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

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.

ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Introduction: Multiple daily insulin injections, while effective for glycemic control, impose considerable costs on healthcare systems and carry inherent risks including hypoglycemia, weight gain, and poor treatment adherence. This study evaluates the glycemic effects of insulin regimen de-escalation from multiple daily injections in poorly controlled type 2 diabetes mellitus (T2DM) patients and explores the predictors of successful insulin de-escalation. Methodology: This is a multi-centred, prospective observational study of adult T2DM patients on multiple daily insulin injections with hemoglobin A1c (HbA1c) 7–12% who underwent de-escalation to one or two injections. Patients were reassessed at 3 months and 6 months. Primary endpoint was change in HbA1c from baseline. Secondary endpoints were changes in body weight, hypoglycemia frequency, treatment adherence and predictors of successful insulin de-escalation defined by at least a 0.3% reduction in HbA1c while on de-escalated regimen. Results: A total of 80 patients were included. HbA1c improved from 9.23 to 8.52% (p <0.001) with total daily insulin dose reduction from 0.81 + 0.35 units per kg to 0.46 + 0.24 units per kg. Symptomatic hypoglycemia decreased from 22.5 to 5.0%. Insulin adherence improved from 50.0 to 92.3%. Body weight decreased by 1.4 kg. Forty-nine patients (61.3%) were successfully de-intensified. Factors associated with successful insulin de-escalation included a high baseline HbA1c, high fasting blood glucose and higher estimated glomerular filtration rate, while increased age, disease duration and being Indian were associated with unsuccessful insulin de-escalation. After adjustment of the confounders, only HbA1c (OR 2.07, 95% CI 1.23–3.46, p = 0.006) and the status of being Indian (OR 0.21, 95% CI 0.05–0.94, p = 0.041) remained as significant positive and negative predictors respectively for successful insulin de-intensification. Conclusion Insulin regimen de-escalation, when combined with optimized oral glucose-lowering agents, improved glycemic control and treatment adherence while reducing hypoglycemia and body weight. These findings support insulin therapy deescalation as a safe, effective strategy for poorly controlled T2DM patients taking multiple daily insulin injections.
Diabetes Mellitus, Type 2 ; Prospective Studies ; Insulins

Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

Objective To investigate the species composition of mosquitoes and breeding conditions of larvae in the rice planting areas of Beijing, and to provide a scientific basis for mosquito control in rice fields. Methods Adult mosquitoes were collected using CO2-baited light traps, and mosquito larvae(including pupae)were sampled via the dipping method. Results A total of 4 genera and 6 species of adult mosquitoes were captured in the study area. The dominant species were Culex pipiens pallens, Cx. tritaeniorhynchus, and Anopheles sinensis. The average adult mosquito density was 5.11 specimens per trap-hour, with slightly lower density in July compared to August. For larvae and pupae,3 genera and 4 species were identified, dominated by Cx. tritaeniorhynchus, An. sinensis, and Aedes vexans. Conclusions The mosquito species composition in Beijing′s rice planting areas is diverse. Mosquito control strategies should prioritize the management of adult mosquitoes, while density control of mosquito larvae in paddy fields can be achieved through intermittent irrigation techniques.

ObjectiveTo investigate the heterogeneity and transcriptomic characteristics of T-cell subsets in the liver of mice with nonalcoholic steatohepatitis （NASH） at the single-cell level using single-cell RNA sequencing （scRNA-seq）， and to provide a reference for studying the mechanism of action of T cells in NASH. MethodsSix male C57BL/6 mice were randomly divided into control group fed with regular diet and NASH group fed with methionine-choline-deficient （MCD） diet， with three mice in each group， and liver tissue was collected for scRNA-seq after 6 weeks of modeling. Specific differentially expressed genes were analyzed between T-cell subsets， and related analyses were performed， including dimension clustering， cell type annotation， t-distributed stochastic neighbor embedding （t-SNE）， violin plot， gene ontology （GO） functional enrichment analysis， and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Immunofluorescent staining was used to observe the expression of the T cell marker Tcrα and the specific marker genes Tcf7 and Cxcr6 in the liver of mice in the two groups. The independent-samples t test was used for comparison of continuous data between two groups. ResultsTwo T cell subsets were identified in the liver of mice， and the percentage of cluster 6 decreased from 58.5% in the control group to 48.7% in the NASH group. The top four specific genes were Nsg2， Cd8b1， Cd8a， and Tcf7. Tcf7， a characteristic marker gene for cluster 6， was expressed in 65% of cells in cluster 6， and therefore， cluster 6 was defined as Tcf7⁺ T cells. The GO and KEGG enrichment analyses showed that the differentially expressed genes of cluster 6 were involved in T cell activation， leukocyte adhesion， binding ubiquitin-like protein ligase， and the signaling pathways for Th17， Th1， and Th2 cell differentiation. The percentage of cluster 7 increased from 41.5% in the control group to 51.3% in the NASH group. The top four specific genes of cluster 7 were Cd40lg， Tcrg-C1， Il2rα， and Cxcr6. Cxcr6 was expressed in 90% of cells in cluster 7， and therefore， cluster 7 was defined as Cxcr6⁺ T cells. The GO and KEGG enrichment analyses showed that cluster 7 was involved in T cell activation， cytokine production， the T cell receptor signaling pathway， and the Th17 cell differentiation and MAPK signaling pathway. Immunofluorescence assay showed that compared with the control group， the NASH group showed a significant reduction in the area with positive co-expression of Tcf7 protein and Tcrα protein （1.80%±0.67% vs 0.33%±0.13%， P<0.05） and a significant increase in the area with positive co-expression of Cxcr6 protein and Tcrα protein （0.50%±0.09% vs 2.66%± 0.33%， P<0.001）. ConclusionThere is a reduction in the percentage of Tcf7⁺ T cells and an increase in the percentage of Cxcr6⁺ T cells in NASH mice， revealing the characteristics and differences of T cells in the liver of NASH mice.

Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

AIM To invesigate the quantitative transmitting rules of benchmark samples of Ganjiang Lingzhu Decoction.METHODS HPLC fingerprints were established,after which principal component analysis and partial least squares discriminant analysis were performed.The contents of 6-gingerol,liquiritin and glycyrrhizic acid were determined,after which their transfer rates and dry paste rate were calculated.RESULTS There were 22 common peaks in the fingerprints for 15 batches of benchmark samples with the similarities of more than 0.9.Various batches of benchmark samples were clustered into 3 categories,4 principal components demonstrated the accumulative variance contribution rate of 92.676％,and liquiritin made a great contribution to grouping.In various batches of medicinal materials-decoction pieces,decoction pieces-standard decoctions and standard decoctions-benchmark samples,the transfer rates of 6-gingerol were 84.72％-100.00％,14.29％-24.14％,88.60％-99.36％,those of liquiritin were 74.38％-100.00％,38.54％-64.20％,96.91％-100.30％,and those of glycyrrhizic acid were 68.28％-103.27％,28.48％-49.79％,92.93％-100.49％,the dry paste rate was 13.75％-16.41％.CONCLUSION The preparation process for benchmark samples of Ganjiang Lingzhu Decoction is stable,6-gingerol,liquiritin and glycyrrhizic acid can be taken as their quality markers.Fingerprint combined with content determination can provides a reference for the quality control of Ganjiang Lingzhu Decoction and their related preparations.