Introduction: New-onset diabetes after transplantation (NODAT) is a clinically significant complication associated with adverse metabolic and graft outcomes and affects patients’ quality of life. Data in paediatric populations are limited. This case series describes the incidence, clinical characteristics, and early outcomes of NODAT in a paediatric kidney transplant cohort. Cases: Thirty patients (aged 5–17 years; 16 males, 14 females; 14 Malay, 15 Chinese, 1 Indian) underwent renal transplantation at Hospital Tunku Azizah between 2019 and 2025. NODAT was identified using standard diagnostic criteria and occurred in four patients (13.3%). Among patients who developed NODAT, three were Malay and one Chinese; all were aged 10–17 years, with a predominance of females (n = 3). All were non-obese (body mass index [BMI]: 11–21.4 kg/m²), and only one had a family history of type 2 diabetes mellitus. Underlying causes of ESRF in these patients included focal segmental glomerulosclerosis (FSGS, n = 2), CAKUT (n = 1), and unknown etiology (n = 1). Two patients received kidneys from living donors, and two from cadaveric donors. Two patients demonstrated reduced C-peptide levels, consistent with impaired insulin secretion. All patients received steroid induction and maintenance therapy alongside tacrolimus-based immunosuppression, with one patient also receiving everolimus. Two patients developed post-transplant CMV viremia, which has been associated with NODAT. The onset of NODAT was early, occurring within 2 weeks post-transplant in three patients and at 1 month in one patient. Insulin therapy achieved glycemic control in all cases. Two patients were able to discontinue insulin within 3–4 months, suggesting recovery of endogenous glycemic regulation, while the remaining two required ongoing insulin therapy. Conclusion NODAT affects a substantial proportion of paediatric kidney transplant recipients and may present despite the absence of conventional risk factors. Early surveillance is essential. The observed potential for insulin independence may indicate a reversible component of β-cell dysfunction, which warrants further investigation in larger cohorts.
Child ; Kidney Transplantation ; Hospitals

OBJECTIVES: End stage renal disease (ESRD) is a major disease that seriously threatens the health of young people, and kidney transplantation is an effective treatment method to improve its prognosis.Young ESRD patients at a critical stage of life development often face significant physical and psychological challenges while waiting for kidney transplantation. Their psychological state directly affects treatment compliance and transplantation outcomes.This study aims to explore the psychological experiences of young patients with end stage renal disease during the waiting period for kidney transplantation, and provide a reference for formulating relevant psychological intervention measures. METHODS: A descriptive qualitative research design was adopted. Using purposive sampling, 20 young ESRD patients awaiting for kidney transplantation at the Transplantation Center of Xiangya Third Hospital, Central South University, from June to August 2024, were recruited. Based on the socio-ecological systems theory, a semi-structured interview outline was developed, and directed content analysis was applied to analyze the interview data. RESULTS: According to the results of qualitative interviews, 3 themes and 9 sub-themes were summarized as follows: Microsystem (disease pain experience, anxiety during transplantation waiting period, cognitive differentiation and coping differences), mesosystem (imbalance of family roles and dependent guilt, physician-patient trust dynamics, ambivalence toward peer support), and macrosystem (decision-making powerlessness caused by information asymmetry, sociocultural stigma and public bias, institutional dependence and passive behavior). CONCLUSIONS Young ESRD patients experience complex psychological experiences during the waiting period for kidney transplantation. Healthcare providers should explore corresponding intervention measures based on patients' psychological status to improve their waiting period experience and promote both physical and mental health.
Humans ; Kidney Transplantation/psychology* ; Kidney Failure, Chronic/surgery* ; Qualitative Research ; Female ; Male ; Adult ; Adaptation, Psychological ; Waiting Lists ; Young Adult ; Adolescent ; Anxiety/psychology*

Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

OBJECTIVE: To investigate the mechanism of human embryonic stem cell-derived mesenchymal stem cells (hESC-MSC) in alleviating brain injury after resuscitation in swine with cardiac arrest (CA). METHODS: Twenty-nine healthy male large white swine were randomly divided into Sham group (n = 9), cardiopulmonary resuscitation (CPR) group (n = 10) and hESC-MSC group (n = 10). The Sham group only completed animal preparation. In CPR group and hESC-MSC group, the swine model of CA-CPR was established by inducing ventricular fibrillation for 10 minutes with electrical stimulation and CPR for 6 minutes. At 5 minutes after successful resuscitation, hESC-MSC 2.5×10⁶/kg was injected via intravenous micropump within 1 hour in hESC-MSC group. Venous blood samples were collected before resuscitation and at 4, 8, 24, 48 and 72 hours of resuscitation. The levels of neuron specific enolase (NSE) and S100B protein (S100B) were detected by enzyme linked immunosorbent assay (ELISA). At 24, 48 and 72 hours of resuscitation, neurological deficit score (NDS) and cerebral performance category (CPC) were used to evaluate the neurological function of the animals. Three animals from each group were randomly selected and euthanized at 24, 48, and 72 hours of resuscitation, and the hippocampus tissues were quickly obtained. Immunofluorescence staining was used to detect the distribution of hESC-MSC in hippocampus. Immunohistochemical staining was used to detect the activation of astrocytes and microglia and the survival of neurons in the hippocampus. The degree of apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL). RESULTS: The serum NSE and S100B levels of brain injury markers in CPR group and hESC-MSC group were significantly higher than those in Sham group at 24 hours of resuscitation, and then gradually increased. The levels of NSE and S100B in serum at each time of resuscitation in hESC-MSC group were significantly lower than those in CPR group [NSE (μg/L): 20.69±3.62 vs. 28.95±3.48 at 4 hours, 27.04±5.56 vs. 48.59±9.22 at 72 hours; S100B (μg/L): 2.29±0.39 vs. 3.60±0.73 at 4 hours, 2.38±0.15 vs. 3.92±0.50 at 72 hours, all P < 0.05]. In terms of neurological function, compared with the Sham group, the NDS score and CPC score in the CPR group and hESC-MSC group increased significantly at 24 hours of resuscitation, and then gradually decreased. The NDS and CPC scores of hESC-MSC group were significantly lower than those of CPR group at 24 hours of resuscitation (NDS: 111.67±20.21 vs. 170.00±21.79, CPC: 2.33±0.29 vs. 3.00±0.00, both P < 0.05). The expression of hESC-MSC positive markers CD73, CD90 and CD105 in the hippocampus of hESC-MSC group at 24, 48 and 72 hours of resuscitation was observed under fluorescence microscope, indicating that hESC-MSC could homing to the damaged hippocampus. In addition, compared with Sham group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of CPR group were significantly increased, and the proportion of neurons was significantly decreased at 24, 48 and 72 hours of resuscitation. Compared with CPR group, the proportion of astrocytes, microglia and apoptotic index in hippocampus of hESC-MSC group decreased and the proportion of neurons increased significantly at 24 hours of resuscitation [proportion of astrocytes: (14.33±1.00)% vs. (30.78±2.69)%, proportion of microglia: (12.00±0.88)% vs. (27.89±5.68)%, apoptotic index: (12.89±3.86)% vs. (52.33±7.77)%, proportion of neurons: (39.44±3.72)% vs. (28.33±1.53)%, all P < 0.05]. CONCLUSIONS Application of hESC-MSC at the early stage of resuscitation can reduce the brain injury and neurological dysfunction after resuscitation in swine with CA. The mechanism may be related to the inhibition of immune cell activation, reduction of cell apoptosis and promotion of neuronal survival.
Animals ; Heart Arrest/therapy* ; Cardiopulmonary Resuscitation ; Swine ; Humans ; Male ; Human Embryonic Stem Cells/cytology* ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/cytology* ; Phosphopyruvate Hydratase/blood* ; Brain Injuries/therapy* ; S100 Calcium Binding Protein beta Subunit ; Apoptosis ; Disease Models, Animal

OBJECTIVE: To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice. METHODS: BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues. RESULTS: BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation. CONCLUSION The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.
Animals ; Mice ; Mesenchymal Stem Cell Transplantation ; Liver Cirrhosis/etiology* ; Male ; Cholestasis/therapy* ; Mice, Inbred C57BL ; Hepatic Stellate Cells ; Mesenchymal Stem Cells

In recent years, digital bone harvesting and grafting technology in dental implantology has emerged as a cutting-edge advancement in the field of oral medicine, gaining widespread application in the treatment of complex bone defect cases. By integrating digital imaging, virtual design, and precise surgical guidance, this technology has significantly enhanced the success rate of dental implants and improved patient outcomes. However, the rapid development of this technology has also highlighted the lack of standardized clinical protocols, necessitating the establishment of unified guidelines through expert consensus. This article provides a detailed overview of the development process of the group standard Clinical Protocol for Bone Harvesting and Grafting under Digital Guidance in Oral Implantology and offers an in-depth interpretation of its key components, aiming to serve as a valuable reference for clinical practice and academic research.
Humans ; Bone Transplantation/methods* ; Surgery, Computer-Assisted/methods* ; Dental Implantation/methods* ; Tissue and Organ Harvesting/methods* ; Clinical Protocols

INTRODUCTION: A successful vaccination programme forms the cornerstone of controlling coronavirus disease 2019 (COVID-19). The unprecedented speed of COVID-19 vaccine development and lack of long-term data have raised fears regarding its safety and efficacy. Vaccine hesitancy can undermine the uptake, and hence success of the vaccination programme. Given the high complication rates of COVID-19 infections in kidney transplant recipients, it is particularly important to identify and address vaccine hesitancy in this population. METHODS: We conducted a cross-sectional survey among kidney transplant recipients attending transplant clinic between 5 April and 5 May 2021. The survey assessed attitudes towards COVID-19, willingness/hesitancy towards COVID-19 vaccination, vaccination concerns and prompts to vaccination. This was scored on a Likert scale with scores ranging from 'strongly disagree' - 1 point to 'strongly agree' - 5 points. RESULTS: One hundred and one completed responses were captured. Of these, 86% respondents reported to agree or strongly agree to vaccination. This was despite significant concerns of allograft rejection (mean score 4.12, standard deviation [SD] 0.97) and decreased immunosuppressant efficacy (mean score 4.14, SD 0.96) with vaccination. Multivariable model showed a positive association with transplant vintage of ≥ 5 years (median 2.41), lower educational levels of secondary school or less (median 5.82) and healthcare provider advocacy (median 1.88) in predicting vaccine acceptance. CONCLUSIONS Vaccine acceptance rate was high among kidney transplant recipients. Vaccine hesitancy remains a concern in those with a transplant vintage of less than 5 years and those with tertiary educational level. Healthcare provider advocacy is important in improving vaccine acceptance rates.
Humans ; Kidney Transplantation ; Singapore/epidemiology* ; Male ; Cross-Sectional Studies ; Female ; COVID-19 Vaccines ; COVID-19/epidemiology* ; Middle Aged ; Adult ; Transplant Recipients/psychology* ; Patient Acceptance of Health Care/statistics & numerical data* ; Vaccination Hesitancy/psychology* ; Surveys and Questionnaires ; Vaccination/psychology* ; Aged ; SARS-CoV-2

BACKGROUND: Effective interventions during the coronavirus disease 2019 (COVID-19) pandemic require an understanding of patients' knowledge and perceptions that influence their behaviour. Our study assessed knowledge of COVID-19 among kidney transplant recipients and donors, hitherto unevaluated. METHODS: We conducted a cross-sectional survey among 325 kidney transplant recipients and 172 donors between 1 May 2020 and 30 June 2020. The survey questionnaire assessed knowledge levels of COVID-19, sociodemographic data, health status, psychosocial impact of COVID-19 and precautionary behaviours during the pandemic. RESULTS: The mean COVID-19 knowledge score of the study population was 7.5 (standard deviation: 2.2) out of 10. The mean score was significantly higher among kidney recipients compared to kidney donors (7.9 [1.9] vs. 6.7 [2.6]; P <0.001). Younger age (21-49 vs. ≥50 years) and higher education (diploma and higher vs. secondary and lower) were associated with significantly higher knowledge scores in donors, but not among recipients ( P -interactions ≤0.01). In both kidney recipients and donors, financial concerns and/or social isolation were associated with lower knowledge levels. CONCLUSIONS Concerted efforts are needed to improve COVID-19 knowledge in kidney transplant recipients and donors, particularly older donors, donors with lower education and patients with financial concerns or feelings of social isolation. Intensive patient education may mitigate the impact of education levels on COVID-19 knowledge levels.
Humans ; COVID-19/epidemiology* ; Kidney Transplantation ; Middle Aged ; Singapore/epidemiology* ; Male ; Female ; Adult ; Cross-Sectional Studies ; Health Knowledge, Attitudes, Practice ; Transplant Recipients/psychology* ; Surveys and Questionnaires ; Tissue Donors/psychology* ; SARS-CoV-2 ; Young Adult ; Aged ; Pandemics

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*