Design,delivery and efficacy testing of therapeutic nucleic acids used to inhibit hepatitis C virus gene expression in vitro and in vivo

Despite major achievements in the treatment ofchronic hepatitis C with the combination ofinterferons and the nucleoside analog ribavirin themajority of patients with chronic hepatitis C virus(HCV) infection cannot be treated effectively.Toimprove this response rate we used antisensetechnologies to inhibit HCV translation as possibleadditional option for experimental treatment.Antisense oligodeoxynucleotides(ODN) are

Therapeutic and Medicinal Uses of <i>Aloe vera</i>: A Review

The plant Aloe vera is used in Ayurvedic, Homoeopathic and Allopathic streams of medicine, and not only tribal community but also most of the people for food and medicine. The plant leaves contains numerous vitamins, minerals, enzymes, amino acids, natural sugars and other bioactive compounds with emollient, purgative, anti-microbial, anti inflammatory, antioxidant, aphrodisiac, anti-helmenthic, antifungal, antiseptic and cosmetic values for health care. This plant has potential to cure sunburns, burns and minor cuts, and even skin cancer. The external use in cosmetic primarily acts as skin healer and prevents injury of epithelial tissues, cures acne and gives a youthful glow to skin, also acts as extremely powerful laxative.

Continuous Wear of Hydrogel Contact Lenses for Therapeutic Use

Purpose: To investigate the efficacy and complications of continuous wear of etafilcon A for therapeutic use. Materials and Methods: The subjects were 228 eyes of 219 outpatients prescribed contact lens (CL) for one week of continuous therapeutic wear during 10 years. The reason for prescription of CLs, the primary disease, the duration of CL wear and the complications were assessed retrospectively. Results: The predominant reason for prescription of CLs was relief of pain or a foreign-body sensation (62.3%) and protection of the corneal epithelium (20.6%). The primary disease was post-penetrating keratoplasty (36.8%), followed by corneal epithelial erosion (14.5%), post-lamellar keratoplasty (14.0%) and bullous keratopathy (12.2%). The average duration of wearing single lens was 6.5 ± 3.2 days. The average duration of wearing CLs in total was 9.2 ± 10.7 months. The most frequent problem associated with continuous wear of CLs was their dropping out of CLs (12.3%). The complications associated with CLs included conjunctivitis with papillary hyperplasia, corneal erosion and superficial punctate keratitis, but corneal ulcer and corneal infiltrates were not found. Conclusion: Serious complications were not shown changing the lenses every week to keep to the prescribed time limit for continuous therapeutic wear, even if corneal epithelial barrier function is impaired.

Comparison of long-lasting therapeutic effects between succimer and penicillamine on hepatolenticular degeneration

AIM To compare the long term effect of succimer (Suc) with that of penicillamine (Pen) in treating hepatolenticular degeneration (HLD). METHODS One hundred and twenty patients with HLD were divided into 2 groups. Group A ( n =60) received Suc 750mg , po. bid. Group B ( n =60) received Pen 250mg , po. qid. The period of maintenance treatment varied from 6 months to 3 years, averaging 1 5 years. Symptoms and therapeutic effects were evaluated by modified Goldstein scale. RESULTS The total effectiveness of group A in two different periods of treatment were 80% and 85% respectively, higher than those of group B (58% and 59% respectively) ( P <0 05). Suc also had obvious curative effects for the patients who failed in the use of Pen. There were fewer side effect in group A than in group B ( P <0 05). Suc and Pen could increase urinary copper excretion effectively and continually. CONCLUSION Suc is more effective and safer than Pen. Clinically, it can replace Pen as first choice drug for long term maintenance therapy of HLD.

Functional dyspepsia of ulcer-dysmotility type:clinical incidence and therapeutic strategy

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Therapeutic role of template-based lymphadenectomy in urothelial carcinoma of the upper urinary tract

Lymphadenectomy for urothelial carcinoma of the upper urinary tract has attracted the attention of physicians. The mapping study of lymphatic spread has shown that a relatively wide area should comprise the regional nodes for tumors of the right renal pelvis or the right upper two-thirds of the ureter. A prospective study showed that an anatomical templatebased lymphadenectomy significantly improved patient survival in tumors of the renal pelvis. This benefit was more evident for patients with p T2 stage tumors or higher. The risk of regional node recurrence is significant reduced by template-based lymphadenectomy,which is likely to be associated with improved patient survival. The removal of lymph node micrometastases is assumed to be the reason for therapeutic benefit following lymphadenectomy. The number of resected lymph nodes can be used to assess the quality of lymphadenectomy,but not to determine the extent of lymphadenectomy. The guidelines currently recommend lymphadenectomy for patients with muscle-invasive disease,even though the current recommendation grades are still low. The present limitation of lymphadenectomy is the lack of standardization of the extent of lymphadenectomy and the randomized trials. Further studies are warranted to collect the evidence to support lymphadenectomy.

Controversies regarding transplantation of mesenchymal stem cells

Mesenchymal stem cells(MSCs)have tantalized regenerative medicine with their therapeutic potential,yet a cloud of controversies looms over their clinical tran-splantation.This comprehensive review navigates the intricate landscape of MSC controversies,drawing upon 15 years of clinical experience and research.We delve into the fundamental properties of MSCs,exploring their unique immuno-modulatory capabilities and surface markers.The heart of our inquiry lies in the controversial applications of MSC transplantation,including the perennial debate between autologous and allogeneic sources,concerns about efficacy,and lingering safety apprehensions.Moreover,we unravel the enigmatic mechanisms surro-unding MSC transplantation,such as homing,integration,and the delicate balance between differentiation and paracrine effects.We also assess the current status of clinical trials and the ever-evolving regulatory landscape.As we peer into the future,we examine emerging trends,envisioning personalized medicine and innovative delivery methods.Our review provides a balanced and informed perspective on the controversies,offering readers a clear understanding of the complexities,challenges,and potential solutions in MSC transplantation.

超高效液相色谱-串联质谱法同时测定5种抗逆转录病毒药物血药浓度

目的建立超高效液相色谱-串联质谱(UPLC-MS/MS)法同时测定人血浆中多替拉韦、拉替拉韦、依非韦伦、拉米夫定和替诺福韦浓度,并应用于治疗药物监测。方法分别以多替拉韦-D5、拉替拉韦-D4、依非韦伦-D5、拉米夫定-^(13)C-^(15)N_(2)、替诺福韦-D7作为内标,样本经乙腈沉淀蛋白法处理后稀释进样分析。色谱柱为Shim-pack XR-ODSⅢ(2.0 mm×50 mm,1.6μm),流动相为0.1%甲酸-0.1%甲酸乙腈,梯度洗脱,流速为0.3 mL·min^(-1),柱温40℃。采用电喷雾离子源,正离子-多反应监测模式扫描分析,待方法学验证后用于人类免疫缺陷病毒(HIV)感染患者治疗药物监测。结果多替拉韦、拉替拉韦、依非韦伦、拉米夫定、替诺福韦血药浓度分别在62.5~3000、10~500、125~6000、10~500、10~500 ng·mL^(-1)范围内线性关系良好,线性相关系数(R^(2))均>0.998;四水平质控样品的日内和日间精密度RSD<7%,准确度为94.0%~109.3%;提取回收率为98.7%~104.5%、不同类型血浆基质效应为95.7%~106.0%,且血浆样本在一定的储存环境中稳定性良好。临床样本检测结果显示接受多替拉韦、依非韦伦、拉米夫定、替诺福韦的HIV患者血药谷浓度分别为107.7~2366.0、740.0~3410.0、38.5~1229.3、31.6~224.4 ng·mL^(-1)。结论该方法准确度高、操作简便、成本低,适用于HIV患者多替拉韦、拉替拉韦、依非韦伦、拉米夫定、替诺福韦的治疗药物监测。

Clinacanthus nutans:a review of the medicinal uses,pharmacology and phytochemistry

Clinacanthus nutans Lindau is known as snake grass belonging to the Acanlhaceae family.This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes,insects and snake bites,lesions caused by herpes simplex virus,diabetes,and gout in Malaysia.Indonesia.Thailand and China.Phylochemieal investigations documented the varied contents of bioaclive compounds from litis plant namely flavonoids,glycosides,glycoglyeerolipids.cerebrosides and monoacylmonogalatosylglycerol.The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory,antiviral,antioxidant,and anti-diabetic activities.The lindings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions.However,further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability tor future drugs.This review summarizes the medicinal uses,phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work.

High-intensity focused ultrasound extracorporeal ablation of liver tissuesin rabbits

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The role of drug utilization evaluation in medical sciences

Background:Drug utilization evaluation(DUE)is defined by the World Health Organization(WHO)and focuses on the medical,social,and economic consequences of pharmaceutical marketing,distribution,prescribing,and usage in society.The WHO recommends a physician to every 1000 people.According to the recent data from the Health Ministry in 2019,in which 1.16 million doctors are of active population with just 80%,or 0.9 million,practicing.As a result,a ratio of 0.68 doctors for every 1000 people,which is much below as per the WHO reports.This article describes history,types,WHO guidelines,need and purpose of DUE.Objective:The main aim of this paper is to provide information about the rational use of medication in outpa­tient and inpatient department with special emphasis of DUEs.It also provides awareness directly to healthcare professionals,researchers,academicians,pharmacist and nurses to reduce the irrationality of medicines.Methods:The method used to compile this review information gathered from websites,Google scholar,PubMed,Research gate,and studies published on DUE from July 20 to Oct 22 were included as source of information.Results:We studied more than 35 published study on DUE,that reveals most of the physicians prescribed branded drugs not generic drugs,but WHO prescribing indicator allows to prescribe generic drugs in the hospital pharmacy to maintain better inventory control.It may also help to prevent pharmacist misunderstanding during dispensing.Conclusion:The use of generic prescription names avoids the possibility of medication product duplication and lowers patient costs.It is important to remember that incorrect medication prescriptions have impact on both patients and their family members.WHO indicators identify irrational prescribing behaviours to make therapy more rational and cost-effective.

USE OF CELL-BASED BIOASSAY FOR THE QUALITY CONTROL OF BOTANICAL THERAPEUTICS

The single most important factor in modernization efforts of traditional oriental medicines is the limited understanding of active compounds responsible for claimed therapeutic effects.Indeed,the unknown identity of biologically active molecules generates major difficulties associated with botanical therapeutics in general.This includes management of raw materials,poor understanding of

抗病毒对肝动脉化疗栓塞治疗乙肝后中晚期肝癌的作用

目的观察抗病毒对肝动脉化疗栓塞(TACE)治疗乙肝后中晚期肝癌的作用。方法 60例HBVDNA阳性的中晚期肝癌患者随机分为治疗组(36例)和对照组(24例),对照组给予常规TACE治疗,治疗组在对照组基础上,口服拉米夫定抗HBV,比较两组治疗1月和3月后的肝功能、Child-Pugh评分、HBVDNA水平,治疗3月后实体瘤缩小疗效、生活质量改善情况及生存期。结果治疗后1月、3月治疗组ALT、TBil、HBVDNA水平均较对照组降低(P<0.05,P<0.01);治疗后3月AST、AFP较对照组降低(P<0.05,P<0.01),ALB较对照组升高(P<0.05),Child-Pugh分级较对照组有改善(P<0.05)。治疗后3月两组实体瘤缩小疗效差异无统计学意义(P>0.05),在提高生活质量、延长生存期方面,治疗组明显优于对照组(P<0.05)。结论抗病毒对TACE治疗的乙肝后中晚期肝癌患者具有重要的作用。

胸腺肽α_1促进拉米夫定抗乙型肝炎病毒的疗效

【目的】探讨胸腺肽α1和拉米夫定联合治疗慢性乙型肝炎的长期疗效和安全性。【方法】按随机对照原则选择80例HBVDNA、HBeAg阳性的慢性乙型肝炎患者,按1∶1随机分配进入单一接受拉米夫定治疗组和胸腺肽α1与拉米夫定联合治疗组。【结果】治疗52周,联合治疗组HBeAg血清转换率52%(16/31)明显高于拉米夫定组5%(2/37),Ρ<0.001。停药1年,持续的HBeAg血清转换率分别为42%(13/31)和8%(3/37),Ρ=0.001。治疗过程,两组HBVDNA定量明显下降,联合治疗组下降更显著,但停药后HBVDNA反弹;治疗后,两组的ALT复常率基本一致,达80%(25/31)和68%(25/37),但停药后拉米夫定组仅有19%持续正常,明显低于联合治疗组。拉米夫定组有10例(27%)发生YMDD变异,联合组仅有1例。治疗后肝组织炎症坏死程度明显地改善,肝纤维化程度降低,HBsAg、HBcAg的表达明显减少。治疗过程无明显的不良反应。【结论】胸腺肽α1与拉米夫定联合治疗慢性乙型肝炎疗效明显优于单一用药组,是安全、有效的治疗慢性乙型肝炎的方案。

叶下珠复方和拉米夫定治疗慢性乙型肝炎的临床疗效比较

【目的】观察比较叶下珠复方、拉米夫定、叶下珠复方合用拉米夫定治疗慢性乙型肝炎的疗效。【方法】 90例慢性乙型肝炎患者随机分 3组 ,分别为叶下珠复方组 (剂量 2 6g/次 ,3次 /d)、拉米夫定组 (剂量 10 0mg/次 ,1次 /d)和叶下珠复方合用拉米夫定组 ,均连续口服 5 2周。治疗前、后定期检测血清肝功能指标及乙型肝炎标志物表面抗原 (HBsAg)、e抗原 (HBeAg)、乙型肝炎病毒脱氧核糖核酸 (HBV DNA)及酪氨酸—蛋氨酸—天冬氨酸—天冬氨酸 (YMDD)含量。【结果】叶下珠复方组肝功能复常率、HBeAg转阴率均高于拉米夫定组 ,而HBV DNA转阴率低于拉米夫定组 (P <0 0 5 ) ,YMDD变异少于拉米夫定组 (P <0 0 5 ) ;两药合用组的HBeAg转阴率与叶下珠复方组相仿 (P >0 0 5 )而高于拉米夫定组 (P <0 0 1) ,HBV DNA转阴率均高于叶下珠复方组和拉米夫定组 (均P <0 0 1) ,肝功能复常率高于拉米夫定组 (P <0 0 5或P<0 0 1) ,YMDD变异也少于拉米夫定组 (P <0 0 5 )。【结论】叶下珠复方与拉米夫定联合用药可提高治疗慢性乙型肝炎疗效 ,减少YMDD变异 ,推迟和避免拉米夫定耐药株产生 ,以及由此而引起的病毒在体内的持续复制。

消胀方联合拉米夫定治疗84例乙型肝炎肝硬化代偿期的临床疗效观察

目的评价消胀方治疗乙型肝炎肝硬化代偿期患者的临床疗效。方法 84例乙型肝炎肝硬化代偿期患者按前瞻性队列研究方法分为治疗组与对照组。治疗组在拉米夫定抗病毒基础上以消胀方(由太子参、白术、陈皮、白茅根、泽泻、泽兰、鳖甲、牡蛎、鸡内金、大腹皮组成),每日1剂,水煎分2次口服;对照组在拉米夫定抗病毒基础上治以扶正化瘀胶囊(主要由丹参、桃仁、绞股蓝、冬虫夏草、五味子组成),每次5粒,每日3次,餐前30min口服,疗程均为12个月。观察并比较治疗前后两组患者的中医证候积分、慢性肝病疾病特异性量表(CLDQ)评分、肝功能、乙肝病毒DNA(HBVDNA),同时对所有患者进行治疗前后B超检查,记录门静脉内径(MPV)、脾静脉内径(SPV)、脾脏长度及厚度的变化。结果治疗后两组患者中医证候积分、CLDQ评分较治疗前均明显降低(P<0.01),且治疗组积分较对照组亦明显减少(P<0.05,P<0.01);两组患者Child-Pugh分级治疗后均明显下降(P<0.01),但组间比较差异无统计学意义;两组患者肝功能较治疗前均明显改善(P<0.01),且治疗组改善较对照组明显(P<0.01);B超结果显示,治疗组患者MPV、SPV、脾长度、脾厚度均有明显降低(P<0.01),对照组仅脾厚度有明显降低(P<0.01);两组患者HBVDNA较治疗前均明显降低(P<0.01),且治疗组降低较为明显(P<0.01)。结论消胀方联合拉米夫定可改善乙型肝炎肝硬化代偿期患者的肝功能、HBVDNA,降低患者的中医证候积分及CLDQ积分,在一定程度上改善患者肝功能Child-Pugh分级,具有较好的疗效。

恩替卡韦治疗慢性乙型肝炎肝硬化失代偿期患者的近期疗效及安全性

目的:观察恩替卡韦治疗慢性乙型肝炎(CHB)肝硬化失代偿期患者的近期疗效及安全性。方法:选取44例CHB肝硬化失代偿期患者,随机分为恩替卡韦组(22例)和拉米夫定组(22例)。两组患者均给予综合治疗,其中恩替卡韦组患者加用恩替卡韦0.5mg/次口服,1次/d;拉米夫定组患者加用拉米夫定100mg/次口服,1次/d。每周检测两组患者HBV DNA、ALT、Alb、TBil、PTA(凝血酶源活动度)及乳酸(Lactate)等指标变化,连续8周。结果:两组患者HBV DNA水平均从治疗第2周开始逐渐下降,但恩替卡韦组患者HBV DNA水平在治疗后第5周下降到低于检测下限(<5×102拷贝/ml),明显快于拉米夫定组。从治疗第5周开始,恩替卡韦组患者Alb、TBil及PTA指标较拉米夫定组患者有更明显的改善。在8周的观察期内,有9例患者死亡(MELD评分均>25),其中恩替卡韦组4例,拉米夫定组5例,两组之间病死率比较差异无显著性意义(P>0.05)。9例死亡患者均有不同程度的高乳酸血症(2.0～4.0 mmol/L),但无乳酸酸中毒发生。结论:恩替卡韦较拉米夫定有更显著的抗病毒活性,可在短期内较迅速改善CHB肝硬化失代偿期患者病情。恩替卡韦或拉米夫定均无明显的药物不良反应。血清乳酸水平的升高主要与患者病情严重有关。

阿德福韦酯联合拉米夫定治疗拉米夫定耐药慢性乙型肝炎疗效观察

目的探讨阿德福韦酯(ADV)联合拉米夫定(LAM)治疗LAM耐药慢性乙型肝炎(CHB)患者的临床疗效及安全性。方法选择LAM耐药的HBeAg阳性CHB患者102例随机分为3组,ADV+LAM组(A组)38例,给予ADV10mg/d联合LAM100 mg/d口服;ADV组(B组)42例,ADV10mg/d口服;LAM组(C组)22例,LAM 100mg/d口服,分别于完成24、48和72周治疗时,观察血清HBV DNA水平、HBV血清学标志、肝功能及不良反应。结果治疗24、48、72周A、B组HBV DNA水平较C组均显著下降(P<0.01),HBV DNA阴转率较C组显著升高(P<0.05,P<0.01),治疗24、48、72周A组和72周B组ALT复常率较C组均显著升高(P<0.05,P<0.01);治疗48、72周A组HBV DNA水平较B组显著下降(P<0.05),治疗72周HBV DNA阴转率和ALT复常率较B组显著升高(P<0.05,P<0.01)。三组血清HBeAg阴转率及血清转换率间差异无统计学意义(P>0.05)。治疗期间A组新的耐药变异率低于C组(P<0.05),均未发现与药物相关的严重不良反应。结论ADV联合LAM治疗LAM耐药CHB患者具有显著的抗病毒和临床疗效,且安全性良好。

拉米夫定治疗慢性乙型肝炎的病原学研究

目的 观察拉米夫定治疗对慢性乙肝患者体内HBVDNA的影响。方法 对拉米夫定治疗组 31例 (po ,10 0mg/d ,2 5周 )和对照 2 0例组进行HBVDNA的斑点杂交和PCR半定量检测 ;未阴转者扩增含YMDD编码区的基因片段测序。结果 拉米夫定治疗组 4周、8周、2 4周、5 2周HBVDNA阴转率分别为 5 5 %、6 8%、80 %、73% ,远高于对照组(P <0 0 5 ) ;治疗组的YMDD变异株检出率亦高于对照组。结论 拉米夫定对HBV有较强的抑制作用 。

拉米夫定或阿德福韦酯选择性治疗失代偿性乙型肝炎肝硬化3年临床观察

目的观察拉米夫定或阿德福韦酯选择性治疗乙型肝炎肝硬化失代偿期患者长疗程疗效及治疗方案的选择。方法乙型肝炎肝硬化失代偿期患者65例,HBV DNA>5 log10拷贝/mL者服用拉米夫定(100mg/d)或再联用阿德福韦酯(10mg/d);HBV DNA<5 log10拷贝/mL者可单用拉米夫定或阿德福韦酯;病毒持续不下降或反弹要求拉米夫定联用阿德福韦酯。观察治疗前后患者临床症状体征、生化指标、病毒学改变情况。结果65例患者中43例生存至研究结束,3年生存率为66.1%。患者治疗后肝功能正常或好转,病情缓解稳定,生活质量改善,HBV DNA下降约3 log10拷贝/mL,Child-Pugh积分下降>3。结论拉米夫定或阿德福韦酯选择性治疗乙型肝炎肝硬化失代偿期患者,可延长患者生存时间,改善肝功能,阻止病情进展,提高生活质量。