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

Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Currently,electroencephalogram(EEG),functional near-infrared spectroscopy(fNIRS),and functional magnetic resonance imaging have been widely studied and applied to neuropsychiatric disorders.In recent years,the devices which can realize the simultaneous acquisition of EEG and fNIRS has been developed and gradually applied in the studies on neuropsychiatric disorders.The review provides an introduction of the techniques of synchronized detection and data analysis for EEG-fNIRS,summarizes the analysis methods and new findings of the recent studies of stroke,epilepsy,and other neuropsychiatric disorders using EEG-fNIRS,and also discusses the future research directions.

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 impact of early and late antibody-mediated rejection (AMR) on treatment options and allograft outcomes after kidney transplantation (KT).Methods:From January 2013 to December 2022, the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria. Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group (n=19) while the remainders assigned as late AMR group (n=122). The outcome endpoints included recipient survival rate, death-censored graft survival rate, follow-up estimated glomerular filtration rate (eGFR) and immunodominant donor-specific antibody (DSA) intensity. Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact. Treatment regimens for AMR were collected and categorized.Results:The median follow-up duration was 2.6(1.2, 5.2) year. No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure, with 34 cases (77.2%) due to AMR progression. The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group [100% vs 60.1%(50.5%, 71.6%), P=0.002]. The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group [19.3(-2.6, 38.1) vs -3.3(-14.0, 5.4), P=0.001]. One-year mean fluorescent intensity (MFI) of early AMR group was 1 158(401.5, 3 126.5). It was significantly lower than that when diagnosed with early AMR [3 120.5(2 392.8, 9 340.0)] and one-year MFI of late AMR group [8 094(2 251.5, 13 560.5)] ( P=0.005, P<0.001). Early AMR group primarily received standard treatment (3/19, 15.8%) and regimens centered on rituximab and/or bortezomib (7/19, 43.8%). Late AMR group mainly received standard (16/122, 13.1%) or intensified regimens (9/122, 7.4%) and regimens focused upon rituximab and/or bortezomib (32/122, 26.2%) and MP monotherapy (21/122, 17.2%). Conclusion:The outcome for early AMR is significantly better than that for late AMR. For early AMR, early and robust immunosuppression is recommended. For late AMR, early detection and timely treatment are crucial and individualized strategies should be implemented.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

There are many kinds of variabilities of fetal venous system tending to complicated with complex cardiovascular malformations.Prenatal ultrasound is of great importance for evaluation of fetal venous system.High-definition flow(HD-Flow)combined with spatiotemporal image correlation(STIC)could not only display micro blood flow in fetal venous system,but also show the spatial alignment and flow direction in real time.The research progresses of HD-Flow combined with STIC for evaluating fetal venous system abnormalities were reviewed in this article.

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.