OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

Hepatic fibrosis is the common key pathological link of various chronic liver diseases and can progress to malignant diseases such as liver cirrhosis and hepatocellular carcinoma； however， there is still a lack of effective targeted therapeutic drugs at present. Traditional Chinese medicine （TCM） has a marked clinical effect in the prevention and treatment of hepatic fibrosis， yet its precise clinical application and global promotion are greatly limited by the complex components of compound prescriptions and unclear mechanism of action. In recent years， multimodal high-throughput omics technology has achieved rapid development， providing strong technical support for elaborating on the scientific connotation of TCM in the treatment of complex diseases due to its advantages of systematic profiling， big-data analytics， and precise target prediction. In particular， integrated transcriptomic， proteomic， and metabolomic strategies comprehensively elucidate key signaling networks， cellular phenotypic transitions， and extracellular matrix metabolic homeostasis modulated by TCM compounds and monomers and assist in the screening and assessment of effective component groups and novel biomarkers. This article systematically reviews the advances in basic research on TCM prevention and treatment of hepatic fibrosis based on multi-omics technologies in the past five years， summarizes the “drug-target-pathway-phenotype” regulatory network， and elaborates on the core mechanisms of TCM in regulating hepatic stellate cell activation and reversing hepatic fibrosis. Future studies should further delve into the interdisciplinary integration and dynamic analytical methodologies of multi-omics technologies， precisely identify the core regulatory target networks modulated by TCM， and systematically unravel the scientific connotation of compatibility rule in compound prescriptions， in order to provide a theoretical basis for developing efficient targeted drugs for hepatic fibrosis and individualized diagnosis and treatment strategies.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

BACKGROUND:The development and evolution of atlas are complex,and there are a few research reports. CT imaging can show the normal development process,anatomical structure,developmental variation and deformity of the axis. It has important clinical value to clarify the time of occurrence of ossification center of axis and closure of epiphyseal plate and its evolution process and law.OBJECTIVE:To present the anatomical structure of the normal development and variation of children's axis based on CT images.METHODS:CT images obtained from 732 children aged 0 to 15 years who underwent neck scans between June 2016 and November 2019 were retrospectively analyzed. The observation indicators encompassed the axis odontoid,bilateral pedicle,vertebral ossification center,secondary ossification center at the tip of odontoid,pedicle,base of odontoid,and posterior median epiphyseal plate,as well as any variations or deformities in axis development. The changes in these indicators were analyzed and compared across different age groups. SPSS 17.0 statistical software package was utilized for data classification and statistical analysis. RESULTS AND CONCLUSION:(1) A total of 732 subjects were examined,comprising 718 cases (98.1％) with normal development of the axis and 14 cases (1.9％) exhibiting deformity or dysplasia. (2) The axis demonstrated the presence of five ossification centers,including those of the bilateral pedicles,odontoid process,and vertebral body,which were observed at birth. The median age for the secondary ossification center located at the tip of the odontoid process was determined to be 5.7 years,with an interquartile range of 4.1 to 7 years. The earliest recorded occurrence was observed at 8 months and 22 days,while the latest occurrence was noted at 12 years and 10 months. (3) The median age at which fusion took place was 6 years,with an interquartile range of 5-8 years. The maximum age at which non-fusion was observed was 8 years and 9 months,while the minimum age at which fusion occurred was 4 years and 3 months. (4) The median age at which bilateral epiphyseal plate closure occurred was approximately 3.8 years,with an interquartile range of about 2.9-4.6years. The earliest observed closure was at 2 years and 3 months,while the latest observed unclosure was at 6 years old. (5) The median age at which odontoid base epiphyseal plate closure occurred was 5.2 years,with an interquartile range of 3.5-6.8 years. The minimum age for closure was 2 years and 6 months,and the latest age for non-closure was 9 years and 6 months. (6) The posterior median epiphyseal plate typically closed at a median age of 1.5 years,with an interquartile range of 1.0-2.1 years. However,two cases exhibited delayed closure,occurring at ages 2 years and 5 months,and 14 years,respectively. Theearliest closure observed was at 6 months and 20 days. (7) Axis malformation or developmental abnormalities,including 7 cases of accessory ossification center and accessory epiphyseal plate,3 cases of free ossified small bones in the axis,2 cases of posterior median epiphyseal plate failure,2 cases of secondary ossification centers in the absence of the apex of odontosis,and 1 case of absence at ossification center in the odontoid of the armature vertebrae. (8) It is concluded that the utilization of multi-slice spiral CT scanning in conjunction with the multi-plane reconstruction technique enables comprehensive visualization of the anatomical structure of the axis,facilitating precise assessment of both its typical developmental variations and deformities.

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Objective To develop models for predicting response to chemotherapy combined with immunotherapy in patients with esophageal squamous carcinoma with various machine learning algorithms,and then select the optimal model.Methods A retrospective study was performed for 174 patients with esophageal squamous cell carcinoma undergoing chemotherapy combined with immunotherapy admitted in Department of Thoracic Surgery of the First Affiliated Hospital of Army Medical University from January 2022 to December 2023.The CT scans and clinical information were collected before treatment.They were randomly divided into a training set(n=122)and a testing set(n=52)in a ratio of 7∶3.CT radiomic features were extracted and selected,and then 5 machine-learning algorithms were employed to establish the prediction models,including radiomics model and clinical-radiomics model.Five-fold cross-validation was conducted on the training set,and the performance of the prediction models was evaluated on the testing set using receiver operating characteristic(ROC)curve and the F1 score.The best-performing model was further explained using local interpretable model-agnostic explanations(LIME)algorithm.Results Among the 174 patients,115(66.1%)achieved clinical remission.From the clinical information and CT images,1 clinical features and 10 radiomic features were identified.The area under of ROC curve(AUC)for the radiomics and clinical-radiomics models was 0.750(95%CI:0.616～0.883),and 0.766(95%CI:0.637～0.895),respectively.The F1 score of the optimal clinical-radiomics model was 0.829.LIME algorithm indicated that this best model demonstrated reliability in predicting individual samples.Conclusion The clinical-radiomics prediction model based on machine learning algorithm performs well,and can provide a reference for doctors'clinical decision-making by predicting the response to chemotherapy combined with immunotherapy in patients with esophageal squamous cell carcinoma.

Objective To evaluate the impact of traditional Chinese medicine(TCM)syndromes on percutaneous microwave ablation(MWA)treatment in patients with colorectal cancer liver metastases(CRLM)and to construct a multidimensional prediction model prognostic based on TCM syndrome classification.Methods Clinical data were collected from 86 CRLM patients who underwent MWA at Zhongshan Hospital of Traditional Chinese Medicine between October 2012 and October 2023.The clinical information covered TCM syndrome types of qi-blood deficiency and spleen-kidney yang deficiency,tumor characteristics,and treatment parameters.Logistic regression was used to screen feature variables for constructing the prognostic predication model,and cross validation was performed to evaluate the prognostic predictive performance.Results(1)Among the 86 CRLM patients,31(36.05%)had spleen-kidney yang deficiency syndrome,while 55(63.95%)had qi-blood deficiency syndrome.(2)Compared to the patients with spleen-kidney yang deficiency syndrome,patients with qi-blood deficiency syndrome exhibited significantly long progression-free survival(PFS)and high progression-free survival rate(P＜0.01),while no significant differences were presented in the incidences of postoperative adverse events such as pain,fever,infection,liver function impairment,or ascites/pleural effusion among the patients with the two syndrome types(P＞0.05).(3)Multivariate logistic regression analysis revealed that TCM syndrome type,maximum diameter of metastatic liver tumor,timing of liver metastasis,and Ki-67 expression rate of primary tumors were the independent prognostic factors for 1-year PFS(P＜0.05 or P＜0.01).(4)The constructed model demonstrated high predictive accuracy for PFS,with an area under the receiver operating characteristic(ROC)curve(AUC)of 0.905(95%CI:0.830-0.980).Conclusion TCM syndromes have significant influence on the prognosis of CRLM patients undergoing MWA,and the patients with qi-blood deficiency syndrome have favorable prognosis.This study pioneers a multidimensional prognostic prediction model integrating TCM syndromes for MWA-treated CRLM patients,highlighting the unique value of TCM syndromes in assessing disease progression and predicting prognosis.

Objective To explore the influencing factors of early neurological deterioration(END)in patients with acute anterior circulation large-vessel occlusive mild stroke who were treated with medications alone within 72 h after onset.Methods Retrospective consecutive data were collected of patients with acute large-vessel occlusive mild stroke who presented to the Advanced Stroke Center of Linyi People's Hospital within 24 h of onset from January 2021 to December 2022.END was defined as an increase of ≥ 4 points in the National Institutes of Health stroke scale(N1HSS)score within 72 h after onset compared to the admission score.Patients were divided into the neurological deterioration group and the stable condition group(NIHSS score did not increase or increased by 1-3 points within 72 h after onset compared to the admission score).Baseline and clinical data of all patients were collected,including sex,age,cerebrovascular disease risk factors(hypertension,diabetes mellitus,hyperlipidemia,coronary heart disease,atrial fibrillation,smoking,alcohol consumption,stroke history),NIHSS score at admission,time from onset to admission,systolic blood pressure at admission,diastolic blood pressure at admission,laboratory test indicators at admission(blood glucose,glycosylated hemoglobin,homocysteine,total cholesterol,triglyceride,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,neutrophils,lymphocytes and neutrophil-to-lymphocyte ratio),responsible occlusion artery(internal carotid artery,middle cerebral artery,anterior cerebral artery),affected cerebral hemisphere,collateral circulation score,and medications used within 72 h after admission(intravenous thrombolysis+dual antiplatelet therapy,tirofiban+dual antiplatelet therapy,argatroban+dual antiplatelet therapy,argatroban alone,dual antiplatelet therapy alone).Variables with statistically significant differences in univariate analysis were included in multivariate Logistic regression analysis to explore the independent influencing factors for END in patients with acute anterior circulation large-vessel occlusive mild stroke treated with medications alone.Results A total of 208 patients with acute anterior circulation large-vessel occlusive mild stroke were included,with 143 males and 65 females,aged 38-85 years,with an average age of(64±9)years.Among them,86 patients were in the neurological deterioration group and 122 in the stable condition group.(1)There were statistically significant differences between the neurological deterioration group and the stable condition group in terms of history of diabetes mellitus(39.5％[34/86]vs.17.2％[21/122]),smoking history(43.0％[37/86]vs.29.5％[36/122]),left cerebral hemisphere lesion(57.0％[49/86]vs.41.0％[50/122]),collateral circulation score(4[3,5]vs.5[4,5]),time from onset to admission(7.0[3.0,17.0]hvs.4.3[2.0,11.0]h),blood glucose at admission(7.4[5.8,10.0]mmol/L vs.6.7[5.8,7.7]mmol/L),neutrophil-to-lymphocyte ratio(3.8[2.4,5.1]vs.3.0[2.1,4.3]),dual antiplatelet therapy alone(19.8％[17/86]vs.6.6％[8/122]),and argatroban+dual antiplatelet therapy(8.1％[7/86]vs.29.5％[36/122];all P＜0.05).There were no statistically significant differences in the results of the remaining univariate analyses(all P＞0.05).(2)Multivariate Logistic regression analysis showed that diabetes mellitus(OR,2.674,95％CI 1.121-6.377,P=0.027)and left cerebral hemisphere vessel occlusion(OR,2.030,95％CI I.083-3.806,P=0.027)were independent risk factors for END in acute anterior circulation large-vessel occlusive mild stroke.Argatroban+dual antiplatelet therapy(OR,0.267,95％CI 0.116-0.613,P=0.002)and high collateral circulation score(OR,0.551,95％CI 0.368-0.824,P=0.004)were independent protective factors for END in acute anterior circulation large-vessel occlusive mild stroke.Conclusions Acute anterior circulation large-vessel occlusive mild stroke patients with diabetes mellitus or left cerebral hemisphere lesions are prone to END.The combination of argatroban and dual antiplatelet therapy and good collateral circulation can reduce the risk of END.

Objective To achieve non-invasive and precise prediction of mean arterial pressure(MAP)based on a fully convolutional neural network(FCNN).Methods A high-precision blood pressure data acquisition system compliant with international metrological standards was used in conjunction with the'gold standard'auscultation method to collect blood pressure and pulse waveform data from patients.True MAP values were derived via Gaussian fitting of pulse waveform data,constructing a traceable dataset.The FCNN was applied to this dataset to develop a novel MAP prediction method.Additionally,the predictive accuracy of the FCNN was compared with linear regression and conventional empirical formulas.Results The mean squared errors(MSE)for MAP prediction using the FCNN,linear regression,and empirical formulas were 19.76,21.40,and 30.97,respectively.The coefficients of determination(R2)were 0.90,0.89,and 0.84,and the prediction accuracies were 0.90,0.89,and 0.85,respectively.Conclusions By using systolic blood pressure,diastolic blood pressure,age,and arm circumference as input parameters,the FCNN-based MAP prediction method significantly reduces the bias of empirical formulas.This approach not only improves the accuracy of hemodynamic boundary condition acquisition but also contributes to refining the metrological traceability system of non-invasive blood pressure measurement.