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.

Blastocystis hominis as a cause of chronic diarrhea in low-resource settings:A systematic review

BACKGROUND Blastocystis hominis(B.hominis),an anaerobic unicellular protist parasite,is known for its diverse clinical manifestations upon infecting the human gastrointestinal tract.Although globally distributed,it is particularly prevalent in developing nations.Examining the symptoms and treatment outcomes of B.hominis infection in low-resource settings holds immense significance,providing healthcare practi-tioners with valuable insights to enhance patient care.AIM To synthesize existing evidence on the symptomatology and treatment outcomes of B.hominis infection in low-resource settings.METHODS Following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines,a systematic review was conducted.The search spanned electronic databases including PubMed,Scopus,and Google Scholar.After a comprehensive screening process,a thorough examination of the papers,adhering to inclusion and exclusion criteria,and data extraction from eligible studies was conducted.The findings underwent summarization through simple descriptive analysis.RESULTS The search yielded 1200 papers,with 17 meeting inclusion criteria.Chronic diarrhea due to B.hominis infection was reported in only two studies,while abdominal pain,diarrhea,flatulence,constipation,and nausea/vomiting emerged as the most commonly documented symptoms.Recovery rates after one week of treatment ranged from 71.8%to 100%,and after two weeks,from 60%to 100%.CONCLUSION In low-resource settings,chronic diarrhea resulting from B.hominis infection is infrequent.Common symptoms include abdominal pain,diarrhea,flatulence,constipation,and nausea/vomiting.Post-treatment,clinical outcomes are notably favorable,supporting the recommendation for treatment.Metronidazole is advocated as the first-line agent,with consideration for switching to a second-line option in cases of treatment failure or poor response.

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.

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

多西他赛和顺铂同步放化疗治疗局部晚期鼻咽癌临床观察

目的观察局部晚期鼻咽癌同步放化疗的疗效及毒副反应。方法 70例局部晚期鼻咽癌,采用静脉化疗2周期,化疗方案:多西他赛75 mg/m2,分于第1,8天给药;顺铂(DDP)25 mg/(m2.d)d1-3天,21天为1周期。同时给予同步放疗,鼻咽部原发灶给予6 MV-X线和15 MV-X线DT 70 Gy^78 Gy/7-8周。结果 70例中CR 20例,PR 37例,总有效率81.4%。1年、3年生存率分别为98.4%、83.9%。主要毒副反应为骨髓抑制、急性口腔黏膜炎、恶心呕吐、皮肤反应。结论多西他赛和顺铂同步放化疗治疗局部晚期鼻咽癌疗效较好,毒副反应可以耐受。

多西他赛治疗失败后的去势抵抗性前列腺癌及其骨转移治疗进展

去势抵抗性前列腺癌(CRPC)的标准治疗目前以多西他赛为化疗基础,但是对于多西他赛治疗失败后的CRPC尚缺乏有效的治疗手段。近年来,一些新的治疗药物已被批准用于临床治疗,还有一些药物则已经进入临床Ⅱ期或Ⅲ期试验,这些药物的作用机制包括稳定微管蛋白、抑制雄激素合成、阻断雄激素受体、骨靶向、调节免疫功能等。本文综述多西他赛治疗失败后的CRPC的治疗新选择。

胃癌根治术后静脉联合腹腔热灌注辅助化疗的临床疗效观察

目的探讨进展期胃癌D2淋巴结根治术后患者行静脉联合腹腔内热灌注辅助化疗的临床疗效。方法选取139例进展期胃癌D2淋巴结根治术后患者,按随机数字表法分为试验组与对照组。试验组69例化疗方案:多西他赛75 mg/m^2,静脉滴注1 h,d1;奥沙利铂130 mg/m^2,静脉滴注3 h,d1;氟尿嘧啶2 500 mg/m^2,加入0.9%氯化钠2 000 mL,加热至45℃后匀速灌入腹腔;21 d为1个周期。对照组70例化疗方案:多西他赛75 mg/m^2,静脉滴注1 h,d1;奥沙利铂130 mg/m^2,静脉滴注3 h,d1;氟尿嘧啶500 mg/m^2,持续静脉滴注d1～d5;21 d为1个周期。随访5～8年,观察两组不良反应、转移复发情况及生存情况。结果两组患者不良反应发生率比较,差异均无统计学意义(均P>0.05)。试验组与对照组复发转移率为37.7%(29/69)和60.0%(42/70),差异具有统计学意义(P=0.034),其中腹膜转移率为11.6%(8/69)和25.7%(18/70),差异具有统计学意义(P=0.033);复发率及其他部位转移率比较,差异均无统计学意义(均P>0.05)。试验组和对照组术后1、3和5年无瘤生存率(disease-free survival,DFS)分别为95.6%、65.2%、57.9%和94.3%、48.6%、40.0%;两组整体DFS比较,差异具有统计学意义(P=0.031)。试验组和对照组术后1、3和5年总生存率(overall survival,OS)分别为100.0%、81.1%、60.9%和100.0%、62.8%、42.9%;两组整体OS比较,差异具有统计学意义(P=0.025)。结论进展期胃癌D2淋巴结根治术后患者行静脉联合腹腔热灌注辅助化疗安全、有效,能降低转移率,提高远期生存率。

多西他赛体外干预前列腺癌PC-3细胞转移能力的实验研究

目的:研究不同浓度多西他赛体外对人前列腺癌PC-3细胞侵袭力及MMP-2、MMP-9表达水平的影响。方法:在0.1血浆峰值浓度(peakplasma concentration,PPC)、1.0PPC、10.0PPC的多西他赛作用下,用Transwell小室对前列腺癌PC-3细胞的侵袭力与转移能力进行检测,并采用荧光定量RT-PCR方法检测转移相关水解蛋白酶MMP-2和MMP-9的变化。结果:经0.1PPC、1.0PPC和10.0PPC的多西他赛处理后,在1.0PPC和10.0PPC下,人前列腺癌PC-3细胞趋化、侵袭能力均下调,而0.1PPC浓度下,人前列腺癌PC-3细胞趋化能力变化不大,而侵袭能力明显降低。在各处理组PC-3细胞中,0.1PPC、1.0PPC和10.0PPC组的MMP-2mRNA的表达水平分别为0.40±0.12、0.36±0.16和0.26±0.09,MMP-9mRNA的表达水平分别为0.35±0.10、0.31±0.12和0.19±0.08,均显著低于两者相应的空白对照组,提示MMP-2和MMP-9转录水平明显降低。结论:多西他赛能够通过下调MMP-2和MMP-9基因的转录而抑制人前列腺癌PC-3细胞的侵袭力。

多西他赛或培美曲塞联合铂类治疗吉非替尼治疗失败NSCLC的临床比较

目的探讨多西他赛与培美曲塞分别联合铂类治疗吉非替尼治疗失败NSCLC患者的疗效及不良反应。方法选取吉非替尼治疗失败NSCLC患者110例,随机数字法分为A组(n=55)和B组(n=55),分别在铂类应用基础上加用多西他赛或培美曲塞辅助治疗。比较两组患者近期疗效、总生存、无进展生存、EORTC QLQ-C30评分和KPS评分改变以及严重不良反应发生率等。结果两组患者客观缓解率(objective response rate,ORR)和疾病控制率(disease control rate,DCR)比较差异均无统计学意义(均P>0.05)。B组患者无进展生存时间长于A组,差异具有统计学意义(P<0.05)。两组总生存时间比较差异无统计学意义(P>0.05)。两组治疗后EORTC QLQC30评分和KPS评分均高于治疗前,且B组治疗后各项评分高于A组(均P<0.05)。B组Ⅲ~Ⅳ级白细胞减少、血红蛋白减少、血小板减少、恶心呕吐、皮疹及肝功能损伤发生率低于A组(均P<0.05);两组Ⅲ~Ⅳ级腹泻和脱发发生率比较差异均无统计学意义(均P>0.05)。结论多西他赛或培美曲塞联合铂类治疗吉非替尼治疗失败NSCLC患者疗效接近,但培美曲塞联合铂类方案可有效延长无进展生存时间,提高生活质量,以及减少严重不良反应发生。

奈达铂联合多西他赛治疗晚期非小细胞肺癌的临床疗效观察

【目的】观察比较奈达铂联合多西他赛化疗方案与顺铂联合多西他赛化疗方案治疗晚期非小细胞肺癌（NSCLC ）的近期疗效及不良反应。【方法】本院70例晚期NSCLC患者根据使用化疗药物不同分为两组，分别为奈达铂联合多西他赛治疗36例，顺铂联合多西他赛治疗34例。具体用药方案为奈达铂组：采用奈达铂25 mg/（m^2· d），d1～3给予，多西他赛75 mg/m^2，d1。顺铂组：采用顺铂25 mg/（m^2· d），d1～3给予，21 d为1个周期，化疗2个周期后按WHO标准评价疗效及不良反应。【结果】奈达铂组：完全缓解（CR）1例，部分缓解（PR）14例，稳定（SD）18例，进展（PD）3例，有效率（RR）为41．7％（15/36）；顺铂组：CR 1例，PR 13例，SD 18例，PD 2例，有效率（RR）41．2％（14/34），两组有效率比较差异无显著性（ P ＞0．05）。消化道反应：奈达铂组和顺铂组分别为5．6％（2/36）和29．4％（10/34），两组相比较差异有显著性（ P ＜0．01）；肾毒性分别为0（0/36）和5．9％（2/34）（ P ＜0．05）；骨髓抑制：白细胞减少奈达铂组为72．2％（26/36），顺铂组为70．6％（24/34），两组相比较差异无显著性（ P＞0．05）。【结论】奈达铂联合多西他赛方案治疗晚期NSCLC的有效率不低于顺铂联合多西他赛方案，胃肠道毒性较顺铂联合多西他赛组轻，不良反应主要为骨髓抑制，两组白细胞下降无差异，但血小板下降较顺铂联合多西他赛组明显。

Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.

Probiotic mixture VSL#3:An overview of basic and clinical studies in chronic diseases

Probiotics are known as“live microorganisms”and have been proven to have a health effect on hosts at the proper dose.Recently,a kind of probiotic mixture including eight live bacterial strains,VSL#3,has attracted considerable attention for its combined effect.VSL#3 is the only probiotic considered as a kind of medical food;it mainly participates in the regulation of the intestinal barrier function,including improving tight junction protein function,balancing intestinal microbial composition,regulating immune-related cytokine expression and so on.The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans(including children).We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies,including digestive systemic diseases(gastrointestinal diseases and hepatic diseases),obesity and diabetes,allergic diseases,nervous systemic diseases,atherosclerosis,bone diseases,and female reproductive systemic diseases.