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

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

Objective To assess the intervention effect of nicotinamide mononucleotide (NMN) on the mouse model of hematotoxicity induced by subacute benzene exposure. Methods Benzene exposure and NMN intervention were adopted in a 2×2 factorial design, as benzene exposure and non-exposure, and NMN intervention and non-intervention. Male specific pathogen-free C57BL/6J mice were randomly assigned to negative control group, NMN control group, simple benzene exposure group and NMN intervention group, with 12 mice in each group. Benzene exposure of mice in simple benzene exposure group and NMN intervention group was conducted by dynamic inhalation of benzene at a concentration of 325 mg/m³ for six hours per day, five days per week for four weeks (28 days). Mice in the negative control and NMN control group inhaled clean air. During benzene exposure, mice in the NMN control group and NMN intervention group received NMN in drinking water at a dose of 300 mg/kg body weight. Peripheral blood samples of mice were collected for complete blood count analysis and calculation of composite inflammatory indices after 28 days. Results Interaction analysis showed that the counts of peripheral white blood cell, neutrophil, lymphocyte, and platelet of mice in the simple benzene exposure group were lower than those in the negative control group (all P<0.05). Neutrophil and platelet counts in the NMN intervention group were higher than those in the simple benzene exposure group (all P<0.05). The results of main effect analysis showed that the monocyte count of peripheral blood, systemic inflammatory index, systemic inflammatory response index, neutrophil/lymphocyte ratio and platelet/lymphocyte ratio of mice in the benzene exposure group increased (all P<0.05), and the basophil count and lymphocyte/monocyte ratio decreased (all P<0.05), compared with the control group. Conclusion Oral NMN alleviates subacute benzene-induced decreases in peripheral neutrophil and platelet counts in mice. This protective effect may be related to the targeted intervention of NMN on mitochondrial energy metabolism disorder and oxidative damage induced by benzene exposure in male mice.

A close relationship between fatty acid metabolism and cancer development is well-established.The hydroxyacyl-coenzyme a dehydrogenase(HADH),a key enzyme in fatty acid beta-oxidation,has recently been identified as an anti-oncogenic factor in various cancers and an oncogenic factor in conditions like acute myeloid leukemia.In cancer cells,HADH not only directly catalyzes fatty acid beta-oxidation but also indirectly influences multiple signaling pathways such as PPAR,TNF-α,JAK-STAT3,PI3K/Akt,IFN-γ,MAPK,and non-canonical Wnt signaling pathways,affecting cancer cell proliferation and migration.HADH shows promise as a potential tumor biomarker for diagnosis,treatment,and prognosis in different cancer types,holding significant clinical value.

The end-of-life care education of medical students is related to the development of hospice care in the future. This paper comprehensively reviewed the setting up situations of end-of-life care education courses at home and abroad, as well as the status quo of courses' implementation, including teaching contents, teaching methods, assessment methods, teaching staff, teaching evaluations and effects. Based on these aspects, we have made some thoughts and suggestions, in order to provide reference for the development of end-of-life care education courses in medical colleges and universities in China.

The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P < 0.05) and IRF4 (P < 0.001) and between white blood cell (WBC) count and IRF4 expression (P < 0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P < 0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%,10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.
Biomarkers ; Humans ; Hydroxyurea/therapeutic use* ; Interferon Regulatory Factors/genetics* ; Janus Kinase 2/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Phenotype ; Primary Myelofibrosis/genetics* ; Thrombocythemia, Essential/genetics*

Objective:To evaluate the application effect of the nurse-led catheter extraction assessment model for children in PICU.Methods:From January to May 2020, 100 children with short-term catheter in PICU of Guangzhou Women and Children Medical Center were selected by convenient sampling method as the experimental group, the need for urethral catheter indwelling was assessed daily using an evidence-based assessment scale in PICU children, and the unnecessary indwelling catheters were removed timely, and 109 children with indwelling urethral catheters from August to December 2019 were collected as the control group, the catheter was removed by the nurse on medical advice, recorded and compared days of indwelling of catheters, the incidence of patients with catheter-associated urinary tract infection , resetting of catheters and the length of stay in ICU between the two groups.Results:The median and interquartile spacing of the days with indwelling catheter were 5.0 (6.0) days in the experimental group and 6.0 (6.0) days in the control group ( Z=-2.01, P<0.05) . In the experimental group, the incidence of catheter-associated urinary tract infection was 1.000 percent (1/100), and in the control group, the incidence of catheter-associated urinary tract infection was 1.835 percent (2/109); in the experimental group, 2 cases of urethral catheter were reset, and in the control group, 2 cases of urethral catheter were reset; the median and interquartile spacing of the length of stay in ICU was 6.5 (7.0) days in the experimental group and 7.0 (8.0) days in the control group. The differences of the above three indexes between the two groups were statistically significant ( χ2=0.26, 0.01, Z=-0.96, all P>0.05). Conclusions:The nurse-led catheter extraction assessment model for children can effectively shorten the catheter indwelling days for children in PICU, which has certain clinical practice significance for reducing the incidence of catheter-associated urinary tract infection.

Objective:To investigate the efficacy of a machine learning model based on radiomics of brain lesions on T 2WI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD). Methods:Totally 223 MS and NMOSD patients who were treated from January 2009 to September 2018 in Beijing Tiantan Hospital Affiliated to Capital Medical University, Donghu Branch of the First Affiliated Hospital of Nanchang University, Tianjin Medical University General Hospital, and Xuanwu Hospital of Capital Medical University were analyzed retrospectively, and according to the proportion of 7∶3, 223 patients were completely randomly divided into training set (156 cases) and test set (67 cases). A total of 74 patients with MS and NMOSD who were treated in Huashan Hospital Affiliated to Fudan University and China-Japan Friendship Hospital of Jilin University from January 2009 to September 2018 and in Xianghu Branch of the First Affiliated Hospital of Nanchang University from March 2020 to September 2021 were collected as an independent external validation set. All patients underwent brain cross-sectional MR T 2WI, radiomics features were extracted from T 2WI, and features were selected by max-relevance and min-redundancy and least absolute shrinkage and selection operator algorithms. Then various machine learning classifier models (logistic regression, decision tree, AdaBoost, random forest or support vector machine) were constructed to differentiate MS from NMOSD. The area under curve (AUC) of receiver operating characteristics was used to evaluate the performance of each classifier model in the training set, test set and external validation set. Results:Based on multi-center T 2WI, a total of 11 radiomics features related to the discrimination between MS and NMOSD were extracted and classifier models were constructed. Among them, the random forest model had the best efficiency in distinguishing MS from NMOSD, and its AUC values for distinguishing MS from NMOSD in the training set, test set and external validation set were 1.000, 0.944 and 0.902, with specificity of 100%, 76.9% and 86.0%, and sensitivity of 100%, 92.1% and 79.7%, respectively. Conclusion:The random forest model based on the radiomic features of T 2WI of brain lesions can effectively distinguish MS from NMOSD.

Objective:To study the changes of proliferation and oxidation indexes of Cochlear hair cell line (HEI-OC1 cells) exposed to ethylbenzene.Methods:From July to December 2019, 11 groups with ethylbenzene concentrations of 0, 30, 60, 90, 300, 600, 900 μmol/L and 3, 6, 9, 10 mmol/L, were used to determine the proliferation activity of HEI-OC1 cells exposed to ethylbenzene for 24 hours, and the cells were treated with 0, 1, 2, 4, 8, 16, 32, 64 mmol/L ethylbenzene for 24 hours, then the 50% inhibitory concentration of ethylbenzene was calculated. After HEI-OC1 cells were exposed to 0, 6, 9 and 12 mmol/L ethylbenzene for 24 hours, the malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured.Results:Compared with 0 mmol/L concentration group, the survival rate of HEI-OC1 cells at 6, 9, 12 mmol/L concentration was significantly decreased ( P<0.01) . The 50% inhibitory concentration of ethylbenzene on HEI-OC1 cells was 12.86 mmol/L ( R2=99.05) . There were significant differences in SOD and GSH-Px activity in HEI-OC1 cells treated with ethylbenzene at different concentrations (0, 6, 9, 12 mmol/L) for 24 hours ( F=65.11, 6.48, 22.85, P<0.05) . Compared with 0 mmol/L concentration group, the MDA content of HEI-OC1 cells was significantly increased in 9 and 12 mmol/L concentration groups, the SOD activity was significantly decreased in 12 mmol/L concentration group, and the GSH-Px activity was significantly decreased in 6 and 12 mmol/L concentration groups. Conclusion:Ethylbenzene can inhibit the proliferation of HEI-OC1 cells and cause oxidative damage.

Objective:To screen the biomarkers in the exhaled breath of mice exposed to benzene by using exhaled breath online analysis system.Methods:Thirty 8-week-old male C57BL/6 mice were randomly divided into six groups (0, 3, 32, 324, 648, and 1 296 mg/m 3) and treated with benzene vapour for 28 days. At the end of the exposure, the peripheral blood cell counts and blood glutathione (GSH) were detected. The content of malondialdehyde (MDA) in HL60 cells treated by mice plasma was examined. Exhaled breath data from mice were collected by Secondary electrospray ionization source high resolution mass spectrometry (SESI-HRMS). Targeted analysis underlying benzene metabolites and oxidative stress metabolites was performed to screen the biomarkers in exhaled breath. Results:After benzene exposure, the number of peripheral blood cells was decreased in different degrees, particularly in the white blood cells (WBC) number. The WBC in 32 and 324 mg/m 3 groups was declined by 27.76% and 52.87%, respectively compared to that in control group ( P<0.05). Meanwhile, compared with the control group, the GSH content of peripheral blood cells from 324 mg/m 3 group decreased by 13.16% ( P<0.05). In addition, MDA content was increased by 18.11% in HL60 cells treated with plasma from 324 mg/m 3 group mice ( P<0.05). The phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid ( t,t-MA) in the exhaled gas of mice could be used as biomarkers for benzene exposure ( R 2>0.8, P<0.001). The peak intensity of five small molecular metabolites related to oxidative stress (ω-carboxylic fatty acid C 5H 10O 3, ω-carboxylic fatty acid C 6H 12O 3, glutamate, cysteine and MDA) increased with the increase of benzene concentration ( P<0.05), which was negatively correlated with WBC decline ( P<0.001), suggesting that these molecules mignt be used as biomarkers of benzene-induced toxicity. Conclusions:Phenol, hydroquinone/catechol, benzenetriol and trans, trans-Muconic acid ( t,t-MA) in exhaled breath of mice could be used as biomarkers for benzene exposure; ω-carboxylic fatty acid C 5H 10O 3, ω-carboxylic fatty acid C 6H 12O 3, glutamate, cysteine and MDA might be used as markers of benzene-induced toxicity.