Covalent linkage with acetylcholinesterase (AChE) to form ligand-target adduct (L-T) is primarily responsible for pesticide poisoning, notably those carbamates (CARs) and organophosphorus (OPs), which frequently occurs in clinic. Because covalent modification resists proteolysis, L-T measurement can be accomplished by monitoring modified peptide(s) that further act as a quantitatively bidirectional indicator for both ligand and target. Covalent modification locates at hydroxyl group of Ser225 residue. Modified peptide relative response (AM) and the response ratio (RM/U) between modified and unmodified peptides were specifically concerned. When providing adequate AChE, RM/U was correlated linearly with ligand concentration, and similarly, linear relationships occurred between RM/U and AChE content when the given ligand was sufficient. Agreement emerged for the sigmoid trajectories between AM against carbamate concentration and colorimetric Ellman assay. AM against ligand concentration curve uniquely enabled inhibition measurement of the mixed pesticides. Structural annotation of modified peptide facilitated the unknown toxin(s) identity annotation. Together, the measurement of modified peptide that reflects L-T identity and concentration, enabled the qualitative and quantitative analysis of either ligand or target, as well as toxicological performance evaluation of individual ligands and even ligand mixtures.

Natural medicines, particularly Traditional Chinese Medicine (TCM), are gaining global recognition for their therapeutic potential in addressing human symptoms and diseases. TCM, with its systematic theories and extensive practical experience, provides abundant resources for healthcare. However, the effective application of TCM requires precise syndrome diagnosis, determination of treatment principles, and prescription formulation, which demand decades of clinical expertise. Despite advancements in TCM-based decision systems, machine learning, and deep learning research, limitations in data and single-objective constraints hinder their practical application. In recent years, large language models (LLMs) have demonstrated potential in complex tasks, but lack specialization in TCM and face significant challenges, such as too big model scale to deploy and issues with hallucination. To address these challenges, we introduce Tianyi with 7.6-billion-parameter LLM, a model scale proper and specifically designed for TCM, pre-trained and fine-tuned on diverse TCM corpora, including classical texts, expert treatises, clinical records, and knowledge graphs. Tianyi is designed to assimilate interconnected and systematic TCM knowledge through a progressive learning manner. Additionally, we establish TCMEval, a comprehensive evaluation benchmark, to assess LLMs in TCM examinations, clinical tasks, domain-specific question-answering, and real-world trials. The extensive evaluations demonstrate the significant potential of Tianyi as an AI assistant in TCM clinical practice and research, bridging the gap between TCM knowledge and practical application.

BACKGROUND:Health problems associated with energy metabolism imbalance have received increasing attention. Our team was the first to propose the concept of gastrointestinal heat retention syndrome (GHRS). Triggered by high-calorie diets and excessive energy intake, GHRS is strongly associated with recurrent respiratory infections and other pediatric conditions in children. Existing research on GHRS has primarily focused on risk factor analyses, and no interpretable exploratory self-assessment model for estimating prevalence probability is currently available for routine household use. OBJECTIVE:This study aims to develop and validate an interpretable machine learning model to help caregivers conduct exploratory self-assessments of the probability that children meet the criteria for pediatric GHRS and to provide a practical assessment tool for household use. METHODS:This study conducted a questionnaire survey of kindergarten children in Longgang District, Shenzhen, China. Samples with missing information on GHRS-related symptoms and signs were excluded. Independent correlates were identified using univariate logistic analysis, collinearity testing, Least Absolute Shrinkage and Selection Operator regression, and multivariable logistic regression. After handling missing data and preprocessing, the dataset was randomly divided into training and test sets in an 8:2 ratio. SMOTETomek (Synthetic Minority Oversampling Technique Tomek Links) was included as a conservative resampling step in the training pipeline, and optimal features were selected using a combination of Pearson correlation analysis and recursive feature elimination. In addition, a Random Forest (RF) sensitivity analysis without SMOTETomek was performed, and the minimum required sample size was estimated according to the events per variable (EPV) rule. Seven machine learning models were developed and evaluated in terms of discrimination, calibration, and clinical utility. The SHAP (Shapley Additive Explanations) method was used to interpret the optimal model, which was subsequently deployed online using the Streamlit framework. RESULTS:A total of 120,198 questionnaires were collected, of which 108,447 were deemed valid and included in the analysis. The ratio of GHRS-positive to GHRS-negative cases was nearly balanced. The study identified 59 independent correlates of GHRS, including 10 protective factors and 49 risk factors. After data cleaning, a complete-case dataset of 49,798 participants was obtained, exceeding the minimum sample size requirement of 3747 cases based on the EPV rule. During internal validation, the RF model demonstrated acceptable discriminatory performance, stable calibration, and high net benefit in decision curve analysis, and was therefore selected as the primary analytical model. SHAP analysis identified 5 key predictive features. The resulting online tool collects information through 75 single-choice questions and automatically provides an estimated probability of GHRS together with lifestyle recommendations. CONCLUSIONS:Using cross-sectional data, this study developed and validated an interpretable model that enables caregivers to perform exploratory self-assessments of the probability that children meet the study-specific GHRS scale criteria. As a household self-screening tool, the model helps caregivers estimate this probability based on readily obtainable information and model-generated risk estimates.

AimObesity in children have become major public health issues worldwide. The study aimed to determine the prevalence of overweight and obesity among children in Longgang District, Shenzhen, China, in the context of COVID-19 and analyze associated risk factors.MethodsA cross-sectional study was conducted through online survey from May to July 2021. World Health Organization child growth standards and the health industry standards of the People’s Republic of China were used as the diagnostic criteria for overweight and obesity. The prevalences of overweight and obesity were calculated, and risk factors of obesity were analyzed using binary logistic regression.ResultsThe parents or guardians of 124,593 children were administered, and 108,581 subjects were included. The prevalences of overweight and obesity among kindergarten children in Longgang District, Shenzhen, were 8.3 and 7.9%, respectively. The risk factors for childhood obesity included congenital, family, and lifestyle factors.ConclusionIn 2021, the obesity prevalence of kindergarten children in Longgang District was close to some high-income countries and higher than Shenzhen before the outbreaks of COVID-19. This finding may be associated with social, family, and personal factors. Exploration of evidence-based, effective means of modifying children’s health habits, and social support is urgently needed.

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.

Background:Viral encephalitis (VE), a central nervous system disorder with high mortality and disability rates, poses a serious threat to childhood development. Xiyanping injection (XYPI), an andrographolide sulfonate preparation widely used in China, exhibits anti-inflammatory, antiviral, antitumor, antibacterial and neuroprotective properties. Methods:We conducted a retrospective study of 635 pediatric inpatients with VE who were hospitalized at seven medical centers in China between January 2015 and December 2021. Risk factors for poor prognosis were compared between inpatients treated with XYPI (n = 480) and those without XYPI treatment (n = 155). Propensity score matching was performed to reduce potential confounding. Clinical symptoms, hospitalization costs, complications and sequelae were evaluated simultaneously. Results:Multivariate Logistic regression identified XYPI treatment as an independent protective factor for poor prognosis (odds ratio [OR] = 0.251, 95% confidence interval [CI]: 0.113-0.559, p < 0.001). XYPI significantly shortened the duration of fever and headache, reduced hospitalization costs, and lower the incidences of respiratory infections, myocardial injury, and sequelae (all p < 0.05). Conclusion:Adjuvant XYPI therapy may improve clinical outcomes and reduce the economic burden in pediatric VE; however, randomized trials are warranted to validate these findings.

Objective To explore the effect of high-fat diet and fecal microbiota transplantation (FMT) on “intestinal flora-SCFAs-GPR43-gastrointestinal peptide” pathway, and provide evidence and clues for the prevention and treatment of obesity caused by eutrophic diet.Methods 160 male SD rats were used in this study, 50 of them were randomly selected to be fed a standard rat diet, while the remaining 110 rats were fed a high-fat diet (D12492). After excluding the rats that did not meet the obesity criteria, the remaining rats were subjected to treatment with normal microbiota enema and obesity-associated microbiota enema. The rats were divided into normal control group 1 (NC1), normal control group 2 (NC2), obesity model group (M), obesity fecal microbiota transplantation group (FMT1), and normal fecal microbiota transplantation group (FMT2). The study observed the general situation, the index of liver, spleen and thymus in rats. Morphological changes of colon and liver tissues were examined under an optical microscope, and the alterations in gut microbiota were detected by 16s rDNA. Gas chromatography-mass spectrometry (GC-MS) was ued to measure the levels of short-chain fatty acids (SCFAs), including acetic acid, propionic acid, and butyric acid. Immunohistochemistry (IHC) was used to evaluate the expression of GPR43 in liver tissue. Additionally, gastrointestinal peptides in rat serum were quantified using the ELISA method, while cholesterol and triglyceride levels in serum were measured using an automatic biochemical analyzer.Results The high-fat diet successfully induced obesity rat models. This led to significant changes in gut environment and the survival environment of microbiota, such as Lactobacillus, reflecting the intestinal microecological disorders in rats with high-fat diet induced obesity, Different dietary interventions can lead to varing developments in gut microbiota. After antibiotic intervention, gut microbiota in rats were significantly suppressed, with reduced species diveristy and abundance, establishing an antibiotic-induced rat model. High-fat diet interventions resulted in significant changes in the relative abundances of specific gut bacterial species. Further analysis of microbial metabolites displayed that a high-calorie diet reduced the content of short-chain fatty acids (SCFAs) in feces, and subsequently reduced the expression of GPR43, resulting in improved abnormal expression of downstream gastrointestinal peptide.Conclusions High-fat diet affects the intestinal flora-SCFAs-GPR43-gastrointestinal peptide pathway, leading to related pathological reactions, such as intestinal flora imbalance and short-chain fatty acid metabolism disorders, which in return activates GPR43, and releases PYY, GLP-1, GAS, MTL, causing lipid and energy metabolism disorders in the body. Fecal microbiota transplantation (FMT) can colonize the intestinal tract of obese rats, improving the abundance, diversity and the structure of the flora, activating GPR43 and the downstream mechanisms. This regulation of peptide hormone secretion by endocrine cells can improve metabolic disorders caused by a high-fat diet and may play a significant role in preventing and treating obesity.

Lung macrophage polarization imbalance is an important cause of aggravated pulmonary inflammation. The gut microbiota metabolites short-chain fatty acids (SCFAs) are an important regulator of macrophage polarization. A high-calorie diet has been shown to aggravate pneumonia and delay recovery, especially in children. However, the underlying mechanisms remain unclear. Our previous studies showed that a high-calorie diet can disrupt the gut microbiota structure and SCFA metabolism to aggravate LPS-induced lung inflammatory damage in juvenile rats. In this study, we investigated whether pneumonia aggravated owing to a high-calorie diet is associated with SCFA-driven macrophage phenotype changes in distal lung tissues and related mechanisms. Our data revealed that a high-calorie diet significantly aggravated pulmonary inflammatory injury in juvenile mice with LPS-induced pneumonia and also increased lung tissue M1-like (CD206-CD86+)/M2-like (CD206+CD86-) macrophage polarization imbalance. We found that a high-calorie diet decreased SCFA levels in mouse stool, serum, and lung tissues, which was most pronounced for acetate. Furthermore, we found that acetate reduction mediated by a high-calorie diet exacerbated M1-like (CD206⁻CD86⁺)/M2-like (CD206⁺CD86⁻) macrophage polarization imbalance in the lung tissue of pneumonia model mice and was associated with inhibiting histone deacetylase (HDAC), rather than G-protein-coupled receptor 43 (GPR43) signaling. More critically, we found that acetate supplementation had the most significant impact on HDAC9 and HDAC10 in the lung macrophages of pneumonia model mice fed a high-calorie diet. Furthermore, overexpression of Hdac9 and Hdac10 significantly attenuated the improvement effects of acetate on lung tissue M1-like (CD206-CD86+)/M2-like (CD206+CD86-) macrophage polarization in pneumonia model mice fed a high-calorie diet, and this mechanism was associated with the HIF-1α–glycolysis axis. Taken together, we demonstrated that a high-calorie diet could cause acetate levels to decrease in mice with LPS-induced pneumonia. This decrease in acetate was associated with a diminished inhibitory effect on HDAC9/10, potentially contributing to upregulation of HIF-1α expression and increased glycolysis. These changes may be linked to an imbalance in M1-like (CD206−CD86+)/M2-like (CD206+CD86−) macrophage polarization and aggravate lung tissue inflammatory injury. Our findings show that acetate supplementation may be a potential treatment strategy to prevent and treat pneumonia and other infectious diseases.

BACKGROUND:Sleep disturbances in preschool children are associated with dietary patterns and eating behaviors. Gastrointestinal symptoms, which frequently result from poor dietary factors, may further impair sleep. This study examines the mediating effect of gastrointestinal symptoms in the association between dietary factors and sleep disturbances. METHODS:A cross-sectional online investigation recruited 7425 participants in Beijing, with 7170 included in the final analysis. Validated scales, including the Sleep Disturbance Scale for Children, Chinese Preschoolers' Eating Behavior Questionnaire, Preschool Nutrition Quotient Questionnaire, and Gastrointestinal Symptom Rating Scale, were used to assess dietary composition, eating behaviors, gastrointestinal symptoms, and sleep disturbances. RESULTS:Gastrointestinal symptoms exacerbate the damage to sleep caused by unhealthy dietary factors. Proportions mediated of gastrointestinal symptoms ranged from 17.98 % to 31.35 % on the total score of the Sleep Disturbance Scale for Children. A dietary pattern high in beverages and low in bean and fish products adversely affected sleep through gastrointestinal symptoms. The association between unhealthy eating behaviors and sleep disturbances has been validated, with proportion mediated of 61.89 % between sleep breathing disorders and low satiety responsiveness. LIMITATIONS:As a cross-sectional study, these results cannot rule out reverse causality-where sleep disturbances may influence eating behavior. or gastrointestinal symptoms. CONCLUSIONS:These findings emphasize the importance of correcting unhealthy dietary factors as key drivers of sleep disturbances. Interventions aimed at improving gastrointestinal health can simultaneously mitigate the harmful effects of unhealthy dietary factors, offering dual benefits for sleep in preschool children.

The hypothalamic-pituitary-adrenal (HPA) axis plays an important regulatory role in inflammatory responses to systemic or local infection in the host. A high-calorie diet, which can aggravate pediatric pneumonia and delay recovery, is intimately associated with HPA axis disorder; however, its underlying mechanisms remain unknown. This study examined whether the mechanism by which a high-calorie diet aggravates pneumonia is related to HPA axis disorder. In this study, juvenile rats were fed a high-calorie diet and/or nebulized with lipopolysaccharide (LPS) for model construction. Our data shows that a high-calorie diet increases interleukin-1 beta(IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels in lung tissues and aggravates LPS-induced inflammatory injury in the lungs of juvenile rats. Additionally, we found that a high-calorie diet decreases the expression level of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in juvenile rats with pneumonia, resulting in HPA axis disorder. Hypothalamus proteomics and Western blot results proved that a high-calorie diet upregulated the expression level of hypothalamus hypoxia-inducible factor-1 alpha (HIF-1α) in juvenile rats with pneumonia, and this mechanism is associated with reduced HIF-1α ubiquitination. We further observed that HPA axis disorder was significantly abated and inflammatory damage in rat lung tissues was significantly alleviated after in vivo HIF-1α pathway inhibition. This shows that pneumonia aggravation by a high-calorie diet is associated with interference in the HIF-1α-mediated HPA axis. A high-calorie diet boosts HIF-1α signaling in the hypothalamus and exacerbates LPS-induced pneumonia by disrupting the HPA axis. This sheds light on lung inflammation and strengthens the lung-brain connection.

ETHNOPHARMACOLOGICAL RELEVANCE:Pneumonia represents a common acute respiratory infection that presents a major health concern worldwide. The Ma Xing Shi Gan Decoction (MXSG) is a famous formulation utilized for respiratory ailments for millennia and celebrated for its impressive therapeutic benefits. However, the specific mechanism of MXSG alleviating pneumonia remains unclear. AIM OF THE STUDY:This research aimed to investigate the involvement of the NLRP3 inflammasome and autophagy in pneumonia induced by lipopolysaccharide (LPS), and to examine the therapeutic mechanisms associated with MXSG. MATERIALS AND METHODS:The principal MXSG components were characterized through the application of high-performance liquid chromatography coupled with mass spectrometry. To investigate how MXSG impacts the inflammatory response and autophagy, and NLRP3 inflammasome activation, a rat model of pneumonia was created via LPS inhalation. Additionally, LPS-stimulated J774A.1 macrophages were utilized for in vitro investigations. Furthermore, the processes through which MXSG promotes autophagy and subsequently suppresses excessive NLRP3 inflammasome activation were examined utilizing 3-methyladenine (3-MA, which inhibits autophagy), compound C (CC, an inhibitor of AMPK), and siAMPK (siRNA targeting AMPK). To evaluate the binding affinity of the primary active compounds in MXSG with the essential proteins associated with autophagy, molecular docking studies were conducted. RESULTS:A comprehensive analysis revealed the identification of 828 active compounds within MXSG. In vivo, MXSG significantly alleviated lung inflammation in rats with pneumonia induced by LPS. The mechanism included improving autophagy and the subsequent inhibition of excessive NLRP3 inflammasome activation via the AMPK/mTOR/ULK1 pathway. Notably, 3-MA and CC greatly reduced the suppressive impact of MXSG on NLRP3 inflammasome activation. Molecular docking revealed that the active compounds of MXSG (amygdalin, licoricesaponin G2, and daidzein) exhibited high binding affinities to autophagy-related proteins (AMPK, mTOR, and ULK1). In vitro, MXSG demonstrated anti-inflammatory properties in LPS-activated J774A.1 macrophages and suppressed excessive NLRP3 inflammasome activation by promoting autophagy. Similarly, silencing AMPK genes notably diminished the suppressive effects of MXSG on NLRP3 inflammasome activation. This confirms that MXSG enhances autophagy and inhibits NLRP3 inflammasome activation is dependent on the AMPK/mTOR/ULK1 pathway. CONCLUSION:MXSG activates the AMPK/mTOR/ULK1 pathway, promoting autophagy and inhibiting excessive NLRP3 inflammasome activation induced by LPS. This subsequently reduces inflammatory cytokine (IL-1β, IL-18) levels, thereby mitigating LPS-triggered lung inflammation. The primary active compounds of MXSG that promote autophagy are amygdalin, licoricesaponin G2, and daidzein. These findings offer fresh perspectives on how MXSG mitigates pneumonia, highlighting the anti-inflammatory effects, and reveal potential therapeutic targets for future use in integrative medicine.

Objectives: High-calorie diets are linked to increased risks of chronic inflammation and immune dysfunction, yet their role in modulating pneumonia severity remains unclear. Focusing on the interactions among gut-originating short-chain fatty acids (SCFAs), neutrophil function, and histone deacetylases (HDACs), this research examined the exacerbating effects of a high-calorie diet on pneumonia in rats. Methods: Male Sprague-Dawley rats (3 weeks old, 110 ± 10 g) were allocated among four groups: normal diet (N), high-calorie diet (G), LPS-induced pneumonia (P), and high-calorie diet combined with lipopolysaccharide (LPS)-induced pneumonia (GP). LPS was administered via aerosolization for three days. Fecal, serum, and lung SCFA levels were quantified via GC-MS. Neutrophil extracellular traps (NETs) formation, neutrophil apoptosis, and HDAC activity were assessed using immunofluorescence, TUNEL assays, and qRT-PCR. Propionate supplementation and HDAC inhibitor (trichostatin A) interventions were applied to validate mechanistic pathways. Results: The group GP exhibited exacerbated lung inflammation, increased NETs release, and reduced neutrophil apoptosis compared to the group P. Propionate levels in feces, serum, and lung tissues decreased sharply in GP rats, correlating with elevated HDAC1/2/3/6 activity and reduced histone acetylation. Propionate supplementation or HDAC inhibition significantly attenuated lung injury, suppressed NETs, and restored neutrophil apoptosis. Conclusions: High-calorie diets exacerbate pneumonia by depleting gut-derived propionate, which drives HDAC-mediated NETs overproduction and impairs neutrophil apoptosis. Restoring propionate levels or targeting HDACs may offer therapeutic strategies for diet-aggravated respiratory diseases. Mechanistically, propionate-mediated HDAC inhibition demonstrates proof-of-concept efficacy in modulating H4 acetylation, warranting further investigation in disease-specific pneumonia models.

Oral nucleotide analogues (NAs) and peginterferon-α injections are commonly used for the treatment of patients with chronic hepatitis B (CHB). This study aims to evaluate the effects of different antiviral therapies on the degree of liver inflammation and fibrosis in CHB patients. This was a retrospective cohort study. A total of 101 CHB patients were admitted to the Liver Center of Xiamen Hospital of Traditional Chinese Medicine from 2017 to 2021 and were divided into three groups for different antiviral treatments: NAs therapy group (n = 36), peginterferon-α therapy group (n = 38) and nonantiviral therapy group (n = 27). The differences in degrees of liver inflammation and liver fibrosis between two histopathologic biopsies before and after treatment were analysed and compared to evaluate the efficacy of different treatments. The degrees of liver inflammation and liver fibrosis were improved after NAs or peginterferon-α therapy. In terms of improving the degree of liver inflammation, peginterferon-α therapy (74%) and NAs therapy (44%) were better than nonantiviral therapy (11%, p < 0.05), although no significant difference was shown between peginterferon-α therapy and NAs therapy (p = 0.974). For liver fibrosis improvement, peginterferon-α therapy showed significantly better efficacy than NAs therapy (68% vs. 33%, p = 0.044), while NAs therapy was better than nonantiviral therapy (33% vs. 11%, p = 0.028). Peginterferon-α and NAs can significantly improve the degree of liver inflammation and liver fibrosis in CHB patients. Peginterferon-α is superior to NAs in delaying and reversing liver fibrosis. This study provides a new basis for peginterferon-α therapy to prevent progression of fibrosis in CHB patients.

Objective: To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie diet-induced pneumonia through proteomics analysis. Methods: Based on the Gene Expression Omnibus (GEO) database, lung tissue samples from normal and high-fat diet (HFD) fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses. In the animal experiments, mice were randomly divided into the control (N), high-calorie diet pneumonia (M), and Yinlai decoction treatment (Y) groups. Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d. The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d. Pathological evaluation of the lung tissue was performed. Differentially expressed proteins (DEPs) in the lung tissue were identified using quantitative proteomics and bioinformatics analyses. The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory (MGL) Tools. DEPs were verified by western blot. Results: GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue. The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet. A total of 47 DEPs were identified between the Y and M groups. Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle (TCA) and oxidative phosphorylation. The protein-protein interaction network revealed that Atp5a1, Pdha1, and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction. Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide, praeruptorin B, chrysoeriol, and other components in Yinlai decoction to Atp5a1. Conclusion: The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation. Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.

BackgroundInfluenza virus is one of the most common pathogens that cause viral pneumonia. During pneumonia, host immune inflammation regulation involves microbiota in the intestine and glycolysis in the lung tissues. In the clinical guidelines for pneumonia treatment in China, Ma Xing Shi Gan Decoction (MXSG) is a commonly prescribed traditional Chinese medicine formulation with significant efficacy, however, it remains unclear whether its specific mechanism of action is related to the regulation of intestinal microbiota structure and lung tissue glycolysis.ObjectiveThis study aimed to investigate the mechanism of action of MXSG in an animal model of influenza virus-induced pneumonia. Specifically, we aimed to elucidate how MXSG modulates intestinal microbiota structure and lung tissue glycolysis to exert its therapeutic effects on pneumonia.MethodsWe established a mouse model of influenza virus-induced pneumoni, and treated with MXSG. We observed changes in inflammatory cytokine levels and conducted 16S rRNA gene sequencing to assess the intestinal microbiota structure and function. Additionally, targeted metabolomics was performed to analyze lung tissue glycolytic metabolites, and Western blot and enzyme-linked immunosorbent assays were performed to assess glycolysis-related enzymes, lipopolysaccharides (LPSs), HIF-1a, and macrophage surface markers. Correlation analysis was conducted between the LPS and omics results to elucidate the relationship between intestinal microbiota and lung tissue glycolysis in pneumonia animals under the intervention of Ma Xing Shi Gan Decoction.ResultsMXSG reduced the abundance of Gram-negative bacteria in the intestines, such as Proteobacteria and Helicobacter, leading to reduced LPS content in the serum and lungs. This intervention also suppressed HIF-1a activity and lung tissue glycolysis metabolism, decreased the number of M1-type macrophages, and increased the number of M2-type macrophages, effectively alleviating lung damage caused by influenza virus-induced pneumonia.ConclusionMXSG can alleviate glycolysis in lung tissue, suppress M1-type macrophage activation, promote M2-type macrophage activation, and mitigate inflammation in lung tissue. This therapeutic effect appears to be mediated by modulating gut microbiota and reducing endogenous LPS production in the intestines. This study demonstrates the therapeutic effects of MXSG on pneumonia and explores its potential mechanism, thus providing data support for the use of traditional Chinese medicine in the treatment of respiratory infectious diseases.

OBJECTIVES:To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS:Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS:Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION:The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.

Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic matrix deposition and irreversible aberrant tissue remodeling. Their mechanisms of action are associated with the activation of macrophages and a disturbed immune environment. We aim to determine how these activated macrophages influenced the pathogenesis of pulmonary fibrosis. We found the fibrotic areas of IPF patients contained more serum and glucocorticoid-induced kinase 1 (SGK1)-positive and M2-type macrophages. Similarly, bleomycin (BLM)+LPS significantly triggered high expression of SGK1 in the IPF mice, accompanied by destroyed lung structure and function, increased fibrosis markers and disturbed immune microenvironment. Mechanistically, SGK1 markedly promoted the reprogramming of M2-type macrophages in fibrotic lungs by triggering glycogen synthase kinase 3beta (GSK3β)-tat-interacting protein 60 (TIP60)- histone-3 lysine-27 acetylation (H3K27ac) signalings, which further released chemokine (C-C motif) ligand 9 (CCL9) to attract Th17 cells and delivered TGF-β to fibroblasts for synergistically destroying immune microenvironment, which was largely reversed by macrophage depletion in mice. We took macrophages as the entry point to deeply analyze IPF pathogenesis and further provided insights for the development of novel drugs represented by SGK1.

Background: A high-calorie diet (HCD) is a significant pathogenic factor contributing to obesity and can induce dysbiosis in the intestinal flora. Fecal microbiota transplantation (FMT) has been recognized for potentially restoring intestinal microecology. However, precise mechanisms underlying its therapeutic effects remain largely elusive. This study aimed to investigate the impact of FMT on the gut microbiota-short-chain fatty acids (SCFAs)-G protein-coupled receptor 43 (GPR43)-interleukin-18 (IL-18) pathway in HCD-induced rats. The findings provide insights and evidence for preventing and treating pediatric diseases caused Methods: Forty specific pathogen-free (SPF)-grade Sprague-Dawley (SD) rats were randomly allocated into six groups: normal control 1 (NC1), normal control 2 (NC2), normal control 3 (NC3), high-calorie diets model (M), fecal microbe transplantation treatment (FMTT), and Medilac-Vita (MV) groups. Antibiotic intervention simulated the state of antibiotic-treated rats, and a specialized diet was used to replicate the HCD model. Based on group assignments, rats received a normal diet bacterial solution, normal saline enema, or MV. Clinical characteristics and colonic morphology were observed, while changes in gut microbiota, SCFAs, GPR43, and IL-18 were assessed using 16SrDNA, gas chromatography-mass spectrometry (GC-MS), hematoxylin-eosin (HE), immunohistochemistry (IHC), and enzyme-linked immunosorbent assay (ELISA), respectively. Results: FMT effectively restored the gut microbiota of antibiotic-induced rats. In the HCD-induced rats, FMTT significantly alleviated the pathological state and increased alpha indices and beta distances (p < 0.05). Furthermore, significant alterations in the relative abundances of gut bacterial genera associated with SCFAs production were observed. FMTT increased SCFA content in feces, especially acetic acid (p < 0.05). Notably, downstream pathways related to SCFAs, such as GPR43-IL-18, were modulated by FMT in HCD-induced rats (p < 0.05). Recognizing the crucial role of gut microbiota in SCFAs metabolism, a co-occurrence network among the Lactobacillaceae and SCFAs-GPR43-IL-18 was constructed. Conclusion: The Lactobacillaceae-acetic acid-GPR43-IL-18 pathway emerges as a potential biological basis for the pathological state of HCD-induced rats. FMT exhibits corrective properties by influencing this pathway.

ObjectiveThis retrospective study aims to investigate the treatment of tic disorder (TD) in Dongfang Hospital affiliated with Beijing University of Chinese Medicine, explore its underlying mechanism, and provide valuable insights for future research and clinical management of TD.MethodsThe electronic medical records of children with TD, from 2015 to 2021, were extracted from the information system of Dongfang Hospital affiliated with Beijing University of Chinese Medicine. The clinical characteristics of TD, utilization patterns of Chinese herbal medicine and synthetic drugs in prescriptions, as well as their pharmacological effects, were statistically described and categorized. In addition, association rules and network pharmacology were employed to identify core prescriptions (CPs) and elucidate their microscopic molecular mechanisms in treating TD.ResultsThe age range of the children was from 6 to 11 years, with a higher proportion of male participants than female ones. The average duration of treatment was 6 weeks. Regimen Z for the treatment of TD can be summarized as follows: Chinese herbal medicine [Saposhnikoviae Radix (FangFeng), Puerariae Lobatae Radix (GeGen), Uncariae Ramulus cum Uncis (GouTeng), Acori Tatarinowii Rhizoma (ShiChangPu), Chuanxiong Rhizoma (ChuanXiong)] and vitamins [lysine, inosite, and vitamin B12 oral solution] form the basic treatment, combined with immunomodulators, antibiotics, electrolyte-balancing agents, and antiallergic agents. CPs primarily exerted their effects through the modulation of gene expression (transcription), the immune system, and signal transduction pathways, with interleukin-4 and interleukin-13 pathways being particularly crucial. Among the lysine synthetic drugs used, inosite and vitamin B12 oral solution were the most frequently prescribed.ConclusionThe regimen Z drug treatment holds significant importance in the field, as it exerts its therapeutic effects through a multitude of pathways and intricate interventions. Chinese herbal medicine primarily regulates immune system–related pathways, while synthetic drugs predominantly consist of vitamins.

名老中医学术思想和临床经验是中医药传承发展中的重要内容.名老中医传承研究取得了诸多成果,但仍存在研究数据质量有待提高、缺乏医道层次的研究和方法研究落地不足等问题.本文引入了钱学森系统工程方法学体系,从复杂系统思维认识名老中医诊疗过程,应用"从定性到定量""循环迭代"的综合集成法,总结名老中医的学术经验.首先集成专家意见形成假设,进而构建多参数、多算法的综合模型,并且进行模型验证与迭代,最后,将人的"心智"与计算机的"智能"相结合,构建以人为主、人机结合的传承方式.应用此方法学体系将更为全面、客观、可靠、高效地将名老中医"经验"转化为"知识",让名老中医经验可复制、可传播、可积累、可创新,为中医药事业的继承和发展创新提供新思路.