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 investigate the characteristics of macrophage depletion by clodronate liposomes(CL)in a carbon tetrachloride(CCl4)-induced liver fibrosis mouse model,and to analyze the transcriptomic features.Methods Thirty-two C57BL/6 mice were divided randomly into plain control liposomes for clophosome(PL)and clodronate liposome(CL)groups(n=16 mice per group),and administered intraperitoneal injections of PL and CL,respectively.On day 5,each group was further divided into normal(N)and model(M)subgroups(n=8 mice per subgroup).Mice in group M received 10％CCl4 intraperitoneally to induce liver fibrosis,while mice in group N received an equal volume of olive oil.After 4 weeks,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured,and hepatic inflammation and collagen deposition were evaluated by hematoxylin/eosin and Sirius red staining,respectively.Total RNA was extracted from liver tissues for transcriptomic sequencing and subsequent differential gene expression analysis.Results Serum ALT and AST levels were significantly elevated in the PL-M group(P＜0.01),with fibrosis staging primarily at S3,compared with S1 in the CL-M group.Totals of 1462 and 2119 differentially expressed genes(|log fold change|＞2 and P＜0.05)were identified in the PL and CL groups,respectively.Gene Ontology analysis revealed enrichment in multiple biological processes,cellular components,and molecular functions in both models,and Kyoto Encyclopedia of Genes and Genomes analysis identified 29 significantly enriched pathways(P＜0.05).The upregulation of genes including Lgals7 and Timp1 and the downregulation of Mup-ps16 and Mup15 were validated by reverse transcription-quantitative polymerase chain reaction,consistent with transcriptomic trends(P＜0.05).Conclusions This study highlights the characteristics and transcriptomic features of macrophage depletion in the CCl4-induced liver fibrosis model,providing a theoretical reference for research on the immune mechanisms of liver fibrosis.

To explore the effects of different blood loss on liver and kidney function,blood lactic acid levels,and oxidative stress indexes after hemorrhagic shock resuscitation in dogs,10 healthy Chinese rural dogs were randomly divided into 1.5 h blood loss resuscitation group(HSRA group)and 3.5 h blood loss resuscitation group(HSRB group).The changes in liver and kidney function,blood lactic acid,and oxidative stress-related indexes were detected at 2,6,24,48 and 72 h after re-suscitation.The results showed that the liver function indexes of TBIL,ALT,and AST in the HSRB group were higher than those in the HSRA group at each time point after resuscitation.There was no significant change in renal function indexes between the two groups.The level of Lac in the HSRB group was significantly higher than that in the HSRA group at 2 and 6 h after resuscitation.CAT activity in the HSRB group was significantly lower than that in the HSRA group at 2 h after resuscitation.GSH-px activity in the HSRB group was significantly lower than that in the HSRA group at 2,6 and 24 h after resuscitation.SOD activity in the HSRB group was significantly lower than that in the HSRA group at 24 h after resuscitation.MDA content in the HSRB group was sig-nificantly higher than that in the HSRA group at 2,6,24 and 48 h after resuscitation.The results showed that HS could cause liver injury and oxidative stress after resuscitation,and the degree of liver injury and oxidative stress injury in dogs increased with the prolongation of blood loss.

Objective To investigate the status and influencing factors of psychological distress associated with weight loss among young and middle-aged adults with obesity,so as to provide a theoretical basis for developing personalized interventions and improving psychological well-being.Methods A convenience sampling method was used to select young and middle-aged obese patients who visited the weight management clinic of a Grade A tertiary hospital in Jiangxi Province from October 2024 to May 2025.Data were collected using a general information questionnaire,the distress thermometer,the perceived social support scale,the brief illness perception questionnaire,and the simplified coping style questionnaire.Binary logistic regression was applied to identify factors influencing psychological distress.Results A total of 204 valid questionnaires were collected.The detection rate of significant psychological distress was 58.82%(120 cases).Regarding weight loss methods,32.84%of participants opted for medication.The top five issues reported on the psychological distress problem list were:appearance/body image,work/studies,lack of time/energy to care for elderly parents or children,bathing/dressing,and relationship with a partner.Binary logistic regression indicated that age,body mass index,waist circumference,history of chronic disease,perceived social support,illness perception,and negative coping style were significant influencing factors of psychological distress(P﹤0.05).Conclusions The rate of significant psychological distress is relatively high among young and middle-aged obese patients and is influenced by multiple factors.Medical staff may develop personalized interventions based on these factors to reduce the incidence of psychological distress.

Objective To investigate the characteristics of macrophage depletion by clodronate liposomes(CL)in a carbon tetrachloride(CCl4)-induced liver fibrosis mouse model,and to analyze the transcriptomic features.Methods Thirty-two C57BL/6 mice were divided randomly into plain control liposomes for clophosome(PL)and clodronate liposome(CL)groups(n=16 mice per group),and administered intraperitoneal injections of PL and CL,respectively.On day 5,each group was further divided into normal(N)and model(M)subgroups(n=8 mice per subgroup).Mice in group M received 10％CCl4 intraperitoneally to induce liver fibrosis,while mice in group N received an equal volume of olive oil.After 4 weeks,serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured,and hepatic inflammation and collagen deposition were evaluated by hematoxylin/eosin and Sirius red staining,respectively.Total RNA was extracted from liver tissues for transcriptomic sequencing and subsequent differential gene expression analysis.Results Serum ALT and AST levels were significantly elevated in the PL-M group(P＜0.01),with fibrosis staging primarily at S3,compared with S1 in the CL-M group.Totals of 1462 and 2119 differentially expressed genes(|log fold change|＞2 and P＜0.05)were identified in the PL and CL groups,respectively.Gene Ontology analysis revealed enrichment in multiple biological processes,cellular components,and molecular functions in both models,and Kyoto Encyclopedia of Genes and Genomes analysis identified 29 significantly enriched pathways(P＜0.05).The upregulation of genes including Lgals7 and Timp1 and the downregulation of Mup-ps16 and Mup15 were validated by reverse transcription-quantitative polymerase chain reaction,consistent with transcriptomic trends(P＜0.05).Conclusions This study highlights the characteristics and transcriptomic features of macrophage depletion in the CCl4-induced liver fibrosis model,providing a theoretical reference for research on the immune mechanisms of liver fibrosis.

Objective:To investigate the prevalence and severity of symptom burden among long-term survivors of oropharyngeal cancer after radiotherapy, to identify core symptom clusters, and to explore their correlation with quality of life.Methods:A previous retrospective study was conducted by the Cancer Hospital, Chinese Academy of Medical Sciences on patients with oropharyngeal cancer who underwent radiotherapy between January 2010 and December 2020. Patients who were still alive as of December 2023 were further followed and analyzed. From December 2023 to August 2024, symptom burden and quality of life were assessed using the Chinese version of the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Exploratory factor analysis (principal component analysis with Promax rotation) were used to identify symptom clusters. Spearman correlation analysis was performed to explore the relationship between total symptom cluster scores and standardized domain scores of quality of life. Multivariate linear regression analysis was further employed to determine the relationship between identified symptom clusters and overall quality of life.Results:A total of 273 patients were included, with a median follow-up duration of 6.2 years (range: 3.5-14.5 years) and a median age of 61 years (range: 27-88 years) at follow-up. The top 5 incidence rates of symptom reported by patients were mucus problems in the mouth or throat (147 cases, 53.8%), dental or gum issues (143 cases, 52.4%), xerostomia (140 cases, 51.3%), difficulty swallowing or chewing (95 cases, 34.8%), and taste disturbance (79 cases, 28.9%). Among them, xerostomia was the most serious symptom. The most frequently reported interference was impact on work (including household chores) (55 cases, 20.1%). Exploratory factor analysis identified 3 symptom clusters: fatigue-nausea cluster, eating-voice cluster, and xerostomia-sleep cluster, all of which were significantly correlated with lower overall quality of life of patients (all P<0.001). Conclusion:Long-term survivors of oropharyngeal cancer after radiotherapy experience substantial symptom burden. The fatigue-nausea, eating-voice, and xerostomia-sleep clusters are the core symptom clusters impacting quality of life.

Objective To investigate the status and influencing factors of psychological distress associated with weight loss among young and middle-aged adults with obesity,so as to provide a theoretical basis for developing personalized interventions and improving psychological well-being.Methods A convenience sampling method was used to select young and middle-aged obese patients who visited the weight management clinic of a Grade A tertiary hospital in Jiangxi Province from October 2024 to May 2025.Data were collected using a general information questionnaire,the distress thermometer,the perceived social support scale,the brief illness perception questionnaire,and the simplified coping style questionnaire.Binary logistic regression was applied to identify factors influencing psychological distress.Results A total of 204 valid questionnaires were collected.The detection rate of significant psychological distress was 58.82%(120 cases).Regarding weight loss methods,32.84%of participants opted for medication.The top five issues reported on the psychological distress problem list were:appearance/body image,work/studies,lack of time/energy to care for elderly parents or children,bathing/dressing,and relationship with a partner.Binary logistic regression indicated that age,body mass index,waist circumference,history of chronic disease,perceived social support,illness perception,and negative coping style were significant influencing factors of psychological distress(P﹤0.05).Conclusions The rate of significant psychological distress is relatively high among young and middle-aged obese patients and is influenced by multiple factors.Medical staff may develop personalized interventions based on these factors to reduce the incidence of psychological distress.

Objective:To explore the effects of Xiaoyao Conger Decoction pretreatment on model rats of tinnitus with syndrome of liver-qi stagnation and spleen deficiency (TLSSD) and its preliminary mechanisms.Methods:The rats were divided into four groups: a blank group, a model group, a positive group, and Xiaoyao Conger high- and low-dosage groups, with 7 rats in each group according to random number table method. Except for the blank group, the TLSSD model was prepared by the composite etiological method in all groups of rats. The positive group received a gavage of carbamazepine at 15 mg/kg, while Xiaoyao Conger high- and low-dosage groups were given 30 g/kg and 15 g/kg of Xiaoyao Conger Decoction, respectively. The blank and model groups were administered an equal volume of saline once daily for 4 weeks. The frequency of conditioned avoidance response behaviors in rats was recorded before and at 2 and 4 weeks post-drug administration; TCM syndrome scores were documented before and after treatment; auditory brainstem response (ABR) thresholds were monitored at frequencies of 4, 12, 20, and 28 kHz; IL-1β mRNA expression in the inferior colliculus and cochlea was detected by RT-qPCR; and the levels of γ-aminobutyric acid (GABA) and glutamic acid (Glu) in hippocampal tissues were determined by LC-MS/MS.Results:The model group exhibited symptoms of liver depression, including irritability, yellow fur, and a dark red tongue, along with signs of spleen deficiency such as lethargy, decreased activity, and loose stools. Compared to the model group, rats in the Xiaoyao Conger high- and low-dosage groups demonstrated a reduction in conditioned avoidance response behaviors ( P<0.05 or P<0.01), a decrease in TCM syndrome scores ( P<0.05 or P<0.01), lower ABR thresholds at 12, 20, and 28 kHz ( P<0.01), reduced levels of IL-1β mRNA in the inferior colliculus and cochlea ( P<0.05 or P<0.01), and decreased hippocampal Glu levels ( P<0.01). Conclusion:The therapeutic effect of Xiaoyao Conger Decoction pretreatment on TLSSD rats may be related to its ability to improve the mood disorders and stress, reduce the neuroinflammatory response, regulate the CNS neurotransmitter balance, and correct the overexcitability of the auditory centre, etc.

In this paper, the causes of dimethylacetamide poisoning in a small and micro enterprise were analyzed through on-site occupational health investigation, clinical data summary of poisoned patients and occupational hazard factors detection results. The incident was a group poisoning incident caused by exposure to dimethylacetamide, resulting in different degrees of toxic liver disease in 6 workers. Although the concentration of dimethylacetamide in the air in the workplace was excessive, percutaneous absorption may be the main cause of poisoning. The characteristics of percutaneous absorption of dimethylacetamide need to be paid great attention to, which can be used for reference to prevent similar incidents in the future.