布地奈德福莫特罗粉吸入剂联合常规治疗稳定期支气管扩张症患者的疗效及对炎症因子和CAT评分的影响

摘 要 目的：观察布地奈德福莫特罗粉吸入剂联合常规治疗对稳定期支气管扩张症的临床疗效,及对患者血清炎症因子白细胞介素17(IL 17)、干扰素γ(IFN γ）及慢性阻塞性肺疾病评估测试(CAT)评分的影响。方法: 稳定期支气管扩张患者120例随机分为对照组和观察组各60例。对照组采用常规治疗方法,观察组在常规治疗基础上加用布地奈德福莫特罗粉吸入剂,两组疗程均为3个月。比较两组患者治疗前后急性加重次数、临床症状评分、呼吸困难评分、动脉血氧分压( PaO2)、动脉血二氧化碳分压(PaCO2)、第1秒用力呼气容积（FEV1）、用力肺活量(FVC)、呼气峰值流速(PEF)、6 min 步行试验（6MWT）、肺泡灌洗液细胞分类比例、CAT评分、血清IL 7、IFN γ水平。结果: 治疗后,观察组患者的临床症状评分、呼吸困难评分均较治疗前显著下降（P<0.05）,且观察组的临床症状评分、呼吸困难评分、呼吸加重次数均显著低于对照组治疗后（P<0.05）。治疗后,两组患者 PaO2、FEV1、6MWT均较前显著升高,CAT评分、IL 7、TNF γ浓度则较前显著降低,中性粒细胞比例明显下降,巨噬细胞比例明显上升（P<0.05）;且观察组上述指标均明显优于对照组（P＞0.05）。两组PaCO2、FVC、PEF,以及淋巴细胞比例等指标无显著变化（P>0.05）。结论: 布地奈德福莫特罗粉吸入剂对稳定期支气管扩张症疗效确切,可有效缓解临床症状,减少炎性反应。     

丹参多酚酸盐联合常规治疗急性脑梗死疗效及对血清白细胞介素-6影响观察

摘 要 目的：观察丹参多酚酸盐联合常规治疗对急性脑梗死患者的疗效及对血清炎性因子白细胞介素 6（IL 6）的影响。方法: 70例急性脑梗死患者随机分为观察组和对照组各35例,均给予脑梗死常规治疗,观察组在此基础上加用丹参多酚酸盐注射液200 mg+0.9%氯化钠注射液250 ml,ivd,qd。两组疗程均为2周。另选取30例健康体检者为健康对照组。分别于治疗第3天、第7天、第10天及第14天评定两组患者神经功能缺损评分（NIHSS评分）;于发病24 h内,治疗第3天、第7天、第10天及第14天检测两组患者血清IL 6水平,并与健康对照组的血清IL 6水平相比较。结果: 治疗第7天开始观察组NIHSS评分较入院时显著下降（P<0.05）,此后NIHSS评分持续下降;对照组NIHSS评分则在治疗第10天开始显著下降（P<0.05）。治疗第7天后,观察组NIHSS评分均显著低于对照组同期（P<0.05）。两组入院24 h内血清IL 6水平均显著高于健康对照组（P<0.05）。观察组血清IL 6水平从治疗第7天开始逐渐下降,治疗第14天时与健康对照组差异无统计学意义(P>0.05)。对照组血清IL 6水平在治疗第10天后逐渐下降,但对照组各时段血清IL 6水平均高于健康对照组（P<0.05）。治疗第7天开始观察组血清IL 6水平明显低于对照组（P<0.05）;且观察组血清IL 6水平最高值明显低于对照组最高值（P<0.05）。结论: 丹参多酚酸盐联合常规治疗能有效降低脑梗死患者NIHSS评分,降低其血清IL 6水平,效果优于单纯常规治疗。     

坦度螺酮联合奥卡西平治疗癫痫合并焦虑抑郁患者的症状改善观察及机制探讨

摘 要 目的：探讨坦度螺酮联合奥卡西平对癫痫合并焦虑抑郁患者的症状改善,以及对患者血清5-HT1A受体及额叶皮质水平的影响。方法：癫痫合并焦虑、抑郁患者80例随机分为对照组和观察组各40例,对照组常规给予奥卡西平片治疗;观察组在对照组基础上加用坦度螺酮胶囊治疗。治疗8周后,比较两组患者治疗前后汉密尔顿焦虑量表（HAMA）评分、汉密尔顿抑郁量表（HAMD）评分、血清5-HT1A受体水平、额叶皮质水平及药品不良反应发生率。结果：治疗8周后,两组患者HAMA、HAMD评分均较治疗前明显降低（P＜0.05）,且观察组显著低于对照组（P＜0.05）。两组男、女患者血清5-HT1A水平均较治疗前明显升高（P＜0.05）,且观察组男、女患者血清5-HT1A水平均高于对照组（P＜0.05）。对照组患者左额叶谷氨酸复合物（Glx）/肌酸（Cr）治疗前后比较差异无统计学意义（P＞0.05）,其他指标治疗前后比较差异均有统计学意义（P＜0.05）;观察组患者各项指标治疗前后比较差异均有统计学意义（P＜0.05）。且治疗后对照组患者左额叶Glx/Cr、胆碱复合物（Cho）/Cr及右额叶Cho/Cr、N-乙酰天门冬氨酸（NAA）/Cr水平低于观察组,右额叶Glx/Cr及左额叶NAA/Cr水平高于观察组（P＜0.05）。两组药品不良反应发生率比较,差异无统计学意义（P＞0.05）。结论：坦度螺酮联合奥卡西平对癫痫合并焦虑抑郁患者疗效肯定,安全性高,能有效改善患者血清5 HT1A受体及额叶皮质水平,减轻焦虑及抑郁症状,提高患者生活质量。     

不同剂型桂枝葛根汤治疗颈性眩晕的疗效比较

摘 要 目的：观察不同剂型桂枝葛根汤治疗颈性眩晕的疗效差异,并初步探讨其作用机制。方法：96例颈椎病患者随机分为饮片组、配方颗粒组和葛根定眩胶囊组各32例,分别采用桂枝葛根汤饮片、配方颗粒和葛根定眩胶囊治疗14 d,比较3组患者的疗效和治疗前后血流动力学指标变化,酶联免疫法测定3组患者治疗前后IL-6及IL 1β的表达。结果：3组总有效率比较,差异无统计学意义（P＞0.05）。治疗后3 组患者眩晕和头痛评分均较治疗前明显改善（P＜0.01）,饮片组眩晕评分优于胶囊组（P＜0.05）。治疗后3组患者基底动脉和双侧椎动脉的Vs和Vm均较治疗前明显增加（P＜0.01),且配方颗粒组和胶囊组椎动脉的Vm低于饮片组（P＜0.05或P＜0.01）。治疗后,饮片组和配方颗粒组血清IL 6水平较治疗前明显降低(P<0.05),饮片组和胶囊组血清IL-1β水平较治疗前明显降低(P<0.05);胶囊组血清IL-6水平显著高于其他两组(P<0.05),饮片组血清IL 1β水平显著低于配方颗粒组和胶囊组(P<0.05)。结论：桂枝葛根汤三种剂型治疗颈性眩晕的总有效率相当,部分疗效指标饮片相比配方颗粒和胶囊更优。此作用可能与增加脑血流及抑制相关炎症因子IL-6及IL-1β的表达有一定关联。     

保妇康栓治疗宫颈柱状上皮异位疗效及对子宫颈组织ICMI-1mRNA、TGF-β1m RNA及炎性细胞因子水平的影响

摘 要 目的： 探讨保妇康栓治疗宫颈柱状上皮异位的疗效及对子宫颈组织细胞间黏附分子1（ICMI 1）、转化生长因子SymbolbA@1（TGF SymbolbA@1）mRNA表达以及炎性细胞因子的影响。方法: 宫颈柱状上皮异位患者102例随机分为观察组和对照组,每组51例。观察组给予保妇康栓治疗,对照组给予冷冻治疗。均连续治疗7 d。观察两组临床疗效和不良反应情况,比较两组患者治疗前后子宫颈组织ICMI 1 mRNA和TGF SymbolbA@1 mRNA表达及血清炎性细胞因子水平变化。结果: 观察组总有效率为94.12%,明显优于对照组（P＜0.05）。两组治疗后ICMI 1 mRNA和TGF SymbolbA@1 mRNA均较治疗前明显降低（P＜0.05）,且观察组明显低于对照组（P＜0.05）。对照组治疗前后白介素 6（IL 6）和白介素 1（IL 1）无明显变化（P＞0.05）;观察组治疗后IL 6和IL 1较治疗前明显降低（P＜0.05）,且低于对照组（P＜0.05）。两组治疗前后月经期和月经周期无明显变化,未见不良反应发生。结论: 保妇康能有效治疗宫颈柱状上皮异位,降低宫颈柱状上皮异位患者子宫组织ICMI-1mRNA、TGF-β1m RNA表达以及血清炎性细胞因子水平。     

恩替卡韦联合苦参素治疗慢性乙型肝炎疗效及对患者外周血免疫球蛋白、TNF-α和IL-6的影响

摘 要 目的：观察恩替卡韦联合苦参素治疗慢性乙型肝炎的疗效,及对患者外周血免疫球蛋白、肿瘤坏死因子 α（TNF α）和白细胞介素6（IL 6）水平的影响。方法：采用随机双盲对照试验方法,70例慢性乙型肝炎患者随机分为观察组35与对照组各35例。对照组给予恩替卡韦分散片0.5 mg,po,qd;观察组在此基础上加用苦参素胶囊0.2 g,po,tid。两组疗程均为12个月。观察并记录两组患者治疗前后血清HBV DNA及ALT水平、外周血免疫球蛋白（IgM、IgA、IgG）及血清TNF α、IL 6水平变化,比较两组治疗后ALT复常率、HBV DNA阴转率、HBeAg/HBeAb转换率、HBeAg阴转率。结果：治疗后,两组患者ALT水平均较治疗前明显下降（P<0.01）,但两组间比较差异无统计学意义（P>0.05）;两组患者HBV DNA水平也较治疗前明显下降（P<0.01）,且观察组明显低于对照组（P<0.01）。观察组ALT复常率、HBV DNA阴转率、HBeAg/HBeAb转换率、HBeAg阴转率均显著低于对照组（P<0.05）。治疗后,观察组外周血IgM、IgA、IgG含量,以及血清TNF α、IL 6水平较治疗前显著增加（P<0.01或P<0.05）,且均明显高于对照组（P<0.05）。结论：恩替卡韦联合苦参素抗HBV疗效显著,并且能显著提高外周血免疫球蛋白含量,增强免疫应答水平、降低血清TNF α、IL 6含量,控制肝内炎症发展,值得在临床应用中推广。     

舌下免疫治疗对过敏性哮喘患儿血清免疫指标的影响及临床观察

摘 要 目的：比较过敏性哮喘患儿舌下免疫治疗（SLIT）前后外周血血清IL 2、IL 6、IL 21及TGF β1水平变化,观察其疗效。方法: 112例过敏性哮喘患儿随机分为观察组和对照组各56例,根据病情调整吸入性糖皮质激素治疗方案,观察组同时加用粉尘螨滴剂舌下含服,疗程2年。采用ELISA法检测治疗前后患儿血清IL 2、IL 6、IL 21及TGF β1水平,观察患儿哮喘症状评分及肺功能变化,评价临床疗效。结果: 105例（观察组53例,对照组52例）完成治疗。观察组患儿血清IL 2及TGF β1水平较治疗前明显升高,IL 6及IL 21水平较治疗前明显降低（P<0.05）;日、夜间症状评分较治疗前明显降低（P<0.05）,肺功能指标较治疗前明显升高（P<0.05）。治疗2年后观察组患儿各项指标均明显优于对照组（P＜0.05）。结论: SLIT治疗有助于恢复过敏性哮喘患儿免疫失衡,对改善哮喘患儿日夜间哮喘症状评分及肺功能有效。     

百令胶囊辅助治疗对糖尿病肾病患者血清炎性因子的影响

摘 要 目的: 观察百令胶囊辅助治疗对糖尿病肾病（DN）患者血清炎性因子的影响。方法: 68例DN患者随机分为对照组和治疗组各34例,对照组给予饮食、降糖、降压、纠正贫血、保护肾功能及健康教育等综合治疗,治疗组在此基础上加用百令胶囊1.0 g,po,tid,疗程4周。比较两组患者治疗前后血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）,以及Scr、BUN、腰围、体质指数、腰臀比等指标的变化。结果:两组治疗后血清IL-6、TNF-α、CRP水平均较治疗前降低（P＜0.05）,治疗组下降程度更明显,与对照组相比,差异有统计学意义（P＜0.05）。两组患者治疗前后Scr、BUN、腰围、体质指数、腰臀比等比较,差异无统计学意义（P>0.05）。结论:百令胶囊辅助治疗可明显降低患者血清IL 6、TNF GFR及CRP等炎症因子水平,保护肾脏功能。     

羧甲司坦辅助治疗稳定期慢性阻塞性肺疾病观察

摘 要 目的：观察羧甲司坦辅助治疗稳定期慢性阻塞性肺疾病（COPD）的临床疗效、不良反应及对炎症因子的影响。方法：114例稳定期COPD患者随机分为对照组和观察组各57例,对照组给予常规治疗,观察组在对照组基础上加用羧甲司坦片,12个月为一疗程。比较两组患者肺功能、6 min步行距离（6MWT）、1年内急性加重次数,圣乔治呼吸问题调查问卷（SGRQ）评价生活质量,测定诱导痰中炎症因子(IL-1β、IL-6、IL-8、TNF-α）含量,记录药品不良反应。结果：治疗后,两组患者的肺功能、6MWT、1年内急性加重次数均较前明显改善（P<0.05）,且观察组6MWT、急性加重次数明显优于对照组（P<0.05）;两组患者SGRQ量表各项评分均较前下降（P<0.05）,且观察组部分评分优于对照组（P<0.05）;两组患者痰炎症因子水平均较前显著降低（P<0.05）,且观察组明显低于对照组（P<0.05）。两组药品不良反应发生率相近（P>0.05）。结论：羧甲司坦可明显提高稳定期COPD患者的运动能力和生活质量,降低急性加重次数,这可能与其降低气道炎症因子水平有关。     

阿托伐他汀联合法舒地尔治疗慢性肺源性心脏病心力衰竭的临床观察

摘 要 目的：探讨阿托伐他汀联合法舒地尔治疗慢性肺源性心脏病心力衰竭的疗效,为临床治疗提供理论依据。方法: 130例慢性肺源性心脏病合并心力衰竭患者随机分为对照组和他汀组,每组65例。对照组实施常规对症治疗,并给予法舒地尔注射液30 mg,ivd,bid。他汀组在对照组基础上加用阿托伐他汀片20 mg·d-1。两组均连续治疗12周。观察两组临床疗效和药品不良反应,比较两组治疗前后动脉血氧分压（PaO2）、二氧化碳分压（PaCO2）、血氧饱和度(SaO2)、肺动脉收缩压(SPAP)、右心室射血分数（RVEF）、右心室 Tei 指数及血浆内皮素 1（ET 1）、一氧化氮（NO）、脑钠肽（BNP）水平变化。结果: 他汀组治疗后总有效率为89.23％,明显高于对照组的75.38％（P＜0.05）。治疗后,他汀组PaO2、SaO2、RVEF、NO较治疗前明显增高（P＜0.05）,PaCO2、BNP、SPAP、Tei指数、ET 1则较治疗前明显下降（P＜0.05）,且以上指标均明显优于对照组（P＜0.05）。两组药品不良反应发生率差异无统计学意义（P＞0.05）。结论: 阿托伐他汀联合法舒地尔治疗慢性肺源性心脏病心力衰竭的疗效肯定,可有效降低患者的肺动脉压、改善右心功能。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.