Acute treatment of bilateral rTMS combined with antidepressants on the plasma fatty acids for major depressive episodes.

Bilateral repetitive transcranial magnetic stimulation (B-rTMS) has been largely used in the treatment of major depressive disorder (MDD). Nonetheless, information on the acute treatment by B-rTMS combined with antidepressants (ADs) on the plasma fatty acids in MDD is limited. The present study focused on depressive symptoms; Plasma was obtained from 27 adult patients with MDD at baselinephase (MDD), after 2 weeks of treatment (MDD-2w), and 27 healthy controls (HC). Meanwhile, we evaluated the composition of short-chain fatty acids (SCFAs) and medium-and long-chain fatty acids (MLCFAs) in the plasma. Consequently, the levels of Isobutyric acid, Caproic acid, and Propionic acid were low both in the MDD and MDD-2w groups and negatively correlated with the scores of HAMD and HAMA. Besides, minimal changes were observed between the MDD and HC groups, whereas significant MLCFA levels were high in the MDD-2w group. Moreover, we developed combined panels that could effectively differentiate MDD from HCs (AUC=0.99), MDD-2w from HC (AUC=0.983), and MDD from MDD-2w (AUC=0.852). These findings may provide a reference for the use of B-rTMS combined with ADs against the acute phase of depressive episodes and shed light on the relationship between plasma FAs and MDD.

Monitoring Hepatocellular Carcinoma Using Tumor Content in Circulating Cell-Free DNA.

PURPOSE: The objective of the study was to evaluate the use of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. EXPERIMENTAL DESIGN: We included 67 patients with hepatitis B virus-related HCC, of whom 17 had paired pre- and posttreatment samples, and 90 controls. Additionally, in a prospective cohort with hepatitis B virus surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA. RESULTS: High tumor content was associated with advanced tumor stage (P < 0.001) and poor survival after HCC diagnosis [HR = 12.35; 95% confidence interval (CI) = 1.413-107.9; P = 0.023]. Tumor content turned negative after surgery (P = 0.027), whereas it remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95% CI = 92.2%-99.7%). In pre-HCC samples, the tumor content increased from 0.014 at 4 years before diagnosis to 0.026 at 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95% CI = 11.5%-37.8%) within 1 year before diagnosis to 30.4% (95% CI = 13.2%-52.9%) at the Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 81.8% (95% CI = 59.7%-94.8%) at stage B, and 95.5% (95% CI = 77.2%-99.9%) at stage C. CONCLUSIONS: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC 1 yearearlier than clinical diagnosis and in predicting patient prognosis.

Circulating DNA genome-wide fragmentation in early detection and disease monitoring of hepatocellular carcinoma.

Genome-wide circulating cell-free DNA (ccfDNA) fragmentation for cancer detection has been rarely evaluated using blood samples collected before cancer diagnosis. To evaluate ccfDNA fragmentation for detecting early hepatocellular carcinoma (HCC), we first modeled and tested using hospitalized HCC patients and then evaluated in a population-based study. A total of 427 samples were analyzed, including 270 samples collected prior to HCC diagnosis from a population-based study. Our model distinguished hospital HCC patients from controls excellently (area under curve 0.999). A high ccfDNA fragmentation score was highly associated with an advanced tumor stage and a shorter survival. In evaluation, the model showed increasing sensitivities in detecting HCC using 'pre-samples' collected ≥4 years (8.3%), 3-4 years (20.0%), 2-3 years (31.0%), 1-2 years (35.0%), and 0-1 year (36.4%) before diagnosis. These findings suggested ccfDNA fragmentation is sensitive in clinical HCC detection and might be helpful in screening early HCC.

Influence of disease course and comprehensive management on blood glucose level in children and adolescents with type 2 diabetes mellitus.

AIMS/INTRODUCTION: The aim of the present study was to evaluate the status of glycemic control, and assess the effects of the disease course and comprehensive management measures on the blood glucose level in children and adolescents with type 2 diabetes mellitus. MATERIALS AND METHODS: The study collected the clinical data of type 2 diabetes patients in Beijing Children's Hospital from January 2015 to September 2020. Patients were grouped based on the disease course to compare their glycated hemoglobin (HbA1c) level, islet ß-cell function, insulin resistance and comprehensive management measures. RESULTS: Of the 170 participants, the median disease course was 2.0 years (interquartile range [IQR] 1.0-4.0 years). The baseline HbA1c was 11.2% (IQR 9.2-12.4%). According to the grouping by the disease course, the median HbA1c was the lowest (5.7% [IQR 5.3-6.1%]) in the half-year course group and the highest in the 4-year course group (9.0 [IQR 6.8%-11.3%]). Compared with the group with a disease duration <2 years, patients in the >4 years group had a lower proportion of patients with HbA1c <7% (29.2% vs 66.2%), a lower homeostasis model assessment of ß-cell function, and a lower proportion with a controlled diet, moderate-intensity exercise, regular follow up and no drug treatment. We deemed HbA1c as the dependent variable, and found that disease duration, homeostasis model assessment of ß-cell function at follow up, continuous moderate-intensity exercise, regular review and treatment regimen were significant influencing factors for glycemic control. CONCLUSIONS: Children and adolescents with type 2 diabetes and a prolonged disease course showed poor glycemic control and decreased islet ß-cell function. A good lifestyle, especially moderate-intensity exercise, can help such cases better control their blood glucose level.

EBV antibody and gastric cancer risk: a population-based nested case-control study in southern China.

BACKGROUND: We aim to clarify the controversial associations between EBV-related antibodies and gastric cancer risk. METHODS: We analysed the associations between serological Epstein-Barr nuclear antigen 1 immunoglobulin A (EBNA1-IgA) and viral capsid antigen immunoglobulin A (VCA-IgA) by enzyme-linked immunosorbent assay and the risk of gastric cancer in a nested case-control study originated from a population-based nasopharyngeal carcinoma (NPC) screening cohort in Zhongshan, a city of southern China, including 18 gastric cancer cases and 444 controls. Conditional logistic regression was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). RESULTS: All the sera of cases were sampled before diagnosis and the median time interval was 3.04 (range: 0.04, 7.59) years. Both increased relative optical density (rOD) values of EBNA1-IgA and VCA-IgA were associated with higher risks of gastric cancer with age adjusted ORs of 1.99 (95%CI: 1.07, 3.70) and 2.64 (95%CI: 1.33, 5.23), respectively. Each participant was further classified as high or medium/low risk based on a combination of two anti-EBV antibody levels. Participants in the high-risk group had substantially higher odds of developing gastric cancer than that in the medium/low risk group with an age adjusted OR of 6.53 (95%CI: 1.69, 25.26). CONCLUSIONS: Our research reveals positive associations between EBNA1-IgA and VCA-IgA and gastric cancer risk in southern China. We thus postulate that EBNA1-IgA and VCA-IgA might appear to be potential biomarkers for gastric cancer. More research to further validate the results among diverse populations and investigate its underlying biological mechanism is needed.

Rubber band ligation versus coagulation for the treatment of haemorrhoids: a meta-analysis of randomised controlled trials.

Non-surgical therapies have the advantage of lower postoperative pain and complication rates compared with surgical therapies. Rubber band ligation and coagulation are two kinds of non-surgical therapies. The aim of this study is to compare the clinical outcomes of rubber band ligation and coagulation. A systematic review was conducted to identify randomised clinical trials that compare rubber band ligation and coagulation treatments for haemorrhoids. PubMed and Web of Science were searched, from inception to April 30th,2022. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-nine studies were identified. Nine trials met the inclusion criteria. All trials were of moderate methodological quality. No significant difference was found between rubber band ligation and coagulation in terms of efficacy rate, postoperative prolapse rate, recurrence rate and postoperative urine retention rate after treatment. Patients undergoing rubber band ligation had higher postoperative pain rate and lower postoperative bleeding rate than patients undergoing coagulation. The subgroup analysis showed that there was no significant difference between rubber band ligation and infrared coagulation or non-infrared coagulation in terms of efficacy rate, postoperative bleeding and postoperative urine retention rate after treatment. Patients undergoing rubber band ligation had a higher postoperative pain rate than patients undergoing infrared coagulation or non-infrared coagulation. We believe that coagulation for haemorrhoids still has a good future. PROSPERO registration number CRD42022311281.

Pre-diagnostic anti-EBV antibodies and primary liver cancer risk: a population-based nested case-control study in southern China.

BACKGROUND: We aimed to investigate associations between pre-diagnostic anti-Epstein-Barr virus (EBV) antibodies, including interactions with hepatitis B virus (HBV), and risk of primary liver cancer in southern China. METHODS: In a population-based nested case-control study, we measured pre-diagnostic immunoglobulin A (IgA) against EBV nuclear antigen 1 (EBNA1) and viral capsid antigen (VCA) in 125 primary liver cancer cases and 2077 matched controls. We also explored the interaction between HBV surface antigen (HBsAg) and anti-EBV antibodies. RESULTS: Participants with positive EBNA1-IgA, positive VCA-IgA or single-positive anti-EBV antibodies had two-fold odds of developing liver cancer, compared with seronegative subjects. The odds ratios (ORs) between the relative optical density of EBNA1-IgA and VCA-IgA and primary cancer, controlling for age and HBsAg, were 1.59 (95% confidence interval (CI): 1.17, 2.14) and 1.60 (95% CI: 1.07, 2.41), respectively. Subjects with both HBsAg and anti-EBV antibody seropositivity were at 50-fold increased risk compared with those negative for both biomarkers (OR: 50.67, 95% CI: 18.28, 140.46), yielding a relative excess risk due to interaction of 30.81 (95% CI: 3.42, 114.93). CONCLUSION: Pre-diagnostic seropositivity for EBNA1-IgA and/or VCA-IgA was positively associated with primary liver cancer risk, especially in combination with HBsAg positivity. EBV may interact with HBV in the development of primary liver cancer, and anti-EBV antibodies might be potential biomarkers for primary liver cancer in this high-risk population.

Incidence of Childhood Type 1 Diabetes in Beijing During 2011-2020 and Predicted Incidence for 2025-2035: A Multicenter, Hospitalization-Based Study.

INTRODUCTION: China has a low incidence of type 1 diabetes mellitus (T1DM); however, based on the large population, the absolute numbers are high. Our aim was to assess the incidence of childhood T1DM in Beijing during 2011-2020, predicted incidence for 2025-2035, and to determine the incidence of diabetic ketosis or diabetic ketoacidosis (DK/DKA) in this population. METHODS: Data on patients aged less than 15 years of age with newly diagnosed T1DM between January 1, 2011 and December 31, 2020 was obtained from five tertiary hospitals in Beijing and retrospectively analyzed. RESULTS: In all, 636 children aged less than 15 years were diagnosed with T1DM during 2011-2020. The incidence of T1DM was 3.11-5.46 per 100,000 per year, with an average increase of 5.10% per year. The age-specific incidence for ages 0-4 years, 5-9 years, and 10-14 years was 2.97, 4.69, and 4.68 per 100,000 per year, respectively. The highest average annual increase (7.07%) in incidence was for the youngest age group. DK or DKA was present at the time of diagnosis of T1DM in 84.6% of patients. The age-specific incidence of T1DM among children aged less than 15 years was predicted to be 7.32, 11.4, and 11.52 per 100,000 in 2035 for ages 0-4 years, 5-9 years, and 10-14 years, respectively. CONCLUSIONS: The was a gentle increase in the incidence of childhood T1DM during 2011-2020 in Beijing. This increase is expected to continue for the next 15 years.

The Current Status of Antisense Gene Therapies for Bacteria-caused Diseases Challenges and Opportunities.

Bacteria-caused diseases continue to pose a serious threat to human health. The current situation of overused antibiotics against those diseases further spurs and exacerbates the ever-increasing drug resistance problems, which really leaves us very few options to combat those nasty bugs. Gene therapies based on the antisense oligonucleotide, though developed more than 40 years ago, did not reform the current treatments as originally expected. Along with the advances of new delivery technologies, this old field thrives again. In addition, newly evolving gene-editing tools based on the CRISPR-Cas system shed new light on this old field, bringing a breeze of hope to gene therapies for bacteria-caused diseases. As a fast-growing field, we strive to summarize in this review the recent progress in using gene therapies in those areas, analyze the potential challenges or problems from using antisense or gene-editing tools for targeting bacterial diseases and seek to explore any potential solutions to the current dilemmas. As a short review, we will focus our discussion mainly on antisense oligonucleotide-based gene therapies while briefly touching on the CRISPR-Cas based ones as the latter is just beginning to get more attention for application in the prokaryotic kingdom.

An effective preselection criterion for MODY with an increasingly positive genetic testing rate by NGS: results from two cohorts of Chinese children.

The purpose of this study was to determine the frequency of maturity-onset diabetes of the young (MODY) in two selected cohorts of Chinese children with diabetes and clinically suspected MODY, using next-generation sequencing (NGS). Ninety-three children who met the comprehensive criteria of suspected MODY were enrolled in two cohorts. A custom NGS panel or a whole exon group was used for sequencing. We identified 55/93 (59.1%) children with pathogenic and likely pathogenic MODY variants. Forty-two (76.3%) were confirmed to have the GCK (MODY2) mutation. Additionally, five had the HNF1A (MODY3), two the HNF1B (MODY5), one the 17q12 microdeletion (MODY5), two the HNF4A (MODY1), two the ABCC8 (MODY12), and one the PDX1 mutation (MODY4). Of these, 13 novel variants were detected in different genes. By comparing the gene-positive with gene-negative children, we found that discriminatory factors for MODY at diagnosis included lower HbA1c [7.4% vs. 10.2% (53 vs. 86 mmol/mol); P = 0.002], lower body mass index z score (0.2 vs. 1.0; P = 0.01), lower onset age (8.1 vs. 11.2 years; P = 0.001), and lower C-peptide (1.4 vs. 2.5 ng/mL; P = 0.02). In conclusion, the criteria used in this study for screening MODY are effective, and MODY2 is the most common subtype (76%), followed by MODY3 and MODY5. Some rare MODY subtypes have been reported in Chinese children.NEW & NOTEWORTHY We proved the clinical suspicion of maturity-onset diabetes of the young (MODY) according to the comprehensive criterion for next-generation sequencing testing, which helps to identify both common and rare MODYs, leading to accurate diagnosis and personalized treatment.

Phase 1 multicenter, dose-expansion study of ARX788 as monotherapy in HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma.

ARX788 is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate with AS269 as cytotoxic payload. In this phase 1 multicenter dose-expansion clinical trial, patients with HER2-positive advanced gastric/gastroesophageal junction adenocarcinoma failing to respond to prior trastuzumab-based standard treatment were enrolled. Between July 15th, 2019, and March 14th, 2022, 30 participants were enrolled. Twenty-eight (93.3%) patients experienced at least one drug-related adverse event (AE) and 13.3% experienced grade 3 ARX788-related AEs. The confirmed objective response rate is 37.9% (95% confidence interval [CI]: 20.7%-57.7%) and the disease control rate is 55.2% (95% CI: 35.7%-73.6%). With a median follow up of 10 months, the median progression-free survival and overall survival are 4.1 (95% CI: 1.4-6.4) and 10.7 months (95% CI: 4.8-not reached), respectively. The median duration of response is 8.4 (95% CI: 2.1-18.9) months. ARX788 is well tolerated and has promising anti-tumor activity in patients with HER2-positive advanced gastric adenocarcinoma (ChinaDrugTrials.org.cn: CTR20190639).

The critical BMI hypothesis for puberty initiation and the gender prevalence difference: Evidence from an epidemiological survey in Beijing, China.

Background: Although previous studies suggested that there is a certain level of body fat mass before puberty can be initiated, most studies have focused on girls. Objective: To investigate the relationship between precocious puberty and physical growth in school-aged children in Beijing, China. Methods: 7590 Chinese children (3591 girls and 3999 boys) aged 6-11 years were recruited in Beijing, China. Body mass index (BMI) categories were defined by WHO Child Growth Standards and central obesity were defined by sex-specific waist-to-height ratio cut-offs (≥0.46 for girls, ≥0.48 for boys). Sexual development was assessed using Tanner criteria. Results: The prevalence of general obesity and central obesity among boys was higher than that in girls. Girls had a significantly higher precocious puberty rate than boys (5.93% vs. 0.87%), particularly in those aged 7 years old (9.20%). Children in the general obesity and central obesity groups have a higher prevalence of precocious puberty and earlier median ages for the attainment of Tanner B2/T2. For girls with Tanner stages≥II at 6-year-old and 7-year-old, the mean BMI was equivalent to the 50th centile of a normal 9.9-year-old and 11.9-year-old girl, respectively. The mean BMI of boys with Tanner stages≥II at 7-year-old and 8-year-old was correspondent to the 50th centile of a normal 14-year-old and 15.3-year-old boy, respectively. For girls, general obesity appears to contribute to the risk of the development of precocious puberty to a greater extent than central obesity does. For boys, central obesity, but not general obesity, was an independent risk factor for precocious puberty. Conclusions: The prevalence of childhood obesity and precocious puberty was high in China. Precocious puberty was correlated with a large BMI. Boys had a higher threshold of BMI for puberty development than girls. Children with precocious puberty, particularly those with central obesity, should be aware of adverse cardiovascular events.

The Effect of BMI, Age, Gender, and Pubertal Stage on Bone Turnover Markers in Chinese Children and Adolescents.

Objectives: To ascertain the associations of serum bone turnover markers (BTMs) levels with body mass index (BMI) in Chinese children and adolescents, and whether the influence of BMI, age, pubertal stage on BTMs varied by gender. Methods: A total of 500 students (180 controls and 320 children and adolescents with overweight/obesity) aged 9-14 years were randomly selected from the Chinese National Survey on Students Constitution and Health Cohort. Serum levels of BTMs, including bone formation marker bone alkaline phosphatase (BAP), collagen type 1 C-terminal propeptide (CICP), and bone resorption markers C-terminal telopeptide of type-I collagen (CTX) were determined by commercial enzyme-linked immunosorbent assay kits. The associations among BMI, age, gender, pubertal stage, and BTMs were analyzed. Results: Serum levels of CICP and CTX in overweight/obese children and adolescents were lower than those in controls (p<0.05). Moreover, after subgroup analysis stratified by gender, the decreased serum CICP and CTX levels in overweight/obese children and adolescents were observed only in boys (p<0.05). After adjustment of age and pubertal stage, there was a negative correlation between serum BAP and BMI in both boys and girls (p<0.05). However, the correlations between serum CICP, CTX levels, and BMI were significant in boys but not in girls. Serum BAP and CICP levels were independently correlated with BMI, age, gender, and pubertal stage, while CTX levels were independently correlated with BMI, age, and gender (p<0.05). BAP, CICP, and CTX levels showed a clear age, gender, and pubertal stage dependence with significantly higher values in boys (p<0.05). Conclusions: Our findings support the associations between serum BTMs levels and BMI in Chinese children and adolescents, and suggest age, gender, and pubertal stage differences in this relationship that warrant future studies.

A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening.

Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10-7 to 4.79 × 10-44). By incorporating the PRS into EBV-serology-based NPC screening, the test's positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.

Effectiveness of online expressive writing in reducing psychological distress among the asymptomatic COVID-19 patients in Fangcang Hospitals: A quasi-experiment study.

Objective: This study aimed to assess the applicability and effectiveness of an online format of expressive writing (EW) in reducing psychological distress among the asymptomatic COVID-19 patients in Fangcang Hospitals with a quasi-experiment. Method: Altogether 244 patients were assigned to the EW group(n=122) and the control group(n=122). Besides the routine psychological intervention (broadcast relaxation training at a fixed time) in Fangcang hospitals, The EW group was engaged in 8-day theme-based adaption EW intervention, whereas the control group received no interventions. All the participants were tested with the Brief Profile of Mood States (BPOMS) and Inpatient Mental Health Preliminary Screening Scale(IMHPS) before and after the intervention. After the intervention, the writing quality and intervention satisfaction of the EW group were evaluated by a self-designed writing quality questionnaire and EW satisfaction questionnaire. Results: The results indicated that the EW significantly improved in the BPOMS test, whereas the control group showed no significant change. The IMHPS score in the control group was statistically deteriorated than that before intervention, whereas the EW group showed no significant change. The writing quality was highly correlated with the score change of BPMOS. The overall satisfaction of patients with EW was 81.13%. Conclusion: EW can reduce psychological distress among the asymptomatic COVID-19 patients in Fangcang Hospitals. The higher the quality of writing, the greater the improvement of mood states. As a new form of psychological intervention in Fangcang hospitals with high patient satisfaction, EW has a value of popularization and application.

Associations Between Sleep Duration, Wake-Up Time, Bedtime, and Abdominal Obesity: Results From 9559 Chinese Children Aged 7-18 Years.

Objective: To investigate the associations of sleep duration, wake-up time, bedtime, and childhood abdominal obesity, and to test whether there is a weekday/weekend difference and the potential modifying role of sex. Methods: This cross-sectional study was based on the Students' Constitution and Health Survey and included 9559 students (4840 boys and 4719 girls) aged 7-18 years (7227 aged 7-12 years, 2332 aged 13-18 years). They were divided into two groups (control group and group with abdominal obesity). The physical measurements included children and youth body height, body weight, and waist circumference (WC). A parent-report questionnaire was used to collect the information about parent characteristics as well as lifestyle and sleep patterns (sleep duration, bedtime, and wake-up time of weekdays and weekends) of children and youth. Results: The prevalence of abdominal obesity was 30.57% and the percentages of sleep duration <9 hours/day, wake-up time before 07:00 am on weekdays and weekends, bedtime after 10:00 pm on weekends were significantly higher in the group with abdominal obesity. After adjusting for confounders, sleep duration <9 hours/day on weekends was inversely related to abdominal obesity in the overall subjects, regardless of their sex and age, while bedtime after 10:00 pm on weekends was inversely related to abdominal obesity only in the overall subjects, boys, and children aged 7-12 years. Logistic regression models in all subjects showed that shorter hours of weekends sleep duration were associated with greater risks of abdominal obesity, even after adjusting for all confounders, including wake-up time and bedtime. The adjusted odds ratios and 95% confidence intervals of abdominal obesity (with ≥10 hours/day as the reference group) for children with 9-10 hours/day, 8-9 hours/day, and <8 hours/day of weekend sleep duration were 1.23 (1.04-1.46), 1.59 (1.32-1.91) and 1.83 (1.42-2.36), respectively. Specifically, after stratification by sex and age, this phenomenon was only observed in boys and children aged 7-12 years. Conclusions: Sleep duration and bedtime on weekends were independently associated with the risk of childhood abdominal obesity, particularly in boys and children aged 7-12 years.

High Prevalence of Obesity but Low Physical Activity in Children Aged 9-11 Years in Beijing.

OBJECTIVE: To investigate the prevalence and associated factors of childhood overweight/obesity in the Shunyi district of Beijing, China. METHODS: This study adopted a cross-sectional survey and included 10,855 children aged 6-18 years in the Shunyi district of Beijing, China. Analyses were stratified by age group (6-8, 9-11, 12-14, and 15-18 years). RESULTS: The prevalence of overweight and obesity among children aged 6-18 years was high with 17.62% and 29.05% in boys, 17.57% and 18.04% in girls, respectively. Both boys and girls aged 9-11 years had the highest rate of obesity in comparison with the other age groups, though the differences in children aged 9-11 years and 12-14 years were not statistically significant. Compared with age 6-8 years, age 9-11 years (OR=1.59, 95% CI 1.41-1.79, P<0.01) and 12-14 years (OR=1.26, 95% CI 1.48-1.73, P<0.01) were independently positively associated with obesity. Importantly, in all subjects, the percentages of being physically active (exercise time ≥120 minutes/week) were lower in children aged 9-11 years in comparison to children in other age groups. This phenomenon remained when this comparison was performed respectively in the normal-weight, overweight, and obesity groups. Even after adjustment for other potential confounders, the probability of being physically active (exercise time ≥120 minutes/week) was lower in children aged 9-11 years (OR=0.86, 95% CI 0.78-0.94, P<0.01), but higher in children aged 12-14 years (OR=1.91, 95% CI 1.69-2.17, P<0.01) and aged 15-18 years (OR=2.22, 95% CI 1.85-2.66, P<0.01), when compared with children aged 6-8 years. CONCLUSION: Children aged 9-11 years had a higher prevalence of obesity, but a lower percentage of being physically active. Targeted intervention programs in this key group are needed to address this problem in China.

Clinical and genetic characteristics of hypophosphatasia in Chinese children.

BACKGROUND: Hypophosphatasia (HPP) is a rare inherited disorder, which is caused by loss-of-function mutations in the ALPL gene. HPP is a heterogeneous disease that has a wide spectrum of phenotypes. Few studies were carried out in the Chinese population with HPP, especially in children. METHODS: The clinical and genetic characteristics of 10 Chinese children with HPP who were referred to the Beijing Children's Hospital were described. Previously reported HPP cases of children in China were also reviewed. RESULTS: A total of 33 cases were identified, which included 2 perinatal lethal HPP, 10 infantile HPP, 10 childhood HPP, and 11 odonto HPP. The male-to-female ratio was 24:9. The average age at onset was 0.69 years (ranged from 2 h after birth to 14 years), while the average age at clinical diagnosis was 3.87 years (ranged from 2 h after birth to 19 years). Serum alkaline phosphatase (ALP) levels were significantly decreased in patients with perinatal lethal/infantile HPP when compared with those with the mild forms of HPP childhood/odonto HPP (P < 0.01). Although serum phosphate levels were not different (P > 0.05), serum calcium levels were elevated, and serum intact parathyroid hormone levels were decreased in patients with perinatal lethal/infantile HPP in comparison with those with the childhood/odonto HPP (P all < 0.01). Genetic analyses identified 40 mutations in 31 HPP cases, including 28 missense mutations, 9 frameshift mutations, 2 splice junction alterations, and 1 regulatory mutation. Of which, 5 novel mutations were identified in our present study: 2 frameshift mutations (p.Arg138GlyfsTer27, p.Leu511Profs*272); 2 missense mutations (p.Ala176Val, p.Phe268Leu), and 1 splice junction alteration (c.297+5G>A). Compound heterozygous mutations accounted for 80.6% of all variants. No mutational "hot-spot" was found. Most mutations of ALPL were located in exons 5, 7, 10, and 3. Notably, subjects that carrying single heterozygous mutations showed milder phenotypes of HPP, while subjects with nonsense mutations were associated with a severer phenotype. CONCLUSIONS: HPP is a rare disease with often delayed diagnosis, and the incidence of HPP in China may be seriously underestimated. The present study expands the phenotypic and genotypic spectrum and the understanding of HPP in Chinese children. These findings will be useful for clinical assessment and shorten the diagnosis time for pediatric HPP in China.

Clinical features and predictors of remission in children under the age of 7 years with Graves' disease.

IMPORTANCE: Graves' disease (GD) is rare in children under the age of 7 years. Children with this disease exhibit greater thyrotoxicity at diagnosis and require a longer course of medical therapy, compared with pubertal and postpubertal children and adults. OBJECTIVE: To investigate the clinical features and identify predictors of remission in children under the age of 7 years with GD. METHODS: This retrospective study included 77 children who were diagnosed with GD under the age of 7 years and were treated in the Department of Endocrinology, Beijing Children's Hospital from 2010 to 2018. Clinical manifestations, laboratory data, and follow-up records were collected for all patients. Children who achieved remission of treatment with methimazole were compared with those who had persistent disease to identify which variables were associated with remission; multiple logistic regression and Cox regression analyses were used to evaluate interactions among predictive variables. RESULTS: Sixty-three boys and 14 girls were included; the median age at diagnosis was 4.2 years (interquartile range: 3.2-5.3 years). Forty-six (56.7%) patients had no family history of thyroid disease, 17 patients had family history of thyroid disease and 14 patients with unknown family history. Of the 77 patients, 18 (23.4%) patients achieved remission of treatment with methimazole and 59 patients did not; moreover, 51 (66.2%) had Graves' ophthalmopathy. Univariate analyses revealed no significant differences between the remission group and non-remission group in terms of age at diagnosis, sex, initial goiter size, or initial thyroid hormone concentration. However, there were a trend of correlation between the initial level of thyroid peroxidase antibody (TPOAb) and remission status (univariate analysis OR 1.002, P = 0.038; multivariate analysis OR 1.004, P = 0.019). Similar results were observed in univariate analysis of the initial thyrotropin receptor antibody (TRAb) level, but this association was not significant in multivariate analysis. Cox regression analyses revealed that children with high TRAb level required longer duration of remission, compared with low TRAb level (OR 0.950, 95% CI 0.904-0.997, P = 0.037). INTERPRETATION: Initial TRAb level was an independent predictor of remission outcome in young children under the age of 7 years with GD. Initial TRAb level may predict the likelihood of remission in patients with young-age-of-onset GD.

Efficacy and safety of octreotide treatment for diazoxide-unresponsive congenital hyperinsulinism in China.

IMPORTANCE: Octreotide is an off-label medicine for congenital hyperinsulinism (CHI), but is currently widely used for treatment of patients with CHI. Thus far, variable efficacy and adverse effects have been reported for octreotide. OBJECTIVE: The present study evaluated the efficacy and safety of a subcutaneous octreotide injection for treatment of diazoxide-unresponsive CHI in China. METHODS: This study was a retrospective review of children with diazoxide-unresponsive CHI who were treated with a subcutaneous octreotide injection. The efficacy and side effects of the treatment were assessed. RESULTS: Twenty-five Chinese children (15 boys) were involved in the study. Their median age at diagnosis was 8 weeks (range, 1-24 weeks) and median age at the final follow-up was 1.8 years (range, 0.3-3.3 years). Octreotide therapy effectively increased blood glucose levels in all patients. The intravenous glucose infusion rate was reduced in all patients. Twenty-one patients gradually discontinued the intravenous glucose infusion while receiving octreotide combined with frequent carbohydrate/glucose-rich feeding. Among patients with a monoallelic ATP-sensitive potassium (KATP) channel mutation, 50.0% showed gradual remission during follow up, indicating that the octreotide treatment may be a feasible alternative to surgery, especially for patients with monoallelic KATP-channel mutations. Transient elevation of liver enzymes occurred in 20.0% of patients, while asymptomatic gallbladder pathology occurred in one patient. The growth rates of these patients were normal (height standard deviation score was 0.3 ± 1.5 at the final follow-up). INTERPRETATION: Octreotide was a well-tolerated, effective therapy for most children with diazoxide-unresponsive CHI.