1.Risk factors for 90-day mortality in patients with acute-on-chronic liver failure and establishment of a predictive model
Jing SUN ; Tingji WANG ; Zhijiao DUAN ; Li ZHANG ; Yanmei LI
Journal of Clinical Hepatology 2026;42(1):151-159
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.
2.Constructing adverse outcome pathway for per- and polyfluoroalkyl substances and retinoblastoma based on PI3K-AKT/MAPK signaling pathway
Yuyan GUI ; Tingji WANG ; Minghao WANG ; Yaqi XU ; Yunhui ZHANG
Journal of Environmental and Occupational Medicine 2024;41(12):1361-1368
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.
3.Clinical observation of green laser vaporization for the treatment of bladder tumor in 522 patients
Zhihua ZHANG ; Yatong CHEN ; Zhaoyi LI ; Tingji ZHANG ; Qiqing FENG ; Jian LI
Tianjin Medical Journal 2017;45(9):976-979
Objective To investigate the safety and efficacy of photoselective green laser vaporization of bladder tumor (PVBT). Methods A total of 522 patients with bladder tumor were enrolled in present study from January 2010 to May 2015, including 405 cases of non muscle-invasive bladder cancer (NMIBC) and 117 cases of muscle-invasive bladder cancer (MIBC). All of patients were treated with PVBT and intravesical instillation of epirubicin. Patients with MIBC received intravenous chemotherapy (kisi-hama and cisplatin). Results The hospitalization time was (7.32±1.28) days, the operation time was (27.08±5.36) min, and the indwelling urinary catheter was (2.42±0.34) days for patients in NMIBC group. During the follow-up period (12-60 months), 38 cases (9.4%) relapsed, of which 3 cases underwent radical cystectomy, and other 35 cases underwent PVBT again. All 405 patients were alive at the end of follow-ups. The hospitalization time was(26.18 ± 1.92) days, the operation time was (38.32 ± 6.54) min, and the time of indwelling urinary catheter was (2.72 ± 0.85) days for patients of MIBC group. During the follow-up period (12-60 months), 19 cases (16.2%) relapsed. Among them, 4 patients underwent radical cystectomy, and other 15 cases underwent PVBT. Six patients died from distant organ metastasis (including 2 cases of pulmonary metastasis and 4 cases of bone metastasis), and other 111 patients survived. Conclusion PVBT is safe and effective in the clinical application, especially for NMIBC and MIBC patients who are unable or unwilling to undergo radical cystectomy.
4.Correlation of peroxisome pathway reactive oxygen species oxidative stress gene and its correlation with the antitumor sensitivity of artesunate against pancreatic cancer
Jihui DU ; Houde ZHANG ; Jing WEI ; Lei WANG ; Tingji SUN
Journal of International Oncology 2016;43(7):503-507
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.
5.Relationship between content of hepatocyte growth factor and nuclear matrix protein 22 in urine and the stage and grade of bladder uroepithelium carcinoma
Ruipeng HOU ; Tingji ZHANG ; Guangbo ZHU ; Xiaobo WANG
Cancer Research and Clinic 2011;23(3):179-181
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.
6.Transitional cell carcinoma of the bladder in patients under 30 years of age
Xin LI ; Fangliu GU ; Tingji ZHANG
Chinese Journal of Urology 2001;0(09):-
Objective To evaluate the diagnosis and treatment of transitional cell carcinoma of the bladder in patients under 30 years of age. Methods A retrospective study of 22 cases of transitional cell carcinoma of bladder in patients under 30 years of age treated between 1980 and 1999 was carried out. Results In most patients evaluation was prompted by gross hematuria(77.3%).Preoperative B-ultrasonography and urinary cytology correlated well with cystoscopic and biopsy findings.18 cases were treated by means of transurethral resection, and 4 cases by partial resection of bladder. 17 patients have been followed up for 6~107 months.5 patients had recurred. Conclusions Transitional cell carcinoma of the bladder ocurrs rarely during the first three decades of life. The tumors were of low grade,noninvasive,and associa- ted with a low recurrence and an excellent prognosis. The treatment of choice is transurethral resection. Regular follow-up is essential.

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