ObjectiveTo investigate the mechanism of action of modified Chaihu Shugan Powder in the treatment of abnormal gallbladder relaxation in gallbladder cholesterol stone （CS） with liver depression syndrome， and to provide a basis for clinical medication. MethodsMice were given a high-fat lithogenic diet combined with chronic unpredictable mild stress （CUMS） to establish a model of CS. A total of 45 male C57BL/6 mice were randomly divided into blank group （6 mice fed a normal diet） and CS group （39 mice fed a high-fat lithogenic diet）. After CS modeling， the CS group was further randomly divided into four subgroups of CS group， CS liver depression group， traditional Chinese medicine group （treated with modified Chaihu Shugan Powder）， and Western medicine group （treated with ursodeoxycholic acid）， with 9 mice in each group. All subgroups were fed with the high-fat lithogenic diet， and all mice except those in the CS group were given 21 days of CUMS for modeling. Samples were collected after intervention. The serum levels of cholecystokinin （CCK）， liver function parameters， and blood lipid profiles were measured； HE staining was performed for liver and gallbladder tissue； qPCR and Western blot were used to measure the mRNA and protein expression levels of G protein-coupled bile acid receptor 1 （TGR5） and glucagon-likepeptide-1/2 （GLP-1/2） in the intestine and TGR5 and glucagon-like peptide-2 receptor （GLP-2R） in gallbladder； metabolomics methods were used to determine bile acid composition in intestinal contents. The independent-samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test or the Games-Howell method was used for further comparison between two groups. ResultsCompared with the blank group， the CS group showed significant gallstone formation， bile turbidity， hepatic steatosis， abnormal gallbladder wall structure， and significant increases in anxiety- and depression-like behaviors based on behavioral tests； significant increases in the level of total cholesterol in bile and the serum levels of alanine aminotransferase， aspartate aminotransferase， and low-density lipoprotein and significant reductions in the level of total bile acid （TBA） in bile and the serum levels of CCK and high-density lipoprotein （HDL） （all P<0.05）； significant increases in the mRNA expression levels of GLP-1/2 and TGR5 in the intestine and the protein expression levels of GLP-2R and TGR5 in the gallbladder and significant reductions in the mRNA expression levels of GLP-2R and TGR5 in the gallbladder （all P<0.05）； significant changes in multiple bile acid components in intestinal contents （all P<0.05）. Compared with the CS group， the CS liver depression group had further aggravation of pathological and behavioral manifestations， changes in bile acid composition， significant increases in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine， and significant increases in the protein and mRNA expression levels of TGR5 and GLP-2R in the gallbladder （all P<0.01）. Compared with the CS liver depression group， both treatment groups had an improvement in gallbladder morphology， alleviation of stones and liver injury， and recovery of liver function and blood lipid levels， as well as significant reductions in the protein and mRNA expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder （all P<0.05）； the traditional Chinese medicine group showed significant increases in glycodeoxycholic acid （GDCA）， tauro-α-muricholic acid （T-α-MCA）， and taurochenodeoxycholic acid （TCDCA） （all P<0.05）， while the Western medicine group showed significant increases in taurohyodeoxycholic acid， T-α-MCA， TCDCA， GDCA， and glycoursodeoxycholic acid （all P<0.05）. Compared with the Western medicine group， the traditional Chinese medicine group had significantly greater behavioral improvements， significantly higher levels of TBA in bile and serum HDL （both P<0.01）， significant reductions in the protein expression levels of TGR5 and GLP-1/2 in the intestine and TGR5 and GLP-2R in the gallbladder， and a significant reduction in the mRNA expression level of TGR5 in the intestine （all P<0.01）， as well as a significant increase in tauroursodeoxycholic acid and significant reductions in glycoursodeoxycholic acid， taurohyodeoxycholic acid， TCDCA， and taurolithocholic acid （all P<0.05）. ConclusionModified Chaihu Shugan Powder can improve liver function and abnormal gallbladder relaxation in CS with liver depression syndrome by regulating the bile acid-TGR5 axis， thereby exerting the therapeutic effect of soothing the liver， resolving depression， moving Qi， and promoting bile flow.

ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure （ALF） by observing its effect on a mouse model of ALF after prophylactic administration， and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group， model group， Jiedu Huayu granules group （JDHY group）， and farnesoid X receptor （FXR） agonist （GW4064） group using a random number table， with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling， those in the normal group and the model group were given 0.9% NaCl solution by gavage， and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling， and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin （TBil）， total bile acids （TBA）， gamma-glutamyl transferase （GGT）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in mice from each group； HE staining was used to observe liver pathological changes； RT-PCR was used to measure the mRNA expression levels of FXR， fibroblast growth factor 15 （FGF15）， fibroblast growth factor receptor 4 （FGFR4）， small heterodimer partner （SHP）， and bile salt export pump （BSEP） in mice， and Western blot was used to measure the protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP. A one-way analysis of variance was used for comparison between groups， and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group， the model group had significant increases in the serum levels of TBil， ALT， AST， TBA， and GGT （all P<0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil， ALT， AST， TBA， and GGT （all P <0.01）. HE staining showed that compared with the model group， the JDHY group and the GW4064 group had milder pathological injury， a reduction in the area of hepatocyte necrosis， and alleviation of cellular swelling and edema. Compared with the normal group， the model group had significant reductions in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.01）， and compared with the model group， the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR， FGF15， FGFR4， SHP， and BSEP in liver tissue （all P <0.05）. ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.

BackgroundNon-suicidal self-injury （NSSI） behavior has become a global public health concern affecting the physical and mental health of adolescents. The experiential avoidance model posits that childhood trauma contributes to NSSI behavior through the mediating pathway of emotional dysregulation. However， existing research has predominantly focused on isolated psychological or social factors， with limited attention to their interactive effects of emotional dysregulation and social anxiety， both of which fall within the psychosocial domain. ObjectiveTo examine the relationship between childhood trauma and NSSI among adolescents， and to analyze the mediating role of emotional dysregulation and the moderating role of social anxiety， so as to provide evidence for targeted interventions for NSSI behavior of adolescents. MethodsA total of 282 adolescent inpatients who consecutively admitted to the Department of Psychiatry of Guangdong Provincial People's Hospital from March to December 2025 and met the Diagnostic and Statistical Manual of Mental Disorders，fifth edition（DSM-5）criteria for NSSI were enrolled as study participants. Participants were assessed using the general information questionnaire， the Adolescent Self-Harm Questionnaire， the Childhood Trauma Questionnaire （CTQ）， the Difficulties in Emotion Regulation Scale （DERS）， and the Social Anxiety Scale for Adolescents （SAS-A）. Pearson correlation analysis was used to examine correlations among scale scores. model 4 and model 58 of the Process 4.1 were used to test the mediating effect of emotional dysregulation and the moderating effect of social anxiety， respectively. ResultsCTQ score was positively associated with score of the Adolescent Self-Injury Questionnaire （r=0.279， P<0.01）. Emotional dysregulation significantly partially mediated the relationship between childhood trauma and NSSI behavior， with a mediating effect of 0.112 （95% CI： 0.043–0.208）， accounting for 40.14% of the total effect. Social anxiety moderated the association between childhood trauma and emotional dysregulation，the effect value was 0.102 （95% CI： 0.008–0.196）， as well as the relationship between emotional dysregulation and NSSI behavior， the effect value was 0.130 （95% CI： 0.033–0.226）. ConclusionEmotional dysregulation may mediate the relationship between childhood trauma and NSSI behavior among hospitalized adolescents， while social anxiety moderates both the first and second paths of this mediating process. ［Funded by Guangdong Medical Science and Technology Research Fund Project （number， A2022538）］

Objective: To analyze the distribution characteristics of school bullying related contents on the Douyin platform, and to provide a scientific basis for the prevention and intervention of school bullying in the online environment. Methods: Web crawler technology was employed to collect data related to school bullying from Douyin in May 2025, using 21 keywords including "school violence" and "child being beaten". A dataset comprising video titles, publisher types, and interaction metrics was constructed. After manual screening and classification, the content themes, engagement characteristics, and sentiment tendencies of titles were analyzed. Results: A total of 2 388 valid videos released between January 2019 and May 2025 were included. Physical bullying (767 cases, 32.12%) and verbal bullying (534 cases, 22.36%) were the most common types. Content themes differed significantly across account types ( χ 2=782.85, P <0.01). Official media accounts predominantly focused on case reports ( AR = 14.52 ) and legal updates ( AR =5.49), and social media influencer accounts preferred scenario reenactments ( AR =4.07) and film clips ( AR =3.83), while ordinary users focused on coping strategies ( AR =8.76). Account types had a stronger effect on engagement metrics than content themes (all P <0.01). Sentiment analysis of titles revealed that official media accounts tended toward negative sentiment ( AR = 6.41), social media influencer accounts toward neutral sentiment ( AR =2.47), and ordinary users toward positive sentiment ( AR =4.44). Keyword analysis showed high frequency terms related to responsible parties such as "children" "parents", and "classmates" , while demand oriented words like "how" were prominent. Conclusions School bullying related contents on Douyin demonstrate significant dissemination stratification by account type, and the dissemination effect is significantly influenced by the type of content publisher. There is a clear public demand for practical guidance on bullying prevention and intervention strategies.

ObjectiveTo investigate molecular alterations in tumor cells of multiple myeloma （MM） before and after B-cell maturation antigen （BCMA）-directed chimeric antigen receptor T-cell （CAR-T） therapy， with a focus on changes in invariant chain （CD74） expression and its potential association with macrophage migration inhibitory factor （MIF）. MethodsPaired bone marrow samples collected before BCMA CAR-T infusion and at ≥3 months after infusion were analyzed. Differential gene expression， functional enrichment， and cell-cell communication analyses were performed in malignant plasma cell-related populations. In vitro coculture experiments and MIF stimulation assays were conducted using the U266 cell line， and cell proliferation was assessed by CCK-8 and EdU incorporation assays. ResultsCD74 expression was upregulated in MM cells at ≥3 months after BCMA CAR-T therapy， and CD74 expression was consistently higher in post-treatment samples than in paired pre-treatment samples across all four cases. Genes upregulated after treatment were mainly enriched in antigen processing and presentation， cell adhesion， and immune-related processes. Cell-cell communication analysis revealed prominent interaction signals involving MIF-related pathways. In vitro experiments showed that coculture conditions induced changes in membrane CD74 expression in tumor cells， and MIF stimulation promoted proliferation of U266 cells. ConclusionCD74 expression is upregulated in tumor-associated MM cells following BCMA CAR-T therapy and is accompanied by the activation of the MIF-CD74 axis， suggesting a potential role in post-treatment adaptive changes and warranting further investigation into its therapeutic relevance.

Objective To investigate the mechanisms of 6-hydroxygenistein(6-OHG)in the treatment of high-altitude hypoxia-induced lung injury.Methods The intersection targets of 6-OHG and high-altitude hypoxia-induced lung injury were identified using databases,including Swiss Target Prediction,SuperPred,GeneCards,and OMIM.The STRING database and Cytoscape software were used to construct a protein interaction network for the intersection targets of drugs and diseases,and targets with degree values greater than the median were identified as key targets.GO and KEGG enrichment analyses of key targets were performed using the DAVID database to identify relevant signaling pathways.The Maestro 13.7 software was used for molecular docking validation.A large hypobaric hypoxic chamber was used to establish a high-altitude lung injury model in mice.A total of 42 male BALB/c mice were randomly assigned to 3 groups(n=14 in each group),including a normal control group,which was exposed to the environmental conditions at the altitude of 1400 m and received a single intraperitoneal injection of normal saline,a model group,which received a single intraperitoneal injection of normal saline,and a 6-OHG group,which received a single intraperitoneal injection of 6-OHG at 100 mg/kg.Then,1 h after drug administration,mice in the model and 6-OHG groups were placed in a large hypobaric hypoxic simulation chamber for animal experiments.Then,they ascended to an altitude of 8 000 m at a speed of 10 m/s,remained in that environment for 24 h,and then descended to an altitude of 3500 m.Mice in the three groups were sacrificed,and their lung tissues were extracted to measure the water content in the lungs.Pathological changes were observed using HE staining,and the levels of malondialdehyde(MDA),H2O2,total superoxide dismutase(T-SOD),and glutathione(GSH)were measured.Western blot was performed to determine the expression levles of p-PI3K/PI3K,p-AKT/AKT,hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF)proteins.Results Key targets such as serine/threonine protein kinase 1(AKT1),HIF-1α,epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9),and peroxisome proliferator-activated receptor A(PPARA)were identified.GO and KEGG enrichment analyses showed that the targets of 6-OHG in the treatment of high altitude hypoxia-induced lung injury were mainly involved in PI3K/AKT,HIF-1α/VEGF,tumor necrosis factor(TNF),and other signaling pathways.The results of animal experiments demonstrated that compared with the model group,the 6-OHG group showed significant improvement in the pathological damage of lung tissues induced by high altitude hypoxia,presenting statistically significant differences in the levels of MDA,H2O2,GSH,and T-SOD(P＜0.01).The results of Western blot assay revealed statistically significant differences in the p-PI3K/PI3K,p-AKT/AKT,HIF-1α,and VEGF levels in the lung tissues of the 6-OHG group compared with those of the model group(P＜0.01).The molecular docking results showed that 6-OHG could form stable binding with PI3K,AKT,HIF-1α,and VEGF.Conclusion 6-OHG may alleviate lung injury induced by high altitude hypoxia in mice by activating the PI3K/AKT signaling pathway and inhibiting the HIF/VEGF signaling pathway.

Objective To report two cases of type A insulin resistance syndrome with new insulin receptor gene mu-tations.Methods Clinical data,laboratory examination,imaging examination and mutation scanning of insulin re-ceptor gene were collected,and type A insulin resistance syndrome reported by domestic and foreign scholars were analyzed retrospectively.Results One case had dry mouth,polydipsia and hyperandrogenemia,and another case had primary amenorrhea,both of them had insulin resistance.Two cases had heterozygous missense mutation in in-sulin receptor gene C.3449T＞c(p.L1150P).The mothers of the two probands all carried this mutation,while the fathers did not.This mutation has not been reported previously.Literature review shows that the onset age of this disease is young,and it is more common in women.BMI 20.37±5.47 kg/m2,fasting blood-glucose 4.50 mmol/L(4.10,13.00),the proportion of insulin resistance is 100％,92.0％has acanthoid nigricans,and the proportion of Testosterone above normal is 81.3％,diabetes complications appear earlier.Conclusions Genetic analysis is helpfulfor the etiological diagnosis in children with severe insulin resistance.

Objective To explore the relationship between serum Interleukin-27(IL-27),Cystatin C(CysC),and Glyceraldehyde-3-phosphate dehydrogenase(GAPDH)antibodies and the severity of disease in children with Neuromyelitis optica spectrum disorder(NMOSD),as well as their impact on prognosis.Methods A total of 102 children with NMOSD admitted to Kunming Children's Hospital from July 2019 to July 2023 were selected,along with 102 healthy during the same period.Serum levels of IL-27,CysC,and GAPDH antibodies were compared between children with NMOSD and healthy children.The levels of serum IL-27,CysC,and GAPDH antibodies were compared among children with varying disease severity.The correlations between serum IL-27,CysC,GAPDH antibodies and disease condition,cerebrospinal fluid markers were analyzed.And 102 children with NMOSD received individualized treatment and were followed up for 1 year.The prognosis was evaluated based on disease relapse,and patients were divided into recurrence group and non-recurrence group.The clinical data,serum IL-27,CysC,and GAPDH antibody levels were compared between the two groups.the impact of serum IL-27,CysC,and GAPDH antibodies on disease recurrence was analyzed,and the predictive value of serum IL-27,CysC,and GAPDH antibodies for disease recurrence was evaluated.Results Children with NMOSD had lower levels of serum IL-27 and CysC and higher levels of GAPDH antibodies than healthy children(P<0.05).Serum IL-27 and CysC levels were negatively correlated with Aquaporin 4(AQP4)-IgG antibody positivity,the number of spinal cord-involved segments,Expanded disability status scale(EDSS)scores,cerebrospinal fluid protein content,and white blood cell count.In contrast GAPDH antibodies were positively correlated with these parameters(P<0.05).After 1-year follow-up,2 cases were lost to follow-up,21 cases relapsed,and 79 cases did not,which were included in the relapse group and non-relapse group,respectively.There were significant differences in the number of spinal cord-involved segments,EDSS scores,and cerebrospinal fluid protein content between the relapse group and non-relapse group(P<0.05).The levels of serum IL-27 and CysC were lower and the levels of GAPDH antibodies were higher in the relapse group than the non-relapse group(P<0.05).Serum IL-27,CysC,and GAPDH antibodies were significantly associated with disease relapse(P<0.05).The Area under the curve(AUC)values for predicting disease recurrence in children with NMOSD based on serum IL-27,CysC,and GAPDH antibodies were 0.748,0.791,and 0.747,respectively,with optimal cutoff values of 38.77 pg/mL,0.79 mg/L,and 55.81 pg/mL,respectively.The combined prediction of disease relapse using these three markers had an AUC of 0.900,which was superior to individual prediction values(Z=2.215,2.137,2.220,P=0.024,0.033,0.023).Conclusion The levels of serum IL-27,CysC,and GAPDH antibodies are significantly correlated with the disease severity and prognosis in children with NMOSD,and can effectively predict the risk of disease recurrence.Combined detection provides more reliable predictive value.

Objective: To investigate the effects of different doses of X ⁃rays irradiation combined with allogeneic lymphocyte infusion on the establishment of aplastic anemia in mice. Methods: Forty BALB/c mice were randomly divided into four groups : the 3 Gy group (n = 9) , the 4 Gy group (n = 9) , the 5 Gy group (n = 10) , and the con⁃trol group (n = 12) . In the 3 Gy , 4 Gy , and 5 Gy groups , the experimental mice were exposed to corresponding do⁃ses of X ⁃ray and then intravenously infused with 0. 2 mL mixed suspension of the thymus and spleen cells from DBA/2 mice , at a concentration of 1 × 107 cells/mL , within 4 hours after irradiation. The control group did not un⁃dergo X ⁃ray irradiation and infused with an equivalent volume of physiological saline instead. Blood samples were collected from the orbital venous plexus of BALB/c mice and analyzed using an animal automated hematology analy⁃zer to measure peripheral blood parameters , including red blood cells ( RBC) , white blood cells ( WBC) , and platelets (PLT) . The general condition of mice was monitored daily , and survival rates were recorded for each group. At the experimental endpoint , the tibias were harvested for hematoxylin and eosin (HE) staining , while the femurs were used to prepare bone marrow smears for morphological examination. For the 5 Gy group , T ⁃cell subsets(ELISA) at the endpoint. Results : In the 3 Gy group , pancytopenia was observed , but platelet recovery occured rapidly , returning to normal levels by day 17 post⁃modeling. No deaths occurred during the observation period. At myeloid⁃to⁃erythroid (M/E) ratio , and no significant morphological abnormalities were noted in cells at any devel⁃with hematopoietic cells. In the 4 Gy group , pancytopenia persisted throughout the observation period. The survival rate was 90% . Endpoint analysis showed hypocellular marrow by morphological examination. HE staining indicated minimal fatty infiltration in the bone marrow tissue. In the 5 Gy group , pancytopenia was observed , though erythro⁃cyte counts returned to normal levels by day 24. The survival rate during the observation period was 50% . Endoint analysis revealed vacuolization of marrow particles and reduced hematopoietic cells with predominantly non⁃hematopoietic cells in bone marrow morphology. HE staining demonstrated severe fatty infiltration in the bone mar⁃row tissue , with scarcity of immature cells and hematopoietic precursor cells. Flow cytometry analysis showed a de⁃creased proportion of CD4 + T cells (% ) and an increased proportion of CD8 + T cells (% ) . ELISA confirmed elevated secretion of negative hematopoietic regulators : interferon⁃gamma ( IFN⁃γ) and tumor necrosis factor⁃alpha (TNF⁃α ) . Conclusion Combined administration of varying radiation doses with allogeneic lymphocyte infusion consistently induced peripheral blood cytopenia in mice , characterized by reductions in RBC , WBC , and PLT counts. Integrated analysis of bone marrow morphology , histopathological assessment via HE staining , and immuno logical parameters confirmed that a mouse model of aplastic anemia can be successfully established using 5 Gy X ⁃ ray irradiation coupled with infusion of 2 × 106 allogeneic lymphocytes.