Cytokine Storm in Acute Viral Respiratory Injury: Role of Qing-Fei-Pai-Du Decoction in Inhibiting the Infiltration of Neutrophils and Macrophages through TAK1/IKK/NF-[Formula: see text]B Pathway.

COVID-19 has posed unprecedented challenges to global public health since its outbreak. The Qing-Fei-Pai-Du decoction (QFPDD), a Chinese herbal formula, is widely used in China to treat COVID-19. It exerts an impressive therapeutic effect by inhibiting the progression from mild to critical disease in the clinic. However, the underlying mechanisms remain obscure. Both SARS-CoV-2 and influenza viruses elicit similar pathological processes. Their severe manifestations, such as acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and viral sepsis, are correlated with the cytokine storm. During flu infection, QFPDD reduced the lung indexes and downregulated the expressions of MCP-1, TNF-[Formula: see text], IL-6, and IL-1[Formula: see text] in broncho-alveolar lavage fluid (BALF), lungs, or serum samples. The infiltration of neutrophils and inflammatory monocytes in lungs was decreased dramatically, and lung injury was ameliorated in QFPDD-treated flu mice. In addition, QFPDD also inhibited the polarization of M1 macrophages and downregulated the expressions of IL-6, TNF-[Formula: see text], MIP-2, MCP-1, and IP-10, while also upregulating the IL-10 expression. The phosphorylated TAK1, IKK[Formula: see text]/[Formula: see text], and I[Formula: see text]B[Formula: see text] and the subsequent translocation of phosphorylated p65 into the nuclei were decreased by QFPDD. These findings indicated that QFPDD reduces the intensity of the cytokine storm by inhibiting the NF-[Formula: see text]B signaling pathway during severe viral infections, thereby providing theoretical and experimental support for its clinical application in respiratory viral infections.

[Clinical application evaluation of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine].

Clinical application evaluation research of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine intends to evaluate the quality level and clinical application of the guideline. A questionnaire and prospective case survey methods were used to evaluate the applicability evaluation based on the clinician questionnaire and the application evaluation based on clinical case observation. The applicability evaluation, familiarity and utilization rate of doctors' guidelines were 85.06%, 62.76%; Sort by technical grade, intermediate grade doctors have a higher familiarity rate and utilization rate, while the junior grade doctor's is lower; Guide quality level of applicability evaluation, other items' rational percentage are better than 96% except the items of health preserving and prevention and other treatment is relatively low; Items' applicable percentage of applicability evaluation are more than 91% except the item of guide simplicity. Comprehensive applicability evaluation, The percentage of the guideline applicable to clinical practice accounted for 94.94%. The consistency rate of syndrome differentiation and clinical application is more than 96% in addition to prescription medication, other treatments and health preserving and prevention of the guidelines apply consistency of application evaluation. The percentage of good treatment effect accounted for 92.96% of application effect evaluation. The safety percentage is 99.89% and economy is 97.45%. The research shows that of Guidelines for the Diagnosis and Treatment of Common Diseases of Pediatrics in Traditional Chinese Medicine quality level is good and is basically applicable to pediatric clinical practice which can be used as a standardized recommendation of pediatric common diseases' treatment specification. A small part of the guidelines are not applicable and need to be further consummated. Health preserving and prevention and other treatment of the guideline need to be revised.

[Being Exposed to Specific Syndromes of Chinese Medicine and Being Compatible with Components of Chinese Herbs Are Important Ways to Control Toxicity of Toxic Chinese Herbs].

Being exposed to specific syndromes of Chinese medicine (CM) and being compatible with other Chinese herbs are two necessary methods for controlling the toxicity of toxic Chinese herbs. The complexity of Chinese herbal components causes the difficulties in in-depth study of toxicity control. Under the guidance of systems biology, authors studied protein expression profiles and metabolite spec- trums by Chinese herbal compatible components intervening animal model with specific syndrome of CM, thus clarifying corresponding biomarkers relevant to toxicity reducing and control. Authors found out key molecules and pathways for toxicity reducing and control by molecular network technologies using and o- verlaying information integrating. All these mentioned above were finally verified by molecular biologic methods, therefore, revealing the molecular mechanism of toxicity control effects of Chinese herbal compatible components in specific syndromes of CM.

[Explore pharmacological mechanism of glycyrrhizin based on systems pharmacology].

To explore the pharmacological mechanism of glycyrrhizin with series methods of systems pharmacology, main diseases related to glycyrrhizin were obtained by text mining tool; and the target proteins of glycyrrhizin were obtained via the database of Polysearch and PubChem. Then, the target proteins interaction network of glycyrrhizin was built using the software called Cytoscape. Next, the protein groups related to glycyrrhizin were analyzed by using Gene Ontology (GO) tool, and the action pathway of its target proteins was analyzed by using enrichment method. Text mining results showed that the related diseases of glycyrrhizin included chronic hepatitis C, chronic hepatitis, hepatitis, HIV virus, liver cancer and so on. Gene ontology analysis indicated that glycyrrhizin played a role mainly through modification of proteins and chromatin. The signaling pathway enrichment results showed that the main action proteins of glycyrrhizin were related to MAPK signaling pathway, toll-like receptor signaling pathway, neurotrophic factor signaling pathway, cancer and apoptosis pathways. So we can conclude that glycyrrhizin may exert its biological functions primarily by regulating multiple pathways such as MAPK signaling pathway and Toll-like receptors signaling pathway. The pharmacological action of a drug can be rapidly and comprehensively analyzed by the ways of systems pharmacology.

[Zheng Classification in Chinese Medicine: from Its Integration with Disease Diagnosis to Clinical Effectiveness Assessment and Combinational New Drug Discovery].

As the core of traditional Chinese medicine theory, Zheng (syndrome, or pattern) classification will promote personalized medicine by changing the clinical diagnosis into a more precise mode when integrating Zheng classification with disease diagnosis approaches. The author adopted rheumatoid arthritis (RA) as a disease model, to explore the scientific fundamentals of Zheng classification based on disease diagnosis using systemic biological approaches and evidence-based medicine design, as well as developed novel approaches on the methodology of clinical effectiveness evaluation on Chinese medicine and R&D of combinational drugs design based on Fu Fang (Chinese herbal formula). Some unique research design and methods are herein introduced.

QiShenYiQi Pills, a compound in Chinese medicine, protects against pressure overload-induced cardiac hypertrophy through a multi-component and multi-target mode.

The present study aimed to explore the holistic mechanism for the antihypertrophic effect of a compound in Chinese medicine, QiShenYiQi Pills (QSYQ) and the contributions of its components to the effect in rats with cardiac hypertrophy (CH). After induction of CH by ascending aortic stenosis, rats were treated with QSYQ, each identified active ingredient (astragaloside IV, 3, 4-dihydroxy-phenyl lactic acid or notoginsenoside R1) from its 3 major herb components or dalbergia odorifera, either alone or combinations, for 1 month. QSYQ markedly attenuated CH, as evidenced by echocardiography, morphology and biochemistry. Proteomic analysis and western blot showed that the majority of differentially expressed proteins in the heart of QSYQ-treated rats were associated with energy metabolism or oxidative stress. Each ingredient alone or their combinations exhibited similar effects as QSYQ but to a lesser extent and differently with astragaloside IV and notoginsenoside R1 being more effective for enhancing energy metabolism, 3, 4-dihydroxy-phenyl lactic acid more effective for counteracting oxidative stress while dalbergia odorifera having little effect on the variables evaluated. In conclusion, QSYQ exerts a more potent antihypertrophic effect than any of its ingredients or their combinations, due to the interaction of its active components through a multi-component and multi-target mode.

[A cold/heat property classification strategy based on bio-effects of herbal medicines].

The property theory of Chinese herbal medicine (CHM) is regarded as the core and basic of Chinese medical theory, however, the underlying mechanism of the properties in CHMs remains unclear, which impedes a barrier for the modernization of Chinese herbal medicine. The properties of CHM are often categorized into cold and heat according to the theory of Chinese medicine, which are essential to guide the clinical application of CHMs. There is an urgent demand to build a cold/heat property classification model to facilitate the property theory of Chinese herbal medicine, as well as to clarify the controversial properties of some herbs. Based on previous studies on the cold/heat properties of CHM, in this paper, we described a novel strategy on building a cold/heat property classification model based on herbal bio-effect. The interdisciplinary cooperation of systems biology, pharmacological network, and pattern recognition technique might lighten the study on cold/heat property theory, provide a scientific model for determination the cold/heat property of herbal medicines, and a new strategy for expanding the Chinese herbal medicine resources as well.

Duration of viral shedding of influenza A (H1N1) virus infection treated with oseltamivir and/or traditional Chinese medicine in China: a retrospective analysis.

OBJECTIVE: H1N1 was a new and potentially serious infectious disease, in human, the severity of influenza can vary from mild to severe, thus to find an effective and safety way to control the influenza pandemic is of crucial importance. This retrospective study describes the duration of viral shedding in H1N1 patients that were hospitalized and treated in China. METHODS: Clinical data were collected from May to July, 2009 in China for 963 patients with influenza A (H1N1) virus infection. Patients were treated based on the guidelines issued by the Chinese Ministry of Health. The primary outcome was duration of viral shedding and statistical comparisons were performed. RESULTS: In the patients with body temperature greater than 38.0 degrees C, there were no differences in virus shedding duration among the patients taking oseltamivir within two days, patients undergoing Traditional Chinese Medicine (TCM) therapy or those receiving no drug therapy. In patients with body temperature > or =38.1 degrees C, TCM therapy reduced the viral shedding duration (P < 0.05, vs. oseltamivir therapy). Furthermore, taking oseltamivir two days after onset of symptoms might prolong the virus shedding duration (P < 0.05, vs. taking oseltamivir less than 2 days of onset). CONCLUSION: TCM therapy is effective for reducing the length of virus shedding in patients with body temperature > or =38.0 degrees C. Oseltamivir used for reducing virus shedding duration should be taken within two days of onset.

Interactions between phytochemicals from traditional Chinese medicines and human cytochrome P450 enzymes.

Traditional Chinese medicine (TCM) formulas with fixed combinations rely on "sovereign, minister, assistant and guide" and fuzzy mathematical quantitative law, leading to greater challenges for the identification of active ingredients. Transformation and metabolic studies involving the Phase I drug-metabolizing enzyme cytochrome P450 (CYP) might potentially solve some of these challenges. The pharmacological effects can not be attributed to one active ingredient in TCMs, but integrated effects resulting from the combined actions of multiple ingredients. However, it is only after long-term administration that most ingredients exert their actions, which can result in prolonged exposure to herbs in vivo. Therefore, interactions between herbal compounds and CYPs appear to be inevitable. Yet unlike Western drugs, experimental determination of the absorption and disposition properties is not commonly carried out for TCMs. Moreover, the use of TCM as injections is an innovation aimed to improve efficiency in extensive clinical use in Mainland China. Therefore, in recent years, cases of adverse drug reactions (ADR) mainly concerning allergic reactions involving TCMs such as ShenMai injection and QingKaiLing injection have been reported, which have attracted attention with regard to the legal responsibilities for TCM approval. The lack of information on the ADME characteristics, especially the metabolic stability and interaction potential between CYPs and herbs, increases ADR occurrence due to TCMs. In this article, we review the most common herbs used in TCM prescriptions and fixed combinations of their usable frequency, and summarize the current understanding of the ability of phytochemical ingredients to act as substrates, inhibitors or inducers of human CYP enzymes, through which the key role of CYP enzymes on the herb disposition and toxicity is highlighted. The potential interaction between herbal phytochemicals and CYP enzymes dominates the target exposure, which further helps to elucidate the herbal pharmacological basis, assess the individual toxic risk of herbal remedies and gain mechanistic insight into herb-drug interactions (HDIs).

Assessing the quality of the first batch of evidence-based clinical practice guidelines in traditional Chinese medicine.

OBJECTIVE: To assess the quality of the first batch of Chinese evidence-based clinical practice guidelines (CPGs) in Traditional Chinese Medicine (TCM) using the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. METHODS: Evidence-based CPGs in TCM supported by the World Health Organization Western Pacific Regional Office (WHO/WPRO) and whose development was organized by the China Academy of Chinese Medical Sciences were identified and manually retrieved. CPGs were assessed using the AGREE instrument, and the data in each CPG were analyzed in terms of the six domains in the AGREE instrument: scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence. RESULTS: Twenty-eight CPGs were identified, of which 26 were included in the study. The AGREE instrument rated the 26 CPGs in terms of the six domains. The assessment results showed the following average scores: for editorial independence, 84.16%; for rigor of development, 80.95%; for scope and purpose, 79.96%; for clarity and presentation, 70.88%; for stakeholder involvement, 61.28%; for applicability, the average score was only 27.09%. In summary, nine CPGs were rated as "strongly recommended", six as "recommended with provision or alternation", and 11 as "unsure". CONCLUSION: Most of the first batch of Chinese evidence-based CPGs in TCM had significant shortcomings in applicability. It is suggested that special attention be paid to enhancing the quality of applicability when developing evidence-based CPGs in TCM.

[Effects of Huoxiang Zhengqi liquid on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea].

OBJECTIVE: To explore the effects of Huoxiang Zhengqi liquid (HXZQ) on enteric mucosal immune responses in mice with Bacillus dysenteriae and Salmonella typhimurium induced diarrhea (BSD). METHOD: Mice were randomly divided into four groups with 10 mice in each group: control group (control), BSD group, Huoxiang Zhengqi liquid treated BSD groups at high dosage and low dosage (HXZQ high, HXZQ low). HXZQ was administrated from the day of diarrhea induction at dosage of 5.21 g kg(-1) and 0.52 g kg (-1) respectively. Peyer's patch and periphery lymphocytes were prepared for flow cytometry, and level of TNF-alpha in periphery and enteric tissue homogenate were determined with ELISA. Student's t-test was used for statistics. RESULT: Mice in BSD group started showing continuous diarrhea at the day of induction till the fourth day when the mice were sacrificed. Diarrhea in the mice of HXZQ high and low groups lasted for 36 and 54 h respectively. There were more CD4+ and CD8+ cells in periphery, less CD4+ cells in peyer's patch in BSD mice comparing to normal mice. In peyer's patch, there were more CD8+ cells in mice in HXZQ high and low groups and more CD4+ in mice in HXZQ high group. Higher level TNF-alpha in periphery and intestinal tissue homogenate in BSD group were observed. Mice in HXZQ high group showed the decreased level TNF-alpha in periphery and enteric tissue homogenate. CONCLUSION: The immune regulation on peyer's patch CD4+ and CD8+ cells and suppression on TNF-alpha level in enteric homogenate might partially explain the effect of HXZQ on improvement of BSD.

[Methodological thoughts on clinical efficacy evaluation with multiple clinical trials].

Some clinical trials showed that the efficacy of traditional Chinese medicine was not good as the efficacy of western medicine even thoush clinical doctors have been using traditional medicine effectively. Such a result originated from improper application of western medical thoughts in routine clinical efficacy evaluation. To find differences from effective cases with non-effective cases and put the differences into the indication of next clinical trial would conform to the differentiation theory in traditional Chinese medicine. The differences, whether positively or negatively related to the efficacy, could be obtained from all information including symptom evaluation, tongue appearance, pulse feeling and biological parameters with non-linear and other statistical methods. More specific indication finding would be the key task for clinical efficacy evaluation via multiple clinical trials.