Objective:To investigate the clinical value of the Nomogram model based on two-dimensional shear wave elastography(2D-SWE)combined with biochemical indicators in the diagnosis of moderate and severe metabolic-associated fatty liver disease(MAFLD).Methods:A total of 170 patients with MAFLD diagnosed by ultrosound image in the health management center of the Second People's Hospital of Wuhu from Jan 2023 to Dec 2023 were divided into mild,moderate and severe groups according to two-dimensional ultrasound images,and 111 healthy volunteers were recruited as control group in the same period.Multivariate logistic regression analysis was used to screen independent risk factors for moderate and severe MAFLD and construct a predictive model.The diagnostic efficacy of the ROC model was plotted,and the Nomogram model was used to conduct internal verification.Results:Multivariate logistic regression analysis showed that liver stiffness measurement(LSM),platelet count(PLT)and hepatic steatosis index(HSI)were the independent risk factors for the diagnosis of moderate and severe MAFLD.The area under the curve(AUC)of LSM,PLT and HSI was 0.940(95%CI:0.911-0.969),with a sensitivity was 87.5%and a specificity was 88.1%.The internal validation showed that the model had high accuracy and stability.Conclusion:The Nomogram model based on LSM combined with PLT and HSI can effectively diagnose moderate and severe MAFLD,providing a reliable evidence for early clinical intervention and adjustment of therapeutic measures.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Osteopontin (OPN) is a secreted extracellular matrix glycoprotein that exists in body fluids and mediates multiple biological functions. The expression of OPN is particularly critical and active after ischemic stroke, and has dual significance for the body. The rapid increase of OPN has certain protective effects on the body, such as anti-inflammatory and promoting wound healing; if the rate of increase is relatively slower, it will have adverse effects on the body, such as promoting thrombosis and inducing inflammatory reactions. This article reviews the research progress of OPN in ischemic stroke.

Objective:To observe the efficacy of eculizumab in children with atypical hemolytic uremic syndrome.Methods:It was a single-center observational study. The clinical data of children diagnosed with atypical hemolytic uremic syndrome and treated with eculizumab in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2023 to May 2024 were retrospectively collected. Eculizumab was used at the conventional dose based on the children 's weight. Event-free survival (no death or end-stage renal disease) rate, complete remission rate and recurrence rate of thrombotic microangiopathy in children with atypical hemolytic uremic syndrome after eculizumab treatment were analyzed. The complete remission time of estimated glomerular filtration rate, hemoglobin, platelet, lactic dehydrogenase, urine routine and the adverse reactions during the treatment were observed. Whole exome sequencing was used to conduct genetic testing based on blood samples of the children and their parents.Results:There were 4 children enrolled in the study. Four children were all Han Chinese, including 3 males and 1 female. The median age of onset was 8 years (ranging from 7 to 10 years). Two patients had complement gene abnormalities, both of which were homozygous deletions of complement factor H-related 1 and complement factor H-related 3. All the patients were free of plasma exchange or perfusion after treatment with eculizumab, and the 6-month event-free survival rate and thrombotic microangiopathy complete remission rate were both 4/4. The complete remission time was 19 (14-28) days. The time for the complete recovery of platelets, lactate dehydrogenase, estimated glomerular filtration rate and hemoglobin in 4 children was 4 (1-5), 19 (14-28), 10 (5-14) and 29 (20-42) days, respectively. Except for 1 patient whose urine routine fluctuated between negative and weakly positive expression, the other 3 patients had normal urine routine. All the patients discontinued eculizumab. Two patients without gene mutations discontinued eculizumab after 7 doses, and there was no recurrence during the 1-year follow-up after drug withdrawal. Two patients with genetic abnormalities discontinued eculizumab after 26 weeks of treatment, and no recurrence was found during the 3-month follow-up after drug withdrawal. One patient developed rash approximately 7 days after receiving the third dose of eculizumab. The rash was relieved after anti-allergic treatment, and there was no recurrence after the continued use of eculizumab.Conclusion:Eculizumab is effective and safe in the treatment of children with atypical hemolytic uremic syndrome. Discontinuation of eculizumab can be considered in patients without gene mutations when their condition is stable, but close monitoring and follow-up are needed after drug withdrawal.

Objective:To investigate the clinical value of the Nomogram model based on two-dimensional shear wave elastography(2D-SWE)combined with biochemical indicators in the diagnosis of moderate and severe metabolic-associated fatty liver disease(MAFLD).Methods:A total of 170 patients with MAFLD diagnosed by ultrosound image in the health management center of the Second People's Hospital of Wuhu from Jan 2023 to Dec 2023 were divided into mild,moderate and severe groups according to two-dimensional ultrasound images,and 111 healthy volunteers were recruited as control group in the same period.Multivariate logistic regression analysis was used to screen independent risk factors for moderate and severe MAFLD and construct a predictive model.The diagnostic efficacy of the ROC model was plotted,and the Nomogram model was used to conduct internal verification.Results:Multivariate logistic regression analysis showed that liver stiffness measurement(LSM),platelet count(PLT)and hepatic steatosis index(HSI)were the independent risk factors for the diagnosis of moderate and severe MAFLD.The area under the curve(AUC)of LSM,PLT and HSI was 0.940(95%CI:0.911-0.969),with a sensitivity was 87.5%and a specificity was 88.1%.The internal validation showed that the model had high accuracy and stability.Conclusion:The Nomogram model based on LSM combined with PLT and HSI can effectively diagnose moderate and severe MAFLD,providing a reliable evidence for early clinical intervention and adjustment of therapeutic measures.

Objective:To observe the efficacy of eculizumab in children with atypical hemolytic uremic syndrome.Methods:It was a single-center observational study. The clinical data of children diagnosed with atypical hemolytic uremic syndrome and treated with eculizumab in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2023 to May 2024 were retrospectively collected. Eculizumab was used at the conventional dose based on the children 's weight. Event-free survival (no death or end-stage renal disease) rate, complete remission rate and recurrence rate of thrombotic microangiopathy in children with atypical hemolytic uremic syndrome after eculizumab treatment were analyzed. The complete remission time of estimated glomerular filtration rate, hemoglobin, platelet, lactic dehydrogenase, urine routine and the adverse reactions during the treatment were observed. Whole exome sequencing was used to conduct genetic testing based on blood samples of the children and their parents.Results:There were 4 children enrolled in the study. Four children were all Han Chinese, including 3 males and 1 female. The median age of onset was 8 years (ranging from 7 to 10 years). Two patients had complement gene abnormalities, both of which were homozygous deletions of complement factor H-related 1 and complement factor H-related 3. All the patients were free of plasma exchange or perfusion after treatment with eculizumab, and the 6-month event-free survival rate and thrombotic microangiopathy complete remission rate were both 4/4. The complete remission time was 19 (14-28) days. The time for the complete recovery of platelets, lactate dehydrogenase, estimated glomerular filtration rate and hemoglobin in 4 children was 4 (1-5), 19 (14-28), 10 (5-14) and 29 (20-42) days, respectively. Except for 1 patient whose urine routine fluctuated between negative and weakly positive expression, the other 3 patients had normal urine routine. All the patients discontinued eculizumab. Two patients without gene mutations discontinued eculizumab after 7 doses, and there was no recurrence during the 1-year follow-up after drug withdrawal. Two patients with genetic abnormalities discontinued eculizumab after 26 weeks of treatment, and no recurrence was found during the 3-month follow-up after drug withdrawal. One patient developed rash approximately 7 days after receiving the third dose of eculizumab. The rash was relieved after anti-allergic treatment, and there was no recurrence after the continued use of eculizumab.Conclusion:Eculizumab is effective and safe in the treatment of children with atypical hemolytic uremic syndrome. Discontinuation of eculizumab can be considered in patients without gene mutations when their condition is stable, but close monitoring and follow-up are needed after drug withdrawal.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Neuroinflammatory response may accelerate tissue damage after ischemic stroke and affect neuronal death and neurogenesis. Microglia are an important line of defense against central nervous system injury, which are rapidly activated after cerebral ischemia and exert their effects by releasing various inflammatory mediators. Therefore, promoting the transition of microglia from M1 phenotype to M2 phenotype or maintaining dynamic balance between the two during the inflammatory process after ischemic stroke may be the important therapeutic targets for reducing inflammation after cerebral ischemia.

Objective:To assess the efficacy of Rituximab (RTX) in treating children with refractory nephro-tic syndrome.Methods:A retrospective study was carried out.Twenty-two children diagnosed with refractory nephrotic syndrome in the Department of Nephrology of Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from November 2018 to November 2020 were included in the study.All patients were treated with RTX.Patients with CD 19+ B lymphocytes≥1% total lymphocytes in peripheral blood were supplemented with one dose of RTX (375 mg/m 2), and each patient received 3-4 doses of RTX on average.The patients were treated with Mycophenolate mofetil after early discontinuation of calcineurin inhibitors (CNI). The Kaplan-Meier method was used to analyze the proteinuria relapse-free rate and the incidence of frequently recurrent nephrotic syndrome or steroid-dependent nephrotic syndrome in children after RTX treatment.The relapse times before and after using RTX were analyzed by the Wilcoxon signed rank test.Besides, the body mass indexes (BMI) and height of children before and after RTX treatment were compared by the rank sum test. Results:Of 22 patients studied, 20 patients accomplished the therapeutic protocol.One-year and two-year proteinuria relapse-free survival rates were 85% and 40%, respectively.The recurrence rate was reduced under the discontinuation of CNI.Compared with those before RTX treatment, the BMI and height of all children were significantly improved at 1 year and 2 years after RTX treatment (all P<0.05). However, no significant improvement was observed between 1 or 2 years after RTX treatment (all P>0.05). Conclusions:The use of RTX can effectively reduce the recurrence rate of refractory nephrotic syndrome even when hormones and other immunosuppressants are discontinued.At the same time, RTX can significantly improve the BMI and height of children.RTX is safe and effective for treatment of refractory nephrotic syndrome.

Objective:To investigate and analyze the clinical phenotypes and genotypes in children diagnosed with nephronophthisis (NPHP), and to provide references for clinical diagnosis.Methods:Clinical data of 9 children with NPHP diagnosed by genetic testing in the Department of Nephrology, Wuhan Children′s Hospital from April 2017 to January 2022 were retrospectively collected. The clinical characteristics and genetic test results were analyzed.Results:The median onset age was 11.2(3.4, 14.2) years old in 9 patients, including 5 females and 4 males. There were 8 cases of glomerular proteinuria, 8 cases of renal tubular proteinuria, and 7 cases of reduced urinary gravity in 9 patients. All the children had varying degrees of impaired renal function at the time of diagnosis. Seven cases entered chronic kidney disease (CKD) stage 5, 1 case entered CKD stage 3, and 1 case entered CKD stage 4 at the time of diagnosis. All the children had renal ultrasound abnormalities of varying degrees: size change (3/9), echo enhancement (8/9) and cysts (3/9). Extrarenal phenotypes were present in 3 children. Genetic test showed that 6 patients had mutation of NPHP1 gene, 1 patient had mutation of WDR19 gene, 1 patient had mutation of NPHP3 gene and 1 patient had mutation of NPHP5 gene. Conclusions:Deletion mutation of NPHP1 gene is the most common, while NPHP3, NPHP5 and extremely rare WDR19 mutations have also been found in NPHP patients. The clinical manifestations of NPHP are not typical, so it is necessary to find a specific diagnosis method in the early.