Liver transplantation is the preferred treatment for end-stage liver disease, but recipients require long-term immunosuppressive therapy to control rejection, which may lead to complications and affect their long-term survival. Immune tolerance refers to the ability of organ transplant recipients to maintain their immune system's tolerance to the graft without relying on long-term immunosuppressants. Immune tolerance is an ideal goal pursued in the field of organ transplantation, which can reduce adverse drug reactions and improve long-term survival rates. Cell therapy has emerged as a promising strategy to induce such tolerance after liver transplantation. Therefore, this article reviews the application progress of cell therapies such as regulatory T cells, regulatory dendritic cells, mesenchymal stem cells, hematopoietic stem cells, etc. in inducing immune tolerance after liver transplantation, in order to provide reference for the clinical application of immune tolerance induction after liver transplantation.

[Objective] To evaluate the efficacy and practicality of autologous platelet-rich plasma (aPRP) in patients undergoing total aortic arch replacement for aortic dissection. [Methods] A retrospective analysis was performed on 483 patients diagnosed with type A aortic dissection who underwent total aortic arch replacement between January 2016 and November 2023. Patients were categorized into two groups based on whether they received aPRP. Baseline characteristics, intraoperative blood product usage and postoperative outcomes were compared between the two groups. [Results] The aPRP group exhibited reduced usage of allogeneic platelets (1.55±1.04 vs 1.60±1.27)U, allogeneic plasma (480.89±432.49 vs 746.50±508.81)mL, allogeneic RBC (red blood cell)(5.95±1.91 vs 6.17±3.52)U, bivalirudin (2.66±1.51 vs 3.31±1.59)U and coagulation factor Ⅶ (0.67±1.03 vs 1.22±1.43)mg compared to the non-aPRP group (P<0.05). The incidence of postoperative hypoxemia was lower in the aPRP group (43.98% vs 48.41%), and the duration of mechanical ventilation was significantly shorter[median 50.91 (interquartile range 18.71, 113.71) vs 83.40 (37.73, 151.98) hours]. There were no significant differences between the two groups in terms of postoperative mortality, continuous bedside hemofiltration, cerebral infarction, cerebral hemorrhage, paraplegia or re-exploration for hemostasis(P>0.05). [Conclusion] The application of aPRP in total aortic arch replacement effectively diminishes intraoperative blood product usage and the incidence of lung injury-related complications. However, it does not demonstrate significant benefits in terms of mortality, cerebral infarction and other complications.

Background and aims:Despite growing evidence linking pretransplant exposure to immune checkpoint inhibitors(ICIs)to increased allograft rejection risk after liver transplantation(LT),a lack of comparative studies to definitively establish the correlation between ICI exposure and adverse short-term outcomes after LT exists.This study aimed to analyze the impact of preoperative ICI exposure on short-term post-LT prognosis and allograft rejection risk.Methods:This retrospective cohort study included 121 recipients who underwent LT for hepatocellular carcinoma(HCC)between June 2019 and March 2023.The recipients were categorized into ICI(n=35)and non-ICI(n=86)exposure groups based on pretransplant ICI exposure.Demographics,clinical characteristics,and short-term outcomes were compared between the cohorts.Kaplan-Meier analysis evaluated the impact of ICI exposure on graft survival.Univariate and multivariate logistic regression models assessed the impact of patient characteristics on allograft rejection.Results:Recipients with or without ICI exposure exhibited comparable demographic baseline charac-teristics.The incidences of early allograft dysfunction and biliary and vascular complications were similar between both groups.Post-transplant infection incidence was 37.1％and 20.9％in the ICI and non-ICI groups,respectively(P=0.064).Allograft rejection rates were significantly higher in the ICI group than in the non-ICI group(22.9％vs.5.8％,P=0.015).The ICI group exhibited a higher 90-day post-transplant mortality rate than that of the non-ICI group(14.3％vs.2.3％,P=0.034).Logistic regression analyses demonstrated that allograft rejection independently correlated with 90-day post-transplant mortality,with ICI exposure being an independent risk factor for allograft rejection.In recipients with ICI exposure,a shorter interval between ICIs and LT(washout period)was significantly associated with a higher allograft rejection risk,with the optimal washout period identified as 21 days for predicting 90-day rejection-free survival(P=0.0001).Moreover,in recipients with allograft rejection,the peripheral CD4+/CD8+T cell ratio was much lower in the ICI group than in the non-ICI group.Conclusions:Pretransplant ICI exposure was an independent risk factor for allograft rejection and was significantly associated with 90-day post-transplant mortality after LT for HCC.A ≤21-day washout period was significantly associated with allograft rejection.Future multicenter studies with larger cohorts and prospective designs are essential to validate these findings,confirm causality,and establish standardized clinical guidelines for ICI use before transplantation.Trail registration:ClinicalTrials.gov NCT05913583.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.

Purpose::The removal of small foreign bodies embedded within the deep soft tissues of the maxillofacial region is a complex and challenging task for maxillofacial surgeons. The purpose of this study was to explore the efficacy of the combination of intraoperative CT and surgical navigation for the removal of small foreign objects in the maxillofacial region.Methods::A serial case study was conducted involving all consecutive patients who underwent surgical removal of small foreign bodies in the maxillofacial region. The combination of intraoperative CT and a surgical navigation system was used at a single medical institution from January 2018 to December 2022. Comprehensive data, including patient demographics, characteristics of the foreign bodies, previous surgical interventions, duration of the surgical procedure, and removal success rate were collected for this study. Relevant data were recorded into Microsoft Excel sheet and analyzed using SPSS version 22.0.Results::Nine patients (6 males and 3 females) were included in this study, with an average age of 37 years. Each patient had previously undergone an unsuccessful removal attempt utilizing conventional surgical methods based on preoperative CT imaging or C-arm guidance at a local healthcare facility. Four patients also experienced unsuccessful attempts with preoperative CT image-based navigation systems. However, by employing the combined approach of intraoperative CT and surgical navigation, the foreign bodies were successfully removed in all 9 patients. The mean duration of the surgical procedure was 59 min, and the average size of the foreign bodies was approximately 26 mm 3. Postoperative follow-up exceeding 6 months revealed no complications. Conclusion::The combined use of a surgical navigation system and intraoperative CT represents a potent and effective strategy for the precise localization and subsequent removal of small foreign bodies from the soft tissue structures of the maxillofacial region. This integrative approach appears to increase the success rate of surgical interventions in such cases.

Objective To summarize the clinical experience of pulmonary lobectomy by uniportal video-assisted thoracoscope in parallel position.Methods The clinical data of 90 patients who underwent uniportal video-assisted thoracoscopic lobectomy in Zhongshan Hospital(Xiamen Branch),Fudan University were retrospectively analyzed.Among them,41 patients underwent lobectomy by uniportal thoracoscope in parallel position,and 49 patients underwent lobectomy by uniportal thoracoscope in non-parallel position.The perioperative related indicators of the two groups were compared.Results There was no significant statistical difference between the parallel uniportal thoracoscopic group and the non-parallel uniportal thoracoscopic group in terms of operation time[(135.2±18.1)min vs.(132.7±25.6)min],intraoperative blood loss[(100.1±27.2)mL vs.(117.3±33.5)mL],postperative extubation time[(3.0±0.7)d vs.(3.1±0.9)d],hospitalization time after operation[(4.3±1.3)d vs.(4.8±1.5)d]and relapse rate after surgery in 3 year(7.32%vs.10.20%).Conclusion Lobectomy by uniportal thoracoscope in parallel position was safe and feasible in technique.

Objective To explore the mechanism of butylphthalide(NBP)in regulating microglia acti-vation and inflammatory cytokine expression in the hippocampus of the mouse model of delayed encephalopathy af-ter carbon monoxide poisoning(DEACMP).Methods Wild-type C57 adult mice with normal cognitive function were selected,and DEACMP was modeled by static inhalation of carbon monoxide.The mice were randomized in-to three groups:DEACMP,control,and NBP.The NBP group was administrated with NBP suspension at 6 mg/kg by gavage for 21 days,and the DEACMP and control groups were administrated with the same amount of vegeta-ble oil by gavage.The hippocampal injury was observed by HE staining.The protein level of ionized calcium-bind-ing adapter molecule 1(IBA1)was determined by Western blotting,and the levels of downstream inflammatory cytokines were measured by ELISA.Results Compared with the control group,the DEACMP and NBP groups showed prolonged escape latency(P=0.001,P=0.029),reduced nerve cells(P=0.001,P=0.035),up-regulated expression of IBA1(P=0.001,P=0.042),increased mean fluorescence intensity of IBA1(P=0.001,P=0.021),and elevated levels of tumor necrosis factor-α(TNF-α)(P=0.002,P=0.024),inter-leukin(IL)-6(P=0.001,P=0.015),and IL-1β(P=0.001,P=0.023).Compared with the DEACMP group,the NBP group showed shortened escape latency(P=0.025),increased nerve cells(P=0.039),down-regulated expression of IBA1(P=0.035),decreased average fluorescence intensity of IBA1(P=0.031),and lowered levels of TNF-α(P=0.028),IL-6(P=0.037),and IL-1 β(P=0.034).Conclusion NBP can inhibit the activation of microglia and reduce the expression of inflammatory factors,thereby alleviating cog-nitive dysfunction and brain tissue damage caused by DEACMP.

Objective To investigate the application of pre-hemostatic suturing in adolescent circumcision with a stapler.Methods A total of 120 patients with long foreskin treated in our hospital were included,and they were divided into two groups by random number table method,among which the patients in the observation group received circumcision with a stapler after pre-hemostatic suturing of the foreskin vessels,and these in the control group received conventional circumcision with a stapler.The operation time,intraoperative blood loss,postoperative healing time and occurrence of postoperative hematoma of the two groups were analyzed.Results There was no significant difference in the operation time between the two groups(P＞0.05).The intraoperative blood loss in the observation group was less than that in the control group,the postoperative healing time was shorter than that in the control group,and the incidence of postoperative hematoma was lower than that in the control group,with statistically significant differences(P＜0.05).Conclusion The application of pre-hemostatic suturing in circumcision with a stapler can improve surgical safety,with ease of learning,which may increase the benefit of patients.