Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

This study integrates metabolomics and transcriptomics to explore the immediate effects of Angong Niuhuang Pills(ANP) in intervening traumatic brain injury(TBI) in rats. A TBI model was successfully established in rats using the optimized Feeney free-fall impact technique. Rats were randomly divided into sham operation(sham) group, model(Mod) group, positive drug(piracetam) group, ANP low-dose(ANP-L) group, and ANP high-dose(ANP-H) group according to a random number table. Nissl staining and immunofluorescence were used to count the number of Nissl bodies and detect B-cell lymphoma-2(Bcl-2) gene, caspase-3, and tumor protein 53(TP53) expression in brain tissue, and enzyme-linked immunosorbent assay(ELISA) was used to measure prostaglandin-endoperoxide synthase 2(PTGS2) level in rat brain tissue. Metabolomics and transcriptomics analyses were conducted for brain tissue from sham, Mod, and ANP-H groups. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out to indicate the mechanisms of ANP in the intervention of TBI. Integrative metabolomics and transcriptomics analysis revealed the metabolic pathways involved in ANP's intervention in TBI. The results showed that ANP significantly increased the number of Nissl bodies in TBI rat brain tissue, upregulated Bcl-2 expression, and downregulated the levels of caspase-3, TP53, and PTGS2. Compared to the Mod group, the ANP-H group significantly upregulated 12 differential metabolites(DMs) and downregulated 25 DMs. Five key metabolic pathways were identified, including glycerophospholipid metabolism, pyrimidine metabolism, glycine, threonine, and serine metabolism, arginine and proline metabolism, and D-amino acid metabolism. Transcriptomics identified 730 upregulated and 612 downregulated differentially expressed genes(DEGs). Enrichment analysis highlighted that biological functions related to inflammatory responses and apoptotic processes, and key signaling pathways, including phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt) and mitogen-activated protein kinase(MAPK) were significantly enriched. The data of transcriptomics and metabolomics pinpointed three key metabolic pathways, i.e., glycerophospholipid metabolism, pyrimidine metabolism, and glycine, threonine, and serine metabolism.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Brain Injuries, Traumatic/metabolism* ; Male ; Metabolomics ; Rats, Sprague-Dawley ; Transcriptome/drug effects* ; Cyclooxygenase 2/genetics* ; Brain/metabolism* ; Caspase 3/genetics* ; Humans ; Tumor Suppressor Protein p53/genetics*

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10^-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1β in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.
Animals ; Acute Lung Injury/pathology* ; Lipopolysaccharides ; Ursidae ; Gastrointestinal Microbiome/drug effects* ; Bile/chemistry* ; Lipopolysaccharide Receptors/metabolism* ; Powders ; Male ; Lung/drug effects* ; Mice ; Peroxidase/metabolism* ; Signal Transduction/drug effects* ; Cytokines/metabolism*

ObjectiveThis study aimed to investigate the effects of 4-week high-intensity interval training (HIIT) on synaptic plasticity in the prefrontal cortex (PFC) of rats exposed to chronic unpredictable mild stress (CUMS), and to explore its potential mechanisms. MethodsA total of 48 male Sprague-Dawley rats were randomly divided into 4 groups: control (C), model (M), control plus HIIT (HC), and model plus HIIT (HM). Rats in groups M and HM underwent 8 weeks of CUMS to establish depression-like behaviors, while groups HC and HM received HIIT intervention beginning from the 5th week for 4 consecutive weeks. The HIIT protocol consisted of repeated intervals of 3 min at high speed (85%-90% maximal training speed, S_max) alternated with one minute at low speed (50%-55% S_max), with 3 to 5 sets per session, conducted 5 d per week. Behavioral assessments and tail-vein blood lactate levels were measured at the end of the 4th and 8th weeks. After the intervention, rat PFC tissues were collected for Golgi staining to analyze synaptic morphology. Enzyme-linked immunosorbent assays (ELISA) were employed to detect brain-derived neurotrophic factor (BDNF), monocarboxylate transporter 1 (MCT1), lactate, and glutamate levels in the PFC, as well as serotonin (5-HT) levels in serum. Additionally, Western blot analysis was conducted to quantify the expression of synaptic plasticity-related proteins, including c-Fos, activity-regulated cytoskeleton-associated protein (Arc), and N-methyl-D-aspartate receptor 1 (NMDAR1). ResultsCompared to the control group (C), the CUMS-exposed rats (group M) exhibited significant reductions in sucrose preference rates, number of grid crossings, frequency of upright postures, and entries into and duration spent in open arms of the elevated plus maze, indicating marked depressive-like behaviors. Additionally, the group M showed significantly reduced dendritic spine density in the PFC, along with elevated levels of c-Fos, Arc, NMDAR1 protein expression, and increased concentrations of lactate and glutamate. Conversely, BDNF and MCT1 contents in the PFC and 5-HT levels in serum were significantly decreased. Following HIIT intervention, rats in the group HM displayed considerable improvement in behavioral indicators compared with the group M, accompanied by significant elevations in PFC MCT1 and lactate concentrations. Furthermore, HIIT notably normalized the expression levels of c-Fos, Arc, NMDAR1, as well as glutamate and BDNF contents in the PFC. Synaptic spine density also exhibited significant recovery. ConclusionFour weeks of HIIT intervention may alleviate depressive-like behaviors in CUMS rats by increasing lactate levels and reducing glutamate concentration in the PFC, thereby downregulating the overexpression of NMDAR, attenuating excitotoxicity, and enhancing synaptic plasticity.

An effective method for simultaneously detecting four semivolatile earthy-musty odors in freshwater fish by gas chromatography-mass spectrometry(GC-MS)was developed.The concurrent extraction of geosmin(GSM),2-methylisoborneol(MIB),2-isopropyl-3-methoxypyrazine(IPMP),and 2-isobutyl-3-methoxypyrazine(IBMP)in fish tissue was conducted with n-hexane.The optimized QuEChERS material was implemented,and it was found that C18,primary secondary amine(PSA)and MgSO4 could adsorb the target analytes in n-hexane.So only the graphitized carbon black(GCB)could be used to purify the extraction.The adsorption rates of different materials for the four kinds of odors materials were explored in n-hexane and ethyl acetate.The experimental results revealed that the adsorption rates of silica for the four targets were 99.5%-100%in n-hexane and 0.7%-5.0%in ethyl acetate respectively.Then the silica solid phase extraction(SPE)method was utilized to eluent the compounds using 1.0 mL n-hexane/ethyl acetate in different proportions.The results of the comparative analysis demonstrated that n-hexane/ethyl acetate(4∶1,V/V)was the optimized eluent.Based on the obtained results,n-hexane extraction and GCB purification combined with silica SPE were used to isolate GSM,MIB,IPMP and IBMP from fish and the method was validated.It was found that the method showed good linearity in the range of 0.5-200 ng/mL,and with detection limits of 0.6 μg/kg for GSM and MIB,0.2 μg/kg for IPMP and IBMP.The limits of quantitation(LOQ)were 1.0 μg/kg for GSM and MIB,0.6 μg/kg for IPMP and IBMP.Good recoveries(77.5%-112.0%)and relative standard deviations(1.56%-9.42%)were also obtained.The use of silica SPE greatly mitigated the issue that the off-flavor compounds were easily lost in the gas blowing concentration process.There was no cross contamination in this method because the sample pretreatments were conducted separately,which was different with the most commonly used HS-SPME method for detecting semi-volatile substances.The sensitivity of this method was high enough to produce good quantitative results below the odor thresholds of the examined off-flavor compounds.

Objective To observe the effects of electroacupuncture(EA)on TGF-β1/Smads signaling pathway and epithelial-mesenchymal transition(EMT)related proteins in rats with neurogenic bladder(NB)after spinal cord injury;To explore the possible mechanism of EA in improving NB fibrosis.Methods Totally 36 female SD rats were randomly selected,with 10 rats in the sham-operation group and the remaining 26 rats undergoing complete transection of the spinal cord beneath the T8 vertebrae to establish a NB rat model.The modeling rats were randomly divided into model group and EA group,with 10 rats in each group.EA group was applied to"Ciliao","Zhongji"and"Sanyinjiao",20 min per time,once a day for 7 days.The general condition of the rats in each group was observed,the ultrasound index of the bladder was detected by ultrasound technique,the bladder function of the rats was detected by urodynamics,the body mass of the rats and the wet weight of the bladder were recorded,and the bladder index was calculated.HE staining was used to observe bladder tissue morphology,the degree of bladder tissue fibrosis and bladder wall thickness were detected by Masson staining.The positive expressions of E-cadherin,N-cadherin and Vimentin in bladder tissue were detected by immunohistochemistry.The protein expressions of TGF-β1,p-Smad2/3,E-cadherin,N-cadherin and Vimentin were detected by Western blot.Results Compared with the sham-operation group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the model group significantly increased(P<0.001),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly increased(P<0.001),the bladder index increased significantly(P<0.001),the bladder epithelial cells were thickened and arranged irregularly,the bladder collagen volume fraction and bladder wall thickness significantly increased(P<0.001),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue increased(P<0.01),and the expression of E-cadherin decreased(P<0.001).Compared with the model group,the upper and lower diameter,anteroposterior diameter,transverse diameter,bladder volume of the EA group decreased significantly(P<0.05),the maximum bladder pressure,leak point pressure difference,perfusion time and maximum bladder capacity significantly decreased(P<0.05),the bladder index significantly decreased(P<0.05),the thickness of the bladder epithelial cell layer became thinner and arranged more neatly,and the bladder collagen volume fraction and bladder wall thickness of the bladder were significantly reduced(P<0.05),the expressions of TGF-β1,p-Smad2/3,N-cadherin and Vimentin in bladder tissue significantly decreased(P<0.05),and the expression of E-cadherin significantly increased(P<0.05).Conclusion EA may reduce the EMT of bladder epithelial cells and decrease the degree of bladder tissue fibrosis by inhibiting the activation of the TGF-β1/Smads signaling pathway,thereby improving bladder function in NB rats after spinal cord injury.