OBJECTIVE To investigate the mechanism of Huangqin decoction in improving ulcerative colitis （UC） through the gut microbiota-tryptophan metabolism-aryl hydrocarbon receptor （AhR） axis. METHODS Mice were randomly divided into normal group （normal saline）， model group （normal saline）， microbiota depletion-model group （normal saline）， microbiota depletion-Huangqin decoction group （9.1 g/kg， by crude drug， similarly hereinafter）， Huangqin decoction group and mesalazine group （positive control group， 0.4 g/kg）， with 6 mice in each group. Microbiota depletion was achieved by providing free access to a mixed antibiotics for 10 days. The UC model was induced by administering 2.5% dextran sulfate sodium solution for 7 days. After successful modeling， each treatment group received corresponding drugs or normal saline intragastrically once daily for 10 days. After the final administration， body weight change ratio， disease activity index （DAI） score， and colon length were evaluated； colon pathological changes were observed； serum levels of interleukin-6 （IL-6）， IL-10， IL-22， and tumor necrosis factor-α （TNF-α） were measured； the expressions of Occludin， zonula occluden-1 （ZO-1）， and AhR in colon tissue were detected； fecal samples were subjected to high-throughput sequencing to analyze targeted tryptophan metabolomics. RESULTS Compared with the model group， Huangqin decoction group showed reduced infiltration of inflammatory cells in the colon tissue and restoration of the intestinal mucosal structure. Body weight change ratio， colon length， serum content of IL-10， the expressions of Occludin， ZO-1 and AhR in colon tissue and the contents of tryptophan metabolites indole-3-propionic acid （IPA）， N -acetylserotonin （NAS） and indole-3-acetic acid （IAA） were all significantly increased （ P ＜0.05）； DAI score， serum levels of IL-6， TNF-α， and IL-22 and the content of tryptophan metabolite indole-3-ethanol were significantly decreased （ P ＜0.05）； gut microbiota structure was improved， with increased relative abundances of beneficial bacteria such as Lactobacillus ， and decreased relative abundances of pathogenic bacteria such as Escherichia-Shigella . However， after antibiotic-induced microbiota depletion， although Huangqin decoction significantly increased the content of NAS in the feces of mice， the expression of AhR protein in colon tissue did not increase concurrently. CONCLUSIONS Huangqin decoction can repair the intestinal mucosal barrier in UC mice by regulating the gut microbiota and promoting the production of IPA and IAA， thereby activating AhR. This suggests that an intact gut microbiota is an important prerequisite for Huangqin decoction to exert its AhR-regulating effects.

Chronic liver diseases are a group of diseases in which the liver is subjected to a variety of injuries over a long period of time， resulting in irreversible pathological changes that last longer than 6 months. Emodin （EMO） is a natural anthraquinone derivative derived from Rheum officinale， and its pharmacological effect has been extensively studied， exhibiting a variety of biological properties and involving multiple signaling molecules and pathways. Western medicine or surgical treatment is currently the main treatment regimen for chronic liver diseases， and the advance in treatment is limited by various reasons such as side effects and high costs. Due to its natural origin and efficacy， EMO has unique advantages in the treatment of chronic liver diseases and has now become a research hotspot. This article summarizes the therapeutic effect of EMO on chronic liver diseases and its mechanism， in order to provide a certain scientific basis for the traditional Chinese medicine treatment of chronic liver diseases and the development of drugs in clinical practice.

ObjectiveTo investigate microbial contamination status and distribution characteristics in laboratory animal barrier facilities, so as to provide a scientific basis for environmental quality control in barrier facilities. MethodsIn accordance with the national standard "Laboratory Animals—Environment and Housing Facilities" and the "Standard Operating Procedures" of the barrier facility, bacterial monitoring was performed on samples of air-settling bacteria, materials, and personnel gloves in the single-corridor barrier facility of the Animal Core Facility, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CEMCS). The monitoring data from January 2020 to December 2024 were collected, organized and statistically analyzed, and partial samples were subjected to species identification using PCR and sequencing methods. ResultsA total of 7 898 samples were collected from 2020 to 2024, including 3 175 air-settling bacteria samples, 3 353 material samples, and 1 370 glove samples. The overall compliance rate was 95.7% (7 559/7 898), among which the compliance rate of air-settling bacteria was 97.1% (3 084/3 175), that of materials was 93.2% (3 125/3 353), and that of personnel gloves was 98.5% (1 350/1 370). Over the five years, the compliance rates of all three types of monitored samples were above 90%. There were statistically significant differences in the compliance rates of air-settling bacteria and material samples among different quarters (P<0.05). Further investigation was conducted on samples collected from January to March 2024, and 190 bacterial strains were obtained through isolation and culture, including 126 strains from air-settling bacteria, 52 strains from materials, and 12 strains from personnel gloves. The strains were identified by PCR amplification and sequencing, and the 190 bacterial strains belonged to 9 genera and 20 species. Gram-positive bacteria accounted for the majority, with Staphylococcus as the dominant genus, accounting for 77.9% (148/190). ConclusionMicroorganisms carried by air, materials, and personnel gloves in barrier facilities are mainly Gram-positive bacteria. Regular monitoring of air-settling bacteria, materials, and personnel gloves in barrier facilities enables timely detection and control of potential risks during husbandry management and facility operation, which is of great significance for maintaining the sound operation of the barrier facility system and ensuring the quality of animal experiments.

ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.

ObjectiveTo investigate the protective effect of α-ketoglutarate （α-KG） on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research （ICR） mice were mated in a ratio of 2∶1 between females and males， and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups： control group， arsenic group， α-KG group， arsenic+α-KG group. On gestational day 0-16 （GD0-GD16）， the arsenic and arsenic+α-KG groups were exposed to sodium arsenite （NaAsO₂ ，15 mg/L） in drinking water everyday， and the α-KG and arsenic+α-KG groups were gavaged with α-KG （2 g/kg） everyday. On GD16， pregnant mice were euthanized to collect fetal liver， and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides （TGs） and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry （LC-MS/MS）. Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction （qPCR） was used to detect the expression level of genes related to lipid synthesis， transport， and degradation， and phosphatidylinositol 3' -kinase/ protein kinase B （PI3K/AKT） in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver； body weight and crown-rump length were reduced （P_TuKey<0.05）； the level of hepatic TGs was elevated in arsenic group （P_TuKey<0.05）； oil-red O staining showed a significant increase in lipid droplets in arsenic group （P_TuKey<0.01）； the expression of lipid synthesis-related genes were significantly upregulated （P_TuKey<0.05）； the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated （P_TuKey<0.05）； the expression of PI3K， AKT decreased（P_TuKey<0.05）. Compared with the arsenic group， the body weight and crown-rump length of fetus increased in the arsenic+α-KG group （P_TuKey<0.05）； the level of hepatic TGs decreased in the arsenic+α-KG group （P_TuKey<0.05）； oil red O staining showed lipid droplets significantly decreased （P_TuKey<0.01）； the expression of lipid synthesis-related genes were downregulated （P_TuKey<0.05）， the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated （P_TuKey<0.05）； the expression levels of PI3K and AKT increased （P_TuKey<0.05）. Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Objective: To explore the relationship between related factors of non-suicidal self-injury behavior (NSSI) among middle school students in Guizhou Province, so as to provide the evidence for preventing high risk behaviors in adolescents. Methods: A stratified cluster random sampling method was used to select 1 034 junior and senior middle school students from Zunyi City, Qiannan Prefecture and Tongren City in Guizhou Province from April to October in 2023. Questionnaire survey was conducted to collect information including Adolescent Self injury Scale and Family Assessment Device. The R 4.4.1 software was employed for network analysis visualization, centrality indicators, and result stability assessment. Results: The detection rate of NSSI behavior among middle school students in Guizhou province was 29.6%, with a detection rate of 25.5% for boys and 33.1% for girls, showing a statistically significant difference ( χ 2=7.07, P <0.05). There were statistically significant differences in scores of emotional communication, egoism, family rules, positive communication, problem solving, expression of positive emotions and management of negative emotions self-efficacy, and bullying victimization in various dimensions between middle school students with and without NSSI ( Z =-13.66 to -7.05, P <0.01). NSSI among middle school students was positively correlated with social/relational bullying, depression and anxiety, and there were relatively close connections in the network ( r =0.35, 0.43, 0.42, P <0.01). Centrality indicators showed that the highest in strength and closeness centrality were stress ( Z =1.29, 1.58), the highest in betweenness centrality was for emotional communication ( Z =1.91), and the highest in expected influence index was for physical bullying ( Z =1.44)( P < 0.05). Conclusions Stress, emotional communication and physical bullying have significant impacts in the network of factors related to NSSI. Social/relational bullying, depression and anxiety have strong direct correlations with NSSI behavior among middle school students.

ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

OBJECTIVE To investigate the effects and mechanism of Wenpi tongluo kaiqiao formula （WPTL） against neuronal necroptosis in Alzheimer’s disease （AD） mice based on the Z-DNA binding protein 1 （ZBP1）/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS Forty APP/PS1 transgenic AD mice were randomly divided into model group， WPTL low-dose （WPTL-L） group （10.4 g/kg， calculated by the raw medicine）， WPTL high-dose （WPTL-H） group （20.8 g/kg， calculated by the raw medicine） and donepezil hydrochloride group （3 mg/kg）， with 10 mice in each group； another 10 C57BL/6J mice were selected as normal control group. Intragastric administration， once a day， for 30 consecutive days. Twenty-four hours after the last administration， Morris water maze test was performed to evaluate learning and memory abilities； the pathological morphology of hippocampal tissues was observed； the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-4 （IL-4） were determined； the expressions of amyloid precursor protein （APP）， Tau protein， and ZBP1/MLKL signaling pathway-related proteins in hippocampal tissues were detected； the positive expression of phosphorylated receptor-interacting protein kinase 3 （p-RIPK3） in the neurons of hippocampal tissues and mRNA expression of ZBP1 were measured in hippocampal tissues. RESULTS Compared with normal control group， the escape latency of mice in model group was prolonged significantly on day 3 to 5 （P＜0.05）， the times of crossing platform reduced significantly （P＜0.05）， and obvious pathological changes were observed in the hippocampal tissue. The level of TNF- α， the expressions of APP， p-Tau and ZBP1， the phosphorylation levels of RIPK1， RIPK3 and MLKL， the fluorescence intensity of p-RIPK3 as well as the mRNA expression of ZBP1 were significantly increased （P＜0.05）， while the serum level of IL-4 was decreased significantly （P＜0.05）. Compared with model group， above indexes were reversed significantly in administration groups （P＜0.05）， and pathological damage of hippocampal tissue was alleviated. CONCLUSIONS WPTL can inhibit the ZBP1/MLKL signaling pathway， reduce neuronal necroptosis in AD mice， and inhibit inflammatory responses， thereby improving learning and spatial memory abilities in AD mice.