We examined the effects of coronary heart disease (CHD), hypertension and diabetes on the development of severe COVID-19. We performed a comprehensive, systematic literature search for studies published between December 2019 and July 5, 2020 in five databases. The prevalence of severe COVID-19 in patients with CHD, hypertension and diabetes was evaluated through a meta-analysis. Thirty-five articles with 8,170 patients were included, and all the available studies were case series. The pooled odds ratio for the development of severe COVID-19 was 3.21 for patients with CHD (fixed-effects model, 95% CI: 2.58-3.99), 2.27 for patients with hypertension (random-effects model, 95% CI: 1.79-2.90) and 2.34 for patients with diabetes (random-effects model, 95% CI: 1.79-3.05). The heterogeneity of the studies was moderate for the effect of CHD on COVID-19 severity, but was high for the effects of diabetes and hypertension. Funnel plots and Egger's tests revealed no publication bias in the CHD and hypertension analyses, but suggested publication bias in the diabetes analysis. This bias was corrected using the trim-and-fill method, and was ultimately found to have no effect on the results. Our findings suggest patients with CHD, hypertension and diabetes are at greater risk for developing severe COVID-19 than those without these conditions.

Background and Objective. Irritable bowel syndrome (IBS) is a prevalent disorder of the gastrointestinal system with complex pathogenesis. Shenling Baizhu powder (SLBZP) is a Chinese herbal compound with multicomponent and multitarget characteristics. Increasing volumes of evidence demonstrate that it has a notable therapeutic impact on IBS. This study therefore is aimed at exploring the potential effective components of SLBZP and their mechanisms in IBS treatment utilizing network pharmacology. Methods. Metabolomics was used to detect the secondary metabolites in SLBZP; the target protein was acquired by target fishing according to the compound’s structure. The SymMap database was used to search herbal medicines for the target protein. The target gene of IBS gave rise to the common gene protein which is the potential target of SLBZP in IBS therapy. The interactions between target proteins were analyzed in a STRING database, the protein relationship network was analyzed using Cytoscape software, and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the core target gene group was carried out in a DAVID database in order to construct the “compound‐traditional Chinese medicine/molecule‐target‐pathway” network. Molecular docking was used to verify the core protein and its related small molecular compounds. Result. There were 129 types of secondary metabolites in SLBZP. 80 target proteins of these metabolites were potential core targets for IBS treatment including acetylcholinesterase (AChE), arachidonate‐5‐lipoxygenase (ALOX5), B‐cell lymphoma‐2 (BCL2), recombinant cyclin D1 (CCND1), and catenin‐β1 (CTNNB1), among others. Results from these targets indicated that the most enriched pathway was the tumor necrosis factor (TNF) signaling pathway (p < 0.001) and that the most abundant pathway was signal transduction. In the network nodes of the TNF signaling pathway, the Chinese medicines with the highest aggregation were Lablab semen album and Glycyrrhizae radix et rhizoma (degree = 11). The small molecules with the highest aggregation were oxypeucedanin and 3,5,6,7,8,3 ^′,4 ^′‐heptamethoxyflavone (degree = 4). Molecular docking results confirmed that daidzein 7‐O‐glucoside (daidzin) had the highest degree of binding to TNF proteins in the TNF signaling pathway. Conclusion. This study shows that SLBZP can treat IBS by influencing multiple targets and pathways, of which the TNF signaling pathway may be the most significant. This typifies the pharmacological characteristics of traditional Chinese medicine, i.e., multiple targets, numerous pathways, and specific therapeutic effects on diseases. SLBZP can therefore be used as a candidate drug for clinical IBS by intervening in human signal transduction.

Gastrointestinal heat retention syndrome (GHRS) refers to a condition that is associated with increased gastrointestinal heat caused by a metabolic block in energy. It is common in children and is closely related to the occurrence and development of recurrent respiratory tract infection, pneumonia, recurrent functional abdominal pain, etc. However, there are no standardized diagnostic criteria to differentiate the GHRS. Therefore, this study is aimed to establish a diagnostic model for children’s GHRS and explore the possible biological basis by using systems biology to achieve. Furthermore, Delphi method and the clinical data of Lasso analysis were used to screen out the core symptoms. Nineteen core symptoms of GHRS in children were screened including digestive symptoms such as dry stool, poor appetite, vomiting, and some nervous system symptoms such as night restlessness and irritability. Based on the core symptoms, a GHRS diagnosis model was established using the eXtreme Gradient Boosting (XGBoost) method, and the accuracy of internal verification reached 93.03%. Relevant targets of the core symptoms in the Human Phenotype Ontology (HPO) were retrieved, and target interactions were linked through the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and core targets were selected after topological analysis using Cytoscape. Relevant biological processes and pathways were analyzed by applying the DAVID and KEGG databases. The enriched biological processes focused on the cell proliferation, differentiation, apoptosis, and mitochondrial metabolism, which were mainly associated with PI3K-AKT, MAPK network pathways, and the Wnt signaling pathway. In conclusion, we established a diagnosis model of GHRS in children based on the core symptoms and provided an objective standard for its clinical diagnosis. And, the Wnt signaling pathway and the estrogen receptor-activated PI3K-AKT and MAPK network pathways may play important roles in the GHRS processing.

Insomnia is one of the most common sleep disorders. Traditionally, its pathophysiology has been interpreted mainly from the perspective of the central nervous system (CNS). However, accumulating evidence suggests that the microbiota–gut–brain axis (MGBA), a bidirectional communication network linking the gut and the CNS, may play an important role in the development, maintenance, and treatment of insomnia. This review summarizes the major signaling pathways of the MGBA and discusses its potential mechanisms in insomnia. Current evidence indicates that gut microbiota and their metabolites may influence sleep–wake homeostasis through neural, immune, endocrine, and circadian pathways. At the same time, insomnia-related stress responses, immune imbalance, and lifestyle disturbances may in turn affect the gut microbiota, thereby forming a bidirectional regulatory network. Animal and clinical studies further support a close association between gut microbial dysbiosis and insomnia. In addition, this review systematically summarizes factors that may affect the MGBA, including diet, lifestyle, psychosocial stress, medications, and medical exposures. On this basis, MGBA-targeted interventions, such as dietary modification, prebiotics and probiotics, lifestyle interventions, fecal microbiota transplantation, and natural medicines, may provide promising new strategies for the prevention and treatment of insomnia. Nevertheless, the current evidence still relies largely on animal studies and cross-sectional research, and further longitudinal studies and high-quality interventional trials are needed to clarify causality, long-term efficacy, and standardized therapeutic approaches.

Viral pneumonia (VP), particularly that induced by influenza A virus (IAV), remains a major global health challenge and a leading cause of acute respiratory infections. Ma Xing Shi Gan Decoction (MXSG), a classical traditional Chinese medicine formula recorded in the ancient text Treatise on Cold Damage, has been widely used for centuries in China to treat febrile respiratory diseases and pneumonia. However, the molecular basis underlying its therapeutic effects remains incompletely defined. This study provides experimental evidence linking MXSG to modulation of VP and host metabolic-autophagy pathways. To investigate whether MXSG is associated with reduced IAV nucleoprotein (NP) levels and concurrent modulation of key glycolytic enzymes, HMGB1 lactylation, and autophagosome accumulation. Buddleoside was evaluated as an exploratory constituent. A mouse model of VP was established by intranasal inoculation with IAV, while A549 cells were infected with IAV for in vitro studies. In vivo effects on glycolysis and autophagy were evaluated by assessing lung inflammatory cytokines, viral NP levels, glycolytic enzymes, and autophagy markers. Oxamate and diphenyleneiodonium chloride (DPI) were used as tools to interfere with lactate production. UPLC-MS/MS and molecular docking were performed to identify potential pathway-relevant constituents. In vitro, validation included lactate supplementation, oxamate treatment, buddleoside exposure, and HMGB1 overexpression. In vivo, MXSG reduced IAV NP levels and alleviated lung inflammatory injury. MXSG treatment was associated with decreased expression of glycolysis-related enzymes, reduced lactate accumulation, lower HMGB1 lactylation levels, and reduced autophagosome accumulation. Under DPI-mediated lactate accumulation, the inhibitory effect of MXSG on autophagosome accumulation was partially attenuated. Docking analysis suggested potential interaction between buddleoside and LDHA. In vitro, MXSG modulated lactate levels, HMGB1 lactylation, and autophagy-related markers, accompanied by decreased NP levels. MXSG reducing NP levels is associated with modulation of expression levels of glycolytic enzymes and reduced lactate production, and was accompanied by decreases in HMGB1 lactylation with expression and HMGB1-associated autophagosome accumulation providing a potential metabolic basis for MXSG-associated regulation of autophagy-related processes. These findings suggest a possible association between metabolic-autophagy signaling and MXSG-associated reductions in viral NP levels, but remain correlative and require further validation.