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

A traditional Chinese medicine (TCM) monomer is a bioactive compound extracted from Chinese herbal medicines possessing determined biological activity and pharmacological effects, and has gained much attention for treating neuronal diseases. However, the application of TCM monomers is limited by their low solubility and poor ability to cross the blood-brain barrier (BBB). Exosomes are small extracellular vesicles (EVs) ranging in size from 30 to 150 nm in diameter and can be used as drug delivery carriers that directly target cells or tissues with unique advantages, including low toxicity, low immunogenicity, high stability in blood, and the ability to cross the BBB. This review discusses the biogenesis, components, stability, surface modification, isolation technology, advantages, and disadvantages of exosomes as drug carriers and compares exosomes and other similar drug delivery systems. Furthermore, exosome-encapsulated TCM monomers exert neuroprotective roles, such as anti-inflammation, anti-apoptosis, anti-mitophagy, and anti-oxidation, in various neuronal diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and cerebral ischemia and reperfusion (CI/R) injury, as well as anti-drug resistance, anti-tumorigenesis, anti-angiogenesis, and promotion of apoptosis in brain tumors, providing more inspiration to promote the development of an exosome-based delivery tool in targeted therapy for neuronal diseases.

Objective:To explore the current status of kinesiophobia in pregnant women with pregnancy-related low back pain (PLBP) and its influencing factors, so as to inform the clinical development of intervention programs.Methods:Convenience sampling was used to select 270 pregnant women with PLBP who underwent routine obstetric examination from August to November 2023 at the Obstetrics Clinic of Affiliated Obstetrics and Gynecology Hospital of Jiangnan University. Pregnant women were surveyed using the General Information Questionnaire, Tampa Scale for Kinesio-Phobia, Falls Efficacy Scale-International, Pregnancy Exercise Self-efficacy Scale, and Low Back Pain Knowledge Questionnaire. Multiple linear regression was used to explore the factors influencing kinesiophobia in pregnant women with PLBP.Results:In 270 pregnant women with PLBP, the kinesiophobia score was (47.78±8.80) and the prevalence of kinesiophobia was 89.3% (241/270). Multiple linear regression analysis showed that lower extremity edema, pain, fear of falling, exercise self-efficacy, and knowledge of low back pain were the factors influencing kinesiophobia in pregnant women with PLBP ( P<0.05) . Conclusions:Pregnant women have a high level of kinesiophobia, and there are many influencing factors. Healthcare professionals should consider a variety of factors to develop an intervention program to reduce kinesiophobia and increase activity levels in pregnant women with PLBP.

A traditional Chinese medicine(TCM)monomer is a bioactive compound extracted from Chinese herbal medicines possessing determined biological activity and pharmacological effects,and has gained much attention for treating neuronal diseases.However,the application of TCM monomers is limited by their low solubility and poor ability to cross the blood-brain barrier(BBB).Exosomes are small extracellular vesicles(EVs)ranging in size from 30 to 150 nm in diameter and can be used as drug delivery carriers that directly target cells or tissues with unique advantages,including low toxicity,low immunogenicity,high stability in blood,and the ability to cross the BBB.This review discusses the biogenesis,components,stability,surface modification,isolation technology,advantages,and disadvantages of exosomes as drug carriers and compares exosomes and other similar drug delivery systems.Furthermore,exosome-encapsulated TCM monomers exert neuroprotective roles,such as anti-inflammation,anti-apoptosis,anti-mitophagy,and anti-oxidation,in various neuronal diseases,including Alzheimer's disease(AD),Parkinson's disease(PD),multiple sclerosis(MS),and cerebral ischemia and reperfusion(CI/R)injury,as well as anti-drug resistance,anti-tumorigenesis,anti-angiogenesis,and promotion of apoptosis in brain tumors,providing more inspiration to promote the development of an exosome-based delivery tool in targeted therapy for neuronal diseases.

Objective:To explore the current status of kinesiophobia in pregnant women with pregnancy-related low back pain (PLBP) and its influencing factors, so as to inform the clinical development of intervention programs.Methods:Convenience sampling was used to select 270 pregnant women with PLBP who underwent routine obstetric examination from August to November 2023 at the Obstetrics Clinic of Affiliated Obstetrics and Gynecology Hospital of Jiangnan University. Pregnant women were surveyed using the General Information Questionnaire, Tampa Scale for Kinesio-Phobia, Falls Efficacy Scale-International, Pregnancy Exercise Self-efficacy Scale, and Low Back Pain Knowledge Questionnaire. Multiple linear regression was used to explore the factors influencing kinesiophobia in pregnant women with PLBP.Results:In 270 pregnant women with PLBP, the kinesiophobia score was (47.78±8.80) and the prevalence of kinesiophobia was 89.3% (241/270). Multiple linear regression analysis showed that lower extremity edema, pain, fear of falling, exercise self-efficacy, and knowledge of low back pain were the factors influencing kinesiophobia in pregnant women with PLBP ( P<0.05) . Conclusions:Pregnant women have a high level of kinesiophobia, and there are many influencing factors. Healthcare professionals should consider a variety of factors to develop an intervention program to reduce kinesiophobia and increase activity levels in pregnant women with PLBP.

Individuals with type 1 diabetes or advanced type 2 diabetes suffer insufficient insulin secretion, leading to symptoms of hyperglycemia. To maintain the normal blood glucose levels, those people with diabetes must administer insulin multiple times a day. However, insulin requirements are influenced by several factors such as diet, exercise, and illness, combined with the narrow therapeutic index, making accurate insulin dosage challenging. Excessive insulin administration can even pose life-threatening risks. In addition, frequent daily insulin injections place considerable physiological and psychological burdens on patients. To tackle these challenges, researchers have embarked on the development of closed-loop insulin delivery systems. These systems adjust insulin dosages in real-time changes based on the patient’s blood glucose levels, therefore enhancing both the safety and effectiveness of insulin therapy. This review categorizes closed-loop insulin delivery systems into two types: electronic-based and material-based systems, based on their compositional attributes. The exploration of both types covers their components, developmental history, clinical applications, current pros and cons, and future directions. The relative strengths and limitations of these two categories of closed-loop insulin delivery systems are also compared and discussed.

A 51-year-old schizophrenic patient with long-term clozapine treatment developed intestinal obstruction combined with infection. Subsequently, the patient′s clozapine plasma concentration abnormally increased to 3 094.80 μg/L (reference range 350-600 μg/L), accompanied with pulmonary infection. Patient′s symptoms showed significant improvement after clozapine was discontinued, along with intravenous fluid reinfusion and antibiotic treatment. This current article also provided a literature review of 16 reported cases of infection with abnormally elevated clozapine plasma concentration. Clozapine plasma concentration and blood routine should be monitored in clozapine users, and adverse reactions should be treated in time. For clozapine users with infection but normal leukocyte count, multiple bacterial infection indicators such as the neutrophil proportion and C-reactive protein should begiven comprehensive consideration, and antibiotics should be used when appropriate. If clozapine plasma concentration is abnormally high, clozapine can be discontinued and intravenous fluid reinfusion can accelerate clozapine elimination. After the patient′s condition stabilizes, clozapine could be reused.

A 51-year-old schizophrenic patient with long-term clozapine treatment developed intestinal obstruction combined with infection. Subsequently, the patient′s clozapine plasma concentration abnormally increased to 3 094.80 μg/L (reference range 350-600 μg/L), accompanied with pulmonary infection. Patient′s symptoms showed significant improvement after clozapine was discontinued, along with intravenous fluid reinfusion and antibiotic treatment. This current article also provided a literature review of 16 reported cases of infection with abnormally elevated clozapine plasma concentration. Clozapine plasma concentration and blood routine should be monitored in clozapine users, and adverse reactions should be treated in time. For clozapine users with infection but normal leukocyte count, multiple bacterial infection indicators such as the neutrophil proportion and C-reactive protein should begiven comprehensive consideration, and antibiotics should be used when appropriate. If clozapine plasma concentration is abnormally high, clozapine can be discontinued and intravenous fluid reinfusion can accelerate clozapine elimination. After the patient′s condition stabilizes, clozapine could be reused.