TCERG1L hypermethylation is a risk factor of diabetic retinopathy in Chinese children with type 1 diabetes

●AIM:To identify the differential methylation sites(DMS)and their according genes associated with diabetic retinopathy(DR)development in type 1 diabetes(T1DM)children.●METHODS:This study consists of two surveys.A total of 40 T1DM children was included in the first survey.Because no participant has DR,retina thinning was used as a surrogate indicator for DR.The lowest 25%participants with the thinnest macular retinal thickness were included into the case group,and the others were controls.The DNA methylation status was assessed by the Illumina methylation 850K array BeadChip assay,and compared between the case and control groups.Four DMS with a potential role in diabetes were identified.The second survey included 27 T1DM children,among which four had DR.The methylation patterns of the four DMS identified by 850K were compared between participants with and without DR by pyrosequencing.●RESULTS:In the first survey,the 850K array revealed 751 sites significantly and differentially methylated in the case group comparing with the controls(|Δβ|>0.1 and Adj.P<0.05),and 328 of these were identified with a significance of Adj.P<0.01.Among these,319 CpG sites were hypermethylated and 432 were hypomethylated in the case group relative to the controls.Pyrosequencing revealed that the transcription elongation regulator 1 like(TCERG1L,cg07684215)gene was hypermethylated in the four T1DM children with DR(P=0.018),which was consistent with the result from the first survey.The methylation status of the other three DMS(cg26389052,cg25192647,and cg05413694)showed no difference(all P>0.05)between participants with and without DR.●CONCLUSION:The hypermethylation of the TCERG1L gene is a risk factor for DR development in Chinese children with T1DM.

Pressure pain sensitivity: A new stress measure in children and adolescents with type 1 diabetes?

Type 1 diabetes(T1D)is associated with general-and diabetes-specific stress which has multiple adverse effects.Hence measuring stress is of great importance.An algometer measuring pressure pain sensitivity(PPS)has been shown to correlate to certain stress measures in adults.However,it has never been investigated in children and adolescents.The aim of our study was to examine associations between PPS and glycated hemoglobin(HbA1c),salivary cortisol and two questionnaires as well as to identify whether the algometer can be used as a clinical tool among children and adolescents with T1D.Eighty-three participants aged 6-18 years and diagnosed with T1D were included in this study with data from two study visits.Salivary cortisol,PPS and questionnaires were collected,measured,and answered on site.HbA1c was collected from medical files.We found correlations between PPS and HbA1c(rho=0.35,P=0.046),cortisol(rho=-0.25,P=0.02)and Perceived Stress Scale(rho=-0.44,P=0.02)in different subgroups based on age.Males scored higher in PPS than females(P<0.001).We found PPS to be correlated to HbA1c but otherwise inconsistent in results.High PPS values indicated either measurement difficulties or hypersensibility towards pain.

Type 2 diabetes in children and adolescents:Exploring the disease heterogeneity and research gaps to optimum management

Over the past 20 years,the incidence and prevalence of type 2 diabetes mellitus(T2DM)in children and adolescents have increased,particularly in racial and ethnic minorities.Despite the rise in T2DM in children and adolescents,the pathophysiology and progression of disease in this population are not clearly understood.Youth-onset T2DM has a more adverse clinical course than is seen in those who develop T2DM in adulthood or those with T1DM.Furthermore,the available therapeutic options are more limited for children and adolescents with T2DM compared to adult patients,mostly due to the challenges of implementing clinical trials.A better understanding of the mechanisms underlying the development and aggressive disease phenotype of T2DM in youth is important to finding effective prevention and management strategies.This review highlights the key evidence about T2DM in children and adolescents and its current burden and challenges both in clinical care and research activities.

Correlation Analysis of Traditional Chinese Medicine Syndrome Types and Influencing Factors of Asthmatic Bronchitis in Children

Objective:To explore the correlation between traditional Chinese medicine(TCM)syndrome types and the influencing factors of asthmatic bronchitis in children,as well as to provide clinical syndrome differentiation basis and reference for the treatment of children with asthmatic bronchitis.Methods:The clinical data of 197 inpatients with asthmatic bronchitis in our hospital from March 2021 to March 2022 were collected,referring to“Zhu Futang Practical Pediatrics”(7th Edition,2002)and“Chinese Medicine Industry Standards-Standards for Diagnosis and Efficacy of Pediatric Diseases and Syndromes of Traditional Chinese Medicine”(1994,State Administration of Traditional Chinese Medicine)for diagnosis,classification,and analysis of TCM syndrome types and the influencing factors of asthmatic bronchitis in children.Results:(i)cold asthma syndrome contributed to the majority of TCM syndrome types of pediatric asthmatic bronchitis;(ii)gender had a great influence on TCM syndromes types in children with asthmatic bronchitis,and the differences among the TCM syndrome types were statistically significant(P<0.05);(iii)there was no significant difference in the distribution of TCM syndrome types of pediatric asthmatic bronchitis among different age groups(P>0.05);(iv)birth status had no effect on the distribution of TCM syndrome types of pediatric asthmatic bronchitis(P>0.05);(v)no significant correlation was observed between the mode of delivery and the distribution of TCM syndrome types in children with asthmatic bronchitis(P>0.05);(vi)children with cold asthma syndrome,heat asthma syndrome,and mixed cold and heat syndrome were not breastfed,and there was no significant difference in the feeding methods of children with mixed deficiency and excess syndrome(P>0.05);(vii)no significant correlation was observed between the TCM syndrome types of pediatric asthmatic bronchitis and family history of asthma/allergy(P>0.05);(viii)a significant correlation was observed between different TCM syndrome types and history of drug and food allergy(P<0.05);(ix)normal or high eosinophil percentage was commonly observed in children with asthmatic bronchitis,and there was no significant difference among the different TCM syndrome types(P>0.05).Conclusion:The TCM syndrome types of pediatric asthmatic bronchitis are related to gender,feeding history,allergy history,and other factors,which may be influencing factors of the TCM syndrome types of pediatric asthmatic bronchitis.

Impacts of Types and Degree of Obesity on Non-Alcoholic Fatty Liver Disease and Related Dyslipidemia in Chinese School-Age Children?

Objective To explore the impacts of types and degree of obesity on non‐alcoholic fatty liver disease （NAFLD） and related lipids disturbance in Chinese school‐age children. Methods A total of 1 452 school‐age Children of 7 to 17 years were recruited in Beijing with representative cluster sampling method. Data of anthropometric measurements including weight, height and waist circumference were collected from March to May of 2007. Body mass index（BMI）was calculated. Blood samples were obtained and lipid profiles including triglyceride （TG）, total cholesterol （TC）, high‐density lipoprotein cholesterol （HDL‐C） and low‐density lipoprotein cholesterol （LDL‐C） were measured, while glutamate‐pyruvate transaminase （ALT） and glutamic‐oxalacetic transaminase （AST） were determined to evaluate liver function. The liver was also scanned by sonography, and abnormal hepatic sonograms were documented. NAFLD was diagnosed according to the criteria recommended by the Fatty Liver and Alcoholic Liver Disease Study Group under the Chinese Liver Disease Association. Analysis of covariance （ANOVA）, Chi‐square test for trend and binary logistic regression analysis were performed. Results The dyslipidemia and ultrasonographic fatty liver deteriorated with the degree of obesity defined either by BMI or waist circumference. Compared with BMI, waist circumference contributed more to the development of dyslipidemia, fatty liver and NAFLD. The highest levels of TG, TC, LDL‐C, and lowest level of HDL‐C were seen in the mixed obese group followed by abdominal obese, peripheral obese and non‐obese ones. Adjusted for gender and age, the odds ratios （ORs） and their 95% confidence intervals of peripheral obesity, abdominal obesity and mixed obesity were 0, 10.93 （0.98‐121.96） and 79.16 （10.95‐572.44） for predicting NAFLD; 12.61 （1.24‐127.78）, 19.39 （5.23‐71.85）, and 93.21 （29.56‐293.90） for predicting ultrasonographic fatty liver; 1.78 （0.59‐5.44）, 3.01 （1.91‐4.77）, and 4.64 （3.52‐6.12） for predicting dyslipidemia, respectively compared with the non‐obese control group. The trend of hazards over groups was statistically significant （P0.01）. Conclusion The levels of lipid profile and the prevalence of NAFLD and dyslipidemia increased in parallel with the degree of obesity; As compared with the non‐obese control, the mixed obesity had the strongest association with NAFLD and dyslipidemia, followed by abdominal obesity and peripheral obesity in Chinese school‐age Children.

Molecular Epidemiological Analysis of Group A Streptococci Isolated from Children in Chaoyang District of Beijing, 2011:emm Types, Virulence Factor Genes and Erythromycin Resistant Genes

Group A streptococcus （GAS） causes a wide range of diseases in the human population. GAS diseases are more common in children than in adults, with clinical manifestations ranging from pharyngitis and impetigo to invasive infections and post streptococcal sequelae, such as acute rheumatic fever and acute post-streptococcal glomerulonephritis[1]. GAS harbors a host of virulence factors that contribute to its complex pathogenicity and differences in the disease severity and frequency. M protein, one of the major virulence factors, is encoded by the emm gene induces a type of specific host immune response and confers antiphagocytic properties.

A Potential Role for GLUT4 in Predicting Sepsis in Critically Ill Children

Background: This study investigated serum Glucose transporter (GLUT) 4 levels and examined the relationship between serum GLUT4 levels and sepsis in critically ill children. Methods: This was a retrospective study of 77 critically ill children and 33 non-diabetic healthy children (controls) who were admitted between 07/2015 and 05/2016. Patient data, clinical information, and blood samples were collected on admission, alongside a large number of laboratory parameters that were routinely assessed. Critically ill patients were divided into sepsis and non-sepsis/systemic inflammatory response syndrome (SIRS). Serum GLUT4 was measured using western blotting and enzyme-linked immunosorbent assays. Insulin resistance indexes, clinical data, laboratory parameters, and inflammatory cytokines were assessed. Results: GLUT4 serum levels were higher in critically ill children than in healthy children (90.5 vs. 30.3 μg/L, P 0.05). Compared to healthy children, hyperglycemic patients (n = 48) had elevated GLUT4 serum levels (30.3 vs. 103.7 g/L, P Conclusions: GLUT4 serum levels might be significantly increased in critically ill children compared with healthy children, particularly those in septic shock. Serum GLUT4 could predict disease severity.

Type 2 diabetes mellitus in children and adolescents

Type 2 diabetes mellitus is emerging as a new clinical problem within pediatric practice.Recent reports indicate an increasing prevalence of type 2 diabetes mellitus in children and adolescents around the world in all ethnicities,even if the prevalence of obesity is not increasing any more.The majority of young people diagnosed with type 2 diabetes mellitus was found in specific ethnic subgroups such as African-American,Hispanic,Asian/Pacific Islanders and American Indians.Clinicians should be aware of the frequent mild or asymptomatic manifestation of type 2 diabetes mellitus in childhood.Therefore,a screening seems meaningful especially in high risk groups such as children and adolescents with obesity,relatives with type 2 diabetes mellitus,and clinical features of insulin resistance(hypertension,dyslipidemia,polycystic ovarian syndrome,or acanthosis nigricans).Treatment of choice is lifestyle intervention followed by pharmacological treatment(e.g.,metformin).New drugs such as dipeptidyl peptidase inhibitors or glucagon like peptide 1 mimetics are in the pipeline for treatment of youth with type2 diabetes mellitus.However,recent reports indicate a high dropout of the medical care system of adolescents with type 2 diabetes mellitus suggesting that management of children and adolescents with type2 diabetes mellitus requires some remodeling of current healthcare practices.

Diagnosis,treatment and prevention of type 2 diabetes mellitus in children and adolescents

During the last two decades,there have been several reports of an increasing incidence of type 2 diabetes mellitus(T2 DM) in children and adolescents,especially among those belonging to minority ethnic groups.This trend,which parallels the increases in prevalence and degree of pediatric obesity,has caused great concern,even though T2 DM remains a relatively rare disease in children.Youth T2 DM differs not only from type 1 diabetes in children,from which it is sometimes difficult to differentiate,but also from T2 DM in adults,since it appears to be an aggressive disease with rapidly progressive β-cell decline,high treatment failure rate,and accelerated development of complications.Despite the recent research,many aspects of youth T2 DM still remain unknown,regarding both its pathophysiology and risk factor contribution,and its optimal management and prevention.Current management approaches include lifestyle changes,such as improved diet and increased physical activity,together with pharmacological interventions,including metformin,insulin,and the recently approved glucagonlike peptide-1 analog liraglutide.What is more important for everyone to realize though,from patients,families and physicians to schools,health services and policy-makers alike,is that T2 DM is a largely preventable disease that will be addressed effectively only if its major contributor(i.e.,pediatric obesity) is confronted and prevented at every possible stage of life,from conception until adulthood.Therefore,relevant comprehensive,coordinated,and innovative strategies are urgently needed.

Effect of hospital discharge plan for children with type 1 diabetes on discharge readiness,discharge education quality,and blood glucose control

BACKGROUND Type 1 diabetes is one of the most common chronic diseases in childhood.The number of type 1 diabetes patients in China still ranks fourth in the world.Therefore,children with type 1 diabetes in China are a group that needs attention.The management of type 1 diabetes mellitus(T1DM)involves many aspects of daily life.It is extremely challenging for children and their families.T1DM children have complex medical care needs.Despite the continuous development of therapeutic medicine and treatment technologies,blood glucose control in children with T1DM is still not ideal.They and their parents need to acquire more knowledge and skills before being discharged.AIM To explore the influence of hospital discharge plan based on parental care needs of children with T1DM on discharge readiness,quality of discharge education and blood glucose control level.METHODS In total,102 parents of children with type 1 diabetes were divided into control group and intervention group according to admission time.Fifty cases from February to June 2019 were selected as the control group,and 52 cases from July to October 2019 were selected as the intervention group to implement the discharge plan.The Readiness for Hospital Discharge Scale,Hospital Discharged Education Quality Scale and children's blood glucose metabolism indicators were used to compare the differences in discharge preparation,discharge education quality and blood glucose control between the two groups of children and their parents.RESULTS On the day of discharge,the two groups of children had the following scores of readiness for discharge:The intervention group score was 225.34±32.47,and the control group score was 208.68±29.31.The P value was 0.007,and the difference was statistically significant.The discharge education quality scores were as follows:The intervention group score was 135.11±19.86,the control group score was 124.13±15.56,the P value was 0.002 and the difference was statistically significant.Three months after discharge,the blood glucose metabolism indicator showed that the glycosylated hemoglobin value of the two groups was(7.45%±1.04%),and that of the control group was(8.04%±1.27%),P=0.012.Therefore,the improvement of parents'readiness for discharge,quality of discharge education and blood glucose metabolism indicators(glycosylated hemoglobin,fasting blood glucose and postprandial blood glucose)in the intervention group were better than those in the control group(P<0.05),and the difference was statistically significant.CONCLUSION The discharge plan for children with T1DM can help the children and their families realize the transition from hospital care to home self-management and improve the parents'readiness for discharge,thereby improving children’s blood glucose control levels.

Mechanisms of altered bone remodeling in children with type 1 diabetes

Bone loss associated with type 1 diabetes mellitus(T1DM)begins at the onset of the disease,already in childhood,determining a lower bone mass peak and hence a greater risk of osteoporosis and fractures later in life.The mechanisms underlying diabetic bone fragility are not yet completely understood.Hyperglycemia and insulin deficiency can affect the bone cells functions,as well as the bone marrow fat,thus impairing the bone strength,geometry,and microarchitecture.Several factors,like insulin and growth hormone/insulin-like growth factor 1,can control bone marrow mesenchymal stem cell commitment,and the receptor activator of nuclear factor-κB ligand/osteoprotegerin and Wnt-b catenin pathways can impair bone turnover.Some myokines may have a key role in regulating metabolic control and improving bone mass in T1DM subjects.The aim of this review is to provide an overview of the current knowledge of the mechanisms underlying altered bone remodeling in children affected by T1DM.

Neurofibromatosis Type 1 in Four Children Cases

Neurofibromatosis Type 1 (NF-1 or Von Recklinghausen disease) is an autosomal dominant genetic disease, characterized by an extreme variability of its clinical expression which is also found in the same family. Our work focuses on the exploitation of four cases of patients with NF-1 who were enrolled in the paediatric neurology consultation at Rabat Children’s Hospital. They are two infants and two children. Otherwise the diagnosis was made in front of the existence of café au lait and lentiginous spots in two boys, also the existence of café au lait spots and abnormalities in brain imaging in two girls. Thus an evolution was marked by a favorable outcome for three patients and neurological sequelae in one patient.

Parents' experience of caring for children with type 1 diabetes in China's Mainland: A qualitative study

BACKGROUND Parents of children with type 1 diabetes mellitus(T1DM)are under heavy caregiving stress,and parental caregivers'experience can affect the health outcomes of children with T1DM.AIM To describe the true inner feelings of parents caring for children with T1DM.METHODS Descriptive research methods were used to classify and summarize parents'experience when adapting to the role of caregivers for children with T1DM.The data was sorted and analyzed using content analysis.Themes of parents'experience caring for children with T1DM were refined,and their feelings were deeply investigated.RESULTS A total of 4 themes and 12 subthemes were identified:(1)Desire for information(disease-related information,home care information,and channels of information acquisition);(2)Skill guidance needs(insulin injection techniques,skills required for symptom management,and skills for parent-child communication);(3)Seeking emotional support(family support,peer support from other parents of children with T1DM,and professional support);and(4)Lack of social support(needs for financial support and needs for social security).Exploring the true experience of parents caring for children with T1DM is of great significance for helping them adapt to their role as caregivers.Nurses should provide professional guidance in terms of information,skills,emotion,and social support to parental caregivers.

Prediabetes in children and adolescents:An updated review

Prediabetes,the precursor of type 2 diabetes mellitus,is an intermediate stage between normal glucose homeostasis and overt diabetes.This asymptomatic metabolic state is increasingly prevalent in pediatric population and is very difficult to detect without appropriate screening.Studies have shown that a certain proportion of children with prediabetes will develop diabetes in a few years.Even more alarming is the evidence that youth-onset diabetes has a more aggressive clinical course with progressive beta-cell decline and accelerated endorgan damage.Despite its importance,several aspects involving prediabetes in childhood are disputed or unknown.This review presents the latest insights into this challenging entity and outlines a simplified screening approach to aid clinical practice.In summary,childhood prediabetes is an important clinical condition indicating the need for proper screening and timely intervention.

Clinical Demographic Patterns of Type 1 Diabetes in Saudi Children in Tabuk City, 2000-2010

We aimed to identify the variation in the clinical background of children diagnosed with type 1 diabetes mellitus (T1DM) at King Salman Military Hospital (KSMH), Tabuk City, Kingdom of Saudi Arabia, from 2000 to 2010. Methods: This retrospective observational study was based on the clinical records of pediatric diabetes outpatients at KSMH. All children aged Results: Of 313 patients recruited, female patients were predominant (p = 0.002). The mean age of onset was 6.46 years (standard deviation, 3.02). One-third of the newly diagnosed patients were overweight (35.5%). Diabetic ketoacidosis (DKA) was the presenting feature in 38.0% of patients, wherein female patients and those aged 0 - 3 years exhibited the highest likelihood of developing DKA (odds ratio, 1.7 and 2.9, respectively). Moreover, underweight children had a greater DKA incidence than healthy, overweight, or obese children (p = 0.02). Conclusion: This study provides additional data on T1DM in the population of the Kingdom of Saudi Arabia. In particular, we found a female predominance at presentation as well as 2 peaks for age at onset. Moreover, the BMI was lower in younger age groups overall, but was greater in older boys. Furthermore, the DKA rates were high in younger children. Thus, our data confirm the presence of variable clinical patterns in the Kingdom of Saudi Arabia, which requires further epidemiological analysis using national registry data.

Knowledge and Understanding of Type 1 Diabetes and Its Management among Saudi Children and Adolescents

Introduction: globally there is an increase of Type 1 diabetes among children. Poorly controlled Type1 diabetes is associated with the complication. Knowledge is a crucial factor in maintaining patient glycaemic control and adherence to treatment. Purpose: to explore knowledge and understanding of Type 1 diabetes and its management among children in Saudi Arabia. Methods: 32 semi structured interviews conducted with children and their parents. It was audio recorded and transcribed. The qualitative data was thematically analysed. NVivo 11 software was used to organise transcript. Results: Children and young people know the aggravating factors and the theoretical aspects of T1DM management but fail to adhere to the treatment regimen practically. Children and adolescents preferred school food;however, parents complained about the quality of school food. Conclusion: The study findings indicate a requirement to employ innovative and engaging ways of communicating with children and adolescents concerning the promotion of a positive lifestyle and healthy practices. There is a need for cooperation between schools and health ministries to increase awareness about T1DM management and complications.

Interaction between Cadmium and Zinc Levels in the Biological Samples of Type 1 Diabetic Mellitus Children, Reside in Different Areas of Sindh, Pakistan

Type 1 Diabetes mellitus (T1DM) is one of the familiar childhood immune-mediated onsets and can lead to early mortalities and morbidities. It can arise at any stage, but the peak of occurrence is reported less than 18 years of age. T1DM cases in Pakistan were less than 2% of the total diabetic population. The current work designed to assess the concentration of cadmium (Cd) and zinc (Zn) in blood, scalp hair and serum samples of T1DM children, age ranged 1 - 14 years of both genders. For comparison purpose, the age-matched referent subjects of both genders were tested. The microwave-assisted acid digestion procedure was used to determine the elemental analysis in the biological samples of T1DM children and referent subjects. The resulted data of certified reference material of blood, scalp hair, and serum validated the certainty of the designed method. The analysis of Zn was performed by flame atomic absorption spectrometry, while the Cd contents were determined by electrothermal atomic absorption spectrometry. T1DM affected children of both genders have lower Zn level in the blood, scalp hair, and serum samples. Whereas, the levels of Cd were found to be higher in the biological samples of T1DM affected children as compared to referent subjects. The finding of the current study is a significant hypothesis for medical experts, to diagnose the deficiency of essential (Zn) and toxicity of heavy/toxic element (Cd) in the biological specimen of T1DM affected children.

Intensive diabetes management and goal setting are key aspects of improving metabolic control in children and young people with type 1 diabetes mellitus

Diabetes control in children remains poor in spite of advances in treatment for last 10 years. The aim of this review was to look at various aspects of intensive therapy in the management of type 1 diabetes such as insulin regimes, role of target setting, psycho-educational approaches and self-management. To achieve good metabolic control, clear goal setting with adequate support for self-management are essential. Psycho-educational and behavioural interventions aimed at specific areas of management have shown significant improvement in quality of life and diabetes control.

Aicardi-Goutières syndrome type 7 in a Chinese child:A case report

BACKGROUND IFIH1 is a protein-coding gene.Disorders associated with IFIH1 include Aicardi-Goutières syndrome(AGS)type 7 and Singleton-Merten syndrome type 1.Related pathways include RIG-I/MDA5-mediated induction of the interferon(IFN)-α/βpathway and the innate immune system.AGS type 7 is an autosomal dominant inflammatory disorder characterized by severe neurological impairment.In infancy,most patients present with psychomotor retardation,axial hypotonia,spasticity,and brain imaging changes Laboratory assessments showed increased IFN-αactivity with upregulation of IFN signaling and IFN-stimulated gene expression.Some patients develop normally in the early stage,and then have episodic neurological deficits.CASE SUMMARY The 5-year-old girl presented with postpartum height and weight growth retardation,language retardation,brain atrophy,convulsions,and growth hormone deficiency.DNA samples were obtained from peripheral blood from the child and her parents for whole-exome sequencing and test of genome-wide copy number variation.Heterozygous mutations in the IFIH1 gene were found.Physical examination at admission found that language development was delayed,the reaction to name calling was average,there was no communication with people,but there was eye contact,no social smile,and no autonomous language.However,the child had rich gesture language and body language,could understand instructions,had bad temper.When she wants to achieve something,she starts crying or shouting.Cardiopulmonary examination showed no obvious abnormality,and abdominal examination was normal.Bilateral muscle strength and muscle tone were symmetrical and slightly decreased.Physiological reflexes exist,but pathological reflexes were not elicited.CONCLUSION We reported the clinical characteristics of a Chinese child with a clinical diagnosis of AGS type 7,which expanded the mutational spectrum of the IFIH1 gene.