Liver fibrosis is a key pathological process in the transition from chronic liver disease to cirrhosis， especially in elderly patients with chronic hepatitis B， and this process is characterized by rapid progression and poor prognosis. T cell function gradually declines with aging， and T cell senescence is recognized as a key immunological mechanism accelerating the progression of liver fibrosis. Current studies have shown that senescent T cells promote the transition from liver fibrosis to liver cirrhosis by altering the liver inflammatory microenvironment， modulating the activity of fibrosis-related cells， and impairing immune surveillance function. This article systematically reviews the molecular mechanisms of T cell senescence and its role in the progression of liver fibrosis in elderly patients with chronic hepatitis B， as well as novel therapeutic approaches targeting immunosenescence with reference to the latest immunological findings and stem cell-based therapeutic strategies， so as to provide theoretical support for precise intervention for such patients.

The ribosomal protein S11(RPS11)from Enterococcus faecalis is was heterologously ex-pressed using the Pichia pastoris system.The RPS11 gene sequence was optimized to match the yeast codon preference,and the recombinant expression vector pPIC9K-RPS11 was constructed.Electroporation was used to transform the vector into the Pichia pastoris GS115 strain,and high-copy recombinant strains were selected through G418 resistance screening.Protein expression was induced with methanol,and the expression was verified by SDS-PAGE.The recombinant protein was applied in a mouse melanoma treatment model to evaluate its therapeutic effects.The results showed that the recombinant expression vector pPIC9K-RPS11 successfully expressed the target protein with an approximate molecular weight of 14 kDa in Pichia pastoris.The optimal fermenta-tion conditions were determined to be an induction temperature of 30 ℃,induction time of 72 h,and methanol concentration of 1％.Analysis using a mouse peritoneal macrophage trained immuni-ty model revealed that recombinant RPS11 possessed biological activity capable of inducing trained immunity.Additionally,therapeutic experiments in a mouse melanoma model demonstrated that recombinant RPS11 significantly inhibited tumor growth.These findings suggest that the recombi-nant RPS11 secreted by Pichia pastoris not only possesses biological activity in inducing trained immunity but also inhibits tumor cell growth in a mouse melanoma model,providing theoretical support for the heterologous expression and potential applications of recombinant RPS11.

The ribosomal protein S11(RPS11)from Enterococcus faecalis is was heterologously ex-pressed using the Pichia pastoris system.The RPS11 gene sequence was optimized to match the yeast codon preference,and the recombinant expression vector pPIC9K-RPS11 was constructed.Electroporation was used to transform the vector into the Pichia pastoris GS115 strain,and high-copy recombinant strains were selected through G418 resistance screening.Protein expression was induced with methanol,and the expression was verified by SDS-PAGE.The recombinant protein was applied in a mouse melanoma treatment model to evaluate its therapeutic effects.The results showed that the recombinant expression vector pPIC9K-RPS11 successfully expressed the target protein with an approximate molecular weight of 14 kDa in Pichia pastoris.The optimal fermenta-tion conditions were determined to be an induction temperature of 30 ℃,induction time of 72 h,and methanol concentration of 1％.Analysis using a mouse peritoneal macrophage trained immuni-ty model revealed that recombinant RPS11 possessed biological activity capable of inducing trained immunity.Additionally,therapeutic experiments in a mouse melanoma model demonstrated that recombinant RPS11 significantly inhibited tumor growth.These findings suggest that the recombi-nant RPS11 secreted by Pichia pastoris not only possesses biological activity in inducing trained immunity but also inhibits tumor cell growth in a mouse melanoma model,providing theoretical support for the heterologous expression and potential applications of recombinant RPS11.

Objective:To investigate the predictive value of preoperative γ-glutamyl transferase/lymphocyte count ratio (GLR) levels for postoperative tumor recurrence in liver transplant recipients with liver cancer.Methods:The clinical data of 158 recipients who were diagnosed with hepatocellular carcinoma (hereinafter referred to as liver cancer) and received liver transplantation at the No. 900 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from January 2008 to October 2022 were retrospectively analyzed. X-tile software, the Kaplan-Meier method, univariate and multivariate Cox regression, and other statistical methods were performed. The predictive value of preoperative GLR levels for postoperative tumor recurrence in liver transplant recipients with liver cancer and the risk factors for tumor recurrence in liver cancer patients post-liver transplantation were analyzed.Results:The X-tile software analysis confirmed that 96.8 was the optimal cutoff value for the preoperative GLR level to predict recurrence. The grouping threshold for survival analysis using the GLR cutoff value was 96.8. The tumor recurrence rates at 1, 3, and 5 years after surgery in the low-level GLR group (90 cases) and the high-level GLR group were 19.3% vs. 44.2%, 31.8% vs. 60.0%, and 34.1% vs. 62.9% (68 cases), respectively, and the differences were statistically significant between the two groups ( P<0.05). The Kaplan-Meier survival curve analysis results showed that the overall postoperative survival rate and recurrence-free survival rate were significantly lower in the high-level GLR group than the low-level GLR group ( P<0.05). The univariate Cox analysis result showed that there were statistically significant differences in preoperative aspartate aminotransferase, alpha fetoprotein, surgery time, maximum diameter of a solitary tumor, presence or absence of microvascular invasion, presence or absence of portal vein tumor thrombus, and preoperative GLR levels between the two groups ( P<0.05). Multivariate Cox analysis results showed that preoperative alpha-fetoprotein ≥400 ng/ml, GLR≥96.8, and the maximum diameter of a solitary tumor ≥5.0 cm were independent risk factors for postoperative tumor recurrence in liver transplant recipients with liver cancer ( P<0.05). Conclusion:GLR levels have a certain predictive value for postoperative tumor recurrence in liver transplant recipients with liver cancer. Furthermore, the postoperative tumor recurrence rate is relatively high when the preoperative GLR level in liver transplant recipients with liver cancer is ≥96.8.

Objective:To compare the aortic remodeling of the Fabulous stent system and standard thoracic aortic endovascular repair (TEVAR) on distal aorta type B aortic dissection (TBAD). Methods:The prospective data collected between Dec 2017 and Oct 2019 from 134 patients with type B aortic dissection (TBAD) who underwent treatment with the "Fabulous" stent system, and retrospective data from 159 TBAD patients receiving standard TEVAR from corresponding multicenter. By using propensity score matching analysis, we compared the prognosis and aortic remodeling outcomes in patients undergoing Fabulous and standard TEVAR treatments during a 1-year postoperative follow-up.Results:In this study, 62 patients in Fabulous group and 62 patients in standard TEVAR were included.There were no significant statistical differences in baseline characteristics between the two groups. In terms of aortic remodeling in bare stent region, Fabulous group had better change trends of diameter of true lumen [10.6 (4.4, 14.5) mm vs. 4.7 (0.9, 10.7) mm, P=0.001] and false lumen [-24.2 (-30.5, -4.9) mm vs. 0.7 (-11.8, 2.3) mm, P<0.001] than those in the standard TEVAR group. The rate of complete false lumen thrombosis was also higher in the Fabulous group (62.9% vs. 37.1%, P=0.042). Conclusion:The Fabulous stent system, when compared to standard TEVAR surgery, demonstrates good aortic remodeling outcomes in the distal aorta.

Humans ; Endovascular Aneurysm Repair ; Stents ; Blood Vessel Prosthesis ; Aortic Dissection/surgery* ; Endovascular Procedures ; Aortic Aneurysm, Thoracic/surgery* ; Treatment Outcome ; Blood Vessel Prosthesis Implantation ; Retrospective Studies

BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Objective To evaluate the predictive values of albumin-bilirubin (ALBI) and easy albumin-bilirubin (EZ-ALBI) scores for early survival (postoperative 3 months) of recipients with liver failure after liver transplantation. Methods Clinical data of 137 recipients diagnosed with liver failure and underwent liver transplantation were retrospectively analyzed. The optimal cut-off values of preoperative ALBI, EZ-ALBI and MELD scores to predict early survival of recipients with liver failure after liver transplantation were determined by the area under the receiver operating characteristic (ROC) curve. The risk factors of early death of recipients with liver failure after liver transplantation were identified by univariate and multivariate Cox regression analyses. The effects of different ALBI and EZ-ALBI levels upon early prognosis of recipients with liver failure after liver transplantation were analyzed. Results The optimal cut-off values of ALBI, EZ-ALBI and MELD scores were 0.21, -19.83 and 24.36, and the AUC was 0.706, 0.697 and 0.686, respectively. Univariate Cox regression analysis showed that preoperative alanine aminotransferase(ALT)≥50 U/L, aspartate aminotransferase(AST)≥60 U/L, ALBI score≥0.21 and EZ-ALBI score≥-19.83 were the risk factors for early postoperative death of recipients with liver failure after liver transplantation (all P < 0.05). Multivariate Cox regression analysis demonstrated that preoperative ALBI score≥0.21 was an independent risk factor for early postoperative death of recipients with liver failure after liver transplantation (P < 0.05). According to the optimal cut-off value of ALBI score, the early survival rates in the ALBI < 0.21 (n=46) and ALBI≥0.21(n=91) groups were 93.5% and 64.8%, and the difference was statistically significant (P < 0.05). According to the optimal cut-off value of EZ-ALBI score, the early survival rates in the EZ-ALBI < -19.83(n=60) and EZ-ALBI≥-19.83(n=77) groups were 88.3% and 63.6%, and the difference was statistically significant (P < 0.05). Conclusions Preoperative ALBI score is of high predictive value for early survival of recipients with liver failure after liver transplantation, which could be utilized as a reference parameter for selecting liver transplant recipients.

Objective:To explore the predictive value of platelet-albumin-bilirubin(PALBI)score for tumor recurrence after liver transplantation(LT)in patients with hepatocellular carcinoma(HCC).Methods:Clinical data were retrospectively reviewed for 102 HCC patients undergoing LT from January 2010 to December 2020.The predictive value of PALBI score for tumor recurrence after LT and the risk factors for tumor recurrence after LT were examined by receiver operating characteristic(ROC)curve, Kaplan-Meier method and univariate/multivariate Cox regression.Results:The optimal cutoff value of preoperative PALBI score for predicting recurrence was -3.82 with ROC curve, Youden's index 0.317 and area under the ROC curve 0.679.Survival analysis was performed using a PALBI cutoff value of -3.82 as boundary group.The results showed that significant differences existed in 1/3/5-year tumor recurrence rates(17.9% vs.50.0%, 26.9% vs.62.5%, 29.5% vs.62.5%)after low PALBI and high PALBI( P<0.05 for all). Univariate analysis indicated that preoperative tumor maximal diameter, tumor number, Milan criteria, alpha fetoprotein(AFP)level, microvascular invasion, portal venous tumor thrombus, and PALBI score were significantly associated with postoperative tumor recurrence( P<0.05 for all). And multivariate analysis revealed that Milan criteria, AFP level and PALBI score were independent risk factors for postoperative tumor recurrence( P<0.05). Conclusions:Preoperative PALBI score offers some predictive value for postoperative tumor recurrence in HCC patients post-LT.When preoperative PALBI score ≥-3.82 in HCC patients, postoperative tumor recurrence rate is relatively high.

Liver dysfunction after liver transplantation is the most common complication of donation after cardiac death. Since there are many risk factors for liver dysfunction after liver transplantation, preventing it has become a hot topic in the field of liver transplantation. This article reviews the related studies on the quality, preservation of donor liver after the death of citizens and the factors during liver transplantation, so as to provide the best precaution strategy for liver dysfunction after liver transplantation.