Predictive effect of systemic immune inflammatory index combined with neutrophil-to-lymphocyte ratio on prognosis of patients with acute-on-chronic liver failure.

OBJECTIVE: To explore the predictive effect of systemic immune inflammatory index (SII) combined with neutrophil-to-lymphocyte ratio (NLR) on prognosis of acute-on-chronic liver failure (ACLF) patients. METHODS: A retrospective analysis was conducted on the data of 160 patients diagnosed with hepatitis B virus (HBV)-ACLF in Hunan Provincial People's Hospital from June 2022 to June 2023. The patients were divided into a survival group and a death group based on their survival status within 90 days after admission. General data, laboratory indicators, and complications were recorded. The risk factors affecting prognosis of HBV-ACLF patients and the correlation between NLR, SII, and model for end-stage liver disease (MELD) score were analyzed, and the predictive effect of NLR and SII on prognosis was evaluated. RESULTS: Compared to the survival group, the age, MELD score, and incidence of infection of the death group were higher, and the expression levels of total bilirubin, aspartate aminotransferase, serum creatinine, white blood count, neutrophil, NLR, SII, and international normalized ratio were increased, while the expression levels of alanine aminotransferase, platelets and lymphocytes were decreased (all P<0.05). NLR, SII and MELD score were all risk factors affecting the prognosis of HBV-ACLF patients (all P<0.001). There was a positive correlation between NLR, SII and MELD score (P<0.001). SII combined with NLR showed good performance in predicting the prognosis within 90 days after admission in ACLF patients. CONCLUSION: SII combined with NLR has a good prognostic effect on ACLF patients.

Diagnostic Accuracy of Procalcitonin for Bacterial Infection in Liver Failure: A Meta-Analysis.

The purpose of our studies was to systematically assess the accuracy and clinical value of plasma calcitonin in patients with liver failure complicated with bacterial infection. In this study, we included prospective observational studies or randomized controlled trials on PCT. The quality of the studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Heterogeneity, pooled diagnostic odds ratio (DOR), pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the summary receiver operating characteristic curve (SROC), and metaregression analysis were performed using Stata16.0 software. Consequently, the studies revealed substantial heterogeneity (I 2 = 96, 95% confidence interval (95% CI) = 94-99). The results of meta-analysis using random effect models suggested that the combined DOR was 10.67 (95% CI = 3.73-30.53). In addition, the threshold effect analysis showed that the threshold effect was 0.23 and the correlation coefficient was -0.48, indicating that there was no threshold effect. In the forest map, the DOR of each study and the combined DOR are not distributed along the same line, and Q = 2.2 × 1014, P ≤ 0.001. Furthermore, the metaregression analysis of PCT study design, bacterial infection site, and mean age displayed that the P values were >0.05. The combined sensitivity was 0.77 (95% CI = 0.54-0.90), the combined specificity was 0.76 (95% CI = 0.70-0.82), the combined positive likelihood ratio was 3.25 (95% CI = 2.33-4.52), the combined negative likelihood ratio was 0.30 (95% CI = 0.14-0.67), and the combined AUC was 0.80 (95% CI = 0.76-0.83). In conclusion, PCT has moderate diagnostic value for adult liver failure complicated with bacterial infection, and it is a better auxiliary diagnostic index for liver failure with bacterial infection. However, the results of procalcitonin must be carefully interpreted combined with medical history, physical examination, and microbiological assessment.

Paris saponin I induces G2/M cell cycle arrest and apoptosis in human gastric carcinoma SGC7901 cells.

The aim of this study was to investigate the effect of Paris saponin I (PS I) on human gastric carcinoma cell growth and apoptosis and to explore the potential mechanisms. The proliferation of SGC7901 cells was monitored by the MTT cell viability assay, while the nuclear morphology of apoptotic cells was assessed by Hoechst 33258 staining. Flow cytometry was performed to analyze the cell cycle progression of propidium iodide (PI)-stained SGC7901 cells and the apoptotic rate of annexin V/PI-stained cells. Western blotting was used to examine the expression of several cell cycle proteins, including cyclin B1 and Cdk1, and the apoptosis-regulated proteins Bcl-2, Bax, cytochrome c, procaspase-9, and procaspase-3. The MTT assay demonstrated that PS I could induce significant dose- and time-dependent inhibition of SGC7901 cell proliferation. Marked morphological changes, including condensation of chromatin, nuclear fragmentation and apoptotic bodies were clearly shown on Hoechst 33258 staining. PSI treatment also resulted in the disruption of the cell cycle at G2/M and the induction of apoptosis. Following PSI treatment, the cell cycle-related proteins cyclin B1 and Cdk1 were down-regulated. Expression of the pro-apoptotic protein Bax was increased, while anti-apoptotic protein Bcl-2 decreased. PSI treatment resulted in elevated cytoplasmic cytochrome c and activation of the apoptotic proteases caspase-9 and caspase-3. These data indicate that PS acts as an inhibitor of proli I feration in SGC7901 cells by inducing cell cycle arrest and mitochondria-dependent apoptosis. PSI is a potential therapeutic agent against human gastric carcinoma.

Paris Saponin Ⅰ Induces G2/M Cell Cycle Arrest and Apoptosis in Human Gastric Carcinoma SGC7901 Cells / 华中科技大学学报（医学）（英德文版）

The aim of this study was to investigate the effect of Paris saponin Ⅰ (PS Ⅰ ) on human gastric carcinoma cell growth and apoptosis and to explore the potential mechanisms.The proliferation of SGC7901 cells was monitored by the MTT cell viability assay,while the nuclear morphology of apoptotic cells was assessed by Hoechst 33258 staining.Flow cytometry was performed to analyze the cell cycle progression of propidium iodide (PI)-stained SGC7901 cells and the apoptotic rate of annexin V/PI-stained cells.Western blotting was used to examine the expression of several cell cycle proteins,including cyclin B1 and Cdkl,and the apoptosis-regulated proteins Bcl-2,Bax,cytochrome c,procaspase-9,and procaspase-3.The MTT assay demonstrated that PSⅠ could induce significant doseand time-dependent inhibition of SGC7901 cell proliferation.Marked morphological changes,including condensation of chromatin,nuclear fragmentation and apoptotic bodies were clearly shown on Hoechst 33258 staining.PSⅠ treatment also resulted in the disruption of the cell cycle at G2/M and the induction of apoptosis.Following PSⅠ treatment,the cell cycle-related proteins cyclin B 1 and Cdk1 were downregulated.Expression of the pro-apoptotic protein Bax was increased,while anti-apoptotic protein Bcl-2decreased.PSⅠ treatment resulted in elevated cytoplasmic cytochrome c and activation of the apoptotic proteases caspase-9 and caspase-3.These data indicate that PSⅠ acts as an inhibitor of proliferation in SGC7901 cells by inducing cell cycle arrest and mitochondria-dependent apoptosis.PSⅠ is a potential therapeutic agent against human gastric carcinoma.

[Effect of HMGB1-siRNA on proliferation and apoptosis of HepG2 cells].

OBJECTIVE: To investigate the effect of decreased expression of high mobility group Box-1 on the proliferation and apoptosis of HepG2 cells. METHODS: Three specific siRNAs of HMGB1 were designed and synthesized, and were transiently transfected into HepG2 cells by Lipofectamine 2000. The HMGB1 expression in HepG2 cells was detected by RT-PCR and Western blotting respectively. The proliferation activity in vitro was assessed by MTT assay. In situ apoptosis was evaluated by terminal deoxynucleotidyl transferase-deoxyuridine triphosphate nick end labeling (TUNEL) assay. RESULTS: All of these specific HMGB1-siRNAs (1, 2, 3) efficiently and specifically inhibited the expression of the HMGB1 gene, and the levels of HMGB1 mRNA were 1.147+/-0.024, 1.014+/-0.042, 0.435+/-0.055, respectively, in HMGB1-siRNAs transfection group, which were significantly lower than that in Lipofectamine 2000 alone group (1.411+/-0.065, P < 0.01). Correspondingly, all of these specific HMGB1-siRNAs (1, 2, 3) could efficiently and specifically inhibit the expression of the HMGB1 protein, and the levels of HMGB1 protein were 0.369+/-0.035, 0.340+/-0.028, 0.097+/-0.020, respectively, in HMGB1-siRNAs transfection group, which were significantly lower than that in Lipofectamine 2000 alone group (0.553+/-0.051, P < 0.01). Of the 3 specific HMGB1-siRNAs, HMGB1-siRNA-3 (siRNAH3) had the highest inhibition rate (80%). The proliferation of HepG2 cells was markedly inhibited by siRNAH3 transfection. Compared to mock-transfection, siRNAH3 transfection dramatically suppressed the proliferation of HepG2 cells (P < 0.01). Moreover, siRNAH3 can induce apoptosis (P < 0.01). CONCLUSION: siRNA targeting HMGB1 mRNA can specifically reduce HMGB1 gene and protein expression. siRNAH3 can effectively suppress the proliferation and induce apoptosis of HepG2 cells.

[Effect of HMGB1 on human hepatoma cell line-HepG2 proliferation].

OBJECTIVE: To investigate the effect of high mobility group box-1 protein (HMGB1) on the proliferative activity of human hepatoma cell line HepG2 and its potential regulating mechanism. METHODS: The cultured HepG2 cells were treated with recombinant HMGB1 (0, 10, 50, and 100 ng/mL, respectively) for 24 h. Cell proliferation was observed by MTT analysis. Western blot and reverse transcriptase-polymerase chain reaction were used to detect the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 protein and mRNA, respectively. RESULTS: Compared with the control group, HMGB1 at 10, 50, and 100 ng/mL obviously increased HepG2 cells proliferation, cyclin D1 and PCNA protein and mRNA expression after the treatment for 24 h, respectively (P<0.05). Anti-HMGB1 significantly inhibited the proliferation and cyclin D1 and PCNA mRNA and protein expression of HMGB1 on HepG2 cells (P<0.05). CONCLUSION: Proliferation of HMGB1 on HepG2 cells may be associated with increasing cyclin D1 and PCNA expression. Anti-HMGB1 may have a therapeutic effect on hepatocellular carcinoma.