依托考昔和美洛昔康在治疗膝骨关节炎中的可行性对比

目的探讨依托考昔和美洛昔康在治疗膝骨关节炎中的可行性。方法选取我院2014年3月~2014年12月收治的100例膝骨关节炎患者进行研究,将其随机分为研究组和对照组,对照组给予美洛昔康治疗,研究组给予依托考昔治疗,比较两组患者Womac关节炎指数、严重程度指数及临床疗效。结果对照组有效率为74.00%,研究组为92.00%,组间比较差异有统计学意义(P0.05)。治疗前两组患者Womac关节炎指数及严重程度指数组间对比差异无统计学意义(P0.05),经过治疗后均有明显降低,较治疗前比较差异均有统计学意义(P0.05)。在治疗1周及3周后研究组患者Womac关节炎指数和严重程度指数均较对照组低,差异有统计学意义(P0.05)。结论与美洛昔康相比,依托考昔在治疗膝骨关节炎时起效速度更快,对膝骨关节炎的临床症状改善效果更佳,值得在临床治疗中推广应用。     

金乌骨通胶囊联合依托考昔治疗膝骨关节炎的临床研究

目的探讨金乌骨通胶囊联合依托考昔治疗膝骨关节炎的临床效果。方法选取2017年1月—2018年10月北京市隆福医院收治的96例膝骨关节炎患者,随机分为对照组和治疗组,每组各48例。对照组口服依托考昔片,60mg/次,1次/d。治疗组在对照组基础上口服金乌骨通胶囊,3粒/次,3次/d,饭后服用。两组均连续治疗3个月。比较两组临床疗效,观察两组治疗前后关节疼痛视觉模拟评分法(VAS)评分、晨僵时间、病情积分、Lequesne指数评分、血流变学参数、肿瘤坏死因子(TNF)-α、白介素(IL)-6、基质金属蛋白酶(MMP)-9水平和关节炎影响测量量表2-短卷(AIMS2-SF)评分变化情况。结果治疗后,对照组和治疗组的总有效率分别是77.1%、91.7%,两组比较差异具有统计学意义(P0.05)。治疗后,两组关节疼痛VAS评分、病情积分较治疗前均显著降低,晨僵时间均显著缩短,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组关节疼痛VAS评分、病情积分显著低于对照组,晨僵时间短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组膝关节休息痛评分、运动痛评分、压痛评分、肿胀评分、晨僵评分、行走能力评分及总分均显著低于治疗前,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组这些Lequesne指数评分显著低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组红细胞变形指数和刚性指数(RDI和RRI)、TNF-α、IL-6、MMP-9较治疗前均显著减小,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组RDI、RRI值、TNF-α、IL-6、MMP-9低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组躯体评分、症状评分、影响评分、社会评分、工作评分及总分均显著上升,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组AIMS2-SF评分均显著高于对照组,两组比较差异具有统计学意义(P0.05)。结论金乌骨通胶囊联合依托考昔治疗膝骨关节炎具有较好的临床疗效,可明显减轻患者疼痛等症状,改善膝关节功能及微循环,减轻机体炎症损伤,提高生活质量,具有一定的临床推广应用价值。     

附桂骨痛胶囊联合依托考昔治疗膝骨关节炎急性期的临床研究

目的探讨附桂骨痛胶囊联合依托考昔治疗膝骨关节炎急性期的安全性与有效性。方法选取2019年10月—2020年9月在天津市津南医院就诊的117例膝骨关节炎急性期患者,按照入院顺序分成对照组(58例)和治疗组(59例)。对照组口服依托考昔片,60 mg/次,1次/d。治疗组患者在对照组用药基础上口服附桂骨痛胶囊,4粒/次,3次/d。两组患者均连续治疗4周。观察两组患者的临床疗效,比较两组治疗前后Lequesne指数评分、血清学指标及不良反应。结果治疗后,治疗组总有效率是94.92%,明显高于对照组的81.03%(P0.05)。治疗后,两组患者疼痛或不适评分、行走距离评分、每日活动能力评分及Lequesne指数总评分均显著下降,与同组治疗前相比较均具有显著性差异(P0.05);且治疗后治疗组疼痛或不适、行走距离、每日活动能力及总评分均要明显低于对照组(P0.05)。治疗后,两组患者白细胞介素-23(IL-23)、基质金属蛋白酶9(MMP-9)及软骨寡聚基质蛋白(COMP)水平均较治疗前显著下降(P0.05);治疗后治疗组各指标相较于对照组下降的更显著(P0.05)。治疗过程中,治疗组不良反应发生率是3.39%,明显低于对照组的13.79%(P0.05)。结论附桂骨痛胶囊联合依托考昔能显著提升膝骨关节炎急性期的临床治疗效果,改善患者的病情程度和关节功能状态,降低血清学指标水平,具有一定的临床推广应用价值。     

依托考昔治疗膝骨关节炎60例的疗效与安全性评价

目的评价依托考昔治疗膝骨关节炎的临床疗效及安全性。方法选择医院2011年1月至2012年10月收治的膝骨关节炎患者120例,随机均分成两组,每组60例。对照组给予口服塞来昔布胶囊(西乐葆)治疗,每日2次,每次200 mg;治疗组给予口服依托考昔片(安康信)治疗,每日1次,每次120 mg。两组均于饭后服用,疗程均为12周。结果治疗组临床总有效率为91.67%,明显高于对照组的76.67%(P<0.05);治疗组药物起效时间显著快于治疗组,且治疗后各时间段膝关节功能活动指数评分显著高于对照组(P<0.05);不良反应发生率对照组为8.33%,治疗组为6.67%,两组差异无统计学意义(P>0.05)。结论依托考昔治疗膝骨关节炎安全有效,起效时间快,可有效改善患者膝关节症状、缓解疼痛,且不良反应少,值得临床推广。     

活血止痛胶囊联合依托考昔治疗膝关节骨性关节炎的疗效观察

目的探讨活血止痛胶囊联合依托考昔治疗膝关节骨性关节炎的临床疗效。方法选取选取2016年2月—2017年2月天津中医药大学第一附属医院骨伤科膝关节骨性关节炎患者60例,随机分为对照组和治疗组,每组各30例。对照组患者饭后口服依托考昔片,1片/次,1次/d。治疗组在对照组治疗基础上口服活血止痛胶囊,6粒/次,2次/d。两组均连续治疗4周。观察两组的临床疗效,比较两组治疗前后VAS评分、WOMAC评分、Lysholm评分、Lequesne指数、患肢红外热成像温度的变化情况。结果治疗后,对照组和治疗组的总有效率分别为86.67%、96.67%,两组比较差异具有统计学意义(P0.05)。治疗后,两组VAS评分、WOMAC评分和Lequesne指数均较治疗前显著降低,Lysholm评分较治疗前显著升高,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组VAS评分、WOMAC评分和Lequesne指数低于对照组,Lysholm评分高于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患膝红外热成像温度均较治疗前显著降低,同组治疗前后比较差异具有统计学意义(P0.05);治疗后治疗组患膝红外热成像温度低于对照组,两组比较差异有统计学意义(P0.05)。结论活血止痛胶囊联合依托考昔治疗膝关节骨性关节炎具有较好的临床疗效,能减轻患者膝关节疼痛和改善膝关节功能,降低患膝红外热成像温度,具有一定的临床推广应用价值。     

通络祛痛膏联合依托考昔治疗膝骨关节炎的临床研究

目的 探讨通络祛痛膏联合依托考昔治疗膝骨关节炎的临床疗效。方法 选取2019年8月—2022年7月东营市东营区人民医院收治的122例膝骨关节炎患者,按随机数字表法将所有患者分为对照组和治疗组,每组各61例。对照组口服依托考昔片,60 mg/次,1次/d。治疗组在对照组治疗基础上使用通络祛痛膏,根据患者痛处面积大小选用1～2贴外贴于患膝,1次/d,每次贴敷时间<12 h。两组疗程均为8周。观察两组的临床疗效,比较治疗前后两组膝关节晨僵时间、疼痛视觉模拟量表（VAS）评分、肿胀评分和活动度,病情严重程度评分、膝骨性关节炎生存质量量表（QOL-KOA）总分、红细胞沉降率（ESR）及血清血小板反应蛋白-1(TSP-1)、Toll样受体4(TLR4)、C反应蛋白（CRP）、高迁移率族蛋白B1(HMGB1)水平。结果 治疗后,治疗组总有效率是95.08%,显著高于对照组的83.61%(P<0.05)。治疗后,两组膝关节晨僵时间均显著缩短,疼痛VAS评分和肿胀评分均显著降低,主、被动活动度均显著增加（P<0.05）;治疗后,这些指标均以治疗组改善更明显（P<0.05）。治疗后...     

膝骨性关节炎联合应用玻璃酸钠及复方倍他米松注射液治疗的临床研究

目的:观察分析膝骨性关节炎患者联合应用玻璃酸钠及复方倍他米松注射液治疗的临床疗效.方法:选择我院2017年11月—2019年11月收治的110例膝骨性关节炎患者为观察对象,按照入院顺序单双号分为两组:治疗组(n=55)、对照组(n=55).对照组患者采用玻璃酸钠关节腔内注射,治疗组患者玻璃酸钠与复方倍他米松注射液联合应用关节腔内注射.比较两组患者的临床疗效,采用视觉模拟评估法(VAS)、Lvsholm关节功能评分、WOMAC的疼痛量表评价两组疼痛程度及膝关节功能,检测比较两组治疗前后关节液基质金属蛋白酶-3(MMP-3)、MMP-9及白细胞介素1β(IL-1β)水平.结果:治疗组患者的治疗总有效率较对照组的显著提高(92.73％VS 78.18％,P<0.05).两组治疗后VAS、Lvsholm及WOMAC评分均降低,关节液MMP-3、MMP-9及IL-1β水平均降低(P<0.05).治疗组治疗后VAS、Lvsholm及WOMAC评分低于对照组,治疗后关节液MMP-3、MMP-9及IL-1β水平低于对照组(P<0.05).结论:玻璃酸钠与复方倍他米松注射液联合应用关节腔内注射治疗膝骨性关节炎可以取得满意效果,患者关节局部疼痛程度及膝关节功能明显改善,考虑作用机制可能与降低关节液MMP-3、MMP-9及IL-1β的水平有关.     

依托考昔与塞来昔布治疗骨关节炎的疗效和安全性对比

目的:比较依托考昔和塞来昔布治疗骨关节炎的临床疗效和安全性.方法:将2015年在我院就诊的120例骨关节炎患者,随机平均分为观察组和对照组,观察组服用依托考昔片60mg(2片/次,1次/d),对照组服用塞来昔布胶囊200mg(1粒/次,2次/d),疗程均为3个月.对两组疗效进行比较,并记录药物治疗期间的不良反应.结果:观察组治疗后,严重性和活动指数评分均显著低于同时段的对照组,差异有统计学意义(P<0.05);两组的不良反应发生率无显著差异(P>0.05).结论:依托考昔治疗骨关节炎疗效优于塞来昔布,不良反应没有增加.     

依托考昔与注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对患者强直性脊柱炎的疗效与安全性评价

目的:评价依托考昔与重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白注射剂(益赛普)联用患者难治性强直性脊柱炎(AS)的疗效与安全性。方法:选取2012年1月—2015年12月间收治的AS患者66例,采用随机数字表法将其分为对照组33例和治疗组33例;对照组患者给予益赛治疗,治疗组在对照组治疗基础上加用依托考昔治疗;治疗后第0、2、6、12周4个时间点评价两组患者临床疗效的评分值、及实验室检查项目测得值的变化情况和不良反应的发生率。结果:两组患者巴斯强直性脊柱炎病情活动指数、活动指数(BASDAI)、总评分值、脊柱痛和超敏C-反应蛋白(Hs-CRP)与治疗后第2、6、12周时均较同组治疗前有显著下降(P<0.05),但第6、12周时均低于治疗前(P<0.05);治疗2周治疗组患者各项指标均低于对照组及同组治疗前(P<0.05)。结论:采用依托考昔与益赛普治疗难治性AS患者起效较快,疗效较确切,安全性较好。     

复方伸筋胶囊联合依托考昔治疗痛风的临床研究

目的探讨复方伸筋胶囊联合依托考昔治疗痛风的临床疗效。方法选取2015年6月—2016年6月在贵阳中医学院第二附属医院进行治疗的痛风患者82例,根据治疗方案的差别分为对照组(41例)和治疗组(41例)。对照组口服依托考昔片,1片/次,1次/d。治疗组在对照组的基础上口服复方伸筋胶囊,4粒/次,3次/d。两组患者均连续治疗7 d。治疗后,比较两组患者的临床疗效,并对治疗前后两组临床症状评分、血清炎性因子和血清黄嘌呤氧化酶(XOD)和血尿酸(UA)水平进行比较。结果治疗后,对照组和治疗组的总有效率分别为80.49%、95.12%,两组比较差异具有统计学意义(P0.05)。两组患者临床症状评分均较同组治疗前显著降低(P0.05),且治疗组上述评分降低的更明显(P0.05);两组患者血清CRP、IL-1β、IL-6和TNF-α水平均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组血清炎性因子水平优于对照组,两组比较差异具有统计学意义(P0.05)。两组血清XOD、UA水平均较同组治疗前显著降低(P0.05),且治疗组上述指标降低的更明显,两组比较差异具有统计学意义(P0.05)。结论复方伸筋胶囊联合依托考昔治疗痛风效果显著,有利于改善临床症状,明显降低机体炎性反应和XOD、UA水平,具有一定的临床推广应用价值。     

人类多能干细胞用于中药毒性和疗效评价的研究进展

中药毒性和疗效评价是评价中药药物安全性评估的重要项目。人类多能干细胞（hPSCs）在疾病建模、药物筛选、分子机制研究以及安全性评价等方面是有力的研究工具。虽然hPSCs作为体外先进研究材料，应用广泛，但在中医药相关领域的研究积累却十分有限。通过调研hPSCs及其分化衍生物在中医药领域的相关应用，讨论hPSCs在中医药领域最大限度利用的可能性以及阻碍，同时展望hPSCs的应用前景，以期为hPSCs在中药毒性和疗效评价领域的相关应用提供一定的理论参考，推进中医药安全性的现代化发展。     

Stem cells for drug screening

Current drug screening methods are insufficiently predictive of clinical toxicity and efficacy. Recent advances in stem cell technology have the potential to improve drug screening. For tests of cardiotoxicity and efficacy of cardioactive drugs, cardiomyocytes derived from human embryonic stem cells and/or human induced pluripotent stem cells, collectively termed human pluripotent stem cells (hPSCs), have been utilized as model alternatives to current drug screening platforms. In this review, we report on recent advances in the differentiation of hPSCs to cardiomyocytes and summarize the evidence for pharmacological responses in hPSC-derived cardiomyocytes.     

人胚胎干细胞在药物毒性风险评估中的研究进展

人胚胎干细胞（hESCs）是来源于胚胎发育早期内细胞团的一类未分化的多能干细胞,具有自我更新和多向分化的生物学特性,在发育生物学、再生医学以及细胞治疗领域等方面已开展了广泛的研究。与常规药物毒性评估所采用的癌细胞或原代细胞不同,干细胞不仅能满足基础毒性评估,由于其多向分化的特点,可经诱导产生各种正常人体器官或组织细胞,为药物临床前评估提供多方面数据。与动物实验模型相比,hESCs不仅避免了种属差异,还具备高通量、低成本的优势,在预测药物毒性效应方面具有广阔的前景。对目前hESCs在药物毒性风险评估中的研究进展进行总结,为体外药物毒性筛选试验提供新思路。     

Present state and future perspectives of using pluripotent stem cells in toxicology research

The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed.     

Evaluation of developmental toxicity using undifferentiated human embryonic stem cells

An embryonic stem cell test (EST) has been developed to evaluate the embryotoxic potential of chemicals with an in vitro system. In the present study, novel methods to screen toxic chemicals during the developmental process were evaluated using undifferentiated human embryonic stem (hES) cells. By using surface marker antigens (SSEA‐4, TRA‐1‐60 and TRA‐1‐81), we confirmed undifferentiated conditions of the used hES cells by immunocytochemistry. We assessed the developmental toxicity of embryotoxic chemicals, 5‐fluorouracil, indomethacin and non‐embryotoxic penicillin G in different concentrations for up to 7 days. While expressions of the surface markers were not significantly affected, the embryotoxic chemicals influenced their response to pluripotent ES cell markers, such as OCT‐4, NANOG, endothelin receptor type B (EDNRB), secreted frizzled related protein 2 (SFRP2), teratocarcinoma‐derived growth factor 1 (TDGF1), and phosphatase and tensin homolog (PTEN). Most of the pluripotent ES cell markers were down‐regulated in a dose‐dependent manner after treatment with embryotoxic chemicals. After treatment with 5‐fluorouracil, indomethacin and penicillin G, we observed a remarkable convergence in the degree of up‐regulation of development, cell cycle and apoptosis‐related genes by gene expression profiles using an Affymetrix GeneChips. Taken together, these results suggest that embryotoxic chemicals have cytotoxic effects, and modulate the expression of ES cell markers as well as development‐, cell cycle‐ and apoptosis‐related genes that have pivotal roles in undifferentiated hES cells. Therefore, we suggest that hES cells may be useful for testing the toxic effects of chemicals that could impact the embryonic developmental stage. Copyright © 2014 John Wiley & Sons, Ltd.     

Intestinal organoids as tissue surrogates for toxicological and pharmacological studies

Recently developed cell culture protocols have allowed for the derivation of multi-cellular structures dubbed intestinal “organoids” from embryonic stem cells (ESCs), induced pluripotent stem cells (IPSCs), and adult intestinal stem cells (ISCs). These structures resemble in vivo intestinal crypts, both in structure and developmental processes, and can be grown quickly and in relatively large quantities. Although much research has focused on developing intestinal organoids for tissue repair, more immediate applications include high-throughput screening for agents that target intestinal epithelium. Here we describe current methods for deriving mouse and human intestinal organoids and discuss some applications aimed at developing novel therapies or preventive agents for diseases of the lower GI tract such as inflammatory bowel diseases and colorectal cancer.     

Application of human pluripotent stem cells and pluripotent stem cell-derived cellular models for assessing drug toxicity

Introduction: Human pluripotent stem cells (hPSCs) are capable of differentiating into all types of cells in the body and so provide suitable toxicology screening systems even for hard-to-obtain human tissues. Since hPSCs can also be generated from differentiated cells and current gene editing technologies allow targeted genome modifications, hPSCs can be applied for drug toxicity screening both in normal and disease-specific models. Targeted hPSC differentiation is still a challenge but cardiac, neuronal or liver cells, and complex cellular models are already available for practical applications.

Areas covered: The authors review new gene-editing and cell-biology technologies to generate sensitive toxicity screening systems based on hPSCs. Then the authors present the use of undifferentiated hPSCs for examining embryonic toxicity and discuss drug screening possibilities in hPSC-derived models. The authors focus on the application of human cardiomyocytes, hepatocytes, and neural cultures in toxicity testing, and discuss the recent possibilities for drug screening in a ‘body-on-a-chip’ model system.

Expert opinion: hPSCs and their genetically engineered derivatives provide new possibilities to investigate drug toxicity in human tissues. The key issues in this regard are still the selection and generation of proper model systems, and the interpretation of the results in understanding in vivo drug effects.     

Stem cell-derived hepatocytes as a predictive model for drug-induced liver injury: are we there yet?

Amongst the different types of adverse drug reactions, drug-induced liver injury is the most prominent cause of patient morbidity and mortality. However, the current available hepatic model systems developed for evaluating safety have limited utility and relevance as they do not fully recapitulate a fully functional hepatocyte, and do not sufficiently represent the genetic polymorphisms present in the population. The rapidly advancing research in stem cells raises the possibility of using human pluripotent stem cells in bridging this gap. The generation of human induced pluripotent stem cells via reprogramming of mature human somatic cells may also allow for disease modelling in vitro for the purposes of assessing drug safety and toxicology. This would also allow for better understanding of disease processes and thus facilitate in the potential identification of novel therapeutic targets. This review will focus on the current state of effort to derive hepatocytes from human pluripotent stem cells for potential use in hepatotoxicity evaluation and aims to provide an insight as to where the future of the field may lie.     

诱导性多能干细胞体外诱导的现状和展望

鉴于人的胚胎干细胞在再生医学、组织工程学和药物研发等领域有极高的应用价值,科学家尝试通过各种途径获得胚胎干细胞样的多能干细胞。其中Yamanaka等率先在体外通过病毒载体诱导的方式实现体细胞重新编程,由此得到诱导性多能干细胞。多种无遗传修饰的诱导方式正在尝试和改进中,例如用小分子化合物来代替外源基因进行重编程引起了很大的兴趣。用基于细胞水平的表型筛选法和信号通路筛选法,已筛选出特异小分子或天然产物,也可以特异地将成熟细胞去分化为干细胞,有望运用于组织修复和再生。而利用重组蛋白在体外将体细胞诱导为干细胞,也获得了初步成功。由诱导性多能干细胞在体外诱导分化出的细胞在治疗相应疾病方面展示出一定疗效。不同类型的干细胞向体细胞的定向分化策略都是基于目前对发育生物学的认识,这些研究揭示了一些共同的可能线索。     

Human embryonic stem cells and lung regeneration

Human embryonic stem cells are pluripotent cells derived from the inner cell mass of preimplantation stage embryos. Their unique potential to give rise to all differentiated cell types has generated great interest in stem cell research and the potential that it may have in developmental biology, medicine and pharmacology. The main focus of stem cell research has been on cell therapy for pathological conditions with no current methods of treatment, such as neurodegenerative diseases, cardiac pathology, retinal dysfunction and lung and liver disease. The overall aim is to develop methods of application either of pure cell populations or of whole tissue parts to the diseased organ under investigation. In the field of pulmonary research, studies using human embryonic stem cells have succeeded in generating enriched cultures of type II pneumocytes in vitro. On account of their potential of indefinite proliferation in vitro, embryonic stem cells could be a source of an unlimited supply of cells available for transplantation and for use in gene therapy. Uncovering the ability to generate such cell types will expand our understanding of biological processes to such a degree that disease understanding and management could change dramatically.