Objective:To investigate the clinical features of Epstein-Barr virus associated lymphoproliferative disease in children and to improve the understanding of this disease.Methods:This study included the children with Epstein-Barr virus associated lymphoproliferative disease admitted to the First Affiliated Hospital of College of Medicine of Zhejiang University from January 2014 to December 2018.Data of these children were collected, including age, clinical manifestations, laboratory results, treatment and outcome.The clinical features and therapeutic effects were analyzed.Results:A total of 114 cases(mean age 6 years, 0~17 years)were enrolled in this study, including 53 males and 61 females.There were 107 cases(93.86%) in the mild group (38 cases of EBV infection and 69 cases of infectious mononucleosis) and 7 cases in the severe group (6.14%). Six cases of the severe group were T cell or NK cell proliferation.Compared with the mild group, the load of EBV-DNA was higher in the severe group, but there was no significant difference( χ2=0.957, P>0.05). The IgM in severe group was significantly lower( Z=-2.041, P<0.05). But the differences in the level of immune function including IgA, IgG, CD4 + cell and CD8 + cell between the severe group and the mild group were not significant.The cases in the mild group had improved after antiviral treatments.Among the severe group, 3 cases survived after treatment, another 1 case was diagnosed as hydroa vacciniforme-like EBV-related proliferative disease (HV-like LPD). After antiviral treatment, the effect was not good, then after high-dose IVIG treatment and Bortezomib combined with methylprednisolone treatment, the EBV-DNA load decreased and the condition improved.While 1 case lost to follow-up, there were 2 cases with EBV-associated hemophagocytic syndrome and 1 case with EBV-associated lymphoma died after chemotherapy or transplantation. Conclusion:EBV-associated lymphoproliferative disease may manifest as a condition similar to infectious mononucleosis.High IgE, low IgM or high DNA load may indicate poor prognosis.Immune function after EBV infection may have different effects on prognosis.When the infected lymphocyte types are NK or T cells, it may indicate poor prognosis.The efficacy of transplantation and chemotherapy in severe cases is still uncertain.

With an estimated incidence of 1/40 000 to 1/4000,Gitelman syndrome is the most common type of inherited renal tubular disease during adolescence or adulthood.Characteristic features of Gitelman syndrome include transient episodes of muscle cramps and fatigue,hypokalemia,hypomagnesemia,hypocalciuria,and metabolic alkalosis.Detection of SLC12A3 mutations,in conjunct with clinical manifestations,may confirm the diagnosis.Recent research suggested that CLCNKB may also be a candidate gene for Gitelman syndrome.Research on genotype-phenotype correlation has provided more information on the genetic etiology of Gitelman syndrome,which may facilitate the diagnosis and treatment for this syndrome and improve their prognosis.

Objective To investigate association of the paired box 4 (PA X 4) gene rs3824004 (574C>A; R192S) and rs2233580 (575G>A; R192H) polymorphism with obesity and metabolic markers in children and adolescents. Methods A total of 103 obese children were randomly selected, and an average age was (10.82±2.57) years, and body mass index (BMI) was (26.82±4.57) kg/m2. At the same period, 100 normal weight children were selected as the control group, and an average age of (10.60±2.84) years, and BMI was (16.79±2.13) kg/m2. The blood pressure, physical measurements, and blood metabolic parameters were measured and compared. The oral glucose tolerance test (OGTT) and insulin release test were performed in the obesity group. The homeostasis model insulin resistance index (HOMA-IR) and the overall insulin sensitivity index (WBISI) were calculated. PA X 4 rs3824004 and rs2233580 polymorphism were detected by PCR.The differences of allele frequency and genotype frequency of polymorphic loci were analyzed, and the correlation between different genotypes and metabolic indexes was analyzed. Results The height, weight, BMI, systolic blood pressure, diastolic blood pressure, waist circumference, hip circumference, waist to height ratio (WHtR), fasting blood glucose (FPG), total cholesterol (TC), low density lipoprotein (LDL), triacylglycerol (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the obesity group were significantly higher than those in the control group, and the high density lipoprotein (HDL) was significantly lower than that in the control group (all P<0.05). The frequency of gene distribution was in accordance with the Hard-Weinberg balance. The frequencies of A allele of rs3824004 in obesity and control groups were 4.9% and 5.0%, respectively, and the frequencies of CA genotype were 9.7% and 10.0%, respectively, and there was no significant difference between two groups (P>0.05). The frequency of GA allele of rs2233580 in obesity group was 25.2%, which was significantly higher than that in control group (P<0.05). The BMI and waist in rs2233580 GA genotype were significantly higher than those in GG genotype (all P <0.05). However,logistic regression analysis showed that there was no correlation between PA X 4 rs2233580 genotype and metabolic markers (all P>0.05).There were no significantly differences in HOMA-IR and WBISI among different genotypes of PA X 4 rs2233580 in obesity group(all P>0.05).Conclusions PA X 4 rs2233580 affects children's BMI and waist circumference and may be involved in the development of childhood obesity, but it is not an independent risk factor for obesity in children and adolescents.

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 assess the efficacy and safety of aromatase inhibitors (AIs) combined growth hormone in treatment of adolescent boys with short stature. METHODS: One hundred and fifty-one short stature pubertal boys with age of 10-14 years and bone age of 13-15 years, who were admitted to the Department of Pediatrics, the First Affiliated Hospital, Zhejiang University School of Medicine, were included in this trial. According to their own or parents' intention, the children were divided into recombinant human growth hormone (rhGH)+AI group ( =108) and rhGH group ( =43). All children were injected subcutaneously with rhGH 0.15-0.2 IU·kg ·d , and those in rhGH+AI group were additionally given 2.5 mg/d letrozole or 1 mg/d anastrozole, orally for 12 months or longer. The children were followed-up every 3 months. During the follow-up visit, the predicted adult height (PAH), sex hormone level, glucose and lipid metabolism, and other indicators were measured, and adverse reactions were monitored. RESULTS: After intervention, there were significant differences in ΔBA(bone age)/ΔCA(chronological age), ΔHtSDS (height standard deviation score based on bone age)and ΔPAH between rhGH+AI group and the rhGH group( < 0.05 or < 0.01). During follow-up, 63.9%of the children in the rhGH+AI group had elevated uric acid and 51.9%had decreased high-density lipoprotein (HDL); 25.9%showed severe acne, excitement, hyperactivity and irritability, 11.1%had knee pain; 4.6%had fracture; 2.8%had mild renal dysfunction; 1.9%had inactivity, drowsiness, memory loss and performance decline; 1.9%showed mild abnormal liver function; 0.9%showed impaired fasting glucose; 0.9%showed granulocytopenia. In the rhGH group, 11.6%of the children presented with knee pain and 2.3%with impaired fasting glucose. CONCLUSIONS AI combined with rhGH can delay the growth of BA and effectively improve the PAH of adolescent boys with larger bone age. However, the occurrence of adverse reactions of AI should be closely monitored during treatment.
Adolescent ; Aromatase Inhibitors ; therapeutic use ; Body Height ; Child ; Growth Disorders ; Human Growth Hormone ; Humans ; Male ; Recombinant Proteins