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.

Gemcitabine治疗晚期非小细胞肺癌的临床研究

目的：评价Ｇｅｍｃｉｔａｂｉｎｅ（中文译名：健择）单药及其与顺氯铵铂联合化疗方案治疗ＩＩ、ＩＶ期非小细胞肺癌（ＮＳＣＬＣ）的临床疗效及其不良反应。材料与方法：１健择单药研究：从１９９７年９月至１９９８年５月入选ＩＩ、ＩＶ期ＮＳＣＬＣ病人２１例，以前未接受过任何化疗、放疗。ＩＩ期病人１１例，ＩＶ期病人１０例。健择１０００ｍｇ／ｍ２，第１，８，１５天各注一次，每２８天为一疗程。２健择与顺氯铵铂联合化疗研究：从１９９７年１０月至１９９８年７月入选ＩＩ、ＩＶ期ＮＳＣＬＣ病人４８例，以前未接受过任何化疗、放疗。ＩＩ期病人１９例，ＩＶ期病人２９例。健择１０００ｍｇ／ｍ２，第１，８，１５天各注一次；顺氯铵铂１００ｍｇ／ｍ２，第一天用，每２８天为一疗程。结果：１健择单药研究：可评价疗效的有１９例，６例获部分缓解（ＰＲ），其中２例（１０５％）经４周以上复查证实。总有效率３１５％［９５％ＣＩ，９４％～４５１５％］。全组均可评价不良反应，少数病人发生轻微胃肠道反应、白细胞下降、血红蛋白下降和血小板下降，只有４８％（各１例）患者发生ＩＩ度的恶心呕吐及白细胞下降，有１例患者发生ＩＩ度感染。全组中位生存期６１３月。２?

Treatment of Unresectable Carcinoma of Pancreas with ^(125)I Implantation and ^(125)I Plus Gemcitabine

Objective: To study the role of 125 I and 125 I plus gemcitabine (GEM) in treatment of unresectable carcinoma of pancreas. Methods: From April 2000 to April 2003, 38 untreated patients with locally advanced pancreatic cancer (LAPC) were collected and randomized into two groups: Arm A 125 I (18 patients) and Arm B 125 I+GEM (20 patients). Eligibility criteria were: cytologically and pathologically proven pancreatic carcinoma, Karnofsky performance status (kps) 60 80, age 18 75 years, adequate hematological, renal and liver function, and controllable pain. Arm A patients were treated with 125 I implants. Arm B patients started chemotherapy within 10 14 d post operatively following the implant procedure. Chemotherapy doses were as follows: GEM 1 000 mg/m 2 weekly × 3 followed by 1 week of rest for 3 cycles. In addition, all patients underwent laparotomy and surgical staging. The surgical procedures performed were biopsy, gastric bypass and biliary bypass. The total activity and number of seeds used were as recommended by Anderson. The mean activity, minimal peripheral dose (MPD), and volume of implants were 20 mCi, 14 000 cGy, and 53 cm 3, respectively. Results: Overall response rate (CR+PR) in Arm A was 37.6% and in Arm B it was 44.5% ( P >0.05). PR median duration in Arm A was 6.7 months and in Arm B it was 4.8 months ( P <0.05). Clinical benefit response was experienced by 11.7 % of Arm A compared with 42.1% of Arm B ( P <0.05). The incidences of hematological toxicity (such as neutropenia) between Arm A and Arm B were 5.8% and 21.1%, respectively ( P >0.05). The survival rates of 12 and 24 month were 32.5%, 16.3% for Arm A and 61%, 38.7% for Arm B ( P =0.04). The rate of complication of Arm A was lower than that of Arm B without statistical significance. Conclusion: To some extent, 125 I or 125 I plus GEM is able to lead to a moderate objective response for LAPC with obstructive jaundice on the base of biliary bypass or/and gastric bypass, but 125 I plus GEM is more effective than 125 I in improvement of the quality of life and survival rate in patients with LAPC.

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

Ｆｕｎｃｔｉｏｎａｌｄｙｓｐｅｐｓｉａｏｆｕｌｃｅｒｄｙｓｍｏｔｉｌｉｔｙｔｙｐｅ：ｃｌｉｎｉｃａｌｉｎｃｉｄｅｎｃｅａｎｄｔｈｅｒａｐｅｕｔｉｃｓｔｒａｔｅｇｙＷＡＮＧＸｉａｏＺｈｏｎｇａｎｄＬＩＮＧｕＺｈｅｎＳｕｂｊｅｃｔｈｅａａｄｉｎｇｓ...

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.

VHH212 nanobody targeting the hypoxia-inducible factor 1α suppresses angiogenesis and potentiates gemcitabine therapy in pancreatic cancer in vivo

Objective:We aimed to develop a novel anti-HIF-1αintrabody to decrease gemcitabine resistance in pancreatic cancer patients.Methods:Surface plasmon resonance and glutathione S-transferase pull-down assays were conducted to identify the binding affinity and specificity of anti-HIF-1αVHH212[a single-domain antibody(nanobody)].Molecular dynamics simulation was used to determine the protein-protein interactions between hypoxia-inducible factor-1α(HIF-1α)and VHH212.The real-time polymerase chain reaction(PCR)and Western blot analyses were performed to identify the expressions of HIF-1αand VEGF-A in pancreatic ductal adenocarcinoma cell lines.The efficiency of the VHH212 nanobody in inhibiting the HIF-1 signaling pathway was measured using a dual-luciferase reporter assay.Finally,a PANC-1 xenograft model was developed to evaluate the anti-tumor efficiency of combined treatment.Immunohistochemistry analysis was conducted to detect the expressions of HIF-1αand VEGF-A in tumor tissues.Results:VHH212 was stably expressed in tumor cells with low cytotoxicity,high affinity,specific subcellular localization,and neutralization of HIF-1αin the cytoplasm or nucleus.The binding affinity between VHH212 and the HIF-1αPAS-B domain was 42.7 n M.Intrabody competitive inhibition of the HIF-1αheterodimer with an aryl hydrocarbon receptor nuclear translocator was used to inhibit the HIF-1/VEGF pathway in vitro.Compared with single agent gemcitabine,co-treatment with gemcitabine and a VHH212-encoding adenovirus significantly suppressed tumor growth in the xenograft model with 80.44%tumor inhibition.Conclusions:We developed an anti-HIF-1αnanobody and showed the function of VHH212 in a preclinical murine model of PANC-1 pancreatic cancer.The combination of VHH212 and gemcitabine significantly inhibited tumor development.These results suggested that combined use of anti-HIF-1αnanobodies with first-line treatment may in the future be an effective treatment for pancreatic cancer.

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.

吉西他滨联合奥沙利铂腹腔热灌注治疗复发性卵巢癌的效果分析

目的探讨吉西他滨联合奥沙利铂腹腔热灌注治疗复发性卵巢癌的效果。方法选择88例复发性卵巢癌患者为研究对象,按照随机数字表法分为对照组和研究组,每组44例。对照组采用吉西他滨联合奥沙利铂治疗,研究组采用吉西他滨联合奥沙利铂腹腔热灌注治疗,比较两组治疗效果、血管内皮生长因子(VEGF)、糖类抗原125(CA125)、人附睾蛋白4(HE4)水平与不良反应发生情况。结果研究组总有效率高于对照组(P<0.05);治疗前,两组VEGF、CA125及HE4水平比较,差异无统计学意义(P>0.05);治疗后,研究组VEGF水平低于对照组,CA125、HE4水平均高于对照组(P<0.05);研究组不良反应发生率低于对照组(P<0.05)。结论吉西他滨联合奥沙利铂腹腔热灌注治疗复发性卵巢癌的效果较好,能有效控制患者的病情,降低不良反应发生率,对提高患者的生存质量有一定的意义,值得临床推广与应用。

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

吉西他滨联合顺铂治疗复发转移性膀胱癌的Ⅱ期临床研究

目的评价吉西他滨联合顺铂治疗晚期膀胱癌的疗效和安全性。方法32例Ⅳ期膀胱癌接受吉西他滨联合顺铂方案化疗：吉西他滨1200mg/m^2,第1天和第8天,顺铂25mg/m^2,第1-3天,21天为1个周期。结果32例患者中完全缓解4例,部分缓解13例,有效率为53.1%,中位肿瘤进展时间（TTP）8.5个月,中位生存时间为14个月,1年生存率58.3%。毒性反应主要为血液学毒性、消化道反应。结论吉西他滨联合顺铂3周方案是治疗晚期膀胱癌安全、有效的化疗方案。

吉西他滨联合顺铂一线治疗晚期三阴乳腺癌疗效分析

目的分析吉西他滨联合顺铂(GP方案)治疗复发转移性三阴乳腺癌的反应率及不良反应,进一步了解该方案治疗可获取的疾病进展时间(TTP)和总生存时间(OS)。方法回顾性分析住院治疗的35例晚期三阴乳腺癌。所有患者均一线接受GC方案(吉西他滨针1 000 mg/m2,d1、d8+顺铂针25 mg/m2,d1-3,每21天重复)化疗。患者每2周期接受疗效评价。统计肿瘤反应率和不良反应,通过后续随访,统计TTP和OS。结果 35例晚期三阴乳腺癌,均有可评价病灶。21例继往接受了含紫杉类药物辅助化疗,14例患者继往接受了含蒽环类药辅助化疗。入组后患者共接受2～6周期GP方案化疗,中位数为3.8周期。完全缓解(CR)2例(5.7%),部分缓解(PR)10例(28.6%),疾病稳定(SD)6例(17.1%),疾病进展(PD)7例(20.0%),总反应率(ORR)为34.3%。中位TTP为7.0月,中位OS为13.0月。结论晚期三阴乳腺癌接受GP方案化疗有较高反应率,耐受性好,但TTP较短,生存时间有限,需要寻找更为有效的治疗靶点。

吉西他滨联合顺铂二、三线治疗晚期三阴乳腺癌临床观察

目的观察吉西他滨／顺铂21天方案（GP方案），二、三线治疗转移性三阴乳腺癌（advanced triplenegative breastcancer，ATNBC）患者的疗效和不良反应。方法34例三阴乳腺癌患者，吉西他滨1．0g／In。第1、8天静脉滴注；顺铂25mg／m2。第1—3天静脉滴注，21天为一疗程，直到疾病进展或无法耐受或最多接受6周期化疗。结果34例患者共完成141个周期化疗，中位化疗周期3．5周期。均可评价疗效和不良反应。其中完全缓解0例（0％），部分缓解11例（32．35％），稳定9例（26．44％），进展14例（41．18％）。有效率（CR＋PR）32．4％（95％可信区间24．15％-40．55％），疾病控制率（CR＋PR＋SD）58．8％，中位疾病进展时间（TTP）3．9月，中位生存期（OS）10.0月。治疗后主要不良反应为血液学毒性，血小板减少发生率为61．8％。结论三阴性乳腺癌预后差，GP方案治疗ATNBC患者安全有效，不良反应可以耐受。

3种化疗方案用于小细胞食管癌的疗效和安全性比较

目的:比较不同化疗方案用于小细胞食管癌的疗效和安全性。方法:回顾性分析58例小细胞食管癌患者资料,按化疗方案的不同分为A组(18例)、B组(26例)和C组(14例)。A组患者静脉滴注顺铂注射液75 mg/m^2,d_(1-3)+紫杉醇注射液175 mg/m^2,d_(1-3)。B组患者静脉滴注顺铂注射液30 mg/m^2,d_(1-3)+依托泊苷注射液100 mg/m^2,d_(1-3)。C组患者静脉滴注酒石酸长春瑞滨注射液25mg/m^2,d_(1-3)+注射用盐酸吉西他滨1 000 mg/m^2,d_(1-3)。3组均以21 d为1个周期,共治疗2个周期。比较3组患者的临床疗效及1、2、3年生存率及Ⅲ~Ⅳ度毒性反应(咳嗽、高热、咳痰、气促、乏力、胸痛、骨髓抑制、消化道反应)发生情况。结果:总有效率及1、2、3年生存率C组>B组>A组,Ⅲ~Ⅳ度咳嗽、高热、咳痰、气促、乏力、胸痛发生率C组<B组<A组,差异均有统计学意义(P<0.05);3组患者Ⅲ~Ⅳ度骨髓抑制、消化道反应发生率比较,差异均无统计学意义(P>0.05)。结论:长春瑞滨联合吉西他滨治疗小细胞食管癌疗效及1、2、3年生存率均显著高于顺铂联合紫杉醇或依托泊苷,且安全性优于顺铂联合紫杉醇或依托泊苷。