Neurofibromatosis type 1 (NF1) presents with a diverse range of symptoms that can affect the skin, bones, eyes, central nervous system, and other organs. This article reports the diagnosis and treatment process of a patient with NF1 complicated by bilateral severe-to-profound sensorineural hearing loss. Genetic testing revealed a heterozygous variant of NF1 NM_ 000267.3: c.4054_ 4058del(p.Ser1352LeufsTer20, supporting the diagnosis of NF1. After thorough evaluation, a right cochlear implantation was performed, yielding satisfactory postoperative results. This case suggests that NF1 patients may exhibit phenotypic heterogeneity and atypicality, providing a reference for clinicians in the diagnosis and treatment of such patients.

Objective To track and evaluate the implementation and application of the occupational health standard Radiation shielding requirements for radiotherapy room—Part 4: Radiotherapy room of ²⁵²Cf neutron afterloading (GBZ/T 201.4-2015) by radiation health technical service agencies, medical institutions, health supervision agencies, and radiotherapy facility design units, and to provide a scientific basis for the further revision and implementation of this standard. Methods Following the Guideline for health standards tracking evaluation (WS/T 536-2017) and the project implementation plan, relevant practitioners were randomly selected for a questionnaire survey. The survey primarily focused on their awareness, standard training, application, and revision suggestions of GBZ/T 201.4-2015. The results were summarized and analyzed. Results A total of 168 evaluation questionnaires were collected from relevant practitioners in 28 provinces. Only 31.6% of the respondents reported being “well familiar” or “ familiar” with the standard, 27.4% of the respondents believed that the standard was widely used, and 45.2% of the respondents believed that the standard could meet the needs of their work. Only 14.9% of the respondents had received relevant training on the standard, more than half of the respondents had not applied the standard within the past 10 years, and 45.2% of the respondents believed that the standard "needs to be revised". Conclusion Due to the small number of californium-252 neutron afterloading radiotherapy devices in operation on the market, the overall awareness of the standard is low, suggesting that relevant authorities need to strengthen training and publicity of the standard, and that certain sections of the standard need to be revised or merged.

Objective To explore the clinical characteristics of autosomal dominant intellectual disability type 21(MRD21)related with CCCTC-binding factor(CTCF)mutations.Methods The clinical data of an outpatient with CTCF mutations,laboratory and genetic test results was retrospectively collected,and relevant literatures were re-viewed.Results A 6-year-old male patient had feeding difficulties during the neonatal period and has experienced constipation since infancy.He has exhibited global developmental delay since early childhood,characterized by intel-lectual and language deficits,as well as autism-like behaviors.There is no history of epileptic seizures.Brain magnet-ic resonance imaging and electroencephalography findings were normal.Physical examination revealed poor eye con-tact,microcephaly and no facial dysmorphism.Whole exome sequencing confirmed by Sanger sequencing detected a de novel heterozygous mutation in CTCF:c.1087-2A＞G.His parents did not have this mutation.Conclusions The clinical manifestations of MRD21 lack specificity.Intellectual disability is the most frequent finding.Other presenta-tions may also include microcephaly,digestive system symptoms like feeding difficulties and constipation,as well as behavioral abnormalities,which are also relatively common.Genetic testing aids in confirming the diagnosis.

Objective:To improve the clinical diagnostic ability of antiphospholipid syndrome (APS) with onset of autoimmune hemolytic anemia (AIHA).Methods:The diagnosis and treatment of one APS patient with AIHA as the initial manifestation were reported and discussed.Results:A young female patient admitted to Peking Union Medical College Hospital on October 15, 2022 suffered from AIHA and persistent lupus anticoagulant (LA) positivity. After being treated with high-dose glucocorticoid, both symptoms and indicators were improved. However, relapses occurred when the glucocorticoid was tapered. Subsequent attempts to combine multiple immunosuppressants and biologics for treatment was ineffective. During the course of the disease, the patient had experienced intermittent intracranial hypertension which was revealed as cerebral venous sinus thrombosis(CVST) by MRV. Laboratory test revealed that antiphospholipid antibodies and antiphospholipid serine/prothrombin antibodies (aPS/PT) were all positive. She was finally diagnosed with APS. After being treated with high-dose glucocorticoids and immunosuppressants, combined with warfarin and aspirin, the patient′s clinical symptoms were significantly improved.Conclusion:AIHA is one of the extra-criteria manifestations of APS. Patients with AIHA and persistent antiphospholipid antibody profiles should be alerted to the possibility of thrombotic events. It is difficult to control APS-CVST-AIHA patients′disease development and recurrence. Early and adequate antithrombotic therapy is essential for improvement of prognosis. Furthermore, some drugs may lead to false positive in LA testing, making aPS/PT a viable alternative method for assessing LA.

Objective:To improve the clinical diagnostic ability of antiphospholipid syndrome (APS) with onset of autoimmune hemolytic anemia (AIHA).Methods:The diagnosis and treatment of one APS patient with AIHA as the initial manifestation were reported and discussed.Results:A young female patient admitted to Peking Union Medical College Hospital on October 15, 2022 suffered from AIHA and persistent lupus anticoagulant (LA) positivity. After being treated with high-dose glucocorticoid, both symptoms and indicators were improved. However, relapses occurred when the glucocorticoid was tapered. Subsequent attempts to combine multiple immunosuppressants and biologics for treatment was ineffective. During the course of the disease, the patient had experienced intermittent intracranial hypertension which was revealed as cerebral venous sinus thrombosis(CVST) by MRV. Laboratory test revealed that antiphospholipid antibodies and antiphospholipid serine/prothrombin antibodies (aPS/PT) were all positive. She was finally diagnosed with APS. After being treated with high-dose glucocorticoids and immunosuppressants, combined with warfarin and aspirin, the patient′s clinical symptoms were significantly improved.Conclusion:AIHA is one of the extra-criteria manifestations of APS. Patients with AIHA and persistent antiphospholipid antibody profiles should be alerted to the possibility of thrombotic events. It is difficult to control APS-CVST-AIHA patients′disease development and recurrence. Early and adequate antithrombotic therapy is essential for improvement of prognosis. Furthermore, some drugs may lead to false positive in LA testing, making aPS/PT a viable alternative method for assessing LA.

Tandem occlusion of the anterior circulation is a specific acute large vessel occlusion, which is defined in most of the literature as a combination of intracranial large vessel occlusion and high degree of stenosis or occlusion of the ipsilateral extracranial internal carotid artery.Tandem occlusion is presented in approximately 15% patients with acute ischemic stroke in the anterior circulation who receive endovascular treatment. In patients with tandem occlusion, endovascular treatment is more effective than drug therapy; however, controversy still exists regarding the optimal management strategy of endovascular treatment. This article reviews the recent advance in endovascular treatment of tandem occlusion in the anterior circulation in recent years, to improve the overall care standard for acute ischemic stroke with tandem occlusion of the anterior circulation.

Objective:To investigate the safety, efficacy and effective dose of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb).Method:This was a cross sectional study. A total of 28 children with GSDⅠb who started oral empagliflozin treatment from January 2021 to June 2023 in the WeChat group of patients with glycogen storage disease were selected as the study objects. Clinical data such as general situation, current situation of medication and adverse reactions of the children were collected through questionnaires from June 18 to 30, 2023. The differences of symptoms and laboratory tests before and after empagliflozin treatment were compared by using paired chi-square test and Wilcoxon signed rank sum test.Results:Totally 28 children with GSD Ⅰb were from 12 different provinces, autonomous regions and municipalities in China. There were 14 males and 14 females. Empagliflozin treatment was started at the age of 4.8 (2.4, 10.8) years, the time of treatment was 14.5 (11.3, 21.5) months, the initial dosage was (0.23±0.11) mg/(kg·d), and the maintenance dosage was (0.28±0.12) mg/(kg·d). Empagliflozin showed positive effects on neutropenia, severity of inflammatory bowel disease like symptoms( Z=-3.70 , -2.65, both P<0.05), The proportion of recurrent oral ulcers, recurrent bacterial infections and anemia was significantly lower than that before medication (18% (5/28) vs. 46% (13/28), 14% (4/28) vs. 46% (13/28), 21% (6/28) vs. 46% (13/28), χ2=4.05, 5.26, 3.05 , all P<0.05). Granulocyte colony-stimulating factor (GCSF) was once used in 5 children with GSD Ⅰb, all of them had completely stopped GCSF after empagliflozin treatment. The most common adverse events during empagliflozin treatment were hypoglycemia (5 children) and urinary infection (3 children). All 28 patients had no serious adverse reactions. Conclusions:Empagliflozin can increase the neutrophil count of children with GSD Ⅰb, and had a favorable effect on symptoms such as recurrent oral ulcers, and recurrent infection. The common adverse events during empagliflozin treatment were hypoglycemia and urinary infection.

Objective:To summarize the clinical phenotype and genetic characteristics of deficiency in ELF4 gene X-linked (DEX).Methods:A case series study was conducted to retrospectively analyze the clinical data and genetic testing results of 2 cases of DEX treated at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and the First Hospital of Jilin University from January 2023 to April 2024. And literature up to April 2024 was searched from the PubMed database, as well as CNKI and Wanfang databases, using keywords such as "ELF4 deficiency" "deficiency in ELF4, X-linked""ELF4 gene". The main clinical manifestations and genotypes of DEX were summarized.Results:Both patients were male, with onset ages of 3 months and 3 years, respectively. Both patients presented with recurrent oral ulcers and abdominal pain. And the laboratory examination showed a significant increase in inflammatory markers. Intestinal examinations showed multiple intestinal ulcers, and both patients developed intestinal fistulas. Whole exome sequencing found ELF4 c.799C>T, p Arg267Trp and ELF4 c. 248-7G>A, both maternal variants. Based on clinical and genetic results, DEX were diagnosed. In terms of treatment, both patients underwent surgical treatment during the acute phase of the disease and received anti-tumor necrosis factor α therapy, but recurrent gastrointestinal symptoms were still observed in Patient 1, while the clinical effect in Patient 2 was still acceptable. However, the inflammatory markers in both patients were not normal even after treatment. Literature review found 18 patients including 2 patients in this study, reported in 5 English articles and no Chinese reports. Thirteen patients had disease onset age before 5. The main clinical manifestations were fever (12/17), oral ulcers (14/18), abdominal pain (8/18), diarrhea (6/18), perianal ulcers (5/17), ileum ulcers (6/16), colon ulcers (7/16), skin involvement (7/17) and recurrent infections (7/18); laboratory examinations found increased erythrocyte sedimentation rate (13/15) as well as C-reactive protein (9/9), and anemia (13/15); in terms of immunological function, there is a decrease in natural killer cells (9/15) as well as a decrease in class switching memory B cells (8/9). The main types of gene variantions were missense variantions (6/18), nonsense variantions (4/18) or frameshift variantions (3/18).Conclusions:DEX should be considered when an early-onset male patient manifested with recurrent fever, oral ulcers or mucosal ulcers, with elevated inflammatory markers, with or without recurrent infection. It is recommended to perform lymphocyte subsets analysis, gastrointestinal endoscopy and genetic testing to support the diagnosis.

Glycogen storage disease type Ⅰb（GSD Ⅰb）is an autosomal recessive genetic disease characterized by abnormal glycogen metabolism.The clinical manifestations include signs of metabolic abnormality of the typical GSD I，and the patients with GSD Ⅰb also have neutropenia and symptoms including recurrent infection，oral and intestinal mucosal ulcers，inflammatory bowel diseases and autoimmune thyroiditis.However，the detailed mechanism of GSD Ⅰb has not been clarified.Treatment with sodium-dependent glucose transporters 2（SGLT2）inhibitors improves both neutropenia and neutrophil function through reducing 1，5-anhydroglucitol（1，5-AG）in plasma，as well as alleviates the related clinical symptoms，so SGLT2 inhibitors are increasingly used in the treatment of GSD Ⅰb.Here it reviews the neutropenia mechanism and recent advances in animal-based research and clinical application of SGLT2 inhibitor therapy for GSD Ⅰb.

Objective To investigate the clinical characteristics of the hepatolenticular degeneration in children,and to clarify the significance of gene diagnosis in children with hepatolenticular degeneration.Methods A total of 75 patients with hepatolenticular degeneration were enrolled in the Department of Pediatrics,Peking Union Medical College Hospital from 2011 to 2018.All of them carried out a generation of gene sequencing for ATPase Cu2+trans-porting beta polypeptide(ATP7B)gene and multiplex ligation-dependent probe amplification(MLPA)analysis.Results Among the 75 pediatric patients,55 patients were asymptomatic and had elevated aminotransferases as the incidental findings.All the pediatric patients had decreased ceruloplasmin.Seventy-two of pediatric patients had 24-hour urinary copper＞40 μg/d.There were 16 cases that had Kayser-Fleischer(K-F)rings.Sixteen six out of 75(21.33%)cases were diagnosed clinically and 15 cases were＞7 years old.All the remaining patients needed genetic diagnosis.Sixty-six patients had two mutations and 9 patients had only one mutation,1 had no mutation.Forty eight different mutations were found to be localized in ATP7B gene.These mutations included 32 missense mutations,6 splice mutations,5 deletion mutations,2 repeated mutations,2 insert mutations and 1 nonsense muta-tions.The most frequently three mutations were c.2333G＞T,p.R778L,c.2621C＞T,p.A874V,c.2975C＞T,p.P992L,whose allele frequencies were 30.49%,14.89%,9.92%.Conclusions The research showed that in young aged patients,the nervous system symptoms are not obvious and the positive rate of laboratory tests are lower than adults so is a challenge to clinical diagnosis.So Genetic testing is of great significance for the early diagnosis and early treatment of disease in pediatric patients.