A meta-analysis for Lianhua Qingwen on the treatment of Coronavirus disease 2019 (COVID-19)

BackgroundTraditional Chinese medicine (TCM) has been proven to played a great important role on the treatment of COVID-19. As one of the drugs recommended in Chinese guidelines, Lianhua Qingwen Granules or Capsules (LQ) are widely used.This systematic review and meta-analysis amis to evaluate the clinical efficacy of LQ on the treatment of COVID-19.MethodsSeven databases (PubMed, EMBASE, CENTRAL, CNKI, VIP, CBM and Wanfang) were searched to include all appropriate clinical trials that explore the efficacy of LQ on the treatment of COVID-19.ResultA total of 3 trials including 245 COVID-19 patients were eventually enrolled.Compared with the control group,the LQ group showed great significant difference on reducing the rate of clinical change to severe or critical condition[RR = 0.38, 95 %CI (0.17,0.85), P < 0.05]and the fever time (SMD =-0.57,95 %CI (-0.96,-0.17), P<0.05),as well as the significant improvement on the disappearance rate of the clinical symptoms: fever [RR = 1.36,95 %CI (1.14,1.61), P < 0.05],cough[RR = 1.99,95 %CI (1.39,2.86), P < 0.05],fatigue[RR = 1.52,95 %CI (1.15,2.01), P < 0.05] and anhelation [RR = 4.18,95 %CI (1.99,8.81), P < 0.05], but no significance on expectoration[RR = 2.46,95 %CI (0.81,7.51), P < 0.05].ConclusionThe clinical application of LQ on the treatment of COVID-19 has significant efficacy in improving clinical symptoms and reducing the rate of clinical change to severe or critical condition. Nevertheless, due to the limited quantity and quality of the included studies, more and higher quality trials with more observational indicators are expected to be published.     

中医学应对疫病的历史回顾与思考

概要回顾中医学关于外感热病诊治规律的相关记载,总结其对外感热病中具有传染性特点的疫病病因、病机、传变及治疗的认识;结合新型冠状病毒肺炎的发病时间及主要临床表现,提出其属中医学“瘟疫”范畴,病位在肺,病因为感受“冬温之毒”,从口鼻而入,侵袭肺络;结合各地诊疗方案提出的证候特点及用药规律研究,指出疫毒袭肺、邪热壅肺、毒热闭肺为其核心病机;分析中药连花清瘟理论组方特点及相关临床与实验研究结果,佐证其在应对新型冠状病毒肺炎疫情中的临床价值。     

连花清瘟联合西医治疗新型冠状病毒肺炎临床疗效的Meta分析

目的系统评价连花清瘟治疗新型冠状病毒肺炎(coronavirusdisease,COVID-19)的疗效情况,为COVID-19临床治疗提供依据。方法计算机检索中国知网、万方、维普、CBM、PubMed及Cochrane Library等数据库,检索时间截至2020年5月27日。采用Cochrane协作网偏倚风险工具对纳入研究进行风险评估及质量评价,Stata 15软件进行Meta分析,Begg’s检验分析发表偏倚。结果最终纳入7项临床疗效研究,包括665例COVID-19患者。Meta分析结果显示,与西医单独治疗相比,连花清瘟联合西医治疗可明显改善COVID-19患者的主要临床症状有效率[RR=1.24,95%CI(1.12,1.38),P0.05],CT好转情况[RR=1.14, 95%CI (1.02, 1.28),P0.05]及降低临床转重型比例[RR=0.48,95%CI(0.31,0.72),P0.05];此外,连花清瘟联合治疗可有效缩短COVID-19患者的发热持续时间[SMD=-0.87,95%CI(-1.22,-0.52),P0.05]、临床症状消失时间[SMD=-1.19,95%CI(-1.56,-0.82),P0.05]及住院时间[SMD=-0.61,95%CI(-0.91,-0.30),P0.05]。结论连花清瘟作为辅助治疗可有效改善COVID-19患者的临床症状及CT好转情况。     

连花清瘟胶囊治疗流行性感冒的有效性及安全性的系统评价

系统评价连花清瘟胶囊治疗流行性感冒的有效性及安全性。计算机检索中国知网(CNKI),万方数字化期刊全文数据库(WANFANG DATA),维普中文期刊数据库(VIP),Pub Med以及the Cochrane library,检索时限均为建库至2017年2月。收集连花清瘟胶囊治疗流感的随机对照试验,2位研究者独立进行文献筛选和资料提取工作并进行交叉核对,如遇分歧讨论解决。运用Revman5.3进行Meta分析。共纳入10个研究,计1 525例患者。Meta分析结果显示:与奥司他韦相比,连花清瘟胶囊在缓解流感症状方面疗效优于奥司他韦,其中头痛消失时间[SMD=-0.25,95%CI为(-0.48,-0.01)]、咽痛消失时间[SMD=-0.53,95%CI(-0.72,-0.34)]、咳嗽消失时间[SMD=-0.39,95%CI(-0.57,-0.21)]、周身酸痛消失时间[SMD=-0.49,95%CI(-0.78,-0.21)]、乏力消失时间[SMD=-0.56,95%CI(-0.82,-0.29)]、退热时间[SMD=-3.47,95%CI(-6.27,-0.67)]。除鼻塞和病毒核酸转阴时间外,2组差异均具有统计学意义。与利巴韦林相比,在临床疗效方面,连花清瘟胶囊优于利巴韦林[RR=1.53,95%CI(1.24,1.90)],2组差异具有统计学意义。与氨咖黄敏胶囊比较,连花清瘟胶囊体温疗效优于对照组[RR=1.37,95%CI(1.19,1.57)]。相比较奥司他韦、利巴韦林、氨咖黄敏胶囊,连花清瘟胶囊治疗流行性感冒具有一定的疗效,且安全性较高;但由于临床研究质量不高,上述结论有待高质量临床试验进一步验证。     

连花清瘟颗粒辅助治疗小儿肺炎支原体肺炎的有效性的Meta分析和系统综述

目的 系统评价连花清瘟颗粒辅助西医治疗小儿肺炎支原体肺炎的临床疗效。方法 通过检索Pubmed、Embase、万方数据库、维普数据库、中国知网数据库和中国生物医学数据库搜集连花清瘟颗粒辅助常规西医疗法治疗小儿肺炎的随机对照试验,检索时限均为建库时间到2020年3月止。结局指标包括临床总有效率、症状改善时间及住院时间等。通过R 3.6.1进行效应值合并。结果 最终纳入参考文献7篇,共837例患者,试验组422例,对照组415例。结果显示试验组临床总有效率高于对照组(RR=1.10, 95%CI[1.02,1.18], P=0.011),退热时间(MD =1.73, 95%CI[2.09,1.37], P<0.001)、咳嗽持续时间(MD =-2.93, 95%CI[-3.56,-2.26], P<0.001)、啰音持续时间(MD =-2.82, 95%CI[-3.51,-2.14], P<0.001)及住院时间(MD=-2.92, 95%CI[-3.19,-2.66], P<0.001)均显著低于对照组。 结论 连花清瘟颗粒辅助西医治疗小儿肺炎支原体肺炎可提高临床治疗有效率,缩短退热时间、咳嗽时间、啰音持续时间及住院时间,加快肺炎患者的康复速度。本研究获得证据级别不高,仍需要更多高质量、多中心、严格设计的临床随机对照试验来验证结论。     

连花清瘟辅助治疗成人肺炎有效性和安全性的Meta分析与系统综述

系统评价连花清瘟治疗成人肺炎的有效性和安全性。通过检索PubMed、EMbase、万方数据库(Wanfang)、维普数据库(VIP)、中国知网数据库(CNKI)收集连花清瘟辅助常规西医疗法治疗肺炎的随机对照试验,检索时限均从建库至2020年3月,由2位研究者独立进行文献筛选和资料提取工作并进行交叉核对,如遇分歧通过第3位研究者仲裁解决。结局指标包括临床总有效率、症状改善时间与不良反应/事件发生率等。采用R 3.6.1进行Meta分析,RevMan 5.3进行质量评价。最终纳入22项研究,共2 007例患者,其中试验组1 017例,对照组990例。Meta分析结果显示试验组临床总有效率高于对照组(RR=1.11, 95%CI[1.08, 1.15],P<0.001),退热时间(MD=-1.81, 95%CI[-2.42,-1.21],P<0.001)、咳嗽持续时间(MD=-2.32, 95%CI[-2.89,-1.76],P<0.001)、啰音持续时间(MD=-2.19, 95%CI[-2.74,-1.63],P<0.001)、影像学转归时间(MD=-2.17, 95%CI[-2.76,-1.58],P<0.001)及治疗后CRP指标(MD=-4.07, 95%CI[-6.39,-1.75],P<0.001)均显著低于对照组,但暂不能证明试验组安全性优于对照组(RR=0.84, 95%CI[0.57, 1.24],P=0.382)。结果表明连花清瘟辅助常规西医疗法治疗肺炎可提高临床总有效率,缩短退热时间、咳嗽时间、啰音持续时间及影像学转归时间,改善CRP指标,加快肺炎患者的康复速度。然而该研究所纳入的文献质量偏低,所得结论仍需要更多高质量、多中心、严格设计的临床随机对照试验来进一步证实。     

HS-SPME-GC/MS法分析连花清瘟胶囊制剂原料中的挥发性成分

[目的]分析连花清瘟胶囊制剂原料中的挥发性成分。[方法]采用顶空固相微萃取法(HS-SPME)萃取连花清瘟胶囊制剂原料中的挥发性成分,通过气相色谱-质谱法(GC/MS)对其中所含挥发性成分进行分析,经NIST05质谱数据库自动检索对未知化学成分进行准确定性,并采用峰面积归一化法计算各个化学成分的相对含量。[结果]从连花清瘟胶囊制剂原料的挥发性成分中共鉴定出53种化合物,占总挥发性成分的98.30%,其中l-menthol含量最高,其相对含量为94.84%,其他含量较高的挥发性成分为patchouli alcohol(1.101%)、α-bulnesene(0.398%)、α-gurjunene(0.256%)、α-guainene(0.210%)、α-patchoulene(0.171%)和β-patchoulene(0.111%)。[结论]HS-SPME-GC/MS法可以简单、快速、准确的分析连花清瘟胶囊制剂原料中的挥发性化学成分。     

清咳平喘颗粒联合沙美特罗替卡松治疗热伤肺络型咳嗽变异性哮喘的临床研究

目的 观察清咳平喘颗粒联合沙美特罗替卡松吸入粉雾剂治疗热伤肺络型咳嗽变异性哮喘的临床疗效。方法 选取2020年3月—2021年3月在哈尔滨市中医医院呼吸科门诊就诊的100例热伤肺络型咳嗽变异性哮喘患者，采用随机数字表法将所有患者分为对照组和治疗组，每组各50例。对照组患者给予沙美特罗替卡松吸入粉雾剂，1吸（泡）/次，2次/d。治疗组在对照组的基础上开水冲服清咳平喘颗粒，10 g/次，3次/d。两组患者均连续治疗4周。观察两组患者临床疗效，比较两组患者的中医证候积分、肺功能指标和血清免疫功能指标水平。结果 治疗后，治疗组患者的总有效率为90.00%，明显高于对照组的总有效率80.00%，差异有统计学意义（P<0.05）。治疗后，两组患者咳嗽、咳痰、喘息、哮鸣音评分均显著降低（P<0.05），且治疗后治疗组患者咳嗽、咳痰、喘息、哮鸣音评分明显低于对照组，差异有统计学意义（P<0.05）。治疗后，两组患者第1秒用力呼气容积（FEV_l）、最大呼气流速（PEF）、FEV₁/FVC均显著升高（P<0.05），且治疗组FEV_l、PEF、FEV₁/FVC显著高于对照组，差异有统计学意义（P<0.05）。治疗后，两组患者血清嗜酸性粒细胞（EOS）、免疫球蛋白E（IgE）水平均显著降低（P<0.05），且治疗组的血清EOS、IgE水平均低于对照组，差异具有统计学意义（P<0.05）。结论 清咳平喘颗粒联合沙美特罗替卡松吸入粉雾剂治疗热伤肺络型咳嗽变异性哮喘具有较好的临床疗效，可缓解患者临床症状，改善肺功能指标，有效恢复患者EOS、IgE至正常水平，具有良好的临床安全性。     

Effects of Lianhua Qingwen on Pulmonary Oxidative Lesions Induced by Fine Particulates (PM2.5) in Rats

Objective To investigate the antagonistic effects of different doses of Lianhua Qingwen on pulmonary injury induced by fine particulates PM2.5 in rats.
Methods Fine particulates suspended in the environment were collected. Forty-eight healthy adult wistar rats were randomly divided into 6 groups with 8 rats in each group. Four groups of rats were exposed to PM2.5 by intratracheally dripping suspensions of fine particulates PM2.5 (7.5 mg/kg)as dust-exposed model rats. Among them 24 rats in three groups received Lianhua Qingwen treatment (crude drug) at a dose of 2 g/kg, 4 g/kg, 8 g/kg per day for 3 daysbefore dust exposure and were defined as low-dose, middle-dose and high-dose Lianhua Qingwen treatment groups respectively. The other dust-exposed model rats without treatment were assigned as PM2.5 control group. The un-exposed rats were set as saline control group (1.5 ml/kg saline) and blank control group. All rats were killed after 24 hours of the exposure. Lung tissue, serum and bronchoalveolar lavage fluid (BALF) were collected. The levels of malonaldehyde (MDA), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) in blood serum and BALF, and superoxide dismutase (SOD) in blood surum were measured using fluorescent quantitation PCR; Expression of NF-E2-related factor 2(NRF-2), heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO1) in lung tissues were measured using Western blot. Pathological changes of lung tissues in each group were also examined.
Results Pathology revealed thickened alveolar septum, congestion of capillary, interstitial edema and infiltration of lymphocyte and neutrophil surrounding bronchiole in the PM2.5 control group, which were significantly relieved in the Lianhua Qingwen treatment groups. Compared to the blank and saline control groups, the PM2.5 control group had significantly higher levels of LDH and MDA (p<0.01) and lower level of GSH-PS (p<0.01) in BALF, significantly higher levels of LDH and MDA (p<0.05) and lower level of GSH-PS (p<0.05) in rat serum. The levels of MDA in blood serum and BALF were significantly lower in each treatment group than that in PM2.5 control group (allP<0.05). In both middle-dose and high-dose treatment group the measurements of LDH in serum and BALF as well as GSH-PX in serum were significant difference from those of PM2.5 control group (allP<0.05). Expressions of NRF-2, HO-1 and NQO1 in lung tissues were significantly different among middle-dose and high-dose treatment group compared with those in PM2.5 control group (allP<0.05).
Conclusion Fine particulates PM2.5 in environment may induce pulmonary oxidative lesions in rats. Middle-dose and high-dose Lianhua Qingwen has antagonist effece on the injuries induced by fine particulates.     

连花清瘟胶囊联合利巴韦林雾化吸入治疗小儿呼吸道合胞病毒感染的疗效观察

目的:观察连花清瘟胶囊联合利巴韦林雾化吸入治疗小儿呼吸道合胞病毒(RAV)感染的临床疗效。方法:选取2016年1月至2016年10月重庆市九龙坡区人民医院收治的呼吸道合胞病毒感染患儿106例作为研究对象,随机分为观察组和对照组,每组53例。对照组患儿给予利巴韦林气雾剂吸入治疗,观察组患儿在对照组基础上口服连花清瘟胶囊,7d为1个疗程。观察2组患儿退热时间,鼻塞、流涕、咳嗽等症状消失时间,并进行疗效判定。治疗前后,采用电化学发光免疫法检测患儿血清白细胞介素-4(IL-4)、白细胞介素-10(IL-10)、白细胞介素-12(IL-12)和干扰素-γ(IFN-γ)的水平。结果:观察组患儿的临床疗效显著优于对照组(Z=2.253,P0.05)。观察组患儿退热时间,鼻塞、流涕、咳嗽等症状消失时间显著短于对照组(P0.05)。治疗后,2组患儿血清IL-12和IFN-γ水平均较治疗前升高,且观察组高于对照组(P0.05);血清IL-4和IL-10水平均较治疗前降低,且观察组低于对照组(P0.05)。结论:连花清瘟胶囊联合利巴韦林雾化吸入治疗小儿呼吸道合胞病毒感染的疗效确切,在退热和改善鼻塞、流涕、咳嗽等症状方面具有明显优势,且能有效纠正患儿Th1/Th2免疫应答失衡。