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.

In the context of the modernization of traditional Chinese medicine （TCM）， the inheritance of the experiences of famous doctors faces significant challenges due to its complex nonlinear characteristics and dynamic evolution. There are still issues in the current inheritance system， such as the homogenization of talent cultivation models， lack of standardized mentoring practices， and monotonous evaluation method， which hinder the systematic inheritance and innovative development of famous doctors' experiences. Based on a systematic review of the current state of artificial intelligence （AI）-assisted inheritance of famous doctors' experiences， this study explores innovative pathways for deep integration of modern information technologies with famous doctors' experiences from key dimensions， including data authenticity assurance， interdisciplinary collaboration mechanisms， and the establishment of dynamic inheritance standards. It proposes a paradigm shift in the inheritance of TCM famous doctors' experiences in the AI era， aiming to build a new TCM inheritance system of "digital intelligence empowerment and cross-disciplinary innovation"， providing theoretical support and practical pathways for the inheritance of famous doctors' experiences in TCM.

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.

Objective:To compare the clinical efficacy and safety of bronchial artery chemoembolization (BACE) combined with anlotinib (BACE+A) versus BACE alone in patients with stage III-IV non-small cell lung cancer (NSCLC).Methods:A total of 94 patients with advanced NSCLC treated at six interventional centers between November 2020 and November 2021 were retrospectively enrolled. Patients were divided into the BACE+A group ( n=46) and the BACE alone group ( n=48) based on treatment regimen. Baseline and perioperative clinical data were collected and compared between the two groups. Treatment response was evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) at 1, 6, and 12 months after the first BACE procedure. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs) were recorded. Kaplan-Meier survival curves were plotted to compare median OS and PFS between groups. Cox proportional hazards regression analysis was used to identify factors influencing OS and PFS. Results:The Kaplan-Meier analysis showed that the median OS was significantly longer in the BACE+A group (18.8 months, 95% CI 16.3-21.3) than in the BACE group (13.4 months, 95% CI 11.6-15.2) ( P=0.001). The median PFS was also significantly longer in the BACE+A group (9.0 months, 95% CI 7.3-10.7) compared to the BACE group (6.1 months, 95% CI 4.9-7.3) ( P=0.001). At 6 and 12 months post-first BACE, the ORR (43.5%, 40.0%) and DCR (89.1%, 83.3%) were significantly higher in the BACE+A group than in the BACE group (ORR: 20.8%, 14.8%; DCR: 66.7%, 59.3%) (all P<0.05). Multivariate Cox regression identified treatment with BACE+A ( HR=0.42, 95% CI 0.27-0.72, P=0.002), tumor stage ( HR=1.80, 95% CI 1.05-3.07, P=0.031), presence of pre-existing complications requiring intervention ( HR=2.72, 95% CI 1.65-4.50, P<0.001), and >2 BACE procedures ( HR=0.32, 95% CI 0.15-0.68, P=0.003) as independent factors influencing OS. Treatment with BACE+A ( HR=0.49, 95% CI 0.32-0.76, P=0.001), tumor stage ( HR=1.72, 95% CI 1.07-2.77, P=0.025), multi-arterial tumor blood supply ( HR=2.76, 95% CI 1.76-4.31, P<0.001), and>2 BACE procedures ( HR=0.40, 95% CI 0.22-0.71, P=0.002) were independent factors influencing PFS. There was no significant difference in BACE-related adverse events between the two groups (all P>0.05). Hypertension, fatigue, hand-foot syndrome, and anorexia were common anlotinib-specific adverse reactions in the combination group, but no grade 4 or higher adverse reactions were observed. Conclusions:BACE combined with anlotinib demonstrates superior efficacy compared to BACE alone in treating advanced NSCLC, significantly prolonging OS and PFS. The safety profile is manageable, with adverse events remaining within tolerable limits.

Objective:To investigate the value of MRI perfusion multiple parameters in preoperative classification of glioma and differential diagnosis of single brain metastases.Methods:A retrospective analysis was conducted on 78 patients initially diagnosed with glioma or single brain metastasis admitted to Cangzhou People's Hospital from January 2018 to July 2024,including 36 cases of glioma and 42 cases of single brain metastasis.Preoperative brain magnetic resonance imaging was performed to measure dynamic sensitive contrast magnetic resonance imaging(DSC-MRI),dynamic enhanced magnetic resonance imaging(DCE-MRI),and microvascular diameter imaging(VSI)parameters.Compare multiple parameters of magnetic resonance perfusion in patients with gliomas,solitary brain metastases,and gliomas of different pathological grades.Draw the working characteristic curve of the subjects and calculate the area under the curve(AUC)to analyze the diagnostic value of multi parameter magnetic resonance perfusion for gliomas.Spearman analysis was used to investigate the correlation between multiple parameters of magnetic resonance perfusion and pathological grading of glioma patients.Results:Cerebral blood volume(rCBV),cerebral blood flow(rCBF),volume transport constant(Ktrans),extracellular space volume ratio(Ve)and VSI values of glioma patients were significantly higher than those of single brain metastases,and the differences were statistically significant(t=25.066,26.892,22.856,70.455,27.984,P<0.05).The sensitivity of rCBV,rCBF,Ktrans,Kep,Ve,and VSI in diagnosing gliomas were 79.44%,78.54%,80.11%,63.32%,74.61%,and 77.29%,respectively.The specificity was 77.27%,76.49%,78.14%,61.38%,72.58%,and 75.13%,respectively.The AUC was 0.861,0.843,0.815,0.532,0.883,and 0.762,respectively;The sensitivity,specificity,and AUC of the combined detection of rCBV,rCBF,Ktrans,Kep,Ve,and VSI for diagnosing gliomas were 85.98%,82.24%,and 0.911,respectively.The diagnostic efficacy of the combined detection for gliomas was superior to that of individual indicators(Z=0.431,0.335,0.512,0.408,0.369,0.358,P<0.05).The rCBV,rCBF,Ktrans,Ve and VSI values of patients with grade Ⅰ,Ⅱ,Ⅲ and Ⅳ glioma increased successively,and the comparison between groups was statistically significant(F=119.972,100.884,74.180,74.180,118.485,P<0.05).The values of rCBV,rCBF,Ktrans,Ve and VSI were significantly positively correlated with the pathological grade of glioma patients(r=0.685,0.726,0.745,0.668,0.714,P<0.05).Conclusion:There are great differences in the multiple parameters of MRI perfusion between brain glioma and single brain metastases.Therefore,MRI perfusion multiple parameters have high differential diagnosis value,and are helpful for preoperative diagnosis and pathological classification of brain glioma,and have clinical guiding significance.

Objective:To examine the current diagnostic and treatment practices, as well as surgical outcomes, for individuals over the age of 60 diagnosed with acute aortic arch dissection(ATAAD)at Tianjin University Chest Hospital.This analysis evaluates the safety and feasibility of performing open surgical procedures on elderly patients affected by aortic dissection.Methods:A retrospective analysis was conducted on 509 patients diagnosed with ATAAD who were registered in the Chest Pain Center data reporting platform(https: //datacs.chinacpc.org/)at Tianjin Chest Hospital, covering the period from June 2015 to December 2021.The patients were divided into two groups: the elderly group, consisting of individuals aged 60 years or older, and the non-elderly group, comprising those under 60 years of age.Their surgical conditions and short-term outcomes were subsequently examined and compared.Results:A total of 509 patients were included, 311 cases(61.1%)were identified within the non-elderly group, with a mean age of 45.78 ± 8.96 years(range: 21-59 years).In contrast, 198 cases(38.9%)belonged to the elderly group, with a mean age of 65.61 ± 4.13 years(range: 60-81 years).A total of 416 patients(81.7%)received surgical intervention.Among those who underwent surgery, the elderly group exhibited a significantly higher proportion of females(38.1% vs.20.6%, P<0.001), and these patients had smaller body surface areas and lower body mass index values.Furthermore, a greater number of elderly patients presented with comorbid conditions such as hypertension, coronary artery disease, chronic obstructive pulmonary disease, and stroke(all P<0.05).The 30-day all-cause mortality rate, incidence of cerebral infarction, and rate of continuous renal replacement therapy(CRRT)utilization were similar in both groups(20.9% vs.18.8%、15.1% vs.10.5%、19.4% vs.18.1%, all P>0.05).However, elderly patients experienced longer postoperative recovery durations, extended periods of ventilator dependency, and a higher incidence of new-onset atrial fibrillation following surgery(all P<0.05). Conclusions:The surgical rate for elderly patients with ATAAD is low, suggesting that there is significant potential for improvement in clinical diagnosis and treatment.Advanced age should not be viewed as a contraindication for surgery; rather, appropriate case selection and personalized treatment plans can enhance the success rate of surgical interventions.

Objective:To evaluate the anti-reflux effect of digestive tract reconstruction using esophageal-tubular gastric asymmetric anastomosis after radical resection of esophageal and esophagogastric junction cancer.Methods:The main steps were as follows:(1)oblique incision of the lower esophagus;(2)curved incision of the tubular anterior gastric wall;(3)the lower end of the esophagus was anastomosed to the tubular gastric incision with a 90-degree torsion; (4)The anterior wall of the anastomosis was reinforced with a transverse-inverted suture,the posterior wall with a folded suture,and the corners of the gastric stump were buried with sutures.The anastomosis operation time,postoperative complications and postoperative hospital stay were recorded;the reconstructed structure and anti-reflux effect of the anastomosis were observed by digestive tract radiography,gastroscopy and follow-up investigation.Results:The Department of Gastrointestinal and Thoracic Surgery of Huaian First People's Hospital, affiliated to Nanjing Medical University, treated 5 patients of esophagogastric junction cancer and 20 esophageal cancer cases between August 2022 and November 2024, including 19 men and 6 women, with a mean age of (66.7±7.4) years. The mean anastomosis time was (35.4±5.9) minutes, the intraoperative blood loss was (117.6±33.4) ml and the mean postoperative hospital stay was(16.6±5.2) days, with no complications such as anastomotic leakage and bleeding. Postoperative digestive tract radiography (Trendelenburg position)showed that all the patients had no contrast reflux,gastroscopy showed no signs of reflux esophagitis and bile reflux gastritis, the anastomosis showed an inverted whiskers valve-like structure. The median follow-up time was (16.8±6.3) months, and all patients had no reflux symptoms such as acid reflux and belching,and no acid suppressive medication was needed.Conclusion:The esophageal-tubular gastric asymmetric anastomosis is a safe and effective antireflux reconstruction technique.

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.

Resistant ovary syndrome(ROS)and premature ovarian insufficiency(POI)fall under the cat-egory of hypogonadotropic amenorrhea,sharing similar clinical features that often pose challenges in differentiation.ROS can be easily misdiagnosed as POI,which presents a significant obstacle to subsequent treatment.Therefore,it is crucial for patients with fertility requirements to have a clear understanding of the etiology,clinical features,and diagnostic criteria of ROS and POI in order to establish an early diagnosis and develop an appropriate treatment plan.This article provides a systematic and comprehensive discussion on the research progress regarding the eti-ology and pathogenesis,clinical features and diagnosis,as well as individualized management of ROS and POI.The aim is to offer reference for clinicians in achieving early clarification of diagnoses,avoiding misdiagnosis or mistreatment,while assisting patients in improving symptoms and realizing their fertility aspirations through person-alized management.