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

Abdominal aortic aneurysm(AAA)is a degenerative vascular disease occurring in the lower segment of the aortic diaphragm,mainly manifested by irreversible dilatation of the entire artery,preferably in the elderly population.The pathogenesis of AAA is complex and involves multiple factors,with genetic variations and immune imbalances playing important roles.Its pathological changes mainly include inflammatory cell infiltration,degradation of stromal elastin,and smooth muscle cell death.Rupture of AAA is the most dangerous complication,with a high mortality.Surgery remains the only effective intervention,but carries certain risks and postoperative complications.Early intervention for small abdominal aortic aneurysms to slow down aneurysm expansion and achieve long-term survival is currently a focus of drug and technology research.This article reviews the pathogenesis of AAA and its intervention strategies,and summarizes the research on existing drugs and the use of new targets and technologies,so as to provide insights for better understanding and treatment of AAA.

Objective To evaluate whether the hand-drawn bronchial map can increase the endobronchial ultrasonography(EBUS)detection rate and the diagnosis rate for peripheral lung lesions.Methods We retrospectively analyzed 105 patients and divided them into hand-drawn navigation-EBUS group(n=71)and traditional navigation-EBUS group(n=34)according to different navigation methods.Collect case data on age,gender,lesion imaging characteristics(density,location,presence or absence of bronchial inflation sign),biopsy frequency,and final diagnosis from two groups of patients,and analyze the EBUS arrival rate,diagnosis rate,and influencing factors.Results Compared to that in the traditional navigation-EBUS group,the EBUS detection rate in the hand-drawn navigation-EBUS group was significantly higher.When lesions were>20 mm and≤30 mm,the diagnosis rate in the hand-drawn navigation-EBUS group was significantly higher than that in the traditional navigation-EBUS group.Multivariate Logistic regression analysis showed that lesions>20 mm(P=0.042)and bronchial generation of lesions≤5th generation(P=0.005)were favorable factors affecting the diagnosis rate of hand-drawn navigation-EBUS.Conclusion A hand-drawn bronchial map greatly increases the EBUS detection rate and diagnostic yield of bronchoscopy for peripheral lung lesions.

Objective To evaluate whether the hand-drawn bronchial map can increase the endobronchial ultrasonography(EBUS)detection rate and the diagnosis rate for peripheral lung lesions.Methods We retrospectively analyzed 105 patients and divided them into hand-drawn navigation-EBUS group(n=71)and traditional navigation-EBUS group(n=34)according to different navigation methods.Collect case data on age,gender,lesion imaging characteristics(density,location,presence or absence of bronchial inflation sign),biopsy frequency,and final diagnosis from two groups of patients,and analyze the EBUS arrival rate,diagnosis rate,and influencing factors.Results Compared to that in the traditional navigation-EBUS group,the EBUS detection rate in the hand-drawn navigation-EBUS group was significantly higher.When lesions were>20 mm and≤30 mm,the diagnosis rate in the hand-drawn navigation-EBUS group was significantly higher than that in the traditional navigation-EBUS group.Multivariate Logistic regression analysis showed that lesions>20 mm(P=0.042)and bronchial generation of lesions≤5th generation(P=0.005)were favorable factors affecting the diagnosis rate of hand-drawn navigation-EBUS.Conclusion A hand-drawn bronchial map greatly increases the EBUS detection rate and diagnostic yield of bronchoscopy for peripheral lung lesions.

Objective:To investigate the diagnostic value of machine learning model based on 18F-FDG PET/CT for polymyalgia rheumatica (PMR). Methods:From November 2014 to December 2022, 177 patients (119 males, 58 females; age: 67.0 ( 61.0, 72.0) years) admitted to the Department of Rheumatology and Immunology, the First People′s Hospital of Changzhou, with suspected PMR and undergoing 18F-FDG PET/CT examination were retrospectively analyzed. Patients were randomly divided into training set and validation set at the ratio of 7∶3. Three machine learning models, including classification and regression tree (CART), the least absolute shrinkage and selection operator (LASSO) algorithm, and logistic regression, were established based on the PET/CT imaging features to aid in the diagnosis of PMR. The diagnostic efficacy of each model was evaluated by ROC curve analysis and differences among AUCs were analyzed by Delong test. Results:There were 78(44.1%, 78/177) PMR patients and 99(55.9%, 99/177) non-PMR patients, and 124 patients in the training set and 53 patients in the validation set. The logistic regression model (training set: AUC=0.961; validation set: AUC=0.930) was superior to the CART (training set: AUC=0.902, z=2.96, P=0.003; validation set: AUC=0.844, z=2.46, P=0.014) in diagnosing PMR, and was similar to LASSO algorithm (training set: AUC=0.957, z=0.95, P=0.340; validation set: AUC=0.930, z=0.00, P=1.000), but with fewer sites evaluated. The simplified PMR-Logit score had the AUC of 0.951 in the overall population, with the sensitivity of 89.74%(70/78) and the specificity of 90.91%(90/99). Conclusion:Machine learning models based on 18F-FDG PET/CT imaging features are expected to be an effective diagnostic tool for PMR.

ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.

Objective To evaluate the short-term clinical efficacy of unilateral biportal endoscopic(UBE)technique in the treatment of adjacent segment disease after lumbar interbody fusion.Methods The clinical data of 21 patients with adjacent segment disease after lumbar interbody fusion who treated with UBE technique and followed up for more than 3 months in our hospital from March 2020 to January 2023 were retrospectively analyzed.The operation time,decrease value of hemoglobin 1 day before and after operation,drainage volume of the operation area,time of bed rest and complications were recorded.The Japanese Orthopaedic Association(JOA)score was used to evaluate lumbar function 1 day before operation,3 days and 3 months after operation to determine the improvement.The visual analogue scale(VAS)score was used to evaluate the pain 1 day before operation,3 days and 3 months after operation.Results The operation time was 60～175 minutes,with an average of(95.38±18.64)minutes;the decrease value of hemoglobin was 2～6 g/L,with an average of(1.42±0.18)g/L;the time of bed rest was 27～88 hours,with an average of(36.42±15.33)hours;the drainage volume of the operation area was 50～315 mL,with an average of(85.56±15.65)mL;and one case of dural tear occurred during the operation,who was converted to open surgery for repairing dural sac.There was statistically significant difference in VAS score before operation compared with that 3 days and 3 months after operation(P<0.05).There was statistically significant difference in the JOA score before operation compared with that 3 days and 3 months after surgery(P<0.05).Conclusion UBE technique is effective in the treatment of adjacent segment disease after lumbar interbody fusion,with the advantages of small trauma,little bleeding and short time of bed rest.However,patients with the serious adjacent segment degeneration and severe spinal stenosis may have dural tear during operation.Once it occurs,active repair should be performed to avoid cauda equina herniation and necrosis,or switch to open surgery,if necessary.

Objective:To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) .Methods:A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period.Results:Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site.Conclusion:The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

This study aims to investigate the effects and the molecular mechanism of Huangdi Anxiao Capsules(HDAX)-containing serum in protecting the rat adrenal pheochromocytoma(PC12) cells from diabetes-associated cognitive dysfunction induced by high glucose and whether the mechanism is related to the regulation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis. The PC12 cell model of diabetes-associated cognitive dysfunction induced by high glucose was established and mcc950 was used to inhibit NLRP3. PC12 cells were randomized into control, model, HDAX-containing serum, mcc950, and HDAX-containing serum+mcc950 groups. Methyl thiazolyl tetrazolium(MTT) assay was employed to determine the viability, and Hoechst 33258/PI staining to detect pyroptosis of PC12 cells. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1 beta(IL-1β) and IL-18. Western blot was employed to determine the protein levels of postsynaptic density protein 95(PSD-95), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), GSDMD-N, and cleaved cysteinyl aspartate specific proteinase-1(caspase-1), and RT-PCR to determine the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1. The immunofluorescence assay was adopted to measure the levels and distribution of NLRP3 and GSDMD-N in PC12 cells. Compared with the control group, the model group showed decreased cell proliferation, increased PI positive rate, down-regulated protein level of PSD-95, up-regulated protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1, up-regulated mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and elevated levels of IL-1β and IL-18. Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1β and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.
Rats ; Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Interleukin-18 ; Pyroptosis/physiology* ; Diabetes Mellitus ; Caspases ; Glucose ; RNA, Messenger