HBV-DNA阴性HBV相关性肝癌患者TACE术后联合恩替卡韦抗病毒治疗对预后的影响

[摘要] 目的：探讨肝动脉化疗栓塞（TACE）联合恩替卡韦治疗HBV-DNA阴性HBV相关性肝癌病例的疗效和预后。方法：于2012年6月至2014年6月选择HBV-DNA阴性的HBV相关性肝癌患者112例,随机分为观察组和对照组各56例。观察组采用TACE联合恩替卡韦治疗,对照组仅行TACE治疗。检测并比较两组对象术前1周、术后1周及2周的肝功能（ALT、AST、TBil、GGT）、血清HBV-DNA,随访并比较治疗的有效率和生存情况。结果：两组TACE术后1周均出现肝功能损害（ALT、AST、TBil和GGT升高）,观察组ALT、AST和TBil均低于对照组 (p <0.05)。术后2周两组ALT、AST、TBil和GGT均有下降,且观察组ALT、AST、TBil和GGT均低于对照组 (p <0.05)。术后3个月观察组治疗有效率为35.72%,高于对照组的16.04%（p<0.05）。观察组和对照组术后12个月生存率分别为82.14%和58.93%（p<0.05）,观察组HBV激活率为6.52%,低于对照组的24.24%（p<0.05）。结论：对HBV-DNA阴性的HBV相关性肝癌病例采用ATCE术联合恩替卡韦治疗,能改善TACE导致的肝功能损害,降低HBV的激活率,延长病例1年生存期。     

肝动脉化疗栓塞术联合恩替卡韦对乙肝病毒脱氧核糖核酸阴性的乙型肝炎病毒相关性肝癌病人预后的影响

目的 探讨肝动脉化疗栓塞(TACE)联合恩替卡韦治疗乙肝病毒脱氧核糖核酸(HBV-DNA)阴性的乙型肝炎病毒(HBV)相关性肝癌病例的疗效和预后.方法 选择HBV-DNA阴性的HBV相关性肝癌病人112例,按随机数字表法分为观察组和对照组,每组56例.观察组采用TACE联合恩替卡韦治疗,对照组仅行TACE治疗.检测并比较两组病人术前1周、术后1周及2周的肝功能[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)、γ-谷氨酰转肽酶(GGT)]、血清HBV-DNA,随访并比较治疗的有效率和生存情况.结果 两组TACE术后1周均出现肝功能损害(ALT、AST、TBil和GGT升高),观察组ALT、AST和TBil均低于对照组 (P<0.05).术后2周两组ALT、AST、TBil和GGT均有下降,且观察组ALT、AST、TBil和GGT均低于对照组 (P<0.05).术后3个月观察组治疗有效率为35.72%,高于对照组的16.04%(P<0.05).术后6个月生存率差异无统计学意义(P>0.05).观察组和对照组术后12个月生存率分别为82.14%和58.93%(P<0.05),观察组HBV激活率为5.36%,低于对照组的14.29%(P<0.05).结论 对HBV-DNA阴性的HBV相关性肝癌病例采用TACE术联合恩替卡韦治疗,能改善TACE导致的肝功能损害,降低HBV的激活率,延长1年生存期.     

恩替卡韦联合康艾注射液治疗HBV相关性中晚期肝癌患者的肝功能、凝血、血常规和HBV-DNA水平变化的临床观察

目的观察恩替卡韦联合康艾注射液治疗HBV相关性中晚期肝癌患者的肝功能、凝血、血常规和HBV-DNA水平变化。方法将60例HBV相关性中晚期肝癌患者在化疗和放疗的基础上,随机分为两组。恩替卡韦联合康艾注射液为观察组(30例)和单用康艾注射液为对照组(30例)进行治疗,观察疗程20周。分析未治疗和治疗后两组患者的肝功能(PA、TBA、ALB、ALT、TBIL)、凝血指标(PT、PTA、APTT、TT、FIB)、血常规(WBC、PLT)和HBV-DNA水平的变化。结果恩替卡韦联合康艾注射液应用观察组的患者,在肝功能(PA、TBA、ALB、ALT、TBIL)、凝血指标(PT、PTA、APTT、TT、FIB)、血常规(WBC、PLT)和HBV-DNA的水平改善方面明显优于对照组(P<0.05)。结论恩替卡韦联合康艾注射液治疗治疗HBV相关性中晚期肝癌治疗具有较好的临床效果,能够有效地改善肝癌患者的肝功能、凝血功能、血常规指标和HBV-DNA水平。     

乙型肝炎继发肝癌患者TACE术围术期使用恩替卡韦的临床观察

目的:观察乙型肝炎(以下简称"乙肝")继发肝癌患者肝动脉化疗栓塞(TACE)术围术期使用恩替卡韦辅助治疗的临床疗效及安全性。方法:选取我院2012年6月-2013年6月拟行TACE术的乙肝继发肝癌患者130例,按照随机数字表法分为对照组和观察组,各65例。对照组患者给予TACE术治疗,化疗药物方案为氟尿嘧啶注射液20 m L+盐酸表柔比星注射液10 m L加入0.9%氯化钠注射液500 m L,ivgtt;观察组患者在TACE术前1周开始给予马来酸恩替卡韦片0.5 mg,po,qd,连续治疗12个月。比较两组患者临床疗效、甲胎蛋白(AFP)水平、乙肝病毒(HBV)DNA定量、丙氨酸转氨酶(ALT)水平、日常生活质量评分和生存率,并记录不良反应发生情况。结果:治疗前,两组患者AFP水平、HBV-DNA定量、ALT水平和日常生活质量评分比较,差异均无统计学意义(P>0.05)。治疗后,观察组患者治疗总有效率显著高于对照组(41.54%vs.20.00%),AFP水平、HBV-DNA定量和ALT水平明显低于对照组,日常生活质量评分明显高于对照组,差异均有统计学意义(P<0.05)。观察组患者随访1、2、3年的生存率均明显高于对照组(分别为75.38%vs.52.31%、53.85%vs.29.23%、32.31%vs.15.38%),差异均有统计学意义(P<0.05)。两组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论:乙肝继发肝癌患者TACE术围术期使用恩替卡韦辅助治疗可有效控制患者疾病进展,保护肝功能,提高日常生活质量,并有助于提高总生存率,且安全性好。     

替诺福韦酯和恩替卡韦治疗乙型肝炎的效果和用药成本比较

目的:比较替诺福韦酯和恩替卡韦治疗乙型肝炎的效果和用药成本。方法:选取2015年9月-2016年9月我院收治的300例乙型肝炎病毒(HBV)感染患者,随机分为替诺福韦酯组和恩替卡韦组,每组150例。替诺福韦酯组患者口服富马酸替诺福韦二吡呋酯片300 mg,每日1次;恩替卡韦组患者口服恩替卡韦片0.5 mg,每日1次,均连续用药48周。比较两组患者给药前和给药24、48周后HBV脱氧核糖核酸(HBV-DNA)水平、HBV-DNA阴转率、丙氨酸转氨酶(ALT)水平、ALT复常率,以及给药48周后的用药成本-效果比和不良反应。结果:两组患者给药前HBV-DNA水平,给药前和给药24、48周ALT水平和ALT复常率比较差异均无统计学意义(P>0.05)。与恩替卡韦组比较,替诺福韦酯组患者给药24周、48周后HBV-DNA水平均明显降低(P<0.05);替诺福韦酯组患者给药24周后的HBV-DNA阴转率略高,但差异无统计学意义(P>0.05),给药48周后的HBV-DNA阴转率明显升高(P<0.05)。替诺福韦酯组的HBV-DNA阴转及ALT复常用药成本-效果比均优于恩替卡韦组(P<0.05),总不良反应发生率低于恩替卡韦组(P<0.05)。结论:替诺福韦酯可有效治疗HBV,其效果和用药成本均优于恩替卡韦。     

恩替卡韦对HBeAg阴性慢性乙型肝炎患者肝脏瞬时弹性的影响

目的探讨恩替卡韦对HBe Ag阴性慢性乙型肝炎(CHB)患者肝脏瞬时弹性值(LSM)的影响及临床意义。方法 72例HBe Ag阴性CHB患者随机分为对照组和治疗组。对照组32例予以拉米夫定100 mg·d-1,po,治疗组40例予以恩替卡韦0.5 mg·d-1,po,疗程48周。检测两组患者治疗前后血清丙氨酸氨基转移酶(ALT)、玻璃酸(HA)及HBV-DNA水平,同时运用肝脏瞬时弹性超声成像(FS)测量LSM值。结果恩替卡韦治疗48周后,患者血清ALT、HA较治疗前显著下降(P<0.05或P<0.01),治疗组治疗前后LSM分别为(14.5±9.2),(8.9±3.3)k Pa,对照组分别为(15.1±8.5),(11.5±3.1)k Pa;治疗组HBV-DNA阴转患者LSM显著低于HBV-DNA阳性患者(P<0.05),但HBVDNA水平与LSM无显著相关性(r=0.501,P=0.140)。结论 LSM下降是恩替卡韦抗病毒治疗有效的表现之一,LSM可作为恩替卡韦治疗HBe Ag阴性CHB患者疗效评估及随访观察的新指标。     

雷替曲塞与氟尿嘧啶对不可切除肝癌患者的疗效观察

目的 观察雷替曲塞与氟尿嘧啶分别联合奥沙利铂及表柔比星经导管肝动脉化疗栓塞术(TACE)治疗不可切除原发性肝癌患者的临床效果。方法 回顾性收集2016年1月至2020年3月行TACE治疗的108例Ⅱb～Ⅲa期原发性肝癌患者根据用药不同分为2组，观察组56例和对照组52例。观察组给予雷替曲塞联合奥沙利铂及表柔比星行TACE治疗，对照组给予氟尿嘧啶联合奥沙利铂及表柔比星行TACE治疗。术后3 d、7 d复查血常规及肝肾功，4～6周复查腹部增强CT或MRI。根据改良实体瘤疗效评价标准(mRECIST)^[9]评估治疗效果。2组患者于术后4～6周评估疗效。结果 观察组CR 4例、PR 26例、SD 16例、PD 10例，ORR 54%,DCR 82%;对照组CR 2例、PR 21例、SD 16例、PD 13例，ORR 46%,DCR 75%;2组ORR、DCR比较差异无统计学意义(P=0.365)。观察组和对照组的中位PFS(mPFS)分别为191 d和137 d,相差54 d,差异有统计学意义(P=0.005)。2组患者的不良反应差异无统计学意义(P>0.05)。结...     

恩替卡韦抗病毒治疗对肝癌HBV感染患者的疗效及其对HBV-DNA和肝功能水平的影响

目的:探究恩替卡韦抗病毒治疗对肝癌患者乙肝病毒(HBV)感染的疗效及其对HBV-DNA和肝功能水平的影响。方法:选取2015年4月—2018年5月间收治的肝癌手术患者120例资料,根据其HBV-DNA指标水平(以1.7×10~4U/mL为界限),将其分为高病毒复制组(n=60()A1组30例和A2组30例)和低病毒复制组(n=60)(B1组30例和B2组30例);将A1组和B1组患者均给予恩替卡韦抗病毒治疗,而A2组和B2组未给予恩替卡韦治疗;比较4组患者治疗后术后并发症的发生率差异,以及肝功能、HBV-DNA指标水平测得值的变化情况。结果:A1组和B1组患者恩替卡韦抗病毒治疗后其肝功能水平均显著低于A2组和B2组(P<0.05),并发症的发生率也明显低于A2组和B2组(P<0.05),HBV-DNA指标水平测得值也明显低于A2组和B2组(P<0.05)。结论:针对肝癌HBV感染患者,术后采用恩替卡韦抗病毒治疗有助于改善其肝功能及HBV-DNA指标水平,且安全性较高。     

恩替卡韦治疗HBeAg阳性慢性重度乙型肝炎临床观察

目的:探讨观察恩替卡韦治疗HBeAg阳性慢性重度乙型肝炎(HBV)的临床效果.方法:将我院收治的81例HBeAg阳性慢性重度乙型肝炎患者根据随机综合序贯法分组,对照组(40例)予以拉米夫定治疗,观察组采用恩替卡韦治疗,观察对比两组治疗效果.结果:观察组ALT复常率、HBeAg转阴率、HBV-DNA转阴率均明显优于对照组(P<0.05);观察组不良反应发生率明显低于对照组(P<0.05).结论:恩替卡韦治疗HBeAg阳性慢性重度乙型肝炎的临床效果突出,具有"疗效好、安全性高"等优势,值得推广.     

分析小柴胡汤与恩替卡韦联合用药对慢性乙型肝炎的临床疗效

目的分析小柴胡汤与恩替卡韦联合用药对慢性乙型肝炎的临床疗效。方法选取我院2015年9月至2016年8月期间收治98例慢性乙型肝炎患者随机分成观察组与对照组,各49例,予以对照组患者单一的恩替卡韦进行治疗,观察组在对照组用药基础上,使用小菜胡汤予以治疗。对比两组患者临床有效率,通过丙氨酸转氨酶(ALT)恢复正常效率、HbeAg转阴率以及HBV-DNA转阴率进行评价。结果对比两组临床治疗后,观察组患者在ALT恢复正常效率、血清Hbe Ag转阴率、HBV-DNA转阴率均高于对照组,两组差异显著,具有统计学意义(P<0.05)。结论小柴胡汤与恩替卡韦联合用药治疗慢性乙型肝炎疗效显著,相较于恩替卡韦单独用药,能更有效的改善肝功能状况,加强HEbAg、HBV-DNA转阴率,值得临床应用及推广。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.