TCMFP: a novel herbal formula prediction method based on network target's score integrated with semi-supervised learning genetic algorithms.

Traditional Chinese medicine (TCM) has accumulated thousands years of knowledge in herbal therapy, but the use of herbal formulas is still characterized by reliance on personal experience. Due to the complex mechanism of herbal actions, it is challenging to discover effective herbal formulas for diseases by integrating the traditional experiences and modern pharmacological mechanisms of multi-target interactions. In this study, we propose a herbal formula prediction approach (TCMFP) combined therapy experience of TCM, artificial intelligence and network science algorithms to screen optimal herbal formula for diseases efficiently, which integrates a herb score (Hscore) based on the importance of network targets, a pair score (Pscore) based on empirical learning and herbal formula predictive score (FmapScore) based on intelligent optimization and genetic algorithm. The validity of Hscore, Pscore and FmapScore was verified by functional similarity and network topological evaluation. Moreover, TCMFP was used successfully to generate herbal formulae for three diseases, i.e. the Alzheimer's disease, asthma and atherosclerosis. Functional enrichment and network analysis indicates the efficacy of targets for the predicted optimal herbal formula. The proposed TCMFP may provides a new strategy for the optimization of herbal formula, TCM herbs therapy and drug development.

[Historical evolution of Xuanfu Daizhe Decoction].

Xuanfu Daizhe Decoction, first seen in Zhang Zhongjing's Treatise on Cold Damage Diseases, was composed of seven medicinal materials: Inulae Flos, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma Recens, Haematitum, Pinelliae Rhizoma and Jujubae Fructus. It was used to treat gastric fullness and hardness and belching due to the wrong treatment of typhoid fever and sweating. With detailed records and description in ancient medical books, Xuanfu Daizhe Decoction was widely adopted in clinical practice by physicians of later generations, which expanded its main therapeutic functions. By comprehensive collation of ancient and modern literature on Xuanfu Daizhe Decoction, this paper systematically explored the historical evolution of the prescription from the source, composition, dosage, processing, clinical application, function interpretation and decocting method. It was found that the composition and processing method of the prescription in the past dynasties were relatively consistent, and there was a gradual decrease in dosage in clinical application. In ancient times, Xuanfu Daizhe Decoction was mainly used to treat nausea, vomiting, hiccups, constipation, etc., while modern clinicians mainly used it for digestive diseases such as reflux esophagitis and gastritis. Through the analysis and textual research, the composition, dosage, processing, function evolution and decocting method of this prescription were determined, which provided reference for the research and development of compound preparations of Xuanfu Daizhe Decoction.

Effect of Qingfei Paidu decoction combined with Western medicine treatments for COVID-19: A systematic review and meta-analysis.

BACKGROUND: Qingfei Paidu decoction (QFPDD) showed to be beneficial for the treatment of coronavirus disease 2019 (COVID-19) in China. PURPOSE: This study aimed to systematically assemble the evidence on the efficacy and safety of QFPDD combined with Western medicine treatments (WMT) for COVID-19. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, CSTJ, CBM, Wanfang Data for clinical trials with a control arm until January 13, 2022. Studies matched the selection criteria were included. Data extraction and quality assessment of the included studies were independently conducted by two reviewers. Review Manager 5.4 was used for meta-analysis. RESULTS: A total of 9 trials including 1108 COVID-19 patients met the selection criteria. Meta-analysis demonstrated that QFPDD combined with WMT reduced aggravation rate (AR) by 71% [risk ratio (RR) = 0.29, 95% confidence intervals (CI) (0.17, 0.51)], increased effective rate (ER) by 13% [RR = 1.13, 95%CI (1.04, 1.22)], shortened 4.78 days of viral shedding [95%CI (-5.79, -3.77)] and 4.45 days of hospital stay [95%CI (-6.05, -2.86)], also decreased the incidence of adverse events (AE) by 56% [RR = 0.44, 95%CI (0.22, 0.89)]. CONCLUSION: QFPDD combined with WMT might reduce the proportion of severe cases and the incidence of AE, shorten the duration of viral shedding and length of hospital stay. More randomized controlled trials (RCTs) are required to confirm our findings in the future.

Application of the Delphi Method in the Construction of an Evaluating and Grading Scale for Evidence of Disease Prevention and Treatment in Ancient Books of Traditional Chinese Medicine.

Objective: This study aimed to develop a scale for evaluating and grading the evidence of prevention and treatment in ancient books of traditional Chinese medicine (TCM), in view of providing a reference for TCM clinicians, supporting the compilation or revision of evidence-based practice guidelines for TCM, improving the level of evidence-based research on ancient TCM books, and supplementing the development of evidence-based ancient TCM books. Methods: The Delphi method was used for consultation among 40 experts in relevant fields. Excel 2016 and SPSS 21.0 were used to analyze the positive coefficient, authority coefficient, degree of concentration, degree of coordination, and degree of expert consensus. Results: In the first round of the questionnaire, a total of 17 evaluation indexes were formulated in three aspects: 5 were deleted, 1 was modified according to the expert opinions, and no additional index was added. In addition, quantitative standards, weight assignment, and grading standards were developed according to the findings of the expert consultation. The positive coefficients of experts in the first and second rounds of questionnaires were 87.5% and 82.9%, respectively. The authority coefficient was 0.835 (>0.7). The coefficient of variation of the first and second rounds were 0.14∼0.29 and 0.09∼0.27, respectively. Kendall's coefficient of concordance of the first and second rounds were 0.135 (p < 0.05) and 0.081 (p < 0.05), respectively. Conclusion: The evaluation indexes and quantitative reference values of the developed scale conform to the characteristics of prevention and treatment evidence in ancient TCM books. It can provide a useful exploration tool for the evaluation and grading of evidences in TCM ancient books.

Medication Rule Analysis of the Diagnosis and Treatment Programs of Chinese Medicine for the Prevention and Treatment of COVID-19 in China.

OBJECTIVES: To summarize the measures and rules of Chinese medicine (CM) and provide reference for clinical application in the prevention and treatment of coronavirus disease (COVID-19). METHODS: The data source was from CM COVID-19 prevention and treatment programs on government websites and official media websites of the different provinces and cities. The search lasted from December 8, 2019 to March 10, 2020. Main variables were medication frequency and combinations of medicines. Cluster analysis and complex network analysis were used by prevention and treatment stage and by area. RESULTS: Among 27 CM diagnosis and treatment plans, 203 therapeutic prescriptions were enrolled, of which the top 4 herbs were: Radix glycyrrhizae, Semen armeniacae amarum, Herba ephedrae, and Herba agastachis, respectively. The core combinations were Herba ephedrae and Semen armeniacae amarum. Forty-eight preventive formulae were identified. Ten herbs, including Radix Astragali seu hedysari, Radix glycyrrhizae, Radix saposhnikoviae, Flos lonicerae, etc. were most frequently used. The core prescription of CM compatibility was Radix astragali seu hedysari, Radix glycyrrhizae, and Radix saposhnikoviae, which is the main component of Yu Ping Feng San. There were 45 prevention and treatment prescriptions in East China; the most used CM was Radix glycyrrhizae, Herba agastachis, Pericarpium citri reticulatae, and Gypsum fibrosum. Fifty prescriptions were identified in North China. According to CM analyses, Herba agastachis, Semen armeniacae amarum, Herba ephedrae, and Poria were most frequently used. CONCLUSIONS: CM for COVID-19 prevention mainly focuses on improving human immunity; for treatment, prescription focuses on clearing the lungs and removing dampness. Prescriptions vary with regions, perhaps due to climatic and environmental differences, which help clinicians to quickly make CM plans and treat patients according to clinical status, further minimizing resource wastage.

[An optimization method of weighted network module partition based on TCM theory of "monarch, minister, assistant and guide"].

The disease-gene-drug multi-level network constructed by network pharmacology can predict drug targets and has been widely used in the study of material basis and mechanism of action of Chinese medicinal prescriptions. However, most of the current studies have normalized the efficacies of Chinese herbal medicines in the compounds during the construction of the network. There is also a lack of in-depth exploration of the mechanism of synergy among multiple components. This study proposed a network module partition method based on group collaboration and the pharmacological network was weighed according to the traditional Chinese medicine(TCM) theory of "monarch, minister, assistant and guide". Taking the Tanyu Tongzhi Prescription as an example, we constructed its pharmacological network for the treatment of myocardial ischemia-reperfusion injury. The group collaboration module in the network was identified and the network changes before and after the weighting were compared based on the network topology analysis to explore a new method to find the core nodes of the network as well as the core drugs that affected the efficacy of the compounds. The results showed that the module partition method based on group collaboration could be used to identify and partition group collaboration mo-dules in pharmacological networks of compounds. The proposed weighted network based on the TCM theory of "monarch, minister, assistant, and guide" could identify and partition the modules based on the characteristics of the pharmacological network. The identification and partition results of modules of Tanyu Tongzhi Prescription in the weighted network were superior to those in the unweighted network. The weighted closeness centrality(WCC) evaluation method was conducive to finding key nodes and relations in the network as compared with traditional methods, thereby providing a basis for analyzing the core components of drugs and extracting more accurate drug components and targets.

[Textual research principles and suggestions on function and indication of ancient classical formulas].

Indication and functions is an important key information in the research and development of the ancient classical formulas, which directly affects the clinical positioning of the compound formulas and their reasonable, effective and safe use after marke-ting. It is also the embodiment of the ultimate vitality of ancient classical formulas. Due to the particularity of ancient classical formulas, it is of great significance to accurately define and describe the functions and indications of classical formulas to exert their unqiue advantages. Based on the analysis of the provenances, classification of clinical indications, and functions of 100 prescriptions in the Catalogue of Ancient Classical Formulas(First Batch), this paper summarized the incompleteness, irregularity and inconsistency in the original text, the differences in terminology between ancient and modern times, and the evolution of the meanings of prescriptions in different dynasties. In addition, under the guidance of the general principle of textual researh on ancient classical formulas, which is to inherit the essence, make the past serve the present, link up the past and the present, and bulid consensus, this paper proposed the following ideas: respecting the original meanings and provenances of ancient classical formulas, taking full consideration of the development and evolution, serving the current clinical application and health needs, accurately linking up the ancient and modern terminologies, standardizing the expression of traditional Chinese medicine(TCM) terminology, highlighting the characteristics of TCM, attaching importance to the textual research principles and suggestions of post-marketing evidence-based and clinical positioning research, so as to determine the the functions and indications of the ancient classical formulas in a scientific, standardized and reasonable way and better guide the clinical application of the classical formulas.

[Hotspots and trends of Ophiopogonis Radix based on CiteSpace knowledge map].

Ophiopogonis Radix is an important Yin-nourishing drug in traditional Chinese medicine(TCM), with the effects of nourishing Yin, promoting fluid production, clearing away heart-fire, and relieving restlessness. It is widely used in clinical practice due to its multiple chemical components and pharmacological effects. The technique "mapping knowledge domains" is an effective tool to quantitatively and objectively visualize the development frontiers and trends of certain disciplines. In this study, TCM research papers related to Ophiopogonis Radix were retrieved from Web of Science(WoS) and CNKI, and the research institutions, journals, and keywords involved were visualized and analyzed using the scientometric software CiteSpace. The co-occurrence network of related research on Ophiopogonis Radix was constructed, and the Ophiopogonis Radix-disease-target network was plotted using Cytoscape 3.8.2. The hot topics in Chinese and English papers were analyzed and the shortcomings in the research on Ophiopogonis Radix were summed up. Furthermore, the development trends were discussed. A total of 1 403 Chinese papers and 292 English papers were included in this study. The analysis of research institutions showed that Beijing University of Chinese Medicine and China Pharmaceutical University were the two research institutions with the largest numbers of papers published. The analysis of journals showed that Hebei Journal of Traditional Chinese Medicine and Journal of Asian Natural Products Research were the two journals with the highest numbers of papers concerning Ophiopogonis Radix. The keyword analysis showed that the research contents of Chinese papers focused on the analysis of medication regularity and clinical observation trials, while the English papers focused on component analysis and pharmacological investigation. Data mining and apoptosis-based pharmacological mechanism might be the research trends in the future.

Clinical characteristics and treatment outcome of COVID-19 patients with stroke in China: A multicenter retrospective study.

OBJECTIVE: Previous studies mainly reported the clinical characteristics of novel coronavirus 2019 (COVID-19) infections, but the research on clinical characteristics and treatment outcomes of COVID-19 patients with stroke is still rare. METHODS: A multi-center retrospective study was conducted at 11 hospitals in 4 provinces of China, and COVID-19 patients with stroke were enrolled from February 24 to May 4, 2020. We analyzed epidemiological, demographic, and clinical characteristics of cases as well as the laboratory test results, treatment regimens and outcomes, and the clinical characteristics and therapeutic outcomes were compared between severe and nonsevere patients, and by age group, respectively. RESULTS: A total of 27 patients [mean age: 66.41 (SD 12.1) years] were enrolled. Among them, 9 (33.3%) were severe patients and 18 (66.7%) were nonsevere patients; 17 (63.0%) were female; 19 (70.4%) were aged 60 years and above. The most common symptoms were fever [19 (70.4%)], fatigue [12 (44.4%)] and cough [11 (40.7%)], respectively. Abnormal laboratory findings of COVID-19 patients with stroke included high levels of C-reactive protein [19 (73.1%)], D-dimer [14 (58.3%)], blood glucose [14 (53.8%)], fibrinogen [13 (50.0%)], and decreased lymphocytes [12 (44.4%)]. Comparing to nonsevere cases with stroke, severe patients with stroke were likely to be older, susceptible to receiving oxygen inhalation, and had more complications (p < 0.05). In addition, there were significant differences in lymphocytes, neutrophils, lactate dehydrogenase, C-reactive protein, creatine kinase between the severe cases and nonsevere cases (p < 0.05). The older patients had a decreased platelet count and elevated fibrinogen, compared with the younger (p < 0.05). All patients (100%) received antiviral treatment, 12 (44.4%) received antibiotics treatment, 26 (96.3%) received Traditional Chinese Medicine (Lung cleansing & detoxifying decoction), and oxygen inhalation was in 18 (66.7%). The median duration of hospitalization was 16 days. By May 4, 2020, a total of 26 (96.3%) patients were cured and discharged, and 1 (3.7%) patients died. CONCLUSION: COVID-19 patients with stroke had poor indicators of coagulation system, and severe and older patients might have a higher risk of complications and unfavorable coagulation system. However, the overall treatment outcome is favorable.

Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: A retrospective multicenter cohort study.

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

Application of the combination index (CI)-isobologram equation to research the toxicological interactions of clothianidin, thiamethoxam, and dinotefuran in honeybee, Apis mellifera.

Due to complex pest control scenarios and the needs of agricultural production, different neonicotinoids may be used in certain agricultural applications. Consequently, honeybees may be exposed to these substances through distribution throughout plant tissues via the vascular system through several pathways, such as surface water, the exudates excreted from plants, and air pollution via drift of dust as well as contaminated pollen and nectar. In the current study, the single and combined toxicity of clothianidin, dinotefuran, and thiamethoxam to honeybees was examined after 48 h exposure by the acute oral method and combination index (CI)-isobologram equation. At the 48 h interval, our results showed that 1) the order of toxicities for the single insecticides was ranked as clothianidin > thiamethoxam > dinotefuran and that 2) all binary and ternary combinations showed synergism or additive effect at the effect (fa) 0.5. Therefore, our results not only provided meaningful guidelines in evaluating the safety risk of the mixtures of the three neonicotinoids towards honeybees but also suggested that there is a significant interest in the study of mixture toxicities of neonicotinoids against honeybees because risk assessment of neonicotinoids against honeybees conducted only in individual insecticides may underestimate the realistic toxicity.