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

Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

In the past, aortic dissection, aortic aneurysm, and other aortic diseases, primarily rely on surgical intervention. In recent years, due to breakthroughs in materials science, endovascular therapy has become the first choice for the surgical treatment of most aortic diseases. However, traditional endovascular repair cannot fully meet the clinical needs for certain complex lesions involving the aortic arch and the originations of visceral arteries. The emergence of physician-modified stent technology has brought new hope for the treatment of complex aortic diseases. This article provides a detailed introduction to the concept, development, technical characteristics, and applications of physician-modified stents in the treatment of aortic diseases, analyzing their advantages and limitations. Physician-modified stents serve as a powerful complement to traditional endovascular interventions and commercial branched stents, yet further research and refinement are still required.

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 evaluate the clinical application of urine sediment score (USS) in early diagnosis, etiological differentiation, staging and prognosis of acute kidney injury (AKI), and to investigate the diagnostic efficacy of independent USS and its combination with blood urea nitrogen(Bun) serum creatinine(sCr) and uric acid(UA) in AKI.Methods:From August 23 to September 28, 2023, 9 020 morning urine samples of hospitalized patients in the First Hospital of Jilin University were detected by Sysmex UF5000.A total of 3 226 ssamples with small and round cell (SRC) > 1/μl and/or CAST>1/μl were screened for microscopic examination, and 404 cases with positive renal tubular epithelial cells and/or cast were enrolled in this study. There were 218 males and 186 females, aged 59.5 (49.0, 71.0) years. The 404 cases were divided into the USS AKI group (345 cases) and the USS non-AKI group (59 cases) according to the USS results based on the microscopic findings. According to Kidney Disease: Improving Global Outcomes (KDIGO) criteria, they were divided into KDIGO criteria AKI group (63 cases) and KDIGO criteria non-AKI group (341 cases), and the AKI group was divided into renal AKI group (33 cases) and non-renal AKI group (30 cases). According to the clinical diagnosis recorded in the medical records, they were divided into clinically diagnosed AKI group (29 cases) and clinically diagnosed non-AKI group (375 cases).The χ 2 test or Fisher exact test was used to compare USS in different AKI causes and stages. Logistic regression was used to calculate the odds ratio of renal AKI and stage 3 AKI. The area under the receiver operating characteristic curve was used to evaluate the sensitivity and specificity of USS, sCr, UA and Bun alone and in combination in the diagnosis of AKI, and the best cut-off value, sensitivity and specificity in the diagnosis of AKI were calculated. P < 0.05 was considered statistically significant. Results:The USS was used to identify the etiology of KDIGO standard AKI group,and there were significant differences in USS between renal AKI group and non-renal AKI group (χ 2=11.070, P<0.001). Compared to USS=1, the odds ratio of renal AKI was 8.125 when USS≥2 (95% CI 2.208—29.901). There was a statistically significant difference in the comparison of USS between groups in each stage of the AKI staging study based on USS (χ 2=15.724, P<0.05). Compared to USS=1, the odds ratio of stage 3 AKI was 9.714 when USS≥2 (95% CI 1.145-82.390). The AUC of independent USS in the diagnosis of AKI was 0.687 (95% CI 0.618-0.757, P<0.001), the specificity was 65.7% and the sensitivity was 61.9%. The AUC of USS combined with Bun, sCr, UA in the diagnosis of AKI was 0.794 (95% CI 0.608-0.980, P<0.05), the specificity was 82.4%, and the sensitivity was 88.9%. Conclusions:There wasan increased likelihood of renal AKI or stage 3 AKI while USS≥2,and whose combination with Bun, sCr and UA will improve the diagnostic efficiency of AKI.

Industry-university-research cooperation is not only the core of technological innovation,but also an important way to enhance industrial competitiveness and achieve high-quality development.Industry-university-research cooperation in Liaoning Province has achieved significant results in promoting technological innovation and economic development,but there are still some problems and challenges.The main problems include insufficient depth of industry-university-research cooperation,scattered innovation resources,lack of long-term stable cooperation mechanisms,as well as talent loss and lack of high-quality innovative talents.Through systematically sorting out the existing models of industry-university-research cooperation,it proposes a series of targeted and operable countermeasures and suggestions.These measures and suggestions provide solid theoretical support for the healthy development of industry-university-research cooperation in Liaoning Province.

Objective:To study the situation of legal regulations for the integration of industry-university-research in Liaoning,improve the concept of legal regulation,optimize the legal regulation methods,so as to promote the deep integration of industry-university-research in Liaoning.Method:Problem-oriented approach was used,and the problems of the current legal regulations for the integration of industry-university-research in Liaoning were reviewed.Result:It was found that legal regulations for the deep integration of industry-university-research in Liaoning were not yet perfect,which was manifested in insufficient coverage of policies and regulations,relatively lagging update of regulations,and insufficient highlighting of local characteristics.Conclusion:In response to the above issues,it is proposed to use measures such as collaborative regulation,incentive regulation and moderate regulation to establish and improve the legal system of the integration of industry-university-research in Liaoning province.

Objective:To explore the diagnostic value of 18F-prostate specific membrane antigen (PSMA) PET/CT PRIMAY score combined with multiparameter MRI (mpMRI) PI-RADS score for clinically significant prostate cancer (CsPCa). Methods:The data of 63 patients with prostate cancer who underwent radical prostatectomy at Beijing Hospital from January 2019 to December 2023 were retrospectively analyzed. The median age was 70 (64, 75) years old with prostate-specific antigen (PSA) level of 8.46 (5.40, 14.80) ng/ml. All patients underwent 18F-PSMA PET/CT and mpMRI examination before surgery, and pathological large sections of prostate specimens were made after surgery. The prostate lesions were diagnosed and located by two radiologists and one pathologist respectively. Lesions with Gleason scores (GS)≥3+ 4 from the surgical pathology were diagnosed with CsPCa, and lesions with negative or GS=6 were diagnosed with non-CsPCa. The PSMA PET/CT images were evaluated using the PRIMARY study criteria (5-level PRlMARY score): no pattern (score of 1), diffuse transition zone or central zone(not focal) (score of 2), focal transition zone(score of 3), focal peripheral zone(score of 4), or an SUV max of at least 12 (score of 5). The degree of uptake of imaging agent in prostate lesions was semi-quantitatively evaluated using lesion-to-background ratios (LBR) of SUV max. MpMRI was evaluated according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The patients were divided into CsPCa group and non-CsPCa group based on patients and lesions. Mann-Whitney U test and chi-square test were used to compare the differences between groups. Multivariate logistic regression analysis was performed to determine the independent predictive factors of CsPCa. Receiver operator characteristic (ROC) curve was used to determine the optimal diagnostic threshold for each independent predictor. Predictive models were constructed for PRIMARY score, PI-RADS score, and their combined application, and the diagnostic performance of each model for CsPCa was compared. Results:Of all 63 patients, there were 54 cases in CsPCa group (85.7%) and 9 cases in non-CsPCa group (14.3%).There was significant difference between CsPCa group and non-CsPCa group in the serum PSA level [9.64 (6.1, 15.3) ng/ml vs. 5.6 (4.6, 7.6) ng/ml]( P<0.05). There was no statistically significant difference in age [71 (64, 75) years vs. 65 (63, 69) years], and number of lesions [2 (1, 2) vs. 2 (1, 3)] (all P>0.05). Of all 109 lesions, there were 81 lesions in CsPCa group(including 49 lesions with Gleason score = 3+ 4, 16 lesions with Gleason score=4+ 3, 14 lesions with Gleason score = 8, and 2 lesions with Gleason score>8) and 28 lesions in non-CsPCa group(including 14 lesions with Gleason score = 3+ 3 and 14 with benign prostate lesions). There was significant difference between CsPCa group and non-CsPCa group in PRIMARY score [4 (3, 5) vs. 2 (1, 4)], LBR [2.69 (2.08, 4.48) vs. 1.89 (1.45, 2.48)], PI-RADS score [4 (3, 5) vs. 2 (2, 3)] (all P<0.05). There was no statistically significant difference in the lesion distribution including the number of lesions located in the transition zone [15(18.5%) vs. 8(28.6%)] and in the peripheral zone[66(81.5%) vs. 20(71.4%)]( P>0.05). Multivariate logistic regression analysis indicated that PRIMARY score ( OR=2.134, 95% CI 1.429-3.187) and PI-RADS score ( OR=2.689, 95% CI 1.618-4.469) were independent predictors of CsPCa (both P<0.01). ROC curves analysis revealed that the cut-off value for diagnosing CsPCa was both 3 for PRIMARY score and PI-RADS score. The accuracy for PRIMARY score, PI-RADS score, and their combined complication in diagnosing CsPCa was 72%, 67%, and 83%, respectively. The sensitivity was 72%, 63%, and 91%, and the specificity was 75%, 79%, and 57%, respectively. The positive predictive value was 89%, 89%, and 86%, and the negative predictive value was 48%, 42%, and 70%, respectively. The area under the curve of the PRIMARY score, PI-RADS score, and their combined complication of the ROC curve for CsPCa were 0.733 (95% CI 0.624-0.842), 0.708 (95% CI 0.599-0.817), and 0.743 (95% CI 0.623-0.862), respectively. The diagnostic efficacy of their combined complication was higher than PRIMARY score or PI-RADS score alone (both P<0.01). Conclusions:Both the 18F-PSMA PET/CT PRIMAY score and the mpMRI PI-RADS score have good diagnostic value for CsPCa. The combined application of the two imaging parameters can improve the accuracy, sensitivity, and negative predictive value, which have a higher diagnostic efficiency of CsPCa.

Syncope is a common emergency in children and adolescents, which has serious influence on the quality of life.After nearly 30 years′ exploration, great progress has been made in the diagnosis and treatment of children′s syncope in China.We have established the diagnosis procedure of syncope in line with health economics.We have also proposed the concept of individualized precise treatment of syncope in children for the first time.The disease spectrum of syncope in children has been continuously enriched.Relevant progresses have been cited by the guidelines of the United States, Europe and Canada, which has also been unanimously recognized by international experts.

Objective:To explore the morbidity features and therapeutic outcomes of rejections in pediatric kidney transplantation (KT) recipients.Methods:Between January 2013 and June 2022, 360 children undergoing KT were recruited.The relevant clinical data were collected for examining the morbidity features and therapeutic outcomes of rejections.The serum levels of creatinine were compared among groups by non-parametric rank test.And Kaplan-Meier and Log-rank methods were employed for examining the incidence of rejection and comparing mortality-censored graft survival rates among patients with different times of rejection.Results:A total of 58 recipients had 82 incidents of rejection with a cumulative incidence of 6.3%, 9.2% and 11.3% at 3/6/12 months respectively.Among 50 incidents of biopsy-proved rejections, the types were T cell-mediated rejection [TCMR, 42.0%(21/50)], antibody-mediated rejection [20.0%(10/50), ABMR] and mixed rejection [38.0%(19/50)].Among 58 incidents of initial rejection, 69% had maintained graft function (MGF) and 31% impaired graft function (IGF) after anti-rejection regimens.Among 80.8%, 85.7% and 75% of recipients with clinical rejection, ABMR or borderline rejection while 36.4% in TCMR patients had MGF.Fifteen kidney allografts lost function in 58 recipients with rejection.Five-year death-censored graft survival was significantly lower in patients with two or more incidents of rejection (30.5%, 95% CI: 12.3%-75.4%) than in those without rejection (92.9%, 95% CI: 89.3%-96.6%) ( P<0.000 1) or with only one rejection (82.9%, 95% CI: 65.9%-100%)( P<0.001). Conclusions:The rejection rate remains high in KT children and it affects graft survival.And TCMR is more likely to cause impaired graft function.Recurrent rejections have a more pronounced impact upon graft survival.