乙型肝炎治疗方案成本 - 效果分 析简

目的 观察对拉米夫定耐药的慢性乙型肝炎患者的疗效,并对其成本-效果进行分析.方法 选择住院患者中对拉米夫定耐药的慢性乙型肝炎患者140例,随机分为两组,各70例.A组给予恩替卡韦（ETV）0.5 mg口服;B组给予阿德福韦酯（ADV） 10 mg及拉米夫定（LAM）100 mg口服,均1日/次,疗程48周.观察两组的HBV-DNA转阴率、ALT复常率及HBeAg/抗HBe血清转换率,并运用成本-效果分析法对结果进行分析.结果 两组HBV-DNA转阴率、ALT复常率及HBeAg/抗HBe血清转换率比较,两组结果差异无显著性（P＞0.05）;B组方案所用成本比A组少.结论 阿德福韦酯联合拉米夫定治疗拉米夫定耐药的慢性乙型肝炎的成本-效果比优于恩替卡韦.     

胸腺五肽联合阿德福韦酯治疗慢性乙型肝炎的疗效观察

目的观察胸腺五肽联合阿德福韦酯(ADV)治疗慢性乙型病毒性肝炎(CHB)的疗效。方法将160例CHB患者随机分为两组,对照组单用ADV治疗,治疗组在ADV治疗的基础上同时使用胸腺五肽,观察两组患者的疗效。结果治疗组与对照组在治疗12周时HBVDNA转阴率分别为72.5%和65%,24周时分别为77.5%和72.5%,经统计处理无显著性差异(P>0.05);36周时转阴率分别为87.5%和80%,48周时分别为90%和82.5%,治疗组高于对照组,经统计处理有显著性差异(P<0.05);两组在治疗12周时HBeAg/抗-HBe血清转换率分别为15%和12.5%,24周时分别为22.5%和20%,无显著性差异(P>0.05);36周时血清转换率分别为32.5%和22.5%(P<0.05),48周时分别为37.5%和22.5%,治疗组高于对照组,经统计处理有显著性差异(P<0.05);两组ALT复常率无显著性差异(P>0.05)。结论胸腺五肽联合阿德福韦酯治疗慢性乙型肝炎可提高患者HBVDNA转阴率和HBeAg/抗—HBe血清转换率。     

复方鳖甲软肝片联合阿德福韦酯治疗慢性乙型肝炎肝纤维化疗效的系统评价

目的:评价复方鳖甲软肝片联合阿德福韦酯治疗慢性乙型病毒性肝炎(CHB)肝纤维化的疗效。方法:计算机检索PubMed(1978～2010.1)、中国生物医学文献数据库(1978～2010.1)、中文科技期刊全文数据库(1989～2010年)纳入的复方鳖甲软肝片联合阿德福韦酯治疗CHB肝纤维化的随机对照试验(RCT)文献,手工检索其他的相关文献,对纳入研究进行方法学质量评价,并采用RevMan 5.0.23软件对其进行Meta分析。结果:共8个符合标准的RCT纳入,复方鳖甲软肝片联合阿德福韦酯治疗CHB肝纤维化指标:玻璃酸比较,联合组优于单用组[SMD=-0.66,95%CI(-0.90,-0.41)];层黏蛋白比较,联合组优于单用组[SMD=-0.51,95%CI(-0.72,-0.30)];Ⅲ型胶原比较,联合组优于单用组[SMD=-0.72,95%CI(-1.13,-0.32)];Ⅳ型胶原比较,联合组优于单用组[SMD=-0.50,95%CI(-0.98,-0.02)]。结论:复方鳖甲软肝片联合阿德福韦酯,能明显改善CHB患者的肝纤维化水平,从而达到较好的治疗效果。     

拉米夫定单用与联用α干扰素治疗乙型肝炎的疗效观察

目的 观察拉采夫定单用与联用α干扰素治疗慢性乙型肝炎的疗效。方法单组28侈lj,单服拉米夫定,100mgqd,疗程均>12mo。联合组22例,拉米夫定100mg qd,2周后加用α干扰素(商品名:安福隆)3MU或5MU,肌肉或皮下注射,每周3次,6mo后停用干扰素,拉米夫定继续使用12mo以上。两组患者在治疗6mo、12mo、18mo时分别进行疗效比较,并且随访6-12mo。结果单用组和联合组6mo时患者ALT复常率分别为92.86%和90.90%, (P>0.05);HBV-DNA转阴率分别为96.43%和95.45, (P>0.05);HBeAg血清转换率分别为25.00%和27.27%, (P>0.05)。12mo时,ALT复常率分别为78.57%和81.81%, (P>0.05);HBV-DNA转阴率分别为92.86%和95.45%, (P>0.05);HBeAg血清转换率分别为32.14%和54.55%,(P<0.05)。18mo时,ALT复常率分别为67.86％和72.72％, (P>0.05);HBV-DNA转阴率分别为71.43%和77.27%, (P>0.05);HBeAga血清转换率分别为32.14%和54.55%, (P<0.05)。联合组患者HBeAg的血清转换率显著高于单用组,而ALT复常率、HBV-DNA转阴率和HBV—YMDD变异率似乎较单用组低,但无显著性差异。结论拉米夫定和α干扰素联合治疗慢性乙型肝炎,安全有效;HBeAg血清转换率高于单用拉米夫定组。     

Treatment paradigms on hepatitis B e antigen-negative chronic hepatitis B patients

The primary goal of treatment in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB) is potent and durable suppression of hepatitis B virus (HBV) replication. It results in biochemical and histological remission of CHB and is the prerequisite for the prevention of cirrhosis, its life-threatening complications and hepatocellular carcinoma. Responses that are durable after the cessation of treatment are referred to as sustained virological responses, whereas those persisting under therapy are referred to as treatment-maintained virological responses. Treatment paradigms of sustained virological response in HBeAg-negative CHB are practically restricted to conventional IFN-α and pegylated interferons (peg-IFNs), and are limited only to patients with compensated liver disease. Long-lasting maintained virological responses without HBV resistance in HBeAg-negative CHB are achievable by all approved nucleos(t)ide analogues (lamivudine, adefovir and entecavir) in highly variable rates, depending on their potency, rapidity of virological response and genetic barrier to resistance. The maintenance of response under 5 years of adefovir treatment represents the most effective treatment paradigm for HBeAg-negative CHB, whereas such long-term data with entecavir and tenofovir monotherapy may become available in the near future. In patients with lamivudine-resistant HBV mutants, the recommended treatment strategy is to add adefovir at the same time as continuing treatment with lamivudine. There are no treatment paradigms as yet of combination therapy from the very outset with two nucleoside analogues for use in treatment-naive patients.     

Treatment paradigms on hepatitis B e antigen-negative chronic hepatitis B patients

The primary goal of treatment in hepatitis B e antigen (HBeAg)-negative patients with chronic hepatitis B (CHB) is potent and durable suppression of hepatitis B virus (HBV) replication. It results in biochemical and histological remission of CHB and is the prerequisite for the prevention of cirrhosis, its life-threatening complications and hepatocellular carcinoma. Responses that are durable after the cessation of treatment are referred to as sustained virological responses, whereas those persisting under therapy are referred to as treatment-maintained virological responses. Treatment paradigms of sustained virological response in HBeAg-negative CHB are practically restricted to conventional IFN-alpha and pegylated interferons (peg-IFNs), and are limited only to patients with compensated liver disease. Long-lasting maintained virological responses without HBV resistance in HBeAg-negative CHB are achievable by all approved nucleos(t)ide analogues (lamivudine, adefovir and entecavir) in highly variable rates, depending on their potency, rapidity of virological response and genetic barrier to resistance. The maintenance of response under 5 years of adefovir treatment represents the most effective treatment paradigm for HBeAg-negative CHB, whereas such long-term data with entecavir and tenofovir monotherapy may become available in the near future. In patients with lamivudine-resistant HBV mutants, the recommended treatment strategy is to add adefovir at the same time as continuing treatment with lamivudine. There are no treatment paradigms as yet of combination therapy from the very outset with two nucleoside analogues for use in treatment-naive patients.     

Experimental chemotherapy of leishmaniasis with adenosine analogue Formycin A, in combination with inhibitor of nucleoside transport, nitrobenzylthioinosinate.

A single dose of the adenosine analogue Formycin A (FoA) (20 mg/kg), combined with nitrobenzyl mercaptopurine ribonucleoside 5'-monophosphate (NBMPR-P) (10 mg/kg), a prodrug of nitrobenzylthioinosine (NBMPR), was effective in reducing the size of the foot pad lesions from 7.4 +/- 0.2 to 3.9 +/- 0.2 of Syrian golden hamsters infected with Leishmania major. There was a statistical difference (p < 0.01) in the size of the foot pad by the fifth day between the infected groups that received treatment and the controls, as well as between the groups that were treated with combined drugs and FoA only. The initial reduction in size of the foot pad noted in the group that received only FoA was transient. The effect of FoA or FoA combined with NBMPR on the in vitro cultured promastigotes was similar, indicating that the transport inhibitor might be manipulating the availability of FoA in the host's macrophages where the leishmania amastigotes are resident. The results further indicate the need to explore the usefulness of combining cytotoxic nucleoside analogues with host protecting nucleoside transport inhibitors in the treatment of protozoan parasitic infections.     

拉米夫定治疗慢性乙肝及乙肝病毒携带者36例

目的观察拉米夫定治疗慢性乙肝(CHB)及乙肝病毒携带者(ASC)的疗效及安全性。方法分CHB治疗组21例,ASC治疗组15例,对照组40例。CHB治疗组予保肝治疗的基础上加用拉米夫定治疗,ASC治疗组仅予拉米夫定治疗,CHB对照组仅予保肝治疗。三组疗程均为1年。结果两治疗组在促进HBeAg,HBV-DNA转阴的疗效优于对照组(P＜0.01);CHB治疗组的肝功能复常率、肝纤维化血清学指标下降幅度明显优于对照组(P＜0.01),无明显不良反应。结论拉米夫定治疗慢性乙肝及乙肝病毒携带者安全有效。     

抗病毒治疗对慢性乙型肝炎患者肝组织病理的影响

目的：通过对慢性乙型肝炎患者抗病毒治疗前后进行肝组织病理检查,分析其抗病毒治疗效果。方法收集2005年8月-2012年10月治疗的慢性乙型肝炎29例,在其抗病毒治疗48周前后进行肝穿刺活检检查,比较治疗前后变化。结果与治疗前相比,完全应答组无论炎症或纤维化程度均明显改善（P＜0．01）,部分应答组炎症程度得到改善（P＜0．05）,纤维化程度则无明显改变（P＞0．05）,而无应答组治疗前后相比,炎症及纤维化程度均无明显改变（P＞0．05）。结论无论予干扰素或核苷（酸）类似物抗病毒治疗,获得病毒学完全应答均可明显改善肝脏炎症、纤维化程度。     

Incorporation of 5-substituted pyrimidine nucleoside analogues into DNA of a thymidylate synthetase-deficient murine FM3A carcinoma cell line

Various 5-substituted 2'-deoxyuridine (dUrd), 2'-deoxycytidine (dCyd), 1-beta-D-arabinofuranosyluracil (araU) and 1-beta-D-arabinofuranosylcytosine (araC) analogues have been investigated for their stimulatory effect on the growth of a thymidylate (dTMP) synthetase-deficient murine mammary carcinoma cell line (FM3A/TS-) that is auxotrophic for thymidine (dThd). Such stimulatory effect may be considered as indicative for the incorporation of the nucleoside analogue into host cell DNA. Based on this premise, several dUrd analogues were found to be incorporated into FM3A/TS- cell DNA (in decreasing order of incorporation): 5-bromo-dUrd greater than 5-chloro-dUrd greater than 5-(3-hydroxy-1-propynyl)-dUrd greater greater than 5-(1-pentynyl)-dUrd approximately 5-(1-propynyl)-dUrd approximately 5-iodo-dUrd greater than 5-(5-carboxy-1-hexenyl)-dUrd greater than 5-(3,3-dimethyl-1-butynyl)-dUrd greater than 5-ethyl-dUrd greater than 5-(5-chloro-1-pentynyl)-dUrd greater than 5-ethynyl-dUrd approximately 5 vinyl-dUrd greater than 5-phenylethynyl-dUrd greater than 5-(5-cyano-1-pentenyl)-dUrd greater than 5-(1-propenyl)-dUrd greater than 5-(1-hexynyl)-dUrd greater than 5-(5-hexyn-1-enyl)-dUrd. Among the 5-substituted dCyd analogues, 5-methyl-dCyd, 5-chloro-dCyd, 5-bromo-dCyd and 5-iodo-dCyd were also found to stimulate cell growth, and are therefore assumed to be incorporated into FM3A/TS- cell DNA. Since the stimulatory effects of these compounds on FM3A/TS- cell proliferation were suppressed in the presence of a Cyd deaminase inhibitor (tetrahydrouridine) or dCMP deaminase inhibitor (2'-deoxytetrahydrouridine), it is surmised that the dCyd analogues are first deaminated to the corresponding dUrd analogues before they are incorporated into DNA. None of the 5-substituted araU or araC analogues tested were able to sustain the growth of FM3A/TS- cells. It is postulated, therefore, that these araU or araC analogues are not incorporated to any appreciable extent into the DNA of FM3A/TS- cells, or, if they are incorporated, prevent cell growth. Thus, the dTMP synthetase-deficient FM3A/TS- cell line represents a unique system to distinguish those pyrimidine nucleoside analogues that are able to sustain cell growth and, therefore, assumed to be incorporated into the host cell DNA from those pyrimidine nucleoside analogues that are not.     

Phosphonoformate and phosphonoacetate derivatives of 5-substituted 2'-deoxyuridines: synthesis and antiviral activity

The synthesis of potential "combined prodrugs" wherein phosphonoformate or phosphonoacetate was attached to the 5'-position of 2'-deoxyuridine, 2'-deoxythymidine, 5-iodo-2'-deoxyuridine (IDU), 5-(2-chloroethyl)-2'-deoxyuridine (CEDU), or 5-(2-bromovinyl)-2'-deoxyuridine (BVDU) or to the 3'-position of CEDU is described. The antiviral activities of these derivatives and of reference compounds were compared in Vero, HEp-2, and primary rabbit kidney cells against herpes simplex virus types 1 and 2 (HSV-1 and -2). The CEDU and BVDU analogues were also evaluated against systemic and intracutaneous HSV-1 infection in mice. The nature of the 5-substituent proved critical for antiviral activity, since only the 5-iodo-, 5-(2-bromovinyl)-, and 5-(2-chloroethyl)-substituted derivatives were inhibitory to the herpesviruses. Furthermore, the type specificity is determined by the nature of the 5-substituent: the IDU analogues were similarly inhibitory to HSV-1 and -2 whereas the CEDU and BVDU analogues inhibited HSV-2 replication only at considerably higher concentrations than HSV-1. In vivo, several derivatives were shown to possess significant antiviral activity; however, none surpassed its respective parent compound, CEDU or BVDU, in potency. It seems improbable, therefore, that a synergistic effect between PFA or PAA and the nucleoside analogue occurred. The extent of in vitro and in vivo activity of the CEDU and BVDU 5'-phosphonoformates and 5'-phosphonoacetates is most plausibly explained by the ease by which the "combined prodrugs" are hydrolyzed and the parent compound, CEDU and BVDU, respectively, is released.     

Synthesis of novel 6-(4-substituted piperazine-1-yl)-9-(β-D-ribofuranosyl)purine derivatives, which lead to senescence-induced cell death in liver cancer cells

Novel purine ribonucleoside analogues (9-13) containing a 4-substituted piperazine in the substituent at N(6) were synthesized and evaluated for their cytotoxicity on Huh7, HepG2, FOCUS, Mahlavu liver, MCF7 breast, and HCT116 colon carcinoma cell lines. The purine nucleoside analogues were analyzed initially by an anticancer drug-screening method based on a sulforhodamine B assay. Two nucleoside derivatives with promising cytotoxic activities (11 and 12) were further analyzed on the hepatoma cells. The N(6)-(4-Trifluoromethylphenyl)piperazine analogue 11 displayed the best antitumor activity, with IC(50) values between 5.2 and 9.2 μM. Similar to previously described nucleoside analogues, compound 11 also interferes with cellular ATP reserves, possibly through influencing cellular kinase activities. Furthermore, the novel nucleoside analogue 11 was shown to induce senescence-associated cell death, as demonstrated by the SAβ-gal assay. The senescence-dependent cytotoxic effect of 11 was also confirmed through phosphorylation of the Rb protein by p15(INK4b) overexpression in the presence of this compound.     

Synthesis of new (+-)-3,5-dihydroxypentyl nucleoside analogues from 1-amino-5-(benzyloxy)pentan-3-ol and their antiviral evaluation

The synthesis and antiviral evaluation of a series of (+-)-3,5- dihydroxypentyl nucleoside analogues related to acyclic nucleoside antiviral agents are reported. All purine and pyrimidine nucleoside analogues described in this paper have been obtained from 1-amino-5-(benzyloxy)pentan-3-ol. A synthesis of this amine is reported from 1-(benzyloxy)but-3-ene after epoxidation and regiospecific diethylaluminum chloride catalyzed opening of the epoxide by trimethylsilyl cyanide. The compounds were tested in vitro in infected MRC5 and CEM cells. None of the compounds exhibited antiviral activity against HSV-1, HCMV, and HIV-1 with the exception of the guanine derivative 7, which inhibited the cytopathic effect of HSV-1 by 50% at 12.5 micrograms/mL.     

48例非酒精性脂肪肝合并慢性乙型肝炎患者临床分析

目的探讨非酒精性脂肪肝合并慢性乙型肝炎患者的临床病理特征。方法对非酒精性脂肪肝合并慢性乙型肝炎患者和慢性乙肝患者的丙氨酸氨基转移酶、门冬氨酸氨基转移酶、碱性磷酸酶、γ-谷氨酸转移酶、空腹血糖、空腹胰岛素、总胆固醇、三酰甘油、HBV-DNA等进行比较,计算体重指数、胰岛素抵抗指数,通过肝脏组织病理学结果观察非酒精性脂肪肝合并慢性乙型肝炎患者病理特征。结果非酒精性脂肪肝合并慢性乙型肝炎患者的空腹血糖、空腹胰岛素、总胆固醇、三酰甘油、体重指数、胰岛素抵抗指数等高于慢性乙肝患者,病毒载量较低,炎症活度多为G1和G2,纤维化程度在S2以下,脂肪变程度多在F2、F3之间,肝脾CT比值低于慢性乙肝患者。结论非酒精性脂肪肝合并慢性乙型肝炎患者的临床病理特征不同于单纯慢性乙肝患者,应积极行肝组织学检查早期诊断,合理抗病毒治疗。