丙酸倍氯米松对比布地奈德雾化吸入治疗儿童哮喘急性发作的Meta-分析

目的 系统评价丙酸倍氯米松对比布地奈德雾化吸入治疗儿童哮喘急性发作的临床疗效和安全性。方法 计算机检索PubMed、EMbase、The Cochrane Library、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和维普中文期刊全文数据库（VIP）和万方数据库,检索时限均为2000年1月-2019年12月,搜集丙酸倍氯米松联用特布他林（试验组）对比布地奈德联用特布他林（对照组）雾化吸入治疗儿童哮喘急性发作的随机对照研究,对符合纳入标准的临床研究进行资料提取和质量评价,采用RevMan 5.3软件对纳入文献进行质量评价和Meta-分析。结果 共纳入11篇文献（3篇英文文献和8篇中文文献）,1 227例患儿。Meta-分析结果显示：试验组临床有效率[RR=0.98,95%CI=0.92~1.04]、哮喘缓解率[RR=0.97,95%CI=0.92~1.01]、临床症状评分[SMD=0.09,95%CI=-0.06~0.24]、咳嗽消失时间[SMD=0.02,95%CI=-0.32~0.36]、呼吸困难改善时间[SMD=-0.03,95%CI=-0.29~0.24]和肺部哮鸣音消失时间[SMD=0.15,95%CI=-0.11~0.41]、住院时间[SMD=0.04,95%CI=-0.09~0.17]、呼气流量峰值[SMD=-0.32,95%CI=-0.85~0.20]和不良反应发生率[RR=1.41,95%CI=0.74~2.69]与对照组比较均无显著性差异（P>0.05）。结论 现有证据显示,丙酸倍氯米松雾化吸入治疗儿童哮喘急性发作的临床疗效和安全性与布地奈德相当,值得临床推广。     

卡维地洛联用螺内酯治疗中国患者慢性心力衰竭的Meta-分析

目的 系统评价卡维地洛联合螺内酯治疗慢性心力衰竭的有效性和安全性。方法 计算机检索PubMed、Cochranelibrary、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普中文期刊全文数据库（VIP）和万方数据库,检索年限为2000年1月至2019年12月,对符合纳入排除标准的随机对照试验（RCT）,进行数据提取和偏倚风险评价,然后采用RevMan 5.3软件进行Meta-分析。结果 最终纳入15个RCTs,共1 594例患者。Meta-分析结果显示：卡维地洛联合螺内酯能显著提高临床有效率（RR=1.25,95% CI=1.18~1.32,P<0.01）、降低心率（SMD=-1.58,95% CI=-1.96~-1.21,P<0.01 ）、提高左心室射血分数（SMD=1.22,95% CI=1.04~1.44,P<0.01）和脑钠肽水平（SMD=- 0.79,95% CI=-0.92~-0.65,P<0.01）,未增加药物不良反应发生率（RR=1.36,95% CI=0.90~2.06,P=0.14）,按照对照组治疗方案不同进行亚组分析结果与上述一致。结论 卡维地洛联合螺内酯治疗慢性心力衰竭的临床疗效优于常规治疗或卡维地洛,而安全性相当。     

帕瑞昔布对比氟比洛芬酯术后镇痛的疗效与安全性的Meta-分析

目的 系统评价帕瑞昔布对比氟比洛芬酯用于术后镇痛的疗效和安全性。方法 计算机检索中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）、万方数据库、PubMed、Cochrane图书馆,收集帕瑞昔布对比氟比洛芬酯治疗术后疼痛随机对照试验（RCT）,检索时间从建库至2019年10月。提取资料并进行文献质量评价后,使用RevMan 5.3软件进行Meta-分析。结果 共纳入14篇RCTs,共984例患者,对照组采用氟比洛芬酯进行治疗,试验组采用帕瑞昔布进行治疗。Meta-分析结果显示：与氟比洛芬酯比较,帕瑞昔布显著降低术后6 h、12 h和24 h的疼痛评分（VAS）［SMD=-0.62、95% CI=-0.89～-0.35,SMD=-0.60、95% CI=-0.99～-0.20和SMD=-0.48、95% CI=-0.80～-0.15］,降低不良反应（ADR）发生率［RR=0.60、95% CI=0.46～0.78］,其中以降低头痛头晕发生率最显著［RR=0.55,95% CI=0.33～0.91］,2组比较差异均有统计学意义（P<0.05）;而对术后1 h、2 h和4 h的VAS评分,术后阿片用量,术后恶心呕吐发生率、皮肤瘙痒发生率、腹痛发生率和尿潴留发生率均无统计学差异。结论 帕瑞昔布用于术后镇痛疗效和安全性优于氟比洛芬酯。     

神经节苷脂联用纳洛酮治疗新生儿缺氧缺血性脑病的循证医学研究

目的 评价神经节苷脂联用纳洛酮治疗新生儿缺氧缺血性脑病（HIE）的有效性和安全性。方法 计算机检索PubMed、EMBASE、Cochrane图书馆、中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）、维普中文期刊全文数据库（VIP）和万方数据库（Wanfang Database）,检索时间均从建库至2019年3月,纳入有关神经节苷脂联用纳洛酮治疗HIE的随机对照试验（RCT）,采用RevMan 5.3软件进行统计学处理。结果 共纳入15篇RCTs,1 116例患儿。Meta-分析显示：与对照组比较,试验组的临床有效率显著提高（RR=1.25,95% CI=1.18～1.33,P<0.01）、NBNA评分显著改善（MD=4.24,95% CI=3.72～4.76,P<0.01）、意识恢复时间显著减少（MD=-2.13,95% CI=-2.54～-1.71,P<0.01）、反射恢复时间显著减少（MD=-2.14,95% CI=-3.31～-1.56,P<0.01）和肌张力恢复时间显著减少（MD=-2.46,95% CI=-3.99～-1.13,P<0.01）、随访后遗症发生率显著减少（RR=0.23,95% CI=0.11～0.46,P<0.01）;按照对照组干预措施不同采用亚组分析结果基本一致。结论 神经节苷脂联用纳洛酮治疗新生儿HIE科有效改善NBNA评分,缩短临床体征恢复时间,减少后遗症的发生。     

丹参川芎嗪注射液联合常规用药治疗慢性心力衰竭的Meta-分析

目的 评价丹参川芎嗪注射液联合常规用药治疗心力衰竭的疗效和安全性。方法 系统地检索Cochrane Library、Pubmed、Web of Science、Embase、万方数据库（Wanfang）、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（SinoMed）和维普中文期刊全文数据库（VIP）中丹参川芎嗪注射液联合常规用药治疗心力衰竭的随机对照研究（RCT）。检索时限从建库至2018年12月6日,提取资料,并使用Review Manager 5.3软件进行Meta-分析。结果 共纳入18项RCTs,共1 548例患者。Meta-分析结果显示：丹参川芎嗪注射液联合常规用药在临床疗效［OR=3.33,95% CI （2.39～4.63）, P<0.000 01］、提升射血分数［SMD=1.05, 95% CI （0.27～1.83）, P=0.009］、下调B型脑钠肽（BNP）水平［SMD=-1.22,95% CI（-2.03～-0.41）,P=0.003］、升高每搏排血量［SMD=1.28,95% CI（0.19～2.38）,P=0.02］和心脏指数［SMD=1.44,95% CI（0.50～2.38）,P=0.003］方面均优于常规用药组,未见明显不良反应。结论 丹参川芎嗪注射液联合常规用药治疗心力衰竭疗效优于常规用药,但由于纳入研究样本量较少、文献质量较低,其治疗心力衰竭的疗效需要更多高质量的临床研究加以证实。     

益生菌制剂治疗儿童手足口病临床疗效和安全性的Meta-分析

目的 系统评价益生菌制剂治疗儿童手足口病的临床疗效和安全性。方法 计算机检索PubMed、Cochrane Library、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和维普中文期刊全文数据库（VIP）和万方数据库,搜集益生菌制剂治疗儿童手足口病的随机对照试验（RCTs）,检索时限均为建库至2019年12月,采用RevMan 5.3软件进行Meta-分析。结果 共纳入16个RCTs,共1 605例患儿。Meta-分析结果显示,与常规治疗相比,联用益生菌制剂能显著提高临床有效率[RR=1.26,95% CI=（1.20,1.32）];缩短退热时间[MD=-0.76,95% CI=（-0.84,-0.36）]、疱疹结痂时间[MD=-1.23,95% CI=（-1.33,-1.13）]、口腔溃疡愈合时间[MD=-1.06,95% CI=（-1.36,-0.72）];减小二胺氧化酶水平[MD=-0.81,95% CI=（-0.96,-0.65）]、D-乳酸水平[MD=-2.40,95% CI=（-2.76,-2.03）]和内毒素水平[MD=-0.14,95% CI=（-0.15,-0.12）];降低TNF-α水平[MD=-0.87,95% CI=（-1.46,-0.28）]、CRP水平[MD=-0.35,95% CI=（-0.47,-0.24）]和IL-6水平[MD=-4.69,95% CI=（-7.09,-2.29）],组间比较差异均有统计学意义（P<0.01）。在不良反应发生率,两组的差异无统计学意义。结论 益生菌制剂能缩短儿童手足口病患者的临床体征改善时间、改善肠黏膜屏障功能、提高免疫功能和降低炎性因子水平,且安全性较好,值得临床推广。     

呋塞米联用小剂量多巴胺治疗利尿剂抵抗性心力衰竭中国患者的Meta-分析

目的 系统评价呋塞米联用小剂量多巴胺治疗中国利尿剂抵抗性心力衰竭的有效性和安全性。方法 检索PubMed、Embase、中国生物医学文献数据库（CBM）、中国学术期刊全文数据库（CNKI）、维普中文期刊全文数据库（VIP）和万方数据库,收集呋塞米联用小剂量多巴胺（观察组）对比单用呋塞米（对照组）对利尿剂抵抗性心力衰竭的随机对照研究（RCT）,检索时间从建库至2019年7月,提取资料并评价质量后,采用RevMan 5.3软件进行Meta-分析。结果 共纳入12篇RCTs,927例中国患者。Meta-分析结果显示观察组临床有效率（RR=1.44,95% CI=1.32~1.56）、左心室射血分数增加值（MD=8.05,95% CI=7.52~8.75）、24 h尿量体积（SMD=2.77,95% CI=1.93~3.62）、6 min步行距离（MD=38.97,95% CI=24.10~53.85）均大于对照组,差异有统计学意义（P<0.01）;血清肌酐水平（MD=-2.86,95% CI=-6.46~0.73）和药物不良反应发生率（MD=1.64,95% CI=0.59~4.57）与对照组比较无显著差异。结论 对于心力衰竭合并利尿剂抵抗的中国患者而言,小剂量多巴胺联用呋塞米改善患者心功能、尿潴留、活动耐受力和抑制肾功能不全等均优于单用呋塞米,且安全性较好。     

新生儿抗生素相关性腹泻危险因素的Meta-分析

目的 系统评价新生儿发生抗生素相关性腹泻（AAD）的危险因素,为临床提供循证医学证据。方法 检索PubMed、Embase、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普中文科技期刊数据库（VIP）和万方数据库等相关数据库,收集新生儿发生AAD危险因素的病例对照研究,检索时限为2000年1月-2018年5月,应用Rev Man 5.2软件进行Meta-分析。结果 共纳入13篇文献,涉及4 273例新生儿,其中AAD组915例,非AAD组3 358例。Meta-分析结果显示：低胎龄（SMD=-0.89,95%CI=-1.16~-0.61,P<0.01）,出生时体质量偏小（SMD=-0.79,95%CI=-0.98~-0.59,P<0.01）,日龄偏小（SMD=-1.08,95%CI=-1.20~-0.96,P<0.01）,抗生素种类（SMD=1.59,95%CI=1.24~1.94,P<0.01）,侵袭性操作（OR=2.06,95%CI=1.85~2.23,P<0.01）,住院天数（SMD=2.21,95%CI=1.86~2.56,P<0.01）和非纯母乳喂养（OR=0.47,95%CI=0.38~9.57,P<0.01）是新生儿发生AAD的危险因素,抗生素预防用药（OR=1.17,95%CI=0.94~1.46,P>0.05）与新生儿发生AAD无关。结论 低胎龄、出生时体质量偏小、日龄小、多种抗生素联合用药、住院时间过长、侵袭性操作和非纯母乳喂养是新生儿发生AAD的危险因素。     

早期应用替罗非班对急性ST段抬高型心肌梗死患者PCI术后冠脉血流及并发症影响的Meta-分析

目的 系统评价早期应用替罗非班对急性ST段抬高型心肌梗死（STEMI）经皮冠状动脉介入（PCI）术后冠脉血流及并发症影响。方法 检索PubMed、Embase、Cochrane图书馆、中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）和维普中文期刊全文数据库（VIP）和万方数据库关于STEMI患者急诊行PCI并早期应用替罗非班的临床对照研究（RCT）,检索年限均为建库起至2020年4月30日。试验组为PCI术前开始应用替罗非班,对照组为PCI术中或术后应用替罗非班,数据提取和质量评价,应用RevMan 5.3软件进行Meta-分析。结果 共纳入15项RCT,共计2 214例患者。Meta-分析结果显示,术前应用替罗非班组较术中或术后用药组,PCI术后TIMI血流分级为3级（RR=1.10,95%CI=1.06~1.15,P<0.01）和（RR=1.10,95%CI=1.03~1.17,P<0.01）、ST段下落幅度（SMD=0.44,95%CI=0.17~0.70,P=0.001）和（SMD=1.85,95%CI=1.53~2.17,P<0.01）、ST段回落率（RR=1.51,95%CI=1.20~1.89,P<0.01）和（RR=1.20,95%CI=1.05~1.39,P=0.01）均显著优于术中或术后用药;术前应用组提高左心室射血分数（LVEF%）（SMD=0.46,95%CI=0.13~0.79,P=0.007）和降低主要心血管不良事件（MACE）发生率（RR=0.53,95%CI=0.39~0.73,P<0.01）均优于术中用药组。术前应用组与术后应用组的LVEF%和MACE发生率比较均无显著性差异。术前应用组出血及并发症发生率与术中及术后应用组比较均无显著性差异。结论 与PCI术中及术后应用替罗非班相比,术前应用更能显著改善STEMI患者微循环障碍、增加心肌组织有效的再灌注、减少心肌梗死范围。     

地塞米松联合地佐辛超前镇痛对外科术后镇痛效果的Meta-分析

目的 系统评价地塞米松联合地佐辛超前镇痛用于外科术后镇痛效果和安全性,为临床应用提供循证医学证据。方法 计算机检索PubMed、Embase、中国生物医学文献数据库（CBM）、中国知网（CNKI）、维普数据库（VIP）和万方数据库,收集地塞米松联合地佐辛（试验组）和单用地佐辛（对照组）超前镇痛用于外科术后镇痛的随机对照研究,检索时限为从建库-2018年5月,提取有效数据后,应用RevMan 5.2软件进行Meta-分析。结果 共纳入13项研究,893例患者。Meta-分析结果显示：试验组术后的VAS评分在2 h （MD=-0.63,95%CI=-0.86~-0.41,P<0.01）、4 h （MD=-0.31,95%CI=-0.41~-0.21,P<0.01）、8 h （MD=-0.85,95%CI=-1.08~-0.62,P<0.01）、12 h （MD=-0.89,95%CI=-1.05~-0.72,P<0.01）、24 h （MD=-1.16,95%CI=-1.49~-0.82,P<0.01）均小于对照组;镇痛药追加率（RR=0.08,95%CI=0.02~0.32,P<0.01）小于对照组;患者镇静满意度（RR=1.18,95%CI=1.07~1.31,P<0.01）高于对照组;恶心、呕吐发生率（RR=0.41,95%CI=0.30~0.56,P<0.01）低于对照组。结论 地塞米松联合地佐辛具有良好的协同作用,可有效减轻术后疼痛,减少恶心呕吐发生,值得临床推广。     

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.