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

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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.

Maillard reaction and immunogenicity of protein therapeutics

The recombinant DNA technology enabled the production of a variety of human therapeutic proteins.Accumulated clinical experience,however,indicates that the formation of antibodies against such proteins is a general phenomenon rather than an exception.The immunogenicity of therapeutic proteins results in inefficient therapy and in the development of undesired,sometimes life-threatening,side reactions.The human proteins,designed for clinical application,usually have the same amino acid sequence as their native prototypes and it is not yet fully clear what the reasons for their immunogenicity are.In previous studies we have demonstrated for the first time that interferon-b(IFN-b)pharmaceuticals,used for treatment of patients with multiple sclerosis,do contain advanced glycation end products(AGEs)that contribute to IFN-b immunogenicity.AGEs are the final products of a chemical reaction known as the Maillard reaction or glycation,which implication in protein drugs' immunogenicity has been overlooked so far.Therefore,the aim of the present article is to provide a comprehensive overview on the Maillard reaction with emphasis on experimental data and theoretical consideration telling us why the Maillard reaction warrants special attention in the context of the welldocumented protein drugs' immunogenicity.

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.

干扰素联合更昔洛韦治疗儿童带状疱疹的疗效及安全性分析

目的探讨干扰素联合更昔洛韦治疗儿童带状疱疹的疗效及安全性。方法100例儿童带状疱疹患儿,采取随机数字表法分为观察组(实施干扰素联合更昔洛韦治疗)与对照组(采取单一更昔洛韦治疗),每组50例。比较两组患儿治疗效果、炎性因子(白细胞介素-6、白细胞介素-10)水平、治疗相关用时。结果观察组患儿治疗总有效率98%高于对照组的70%,数据比较有统计学意义(P<0.05)。治疗后,观察组患儿白细胞介素-6(230.59±22.47)pg/ml、白细胞介素-10(169.19±15.58)pg/ml均高于对照组的(139.29±26.69)、(160.49±22.69)pg/ml,数据比较有统计学意义(P<0.05)。观察组患儿止痛、止疱以及结痂用时分别为(1.79±0.87)、(1.39±0.49)、(3.19±1.29)周,均短于对照组的(4.39±1.09)、(2.79±1.39)、(5.01±1.49)周,数据比较有统计学意义(P<0.05)。结论儿童带状疱疹临床治疗采用更昔洛韦注射液联合干扰素临床疗效显著,可缩短患儿治疗相关用时,具有较高安全性,可于临床推广应用。

高频电刀宫颈环切术联合重组人干扰素α-2b栓治疗宫颈癌前病变的效果分析

目的探讨高频电刀宫颈环切术治疗宫颈癌前病变患者配合重组人干扰素α-2b栓的效果。方法选取200例宫颈癌前病变患者为研究对象,依据随机数字表法分为对照组和研究组,每组100例。对照组采取高频电刀宫颈环切术治疗,研究组在对照组基础上术后给予重组人干扰素α-2b栓治疗,比较两组治疗效果、高危型人乳头瘤病毒(HPV)病毒清除效果及生活质量。结果研究组治疗总有效率高于对照组(P<0.05);术前,两组HPV病毒载量及生活质量评分比较,差异均无统计学意义(P>0.05);术后,研究组HPV病毒载量低于对照组,生活质量评分高于对照组(P<0.05)。结论宫颈癌前病变患者采用高频电刀宫颈环切术联合术后重组人干扰素α-2b栓治疗效果较好,可促使症状消失,病灶缩小,提高HPV病毒清除效果,并改善患者的生活质量,值得临床推广与应用。

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.

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.

Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B

250 million people worldwide continue to be chronically infected with the virus.While patients may be treated with nucleoside/nucleotide analogues,this only suppresses HBV titre to sub-detection levels without eliminating the persistent HBV covalently closed circular DNA(cccDNA)genome.As a result,HBV infection cannot be cured,and the virus reactivates when conditions are favorable.Interferons(IFNs)are cytokines known to induce powerful antiviral mechanisms that clear viruses from infected cells.They have been shown to induce cccDNA clearance,but their use in the treatment of HBV infection is limited as HBVtargeting immune cells are exhausted and HBV has evolved multiple mechanisms to evade and suppress IFN signalling.Thus,to fully utilize IFN-mediated intracellular mechanisms to effectively eliminate HBV,instead of direct IFN administration,novel strategies to sustain IFN-mediated anti-cccDNA and antiviral mechanisms need to be developed.This review will consolidate what is known about how IFNs act to achieve its intracellular antiviral effects and highlight the critical interferon-stimulated gene targets and effector mechanisms with potent anti-cccDNA functions.These include cccDNA degradation by APOBECs and cccDNA silencing and transcription repression by epigenetic modifications.In addition,the mechanisms that HBV employs to disrupt IFN signalling will be discussed.Drugs that have been developed or are in the pipeline for components of the IFN signalling pathway and HBV targets that detract IFN signalling mechanisms will also be identified and discussed for utility in the treatment of HBV infections.Together,these will provide useful insights into design strategies that specifically target cccDNA for the eradication of HBV.

Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection:A prospective,real-life,observational study

AIM: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C,as there are few adherence data in genotype 2/3 infection,even from randomized trials.METHODS: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin.There was no intervention.Adherence was self-reported over the past 4 wk (peg-interferon) or 7 d (ribavirin).Adherence to bitherapy was defined as adherence to the two drugs for ≥ 20 wk.SVR was defined as undetectable RNA ≥ 12 wk after the end of treatment.RESULTS: 370/674 patients received education during the first 3 mo of treatment.After 6 mo,adherence to bitherapy was higher in educated patients (61% vs 47%,P = 0.01).Adherence to peg-interferon was 78% vs 69% (P = 0.06).Adherence to ribavirin was 70% vs 56% (P = 0.006).The SVR (77% vs 70%,P = 0.05) and relapse (10% vs 16%,P = 0.09) rates tended to be improved.After adjustment for baseline differences,education improved adherence [Odds ratio (OR) 1.58,P = 0.04] but not the SVR (OR 1.54,P = 0.06).CONCLUSION: In genotype 2/3 patients,therapeutic education helped maintain real-life adherence to bitherapy.

High-intensity focused ultrasound extracorporeal ablation of liver tissuesin rabbits

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Therapeutic effect of combined use of interferon alpha-1b,interleukin-2 and thalidomide on reversing minimal residual disease in acute myeloid leukemia

Objective To explore the effect of combination regimenof interferon alpha-1b,interleukin-2 and thalidomide(ITI regimen) on minimal residual disease (MRD)in patients with acute myeloid leukemia ( AML) whowere in hematologic remission but MRD-positive. MethodsEighteen patients (17 from Tumor Hospital of ZhengzhouUniversity and 1 from the First People's Hospital ofPingdingshan City) with AML admitted from July 2016 toJune 2018,who were in hematologic remission but MRDpositivewere treated with different doses of ITI regimen,and the MRD levels were monitored. Results Among 18patients who received a conventional dose of ITI regimenfor 1 to 2 months,7 patients had undetectable MRD,3had significant decrease in MRD levels,3 had elevatedMRD level and had hematologic recurrence. Three patientswith elevated MRD level received a higher dose ofITI regimen,2 of them turned to MRD negative and theother 1 patient had decreased MRD level.

标准化干扰素α2b联合布地奈德混悬液治疗儿童支气管哮喘的效果和安全性评价

目的:标准化干扰素α2b联合布地奈德混悬液吸入治疗儿童支气管哮喘。方法:选取2022年1月至2022年11月在蚌埠医学院第一附属医院就诊同时接受治疗的120例诊断为支气管哮喘的患儿作为研究对象,将其采取随机排序分组的方式。60例患儿采取布地奈德雾化吸入治疗方式,为对照组,60例患儿采取标准化干扰素联合布地奈德治疗方式,为研究组。对比两组患儿肺功能指标变化情况、治疗效果、不良反应发生率以及临床各项指标情况。结果:研究组患儿肺功能指标、治疗效果、住院时间、咳嗽消失时间、气促消失时间、哮鸣音消失时间以及不良反应发生情况显著低于对照组(P<0.05)。结论:对于小儿支气管哮喘患儿采取标准化干扰素联合布地奈德治疗方式,可有效缓解支气管哮喘患儿的临床症状,且未见明显不良反应。

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

DDP、5Fu/CF加干扰素治疗晚期鼻咽癌的初步报告

目的：评价ＤＤＰ＋５Ｆｕ／ＣＦ＋ＩＮＦ（干扰素）方案治疗晚期鼻咽癌的疗效和毒性反应。方法：本文采用ＤＤＰ＋５Ｆｕ／ＣＦ＋ＩＮＦ（ＤＤＰ２０ｍｇ／ｍ２×５，５Ｆｕ３００ｍｇ～４００ｍｇ／ｍ２×５，ＣＦ２００ｍｇ×５，ＩＮＦ３×１０６Ｕ×３）方案共治疗晚期鼻咽癌２６例；结果：２５例可评价疗效，总有效率（ＣＲ＋ＰＲ）８０％（２０／２５），ＣＲ率１２％，中位缓解期４８月（２～１２月）。在放疗和／或化疗后复发转移的２１例中，ＣＲ２例，ＰＲ１４例，ＣＲ＋ＰＲ７６２％（１６／２１），而曾用ＤＤＰ／ＴＨＰ＋５Ｆｕ／ＣＦ的１１例中，ＰＲ率８１８％（９／１１），无ＣＲ；毒性反应主要是骨髓抑制和消化道反应等，ＷＨＯⅢ＋Ⅳ级毒性比例分别为：ＷＢＣ下降２２％、口腔炎２３７％、恶性呕吐１０１％和腹泻１１９％；结论：作者认为ＤＤＰ＋５Ｆｕ／ＣＦ＋ＩＮＦ联合化疗方案是治疗晚期鼻咽癌的有效方案，值得进一步研究，但毒性明显。