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

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.

Cyclosporine,prednisone,and high-dose immunoglobulin treatment of angioimmunoblastic T-cell lymphoma refractory to prior CHOP or CHOP-like regimen

Angioimmunoblastic T-cell lymphoma(AITL) is a rare,distinct subtype of peripheral T-cell lymphoma,possessing an aggressive course and poor prognosis with no standard therapy.Twelve patients who have failed at least two initial CHOP or CHOP-like regimens were enrolled in this study and treated with individualized cyclosporine(CsA),prednisone(PDN),and monthly,high-dose intravenous immunoglobulin(HDIVIG).The dose of CsA was adjusted individually based on the blood trough concentration of CsA and renal function.All patients were examined for response,toxicity and survival.The most significant toxicities(≥ grade 2) were infection(16.7%),renal insufficiency(8.3%),hypertension(8.3%),diabetes(8.3%) and insomnia(16.7%).Discontinuation of treatment occurred in one patient(8.3%) due to grade 3 renal toxicity and subsequent grade 4 pulmonary infection.Treatment-related death was not observed.The overall response rate was 75.0%(complete response,33.3%;partial response,41.7%).With a median follow-up of 25.5 months,the median duration of response was 20 months(range,12 to 49 months) and the median progression-free survival(PFS) was 25.5 months(range,10 to 56 months).The 2-year PFS rate was 81.5%.Our findings indicate the combination of CsA,PDN and HDIVIG is an effective salvage regimen for refractory or relapsed AITL with predictable and manageable toxicity.

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.

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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环孢素A和他克莫司的高效液相色谱-串联质谱检测及其室内质控评价

目的建立环孢素A和他克莫司治疗药物监测的高效液相色谱-串联质谱(HPLC-MS/MS)质控方法,应用Westgard多规则理论对质控样品进行评估。方法利用HPLC-MS/MS建立人全血中环孢素A和他克莫司的血药浓度检测方法。对治疗药物监测过程中低、中、高3个浓度水平的质控样品进行统计分析,绘制Levery-Jennings和Z分数质控图,应用Westgard多规则理论进行室内质控评估。结果环孢素A和他克莫司的线性范围分别为10.40~1040.00和0.50~49.50 ng·mL^(-1),定量下限分别为10.40和0.50 ng·mL^(-1),提取回收率分别为108.61%~113.24%和101.99%~109.37%,内标归一化的基质因子分别为106.68%~111.27%和95.70%~97.81%,日内和日间的准确度及精密度均小于15.0%,其他参数也均符合生物样本定量分析要求。Levery-Jennings和Z分数质控图显示,2022年第三季度26组质控样品的检测结果提出警告4次(违反12s规则),未出现失控现象。结论建立的环孢素A和他克莫司治疗药物监测室内质控体系能够有效保障血药浓度检测的准确性。

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.

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

液相色谱电喷雾质谱联用测定器官移植患者全血中环孢素A

目的 :建立液相色谱 -电喷雾质谱联用 (HPLC/ESI+ MS)测定器官移植患者全血中环孢素A(CsA)方法。方法 :0 .5mL患者全血样品用乙醚单步提取 ,色谱柱为岛津C18柱 ,流动相为乙腈 :醋酸铵水溶液 (90∶10 ) ,流速为 0 .95mL·min-1,分流比为 3∶1;质谱条件采用电喷雾正离子源 (ESI+ ) ,毛细管电压为 3.96kV ,一级锥孔电压为 130V ,选择离子监测 (SIR)通道CSA采用 12 0 3+12 2 5m/z,内标环孢素D(CsD)采用 12 17+12 39m/z。结果 :在 9～ 12 0 0 μg·L-1浓度范围内 ,CsA线性关系良好 ,最低检测浓度为 1μg·L-1,日内RSD(n =7)与日间RSD(n =5 )均低于 10 %。方法平均回收率为 98%。结论 :本方法灵敏 ,色谱图几乎无杂质干扰 ,操作步骤简单 ,适于器官移植术后CsA的血药浓度监测 ,也可用于CSA药动学的研究。

特异性荧光偏振免疫法监测肾移植后环孢素A全血浓度2013例次

目的：通过监测肾移植后患者环孢素Ａ（ＣｓＡ）全血浓度，提出ＣｓＡ在三联免疫抑制用药方案中的理想治疗窗。方法：用特异性荧光偏振免疫法测定ＣｓＡ全血浓度，对４０６例患者监测２０１３例次。按术后时间及临床表现分组比较。结果：ＣｓＡ在肾移植后＜１月、１月～＜３月、３月～＜６月、６月～＜１２月、１年～＜２年和２年以上的理想治疗窗应分别为，２５０μｇ·Ｌ－１～４５０μｇ·Ｌ－１，２００μｇ·Ｌ－１～３５０μｇ·Ｌ－１，１８０μｇ·Ｌ－１～３００μｇ·Ｌ－１，１００μｇ·Ｌ－１～２００μｇ·Ｌ－１，１００μｇ·Ｌ－１～１６０μｇ·Ｌ－１和９０μｇ·Ｌ－１～１５０μｇ·Ｌ－１。结论：将ＣｓＡ全血浓度调整到推荐治疗窗内，毒性反应和排异反应明显减少。

肾移植术后服用环孢素A2h血药浓度峰值监测及治疗窗浓度探讨

目的探讨肾移植术后国内患者服用环孢素A(CsA)2h血药浓度峰值在不同时期的监测范围。方法用荧光偏振免疫法(FPIA)同时测定92例肾移植受者CsA谷浓度(C0)和服药2h后峰浓度(C2),并观察排斥反应的发生及肝、肾毒性反应。结果肾移植术后CsA C2在不同时期监测范围建议0mo^1mo为1000~1300μg/L,2mo^3mo为950~1250μg/L,4mo^6mo为900~1100μg/L,7mo^12mo为750~1000μg/L,12mo以上为600~800μg/L。结论在上述治疗窗浓度范围,CsA既能达到满意的免疫抑制效果,又能减少排斥反应和肝、肾毒性的发生。

不同免疫分析仪在环孢素A血药浓度监测中的差异

目的 :考察不同分析方法对环孢素A(CsA)血药浓度监测中的影响。方法 :71例肝肾移植术后CsA样品分别用AxSYM和TDx测定。结果 :TDx监测结果大于AxSYM监测结果。结论 :AxSYM和TDx在环孢素A血药浓度监测中存在差异。

单步萃取反相高效液相色谱法测定人全血中环孢素A的浓度

目的 建立单步萃取反相高效液相色谱法测定人全血中环孢素A(CsA)浓度。方法 采用反相高效液相色谱法 ,罗通定为内标 ,YWG -C18色谱柱 ,乙腈 -甲醇 -水 -异丙醇 (30∶10∶6 0∶1.5 )为流动相 ,流速 1.0ml/min ,柱温 70℃ ,检测波长 2 10nm。结果 CsA全血浓度在 5 2 .6 0～ 10 5 2 .0 0ng·ml-1范围内线性关系良好 ,r =0 .9996 ,最低检测浓度为 2 0ng·ml-1,平均回收率96 .33% ,日内和日间RSD均低于 5 %。结论 本法简便灵敏、准确可靠、经济 。

特异性亲环素A结合法测定环孢素血药浓度

目的 建立测定全血中环孢素A(CsA)浓度的亲环素A结合法。方法 利用重组人亲环素A(rhCyPA)作为结合蛋白 ,3H CsA作示踪剂 ,活性炭吸附分离结合的与游离的两相 ,测定结合相的放射性。结果 方法的有效测定范围为 5 0～ 16 0 0ng·ml- 1 ,批内 (n =8)RSD为 8.2 % ,批间 (n =6 )RSD为 10 .6 % ,标本提取与测定方法的全程回收率为 10 4% ( 2 40ng·ml- 1 )和 10 6 %( 76 4ng·ml- 1 ) ,测定结果与FPIA法高度相关 (r =0 .96 ;P <0 .0 0 1)。对几种CsA类似物与CyPA的亲和力进行测定的结果表明 ,其亲和力CsA >CsC >CsD >CsB。结论 测定CsA浓度的亲环素A结合法灵敏 ,重复性和稳定性好 。

肝移植术后环孢素治疗药物监测

目的:研究肝移植受者环孢素A临床药动学特点,优化环孢素A治疗药物监测方案。方法:采用荧光偏振免疫法测定环孢素A血药浓度,计算临床药动学参数。建立AUC0-12h与浓度变量回归模型。对C0、C2常规监测数据进行分析。结果:环孢素代谢呈二房室开放模型。C0+C2与AUC0-12h相关较为强烈,C2与AUC0-4h和AUC0-12h的相关性高于C0。在估算AUC0→12h的回归模型中,C0+C2最好,SE和R-sq分别为501.0和94.7,其后是C6,C2,C9,C4和C0。结论:环孢素A临床药动学个体差异大。C0+C2两点监测是环孢素A最好的监测方法,可客观评价环孢素A体内药物暴露(AUC0-12h),减少急性排斥和药物中毒发生。C2/C0可以作为评价移植肝功能恢复的灵敏指标。