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.

直接蛋白沉淀结合串联质谱法用于血浆中5-氟尿嘧啶治疗药物监测应用

本文建立一种直接蛋白沉淀结合串联质谱法测定血浆中5-氟尿嘧啶浓度的方法.以0.1 mol·L^(-1)硫酸锌作为蛋白沉淀剂处理血浆样品,离心后取上清液直接测定.以5-氟尿嘧啶-^(13)C,^(15)N_(2)为内标标准品,采用Shimadzu Shim-pack GIST-HP C18-AQ (100 mm×2.1mm I.D.,1.9μm)色谱柱;水(A相)-甲醇(B相)为流动相,梯度洗脱:0—1 min,5%B;1—2 min,5%B→95%B;2—2.5 min,95%B;2.5—2.6 min,95%B→5%B;2.6—5 min,5%B,流速:0.3mL·min-1;柱温:35℃;进样体积:5μL;采用电喷雾离子源,负离子多反应监测模式(MRM)进行质谱定量分析.检测离子对:5-氟尿嘧啶m/z 129.1→42.1,5-氟尿嘧啶-^(13)C,^(15)N_(2)内标标准品m/z 132.1→44.1.该方法校准曲线相关系数大于0.999.质控品测定准确度结果与理论值接近,批内及批间准确度在94.8%—99.0%之间,RSD在0.9%—4.8%之间.5-氟尿嘧啶提取回收率在95.6%—99.8%之间.基质因子在0.92—0.96之间,内标归一化的基质因子在0.99—1.00之间.稳定性各实验条件下每一测定浓度的均值与标示浓度的相对偏差RE均在-5.2%—1.7%之间.该方法前处理简便、分析速度快、灵敏度高、专属性强、稳定性好,可用于5-氟尿嘧啶治疗药物监测.

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

洛铂联合5-氟尿嘧啶与亚叶酸钙治疗晚期食管癌的Ⅱ期临床研究

目的:评价洛铂联合5-FU与亚叶酸钙治疗晚期食管癌患者的疗效及安全性。方法:对40例未经化疗的晚期食管癌患者。给予以下方案化疗:洛铂50mg,静脉滴注,2h;亚叶酸钙200mg/m2,静脉滴注,2h,d1～d3;5-FU400mg/m2,静脉推注,d1～d3;5-FU600mg/m2,持续静脉滴注,22h,d1～d3。每21d重复。完成2个周期后行疗效评价。结果:可评价疗效病例37例,其中CR1例,PR16例,SD15例,PD5例,总有效率为45.9%(17/37)(95%CI为30%～63%),其中初治患者的总体疗效为68.2%(15/22),复治患者中总体疗效为13.3%(2/15);中位疾病进展时间为6个月。主要不良反应为骨髓抑制,其中白细胞下降Ⅲ,Ⅳ度为21.1%,血红蛋白下降Ⅲ,Ⅳ度为10.0%,血小板下降Ⅲ度为3.3%,未发现Ⅳ度反应。结论:该联合方案显示明显的抗肿瘤作用,与其他含铂方案相比,洛铂不良反应相对较轻,耐受性好。

肝动脉灌注羟基喜树碱和栓塞治疗原发性肝癌

目的观察经肝动脉插管栓塞和灌注化疗药物羟基喜树碱、５ＦＵ、丝裂霉素（ＭＭＣ）、顺铂治疗（ＴＡＣＥ）进展期肝癌（ＨＣＣ）２１例的疗效和副作用．方法应用ＴＡＣＥ治疗２１例中晚期ＨＣＣ患者，其中Ⅱ期１５例，Ⅲ期６例．结果接受ＴＡＣＥ患者２１例，治疗总有效率为８０９％，平均生存期９１ｍｏ，半年和一年生存率分别为７１５％和４２４％．Ⅱ期患者获得的平均生存期、半年和一年生存率分别为１０５ｍｏ，８６７％，６０％；明显优于Ⅲ期患者的５３ｍｏ，３６７％，０％（Ｐ＜００１）．多次治疗的平均生存期为１１２ｍｏ，明显优于单次治疗的６８ｍｏ（Ｐ＜００１）．副作用有恶心、呕吐、发热、白细胞下降和肝功能异常．结论羟基喜树碱经肝动脉灌注联合栓塞是治疗进展期ＨＣＣ的有效手段．

苦参碱联合5-FU抑制人胃癌裸鼠移植瘤的生长作用及机制

【目的】研究苦参碱(matrine,Ma)与5-氟尿嘧啶(5-FU)联合应用对人胃腺癌SGC-7901裸鼠移植瘤的抑制作用及可能机制。【方法】将人胃腺癌SGC-7901细胞株接种于BALB／cA裸鼠皮下,形成移植瘤后传3代;取生长旺盛期的瘤组织约1．5 mm3,无菌接种于裸鼠右侧腋窝皮下,待肿瘤生长至100-300mm3后将动物随机分为6组,即模型组、5-FU组(50 mg/kg)、Ma低剂量组(50 mg/kg)、Ma高剂量组(100 mg/kg)、Ma低剂量+5-FU组、Ma高剂量+5-FU组;各组分别按设计剂量腹腔给药,35 d后测量各组裸鼠瘤径和肿瘤体积,计算相对肿瘤体积(VR)和相对肿瘤抑制率(pinhibitory);采用免疫组化法检测荷瘤组织中凋亡相关蛋白bcl-2、bax活性和caspase-3的表达情况。【结果】Ma高剂量+5-FU组抑瘤作用与模型组、 Ma高剂量组、5-FU组比较均显著增强(P<0．05或P<0．01),Ma低剂量+5-FU组抑瘤作用也见增强,但与其他组比较无显著性差异;各给药组均可不同程度下调bcl-2表达,上调bax表达,提高活性caspase-3表达,与模型组比较具有显著性差异(P<0．05或P<0．01);Ma高、低剂量分别与5-FU合用后,该调节作用较单独使用显著增强(P<0．05或P<0．01), 并呈现剂量依赖关系。【结论】苦参碱与5-FU联合应用具有一定的协同增效作用,其机制可能与调节凋亡相关蛋白的表达, 诱导胃癌细胞凋亡有关。

替加氟和氟尿嘧啶分别与草酸铂联合持续静脉滴入治疗晚期胃癌的比较研究

目的：探讨持续静脉滴入替加氟、氟尿嘧（5-FU）分别与草酸铂（L-OHP）联合对晚期胃癌的效果。方法：67例晚期胃癌患者分别接受方案A（32例）和方案B（35例）治疗。方案A：替加氟800mg／m^2，持续静脉滴入（24h），d1～d5；甲酰四氢叶酸（LV）200mg／m^2，静脉滴入（2h），d1～d5；L-OHP135mg／m^2，静脉滴入（2h），d1。方案B：5-FU750mg／m^2，持续静脉滴入（24h），d1～d5；LV与L—OHP应用方法同方案A。均21d为1个周期。结果：67例患者中CR9例，PR34例，有效率64．0％。TTP和MST分别为7．2个月和11．3个月。方案A有效率高于方案B，分别为68．8％和60．0％，但差异无统计学意义（Χ^2=0．557，P=0．456）。初次化疗患者有效率高于既往接受化疗者，分别为73．7％和60．4％。对复治患者方案A有效率为69．6％，方案B为52．0％，尽管方案A组有效率呈现增高的趋势，但差异无统计学意义（Χ^2=1．545，P=0．214）。两种治疗方案的不良反应均易于耐受。结论：持续静脉滴入替加氟、氟尿嘧啶分别与草酸铂联合可以作为晚期胃癌安全有效的治疗方案。

SOX方案及XELOX方案一线治疗晚期胃癌的临床研究

目的比较SOX方案（替吉奥联合奥沙利铂）和XELOX方案（卡培他滨联合奥沙利铂）一线治疗晚期胃癌近期疗效、远期疗效及化疗不良反应。方法 62例晚期胃癌患者随机分为SOX组（n=32）和XELOX组（n=30）,两组均接受〉2周期的化疗,每2周期后评价近期疗效,观察化疗相关不良反应。结果 SOX组有效率、疾病控制率、中位疾病进展时间、中位生存时间分别为43.8%、81.3%、6.2月、11.6月;XELOX组有效率、疾病控制率、中位疾病进展时间、中位生存时间分别为33.3%、73.3%、6.0月、10.9月,两组有效率及生存期比较差异均无统计学意义（均P〉0.05）。两组Ⅲ~Ⅳ级血液学毒性方面差异无统计学意义（P〉0.05）,非血液学毒性方面外周神经毒性及手足综合征发生率XELOX组高于SOX组（均P〈0.05）。结论 SOX及XELOX方案一线治疗晚期胃癌疗效均较高,疗效相近,不良反应均可耐受,XELOX组在外周神经症状及手足综合征方面发生率较SOX组高。

贝伐珠单抗联合以5-FU为基础的双药化疗用于结直肠癌仅肝转移患者新辅助治疗:一项多中心单臂研究

目的通过开放标签的多中心探索性研究评估贝伐珠单抗联合氟尿嘧啶(5-FU)作为新辅助化疗方案对仅肝转移、转移灶初始不可切除且未经治疗的结直肠癌(colorectal cancer,CRC)患者R0切除率的影响。方法在全国7家中心招募既往未经治疗(原发灶已切除)、只存在肝转移灶且不可切除的中国转移性结直肠癌(metastatic colorectal cancer,m CRC)患者。入组患者均接受贝伐珠单抗(静脉注射,5 mg/kg,每2周1次,d1)联合以氟尿嘧啶(5-FU)为基础的双药化疗方案进行新辅助治疗。患者术前和术后共接受≤12个周期的治疗,术前最后1个周期的化疗(无贝伐珠单抗)不计入12个周期内。主要终点为R0切除率,次要终点为R1切除率、客观缓解率(objective response rate,ORR)、无进展生存(progression free survival,PFS)、无瘤生存率(disease free survival,DFS)和安全性。结果本研究共纳入50例患者,其中男性39例,女性11例;患者中位年龄57岁(范围37~73岁),R0切除率为30.0%,R1切除率为0.0%。50例患者的ORR为15.0%,中位PFS为12.06个月(95%CI:6.70~13.31),接受R0切除的15例患者中位DFS为8.57个月(95%CI:1.84~17.74)。总体安全性良好,32例患者(64.0%)共发生159次不良事件(adverse events,AE),其中24次为3级AE,无≥4级AE。最常见的与贝伐珠单抗相关的≥3级AE为高血压(8.0%)。手术安全人群(n=17)中,5例(29.4%)发生手术相关并发症,但均为肝脏局部并发症,仅1例发生肺部感染。结论对于肝脏为唯一转移灶且初始不可切除的CRC患者,使用贝伐珠单抗联合以5-FU为基础的双药化疗进行新辅助治疗可提高R0切除率,且耐受性良好。

缓释粒子内镜植入在胃肠道肿瘤化疗中应用观察

目的:初步评价化疗缓释粒子肿瘤部位植入治疗胃肠恶性肿瘤的临床疗效和不良反应。方法:选择隆起型胃肠道恶性肿瘤患者31例,在消化内镜直视下将5-FU、顺铂的缓释粒子植入到肿瘤间质。结果:完全缓释10例,部分缓释12例,病情稳定6例,3例无缓解,平均有效率为70.9%。患者疼痛缓解率为70.9%,体重增加21例,占67.7%。不良反应除因术中操作出血外,仅见WBC轻度下降、轻度恶性、腹泻,无发生肝肾功能损害。结论:胃肠道恶性肿瘤化疗缓释粒子内镜植入突出了局部靶向治疗,具有微创、安全、有效及并发症发生率低的特点,是综合治疗胃肠道恶性肿瘤新的有效手段之一。