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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治疗药物监测在西罗莫司用于儿童期脉管异常中的研究进展

西罗莫司(sirolimus,SRL)近年来被广泛应用于治疗脉管异常疾病。由于其治疗窗狭窄,药代动力学参数存在较大的个体内和个体间变异性,需要常规进行治疗药物监测以确保疗效和避免不良反应。因此,本文回顾了SRL的血药浓度监测方法以及不同检测方法之间的对比研究,并讨论SRL在脉管异常群体中应维持的浓度范围。SRL浓度检测方法包括免疫法和色谱法两类,免疫法与色谱法相比存在显著的阳性偏倚,液相色谱串联质谱法是大多数实验室采用的“金标准”方法。SRL的目标血药浓度范围多为5~15 ng/mL或10~15 ng/mL。但脉管异常疾病存在多个分类,SRL在该疾病的临床应用情况较为复杂,治疗药物监测也无可供参考的指南。未来需进一步研究,以获取更多高级别的循证医学证据来指导SRL的治疗性监测及个体化用药。

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

西罗莫司药动学的影响因素及治疗药物监测

西罗莫司是一种大环内酯类抗生素,试验表明其具有较强的免疫抑制活性。目前作为一种安全性较高的免疫抑制剂,常与环孢素、激素联合使用,用于预防器官移植的排异反应。本文对西罗莫司免疫活性机制、药动学研究和临床治疗药物监测进行归纳。

不同药物洗脱支架对冠状动脉小血管病变患者预后影响的meta分析

目的:比较莫司类药物洗脱支架(LES)与紫杉醇洗脱支架(PES)在冠状动脉小血管病变患者中的疗效。方法:通过PubMed、Web of Science、ClinicalTrials、中国生物医学文献数据库、中国知网、万方数据和维普数据库对与本次研究主题相关的文献进行检索,对纳入的文献进行方法学质量评价。采用RevMan 5.2及Stata 14.0软件进行相关的统计学分析。结果:八项研究共4738例患者纳入此研究。与PES比较,植入LES能减少主要心血管不良事件(RR=0.64,95%CI:0.53~0.77,Z=4.59,P<0.01)、心肌梗死(RR=0.61,95%CI:0.45~0.82,Z=3.24,P<0.01)、支架内血栓(RR=0.22,95%CI:0.13~0.37,Z=5.71,P<0.01)以及靶病变血运重建(RR=0.56,95%CI:0.44~0.71,Z=4.72,P<0.01)的发生率。与PES比较,LES不能减少心因性死亡(RR=1.08,95%CI:0.62~1.88,Z=0.26,P>0.05)和靶血管血运重建事件的发生率(RR=0.80,95%CI:0.45~1.44,Z=0.74,P>0.05)。结论:对于冠状动脉小血管病变行经皮冠脉介入支架植入术的患者,LES较PES有更好的长期疗效,可作为该类患者的首选支架。

液-质联用在西罗莫司和依维莫司血药浓度监测中的应用进展

西罗莫司和依维莫司是一种新型的免疫抑制剂,相对于环孢霉素(CsA),西罗莫司和依维莫司服用方便、吸收好、起效快,但也存在着用药剂量小、个体吸收差异大、治疗窗窄.因此,测定个体血药浓度以调整用药的剂量和次数、制定个体化治疗方案在临床上有着至关重要的意义.本文就近几年液-质联用在西罗莫司和依维莫司血药浓度监测中的应用研究作以简要综述,以期为临床合理用药提供参考.

西罗莫司血药浓度监测方法的建立及在血管瘤患儿的应用

目的:建立测定人全血中西罗莫司浓度的超高压液相色谱-串联质谱(UPLC-MS/MS)方法。方法:色谱柱为Agilent SB-C_(18)(2.1 mm×50 mm,1.8μm),流动相为水(A)-乙腈(0.1%甲酸,B),流速0.3 mL/min,梯度洗脱。依维莫司为内标,电喷雾离子源,多反应离子监测模式,正离子模式检测。西罗莫司和依维莫司离子对m/z分别为936.5/409.5、980.6/389.3。同时采用该方法对我院血管瘤患儿西罗莫司血药浓度进行监测。结果:西罗莫司在0.625~40.000 ng/mL浓度范围内与相对峰面积线性关系良好(r=0.9997),日内、日间RSD均<10%,提取回收率91.95%~118.50%,基质效应81.67%~107.84%。结论:本方法灵敏、准确、快速,能满足临床常规监测西罗莫司血药浓度的需求。

索拉菲尼 西罗莫司联合动脉化学治疗栓塞术在抑制肝癌肝移植术后肿瘤复发中的作用机制

目的探讨索拉菲尼、西罗莫司联合动脉化学治疗栓塞术(TACE)在抑制肝癌肝移植术后肿瘤复发中的作用机制。方法选取2018—2019年在我院接受肝移植术的80例肝癌患者,按照随机数字表法将其分为研究组40例与对照组40例。肝移植术后给予患者索拉菲尼、西罗莫司预防治疗,研究组则在此基础上实施动脉化学治疗栓塞术治疗,治疗结束后检测患者肝功能指标、急性排斥反应发生情况等,并在随访0.5年后,检测患者接触蛋白(CNTN)-1、血管内皮生长因子(VEGE)-C阳性情况,记录其复发、远处转移及生存情况。结果治疗后,研究组丙氨酸转氨酶(ALT)、总胆红素(TBIL)水平低于对照组(P<0.05),2组患者白蛋白水平比较差异无统计学意义(P>0.05),患者急性排斥反应发生率低于对照组(P<0.05);随访0.5年,研究组CNTN-1、VEGE-C阳性率、复发率、远处转移率低于对照组,生存率高于对照组(P<0.05)。结论索拉菲尼、西罗莫司联合动脉化学治疗栓塞术可抑制肝癌肝移植术后肿瘤复发,有助于改善肝功能,可抑制肿瘤生长速度、细胞增殖及转移,延长患者生存时间,同时耐受性良好。

雷帕霉素对匹罗卡品诱导的癫痫小鼠学习记忆的改善作用

目的：探讨mTOR抑制剂雷帕霉素对匹罗卡品致痫ICR小鼠学习记忆的改善作用。方法：成年雄性ICR小鼠160只，随机分为溶剂对照组、雷帕霉素对照组、模型组、雷帕霉素前给药组和后给药组。其中模型组、前给药组和后给药组均经腹腔注射匹罗卡品（pilocarpine，PILO）诱导小鼠急性癫痫发作，雷帕霉素治疗组分别在致痫前后腹腔给药3d。学习记忆水平的检测采用水迷宫、Y迷宫及旷场等行为学方法。FJB染色用于神经元细胞凋亡的检测。Timm染色用于检测苔藓纤维发芽。结果：PILO致痫后ICR小鼠虽然并未出现明显神经元细胞死亡，但在PILO诱导癫痫后的7～10d出现明显的学习记忆损伤，与对照组相比表现为平台逃避潜伏期延长（P〈0．05）、正确反映次数减少（P〈0．01）和穿格次数下降（P〈0．05）；致痫前给予雷帕霉素治疗能显著逆转PILO所致的平台逃避潜伏期延长（P〈0．001）、正确反映次数减少（P〈0．01）和穿格次数下降（P〈0．01），后给药组亦能逆转PILO所致的平台逃避潜伏期延长（P〈0．05）和穿格次数下降（P〈0．01）。同时，雷帕霉素能明显抑制PILO致痫后苔藓纤维发芽（P〈0．001）。结论：雷帕霉素能改善PILO致痫后小鼠学习记忆障碍，其作用机理有待进一步探讨。

儿童应用西罗莫司血药浓度波动2例原因分析

背景西罗莫司(SRL)在患儿中的应用涉及器官移植、自身免疫病、淋巴管畸形、血管畸形、结节性硬化症等疾病,但SRL具有较大的药代动力学变异性,需进行药物监测。目的提出解决SRL血清药物浓度变化的方案及其原因。设计病例报告。方法描述2例免疫缺陷病患儿应用SRL治疗6个月的临床资料,分析患儿出现药物浓度异常值的原因,并行文献复习。主要结局指标SRL全血谷浓度(Cmin)达到目标范围5~10 ng·mL^(-1)。结果例1,SRL与伏立康唑的药物相互作用、CYP3A5 rs776746C/C基因型是导致药物代谢变慢和血药浓度升高的原因,剂量降至初始剂量的20%,SRL血药浓度逐渐恢复至达标范围。例2,CYP3A5基因rs776746C/C型和ABCB1基因rs1045642 T/T型是药物清除率减低和Cmin异常升高的原因,给药剂量降至初始剂量的50%后,SRL血药浓度逐渐下降至正常,治疗浓度一直在达标范围内。结论在调整治疗方案前考虑确定SRL的Cmin异常值原因的样本、临床和遗传因素应加以考虑,优化患儿的SRL综合治疗管理。