ObjectiveTo investigate the effects of Erchentang （ECD） on the body weight of the mouse model of simple obesity induced by a high-fat diet （HFD） and decipher the underlying mechanisms. MethodsFirstly， single-cell transcriptomics （Sc-RNAseq） was employed to analyze the transcriptional changes in the ileum tissue of mice in the normal group and model group. Then， a mouse model of simple obesity was established with a high-fat diet. The successfully modeled mice were randomly allocated into the following four groups （n=8）： model， low-dose （7.5 g·kg^-1） ECD， medium-dose （15 g·kg^-1） ECD， and high-dose （30 g·kg^-1） ECD. Additionally， 8 mice of the same age were selected as the normal group. The body weight was measured at fixed time points during the 4-week gavage period. The overall efficacy of ECD in alleviating obesity was evaluated through glucose tolerance testing， behavioral analysis， hematoxylin-eosin （HE） staining， and biochemical testing. Protein docking was employed to predict the degree of binding between corresponding proteins. Molecular docking was employed to predict the binding degree between key components of ECD and target proteins. Real-time PCR was employed to determine the mRNA levels of tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， interleukin-1β （IL-1β）， CD68， CD206， zonula occludens-1 （ZO-1）， and Claudin-5 in the ileum. Immunofluorescence staining was used to observe the expression and distribution of Claudin-5 and ZO-1. ResultsThe Sc-RNAseq results indicated that the differentially expressed genes of immune cells in the model group in comparison with the normal group were primarily enriched in biological functions related to lipid metabolism and inflammatory metabolism. Additionally， these genes were associated with the janus kinases（JAK）/signal transducers and activators of transcription （STAT） signaling pathway， an inflammation-related pathway. Compared with the normal group， the model group showed increases in body weight （P<0.01） and blood glucose level （P<0.01）， a decrease in limb strength （P<0.01）， an increase in liver weight （P<0.05）， and elevated serum alanine amino-transferase （ALT） and aspartate transferase （AST） levels （P<0.05， P<0.01）. Additionally， the model group exhibited increased hepatic fat vacuoles， notably enlarged adipocytes in the epididymal and inguinal white adipose tissue， and increased inflammation. Compared with the model group， ECD groups showed reduced body weights （P<0.01） and blood glucose levels （P<0.01）， increased limb strength （P<0.05， P<0.01）， decreased liver weights （P<0.05， P<0.01）， and declined serum ALT and AST levels （P<0.05， P<0.01）. Additionally， ECD reduced hepatic fat vacuoles and the adipocyte volume in the epididymal and inguinal white adipose tissue， and alleviated inflammation. Potential interactions existed between CD68 and ZO-1/Claudin-5， as well as between CD206 and ZO-1/Claudin-5. The key components of ECD， nobiletin， diosmetin， and naringenin， all demonstrated strong binding affinity with the target proteins ZO-1 and Claudin-5. Compared with the normal group， the model group exhibited up-regulated mRNA levels of the pro-inflammatory cytokines TNF-α， iNOS， IL-1β， and CD68 （P<0.05， P<0.01） and down-regulated mRNA levels of the anti-inflammatory cytokine CD206 （P<0.01） and the tight junction proteins Claudin-5 and ZO-1 （P<0.05， P<0.01）. In comparison with the model group， the ECD groups showed down-regulated mRNA levels of TNF-α， iNOS， IL-1β， and CD68 （P<0.05， P<0.01） and up-regulated mRNA levels of CD206， Claudin-5， and ZO-1 （P<0.05， P<0.01）. Compared with the normal group， the model group exhibited down-regulated expression of tight junction proteins Claudin-5 and ZO-1 （P<0.01）. Compared with the model group， ECD groups showed up-regulated expression of Claudin-5 and ZO-1 （P<0.05， P<0.01）. ConclusionECD can significantly ameliorate HFD-induced obesity and excessive body weight gain in mice by improving the inflammatory microenvironment in the ileum and further restoring the integrity of the impaired ileal barrier.

To compare and analyze the clinical manifestations,laboratory characteristics,imaging findings,and treatment outcomes of patients with acute and chronic brucellosis,a retrospective analysis was conducted on 258 patients with brucellosis(202 in the acute group and 56 in the chronic group)hospitalized in Xinkang Hospital in Dalad Banner,Ordos City,Inner Mongolia Autonomous Region,from November 2023 to November 2024.General data,epidemiological characteristics,clinical presentations,laboratory test results,imaging findings,treatment outcomes,and prognosis were collected.The incidences of fever(51.5%vs 7.1%),fatigue(30.2%vs 12.5%),joint pain(42.9%vs 16.1%),and muscle pain(9.9%vs.1.8%)were significantly higher in the acute phase group(all P<0.05).The incidence of osteoarthritis complications was higher in the chronic brucellosis group(51.8%vs 8.9%,χ2=75.697,P<0.01).Univariate ANOVA analysisshowed that the Serum Agglutination Tests(SAT),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL),creatinine(CRE),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),and bone destructionexhibited statistically significant differences between the acute and chronic phases of brucellosis(all P<0.05).Multivariate logistic regression analysis indicated that abnormal ALT(OR=14.18,95%CI:1.11-181.72;P=0.041)and bone destruction(OR=0.16,95%CI:0.04-0.63;P=0.009)were associated with chronic brucellosis.After treatment,all patients experienced have symptom relief in varying degrees,with 157 patients(60.9%)cured and 101 patients(39.1%)symptomatic improved(P<0.01).In conclusion,the incidences of fever,fatigue,and joint pain in patients during the acute phase is significantly higher than that those in patients during the chronic phase,while the incidence of osteoarthritis complications is higher in chronic phase patients.The incidences of abnormal SAT,ALT,AST,TBIL,CRE,CRP,and ESR,and bone destruction varies at different stages of brucellosis.Of those,abnormal ALT and bone destruction show a stronger association with,which can assist the clinical staging of brucellosis.

Viral myocarditis(VMC)is a type of myocarditis caused by Coxsackievirus B3(CVB3)infection.Its pathogenesis is complex that includes direct viral action,host immune and inflammatory response,myocardial structure and function remodeling.The therapeutic effect of single target drugs is limited,while traditional Chinese medicine not only has antiviral effects,but also demon-strates systematic advantages in intervening in VMC due to its"multi-component,multi-target,and multi-pathway"characteristics.This article reviews the pathogenic mechanisms of CVB3-induced VMC,clarifies the interaction between CVB3 and host cells,and ex-plores the intervention mechanisms and developments of traditional Chinese medicine interventions for CVB3-induced VMC.At the same time,the prospects of traditional Chinese medicine treatment for CVB3-induced VMC in this study suggest that future research should strengthen the analysis of multi-target synergistic mechanisms based on traditional Chinese medicine formulas,combine artifi-cial intelligence,genomics,and gene editing technologies to predict drug-target interaction networks,establish standardized and per-sonalized system for integrated traditional Chinese and Western medicine treatment plans,and provide more effective strategies for the prevention and treatment of VMC.

BACKGROUND:Previous studies have shown that Huosui Formula has a synergistic effect on the immune and hematopoietic regulation of patients with myelodysplastic syndrome,but the specific mechanism is not yet clear.OBJECTIVE:To explore the effect and mechanism of Huosui Formula on bone marrow hematopoiesis in rats with myelodysplastic syndrome.METHODS:A total of 70 SD rats were randomly divided into a normal control group(n=10),a model group(n=15),a western medicine group(n=15),a low-dose Huosui Formula group(n=15),and a high-dose Huosui Formula group(n=15).Except for the normal control group,the other four groups were injected with dimethyl benzanthracene via the tail vein to induce the establishment of rat myelodysplastic syndrome models.After modeling,the normal control group and the model group were given normal saline;the western medicine group was given thalidomide capsules 10 mg/kg and retinoic acid tablets 4 mg/kg,and the low-dose Huosui Formula group and the high-dose Huosui Formula group were given 1.5 and 6 g/kg Huosui Formula,respectively,by intragastric administration once a day for 28 consecutive days.Peripheral blood and femoral bone marrow tissue were collected to detect peripheral blood routine and bone marrow biopsy hematopoietic proliferation.Flow cytometry was used to detect T lymphocyte subsets and the expression of CTLA-4 and PD-1 on T lymphocytes.RESULTS AND CONCLUSION:(1)Compared with the normal control group,peripheral blood leukocyte,neutrophil,hemoglobin,platelet,and CD4+,CD4+/CD8+levels were decreased in the model group significantly(P＜0.05),while CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+expressions were significantly upregulated(P＜0.05).(2)In all dosage groups,myelopoietic proliferation was increased compared with the model group,with no significant difference between the groups(P＞0.05).(3)Compared with the model group,leukocytes,hemoglobin,platelets,and CD4+,CD4+/CD8+were significantly elevated in the high-dose Huosui Formula group(P＜0.05),the expression of CD8+was significantly lower(P＜0.05),and the levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+were down-regulated but not statistically significant(P＞0.05).(4)The western medicine group and the high-dose Huosui Formula group showed similar efficacy.The improvement of each index in the high-dose Huosui Formula group was superior to that in the low-dose Huosui Formula group.These findings indicate that Huosui Formula can improve the bone marrow hematopoiesis in myelodysplastic syndrome model rats,increase the levels of CD4+,and CD4+/CD8+while down-regulate the expression levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+.These observations suggest a link to the negative immunoregulation mechanism.

Viral myocarditis(VMC)is a type of myocarditis caused by Coxsackievirus B3(CVB3)infection.Its pathogenesis is complex that includes direct viral action,host immune and inflammatory response,myocardial structure and function remodeling.The therapeutic effect of single target drugs is limited,while traditional Chinese medicine not only has antiviral effects,but also demon-strates systematic advantages in intervening in VMC due to its"multi-component,multi-target,and multi-pathway"characteristics.This article reviews the pathogenic mechanisms of CVB3-induced VMC,clarifies the interaction between CVB3 and host cells,and ex-plores the intervention mechanisms and developments of traditional Chinese medicine interventions for CVB3-induced VMC.At the same time,the prospects of traditional Chinese medicine treatment for CVB3-induced VMC in this study suggest that future research should strengthen the analysis of multi-target synergistic mechanisms based on traditional Chinese medicine formulas,combine artifi-cial intelligence,genomics,and gene editing technologies to predict drug-target interaction networks,establish standardized and per-sonalized system for integrated traditional Chinese and Western medicine treatment plans,and provide more effective strategies for the prevention and treatment of VMC.

Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.

BACKGROUND:Previous studies have shown that Huosui Formula has a synergistic effect on the immune and hematopoietic regulation of patients with myelodysplastic syndrome,but the specific mechanism is not yet clear.OBJECTIVE:To explore the effect and mechanism of Huosui Formula on bone marrow hematopoiesis in rats with myelodysplastic syndrome.METHODS:A total of 70 SD rats were randomly divided into a normal control group(n=10),a model group(n=15),a western medicine group(n=15),a low-dose Huosui Formula group(n=15),and a high-dose Huosui Formula group(n=15).Except for the normal control group,the other four groups were injected with dimethyl benzanthracene via the tail vein to induce the establishment of rat myelodysplastic syndrome models.After modeling,the normal control group and the model group were given normal saline;the western medicine group was given thalidomide capsules 10 mg/kg and retinoic acid tablets 4 mg/kg,and the low-dose Huosui Formula group and the high-dose Huosui Formula group were given 1.5 and 6 g/kg Huosui Formula,respectively,by intragastric administration once a day for 28 consecutive days.Peripheral blood and femoral bone marrow tissue were collected to detect peripheral blood routine and bone marrow biopsy hematopoietic proliferation.Flow cytometry was used to detect T lymphocyte subsets and the expression of CTLA-4 and PD-1 on T lymphocytes.RESULTS AND CONCLUSION:(1)Compared with the normal control group,peripheral blood leukocyte,neutrophil,hemoglobin,platelet,and CD4+,CD4+/CD8+levels were decreased in the model group significantly(P＜0.05),while CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+expressions were significantly upregulated(P＜0.05).(2)In all dosage groups,myelopoietic proliferation was increased compared with the model group,with no significant difference between the groups(P＞0.05).(3)Compared with the model group,leukocytes,hemoglobin,platelets,and CD4+,CD4+/CD8+were significantly elevated in the high-dose Huosui Formula group(P＜0.05),the expression of CD8+was significantly lower(P＜0.05),and the levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+were down-regulated but not statistically significant(P＞0.05).(4)The western medicine group and the high-dose Huosui Formula group showed similar efficacy.The improvement of each index in the high-dose Huosui Formula group was superior to that in the low-dose Huosui Formula group.These findings indicate that Huosui Formula can improve the bone marrow hematopoiesis in myelodysplastic syndrome model rats,increase the levels of CD4+,and CD4+/CD8+while down-regulate the expression levels of CD4+PD-1+,CD8+PD-1+,CD4+CTLA-4+,and CD8+CTLA-4+.These observations suggest a link to the negative immunoregulation mechanism.

Objective:To construct and evaluate a risk warning model for enteral nutrition associated diarrhea(ENAD)in acute stroke patients based on logistic regression and Nomogram.Methods:This study was a retrospective study,a total of 172 patients with acute stroke who were admitted to Yancheng First People's Hospital from January 2022 to May 2024 were selected,and clinical data of patients were collected.Multivariate logistic regression analysis was used to identify the influencing factors of ENAD occurrence,based on the results of the multivariate logistic regression analysis,a Nomogram warning model was constructed,the receiver operating characteristic(ROC)curve was applied to analyze the predictive value of the Nomogram warning model for the risk of ENAD occurrence in patients with acute stroke.Results:Univariate analysis showed that,the occurrence of ENAD in patients with acute stroke was related to fasting time,mechanical ventilation,oral potassium preparations,albumin,number of types of antibiotics used,acute physiology and chronic health status Ⅱ(APACHE Ⅱ)score,enteral nutrition infusion rate,length of stay in the intensive care unit(ICU),use of proton pump inhibitors,duration of antibiotic use,use of gastrointestinal prokinetic drugs,and daily enteral nutrition infusion volume(P＜0.05).The results of multiple logistic regression analysis showed that,high APACHE Ⅱ score,prolonged use of antibiotics,low albumin,use of gastrointestinal prokinetic drugs,oral potassium preparations,prolonged fasting time,and rapid enteral nutrition infusion were risk factors for ENAD in patients with acute stroke(P＜0.05).Construct and validate a Nomogram warning model based on the results of multiple logistic regression analysis.After evaluation,the model fits well with an area under the curve(AUC)of 0.823,indicating high predictive value for ENAD occurrence in patients with acute stroke.Conclusion:High APACHE Ⅱ score,prolonged use of antibiotics,low albumin,use of gastrointestinal prokinetic drugs,oral potassium preparations,prolonged fasting time,and rapid enteral nutrition infusion are risk factors for ENAD in patients with acute stroke.The Nomogram warning model constructed based on the above indicators has high predictive value for the occurrence of ENAD in patients with acute stroke.

OBJECTIVE To explore the anti-tumor effect of Yiqi Yangyin Jiedu Recipe on Lewis lung cancer mice and its influ-ence on immunomodulation.METHODS Lewis lung cancer mouse model was constructed by subcutaneous injection of Lewis lung cancer cells under the armpit and divided into model group,low dose group,medium dose group and high dose group.The tumor vol-ume,tumor inhibition rate and survival rate were calculated.The apoptosis and DNA damage of tumor cells were detected by HE stai-ning,TUNEL assay and comet assay respectively.The expression levels of IFN-γ,IL-2 and TNF-α were detected by ELISA.CD8+,CD8+/CD4+,PD1+,IFN-γ+,CD28+cells were detected by immunofluorescence and flow cytometry.The protein levels of PD1,CD69 and CD28 were detected by Western blot.RESULTS Yiqi Yangyin Jiedu Recipe has anti-tumor effects,prolonging survival,promo-ting apoptosis of tumor cells and aggravating DNA damage of tumor cells.Drug treatment promoted the expression of IFN-γ,IL-2 and TNF-α,increased the proportion of CD8+T,CD8+/CD4+T,IFN-γ+and CD28+cells,and inhibited the proportion of PD1+cells and protein expression,and the protein levels of CD69 and CD28 were significantly increased.CONCLUSION Yiqi Yangyin Jiedu Reci-pe can inhibit the development of tumor,and its regulation of immune function is the potential mechanism of its anti-tumor effect.

Yanchi Tan sheep,a specialty of Ningxia,China,is famous for its excellent meat quality,but the detailed mechanisms of its muscle development and meat quality formation are still unclear.In or-der to preliminarily investigate the unique molecular mechanisms in the muscle development of the sheep,the present study was carried out to collect the longest dorsal muscle(LDM)samples from 6-month-old and 12-month-old female Tan sheep,and we screened the genes and long non-coding RNA(lncRNAs)that may play important roles in regulating the muscle development and meat quality formation through transcriptome sequencing(RNA-seq).The results showed that a total of 504 mRNAs and 1,483 lncRNAs were detected between the two groups of LDMs,with significant differences(P＜0.05).And we also pre-dicted 103 potential lncRNA-mRNA cis-regulatory relationship pairs with significant differences(P＜0.05).Skeletal muscle development-related genes such as MSTN,CDKN1A,FHL1 and skeletal muscle metabolism-related genes such as LPL and SCD were subsequently screened based on the functional anal-ysis of differentially expressed mRNA.Based on the functional analysis of differentially expressed lncRNA target genes,13 lncRNAs potentially related to muscle development(LNC.17926.1,LNC.981.1,LNC.16284.1,etc.)and 8 lncRNAs potentially related to skeletal muscle metabolism(LNC.15496.1,LNC.18149.1,etc.)were identified.5 lncRNAs and 4 mRNAs expressed in both groups were randomly selected for qPCR validation experiments,and their results were consistent with RNA-seq,which corrob-orated with the reliability of the sequencing results.This study lays a solid foundation for future investiga-tions of muscle development,meat quality formation mechanism and molecular breeding in Tan sheep,and provides a scientific basis for improving the meat production performance of other domestic sheep breeds.