益肾康胶囊联合阿魏酸哌嗪治疗慢性肾小球肾炎的临床研究

目的 探讨益肾康胶囊与阿魏酸哌嗪联合治疗慢性肾小球肾炎的临床疗效。方法 选择2019年12月—2021年12月在华中科技大学同济医学院附属梨园医院诊疗的98例肾炎患者,随机分为对照组和治疗组,每组各49例。对照组口服阿魏酸哌嗪片,100～200 mg/次,1次/d。在对照组基础上,治疗组口服益肾康胶囊,2粒/次,1次/d。两组患者治疗4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,尿蛋白指标24 h-尿蛋白定量（24 h-Upro）、尿微量白蛋白（mALB）和β₂-微球蛋白（β₂-MG）,血清白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和γ干扰素（IFN-γ）水平,及不良反应情况。结果 治疗后,治疗组临床有效率为97.96%,显著高于对照组的79.59%（P＜0.05）。治疗后,治疗组症状缓解时间均早于对照组（P＜0.05）。治疗后,两组24 h-Upro、尿mALB、β₂-MG、IL-6、IL-1、TNF-α、IFN-γ水平均降低,治疗组水平低于对照组（P＜0.05）。治疗期间,治疗组不良反应率为8.16%,明显低于对照组的18.36%（P＜0.05）。结论 阿魏酸哌嗪联合益肾康胶囊治疗慢性肾小球肾炎能提高有效治疗率,并改善尿蛋白指标,降低炎性反应的水平。     

肾复康片联合氯沙坦治疗慢性肾小球肾炎的临床研究

目的 探讨肾复康片联合氯沙坦钾片治疗慢性肾小球肾炎的临床疗效。方法 选取2020年12月—2022年6月在商丘市第一人民医院的收治的122例慢性肾小球肾炎患者，根据随机数字表法将全部患者分为对照组和治疗组，每组各61例。对照组口服氯沙坦钾片，1片/次，1次/d。治疗组在对照组治疗的基础上口服肾复康片，6片/次，3次/d。两组持续治疗12周。观察两组的临床疗效，比较两组血尿、蛋白尿的转阴时间以及血清血肌酐（Scr）、尿白蛋白排泄率（UAER）、尿24 h尿蛋白定量（24 h Upro）、尿红细胞、尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、尿激酶型纤溶酶原激活物受体（uPAR）、β₂-微球蛋白（β₂-MG）、白细胞诱素-1（Lkn-1）、白细胞介素-13（IL-13）、基质金属蛋白酶-9（MMP-9）水平。结果 治疗后，治疗组的总有效率为95.08%，明显高于对照组的83.61%（P＜0.05）。治疗后，治疗组血尿、蛋白尿转阴时间均明显短于对照组，差异有统计学意义（P＜0.05）。治疗后，两组血清Scr、UAER和尿24 h Upro、尿红细胞明显低于治疗前（P＜0.05），且治疗组血清Scr、UAER和尿24 h Upro、尿红细胞低于对照组，差异有统计学意义（P＜0.05）。治疗后，两组的NGAL、uPAR、β₂-MG水平低于治疗前（P＜0.05），且治疗组的NGAL、uPAR、β₂-MG低于对照组（P＜0.05）。治疗后，两组血清Lkn-1、IL-13、MMP-9水平低于对照组（P＜0.05）；治疗组的血清Lkn-1、IL-13、MMP-9水平低于对照组（P＜0.05）。结论 肾复康片联合治疗氯沙坦钾片治疗慢性肾小球肾炎的疗效确切，能减轻临床症状、炎症反应和肾功能损伤，安全性良好。     

活血止痛胶囊联合双氯芬酸钠治疗急性软组织损伤的临床研究

目的 探讨活血止痛胶囊联合双氯芬酸钠治疗急性软组织损伤的临床疗效。方法 选取2020年6月—2022年6月如皋市人民医院收治的90例急性软组织损伤病患,按照随机数字表法分为对照组（45例）和治疗组（45例）。对照组口服双氯芬酸钠缓释胶囊,50mg/次,2次/d。在对照组基础上,治疗组口服活血止痛胶囊,4粒/次,3次/d。两组治疗7d。观察两组患者临床疗效,比较治疗前后两组患者症状改善时间,视觉模拟评分法（VAS）,血清炎性因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、前列腺素E₂（PGE₂）和白细胞介素-1β（IL-1β）水平及不良反应。结果 治疗后,治疗组患者总有效率（97.78%）明显高于对照组（80.00%,P＜0.05）。与对照组比较,治疗组症状改善更快（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,两组血清炎性因子IL-1β、IL-6、PGE₂、TNF-α水平均明显降低（P＜0.05）,且治疗组明显低于对照组（P＜0.05）。治疗后,治疗组不良反应发生率明显低于对照组（P＜0.05）。结论 活血止痛胶囊联合双氯芬酸钠治疗急性软组织损伤效果确切,能有效降低机体炎性因子含量,促进软组织的修复、再生、功能恢复。     

龙七胃康片联合艾司奥美拉唑治疗胃溃疡的临床研究

目的 探讨龙七胃康片联合艾司奥美拉唑肠溶胶囊治疗胃溃疡的临床效果。方法 选取2022年1月—2023年6月在郑州市第七人民医院接受治疗的胃溃疡患者94例，随机分为对照组（47例）和治疗组（47例）。对照组患者口服艾司奥美拉唑肠溶胶囊，20 mg/次，2次/d。治疗组患者在对照组的治疗基础上口服龙七胃康片，3片/次，3次/d。两组均治疗4周。观察两组的临床疗效、溃疡愈合情况、临床症状消失时间、胃泌素、C反应蛋白（CRP）、白细胞介素-17（IL-17）的水平。结果 治疗后，治疗组的总有效率为95.74%，显著高于对照组的80.85%（P＜0.05）。治疗后，治疗组溃疡愈合率为87.23%，显著高于对照组的70.21%（P＜0.05）。治疗组腹痛、反酸、嗳气消失时间均显著短于对照组（P＜0.05）。治疗后，两组胃泌素、CRP、IL-17水平均较同组治疗前显著明降低（P＜0.05）；且治疗后，治疗组患者的胃泌素、CRP、IL-17水平低于对照组（P＜0.05）。结论 龙七胃康片联合艾司奥美拉唑肠溶胶囊治疗胃溃疡具有较好的临床疗效，可有效促进溃疡愈合、缩短临床症状消失时间，改善机体的胃肠激素及炎症指标水平，且无明显的药物不良反应。     

小儿麻甘颗粒联合布地奈德治疗小儿毛细支气管炎的临床研究

目的 探讨小儿麻甘颗粒联合吸入用布地奈德混悬液治疗小儿毛细支气管炎的临床治疗效果。方法 选取2020年6月—2022年5月在周口市中医院就诊的82例毛细支气管炎患儿,按照随机数字表法将所有患儿分为对照组和治疗组,每组各41例。对照组雾化吸入吸入用布地奈德混悬液,0.5 mg/次,2次/d。治疗组在对照组基础上口服小儿麻甘颗粒,1岁以下：0.8 g/次,1～3岁：1.6 g/次,4岁及以上：2.5 g/次,4次/d。两组连续治疗7 d。观察两组的临床疗效,比较两组的主要症状消失时间、肺通气功能和血清指标的水平。结果 治疗后,治疗组的总有效率为95.12%,明显高于对照组的总有效率80.49%,组间比较差异具有显著性（P＜0.05）。治疗后,治疗组咳嗽、哮鸣音、气喘、肺部阴影消失时间均明显短于对照组,差异有统计学意义（P＜0.05）。治疗后,两组的呼吸频率（RR）显著降低,呼气峰流速值（PEF）、吸呼比（tI/tE）显著升高（P＜0.05）;治疗组的RR低于对照组,PEF、tI/tE高于对照组（P＜0.05）。治疗后,两组的血清白细胞介素-4（IL-4）、转化生长因子β₁（TGF-β₁）水平明显降低,血清白细胞介素-35（IL-35）水平明显升高（P＜0.05）;治疗组的血清IL-4、TGF-β₁水平低于对照组,血清IL-35水平高于对照组,差异有统计学意义（P＜0.05）。结论 小儿麻甘颗粒联合吸入用布地奈德混悬液可有效治疗小儿毛细支气管炎,能减轻临床症状,改善患儿的肺通气功能,降低炎症反应。     

夏枯草颗粒联合地塞米松治疗慢性淋巴细胞性甲状腺炎的临床研究

目的 探讨夏枯草颗粒联合地塞米松磷酸钠注射液治疗慢性淋巴细胞性甲状腺炎的临床疗效。方法 选取2020年2月—2021年5月天津市宁河区医院收治的92例慢性淋巴细胞性甲状腺炎患者作为研究对象，根据随机数字表法将92例患者分为对照组和治疗组，每组各46例。对照组在甲状腺两侧局部注射地塞米松磷酸钠注射液，每次每侧各2.5 mg，2次/周。治疗组在对照组治疗的基础上口服夏枯草颗粒，2 g/次，2次/d。两组治疗12周统计疗效。观察两组的临床疗效，比较两组患者治疗前后甲状腺最大长径和血清甲状腺球蛋白抗体（TGAb）、甲状腺过氧化物酶抗体（TPOAb）、转化生长因子-β1（TGF-β1）、白细胞介素-17（IL-17）、白细胞介素-35（IL-35）水平。结果 治疗后，治疗组的总有效率（86.96%）明显高于对照组（69.57%），组间比较有显著差异（P＜0.05）。治疗后，两组患者的甲状腺最大长径均显著减少（P＜0.05），治疗组甲状腺最大长径较对照组减少更显著（P＜0.05）。治疗后，治疗组的TGAb、TPOAb水平均显著降低（P＜0.05），且治疗组的TGAb、TPOAb水平明显低于对照组，差异均有统计学意义（P＜0.05）。治疗后，两组的血清TGF-β₁、IL-17水平明显降低，IL-35水平明显升高（P＜0.05），治疗后治疗组的血清TGF-β₁、IL-17水平比对照组低，IL-35水平比对照组高（P＜0.05）。结论 夏枯草颗粒联合地塞米松磷酸钠注射液治疗慢性淋巴细胞性甲状腺炎的疗效确切，能使甲状腺缩小，降低甲状腺自身抗体水平，调节血清炎性因子水平，具有良好的安全性。     

痹祺胶囊联合替扎尼定治疗椎动脉型颈椎病的临床研究

目的 探讨痹祺胶囊联合盐酸替扎尼定片治疗椎动脉型颈椎病的临床疗效。方法 选取2020年5月—2021年9月郑州大学附属郑州中心医院收治的112例椎动脉型颈椎病患者,根据随机数字表法将112例患者分为对照组和治疗组,每组各56例。对照组口服盐酸替扎尼定片,2 mg/次,3次/d;治疗组在对照组基础上口服痹祺胶囊,1.2 g/次,3次/d。两组连续治疗4周。观察两组临床疗效,比较两组疼痛程度、基底动脉的血流速率（V_m）、动脉收缩期峰值流速（PSV）、血管阻力指数（RI）及血清内皮素-1（ET-1）、白细胞介素-1β（IL-1β）、一氧化氮（NO）水平。结果 治疗后,治疗组患者的总有效率（94.6%）明显高于对照组（82.1%）,差异有统计学意义（P＜0.05）。治疗后,两组患者数字疼痛强度量表（NRS）评分较治疗前显著降低（P＜0.05）;治疗组的NRS评分明显低于对照组（P＜0.05）。治疗后,两组的基底动脉V_m、PSV高于治疗前,RI低于治疗前（P＜0.05）;治疗后治疗组的基底动脉V_m、PSV比对照组高,RI比对照组低（P＜0.05）。治疗后,两组的血清ET-1、IL-1β、NO水平明显降低（P＜0.05）;治疗组的ET-1、IL-1β、NO水平比对照组低（P＜0.05）。结论 痹祺胶囊联合盐酸替扎尼定片可提高椎动脉型颈椎病的疗效,能够降低疼痛程度,改善血流动力学水平,调节血清ET-1、IL-1β、NO水平,安全性良好。     

正清风痛宁缓释片联合普瑞巴林治疗带状疱疹后遗神经痛的临床研究

目的 探讨正清风痛宁缓释片联合普瑞巴林治疗带状疱疹后遗神经痛的临床效果。方法 选取2019年1月—2020年12月河南科技大学第一附属医院收治的130例带状疱疹后遗神经痛患者,按随机数字表法分成对照组和治疗组,每组各65例。对照组口服普瑞巴林胶囊,起始剂量75 mg/次,2次/d,连用1周后增至150 mg/次,2次/d。治疗组在对照组基础上口服正清风痛宁缓释片,2片/次,2次/d。连续治疗4周后评价两组疗效。比较治疗前后两组疼痛视觉模拟量表（VAS）评分、失眠严重程度指数（ISI）总分、36项健康调查简表（SF-36）总分及血清白细胞介素（IL）-17、C反应蛋白（CRP）、前列腺素E₂（PGE₂）水平。结果 治疗后,治疗组总有效率为95.4%,显著高于对照组的84.6%（P＜0.05）。治疗后,治疗组止痛起效时间和疼痛缓解时间均较对照组显著缩短（P＜0.05）。治疗后,两组疼痛VAS评分、ISI总分均显著低于治疗前,SF-36总分均显著高于治疗前（P＜0.05）;且治疗后,治疗组疼痛VAS评分、ISI总分和SF-36总分改善均显著优于对照组（P＜0.05）。治疗后,两组血清IL-17、CRP和PGE₂水平均显著下降（P＜0.05）;且治疗后,治疗组血清IL-17、CRP和PGE₂水平均显著低于对照组（P＜0.05）。结论 正清风痛宁缓释片联合普瑞巴林对带状疱疹后遗神经痛患者具有确切的临床疗效,能安全有效地缓解患者疼痛、改善睡眠与生活质量,并可进一步抑制血清IL-17、CRP和PGE₂水平。     

骨疏康颗粒联合雷洛昔芬治疗绝经后骨质疏松症的临床研究

目的 探讨骨疏康颗粒联合盐酸雷洛昔芬片治疗绝经后骨质疏松症的临床疗效。方法 选取2021年1月—2022年12月在漯河市郾城区中医院就诊的120例骨质疏松症患者,按照随机数字表法将120例患者分为对照组和治疗组,每组各60例。对照组患者口服盐酸雷洛昔芬片,1片/次,1次/d。治疗组患者在对照组治疗的基础上餐后温水冲服骨疏康颗粒,1袋/次,3次/d。两组患者连续治疗3个月。观察两组的临床疗效,比较两组自觉疼痛程度、股骨近端、桡尺骨的骨密度和血清骨钙素（BGP）、Ⅰ型胶原C末端肽（CTX-1）、Ⅰ型前胶原氨基末端肽（PINP）、转化生长因子-β₁（TGF-β₁）、白细胞介素-6（IL-6）、胰岛素样生长因子1（IGF-1）水平。结果 治疗后,治疗组患者的总有效率95.00%比对照组的83.33%更高（P＜0.05）。治疗后,两组数字疼痛强度量表（NRS）评分明显降低（P＜0.05）,且治疗组患者NRS评分较对照组更低（P＜0.05）。治疗后,治疗组股骨近端、桡尺骨的骨密度明显高于治疗前（P＜0.05）,且治疗组股骨近端、桡尺骨的骨密度明显高于对照组（P＜0.05）。治疗后,两组的血清BGP、CTX-1水平低于治疗前,血清PINP水平高于治疗前（P＜0.05）;治疗组的血清BGP、CTX-1水平低于对照组,血清PINP水平高于对照组（P＜0.05）。治疗后,两组的血清TGF-β₁、IL-6水平低于治疗前,血清IGF-1水平高于治疗前（P＜0.05）;治疗后,治疗组的血清TGF-β₁、IL-6水平低于对照组,血清IGF-1水平高于对照组,差异有统计学意义（P＜0.05）。结论 骨疏康颗粒联合盐酸雷洛昔芬片可提高骨质疏松症的疗效,有助于降低患者疼痛程度,提高骨密度,改善骨代谢水平,且安全性良好。     

蠲痹抗生丸联合美洛昔康治疗膝骨关节炎的临床研究

目的 探讨蠲痹抗生丸联合美洛昔康治疗膝骨关节炎的临床疗效。方法 选择2019年3月—2021年3月平煤神马医疗集团总医院接诊的78例骨关节炎患者,随机分为对照组和治疗组,每组各39例。对照组口服美洛昔康片,1片/次,1次/d。在对照组基础上,治疗组口服蠲痹抗生丸,2丸/次,2次d。两组患者治疗7周为1个疗程。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,视觉模拟评分法（VAS）和西大略湖和麦克马斯特骨性关节炎指数（WOMAC）评分,血清因子白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和转移生长因子-β（TGF-β）水平,及不良反应情况。结果 治疗后,对照组总有效率为76.92%,显著低于治疗组的97.44%（P＜0.05）。治疗后,治疗组关节肿胀、关节活动受限、关节晨僵、关节疼痛缓解时间明显早于对照组（P＜0.05）。治疗后,两组患者VAS评分、WOMAC评分比治疗前均明显下降（P＜0.05）,且治疗组评分均显著低于对照组（P＜0.05）。治疗后,两组患者血清因子IL-1、IL-6、TNF-α水平均明显降低,而TGF-β明显升高（P＜0.05）,且治疗组各血清因子水平明显好于对照组（P＜0.05）。治疗组患者不良反应发生率为7.69%,明显低于对照组的15.38%（P＜0.05）。结论 蠲痹抗生丸联合美洛昔康治疗膝骨关节炎,症状改善明显,局部炎症反应明显降低,且药物安全有效。     

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.     

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.     

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.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.