恩替卡韦联合丹参酮IIA治疗肝纤维化疗效观察

乙型肝炎病毒（HBV）是我国引起肝纤维化的主要因素之一，肝纤维化主要病理学特征以胶原为主的细胞外基质各成分因合成增多，降解相对不足而在肝内过量沉积。制止或逆转肝纤维化是防止肝硬化的主要途径，临床应用中抗病毒与抗肝纤维化治疗对防止乙型肝炎肝硬化具有重要意义。抗肝纤维化治疗包括针对原发病的病因治疗以及针对肝纤维化的治疗，如抑制肝星状细胞的活化，抑制胶原增生及促进胶原降解等。近年来随着对肝纤维化发生机制认识的不断深入，特别是对以胶原为主的细胞外基质合成与降解调控的了解，国内外文献证实，慢性乙型肝炎（CHB）早期肝纤维化阶段经过治疗大多数可以逆转和治愈。     

抗肝纤维化药物治疗的研究进展

肝纤维化是肝脏受到慢性损伤的一种修复反应,是多种慢性肝病共有的病理改变,可最终导致肝硬化、肝癌。肝纤维化的主要机制是以胶原为主的细胞外基质合成大于降解,从而使细胞外基质在肝脏过度沉积。目前认为,早期肝纤维化是一种可逆性病变,有效控制肝脏基础疾病或抗肝纤维化治疗对肝纤维化的治疗有重要意义。目前,药物治疗是抗肝纤维化治疗的主要方法,抗肝纤维化的药物治疗主要针对控制原发病、保护肝细胞、抑制肝星状细胞活化和增殖、抑制胶原合成、促进胶原降解及调控与纤维化有关的细胞因子、支持对症治疗等方面。本文将近年来肝纤维化药物治疗的研究进展进行综述。     

氯沙坦对肝纤维化鼠细胞外基质的影响

肝纤维化是慢性肝病共有的病理改变，以胶原为主的细胞外基质(ECM)合成增多，降解相对不足，过多沉积在肝内则引起肝纤维化。随着研究的深入，已明确提出了肝纤维化完全可能逆转的论点。因此，寻求理想的抗肝纤维化药物，以阻断或延缓肝纤维化进程，是肝病治疗学的一个重要课题。     

肝纤维化的分子基础与临床诊治现状

慢性肝损伤时,肝星状细胞与肝实质细胞、Kupffer细胞、肝窦内皮细胞等多种细胞相互作用,介导细胞外基质沉积与肝窦毛细血管化,启动肝纤维化进程,其本质是肝损伤后的修复反应。肝穿刺活组织检查技术是肝纤维化诊断的金标准,但有一定出血风险及死亡风险。无创性诊断肝纤维化的手段主要包括血清分子标志物、影像学诊断技术以及预测性统计模型等,但其尚不能完全替代肝穿刺活组织检查。目前,肝纤维化的治疗主要针对原发疾病、以肝星状细胞为靶点的药物研发、以细胞外基质合成/降解平衡为靶点的药物研发等方面。研究肝纤维化分子机制,为探索肝纤维化治疗提供了坚实的理论基础。     

肝纤维化治疗的探索

肝纤维化(hepatic fibrosis)是慢性肝病共有的病理改变,它的形成是一复杂的过程,涉及多种细胞及细胞因子之间的相互作用。其特征是以胶原蛋白为主的细胞外基质(extrecellularmatrix,ECM)各成分合成增多、降解相对不足,过多沉积在肝内引起肝纤维化。由于对肝纤维化发生机制的不断阐明也给其治疗带来了新的发展。其策略主要包括:①去除病因,②抑制肝星状细胞(hepatic stellate cell H9C)的激活,     

肝星状细胞与肝纤维化

肝纤维化是各种慢性肝病损伤修复过程的共同结果,由于肝内纤维生成和降解失衡,导致过多的胶原在肝内沉积,常伴有炎症、缺血缺氧,最终可发展为肝硬化。目前认为,细胞外基质（ECM）过多产生和沉积是肝纤维化的核心表现,活化的肝星状细胞（HSC）仍是细胞外基质的主要细胞来源。因此,肝星状细胞的活化是肝纤维化发生的中心环节。     

中药抗肝纤维化药理研究的进展

肝纤维化是肝脏受到各种慢性损伤的愈合反应,表现为细胞外基质(ECM)大量合成、分泌,而降解绝对或相对不足,使ECM在肝脏内弥漫性沉积.肝纤维化是各种慢性肝病共同的病理过程,并是影响预后的重要因素.近10多年对肝纤维化的形成机制研究取得了令人鼓舞的进展,肝纤维化可以逆转这一观点也逐渐得到论证,并被广泛接受.中医药抗肝纤维化的研究从20世纪70年代中期开始,在临床与实验研究中已取得了长足的成就,尤其近年来随着细胞生物学与分子生物学技术的应用,使中医药抗肝纤维化机制的进展步入了较深的层次.现就近年来中医药抗肝纤维化实验研究的进展作一介绍.     

肝纤维化与基质金属蛋白酶以及其抑制因子

肝纤维化的形成主要是以胶原为中心的细胞外基质(Extracellular matrix,ECM)在肝脏异常沉积为特点,这种异常的沉积不仅是由于ECM合成增多,更大程度上是因为肝纤维化后期ECM合成和降解的平衡遭到破坏,胶原降解绝对或相对减少而引起的。在ECM降解过程中起主导作用的是基质金属蛋白酶(Matrix metalloproteinases,MMPs)。此外,能够抑制MMPs活性的MMP抑制因子(Tissue inhibitor of metalloproteinases,TIMPs)在ECM代谢调节中也起到重要作用。     

转化生长因子β1与肝纤维化的研究状况

转化生子因子β1(TGF-β1)是多肽生长因子家族中的一员,在各种病因导致肝损伤后,TGF-β1可活化肝星状细胞而起动肝纤维化进程,并通过促进细胞外基质合成,抑制其降解,使肝脏发生纤维沉积,还通过对其它多种细胞和细胞因子的广泛影响,使肝纤维化不断进展。TGF-β1水平可很好地反映肝纤维化的状况,针对TGF-β1的治疗研究为抗肝纤维化开辟了一条新途径。     

对肝纤维化与中药抗肝纤维化的再认识

肝纤维化是各种慢性肝病发展成肝硬变的必经阶段。抗纤维化,是通过抑制胶原和基质的合成,促进其降解和吸收;而肝纤维化的治疗,包括原发病的治疗、抗肝纤维化、免疫调控治疗,以及对症治疗、支持治疗,实质上是慢性肝病的治疗问题,两者是不同的概念。中药在这方面具有肯定的疗效。 肝纤维化的形成,简单讲就是肝脏细胞外基质(ECM)的改变。特征为汇管区纤维结缔组织增多,增多的结缔组织形成     

肥胖症的药物治疗现状与展望

肥胖是一个严重的公众健康问题，人们迫切希望能有安全、有效的减肥药物。目前用于减肥的药物主要有两类：即西布曲明和赛尼可，前者主要抑制食物的摄取，后者抑制脂肪的吸收。由于对复杂的体重调节机制的认识越来越深入，很多新的减肥药物正在研制过程之中。目前正在研究的具有较大潜力的减肥药物共有30余种，其中研究较多的有瘦素、黑皮质素受体激动剂、神经肽Y拮抗剂、β3肾上腺素能受体激动剂、胰高血糖素样肽－1激动剂以及激活或增加解偶联蛋白表达的药物。     

四联疗法与序贯疗法在幽门螺杆菌根除补救治疗中的疗效比较

[目的]比较四联疗法与序贯疗法在幽门螺杆菌(Hp)根除补救治疗中的疗效及安全性,旨在寻找一种有效、安全、经济的补救治疗方案。[方法]将首次根除Hp治疗失败的90例慢性胃炎患者,随机分为四联疗法组和序贯疗法组,每组45例。四联疗法组患者治疗方案为埃索美拉唑、枸橼酸铋钾、阿莫西林、莫西沙星,疗程14d。序贯疗法组患者治疗方案为前5d给予埃索美拉唑、阿莫西林;后5d给予埃索美拉唑、克拉霉素、奥硝唑。所有患者在疗程结束停药4周后行14 C尿素呼气试验检测Hp。比较2组患者治疗前后的不良反应。[结果]四联疗法组Hp根除率(91.1%)显著高于序贯疗法组(75.6%),差异有统计学意义(P<0.05)。2组不良反应均很轻微,组间不良反应发生率比较差异无统计学意义(P>0.05)。[结论]对于Hp补救治疗,四联疗法较序贯疗法疗效更好,且不良反应小,患者依从性好,值得在临床上推广。     

Feasibility and Acceptability of Bibliotherapy and Telephone Sessions for the Treatment of Late-Life Anxiety Disorders

This article describes the development of Biblio and Telephone Therapy, or BTT, a cognitive-behavioral treatment program for late-life anxiety disorders. Although studies have examined bibliotherapy for the treatment of late-life depression, none have studied it as a format for treating late-life anxiety. The application of this treatment to four older adults with generalized anxiety disorder (GAD) and/or panic disorder (PD) is described, and benefits, advantages, and limitations are discussed.     

Quadruple,sequential, and concomitant first-line therapies for H. pylori eradication: a prospective,randomized study

BackgroundCurrent Italian guidelines recommend 10-day bismuth-based or bismuth-free (sequential and concomitant) regimens for first-line H. pylori eradication. However, comparison among these regimens is lacking in our country.AimTo perform a ‘head-to-head’ comparison among these three therapies as first-line treatment for H. pylori eradication in clinical practice.MethodsThis was a prospective, open-label randomized study enrolling consecutive patients diagnosed with H. pylori infection never previously treated. Patients were randomized to receive one of the following 10-day therapies: (a) Bismuth-based therapy: esomeprazole 20 mg b.i.d and Pylera 3 tablets q.i.d; (b) Concomitant therapy: esomeprazole 20 mg plus amoxicyllin 1,000 mg, clarithromycin 500 mg and tinidazole 500 mg (all b.i.d.), and (c) Sequential therapy: esomeprazole 20 mg plus amoxicyllin 1,000 mg for 5 days followed by esomeprazole 20 mg plus clarithromycin 500 mg and tinidazole 500 mg for 5 days (all b.i.d). H. pylori eradication was assessed by using UBT 4-6 weeks after the end of therapy.ResultsOverall, 187 patients were enrolled. The eradication rates achieved with Pylera, concomitant and sequential were 85.2%, 95.2%, and 93.6%, respectively, at intention to treat, and 94.5%, 96.7%, and 95.1% at per protocol analyses, without a statistically significant difference. The incidence of severe side-effects was higher with the bismuth-based therapy than with the two bismuth-free regimens (9.8% vs 1.6%; p = 0.046).ConclusionsBismuth-based and bismuth-free therapies are equally effective for first-line H. pylori eradication. However, bismuth therapy was more frequently interrupted for side-effects than bismuth-free therapies.     

230例急性肺动脉血栓栓塞症患者对症治疗、抗凝治疗和溶栓治疗的住院转归

目的:介绍对症治疗、抗凝治疗和溶栓治疗3种治疗方法治疗急性肺动脉血栓栓塞症或慢性肺动脉血栓栓塞症急性再发患者的住院转归。方法:回顾性分析1974-2002年的28年来我院住院收治的230例急性肺动脉血栓栓塞症或慢性肺动脉血栓栓塞症急性再发患者经对症治疗、抗凝治疗和溶栓治疗3种治疗方法的住院有效率、显效率和病死率。结果:对症治疗、单纯抗凝和溶栓+抗凝治疗的住院总有效率分别为60．0％、91．5％和96．6％;其中住院显效率分别为0、0．9％和42．7％;住院病死率分别为17．1％、4．7％和3．4％。结论:通过回顾性临床分析表明,对症治疗、抗凝治疗和溶栓治疗对急性肺动脉血栓栓塞症或慢性肺动脉血栓栓塞症急性再发患者均有效。由于患者治疗方法的选择受历史等因素的影响,对3种治疗方法的临床疗效不能进行比较。     

Antiviral effects and safety of telaprevir, peginterferon alfa-2a, and ribavirin for 28 days in hepatitis C patients

BACKGROUND/AIMS: This study assessed the safety and antiviral effects of telaprevir (VX-950) in combination with peginterferon alfa-2a and ribavirin. METHODS: Twelve treatment-nai ve patients with chronic genotype 1 hepatitis C virus infection received telaprevir (750mg q8h), peginterferon alfa-2a (180mug/week), and ribavirin (1000 or 1200mg/day) for 28 days. Patients could then start off-study treatment with peginterferon alfa-2a and ribavirin for up to 44 weeks, at the discretion of the investigator and patient. RESULTS: The combination of telaprevir, peginterferon alfa-2a, and ribavirin was well tolerated, with no serious adverse events or treatment discontinuations. Rash or pruritus occurred in 5 of the 12 patients; all cases resolved either during or after the end of telaprevir treatment. All 12 patients had undetectable HCV RNA levels by day 28 (rapid viral response, RVR). Eight patients completed 44 weeks of off-study peginterferon alfa-2a and ribavirin treatment. Eight patients achieved a sustained viral response (SVR), including one patient who received only 22 weeks of treatment. CONCLUSIONS: The combination of telaprevir, peginterferon alfa-2a, and ribavirin was generally well tolerated. Events of pruritus and rash resolved during or after end of telaprevir dosing. All 12 patients achieved an RVR.     

生物起搏器的研究进展和展望

心脏生物起搏器是近年来心脏起搏的研究热点,目前主要集中在三大治疗策略;(1)细胞治疗;(2)基因治疗;(3)激素治疗.心脏生物起搏器处于研究初步阶段,应用于临床面临许多问题,但是随着分子生物学和基因-工程技术的发展,心脏生物起搏器必将造福于人类.     

Medical treatment of patients with hypertrophic cardiomyopathy: An overview of current and emerging therapy

Several treatments have demonstrated safety and effectiveness in the treatment of patients with hypertrophic cardiomyopathy; however, no drug has been shown to modify the natural history of the disease or to decrease maximal wall thickness. Improvement in our knowledge of the physiopathology of the disease has permitted the development of new therapeutical approaches, including sarcomere modulators and gene therapy. A sarcomere modulator – mavacamten – has been shown to improve exercise capacity, left ventricular outflow tract obstruction, New York Heart Association functional class and health status in a phase 3 trial. Gene therapy – although still far from human experimentation – also has promising characteristics that may radically revolutionize the treatment of hypertrophic cardiomyopathy in the future. This therapy is currently approved for the treatment of select haematological malignancies, inherited retinal dystrophy and spinal muscular atrophy, and could potentially correct the genetic alterations of the most frequent sarcomeric forms of hypertrophic cardiomyopathy. This review provides an overview of current conventional therapies for the management of patients with hypertrophic cardiomyopathy, discusses emerging therapeutic approaches and presents future perspectives.     

Combination therapy with anabolic and antiresorptive agents

Combination therapy, the use of an anabolic agent with an antiresorptive agent in some sequence, has been evaluated in a number of clinical trials. There is no fracture data on combination therapy except for a small trial using PTH and estrogen. It appears that simultaneous use of a bisphosphonate (alendronate 10 mg per day) with PTH offers no advantage (and appears to blunt PTH's effect) compared with the use of PTH alone based on bone density gains. Previous therapy with alendronate also blunts gains in bone density with PTH therapy. Estrogen and raloxifene, whether given before or with PTH, do not blunt its anabolic effect. Sequential therapy with PTH followed by an antiresorptive agent (alendronate) offers the greatest gains in bone mass. It is possible that alendronate or other bisphosphonates given in a different dosing regimes may have different effects on PTH's anabolic effect. More trial data on combination therapy is needed.