OBJECTIVE: To summarize the clinical features and management of two brothers affected with X-linked inhibitor of apoptosis protein (XIAP) deficiency. METHODS: This study retrospectively analyzed the clinical presentations, treatment, and follow-up of two brothers with XIAP deficiency diagnosed at Shanghai Children's Hospital in 2020, and summarized similar cases recorded in databases such as PubMed, Wanfang, Chinese Medical Association Journals, and WIP from January 2006 to November 2024. This study was approved by the Medical Ethics Committee of our hospital (Ethics No.: 2025R128-E01). RESULTS: Patient 1 was the younger brother, who presented at 8 years of age with growth retardation, folliculitis, erythema nodosum, and perineal abscess. Sequencing revealed that he has carried a hemizygous c.566T>C (p.Leu189Pro) variant of the XIAP gene, which was inherited from his mother. He was allergic to infliximab treatment and underwent allogeneic stem cell transplantation (HSCT) in January 2021. During a follow-up of 3 years and 10 months post-transplantation, he showed no gastrointestinal symptoms and had a good outcome. Patient 2 was the elder brother, who presented at 10 years and 6 months of age with growth retardation, rash, and anal fistula. Genetic testing revealed the same variant. He was treated with oral azathioprine but did not have regular follow-ups. At 14-years-and-6-months of age, he had developed severe gastrointestinal infection and hemophagocytic lymphohistiocytosis, which was alleviated after treatment with antibiotics, glucocorticoids, immunoglobulin, and rituximab. He is currently being prepared for HSCT. A total of 13 publications were retrieved, which involved 64 patients from 23 families, with 23 different variants identified. The main clinical manifestations included splenomegaly (34 cases, 53.1%), hemophagocytic lymphohistiocytosis (27 cases, 42.2%), and inflammatory bowel disease or colitis (20 cases, 31.8%). There were significant phenotypic differences among patients from the same family. Thirteen patients (20.3%) underwent HSCT, with a survival rate of 61.5%. CONCLUSION For male children with early onset, poor treatment response, especially those with unexplained splenomegaly and IBD-like symptoms, early genetic testing is recommended. HSCT is a safe and effective treatment for XIAP deficiency. For patients with developmental delay, early onset, and severe IBD phenotype, early transplantation is recommended.
Humans ; Male ; X-Linked Inhibitor of Apoptosis Protein/deficiency* ; Child ; Genetic Diseases, X-Linked/therapy* ; Phenotype ; Siblings ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation

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*

Large bone defects in load-bearing bone can result from tumor resection, osteomyelitis, trauma, and other factors. Although bone has the intrinsic potential to self-repair and regenerate, the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge. Traditionally, repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites, and autogenous bone grafting remains the "gold standard" treatment. However, the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone, donor-site morbidities, and the risk of rejection. In recent years, the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes. In addition to osteoconductivity and osteoinductivity, optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects, but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength. A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements. In this review, the use of traditional bone grafts in load-bearing bone defects, as well as their advantages and disadvantages, is summarized and reviewed. Furthermore, we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance, structural, and functional bionics to provide ideas and directions for future research.
Humans ; Bone Transplantation/methods* ; Weight-Bearing ; Bone Regeneration ; Bone Substitutes ; Bone and Bones ; Animals ; Tissue Scaffolds

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

OBJECTIVES: The use of stem cells is a promising strategy for seizure treatment owing to their unique characteristics. We investigated the role of endothelial progenitor cells (EPCs) in a pentylenetetrazole (PTZ)‍-induced rat seizure model. A selected panel of long noncoding RNAs (lncRNAs), which maintain an elaborate balance in brain neural regulatory networks as well as the autophagy pathway, was also targeted. METHODS: The impact of intravenously administered EPCs on PTZ-induced kindling in rats was evaluated by measuring the expression of neuronal damage markers, neurotrophic factors, and relevant lncRNA genes. Rat behavior was assessed using Y-maze test and open field test (OFT). RESULTS: EPCs mitigated seizure-associated neurological damage and reversed PTZ-induced working memory and locomotor activity deficits, as evidenced by improved performance in the Y-maze test and OFT. EPC treatment reversed the downregulation of the expression of the lncRNAs Evf2, Pnky, Dlx1, APF, HOTAIR, and FLJ11812. EPCs also boosted vascular endothelial growth factor (VEGF) expression. The ameliorative effect achieved by EPCs was comparable to that produced by valproate. CONCLUSIONS These findings indicate that EPCs ameliorate kindling epileptic seizures and their associated abnormalities and that the effect of EPCs may be mediated via the upregulation of certain regulatory lncRNAs.
Animals ; Pentylenetetrazole ; RNA, Long Noncoding ; Seizures/therapy* ; Rats ; Male ; Endothelial Progenitor Cells/transplantation* ; Rats, Sprague-Dawley ; Kindling, Neurologic ; Vascular Endothelial Growth Factor A/metabolism* ; Disease Models, Animal

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 analyze the application efficacy of employing high-density porous polyethylene （Su-por） in combination with temporoparietal fascial flaps via a minimally invasive scalp incision in auricular reconstruction. Methods:This study carried out a retrospective analysis of 50 patients （50 ears in total） who underwentprimary auricular reconstruction with a Su-por scaffold in our hospital from June 2022 to January 2024. All patients underwent primary auricular reconstruction using a minimally invasive scalp incision with high-density porous polyethylene （Su-por） and temporoparietal fascial flaps. The postoperative treatment effects and complications were statistically analyzed. Results:The reconstructed ears of all patients survived. After 6 months of follow-up, the scar hyperplasia of the scalp minimally invasive incision was not obvious in any patient, and no significant hair loss was observed. The reconstructed auricle of 48 patients had a realistic shape and strong three-dimensional sense. With the extension of follow-up time, the three-dimensional structure of the auricle became clearer, and patient satisfaction increased. Among the remaining two patients, one case of flap necrosis survived after skin grafting and dressing changes. One patient had scar hyperplasia at the incision of the reconstructed ear due to a scar-prone constitution, and the shape of the auricle was not ideal, but the scar hyperplasia at the scalp incision was not obvious. Conclusion:One-stage ear reconstruction with high-density porous polyethylene （Su-por） combined with superficial temporal fascia flap through a minimally invasive scalp incision can better show the fine structure of the reconstructed ear. The minimally invasive scalp incision can effectively reduce the occurrence of scar hyperplasia and postoperative alopecia at the scalp incision.
Humans ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Surgical Flaps ; Tissue Scaffolds ; Polyethylene ; Ear Auricle/surgery* ; Male ; Scalp/surgery* ; Female ; Skin Transplantation ; Fascia/transplantation* ; Porosity ; Adult ; Middle Aged

Objective:To investigate the application value of nasolabial flaps in addressing tissue defects after resection of benign and malignant nasal vestibular lesions. Methods:The clinical data of patients with benign and malignant nasal vestibular lesions were analyzed retrospectively. There were 4 cases of squamous cell carcinoma, 2 cases of black hairy nevus and 1 case of chronic proliferative inflammatory lesions, all of which were repaired by adjacent nasolabial flap. Results:After 6 months of follow-up, none of the patients developed nasal vestibular contracture or nostril stenosis, and postoperative nasal ventilation function was good. Conclusion:The preoperative design of individual nasolabial flaps is very important for maintaining maxillofacial aesthetics, protectingthe nasolabial framework, and preserving postoperative nasal ventilation function.
Humans ; Retrospective Studies ; Middle Aged ; Nose Neoplasms/surgery* ; Surgical Flaps ; Male ; Female ; Adult ; Nose/surgery* ; Plastic Surgery Procedures/methods* ; Carcinoma, Squamous Cell/surgery* ; Aged ; Skin Transplantation

Objective:To compare the differences in postoperative healing rates, hearing improvement, and complication rates between endoscopic butterfly inlay cartilage tympanoplasty and underlay cartilage tympanoplasty in Small-to-Medium-Sized Tympanic Membrane Perforations, and to provide clinical basis for indication of the butterfly inlay cartilage tympanoplasty. Methods:This study enrolled patients with chronic suppurative otitis media or traumatic tympanic membrane perforations who were treated at the Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Chongqing Medical University, between January 2022 and May 2023. Inclusion criteria comprised a dry ear period exceeding 3 months, absence of middle ear or mastoid pathology confirmed by temporal bone CT, and an air-bone gap of less than 40 dB. All surgeries were performed by the same surgeon using tympanoplasty techniques. Based on the surgical approach and perforation size, patients were categorized into four groups: Group A（butterfly cartilage tympanoplasty, perforation ≤3 mm）: 23 cases. Group B（butterfly cartilage tympanoplasty, perforation 3-5 mm）: 17 cases. Group C（full-thickness cartilage underlay tympanoplasty, perforation ≤3 mm）: 12 cases. Group D（full-thickness cartilage underlay tympanoplasty, perforation 3-5 mm）: 22 cases. Data collected included perforation duration, preoperative Eustachian Tube Score（ETS）, pure-tone audiometry, otoscopic findings, and postoperative follow-up data on pure-tone thresholds, otoscopic outcomes, and complications such as graft infection and otorrhea. Results: The mean postoperative follow-up period was 4 months （range: 3-12 months）. A total of 74 patients were enrolled, including 40 undergoing butterfly cartilage tympanoplasty and 34 receiving full-thickness cartilage inlay tympanoplasty. In the <3 mm perforation subgroup, the patients receiving butterfly technique （23 cases） exhibited a postoperative air-bone gap （ABG） improvement of （2.33±8.21） dB, and those receiving the inlay technique （12 cases） showed an ABG improvement of （2.49±7.9） dB, with no statistically significant difference between the two groups （P>0.05）. In the 3-5 mm perforation subgroup, the patients receiving butterfly technique （17 cases） demonstrated an ABG improvement of （8.16±5.69） dB, and those receiving the inlay technique （22 cases） achieved an ABG improvement of （8.08±10.42） dB, which were not significantly different （P>0.05）. Tympanic membrane healing rates across the four subgroups were 95.65%, 94.12%, 100%, and 95.45%, respectively, with no statistically significant differences （P>0.05）. Conclusion:In patients with tympanic membrane perforations ≤3 mm and 3-5 mm, butterfly cartilage tympanoplasty achieves comparable audiological outcomes to full-thickness cartilage underlay tympanoplasty. Compared with the underlay technique, the butterfly method is less invasive, preserves the normal anatomical structure of the tympanic membrane, requires a shorter dry ear period, and yields higher patient satisfaction. Therefore, it can be safely recommended for perforations ≤5 mm that do not require tympanotomy exploration.
Humans ; Tympanic Membrane Perforation/surgery* ; Tympanoplasty/methods* ; Treatment Outcome ; Endoscopy ; Cartilage/transplantation* ; Male ; Female ; Adult ; Middle Aged ; Myringoplasty/methods* ; Otitis Media, Suppurative/surgery* ; Aged