Objective:To explore the clinical characteristics and molecular basis for children and adolescents with monogenic diabetes.Methods:A retrospective analysis was carried out for the clinical manifestations and laboratory data of 116 children and adolescents diagnosed with diabetes at Ningbo Women and Children′s Hospital from January 2020 to March 2023. Whole exome sequencing and mitochondrial gene sequencing were carried out on 21 children with suspected monogenic diabetes.Results:A total of 10 cases of monogenic diabetes were diagnosed, all of which were Maturity-onset Diabetes Of the Young (MODY). Six cases of MODY2 were due to GCK gene mutations, 1 case of MODY3 was due to HNF1A gene mutation, 2 cases of MODY12 were due to ABCC8 gene mutations, and 1 case of MODY13 was due to KCNJ11 gene mutation. Nine of the 10 patients with MODY had no typical symptoms of diabetes. A family history of diabetes was significantly more common in the MODY group compared with the T1DM and T2DM groups ( P<0.05). The BMI of the MODY group was higher than that of the T1DM group ( P<0.05). The initial blood glucose level was lower than that of the T1DM group ( P<0.05), and there was no significant difference compared with the T2DM group. The fasting C-peptide level of the MODY group was higher than that of the T1DM group ( P<0.05), and there was no significant difference compared with the T2DM group. Glycosylated hemoglobin of the MODY group was lower than both the T1DM and T2DM groups ( P<0.05). Conclusion:In this study, MODY has accounted for the majority of monogenic diabetes among children and adolescents, and the common mutations were those of the GCK gene in association with MODY2. Blood glucose and glycosylated hemoglobin of children with MODY were slightly increased, whilst the islet cell function had remained, and the clinical manifestations and laboratory tests had overlapped with those of type 2 diabetes. WES and mitochondrial gene sequencing can clarify the etiology of monogenic diabetes and facilitate precise treatment.

Objective: To examine the impact of heat waves and cold spells on the incidence of hemorrhagic stroke, so as to provide insights into prevention of hemorrhagic stroke. Methods: Data pertaining to the incidence of hemorrhagic stroke in Zibo City from 2015 to 2019 were collected from Shandong Provincial Management Information System for Chronic Diseases and Cause of Death Surveillance, and the meteorological data during the period from 2015 to 2019 were captured from National Meteorological Information Center of China. The air quality index (AQI) was collected from the National Daily Report of Urban Air Quality in China. Heat wave was defined as the highest daily temperature that was no less than the 90th percentile (P90), P92.5, P95 and P97.5 of the highest daily temperature in the warm season for at least 2, 3 or 4 days, and cold spell was defined as the lowest daily temperature that was no more than the P10, P7.5, P5 and P2.5 of the lowest daily temperature in the cold season for at least 2, 3 or 4 days. The effect of heat waves and cold spells on the incidence of hemorrhagic stroke was evaluated using a generalized additive model and described with relative risk (RR) and its 95%CI. Results: A total of 8 844 case with first-onset hemorrhagic stroke were recorded in Zibo City from 2015 to 2019. The lowest daily temperature that was no more than P10, P7.5 or P5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 or P7.5 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.187, 95%CI: 1.031-1.366; highest RR=1.242, 95%CI: 1.042-1.480), and after adjusting the effect of daily mean temperature, the lowest daily temperature that was no more than P10 or P7.5 of the lowest daily temperature in the cold season for at least two days, or that was no more than P10 of the lowest daily temperature for at least 3 days resulted a remarkably increased risk of hemorrhagic stroke (lowest RR=1.236, 95%CI: 1.009-1.513; highest RR=1.274, 95%CI: 1.023-1.585). However, there was no significant association between heat waves and the risk of hemorrhagic stroke. Conclusion Cold spells may increase the risk of hemorrhagic stroke, while no significant association is examined between heat waves and the risk of hemorrhagic stroke.

OBJECTIVE: To analyze the genetic etiology of a Chinese pedigree affected with short stature. METHODS: A child with familial short stature (FSS) who had presented at the Ningbo Women and Children's Hospital in July 2020 and his parents and paternal and maternal grandparents were selected as the study subject. Clinical data of the pedigree was collected, and the proband was subjected to routine growth and development assessment. Peripheral blood samples were collected. The proband was subjected to whole exome sequencing (WES), and the proband, his parents and grandparents were subjected to chromosomal microarray analysis (CMA). RESULTS: The height of the proband and his father was 87.7cm (-3 s) and 152 cm (-3.39 s) respectively. Both of them were found to harbor a 15q25.3-q26.1 microdeletion, which has encompassed the whole of the ACAN gene which is closely associated with short stature. The CMA results of his mother and grandparents were all negative, and above deletion has not been included in population database and related literature, and was rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). After 14 months of rhGH treatment, the height of the proband has increased to 98.5 cm (-2.07 s). CONCLUSION The 15q25.3-q26.1 microdeletion probably underlay the FSS, in this pedigree. Short-term rhGH treatment can effectively improve the height of the affected individuals.
Child ; Female ; Humans ; Male ; Aggrecans/genetics* ; Dwarfism/genetics* ; East Asian People ; Mutation ; Pedigree

Objective:To investigate the prognosis of severe hyperbilirubinemia in full-term infants who met the exchange transfusion criteria and were treated by blood exchange transfusion and phototherapy.Methods:A total of 168 full-term infants with severe hyperbilirubinemia who met the criteria for exchange transfusion and were hospitalized in the Neonatology Department of seven tertiary hospitals in Hebei Province from June 2017 to December 2018 were retrospectively included. According to the treatment protocol, they were divided into two groups: exchange transfusion group (38 cases) and phototherapy group (130 cases). Two independent sample t-test and Chi-square test were used to compare the clinical manifestations and follow-up results between the two groups. Multivariate logistic regression was used to analyze the risk factors for poor prognosis. Results:Neonatal severe hyperbilirubinemia in the exchange transfusion and phototherapy group were both mainly caused by hemolytic disease [42.1%(16/38) and 29.2%(38/130)], sepsis [28.9%(11/38) and 11.5%(15/130)] and early-onset breastfeeding jaundice [15.8%(6/38) and 11.5%(15/130)]. Total serum bilirubin level on admission in the exchange transfusion group was significantly higher than that in the phototherapy group [(531.7±141.3) vs (440.0±67.4) μmol/L, t=3.870, P<0.001]. Moreover, the percentage of patients with mild, moderate and severe acute bilirubin encephalopathy in the exchange transfusion group were higher than those in the phototherapy group [15.8%(6/38) vs 3.8%(5/130), 7.9%(3/38) vs 0.8%(1/130), 13.2%(5/38) vs 0.0%(0/130); χ2=29.119, P<0.001]. Among the 168 patients, 135 were followed up to 18-36 months of age and 12 showed poor prognosis (developmental retardation or hearing impairment) with four in the exchange transfusion group (12.9%, 4/31) and eight in the phototherapy group (7.7%, 8/104). Multivariate logistic regression analysis showed that for full-term infants with severe hyperbilirubinemia who met the exchange transfusion criteria, phototherapy alone without blood exchange transfusion as well as severe ABE were risk factors for poor prognosis ( OR=14.407, 95% CI: 1.101-88.528, P=0.042; OR=16.561, 95% CI: 4.042-67.850, P<0.001). Conclusions:Full-term infants who have severe hyperbilirubinemia and meet the exchange transfusion criteria should be actively treated with blood exchange transfusion, especially for those with severe ABE, so as to improve the prognosis.

OBJECTIVE: To explore the genetic basis for a fetus with autosomal recessive polycystic kidney disease (ARPKD). METHODS: Fetal tissue and peripheral blood samples were respectively obtained from the abortus and the couple. Following extraction of genomic DNA, genetic testing was carried out. RESULTS: The fetus was found to carry compound heterozygous variants of the PKHD1 gene, namely c.5336A>T (p.N1779I) and c.9455delA (p.N3152Tfs*10), which were respectively inherited from the husband and wife. CONCLUSION The c.5336A>T and c.9455delA variants of the PKHD1 gene probably account for the ARPKD in the fetus. Above results have enabled genetic counseling and prenatal diagnosis for the couple.

Objective To explore the gene mutation characteristics and detailed clinical presentations of hyperglycemia caused by GCK mutations in 10 patients.Methods The clinical and follow-up data of 10 patients with hyperglycemia caused by mutation of GCK gene were reviewed.The patients were ascertained between January 1,2014 and August 31,2018 at the Department of Pediatrics,the First Affiliated Hospital of Zhejiang University and Ningbo Women & Children's Hospital.Clinical data were collected,including age,gender,main complaint,family history,fasting blood glucose,fasting blood insulin,2-hour blood glucose,2-hour blood insulin after oral glucose tolerance test,glycosylated hemoglobin,anti-glutamic acid decarboxylase antibody and body mass index.Mutations of GCK gene were detected by Sanger sequencing or high-throughput sequencing of diabetes-related genes in the patients and their family members.Results There were ten patients,8 of them were male,2 were female.The ages at diagnosis varied between 4.7 to 12.3 years.The patients usually did not have obvious clinical symptoms of diabetes mellitus.Most of them were unexpectedly found to have hyperglycemia and with impaired glucose metabolism in three consecutive generations.The fasting blood glucose of patients was 6.8-7.7 mmol/L,2-hour postprandial blood glucose was 7.8-11.6 mmol/L.Fasting blood insulin was 0.5-8.5 mU/L,glucose tolerance test results showed that 2 h postprondial blood insulin was 1.3-55.4 mU/L.The level of glycosylated hemoglobin was 6.1％-6.8％.Anti-glutamic acid decarboxylase antibody was negative in all patients.The GCK mutations identified in patients and one of their parents were located at exon5 (4 cases),exon9 (2 cases),exon2 (1 case),exon4 (1 case),exon6 (1 case) and exon7 (1 case).Conclusions Most of the hyperglycemia patients caused by GCK mutations did not have typical clinical symptoms of diabetes.The fasting blood glucose was slightly elevated.Abnormal glucose tolerance test results were found in all 10 patients.Three consecutive generations of family had impaired glucose metabolism.GCK mutations located at exon 5 were common in 10 cases.There was no correlation between type of mutations and plasma glucose levels in domestic and international researches.When fasting glucose was found abnormal in clinic,a complete family history should be taken and the GCK gene should be sequenced to confirm the diagnosis in time.

Objective To discuss the clinical application value of Omaha system-based targeting nursing care for patients with hepatocellular carcinoma (HCC) who were treated with transcatheter arterial chemoembolization (TACE).Methods A total of 60 advanced HCC patients,who were planned to receive TACE,were prospectively and randomly divided into the control group (n=30) and the observation group (n=30).Routine nursing mode was adopted for the patients in the control group,while Omaha system nursing model was employed for the patients in the observation group.The patients of the observation group were evaluated with Omaha system at the time of admission,the key common problems were screened out and targeted nursing measures were employed.Meanwhile,on the days of admission and discharge all the patients of both groups were asked to fill in the forms of Hamilton depression scale (HAMD-17),Hamilton anxiety scale (HAMA),social support rating scale (SSQ) and numerical pain rating scale (NRS);and the degrees of depression,anxiety,social support and pain were respectively assessed.Results Both nursing modes could improve the degrees of depression and anxiety as well as the social support system of HCC patients,but the curative effect of these two aspects in the observation group were obviously better than those in the control group (P＜0.05).No statistically significant difference in the improvement of pain degree existed between the two nursing models,but Omaha system-based targeting nursing mode could alleviate the patient's pain to a certain extent.Conclusion For patients with advanced HCC,Omaha system-based targeting nursing care can alleviate the patient's negative emotion and promote the patients to establish effective social support system,this nursing mode is superior to conventional nursing mode.Therefore,Omaha system-based targeting nursing has great application potential in clinical practice.

Objective To evaluate the efficacy and safety of different doses of prednisone combined with cyclosporine A(CSA) on the treatment of idiopathic membranous nephropathy (IMN). Methods The data of 64 patients with nephrotic syndrome (NS) diagnosed as IMN by renal biopsy were retrospectively analyzed. Median follow?up time was 10 (7, 19) months. The subjects were divided into 2 groups according to different prednisone dosage. Thirty?two cases were in the low?dose group:prednisone 0.15 mg·kg-1·d-1+CSA, and 32 cases in the moderate?dose group:prednisone 0.4?0.5 mg· kg-1·d-1+CSA. Clinical and laboratory data were collected at baseline, 1, 3, and 6 months after treatment. During follow?up, cumulative recurrence rate and adverse reactions after treatment were recorded. Results Serum albumin (sALB) were significantly increased and 24 h urinary protein (24hUP) significantly decreased after treatment for 1, 3, 6 months compared with baseline data in the two groups. Serum creatine (Scr) increased after treatment with time. The elevation of sALB and the reduction of 24hUP in the moderate?dose group were higher than that of low?dose group at 6 months after treatment (P<0.05). The effective rate of the low?dose and moderate?dose group was 65.6% and 87.5% at 6 months after treatment, respectively (χ2=4.267, P=0.039). Comparison of different doses of CSA in two groups at 6 months after treatment, in low?dose group: the effective rates of CSA<3 mg· kg-1·d-1 and >3 mg·kg-1·d-1 subgroup were 76.5% and 53.3%, respectively (P=0.296); In moderate?dose group:the effective rates of CSA<3 mg·kg-1·d-1 and>3 mg·kg-1·d-1 subgroup were 89.5%and 84.6%, respectively (P=0.077); there were similar effects in patients treated with different dose CSA in the two groups. About 20.4% of the total patients relapsed when followed up for 18 months (low dose group vs moderate?dose group: 9.5% vs 28.6%, P=0.136), which most occurred after prednisone withdrawal or during the reduction of cyclosporine. Renal function decreased in 57.8% patients (low dose group vs moderate?dose group:50%vs 65.6%), mainly in the elderly (9/11) and the long course of treatment of CSA. There was no significant difference on adverse reactions between the two groups (P>0.05). Renal function in patients with high Scr or high blood trough concentration of cyclosporine was difficult to fully recover. Conclusions Remission rate is lower in low?dose prednisone combined with cyclosporine than the moderate?dose group in the treatment of IMN for 6 months. The recurrence rate of IMN or the incidence of adverse reactions are similar between the two groups. Induction therapy of IMN with cyclosporin<3 mg·kg-1·d-1 is safe and effective. The incidence of renal function reduction in the elderly is high, and the renal function is difficult to restore in patients with Scr exceeding normal upper limits.

Purpose To investigate the role of PTEN in podocyte injury in patients with diabetic nephropathy ( DN) . Methods Uri-nary samples from 30 patients with DN and 10 healthy volunteers were collected to detect the level of PCX by ELISA. Renal biopsies were reviewed to observe the morphological changes. All patients with DN were divided into three groups by glomerular lesion. The ex-pression of p-Akt and PTEN in glomeruli was detected by immunohistochemistry. Results The levels of PCX in the urine were signifi-cantly higher in patients with DN compared with those in healthy volunteers, and gradually increased along with glomerular lesion aggra-vating. The expression of p-Akt and PTEN increased in patients with DN compared with healthy volunteers. Although the expression of p-Akt and PTEN decreased with the aggravation of glomerular lesion, they were still higher than that in volunteers. There were obvious-ly positive correlation between the level of PCX and 24-h urinary protein and negative correlation between the level of PCX and the ex-pression level of p-Akt and PTEN. Conclusion PTEN down-regulation may be associated with podocyte injury in DN, which may be associated with the phosphorylation of Akt.

Multiple myeloma is common in the older population and is treated mainly with chemotherapy. However, chemotherapy-related side effects imitate the clinical manifestations of Sheehan's syndrome, which leads to misdiagnosis and missed diagnosis, particularly for older patients without a clear history of postpartum hemorrhage. Therefore, when older women with malignant myelomas show refractory hyponatremia and gastrointestinal disorders while under chemotherapy, a diagnosis of Sheehan's syndrome should be considered. The early detection of the disorder will guarantee timely individualized treatment.