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

In recent years， repetitive transcranial magnetic stimulation （rTMS） has garnered significant attention as a therapeutic approach for sleep disorders in the elderly. However， the prevailing rTMS protocols are predominantly developed based on normative neurophysiological data derived from young adults and fail to incorporate individualized parameters tailored to the brain characteristics of the elderly. To address this gap， the consensus development group synthesized the latest evidence from 2010 to 2025 and established a standardized rTMS protocol specifically for elderly patients with sleep disorders. Adhering to the Appraisal of Guidelines for Research and Evaluation II （AGREE II） framework， systematically screened randomized controlled trials （RCTs） and systematic reviews regarding rTMS in the treatment of sleep disorders across various conditions. Meanwhile， the Grading of Recommendations Assessment， Development and Evaluation （GRADE） system was employed to rigorously grade the quality of evidence and the strength of recommendations. This consensus guideline delineates precise rTMS protocols for the management of sleep disorders in the elderly， highlights the adjustment of stimulation intensity according to scalp-cortex distance recommends either MRI‑guided neuronavigation or the Beam F3/F4 heuristic approach for accurate target localization， thereby providing precise rTMS intervention protocol for sleep disorders in the elderly， aiming to enhance clinical efficacy while ensuring treatment safety. ［Funded by National Key Research and Development Program （number， 2023YFC3603200）； General Program of Shenzhen Science and Technology Innovation Commission （number， JCYJ20240813112859008， JCYJ20240813112900002）； Youth Program of Shenzhen Kangning Hospital （number， KN2023A004）； www.guidelines-registry.cn number， PREPARE-2026CN530］

Objective To summarize the clinical characteristics and analyze prognostic factors of neuroblastoma (NB) in infants (≤12 months) at a single center. Methods A retrospective analysis was conducted on the clinical data of infant patients (≤12 months) diagnosed with NB and treated between January 2014 and December 2022. Clinical features were analyzed, and comparisons between two sample rates were performed using the χ² test. Univariate prognostic analysis was conducted using the log-rank test, and survival outcomes were analyzed using the Kaplan-Meier method. Results A total of 42 infants (≤12 months) with NB were enrolled. Low-risk patients underwent surgical resection alone; intermediate-risk patients received surgery combined with chemotherapy with or without maintenance therapy; high-risk patients were treated with surgery and chemotherapy with or without maintenance therapy or radiotherapy. The 5-year event-free survival (EFS) rate was (92.7±4.9)%, and the 5-year overall survival rate was (95.2±3.6)%. Only two patients died because of tumor recurrence or progression. Univariate analysis identified MYCN amplification and the initial lactate dehydrogenase (LDH) level ≥ five times the upper limit of the normal were significantly associated with poor prognosis (5-year EFS: 33.3% vs. 97.4% and 60.0% vs. 97.3%, P<0.0001 and P=0.0035). Conclusion Infant NB has a favorable overall prognosis. MYCN amplification and markedly elevated initial LDH are associated with poor outcomes.

Objective: To explore the epidemiological characteristics and related factors of overweight and obesity among preschool children in Xuzhou City, so as to provide scientific basis for the formulation of corresponding prevention and control strategies. Methods: From October to November 2021, a random cluster sampling method was adopted to select 2 082 preschool children aged 3-7 years from 6 kindergartens in Xuzhou City and their parents for a questionnaire survey. Multivariate Logistic regression and decision tree model were used to analyze the related factors of overweight and obesity among preschool children. Results: The detection rates of overweight and obesity among preschool children were 19.8% and 12.4%, respectively. Multivariate Logistic regression analysis showed that preschool children with overweight fathers ( OR=1.40, 95%CI =1.01-1.96), obese fathers ( OR= 2.32 , 95%CI =1.56-3.45), mothers with insufficient gestational weight gain ( OR=2.11, 95%CI =1.24-3.59), cesarean section ( OR=1.42, 95%CI =1.06-1.92), artificial feeding within the first 6 months of life ( OR=2.33, 95%CI =1.35-4.04), and daily screen time ≥1 h ( OR=1.54, 95%CI =1.14-2.08) had higher risks of obesity; children born to pre pregnancy underweight mothers had a lower risk of obesity ( OR=0.23, 95%CI =0.12-0.44); preschool children with obese fathers ( OR=1.66, 95%CI = 1.19- 2.32) and macrosomic infants ( OR=1.82, 95%CI =1.32-2.51) had higher risks of overweight (all P <0.05). The decision tree model revealed that the factors associated with overweight and obesity among preschool children were ranked by importance from highest to lowest as follows: paternal body mass index, residential location, maternal pre pregnancy body mass index, gestational weight gain, birth weight, children s daily screen time, and feeding pattern with the first 6 months of life. Conclusions The problem of overweight and obesity among preschool children in Xuzhou City is prominent. In addition to considering prenatal factors, early life feeding practices, and behavioral factors, prevention and control strategies should also focus on paternal factors.

With the growing popularity of periocular cosmetic procedures, including injectable fillers, laser therapy, and eyeliner tattooing, the incidence of meibomian gland dysfunction(MGD)and other meibomian gland disorders has increased correspondingly. Nevertheless, the standardized diagnosis and management of these conditions remain controversial. Based on multidisciplinary clinical practice and up-to-date evidence-based medical evidence, this expert consensus systematically elaborates on the pathogenesis, clinical manifestations, and diagnostic criteria of cosmetic procedure-related MGD. It highlights the necessity of detailed medical history collection and comprehensive ocular surface assessment. A stepwise therapeutic strategy, covering conservative nursing management, pharmacological intervention, and physical therapy, is proposed for standardized clinical treatment. In addition, this consensus standardizes the preoperative evaluation workflow for periocular cosmetic procedures, optimizes operational techniques to prevent meibomian gland injury, and stresses the significance of standardized postoperative follow-up for reducing iatrogenic ocular complications. This consensus intends to improve clinicians'cognition and standardized management of periocular cosmetic procedure-related MGD, and facilitate a benign balance between cosmetic procedural safety and ocular surface health.

Nonspecific orbital inflammation(NSOI)is an orbital inflammation that is not associated with an infection. Even though it's often considered the most common diagnosis in orbital biopsies, it's still an exclusionary diagnosis that means systemic illnesses and other possible causes have to be ruled out. Though it is always an excluded clinical diagnosis, acute orbital symptoms such discomfort, exophthalmos, periorbital edema, chemosis, diplopia, and vision impairment are commonly associated with NSOI. Clinical diagnosis and management of NSOI provide a substantial difficulty. There are presently no recognized diagnostic criteria or standard treatment strategy for NSOI, and the clinical symptoms and histological features show significant variation. This guide was formulated under the auspices of the Ocular Oncology Committee of the Opthalmology Branch of the Chinese Medical Doctor Association, Opthalmology Committee of International Association of Intelligent Medicine, Opthalmology Committee of International Association of Translational Medicine making a detailed summary of the definition, classification, diagnosis and treatment of the NSOI, with a view to aiding clinicians to improve diagnostic efficiency and formulate a better treatment plan for patients.

According to the theory of "toxin accumulation damaging yin"， the accumulation of pathological products and the disruption of homeostasis in the pre-metastatic niche （PMN） of malignant tumors correspond to "toxin accumulation" and "yin damage" respectively. During the dynamic evolution of PMN， the main pathogenesis in the initial stage is healthy qi deficiency and phlegm congestion， obstruction in the ying （营） and wei （卫） level， for which the therapeutic approach is fortifying spleen and warming yang， reinforcing healthy qi， consolidating the root， and assissting in resolving phlegm. In the progression stage， the predominant mechanism is mutual binding of phlegm and stasis， with collateral damage and pathological transformation. Treatment should focus on resolving phlegm and eliminating stasis， using insect-derived medicinals to attack accumulation and block pathological transmission. In the terminal stage， the main pathogenesis involves phlegm-stasis transforming into fire， with depletion of qi and yin， for which it is suggested to replenish qi and nourish yin， combine clearing and tonifying methods to control fire-toxin. After the PMN has formed， pathogenic toxin may flow along the collaterals， tending to lodge in corresponding viscera with functional imbalance and deviation between deficiency and excess， eventually giving rise to malignant tumors. Understanding the pathogenesis of the PMN in the malignant tumors based on the "toxin accumulation damaging yin" theory may provide a valuable perspective for developing traditional Chinese medicine strategies for the prevention and treatment of tumor metastasis.

Aim To explore the role and mechanism of epimedokoreanin B(EKB)in HepaRG cell pyroptosis through endoplasmic reticulum stress and NLRP1-me-diated pyroptosis pathway.Methods The effect of EKB on the viability of HepaRG cells at different con-centrations was determined by MTT assay,and the cell growth status was recorded by Incucyte.Four groups of HepaRG cells were set up.The control group was cul-tured with complete medium for 24 h;the drug admin-istration group was cultured with three concentration gradients of 6.25,12.5 and 25 μmol·L-1 of EKB for 24 h.Western blot was used to detect the expression levels of endoplasmic reticulum stress-related proteins and pyroptosis-related proteins in the cells of each group.Results HepaRG cells showed cytotoxicity at a concentration of 6.25 μmol·L-1 for 24 h,and the half maximal inhibitory concentration(IC50)was 12.41 μmol·L-1.Incucyte recordings of the cell growth status showed that the cells in the control group were in good growth status,and the vesicular pyropto-sis cells appeared in the different concentrations of EKB and the cells swelled and ruptured after 24 h.Western blot showed that the protein expression levels of endoplasmic reticulum stress-related proteins pERK,eIF-2α,ATF-4,GRP78,and CHOP significantly in-creased in HepaRG cells at 25 μmol·L-1 of EKB compared with the control group.The proteins of the classical pathway of cellular pyroptosis mediated by NLRP1,caspase-1,cleaved caspase-1,GSDMD,GS-DMD-N significantly increased in HepaRG cells.Con-clusion EKB administration induces HepaRG cell py-roptosis,and EKB activates HepaRG cells to undergo endoplasmic reticulum stress and activates the NLRP1/caspase-1/GSDMD-mediated pyroptosis pathway.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.