Objective:To discuss the clinical and genetic characteristics of neurodevelopmental disorder with or without early-onset generalized epilepsy (NEDEGE) caused by NBEA gene variation. Methods:The clinical and genetic records of a patient who was diagnosed with NEDEGE caused by NBEA gene variation at the Department of Neurology, Guangzhou Women and Children′s Medical Center in April 2024 were collected retrospectively. Using " NBEA or neurobeachin" "Autism spectrum disorders or ASD" "Epilepsy" "Neurodevelopmental disorders" as the keywords, relevant articles were searched at CNKI, Wanfang and PubMed databases from establishment of these databases to December 2024. Clinical and genetic features of NEDEGE were summarized in the combination of this case. Results:The proband, a 3 years old boy, was backward in development since childhood. He had autism spectrum disorder-like manifestations such as stereotyped behavior and poor eye contact. At the age of 2, he developed generalized seizures. The whole exome sequencing showed a de novo heterozygous variation of c.244CT(p.Gln82 *) in the NBEA gene (NM-001385012.1), and he was diagnosed with NEDEGE. A total of 10 articles (all in English) were retrieved, reporting 36 cases of NBEA gene related NEDEGE (including this case), 4 of whom coming from China. Twenty-four individuals suffered from mild to severe intellectual disability, and most were moderate.Twenty-eight patients had language delay, including 4 cases of complete loss of language function, and 24 patients had seizures, and 19 patients had autism or autima-like behavior problems. Conclusions:This case enriches the mutation spectrum of the NBEA gene, and the c.244CT is the first reported related variation in the Chinese population. The clinical symptoms of NEDEGE related to NBEA gene mutations are most pronounced in neurodevelopmental disorders, followed by seizures and autistic behavior.

Objective:To observe the changes in serum estradiol (E 2) levels in pregnant women of different gestational weeks and their predictive value for early intrauterine pregnancy outcomes. Methods:A retrospective study was conducted involving 375 pregnant women who were treated at the Affiliated Yangming Hospital of Ningbo University (Yuyao People's Hospital) from September 2021 to September 2023. The clinical data were categorized based on pregnancy outcomes into three groups: a normal pregnancy group ( n = 150), a threatened miscarriage with continued pregnancy group ( n = 150), and a miscarriage group ( n = 75). The serum estradiol (E 2) levels at different gestational weeks were compared among the three groups: 5 to < 6 weeks (35-41 days), 6 to < 7 weeks (42-48 days), and 7 to 8 weeks (49-55 days). The predictive value of serum E 2 levels for early intrauterine pregnancy outcomes across different gestational weeks was analyzed using Receiver Operating Characteristic (ROC) curves. Results:In the normal pregnancy group, the serum E 2 levels at different gestational weeks were as follows: (1 691.87 ± 532.21) pmol/L for 5 to < 6 weeks, (2 376.64 ± 788.36) pmol/L for 6 to < 7 weeks, and (3 576.30 ± 1,190.06) pmol/L for 7 to 8 weeks. These values were significantly higher than those in the threatened miscarriage with continued pregnancy group [(1 409.28 ± 473.49) pmol/L, (1 893.13 ± 563.15) pmol/L, (2 035.79 ± 612.47) pmol/L, t = 5.15, 11.68, 6.60, all P < 0.05] and the miscarriage group [(906.49 ± 338.09) pmol/L, (923.63 ± 365.39) pmol/L, (950.27 ± 378.89) pmol/L, t = 16.19, 15.45, 21.50, all P < 0.05]. The serum E 2 levels at different gestational weeks in the threatened miscarriage with continued pregnancy group were significantly higher than those in the miscarriage group ( t = 7.48, 10.81, 8.89, all P < 0.05). Both the normal pregnancy group and the threatened miscarriage with continued pregnancy group showed an increasing trend in serum E 2 levels with advancing gestational weeks ( t = 6.74, 18.55, 7.58, 9.82, 11.81, 2.24, all P < 0.05). In contrast, the serum E 2 levels in the miscarriage group also increased with advancing gestational weeks, but the differences were not statistically significant ( P > 0.05). The results from the receiver operating characteristic curve analysis indicated that the areas under the curve for predicting early intrauterine pregnancy outcomes based on serum E 2 levels at different gestational weeks were 0.857, 0.810, and 0.839, demonstrating excellent diagnostic efficacy. Conclusions:Dynamic monitoring of serum E 2 levels is beneficial for predicting early intrauterine pregnancy outcomes and providing guidance for clinical diagnosis and treatment.

Objective:To observe the changes in serum estradiol (E 2) levels in pregnant women of different gestational weeks and their predictive value for early intrauterine pregnancy outcomes. Methods:A retrospective study was conducted involving 375 pregnant women who were treated at the Affiliated Yangming Hospital of Ningbo University (Yuyao People's Hospital) from September 2021 to September 2023. The clinical data were categorized based on pregnancy outcomes into three groups: a normal pregnancy group ( n = 150), a threatened miscarriage with continued pregnancy group ( n = 150), and a miscarriage group ( n = 75). The serum estradiol (E 2) levels at different gestational weeks were compared among the three groups: 5 to < 6 weeks (35-41 days), 6 to < 7 weeks (42-48 days), and 7 to 8 weeks (49-55 days). The predictive value of serum E 2 levels for early intrauterine pregnancy outcomes across different gestational weeks was analyzed using Receiver Operating Characteristic (ROC) curves. Results:In the normal pregnancy group, the serum E 2 levels at different gestational weeks were as follows: (1 691.87 ± 532.21) pmol/L for 5 to < 6 weeks, (2 376.64 ± 788.36) pmol/L for 6 to < 7 weeks, and (3 576.30 ± 1,190.06) pmol/L for 7 to 8 weeks. These values were significantly higher than those in the threatened miscarriage with continued pregnancy group [(1 409.28 ± 473.49) pmol/L, (1 893.13 ± 563.15) pmol/L, (2 035.79 ± 612.47) pmol/L, t = 5.15, 11.68, 6.60, all P < 0.05] and the miscarriage group [(906.49 ± 338.09) pmol/L, (923.63 ± 365.39) pmol/L, (950.27 ± 378.89) pmol/L, t = 16.19, 15.45, 21.50, all P < 0.05]. The serum E 2 levels at different gestational weeks in the threatened miscarriage with continued pregnancy group were significantly higher than those in the miscarriage group ( t = 7.48, 10.81, 8.89, all P < 0.05). Both the normal pregnancy group and the threatened miscarriage with continued pregnancy group showed an increasing trend in serum E 2 levels with advancing gestational weeks ( t = 6.74, 18.55, 7.58, 9.82, 11.81, 2.24, all P < 0.05). In contrast, the serum E 2 levels in the miscarriage group also increased with advancing gestational weeks, but the differences were not statistically significant ( P > 0.05). The results from the receiver operating characteristic curve analysis indicated that the areas under the curve for predicting early intrauterine pregnancy outcomes based on serum E 2 levels at different gestational weeks were 0.857, 0.810, and 0.839, demonstrating excellent diagnostic efficacy. Conclusions:Dynamic monitoring of serum E 2 levels is beneficial for predicting early intrauterine pregnancy outcomes and providing guidance for clinical diagnosis and treatment.

Objective:To discuss the clinical and genetic characteristics of neurodevelopmental disorder with or without early-onset generalized epilepsy (NEDEGE) caused by NBEA gene variation. Methods:The clinical and genetic records of a patient who was diagnosed with NEDEGE caused by NBEA gene variation at the Department of Neurology, Guangzhou Women and Children′s Medical Center in April 2024 were collected retrospectively. Using " NBEA or neurobeachin" "Autism spectrum disorders or ASD" "Epilepsy" "Neurodevelopmental disorders" as the keywords, relevant articles were searched at CNKI, Wanfang and PubMed databases from establishment of these databases to December 2024. Clinical and genetic features of NEDEGE were summarized in the combination of this case. Results:The proband, a 3 years old boy, was backward in development since childhood. He had autism spectrum disorder-like manifestations such as stereotyped behavior and poor eye contact. At the age of 2, he developed generalized seizures. The whole exome sequencing showed a de novo heterozygous variation of c.244CT(p.Gln82 *) in the NBEA gene (NM-001385012.1), and he was diagnosed with NEDEGE. A total of 10 articles (all in English) were retrieved, reporting 36 cases of NBEA gene related NEDEGE (including this case), 4 of whom coming from China. Twenty-four individuals suffered from mild to severe intellectual disability, and most were moderate.Twenty-eight patients had language delay, including 4 cases of complete loss of language function, and 24 patients had seizures, and 19 patients had autism or autima-like behavior problems. Conclusions:This case enriches the mutation spectrum of the NBEA gene, and the c.244CT is the first reported related variation in the Chinese population. The clinical symptoms of NEDEGE related to NBEA gene mutations are most pronounced in neurodevelopmental disorders, followed by seizures and autistic behavior.

Objective:To analyze the intrauterine ultrasound manifestations and postnatal follow-up outcomes of fetuses with 2q13 microdeletion.Methods:This retrospective study involved 23 cases of 2q13 microdeletion, diagnosed via amniotic fluid chromosome karyotyping and single nucleotide polymorphism-array (SNP-array) following amniocentesis, between January 1, 2018, and September 1, 2022, at Wuxi Maternity and Child Health Care Hospital. Descriptive statistical analysis was applied to prenatal diagnostic indications, intrauterine ultrasound findings, prenatal diagnosis results, and postnatal follow-up outcomes.Results:(1) The prenatal diagnostic indications for the 23 cases of 2q13 microdeletion included seven cases (30.4%) of high-risk serological screening, six cases (26.1%) of increased nuchal translucency (NT), two cases (8.7%) of fetal heart defects, two cases (8.7%) of advanced maternal age, two cases (8.7%) of fetal choroid plexus cysts (one of which was also associated with high-risk serological screening), one case (4.3%) of suboptimal fetal nasal bone fusion, one case (4.3%) of non-invasive prenatal testing suggesting chromosomal abnormalities, one case (4.3%) of fetal obstructive polycystic kidneys, one case (4.3%) of fetal subependymal cysts, and one case (4.3%) of fetal growth restriction. (2) Intrauterine ultrasound findings included six cases (26.1%) of NT thickening, four cases (17.4%) of intrauterine growth restriction, two cases (8.7%) of fetal heart defects, two cases (8.7%) of choroid plexus cysts, one case (4.3%) of oligohydramnios, one case (4.3%) of suboptimal fetal nasal bone fusion, one case (4.3%) of short long bones in the fetus, one case (4.3%) of polyhydramnios with large fetal abdominal circumference, one case (4.3%) of large fetal abdominal circumference, short long bones, and subependymal cysts of the brain ventricles, and one case (4.3%) of fetal obstructive polycystic kidneys; the remaining six cases (26.1%) showed no abnormal ultrasound findings. (3) Chromosome karyotyping revealed three cases of chromosomal structural abnormalities, one case of sex chromosome numerical abnormalities, and the remaining 19 cases showed no abnormalities. Amniotic fluid SNP-array results indicated deletions ranging from 104 to 1 745 kb. Parental verification was performed in ten cases, showing maternal inheritance in four cases, paternal inheritance in five, and one case of a de novo mutation. (4) Four cases (17.4%) opted for pregnancy termination, while 19 cases (82.6%) resulted in live births. The 19 live-born children underwent telephone and child health follow-up, with ages at follow-up being 3 years (ranging from 9 to 58.8 months). Apart from two cases that did not undergo newborn congenital heart disease screening, the remaining 17 surviving infants were screened without any abnormalities. Five cases had abnormal growth and development during follow-up: one 18-month-old with mild language developmental delay, one 3-year-old plus 26 days with mild language developmental delay, one 18-month-old with language developmental delay, one 3-year-old with astigmatism, and one 30-month-old with refractive error in both eyes during a physical examination; the other 14 children showed no significant abnormalities in growth and development. Conclusions:The intrauterine ultrasound manifestations of fetuses with 2q13 microdeletion are non-specific, and most of them are inherited from their parents. Postnatal follow-up should pay attention to the development of the nervous system of children.

Objectives:This study aims to investigate the association between cumulative fasting blood glucose(FBG)and presence of coronary artery calcification(CAC). Methods:A total of 1 113 participants were recruited from the Beijing Community-based Cohort of Atherosclerosis.Anthropometric measurements and laboratory examinations including FBG were performed in 1998,2008-2009 and 2013-2014 respectively,and coronary CT scan was performed in 2013-2014.Participants were classified into 4 groups according to the level of cumulative FBG(10-year weighted cumulative value of at least 2 FBGs):<50.0 mmol/L group(n=495),50.0-55.9 mmol/L group(n=345),56.0-69.9 mmol/L group(n=176),and≥70.0 mmol/L group(n=97).CAC score>0 was defined as presence of CAC.Multivariable logistic regression model was applied to analyze the impact of cumulative FBG exposure on the risk of CAC,and subgroup analyses were conducted according to factors such as sex and age. Results:The mean age of enrolled participants was(59.7±6.4)years,523(47.0%)were male and 478(42.9%)had CAC.The proportion of subjects with CAC increased with the increment of cumulative FBG.Compared with the<50.0 mmol/L group,the multivariable-adjusted OR(95%CI)for CAC in the 50.0-55.9 mmol/L group,56.0-69.9 mmol/L group,and≥70.0 mmol/L group were 1.43(1.04-1.98),1.92(1.24-2.99)and 2.79(1.35-5.77),respectively(Ptrend<0.05).The risk for CAC increased by 34%per 10 mmol/L increase in cumulative FBG,with OR(95%CI)of 1.34(1.12-1.59).There was no statistically significant difference in the risk of CAC presence for each 10 mmol/L increase in cumulative FBG level between the subgroups(all P≥0.05). Conclusions:Elevated cumulative FBG is a risk factor for the prevalence of CAC,indicating the importance of maintaining healthy FBG in preventing the occurrence of CAC.

Objective:To investigate the factors affecting the time taken for B cell reconstitution after rituximab (RTX) treatment in children with steroid-sensitive nephrotic syndrome.Methods:This was a retrospective cohort study. The clinical data of 42 children with SSNS who received treatment with RTX in Department of Nephrology, Rheumatology and Immunology, Children′s Hospital Affiliated to Zhengzhou University between December 2019 and May 2023 were analyzed retrospectively. The data of demographics, immunosuppressant treatment and laboratory tests such as CD19 +B cell count, urinary protein quantification were collected. The patients were divided into 2 groups, the early B cell reconstruction group and the late reconstruction group based on the average time of B cell reconstruction. A multivariate logistic regression model was used to analyze the factors impacting the timing of B cell reconstruction, and the predictive value of these factors was assessed by plotting the receiver operating characteristic (ROC) curve. Results:There were 42 children, with 35 males and 7 females. They were aged 3.5 (2.2, 5.9) years at the onset of PNS and (8.4±3.3) years at their first RTX treatment. The time for B cell reconstitution was (152±53) d. There were 20 children in the early reconstruction group and 22 children in the late reconstruction group. There were no statistically significant differences (all P>0.05) between the 2 groups in terms of the cumulative dose of steroids within 1 year before receiving RTX infusion (0.29 (0.16, 0.50) vs. 0.29 (0.19, 0.46) mg/(kg·d)), the percentage of children using tacrolimus before RTX (65%(13/20) vs. 45%(10/22)) and cumulative doses (0.04 (0.03, 0.05) vs. 0.03 (0.03, 0.06) mg/(kg·d)), the steroid doses at the time of RTX infusion (0.73 (0.49, 0.90) vs. 0.71 (0.58, 0.89) mg/(kg·d)), the percentage of children using tacrolimus at the initial RTX infusion (50% (10/20) vs. 41% (9/22)) and the doses (0.03 (0.02, 0.04) vs. 0.02 (0.01, 0.04) mg/(kg·d)), the discontinuation time of tacrolimus post-RTX infusion (71 (42, 91) vs. 64 (42, 91) d). A multivariate analysis revealed a correlation ( OR=0.26, 95% CI 0.10-0.68, P=0.006) between B cell count following the second RTX infusion and the time taken for B cell reconstruction. The area under the ROC curve for B cell count after the RTX infusion in predicting the time to B cell reconstruction was 0.89 (95% CI 0.78-0.99, P<0.001) and the cut-off value was 0.925×10 6/L. Conclusions:The time of B cell reconstruction is not influenced by the previous or concurrent use of tacrolimus, regardless of its duration and the dosage of steroid and tacrolimus prior to the RTX infusion. Insteadly, the peripheral blood B cell count (0.925×10 6/L) following the second RTX infusion for SSNS is identified as an independent predictor of reconstruction time, allowing for a more precise prediction and early intervention to maintain disease remission.

Objective:To summarize the clinical and genetic characteristics, treatment and prognosis of four children with Steroid-resistant nephrotic syndrome (SRNS) due to variants of TRPC6 gene. Methods:Clinical data of four children with SRNS admitted to Children′s Hospital Affiliated to Zhengzhou University between May 2020 and August 2022 were collected. Peripheral blood samples were collected from the children and their parents, and whole exome sequencing was carried out. Sanger sequencing was used to verify the pathogenicity of the candidate variants among the children and their parents.Results:All of the four children were found to harbor heterozygous variants of the TRPC6 gene, including c. 523C>T (p.R175W), c. 1327T>A (p.F443I), c. 430G>C (p.E144Q) (unreported previously), and c. 523C>T (p.R175W), which were all missense variants. Two of the children have shown a simple type, whilst two have shown a nephritis type, none had extrarenal phenotype. Comprehensive renal pathology of three children revealed focal segmental glomerulosclerosis (FSGS). Two children were treated with steroids combined with calcineurin inhibitors (CNIs), among whom one showed significant improvement in symptoms. Conclusion:Discoveries of the novel c. 430G>C variant and the new SRNS phenotype of the c. 1327T>A variant have expanded the mutational and phenotypic spectrum of the TRPC6 gene, which has provided a reference for clinical diagnosis and genetic counseling for the families.

Objective:To investigate the anatomic mechanism and risk factors of intracranial embolism caused by injection at temporal region.Methods:(1) Latex perfusion was performed on the vessels of 8 cranial specimens. The vessels from the superficial temporal artery to the carotid artery were dissected to measure the length, the diameter of starting point and ending point and the volume of vessels (drainage method). (2) Cranial CT angiography of 20 patients (excluding patients with cervical diseases) were obtained from the database of Zhejiang Provincial People’s Hospital from January 2021 to December 2022. The length, the diameter of starting point and ending point, and the volume of vessels were measured. (3) 5 plastic surgeons used pressure simulation measuring equipment to vigorously press the temporal region of the real skull model according to the clinical practice and maintain 2 s to obtain the maximum pressure value. The additional pressure on the temporal region was obtained by subtracting the common carotid artery base pressure [set at 90, 120, 150 and 200 mmHg (1 mmHg = 0.133 kPa)] from the maximum pressure.Results:(1) 8 arteries were collected from 4 skull specimens. The length of vessels was (169.5±7.2) mm, the diameter of the starting point of vessel was (4.29±0.28) mm, the diameter of the ending point of vessel was (1.31±0.15) mm, and the volume was (1.56±0.21) ml. (2) There were 11 males and 9 females among 20 patients aged 23-53 years. The length of vessels was (172.2±7.6) mm, the diameter of the starting point of vessel was (5.63±0.43) mm, the diameter of the ending point of vessel was (1.77±0.16) mm, and the volume was (1.59±0.23) ml. (3) The mean value of additional pressure generated by local pressure on the temporal region by 5 physicians was (127.2±10.1) mmHg (113.8-138.6 mmHg).Conclusion:When the injection volume into the superficial temporal artery was more than 1.6 ml, the artery was damaged, and the temporal area was pressed strongly (the local pressure was more than 110 mmHg above the basic pressure), the injection material might flow into the intracranial from the junction of the common carotid artery and into the internal carotid artery, which was the possible mechanism of the temporal filling leading to intracranial embolism.

Objective To explore the association of Toll-like receptor 7, CTLA-4 gene polymorphisms and severe asthma. Methods From February 2018 to March 2020, 175 asthma patients admitted to the respiratory department of our hospital were selected as the research subjects (109 cases of mild disease and 66 cases of severe disease), and 248 cases of healthy people who were included in the outpatient physical examination of our hospital during the same period were selected as the normal control group. Toll-like receptor 7 and CTLA-4 gene polymorphisms in the above groups were determined, and the relationship between Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma was evaluated by calculating the odds ratio (OR) and 95% confidence interval(CI). The relationship between the genotypes of Toll-like receptor 7 and CTLA-4 polymorphisms and severe asthma were evaluated by logistic regression analysis. Results The proportion of TLR7 rs3853839 CC genotype, CTLA-4 rs231725 AA genotype, TLR7 rs3853839 C allele frequency and CTLA-4 rs231725 A allele frequency in severe asthma group and mild asthma group were higher than those in normal control group(P<0.05). The proportion of TLR7 rs3853839 CC genotype, the proportion of CTLA-4 rs231725 AA genotype, the frequency of TLR7 rs3853839 C allele, and the frequency of CTLA-4 rs231725 A allele in the severe asthma group were higher than those in the mild asthma group(P<0.05). TLR7 rs3853839 CC genotype (OR=10.32, 95%CI=5.59-23.89), CTLA-4 rs231725 AA genotype (OR=13.21, 95%CI=3.58-20.25), TLR7 rs3853839 C allele frequency (OR=11.32, 95% CI=4.25-21.14) and CTLA-4 rs231725 A allele frequency (OR=13.24, 95% CI=6.59-20.21) could increase the susceptibility to severe asthma(P<0.05). TLR7 rs3853839CC genotype, TLR7 rs3853839C allele frequency, CTLA-4 rs231725AA genotype and CTLA-4 rs231725A allele frequency were risk factors for severe asthma(P<0.05). Conclusion TLR7 rs3853839 CC genotype, TLR7 rs3853839 C allele frequency, CTLA-4 rs231725 AA genotype and CTLA-4 rs231725 A allele frequency are associated with the occurrence of severe asthma.