ObjectiveTo investigate the independent predictive factors for 90-day mortality in patients with acute-on-chronic liver failure （ACLF）， to establish a risk predictive model， and to assess its predictive efficacy in comparison with MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ. MethodsA retrospective analysis was performed for the clinical data of 394 patients with ACLF who were admitted to The Affiliated Hospital of Inner Mongolia Medical University and Hohhot Second Hospital from July 2018 to July 2024， and general information and laboratory markers on admission were collected from all patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of quantitative data between two groups， and the chi-square test or the adjusted chi-square test was used for comparison of qualitative data between two groups. The LASSO regression analysis was used to identify related variables， and the multivariate logistic regression analysis was used to establish a predictive model and generate a nomogram. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， calibration curve， and clinical decision curve were used to assess the performance of the model. ResultsA total of 394 patients with ACLF were included in this study， with 136 patients in the training set， 58 in the internal validation set， and 200 in the external validation set. The cohort had a mean age of 52.9±11.7 years， among whom male patients accounted for 72.84% （287/394）， the patients with HBV infection accounted for 22.33% （88/394）， the patients with alcohol-related causes accounted for 45.94% （181/394）， and the patients with other causes （including drug-induced and autoimmune diseases） accounted for 31.73% （125/394）. The overall 90-day mortality rate was 27.41% （108/394）. The multivariate logistic regression analysis showed that diabetes （odds ratio ［OR］= 5.831， 95% confidence interval ［CI］： 1.587 — 21.424， P=0.008）， cystatin C （Cys-C） （OR=2.984， 95%CI： 1.501 — 5.933， P=0.002）， and spontaneous peritonitis （SBP） （OR=5.692， 95%CI： 2.150 — 15.071， P<0.001） were independent risk factors， and a nomogram was generated based on these factors. This model had an AUC of 0.836 in the training set， 0.881 in the internal validation set， and 0.878 in the external validation set， showing a good discriminatory ability. The calibration curve showed a good degree of fitting， with a relatively high net clinical benefit. The subgroup analysis based on etiology showed that the model had an AUC of 0.850 in the patients with HBV infection， 0.858 in the patients with alcohol-induced ACLF， and 0.908 in the patients with other etiologies， indicating that the model had a good discriminatory ability across the populations with different etiologies. Compared with traditional scores， the model （AUC=0.836） had a significantly better predictive value than MELD （AUC=0.619， Z=3.197， P=0.001）， MELD-Na （AUC=0.651， Z=2.998， P=0.003）， MELD 3.0 （AUC=0.601， Z=3.682， P<0.001）， and COSSH-ACLF Ⅱ （AUC=0.719， Z=2.396， P=0.017） alone. ConclusionDiabetes， SBP， and Cys-C are independent risk factors for 90-day mortality in patients with ACLF. Compared with MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ scores， this model has a higher predictive value for 90-day prognosis in patients with ACLF and is suitable for patients with ACLF caused by various etiologies.

Background Exposure to per- and polyfluoroalkyl substances (PFAS) is associated with various cancers, and recent studies suggest it may also increase the risk of retinoblastoma (RB) in newborns. However, the pathogenic mechanisms remain unclear. Objective By constructing an adverse outcome pathway (AOP) framework based on public databases to elucidate the potential mechanisms linking PFAS and RB. Methods Chemical-gene interactions and disease-gene interactions from the Comparative Toxicogenomics Database were retracted to identify key toxicological disruption pathways using Kyoto Encyclopedia of Genes and Genomes (KEGG) and a priori knowledge. The Pathview package in R was employed to predict molecular initiating events, key events, and their associated phenotypes, for further understanding the relevant gene-molecule interaction toxicity pathway network. Molecular docking techniques were utilized to validate the affinity of PFAS for these molecular initiating events. An AOP framework focused on toxicological pathways was developed using classical AOP methodologies. Results The PI3K-AKT/MAPK signaling pathway was identified as a potential toxicological pathway involved in PFAS-related RB development, based on KEGG and a priori knowledge. The activation of receptor tyrosine kinases (RTKs) served as the molecular initiating event, leading to the activation of key oncogenes such as RAS and AKT, as well as nuclear factor kappa-light chainenhancer of activated B cells (NF-κB), along with the inhibition of the tumor suppressor gene P53. In this study, 14 types of PFAS demonstrated good binding affinity with most RTKs, with chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) showing particularly favorable predicted binding. Oncogenes, including the c-kit-encoded tyrosine kinase receptor for stem cell factor, epidermal growth factor receptor, and neurotrophic tyrosine kinase receptor 1, were identified as the receptors with the best predicted binding affinity. Conclusion The PI3K-AKT/MAPK signaling pathway may serve as a potential toxicological mechanism linking PFAS to an increased risk of RB.

Objective To explore the screening of peroxisome pathway reactive oxygen species (ROS) oxidative stress gene and its correlation with the antitumor sensitivity of artesunate against pancreatic cancer. Methods Based on microarray mRNA expressions of 55 tumor cell lines in the National Cancer Institute common database,peroxisome pathway-related key genes which were significant correlation with half-inhibitory concentration (IC50 )values of artesunate antitumor activity against human pancreatic cancer were selected by Kendall test.The candidate genes associated with artesunate sensitivity were identified and their mRNA expressions in pancreatic cancer cells were tested using fluorescent quantitative PCR.The contents of peroxi-dase in pancreatic cancer cells were detected through the DAB staining.Results Thirteen key genes mRNA expressions in peroxidase pathways were significantly correlated with IC50 values for artesunate antitumor activi-ty.Compared with normal liver cells HL-7702 (1.00),CRAT (2.89 ±0.06),PEX11B (1.90 ±0.07)and PEX16 (1.35 ±0.07)mRNA expression levels were significantly increased in pancreatic cancer Panc-1 cells which sensitive to artesunate (t =33.00,P <0.01;t =17.85,P <0.01;t =4.54,P <0.05).While CAT
(1.43 ±0.03),SOD1 (2.07 ±0.04)and SOD2 (1.15 ±0.01)mRNA expression levels were also signifi-cantly increased in Panc-1 cells which sensitive to artesunate (t =11.71,P <0.01;t =35.85,P <0.01;t =13.22,P <0.01).However,PEX12 (0.51 ±0.02),CAT (0.47 ±0.02),PRDX1 (0.43 ±0.01),and SOD1 (0.44 ±0.01)mRNA expression levels in pancreatic cancer BXPC-3 cells which resistant to artesunate were significantly lower than that of HL-7702 cells (t =37.53,P <0.01;t =16.52,P <0.01;t =84.20, P <0.01;t =48.24,P <0.01).DAB staining showed that the positive expression rate of peroxisomal content was apparently higher in Panc-1 cells (61.5%)than that of HL-7702 cells (43.8%),with a significant difference (χ2 =16.11,P <0.01).Conclusion Peroxisome and its related ROS antioxidant enzymes CAT, PRDX1,SOD gene expression may be the important factors that affect artesunate antitumor activity against human pancreatic cancer.

Objective To evaluate the relationship of the hepatocyte growth factor (HGF) and the nuclear matrix protein 22 (NMP22) in urine and the stage and grade of bladder uroepithelium carcinoma.Methods A total of 48 post-operative patients (males 39, females 9) with bladder cancer enrolled in this study were perfused with THP. The voided urine of all the patients before and 6 months after perfusion were recovered selectively. HGF and NMP22 ELISA kits were used to detect bladder cancer. Results The recurrence rate was 12.5 %. The HGF level had positive correlation with the stage and grade of bladder uroepithelium carcinoma (P ＜0.05). The NMP22 level had positive correlation with the grade of bladder cancer. The sensitivity and specificity of HGF, NMP22 and cytology were 100 % (6/6), 83.3 % (5/6), 66.7 %(4/6) and 61.9 % (26/42), 57.1% (24/42), 97.6 % (41/42), respectively. Conclusion The HGF and NMP22 are both valuable tumor markers in the urine of bladder uroepithelium carcinoma. They have intimate relation with the stage and grade of bladder uroepithelium carcinoma. Hence combined with cytology, they could be selected as the significance level of early screening and diagnosing.

Objective To evaluate different operative procedures for renal cell carcinoma. Methods 81 cases of renal cell carcinoma operated were reviewed.Radical nephrectomy was carried out for 73 case of which renal artery embolism was conducted for 38 before operation.Simple nephrectomy was carried out for 6 cases and enucleation of the tumor for 2. Results The pathological stu dies showed that 52 cases were clear cell carcinoma,19 cases of granular cell carcinoma,6 cases being a combination of the above two varieties,4 cases being cystic renal cell carcinoma.65 of 81 cases have been successfully followed up for 12～110 months.The 5 year survival rate for stage Ⅰ,Ⅱ,Ⅲ and Ⅳ tumors were 83.9%,78.9%,33.3% and 16.7% respectively. Conclusions Renal artery embolism before radial nephrectomy is essential for a successful operation to achieve a long term survival.Nephron sparing surgery for a small,localized low stage renal tumor is safe and effective.