Toxicological safety evaluation of Qiguiyin formula in rats at the treatment phase and recovery phase.

ETHNOPHARMACOLOGICAL RELEVANCE: Qiguiyin, a hospital preparation of traditional Chinese medicinal formula, is a combination of Astragalus hamosus L., Angelica sinensis (Oliv.) Diels, Lonicera sempervirens L., Artemisia annua L., and Polygonum cuspidatum Siebold & Zucc. at a ratio of 12:3:3:2:2. It has been used to treat severe pneumonia caused by drug-resistant bacteria in clinical practice, while studies on its toxicological safety are rare in the literature. AIM OF THE STUDY: In the present study, we aimed to develop a new application of Qiguiyin according to the general research routine of traditional Chinese medicine (TCM), and the toxicological effects of the Qiguiyin formula at the treatment phase and recovery phase were also evaluated. MATERIALS AND METHODS: The rats were administered with the Qiguiyin formula at 10, 30, and 50 times of the corresponding dosage in humans for 13 consecutive weeks. During 13 weeks of the treatment phase and 4 weeks of the recovery phase, the general signs of toxicity and mortality were monitored daily, and the body weight and food consumption were determined every week. Moreover, the hematology, biochemistry, urine, organ weights, and histopathology were analyzed, and the reproductive system was examined at the end of the treatment phase or recovery phase, respectively. RESULTS: The toxicological results showed no deaths and no changes in general behavior. Moreover, there was no clinically significant effect of the Qiguiyin formula on body weight or food consumption in rats. Although the Qiguiyin formula resulted in some changes in hematological, biochemical, and urinary indexes, these alterations were not related to the treatment because they remained within normal ranges throughout the 17 weeks. Besides, the main organs were not affected basically. All the above-mentioned results showed no gender difference. Furthermore, a clinical dosage of 50 times of the Qiguiyin formula did not affect the reproductive system of female rats, while it could lead to atrophied seminiferous tubules in two out of 10 male rats. However, such abnormality could not be found at the end of the recovery phase. CONCLUSIONS: Overall, the Qiguiyin formula could be used safely. The administration at doses of less than 1000 g/day for 13 weeks showed no distinct toxicity or side effects.

[Expert consensus on Antiviral Oral Liquid in treatment of influenza in clinical practice].

Antiviral Oral Liquid is modified on the basis of Baihu Decoction in Treatise on Febrility Diseases by ZHANG Zhongjing and Qingwen Baidu Yin in Qing Dynasty, with effects in clearing toxic heat, repelling dampness and cooling blood. It is widely used in clinical treatment of common colds, influenza and upper respiratory tract infection, mumps, viral conjunctivitis and hand-foot-mouth disease, with a good clinical efficacy and safety. Based on a questionnaire survey of clinicians and a systematic review of study literatures on Antiviral Oral Liquid, the international clinical practice guidelines development method was adopted to analyze the optimal available evidences and expert experiences in the "evidence-based, consensus-based and experience-based" principles. The consensus was jointly reached by more than 30 multidisciplinary experts nationwide, including clinical experts of traditional Chinese and Western medicine in the field of respiratory diseases and infectious diseases, and methodological experts. In the study, literatures were retrieved based on clinical problems in the clinical survey as well as PICO clinical problems. The GRADE system was used for the classification and evaluation of evidence, and fully combined with clinical expert experience, so as to reach expert consensus by the nominal grouping method. This expert consensus recommended or suggested indications, usage and dosage, course of treatment, intervention time for treatment, and the safety and precautions of Antiviral Oral Liquid for treatment of influenza, and can provide reference for the rational use of this drug in clinical practice.

Proteomic Analysis of Proteins Associated with Inhibition of Pseudomonas aeruginosa Resistance to Imipenem Mediated by the Chinese Herbal Medicine Qi Gui Yin.

Objective: Antibiotic resistance of Pseudomonas aeruginosa (PA) that lowers the effectiveness of current treatments for pneumonia is a growing problem. Qi Gui Yin is a Chinese herbal medicine that has been used to improve the efficacy of antibiotic therapy against antibiotic-resistant bacteria. This study aimed to elucidate the mechanism by which Qi Gui Yin inhibits antibiotic resistance of PA. Methods: Active components of Qi Gui Yin were analyzed by chromatography. Isobaric Tags for Relative and Absolute Quantification (iTRAQ) technology was used to compare protein expression profiles of PA strains cultured in serum from rats that were and were not treated with Qi Gui Yin. Quantitative polymerase chain reaction (qPCR) analysis was performed to detect gene expression changes. Results: Proteomic analysis identified 76 differentially expressed proteins between PA strains cultured in serum from rats that were or were not treated with Qi Gui Yin. Bioinformatics analysis revealed that the largest number of differentially expressed proteins were associated with resistance mechanisms such as quorum sensing, bacterial biofilm formation, and active pumping. In addition, qPCR analysis confirmed that downregulation of iscU and arcA gene expression was associated with Qi Gui Yin treatment. Conclusions: Serum from Qi Gui Yin-treated rats could effectively inhibit antibiotic resistance of PA. Chlorogenic acid and astragaloside IV are the main components of Qi Gui Yin, which may mediate inhibition of antibiotic resistance. Our findings provide new insights into strategies involving Chinese herbal medicine that can be used to treat pneumonia caused by antibiotic-resistant bacteria.

Protocol for developing clinical practice guidelines on traditional Chinese medicine therapy for influenza.

BACKGROUND: Influenza is the most prevalent acute respiratory infection worldwide. There are many different traditional Chinese medicine (TCM) therapies, which could reduce the duration of fever during influenza. However, there are no clinical practice guidelines (CPG) involving TCM therapies for influenza. Therefore, the present study aimed to establish a protocol for the development of CPG on TCM therapy for influenza. METHODS: The CPG will be developed according to the Institute of Medicine, the Appraisal of Guidelines for Research and Evaluation II, and the World Health Organization (WHO) guideline handbook, and will provide recommendations based on systematic reviews. We have established a guideline working group (including a guideline steering group, a guideline development group, a guideline secretary group, and a system evaluation group), and will formulate clinical questions based on the population, intervention, comparison, and outcomes format. The recommendations will be formed via evidence search, syntheses, and the nominal group technique method. We will also consider patients' values or preferences, peer review results, and declarations of interest in the CPG. The CPG is registered on the International Practice Guidelines Registry Platform (registration no. IPGRP-2019CN044). RESULTS: The protocol will provide a roadmap to develop an evidence-based CPG for influenza treated by TCM systematically. These guidelines would be the first CPG on TCM therapy for influenza, based on the WHO Handbook for Guideline Development, and will provide the necessary evidence for treating influenza using TCM.