血清葡萄糖-6-磷酸异构酶与类风湿关节炎的相关性研究

目的研究血清葡萄糖-6-磷酸异构酶(glucose-6-phosphate isomerase,GPI)升高对类风湿关节炎(RA)的诊断价值及其之间相关性。方法以166例RA患者、110例非RA患者和194例健康正常人为研究对象,用酶联免疫吸附试验(ELISA)方法检测各组GPI血清浓度,记录RA组患者的年龄、性别、ESR、CRP、DAS28、关节肿胀数、关节压痛数、RF、抗CCP抗体和双手X线片分级,并比较分析。结果 RA患者血清中GPI浓度[(0.52±1.01)μg/mL]显著高于其他风湿病组[(0.05±0.34)μg/mL(P<0.05)]及健康对照组[(0.10±0.38)μg/mL(P<0.05)]。GPI与关节肿胀数、关节压痛数、DAS28、ESR、抗CCP成正相关。结论 GPI在RA中有较高的特异性,其升高可能与RA的活动性相关。     

类风湿关节炎患者血清IL-17及TNF-α水平检测的临床意义

目的检测类风湿关节炎(RA)患者血清中的IL-17及TNF-α水平,分析其临床意义。方法收集RA患者60例,采用双抗体夹心酶联免疫吸附试验(ELISA)检测RA患者及20例正常对照者血清IL-17及TNF-α水平,并分析血清IL-17及TNF-α水平与RA各临床及实验室指标的相关性。计量资料的比较采用Mann-Whitney U检验或单因素方差分析,相关性分析采用Spearman相关分析。结果 RA患者血清TNF-α(39.36±15.75vs8.98±3.15)pg/mL及IL-17(18.04±15.23vs5.48±2.22)pg/mL水平显著高于正常对照组(P均<0.05);血清TNF-α与IL-17成显著正相关(r=0.558,P<0.05);RF-IgM、IgA、IgG及抗CCP抗体阳性组RA患者血清TNF-α水平与其自身抗体水平均呈正相关(r=0.359,0.392,0.470,0.392;P均<0.05)。IL-17也与上述四种抗体显著相关(r=0.259,0.352,0.471,0.492;P均<0.05)。TNF-α及IL-17均与DAS28评分相关(r=0.559,0.567;P均<0.05)。结论 IL-17和TNF-α在RA患者血清中高表达,并与RF、抗CCP抗体及DAS28评分正相关,同时RA患者IL-17与TNF-α呈显著正相关,提示IL-17和TNF-α可能协同促进RA发病。     

血清白介素-6、血管内皮细胞黏附分子1、E-选择素在慢性阻塞性肺疾病合并侵袭性肺曲霉病中的表达及意义

目的探究慢性阻塞性肺疾病(COPD)合并侵袭性肺曲霉病(IPA)病人血清白介素-6(IL-6)、血管内皮细胞黏附分子1(VCAM-1)、E-选择素(E-Selectin)表达水平及与半乳甘露聚糖(GM)值的相关性。方法选取2017年1月至2019年1月河南省胸科医院收治的COPD病人136例,根据其是否合并IPA分为COPD合并IPA组47例,COPD未合并IPA组89例。采用酶联免疫吸附(ELISA)法检测血清中IL-6、VCAM-1、E-Selectin水平及GM抗原。采用Pearson法分析COPD合并IPA病人血清IL-6、VCAM-1、E-Selectin表达水平与GM值相关性;采用logistic回归模型分析COPD合并IPA发生的影响因素;采用受试者工作特征曲线(ROC)分析血清IL-6、VCAM-1、E-Selectin水平及GM值对COPD合并IPA的诊断价值。结果COPD合并IPA组病人血清IL-6［(59.57±16.43)ng/L比(6.31±2.05)ng/L］、VCAM-1［(716.93±232.09)μg/L比(364.28±156.41)μg/L］、E-Selectin表达水平［(76.52±24.05)μg/L 比(41.34±15.36)μg/L］及GM 值［(0.92±0.19)比(0.37±0.15)］均明显高于COPD 未合并IPA 组(P<0.05)。COPD合并IPA病人血清IL-6、VCAM-1、E-Selectin表达水平与GM值均呈正相关(P<0.05)。血清IL-6、VCAM-1、E-Selectin、GM值高水平均是COPD合并IPA发生的危险因素(P<0.05)。血清E-Selectin表达水平对COPD合并IPA发生诊断的曲线下面积、灵敏度、特异度均为最高。结论COPD合并IPA病人血清IL-6、VCAM-1、E-Selectin表达水平明显升高,与GM值均呈正相关,可能作为生物标志物,用于评估COPD合并IPA发生。     

抗瓜氨酸化蛋白/肽抗体及类风湿因子在类风湿关节炎早期诊断中的应用

目的:探讨两种抗瓜氨酸化蛋白/肽抗体(ACPA)即第三代抗环瓜氨酸肽(CCP3)抗体、抗突变型瓜氨酸波形蛋白(MCV)抗体及类风湿因子(RF)在类风湿关节炎(RA)诊断中的价值。方法:检测30例早期RA患者(RA组)、32例骨性关节炎(OA)和强直性脊柱炎(AS)患者(OA和AS组)及30例健康体检者(对照组)血清抗MCV抗体、抗CCP3抗体及RF水平。分析3种抗体、疾病活动评分(DAS28)、红细胞沉降率(血沉,ESR)及C反应蛋白(CRP)在RA患者治疗后水平的变化。结果:RA组3种抗体的阳性率均高于对照组及OA和AS组(P<0.01)。抗MCV抗体、抗CCP3抗体及RF对RA诊断的敏感性分别为76.67%、66.67%、63.33%,特异性分别为96.77%、95.16%、83.87%。RF与抗MCV抗体、抗MCV抗体与抗CCP3抗体联合检测对RA诊断的敏感性为83.33%、80.00%。RA患者DAS28、ESR、CRP、抗MCV抗体及RF水平较治疗前降低(P<0.05或P<0.01)。结论:抗MCV抗体对RA早期诊断价值较高。抗体联合检测提高了诊断的敏感性。抗MCV抗体及RF对判断RA疾病活动性有重要意义。3种抗体均具有鉴别RA与OA、AS的价值。     

类风湿关节炎患者血清骨保护素水平及临床意义探讨

目的探讨类风湿关节炎(RA)患者血清骨保护素(OPG)水平及其与疾病活动、功能状态、骨侵蚀及实验室指标的关系。方法入选活动期RA患者84例,健康对照21名,酶联免疫吸附试验(ELISA)检测血清OPG水平,同时记录RA患者的临床资料,分析血清OPG水平与RA临床及实验室指标的关系。结果RA患者血清OPG为(63±18)pg/ml,明显高于健康对照组(35±10)pg/ml(P<0.05)。RA血清OPG水平与年龄、健康评估问卷(HAQ)呈正相关关系,与类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体、抗核抗体(ANA)之间呈正相关关系,与疾病活动、骨侵蚀之间无明显相关。结论RA患者血清OPG水平明显增高,并且与患者的年龄、功能状态相关,与疾病活动无明显相关关系;血清OPG水平与自身抗体RF、抗-CCP抗体、ANA相关,提示OPG参与了RA疾病的发生发展过程。     

类风湿关节炎患者血清中Ghrelin和瘦素水平的变化

目的观察Ghrelin类风湿关节炎(RA)患者血清Ghrelin和瘦素水平的变化,为探讨RA的发病机制提供实验基础。方法选择活动期RA患者32例和健康对照30例。应用酶免疫分析(EIA)方法比较两组血清中Ghrelin和瘦素水平的差异;并分析RA患者血清Ghrelin和瘦素水平的相关性。结果与健康对照组相比,RA组血清Ghrelin浓度显著降低(179.06±65.38)pg/mL vs(124.55±56.23)pg/mL,(P<0.01);而RA组血清瘦素水平明显高于健康对照组(6.46±1.21)ng/mL vs(4.73±0.98)ng/mL,(P<0.01)。相关性分析表明,RA组患者血清Ghrelin与瘦素水平呈直线负相关(r=-0.756,P<0.05)。结论类风湿关节炎患者血清Ghrelin水平下降,而瘦素水平升高;二者在RA发病中的作用及其机制值得进一步研究。     

类风湿关节炎合并间质性肺病的临床特点

目的分析类风湿关节炎(rheumatoid arthritis,RA)合并间质性肺病(interstitial lung disease,ILD)患者的临床特点。方法回顾性分析2009年6月至2011年6月住院的322例RA患者的临床症状、实验室和影像学检查及治疗转归。按有无间质性肺病分为RA无ILD组283例,RA-ILD组39例。对各组患者的临床资料进行系统分析。结果 322例RA患者合并ILD的患病率为12%,且多见于50岁以上患者(85%);RA-ILD组中男性患者的比例较RA无ILD组高,差异有统计学意义(P=0.002);RA-ILD组的发病年龄显著高于RA无ILD组,差异有统计学意义(P=0.000)。RA-ILD组RF滴度较RA无ILD组显著增高,差异有统计学意义(P=0.013),两组间病程、关节肿胀数、关节压痛数、血沉(ESR)、C反应蛋白(CRP)、抗环瓜氨酸肽(CCP)抗体、免疫球蛋白G(IgG)、血小板(BPC)、补体(C3、C4)、抗核抗体(ANA)阳性率、抗SSA抗体阳性率差异无统计学意义(P>0.05)。12例病情反复发作,其中男性2例(17%),女性10例(83%)。结论老年、男性、RF滴度高可能是RA并发ILD的危险因素;女性患者病情易反复,预后不佳;早期诊断和规范治疗可改善患者的预后。     

类风湿关节炎患者血清Dickkopf-1表达与疾病活动的相关性研究

目的:检测类风湿关节炎(RA)患者血清中的Dickkopf-1(DKK-1)水平,并探讨其与RA疾病活动的关系。方法:选择2017年10月—2019年12月在山西省汾阳医院风湿免疫科门诊及住院治疗的RA患者44例。详细记录患者治疗前后的临床特点及实验室检测结果。基于28个关节的肿痛情况进行疾病活动性评价(即DAS28评分)。采用酶联免疫吸附法(ELISA)检测治疗前后血清中DKK-1水平。结果:RA患者血清中DKK-1与压痛关节数(TJC)、肿胀关节数(SJC)、DAS28呈正相关(分别为r=0.309,P=0.049;r=0.320,P=0.042;r=0.311,P=0.048),与红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)、年龄无相关性;治疗前DKK-1在RA患者血清中的表达为(6.62±2.29)μg/L,治疗后为(3.79±1.26)μg/L,两者比较差异有统计学意义(t=7.16,P<0.001)。治疗后TJC,SJC,ESR,CRP,RF,DAS28均较治疗前下降(分别为t=53.14,P<0.001;t=47.78,P<0.001;t=71.83,P=0.022;t=75.59,P=0.049;t=77.60,P=0.032;t=79.29,P<0.001)。结论:DKK-1与RA疾病活动性呈正相关,可视为RA疾病活动的生物标志物。     

激活素A、转化生长因子β1 表达与急性呼吸窘迫综合征短期预后的相关性

目的探讨急性呼吸窘迫综合征(ARDS)病人血清激活素A(ACTA)、转化生长因子β1(TGF-β1)表达与短期预后相关性。方法选取咸阳市第一人民医院2018年1月至2019年12月收治的169例ARDS病人为研究对象，分为存活组(98例)、死亡组(71例)，检测血清ACTA、TGF-β1表达并分析其与预后相关性。结果与存活组相比，死亡组氧合指数(PaO₂/FiO₂)较低［(125.42±27.39)mmHg比(186.32±33.51)mmHg，P<0.05］，急性生理学及慢性健康状况评分Ⅱ(APACHE Ⅱ)［(21.44±2.57)分比(17.71±1.95)分］、ACTA［(968.05±143.10)ng/L比(745.12±123.28)ng/L］、TGF-β1［(21.51±3.84)μg/L比(16.30±2.28)μg/L］表达较高(P<0.05)；ACTA、TGF-β1表达与PaO₂/FiO₂呈负相关(P<0.05)，与APACHE Ⅱ评分呈正相关(P<0.05)；与ACTA、TGF-β1低表达者相比，高表达者死亡率较高(P<0.05)，总生存期较短(P<0.05)；PaO₂/FiO₂≤100 mmHg、高APACHE Ⅱ评分、ACTA高表达、TGF-β1高表达是影响ARDS病人预后的独立危险因素(P<0.05)。结论ARDS病人血清ACTA、TGF-β1为高表达，可能为病情评估、短期预后预测提供参考依据。     

葡萄糖-6-磷酸异构酶、抗CCP抗体,RF联合检测对类风湿关节炎的诊断意义

目的:探讨葡萄糖-6-磷酸异构酶(GPI)、抗CCP抗体及RF联合检测对类风湿关节炎(RA)的诊断意义。方法:对205例RA患者血清和131例非RA患者血清及20例正常人血清检测GPI、抗CCP抗体、RF浓度并进行统计学分析。结果:205例RA患者GPI敏感度和特异度分别为72.7%和96%;抗CCP抗体敏感度和特异度分别为85.9%和90.1%;RF敏感度和特异度分别为81%和83.4%;与非RA对照组和正常对照组比较差异均有统计学意义(P<0.01)。结论:联合检测GPI、抗CCP抗体及RF能提高RA的早期诊断。     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate, eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol

Sepracor in the US is developing arformoterol [R,R-formoterol], a single isomer form of the beta(2)-adrenoceptor agonist formoterol [eformoterol]. This isomer contains two chiral centres and is being developed as an inhaled preparation for the treatment of respiratory disorders. Sepracor believes that arformoterol has the potential to be a once-daily therapy with a rapid onset of action and a duration of effect exceeding 12 hours. In 1995, Sepracor acquired New England Pharmaceuticals, a manufacturer of metered-dose and dry powder inhalers, for the purpose of preparing formulations of levosalbutamol and arformoterol. Phase II dose-ranging clinical studies of arformoterol as a longer-acting, complementary bronchodilator were completed successfully in the fourth quarter of 2000. Phase III trials of arformoterol began in September 2001. The indications for the drug appeared to be asthma and chronic obstructive pulmonary disease (COPD). However, an update of the pharmaceutical product information on the Sepracor website in September 2003 listed COPD maintenance therapy as the only indication for arformoterol. In October 2002, Sepracor stated that two pivotal phase III studies were ongoing in 1600 patients. Sepracor estimates that its NDA submission for arformoterol, which is projected for the first half of 2004, will include approximately 3000 adult subjects. Sepracor stated in July 2003 that it had completed more than 100 preclinical studies and initiated or completed 15 clinical studies for arformoterol inhalation solution for the treatment of bronchospasm in patients with COPD. In addition, Sepracor stated that the two pivotal phase III studies in 1600 patients were still progressing. In 1995, European patents were granted to Sepracor for the use of arformoterol in the treatment of asthma, and the US patent application was pending.     

欧洲刺柏（Juniper）

活性成分与药理作用欧洲刺柏药用部位是其浆果，具有促水排泄、防腐、抗胃肠胀气和抗风湿作用，还可改善胃功能。用作促水排泄药可增加尿量（水丢失），但不增加钠排泄。成分萜品烯-4-醇可增加肾小球滤过率，但刺激肾。欧洲刺柏浆果对单纯疱疹病毒体外显示抗病毒活性，并具抗真菌活性。动物实验显示，欧洲刺柏浆果提取物具有堕胎、抗生育、抗炎、抗胚胎植入、降血压、升血压和降血糖作用。欧洲刺柏浆果油具有兴奋子宫的活性，以及利尿、胃肠道抗菌和刺激作用，该油对平滑肌有阻止解痉作用。     

Oral Presentations (LDD, LPES, LNM, LPAT, LNT, LPPT, LPM)

Probiotic microorganisms have been shown to provide specific health benefits when consumed as food supplements or as food components. The main problem of such products is the poor survival of the probiotic bacteria in the low pH of gastric fluid. However the use of synthetic excipients for enteric coating to prevent the exposure of microorganisms to gastric fluid is limited in food supplementary industry. Therefore the aim of this study was to develop an enteric coating formulation containing shellac as a natural polymer. Shellac possesses good resistance to gastric juice; the major disadvantage of this polymer is its low solubility in the intestinal fluid [1, 2]. Thus films containing different ratios of shellac and water-soluble polymers (sodium alginate, hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidon (PVP)) or plasticizers (glycerol and glyceryl triacetate (GTA)) were prepared in order to analyse the films’ melting temperatures (T_m), the changes in enthalpy (ΔH), their capability of taking up water, and their solubility in different media. The release characteristics of the films were studied by loading pellets with Enterococcus faecium M74 and coating them with formulations containing different amounts of shellac and polymer or plasticized shellac. Using dissolution tests, performed according to USP XXXI paddle method, the resistance of the coatings to simulated gastric fluid (SGF, pH 1.2) and the release of cells in simulated intestinal fluid (SIF, pH 6.8) was investigated.The trials showed that an increasing amount of plasticizer results in a decrease of T_m and ΔH of the films whereat glycerol had a superior plasticization effect to GTA. The compatibility of films made of water-soluble polymers and shellac was also concentration dependent. HPMC and PVP showed superior compatibility with shellac compared to sodium alginate, since films containing shellac and more than 10% [w/w] sodium alginate tended to separate into two phases. In the end five formulations containing shellac and either 5% [w/w] glycerol, 10% [w/w] PVP, 20% [w/w] PVP, 10% [w/w] HPMC, or 5% [w/w] sodium alginate emerged as feasible for enteric coating purposes.