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.

Objective:To investigate the clinical manifestations, long-term survival, and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL).Methods:Case summary.The clinical data of 43 T-ALL children who were diagnosed and treated in Children′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2021 were retrospectively analyzed.They were stratified for treatment according to the CCCG-ALL regimen, and the correlation of prognosis with the condition at initial diagnosis, early treatment response, and induced remission was analyzed.The Kaplan-Meier survival curve was used to analyze the survival rate, and the survival rates were compared between groups by the Log-rank test.The multivariate Cox regression model was used to analyze the impact of multiple factors on the long-term survival of children.Results:T-ALL patients accounted for 9.5% (43/451) of the total number of acute lymphoblastic leukemia patients admitted to the hospital at the same period.The median onset age of the 43 T-ALL patients was 7 years (1-13 years).Of the 43 patients included, 14 patients (32.6%) had concomitant mediastinal widening, 8 patients (18.6%) had concomitant giant mediastinal masses, and 4 patients (9.3%) had early precursor T-cell acute lymphoblastic leukemia (ETP-ALL) at initial diagnosis.These 43 children were treated according to the CCCG-ALL intermediate- and high-risk group regimen.Among them, 33 children (76.7%) achieved sustained remission, 5 children died, and 5 children had a relapse.As of September 30, 2024, the median follow-up time was 62 months (1-170 months), the 10-year event-free survival rate was (80.2±6.4)%, and the 10-year overall survival rate was (86.6±5.8)%.The median relapse time and 10-year cumulative relapse rate of the 5 relapsed children were 28 months (7-58 months) and (13.7±5.8)%, respectively.The relationship of prognosis with clinical characteristics at initial diagnosis and induced remission in 43 T-ALL children was analyzed.The results showed that patients aged ≥10 years, with a grade-1 non-central nervous system at initial diagnosis, ETP-ALL, abnormal chromosome number and structure, non-M1 status of bone marrow and minimal residual disease (MRD)≥ 1% on day 19 of induction treatment, and MRD ≥ 0.01% on day 46 to 55 of induction treatment had poorer long-term survival(all P<0.05).The multivariate analysis showed that age ≥10 years, ETP-ALL, and abnormal chromosome number and structure were risk factors of poor prognosis ( P=0.045, 0.030, 0.021). Conclusions:The CCCG-ALL regimen has a good overall therapeutic effect in children with T-ALL.Age ≥10 years, abnormal chromosome number and structure, ETP-ALL, grade-1 non-central nervous system at initial diagnosis, and early remission are risk factors of poor prognosis.Treatment after relapse in children with T-ALL is difficult.

Primary immune thrombocytopenia(ITP)is an acquired autoimmune disease characterized by isolated thrombocytopenia resulting from increased platelet destruction and impaired platelet production.Although the majority of patients have a relatively good prognosis,10%?20%of children and up to 75%of adults may progress to chronic primary immune thrombocytopenia(CITP).These patients exhibit poor response to multiple therapies,leading to a significant decline in quality of life.At present,the treatment strategies for CITP mainly include first-line therapies such as glucocorticoids and gamma globulin,and second-line therapies such as thrombopoietin receptor agonists(TPO-RAs),rituximab,immunosuppressants,and splenectomy.In recent years,with the in-depth research on CITP,some new biological drugs and immunotherapies,such as Fcγ receptor(FcγR)signal transduction inhibitors,neonatal Fc receptor inhibitors,complement inhibitors,immune-cell-targeted therapies,platelet desialylation,umbilical cord mesenchymal stem cell therapy,and chimeric antigen receptor T cell immunotherapy,have shown good therapeutic potential.By targeting specific pathways in the pathogenesis of CITP,these novel therapies aim to achieve individualized precision treatment,thereby providing patients with more effective therapeutic options.This article reviews the pathogenesis,second-line treatment approaches,and therapeutic advances in CITP.

Primary immune thrombocytopenia(ITP)is an acquired autoimmune disease characterized by isolated thrombocytopenia resulting from increased platelet destruction and impaired platelet production.Although the majority of patients have a relatively good prognosis,10%?20%of children and up to 75%of adults may progress to chronic primary immune thrombocytopenia(CITP).These patients exhibit poor response to multiple therapies,leading to a significant decline in quality of life.At present,the treatment strategies for CITP mainly include first-line therapies such as glucocorticoids and gamma globulin,and second-line therapies such as thrombopoietin receptor agonists(TPO-RAs),rituximab,immunosuppressants,and splenectomy.In recent years,with the in-depth research on CITP,some new biological drugs and immunotherapies,such as Fcγ receptor(FcγR)signal transduction inhibitors,neonatal Fc receptor inhibitors,complement inhibitors,immune-cell-targeted therapies,platelet desialylation,umbilical cord mesenchymal stem cell therapy,and chimeric antigen receptor T cell immunotherapy,have shown good therapeutic potential.By targeting specific pathways in the pathogenesis of CITP,these novel therapies aim to achieve individualized precision treatment,thereby providing patients with more effective therapeutic options.This article reviews the pathogenesis,second-line treatment approaches,and therapeutic advances in CITP.

Objective:To investigate the clinical manifestations, long-term survival, and prognosis of childhood T-cell acute lymphoblastic leukemia (T-ALL).Methods:Case summary.The clinical data of 43 T-ALL children who were diagnosed and treated in Children′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2021 were retrospectively analyzed.They were stratified for treatment according to the CCCG-ALL regimen, and the correlation of prognosis with the condition at initial diagnosis, early treatment response, and induced remission was analyzed.The Kaplan-Meier survival curve was used to analyze the survival rate, and the survival rates were compared between groups by the Log-rank test.The multivariate Cox regression model was used to analyze the impact of multiple factors on the long-term survival of children.Results:T-ALL patients accounted for 9.5% (43/451) of the total number of acute lymphoblastic leukemia patients admitted to the hospital at the same period.The median onset age of the 43 T-ALL patients was 7 years (1-13 years).Of the 43 patients included, 14 patients (32.6%) had concomitant mediastinal widening, 8 patients (18.6%) had concomitant giant mediastinal masses, and 4 patients (9.3%) had early precursor T-cell acute lymphoblastic leukemia (ETP-ALL) at initial diagnosis.These 43 children were treated according to the CCCG-ALL intermediate- and high-risk group regimen.Among them, 33 children (76.7%) achieved sustained remission, 5 children died, and 5 children had a relapse.As of September 30, 2024, the median follow-up time was 62 months (1-170 months), the 10-year event-free survival rate was (80.2±6.4)%, and the 10-year overall survival rate was (86.6±5.8)%.The median relapse time and 10-year cumulative relapse rate of the 5 relapsed children were 28 months (7-58 months) and (13.7±5.8)%, respectively.The relationship of prognosis with clinical characteristics at initial diagnosis and induced remission in 43 T-ALL children was analyzed.The results showed that patients aged ≥10 years, with a grade-1 non-central nervous system at initial diagnosis, ETP-ALL, abnormal chromosome number and structure, non-M1 status of bone marrow and minimal residual disease (MRD)≥ 1% on day 19 of induction treatment, and MRD ≥ 0.01% on day 46 to 55 of induction treatment had poorer long-term survival(all P<0.05).The multivariate analysis showed that age ≥10 years, ETP-ALL, and abnormal chromosome number and structure were risk factors of poor prognosis ( P=0.045, 0.030, 0.021). Conclusions:The CCCG-ALL regimen has a good overall therapeutic effect in children with T-ALL.Age ≥10 years, abnormal chromosome number and structure, ETP-ALL, grade-1 non-central nervous system at initial diagnosis, and early remission are risk factors of poor prognosis.Treatment after relapse in children with T-ALL is difficult.

Surgical technique of lung transplantation exerts significant impact on clinical prognosis of the recipients.Choosing an appropriate surgical incision determines the exposure of intraoperative visual field,which is the first step of surgical success and directly affects subsequent surgical procedures.Lung transplantation incision is usually considered as primary closure.Nevertheless,for patients with high-risk factors such as oversized lung allografts and primary graft failure after lung transplantation,primary closure cannot be achieved.Hence,delayed chest closure is an effective strategy.The selection of incisions and the adoption of delayed chest closure of lung transplantation exert profound impact upon perioperative prognosis,long-term quality of life and surgical complications of the recipients.Therefore,the development and research status of Clamshell incision,anterolateral incision,posterolateral incision and median sternal incision in lung transplantation were reviewed,highlighting the effect of incision patterns on clinical prognosis of lung transplantation and providing reference for the selection of incisions in clinical lung transplantation.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

To summarize the experience of Professor WANG Qingguo in diagnosing and treating wind-cold-dampness arthralgia based on the principle that "the nutrient-defense qi does not merge with wind-cold-dampness qi， so it did not result to arthralgia". By analyzing the relationship between nutrient-defense qi and wind-cold-dampness arthralgia， it is believed that the occurrence of wind-cold-dampness arthralgia is closely related to the movement of nutrient qi and defense qi， and the key to the treatment of this disease is to regulate nutrient qi and defense qi and remove the combination of nutrient-defense qi and wind-cold-dampness qi. The core pathogenesis of wind-cold-dampness arthralgia in the early stage is the initial combination of nutrient-defense qi and wind-cold-dampness qi， and the treatment should harmonize nutrient-defense qi and eliminate the pathogen and release pathogenesis， with Chaihu Guizhi Decoction （柴胡桂枝汤） as the main prescription； the core pathogenesis of the middle stage is nutrient-defense qi and wind-cold-dampness qi cemented together， and the treatment should harmonize and tonify nutrient qi and defense qi and separate the pathogen to alleviate disease， with self-prescribed Chuanteng Tongbi Decoction （穿藤通痹汤） as the main prescription； the core pathogenesis of the late stage is deficiency and stagnation of nutrient-defense qi， wind-cold-dampness qi still exist， and the treatment should tonify and free nutrient qi and defense qi to eliminate pathogen and arthralgia， with self-prescribed Chuanqing Haijia Decoction （穿青海甲汤） plus Duhuo Jisheng Decoction （独活寄生汤） as the main prescription.

Tumour metastasis is the primary cause of mortality in patients with tumours.Platelets are fragments of anucleated cells shed from the cytoplasm of mature megakaryocytes of the bone marrow，and involved in coagulation and the maintenance of vascular wall integrity.Recent studies have demonstrated that platelets participate in the host immune response by secreting granules containing a range of immunomodulatory and antimicrobial molecules，which are critical for tumour metastasis.In tumours，contact between platelets and tumour cells promotes platelet activation and aggregation.Activated platelets release a large number of reactive biomolecules that assist tumour cells in immune escape，migration，stationary adhesion and extravasation.Meanwhile，platelets accelerate tumour cell metastasis by inducing tumour epithelial mesenchymal transition，neoangiogenesis，metastatic ecological niche formation and other mechanisms.This article presents a review of the current state of research on the role of platelets in tumour metastasis，and offers insights into potential therapeutic avenues to enhance the survival of tumour patients.