ObjectiveTo investigate the value of predictive models established based on machine learning methods in predicting the risk of metabolic associated fatty liver disease （MAFLD）， and to analyze its key risk factors. MethodsA retrospective analysis was performed for the 50 variables of 2 168 healthy individuals who underwent physical examination in Department of Health Assessment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， from January 2021 to December 2024， including body composition， past history， and laboratory tests， and according to whether they were diagnosed with MAFLD or not， they were divided into MAFLD group with 265 individuals and non-MAFLD group with 1 903 individuals. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. Randomly split the research data into a training set and a validation set in a 70% to 30% ratio. Predictive factors were screened from the training set data using univariate analysis， LASSO regression， and multivariate Logistic regression analysis. Predictive models were then constructed using seven machine learning methods： Logistic regression， decision tree， random forest （RF）， eXtreme gradient boosting， light gradient boosting machine， support vector machine， and artificial neural network. Model performance was evaluated by plotting receiver operating characteristic curve for the validation set and calculating the area under the curve （AUC）， sensitivity， specificity， and Youden index for each model. Furthermore， the SHapley Additive exPlanation （SHAP） method was used to analyze the contribution of variables in the optimal model. ResultsThe prevalence rate of MAFLD among the 2 168 subjects was 12.22% （265/2 168）. Smoking， diastolic blood pressure， phase angle， visceral fat area， muscle fat ratio， waist-to-hip ratio， aspartate aminotransferase， non-HDL-C/HDL-C ratio， triglyceride-glucose index， and gallstones were independent risk factors for MAFLD （all P<0.05）. The seven predictive models of support vector machine， eXtreme gradient boosting， decision tree， light gradient boosting machine， artificial neural network， RF， and Logistic regression had an AUC of 0.738， 0.754， 0.757， 0.786， 0.795， 0.796， and 0.815， respectively， in the validation set， among which the RF model had the best discriminatory ability （AUC=0.796， 95% confidence interval： 0.754 — 0.839）， with a sensitivity of 81.01%， a specificity of 63.16%， and a Youden index of 44.17%. The SHAP analysis showed that visceral fat area， waist-to-hip ratio， and diastolic blood pressure were the top three predictive factors in terms of importance. ConclusionThe RF model， constructed based on body composition and clinical indicators， has a good performance in predicting the risk of MAFLD， and its interpretability can help to identify high-risk individuals in the early stage in clinical practice.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Obesity is a chronic low-grade inflammation and a risk factor for diseases such as diabetes， hypertension， dyslipidemia， and malignant tumors， demonstrating an increasingly grim development situation. The nuclear factor-kappa B （NF-κB） signaling pathway is a key signaling pathway involved in the immune response and inflammatory response. In obese individuals， the expression of NF-κB is overactivated， which leads to abnormal inflammatory responses in the body. Therefore， it is expected to alleviate inflammation and treat obesity by regulating the NF-κB signaling pathway， which has been proven effective by a large number of studies. The available studies on the NF-κB signaling pathway mostly focus on tumors， and there is no systematic review of the mechanism of this pathway in mediating obesity and the traditional Chinese medicine （TCM） treatment. We reviewed the research progress in the pathological and physiological processes of obesity mediated by NF-κB signaling pathway and TCM treatment， aiming to give insights into the clinical treatment of obesity with TCM and provide reference targets and research directions for exploring the biological foundations and the development of new TCM preparations.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

Objective: To compare the value of a body shape index (ABSI) and body roundness index (BRI) in predicting non-alcoholic fatty liver disease (NAFLD) among non-obese population, so as to provide a reference for the early identification of populations at high risk of NAFLD. Methods: Adults with a body mass index (BMI) of less than 28 kg/m2 who underwent health check-ups in Xiyuan Hospital of China Academy of Chinese Medical Sciences from 2022 to 2024 were selected as the study subjects. Demographic information, disease history, height, weight, waist circumference, blood pressure, and blood lipid indicators were collected, and ABSI and BRI were calculated. NAFLD was diagnosed using abdominal ultrasound. A multivariable logistic regression model was employed to analyze the relationships between ABSI, BRI and NAFLD among non-obese population. A generalized additive model combined with the penalized spline method was used to fit smooth curves to identify nonlinear relationships, and threshold effects were utilized to determine inflection points. The values of ABSI and BRI in predicting NAFLD among non-obese population were used the receiver operating characteristic (ROC) curve. Results: A total of 1 195 individuals were surveyed, including 345 males (28.87%) and 850 females (71.13%). A total of 348 cases of NAFLD were detected among the non-obese population, with a detection rate of 29.12%. The adjusted ABSI (sABSI) in the NAFLD group and non-NAFLD group were 7.95±0.33 and 8.08±0.34, while the BRI were 3.35±0.79 and 4.15±0.64, respectively, with statistically significant differences between the two groups (both P<0.05). Multivariable logistic regression analysis showed that, after adjusting for demographic information, disease history, blood pressure, and blood lipid indicators, both sABSI (OR=1.932, 95%CI: 1.184-3.158) and BRI (OR=1.594, 95%CI: 1.071-2.360) were significantly associated with NAFLD among non-obese population. Nonlinear positive correlations were observed between sABSI, BRI, and NAFLD among non-obese population. When sABSI≤8.46 and BRI≥2.72, both indices were positively associated with NAFLD. The area under the ROC curve for ABSI and BRI in predicting NAFLD risk among non-obese population were 0.619 and 0.782, respectively, with optimal cut-off values of 0.082 and 3.656, respectively. Conclusions ABSI and BRI show a non-linear relationship with NAFLD among non-obese population. BRI demonstrates relatively better performance in predicting NAFLD risk among this population and can serve as an auxiliary indicator for the early identification of NAFLD among non-obese population.

Objective:To explore the application value of integrated Chinese and western medicine in the treatment of sepsis-induced coagulopathy (SIC) induced by bacterial pneumonia sepsis.Methods:A total of 60 inpatients with bacterial pneumonia and sepsis admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from October 2023 to June 2024 were collected in a cross-sectional study. Serum samples were collected, and immune indexes, coagulation function and some laboratory test results of the patients were detected or recorded. Sepsis Associated Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score were evaluated.Results:Among the 60 patients, 71.7%( n=43) were associated with coagulation disorder, 65%( n=39) showed hemorrhagic SIC; A total of 37 patients (61.7%) were treated with integrated traditional Chinese and western medicine, and 23 patients (38.3%) were treated with Western medicine. The main types of syndrome differentiation were toxic-heat syndrome ( n=48, 80.0%) and blood-stasis syndrome ( n=11, 18.3%). Serum human monocyte chemoattractant protein-1 (MCP-1) and platelet count (PLT) in patients with blood stasis syndrome were significantly lower than those in toxic-heat syndrome (all P<0.05). In patients with bacterial pneumonia sepsis, the total score of syndrome of excess of fu-viscera (Fu-shi-zheng) was positively correlated with programmed death ligand-1 (PD-L1) ( r=0.293, P=0.023) and tumor necrosis factor-α (TNF-α) ( r=0.436, P=0.001). The total score of toxin-heat syndrome ( r=0.323, P=0.016) and excess of fu-viscera syndrome ( r=0.354, P=0.008) were positively correlated with prothrombin time (PT). PD-1 was positively correlated with SOFA score ( r=0.343, P=0.007) and APACHE Ⅱ score ( r=0.354, P=0.006). The PD-1 level and SOFA and APACHE Ⅱ scores of the patients treated with integrated Chinese and western medicine were significantly lower than those treated with Western medicine alone (all P<0.05). Conclusions:The combined intervention of traditional Chinese medicine and Western medicine based on " Fuzheng Touxie Jiedu (The method of strengthening the body and removing the toxin)" has strong clinical guiding significance, and can effectively improve the immune function and prognosis of bacterial pneumonia SIC.

Objective:To explore the application value of integrated Chinese and western medicine in the treatment of sepsis-induced coagulopathy (SIC) induced by bacterial pneumonia sepsis.Methods:A total of 60 inpatients with bacterial pneumonia and sepsis admitted to the Dongzhimen Hospital of Beijing University of Chinese Medicine from October 2023 to June 2024 were collected in a cross-sectional study. Serum samples were collected, and immune indexes, coagulation function and some laboratory test results of the patients were detected or recorded. Sepsis Associated Sequential Organ Failure Assessment (SOFA) score and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score were evaluated.Results:Among the 60 patients, 71.7%( n=43) were associated with coagulation disorder, 65%( n=39) showed hemorrhagic SIC; A total of 37 patients (61.7%) were treated with integrated traditional Chinese and western medicine, and 23 patients (38.3%) were treated with Western medicine. The main types of syndrome differentiation were toxic-heat syndrome ( n=48, 80.0%) and blood-stasis syndrome ( n=11, 18.3%). Serum human monocyte chemoattractant protein-1 (MCP-1) and platelet count (PLT) in patients with blood stasis syndrome were significantly lower than those in toxic-heat syndrome (all P<0.05). In patients with bacterial pneumonia sepsis, the total score of syndrome of excess of fu-viscera (Fu-shi-zheng) was positively correlated with programmed death ligand-1 (PD-L1) ( r=0.293, P=0.023) and tumor necrosis factor-α (TNF-α) ( r=0.436, P=0.001). The total score of toxin-heat syndrome ( r=0.323, P=0.016) and excess of fu-viscera syndrome ( r=0.354, P=0.008) were positively correlated with prothrombin time (PT). PD-1 was positively correlated with SOFA score ( r=0.343, P=0.007) and APACHE Ⅱ score ( r=0.354, P=0.006). The PD-1 level and SOFA and APACHE Ⅱ scores of the patients treated with integrated Chinese and western medicine were significantly lower than those treated with Western medicine alone (all P<0.05). Conclusions:The combined intervention of traditional Chinese medicine and Western medicine based on " Fuzheng Touxie Jiedu (The method of strengthening the body and removing the toxin)" has strong clinical guiding significance, and can effectively improve the immune function and prognosis of bacterial pneumonia SIC.

AIM:To explore the impact of sphingosine 1-phosphate receptor 5(S1PR5)on lipopolysaccha-ride(LPS)-induced neuroinflammation and cognitive-behavioral impairments in mice,alongside the anti-inflammatory im-pacts on BV2 cells and associated mechanisms.METHODS:(1)C57BL/6 wild-type(WT)mice and homozygous S1PR5 knockout(KO)mice were utilized and categorized into WT control,WT-LPS,S1PR5 KO control,and S1PR5 KO-LPS groups using the random number method.Neuroinflammatory models in mice were induced by a single intraperitoneal injection of 5 mg/kg LPS in the WT-LPS and S1PR5 KO-LPS groups,while an equivalent volume of saline was injected in-to the WT control and S1PR5 KO control groups.Following 7 days of modeling,the Morris water maze test was conducted,followed by the collection of brain tissues from each group of mice.Hippocampal tissue sections were stained with Nissl.The mRNA expression levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in hippocampal tis-sues were determined using RT-qPCR.Western blot and tissue immunofluorescence techniques were employed to assess the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)in hippocampal tissues.(2)The BV2 cells underwent LPS stimulation to induce an inflammatory response and were treated with either the S1PR5 ago-nist A971432 or lentiviral overexpression of S1PR5.The effects of S1PR5 agonism or overexpression on S1PR5,IL-1β,IL-6,TNF-α,and CD206 were assessed using RT-qPCR.Additionally,CD206 expression was examined via cellular im-munofluorescence.Western blot was employed to analyze the protein levels of microglia polarization markers CD206,in-ducible nitric oxide synthase(iNOS),cyclooxygenase 2(COX2),and NLRP3,as well as p-NF-κB,cleaved caspase-1,and IκBα.RESULTS:(1)Findings from in vivo experiments indicated that S1PR5 KO notably exacerbated LPS-induced memory impairments in mice,alongside increased mRNA levels of IL-1β and IL-6,and increased protein levels of NLRP3 in the hippocampus.(2)The presence of S1PR5 in BV2 cells remained unaffected by variations in A971432 concentration and exposure duration.(3)Activation of S1PR5 or its overexpression significantly mitigated LPS-induced expression of IL-1β,IL-6,and TNF-α,while concurrently enhancing CD206 expression in BV2 cells at the mRNA level.At the protein level,it led to a noteworthy increase in CD206 expression,indicative of M2-type macrophages,and a reduction in the ex-pression of iNOS and COX2,markers of M1-type macrophages.Furthermore,it downregulated NLRP3,p-NF-κB,and cleaved caspase-1 expression,while upregulating IκBα expression.CONCLUSION:S1PR5 deficiency exacerbates cog-nitive deficits in mice by promoting neuroinflammatory responses induced by LPS.

AIM:This study aimed to observe the analgesic effects of Hegu acupoint catgut embedding in a rat model of labor and investigate its influence on biomarkers such as calcitonin gene-related peptide(CGRP)signals at the Hegu acupoint.METHODS:Thirty-six pregnant rats were randomly divided into three groups:control group,Hegu acu-puncture group,and Hegu catgut embedding group.Pain threshold changes were assessed using the tail immersion test and paw withdrawal thermal latency at four time points:pre-induction,before the onset of labor,at the onset of labor,and at the mid-stage of labor.Tissue samples from the Hegu acupoint were collected at the mid-stage of labor to detect the ex-pression of CGRP,substance P(SP),and mast cells using immunofluorescence.The concentrations of ATP and ade-nosine were measured using ELISA.RESULTS:Before labor induction,there was no significant difference in tail immer-sion test and paw withdrawal thermal latency among the three groups(P>0.05).Before the onset of labor,both the acu-puncture and catgut embedding groups exhibited significantly higher tail-flick times and paw withdrawal latencies com-pared to the control group(P<0.05).At labor initiation and mid-labor,the catgut embedding group had significantly higher tail-flick times and paw withdrawal latencies compared to both the control and acupuncture groups(P<0.05).During mid-labor,the expression of CGRP,SP,mast cells,ATP,and adenosine concentrations in the catgut embedding group was significantly higher than that in the control and acupuncture groups(P<0.05),with co-expression of CGRP,SP,and mast cells observed.CONCLUSION:Hegu acupoint catgut embedding effectively alleviates labor pain,and its mechanism may involve increased local expression of CGRP and SP,promoting mast cell degranulation,and increasing ATP release and its conversion to adenosine.

Objective To investigate the potential of a two-component model combining T2 and diffusion weighted imaging(T2-DWI)in the diagnosis of prostate cancer.Methods Thirty-two prostate cancer patients and twenty prostatic hyperplasia patients underwent combined T2-DWI,with TE values set at 50 ms and 70 ms and b values at 50 s/mm2 and 800 s/mm2,respectively.This provided four measurements for each voxel.The signal fractions were calculated from the slow component(SFslow)extracted from the two-component model of T2-DWI,which was fitted with two free parameters.The results were compared with the traditional single exponential apparent diffusion coefficient(ADC)model.Results A significant difference was observed between SFslow(0.77±0.14 vs 0.35±0.10)and ADC[(0.91±0.24)μm2/ms vs(1.98±0.32)μm2/ms]in region of interest(ROI)between peripheral zone tumors and normal prostate tissue(P＜0.001).No significant difference was found between SFslow(0.75±0.13 vs 0.68±0.11)and ADC[(0.88±0.18)μm2/ms vs(0.97±0.13)μm2/ms]in ROI between non-peripheral zone tumors and prostatic hyperplasia.The area under the curve(AUC)of the receiver operating characteristic(ROC)for distinguishing tumors from prostate voxels was 0.962 for two-component SFslow and 0.940 for single exponential ADC models.The Spearman correlation coefficients between tumor SFslow and ADC with Gleason scores were 0.631 and-0.558,respectively.Conclusion SF estimation based on T2-DWI two-component model can effectively differentiate tumors from normal prostate tissue,showing potential in diagnosing prostate cancer.