巴瑞替尼联合柳氮磺吡啶治疗类风湿性关节炎的临床研究

目的 探讨巴瑞替尼联合柳氮磺吡啶治疗类风湿性关节炎的临床疗效。方法 选取2021年5月-2022年12月海南医学院第一附属医院收治的82例类风湿性关节炎患者，随机法分为对照组（41例）和治疗组（41例）。对照组口服柳氮磺吡啶肠溶片，3粒/次，3次/d。在对照组的基础上，治疗组口服巴瑞替尼片，2 mg/次，1次/d。两组用药90 d。观察两组患者临床疗效，比较治疗前后两组患者症状好转情况，类风湿因子（RF）、红细胞沉降率（ESR）和生活质量评分量表（SF-36）评分，及血清细胞因子高迁移率族蛋白1（HMGB1）、白细胞介素-17（IL-17）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平。结果 治疗后，治疗组患者总有效率（97.56%）明显高于对照组（82.93%，P<0.05）。治疗后，治疗组临床症状好转情况均显著好于对照组（P<0.05）。治疗后，两组患者RF、ESR指标明显低于治疗前，而SF-36评分指标显著高于治疗前（P<0.05），且治疗组RF、ESR和SF-36评分指标明显好于对照组（P<0.05）。治疗后，两组患者血清细胞因子HMGB1、IL-17、IL-1β、TNF-α水平明显低于治疗前（P<0.05），且治疗组均显著低于对照组（P<0.05）。结论 巴瑞替尼联合柳氮磺吡啶治疗类风湿性关节炎效果确切，能有效降低ESR、RF和炎症因子水平，改善患者生活质量。     

托法替布联合柳氮磺吡啶治疗类风湿关节炎的临床研究

目的 探讨托法替布联合柳氮磺吡啶治疗类风湿关节炎的临床疗效。方法 选择2020年6月—2022年6月中国人民解放军空军军医大学第一附属医院收治的118例类风湿关节炎患者,采用随机数字表法分为对照组（59例）和治疗组（59例）。对照组患者口服柳氮磺吡啶肠溶片,4片/次,3次/d。在对照组的基础上,治疗组口服枸橼酸托法替布片,5 mg/次,2次/d。两组患者连续服用药物7周。观察两组患者临床疗效,比较治疗前后两组患者症状缓解时间,关节疼痛评分（VAS）,实验室指标红细胞沉降率（ESR）、肿瘤坏死因子-α(TNF-α)、血清类风湿因子（RF）、C反应蛋白（CRP）水平及不良反应。结果 治疗后,治疗组患者总有效率（98.31%）明显高于对照组（83.05%,P<0.05）。治疗后,治疗组出现的关节疼痛、关节肿胀、关节晨僵、食欲减退等症状缓解时间均明显早于对照组（P<0.05）。治疗后,两组VAS评分均明显下降（P<0.05）,且治疗组明显低于对照组（P<0.05）。治疗后,两组患者实验室指标ESR、RF、TNF-α、CRP水平均明显低于治疗前（P<0.05）,且治...     

尪痹胶囊联合艾拉莫德治疗类风湿关节炎的临床研究

目的 探讨尪痹胶囊联合艾拉莫德治疗类风湿关节炎的临床疗效。方法 选取2020年1月—2021年1月郑州市中医院收治的130例类风湿关节炎患者,随机分为对照组（65例）和治疗组（65例）。对照组患者口服艾拉莫德片,25 mg/次,2次/d。治疗组患者在对照组基础上口服尪痹胶囊,5粒/次,3次/d。两组患者均治疗12周。观察两组患者临床疗效,比较治疗前后两组患者主要症状和体征,红细胞沉降率（ESR）、C反应蛋白（CRP）、类风湿因子（RF）和抗环瓜氨酸肽抗体（Anti-CCP）水平,肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和IL-17水平,及Th17比例、Th17/Treg值和Treg细胞比例。结果 治疗后,治疗组总有效率为96.92%,明显高于对照组的87.69%（P<0.05）。治疗后,两组关节疼痛数、关节肿胀数、晨僵时间、VAS评分均较治疗前降低,双手握力上升（P<0.05）,且治疗组主要症状和体征明显好于对照组（P<0.05）。治疗后,两组ESR、CRP、RF、Anti-CCP水平均较治疗前降低（P<0.05）,且治疗组比对照组降低更显著（P<0.05）。治疗后,两组TNF-α、IL-6、IL-17水平均较治疗前降低（P<0.05）,且治疗组较对照组降低更显著（P<0.05）。治疗后,两组Th17比例、Th17/Treg值均降低,而Treg细胞比例均上升（P<0.05）,且治疗组免疫功能明显好于对照组（P<0.05）。结论 尪痹胶囊联合艾拉莫德可以提高类风湿关节炎患者疗效,改善患者临床症状和体征,抑制炎症反应,改善免疫功能,安全性高。     

甲氨蝶呤联合阿达木单抗或来氟米特治疗类风湿关节炎的临床效果及对炎症因子的影响

目的 探讨甲氨蝶呤（MTX）联合阿达木单抗（ADA）或来氟米特（LEF）治疗类风湿关节炎（RA）的效果及对临床症状改善、炎症因子的影响。方法 选取于我院就诊的类风湿关节炎患者88例,按照随机抽签法将其分为ADA组（n=44）和LEF组（n=44）,ADA组采用MTX联合ADA治疗,LEF组采用MTX联合LEF治疗。比较治疗前和治疗3个月后两组患者的临床症状[RA患者病情评价（DAS28）]、生化指标[类风湿因子（RF）、红细胞沉降率（ESR）]和炎症因子[C-反应蛋白（CRP）、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平变化,比较治疗后两组患者的不良反应（恶心呕吐、腹泻、蛋白尿）发生率。结果 治疗前,两组DAS28、GH、RF、ESR、CRP、IL-6和TNF-α水平比较差异均无统计学意义（P>0.05）,治疗3个月后,两组患者的DAS28、RF、ESR、CRP、IL-6、GH和TNF-α较治疗前显著降低（P<0.05）,但两组之间差异无统计学意义（P>0.05）,治疗后,两组患者的恶心呕吐、腹泻、蛋白尿发生率比较,差异均无统计学意义（P>0....     

骨瓜提取物治疗活动期类风湿性关节炎42例临床分析

目的评价骨瓜提取物治疗活动期类风湿性关节炎的疗效和安全性。方法 79例类风湿性关节炎患者分为对照组37例和观察组42例,两组均给予基础治疗,观察组除基础治疗外加用骨瓜提取物（75mg/d）,疗程3周。观察两组治疗后关节疼痛、晨僵时间、疾病活动DAS28评分、ESR、RF、CRP及不良反应。结果骨瓜提取物治疗3周后,观察组晨僵、关节疼痛症状较对照组缓解,观察组ESR较对照组下降,而DAS28评分、RF、CRP两组差异无统计学意义。结论骨瓜提取物对治疗类风湿性关节炎急性症状有一定的疗效,无明显不良反应。     

通滞苏润江胶囊联合塞来昔布治疗类风湿性关节炎的临床研究

目的 探讨通滞苏润江胶囊联合塞来昔布治疗类风湿性关节炎的临床疗效。方法 选取2018年2月-2020年2月在河南省洛阳正骨医院（河南省骨科医院）就诊的86例类风湿性关节炎患者,随机分为对照组和治疗组,每组各43例。对照组口服塞来昔布胶囊,0.2 g/次,2次/d;治疗组在对照组治疗基础上口服通滞苏润江胶囊,7粒/次,2次/d。两组均经8周治疗。观察两组的临床疗效,比较两组临床症状缓解时间、相关评分和血清学因子的情况。结果 经治疗,治疗组的总有效率是97.67%明显高于对照组81.40%（P<0.05）。经治疗,治疗组晨僵、关节压痛、屈伸不利、关节肿胀、关节发热症状缓解时间均显著短于对照组（P<0.05）。经治疗,两组HAQ指数、DAS28评分、VAS评分均较治疗前显著降低（P<0.05）;治疗后,治疗组HAQ指数、DAS28评分、VAS评分显著低于对照组（P<0.05）。经治疗,两组血清类风湿因子（RF）、抗环瓜氨酸抗体（ACCP）、白细胞介素-1β（IL-1β）、白细胞介素-17（IL-17）、白细胞介素-37（IL-37）水平均显著降低,但骨保护素（OPG）显著升高（P<0.05）;治疗后,治疗组RF、ACCP、IL-1β、IL-17、IL-37水平显著低于对照组,而OPG高于对照组（P<0.05）。结论 通滞苏润江胶囊联合塞来昔布治疗类风湿性关节炎具有较好的临床疗效,可显著改善患者相关症状和细胞因子水平,具有一定的临床推广应用价值。     

追风透骨丸联合艾拉莫德治疗类风湿性关节炎的临床研究

目的探讨追风透骨丸联合艾拉莫德片治疗类风湿性关节炎的临床疗效。方法选取2014年3月—2018年3月在成都市新都区人民医院治疗类风湿性关节炎患者102例,根据用药的差别分为对照组(51例)和治疗组(51例)。对照组饭后口服艾拉莫德片,25 mg/次,2次/d;治疗组在对照组基础上饭后口服追风透骨丸,6 g/次,2次/d。两组患者均治疗24周。观察两组患者临床疗效,同时比较治疗前后两组患者关节肿胀分级、20 m步行时间、WOMAC、VAS和DAS28评分及血清学指标。结果治疗后,对照组和治疗组临床有效率分别为76.47%和94.12%,两组比较差异均具有统计学意义(P0.05)。治疗后,两组患者关节肿胀分级显著降低(P0.05),20 m步行时间显著缩短(P0.05),且治疗组患者关节肿胀分级明显低于对照组(P0.05),20 m步行时间明显短于对照组(P0.05)。治疗后,两组WOMAC评分、VAS评分、DAS28评分均显著降低(P0.05),且治疗组WOMAC、VAS和DAS28评分明显低于对照组(P0.05)。治疗后,两组患者C反应蛋白(CRP)、白细胞介素-6(IL-6)、IL-17、类风湿因子(RF)、环氧化酶-2(COX-2)和红细胞沉降率(ESR)水平均显著降低(P0.05),且治疗组这些血清学指标明显低于对照组(P0.05)。结论追风透骨丸联合艾拉莫德片治疗类风湿性关节炎可有效改善患者临床症状,降低血清细胞因子水平,改善关节疼痛,提高患者生活质量。     

低剂量雷公藤多苷治疗中老年活动性类风湿关节炎的临床效果

目的 探讨低剂量雷公藤多苷治疗中老年活动性类风湿关节炎的临床效果。方法 选取2021年1月至2022年11月平湖市中医院收治的70例中老年活动性类风湿关节炎患者作为研究对象,按照随机抽签法将其分为对照组（33例）和观察组（37例）。对照组采用甲氨蝶呤或来氟米特治疗,观察组联合低剂量雷公藤多苷治疗。比较两组患者关节压痛数（TJC）、关节肿胀数（SJC）、C反应蛋白（CRP）、红细胞沉降率（ESR）、视觉模拟评分（VAS）、健康评估问卷（HAQ）、28个关节疾病活动评分（DAS28）。比较两组患者治疗后美国风湿病学会（ACR）20、ACR50缓解率和DAS28达标率。比较两组不良反应发生情况。结果 治疗前,两组患者TJC、SJC、CRP、ESR、VAS、HAQ及DAS28比较,差异无统计学意义（P>0.05）;治疗后,两组患者TJC、SJC均少于本组治疗前,CRP、VAS、HAQ及DAS28均低于本组治疗前,ESR慢于本组治疗前,且观察组患者TJC、SJC均少于对照组,VAS、DAS28均低于对照组,ESR慢于对照组,差异有统计学意义（P<0.05）。治疗后,观察组患者DAS2...     

大活络胶囊联合美洛昔康治疗类风湿性关节炎的临床研究

目的探讨大活络胶囊联合美洛昔康片治疗类风湿性关节炎的临床疗效。方法选取2018年3月-2019年10月在天津市泰达医院就诊的88例类风湿性关节炎患者作为研究对象,按照随机数字表法将全部患者分为对照组和治疗组,每组各44例。对照组患者口服美洛昔康片,7.5 mg/次,2次/d。治疗组患者在对照组治疗的基础上口服大活络胶囊,1.0 g/次,3次/d。两组患者连续治疗8周。观察两组患者临床疗效,并比较治疗前后两组患者症状体征改善情况、血液流变学指标、血清因子水平、类风湿关节炎患者病情评分(DAS28)。结果治疗后,治疗组患者的总有效率(93.18%)高于对照组(77.27%),两组比较差异有统计学意义(P<0.05)。治疗后,两组的肿胀关节数、压痛关节数、晨僵时间、VAS评分均明显降低(P<0.05),且治疗组的症状体征改善情况明显低于对照组(P<0.05)。治疗后,两组的高切血液黏度、血浆黏度、血沉(ESR)、纤维蛋白原(FIB)均低于治疗前(P<0.05);治疗后治疗组的高切血液黏度、血浆黏度、ESR、FIB比对照组低(P<0.05)。治疗后,两组的类风湿因子(RF)、抗链球菌溶血素O(ASO)、C反应蛋白(CRP)、抗环瓜氨酸肽抗体(ACCP)水平均明显低于治疗前(P<0.05);且治疗组血清因子水平均低于对照组(P<0.05)。治疗后,两组的DAS28评分明显降低(P<0.05),且治疗组DAS28评分降低的更明显(P<0.05)。结论大活络胶囊联合美洛昔康片可提高类风湿性关节炎的疗效,减轻患者的临床症状体征,降低疼痛程度,改善血流流变学水平,具有重要临床研究价值。     

七味通痹口服液联合甲氨蝶呤治疗类风湿关节炎的疗效观察及其对血清疼痛介质和炎症因子的影响

目的 探讨七味通痹口服液联合甲氨蝶呤治疗类风湿关节炎的疗效观察及其对血清疼痛介质和炎症因子的影响。方法 选取2019年5月—2020年11月海南省中医院收治的84例类风湿关节炎患者作为研究对象，按照治疗方法将84例患者分为对照组和观察组，每组各42例。对照组口服甲氨蝶呤片，10 mg/次，1次/周。观察组在对照组基础上口服七味通痹口服液，10 mL/次，3次/d。两组连续治疗3个月。观察两组患者的临床疗效，比较两组治疗前后的关节压痛数、肿胀数、晨僵持续时间，同时比较两组视觉模拟评分法（VAS）、血清前列腺素E₂（PGE₂）、血浆P物质（SP）、白细胞介素-17（IL-17）、抗链球菌溶血素O（ASO）、类风湿因子（RF）、C反应蛋白（CRP）和血沉（ESR）水平。结果 治疗后，观察组总有效率为85.71%，显著高于对照组的66.67%，两组间对比差异有统计学意义（P<0.05）。两组治疗后的压痛数、肿胀数、晨僵持续时间、疼痛程度评分显著降低（P<0.05）；治疗后，观察组的压痛数、肿胀数、晨僵持续时间、疼痛程度评分显著低于对照组，差异有统计学意义（P<0.05）。两组治疗后的PGE₂、SP、IL-17水平显著降低（P<0.05）；治疗后，观察组的PGE₂、SP、IL-17水平显著低于对照组，差异有统计学意义（P<0.05）。两组治疗后的ASO、RF、CRP、ESR水平显著降低（P<0.05）；治疗后，观察组的ASO、RF、CRP、ESR水平显著低于对照组，差异有统计学意义（P<0.05）。结论 七味通痹口服液联合甲氨蝶呤可提高类风湿关节炎的疗效，降低患者血清疼痛介质和炎症因子的水平，进一步减轻临床症状体征，具有一定临床研究价值。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.