Efficacy, Safety and Mechanism of Jinzhen Oral Liquid in the Treatment of Acute Bronchitis in Children: A Randomized, Double-Blind, Multicenter Clinical Trial Protocol.

Background: Acute bronchitis (AB) is a common disease in pediatrics. Prolonged AB may develop into chronic bronchitis. Bronchitis caused by the influenza virus can lead to severe hypoxia or insufficient ventilation, causing great harm to patients and increasing the burden on children and society. Presently, there is no specific treatment for AB except symptomatic supportive treatment. It is urgent to find an effective treatment for AB. Jinzhen Oral Liquid (JZOL) has been found to have a broad spectrum of anti-inflammatory and antiviral effects in previous clinical and basic studies and has a good effect on AB in children. However, the large-sample, randomized, double-blind, head-to-head, evidence-based studies are lacking. The purpose of this protocol is to evaluate the efficacy, safety, and mechanism of JZOL in the treatment of AB in children. Methods: This is a randomized, double-blind, parallel-controlled multi-center clinical trial. The sample size is 500 participants in the intervention group and the control group respectively, with a total of 1000 participants. They will be recruited by 10 hospitals in China. The Intervention group takes JZOL and Ambroxol Hydrochloride and Clenbuterol Hydrochloride Oral Solution (AHCHOS) placebo, while the control group receives AHCHOS and JZOL placebo. The dosage of the two drugs varies according to age and weight. The medication lasts for 7 days. The disappearance time of cough is adopted as the primary outcome. Quality control will be carried out at every stage of data management and processing to ensure that all data are reliable and processed correctly. SAS is used for statistical analysis. Intention-to-treat analysis will be carried out in this trial. All statistical tests are conducted using a two-sided test, and p <0.05 would be considered statistically significant. Discussion: We hypothesized that children with AB could get good health benefits from JZOL. This study not only evaluates the clinical efficacy and safety of JZOL but also conducts metagenomics analysis and metabolomics analysis of feces and saliva of participants to study the mechanism of JZOL against AB. Therefore, this protocol evaluates the efficacy, safety, and mechanism of JZOL from a comprehensive perspective, so as to obtain a more solid evidence chain, which will enhance the credibility of the evidence. If successful, this study will provide a high-level evidence-based reference for the treatment of AB in children and future relevant studies.

Xuesaitong oral preparation as adjuvant therapy for treating acute cerebral infarction: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral infarction is the second leading cause of death and the third most common cause of disability. The use of anti-platelet aggregation drugs is prone to bleeding, liver and kidney damage, gastrointestinal reactions, and is not suitable for patients to take for a long time. Xuesaitong oral preparations (XSTOP), a traditional Chinese medicine formula, has shown therapeutic effect on treating cerebral infarction based on the clinical practice and pharmacological mechanism. AIM OF THE STUDY: The study aims to evaluate the effectiveness and safety of XSTOP combined with conventional treatment (CT) in treatment of acute cerebral infarction (ACI), and to provide the reliable evidence for clinical application. MATERIALS AND METHODS: We performed a literature search in Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, PubMed, EMBASE, Cochrane Library and Web of Science from their inceptions to August 2021. Systematic searches for randomized controlled trials (RCTs) of XSTOP in treatment of ACI. Odds ratio (OR) or mean difference (MD) with their 95% confidence interval was calculated between with and without XSTOP therapy. Cochrane risk of bias tool was used to evaluate the methodological quality of the included trials. RESULTS: Eight RCTs involving 827 patients were included in this meta-analysis. By comparing XSTOP plus conventional treatment with conventional treatment alone, the meta-analysis gave the following results: (1) Total effective rate (OR = 4.53, 95% CI[2.85, 7.19], P < 0.0001); (2) National Institutes of Health Stroke Scale (NIHSS) score (MD = -3.22, 95% CI[-4.52, -1.92], P＜0.00001); (3) Plasma viscosity (PV) (MD = -0.74, 95%CI [-0.96, -0.51], P＜0.00001), hole blood high-cut viscosity (HBV) (MD = -0.63, 95%CI [-0.73, -0.53], P = 0.84), whole blood low-cut viscosity (LBV) (MD = -0.37, 95%CI [-0.56, -0.19], P = 0.96), fibrinogen (FIB) (MD = -23.78, 95%CI [-28.57, -18.99], P = 1.00), hematocrit (Hct) (MD = -2.76, 95%CI [-3.16, -2.36], P = 0.96); (4) China Stroke Scale (CSS) score (MD = -6.53, 95% CI[-9.07, -3.99], P＜0.00001); (5) No significant adverse reactions were reported; (6) The evidence was downgraded to "very low" quality, according to GRADE system. CONCLUSION: XSTOP plus CT is conditional recommended to improve the total effective rate, NIHSS score, PV, CSS score, and no serious adverse reactions were noted. The GRADE assessment indicates that the overall certainty quality of evidence is very low. Further large-scale, well-designed and high-quality RCTs are needed to confirm the positive results. As all studies included were conducted in China. It is unclear if the findings of this meta-analysis could be generalized to other populations.

[Report standards for clinical comprehensive evaluation of Chinese patent medicine].

The clinical comprehensive evaluation of drugs is an important basis for the return of clinical value, decision-making of medical and health authorities, and allocation of medical resources. In July 2021, the National Health Commission issued the Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), which required the evaluation to be implemented from the six dimensions(safety, effectiveness, economy, innovation, suitability, and accessibility), and made detailed arrangements for the clinical comprehensive evaluation of drugs. As Chinese patent medicine differs from chemical medicines in terms of effective components and action modes, the clinical comprehensive evaluation of Chinese patent medicine should highlight the characteristics and advantages of traditional Chinese medicine(TCM) on the basis of general requirements of comprehensive clinical evaluation of drugs. At present, in the clinical comprehensive evaluation of Chinese patent medicine, unified report standards have not yet been generated, resulting in the uneven quality of existing reports. To standardize the clinical comprehensive evaluation report of Chinese patent medicine and improve its quality, the editorial team, based on the relevant policy documents of clinical comprehensive evaluation of drugs, formulated the clinical comprehensive evaluation report standards for Chinese patent medicine in combination with the previous practice and expert opinions. The report standards, containing seven sections with 15 items determined, focus on data source, evaluation content, evidence synthesis, quality control, and evaluation results supported with detailed interpretations to help researchers better understand and apply the report standards for clinical comprehensive evaluation of Chinese patent medicine, improve the report quality, and provide references for the decision-making by the national medical management authorities.

[Clinical comprehensive evaluation of Naoxintong Capsules in treatment of cerebral infarction with Qi deficiency and blood stasis syndrome and coronary heart disease angina pectoris].

Through investigating the current research on the effect of Naoxintong Capsules in the treatment of cerebral infarction with Qi deficiency and blood stasis syndrome and coronary heart disease angina pectoris, this study conducted a clinical comprehensive evaluation in "6+1" dimensions [safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine(TCM)], so as to highlight the advantages and clinical value of Naoxintong Capsules. By combining qualitative and quantitative methods, we used the multi-criteria decision analysis(MCDA) model to measure each dimension, and the results thereby were divided into four grades of A, B, C, and D in high-to-low order. Through literature review and evaluation, the adverse effects of Naoxintong Capsules are mainly caused by the gastrointestinal system. Since the safety risk is controllable based on current research, the safety evaluation is grade B. The effectiveness of Naoxintong Capsules combined with conventional western medicine in the treatment of cerebral infarction with Qi deficiency and blood stasis syndrome and coronary heart disease angina pectoris is evaluated as grade A, as compared with conventional therapy alone. The economy of Naoxintong Capsules, compared with Tongxinluo Capsules, is assessed as grade B. According to literature reports, Naoxintong Capsules exhibits outstanding clinical innovation in optimizing the current anti-platelet therapy strategy for patients with coronary heart disease after percutaneous coronary intervention(PCI), and the innovation is class A. Given the capsule formulation is convenient for storage and transportation, and its usage is easy for patients to grasp and accept, the suitability is grade B. The accessibility is grade A considering the price level, availability, and affordability, and the characteristics of TCM are evaluated as grade A from the perspectives of theoretical characteristics and human experience. The results of the comprehensive drug evaluation showed that the clinical value of Naoxintong Capsules is class A for treating cerebral infarction with Qi deficiency and blood stasis syndrome and coronary heart disease angina pectoris. According to the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs(trial 2021 version) issued by the National Health Commission, relevant policy results for basic clinical drug management can be formulated directly by procedure.

[Tabu search algorithm analysis on effect of Xingnaojing Injection in treatment of craniocerebral injury and complications in real world].

In this study, Tabu search algorithm was used to analyze the drug combination of Xingnaojing Injection in the treatment of brain injury and complications in the real world, and the clinical drug combination of Xingnaojing Injection in the treatment of brain injury and complications was selected and summarized. The combination of Xingnaojing Injection, Namefen and Citicoline were recommended in the treatment of brain injury and complications. For brain edema and nerve injury, Mannitol/Glycerol Fructose/Furosemide+Tetrahexose Monosialate Ganglioside Sodium should be recommended. For those with pulmonary infection, Xingnaojing Injection+Xiyanping+Ambroxol Hydrochloride+Tanreqing Injection should be recommended. For those with shock, Hydroxyethyl Starch+Dopamine Hydrochloride/Dobutamine Hydrochloride+Sodium Bicarbonate should be recommended. The combination reflected the characteristics of Chinese and Western medicine. The above medication regimen was only for clinicians' reference. The clinical application should be based on patients' specific conditions, clinical benefits and risks, as well as the incompatibility. On the basis of the findings, further studies can be carried out for prospective clinical efficacy evaluation and safety evaluation for a specific subgroup module.

[Effect of Xingnaojing Injection in treatment of cerebral hemorrhage based on Tabu search algorithm:a real world study].

In this study, Tabu search algorithm was used to analyze the effect of Xingnaojing Injection in the treatment of cerebral hemorrhage in the real world. Through the analysis of the results, the therapies based on the pathogeny of cerebral hemorrhage were screened out: Xingnaojing Injection+hemostatic drugs for promoting blood circulation and removing stasis. Cerebral hemorrhage complicated with brain edema: combined with mannitol or mannitol+aescin. The patients with relevant complications in the acute stage of cerebral hemorrhage could select according to the indications: ①Aminocycline+Oxiracetam+Piperacillin Sodium Sulbactam Sodium+Sodium Lactate Ringer; ②Aminocycline+Oxiracetam+Nifedipine+Captopril+Metoclopramide+Cimetidine; ③Insulin+Pantoprazole+So-dium Nitroprusside. The combined therapies for patients of the stable stage with complicating diseases could select according to the indications: ① Monosialotetrahexosyl Ganglioside Sodium+Deproteinized Calf Blood Serum+Nitroglycerin+Compound Potassium Dihydrogn Phosphate; ② Edaravone+Gangliosides+Captopril+Levofloxacin+Tanreqing Injection+Aminophylline. The analysis of subgroup module of drugs for promoting blood circulation and removing blood stasis suggested that the safety of traditional Chinese medicine should be paid attention to in the treatment of cerebral hemorrhage. This study was based on the data of the real world, but with some problems, such as lack of data and confounding factors. The summarized medication plan is only for the reference of clinicians. The clinical application shall be based on the specific situation of patients and the clinical benefits and risks, and pay attention to the incompatibility.

[Clinical application of Xingnaojing Injection in treatment of 11 674 cases of cerebral infarction: a real world study].

To analyzed the actual clinical application of Xingnaojing Injection in treating cerebral infarction in the real world, selected HIS(hospital information system) database of inpatients in 39 hospitals across the country, and conducted descriptive analysis and association rule analysis on the information of 11 674 patients with cerebral infarction using Xingnaojing Injection. The results showed that the average age of the patients was 69.69 years. TCM syndrome of phlegm stasis and collaterals stagnation was the most(37.56%), followed by wind-phlegm obstruction of collaterals(19.01%). Virtual syndrome accounted for 21.06%. Intravenous drip was the most important route of administration(96.50%). Iv infusion single dose of 10-20 mL(52.44%), other off-label doses accounted for a larger proportion(47.56%). Continuous use of the drug within 3 days(55.45%), 15-28 days accounted for 6.96%, >28 days accounted for 0.89%. The top 10 Western drugs used in combination mainly include antihypertensive drugs, acid-suppressing drugs to protect stomach, drugs to improve brain circulation, drugs to protect brain nerves and drugs to fight infection. The top 10 of Chinese patent medicines are mainly activating blood circulation and removing stasis, clearing heat and clearing the surface, etc. According to the analysis of association rules, three types of clinical drug use modes for the combination of Chinese and Western medicine were obtained, mainly including the first type: Xingnaojing Injection+nifedipine(nifedipine, nifedipyridine, Lixinping)+levoflo-xacin+Huayu Tongmai agent. The second category: Xingnaojing Injection+omeprazole+edaravone+Huayu Tongmai agent; The third category: Xingnaojing Injection+ganglioside and ganglioside derivatives+edaravone+Huayu Tongmai agent. The results show that Xingnaojing Injection is not a standard drug in the treatment of cerebral infarction. At the same time, the combined use of drugs is mainly recommended by the guidelines and conventional treatment drugs, reflecting the clinical application of integrated traditional Chinese and Western medicine.