Status and related factors of anxiety of primary caregivers of children with type 1 diabetes: a prospective study.

Primary caregivers of children with type 1 diabetes mellitus (T1DM) are prone to negative emotions. This study explored the anxiety status of the caregivers and analyzed the related factors. In this prospective study, 245 primary caregivers of T1DM children who were reexamined in the outpatient clinic of Children's Hospital affiliated to Zhengzhou University between April 2020 and Sep 2022 were surveyed with a questionnaire and the Hamilton Anxiety Rating Scale (HAMA). The detection rate of anxiety symptoms in T1DM primary caregivers was 21.2%, with a total score of HAMA score of 11.74 ± 2.50. There were significant differences between the anxiety and non-anxiety groups in treatment method, HbA1C to standard (≤7.0%), severe hypoglycemia in the last 1 year and the number of adolescent cases (χ2 = 15.798, p = 0.000; χ2 = 4.197, p = 0.040; χ2 = 5.291, p = 0.021; χ2 = 14.279, p = 0.000). Multivariable logistic regression analysis showed that insulin pump treatment, HbA1C to standard (≤7.0%) and adolescence were associated with anxiety in primary caregivers (OR = 4.040, 95%CI 1.969-8.289, p = 0.000; OR = 0.472, 95%CI 0.237-0.955, p = 0.037; OR = 2.952, 95%CI 1.495-5.831, p = 0.002). Pediatric endocrine care should pay more attention to the anxiety of the caregivers of adolescent T1DM children treated with insulin pumps while helping the children manage their disease.

[Clinical characteristics and genetic analysis of two children with Familial glucocorticoid deficiency type 1 due to variants of MC2R gene].

OBJECTIVE: To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene. METHODS: Two children with FGD1 diagnosed at the Henan Children's Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed. RESULTS: Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c.433C>T (p.R145C) and c.710T>C (p.L237P) in child 1, and c.145delG (p.V49Cfs*35) and c.307G>A (p.D103N) in child 2, among which c.710T>C (p.L237P) and c.145delG (p.V49Cfs*35) were unreported previously. CONCLUSION: FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.

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.

First Clinical Study on Long-Acting Growth Hormone Therapy in Children with Turner Sydrome.

Study on long-acting growth hormone (LAGH) therapy in Turner syndrome (TS) is a 2-year retrospective study including patients diagnosed with TS from 2018-2021. Patients were divided into four groups: Group 1 to 4 were low dose (0.1 mg/kg/ w), high-dose (0.2 mg/kg/w) LAGH, daily GH (0.38 mg/kg/w), and untreated control. The efficacy and safety data were analyzed. Seventy-five TS cases with the age 7.9±2.9 years and the bone age 6.8±2.8 years were recruited. In year 1: The change of height standard deviation score (ΔHtSDS) and height velocity (HV) in Group 2 were comparable to Group 3, both two groups were higher than Group 1. ΔHtSDS and HV in all GH treatment group were higher than untreated group. IGF1 increased in all treatment groups, only 4 cases had IGF1>3 SD. In year 2: ΔHtSDS and HV in Group 2 and 3 were comparable. Five cases had IGF1>3 SD. Correlation analysis for LAGH efficacy at year 1 indicated that baseline variables correlated with ΔHtSDS include: GH dose, CA (chronological age), and bone age (BA). The HV was positively correlated with baseline GH dose, HtSDS, IGF-1SDS and negatively correlated with baseline CA, BA, and BMI. No GH-related serious adverse effects were observed. The high-dose LAGH treatment in TS patients is effective and safe as daily GH for 2 years. The favorable prognosis factors include sufficient GH dose and early treatment. IGF1 monitoring and weight control are important.

Application of the FreeStyle®Libre Glucose Monitoring System in type 1 diabetes mellitus patients aged 1-4 years.

BACKGROUND: To investigate the analytical accuracy, safety performance, and user satisfaction (guardians of study participants) of the FreeStyle®Libre Glucose Monitoring System in the treatment of type 1 diabetes mellitus (T1DM), in children aged <4 years. METHODS: Sixteen hospitalized children with new onset T1DM, aged 4 months to 4 years, were enrolled in this study. Patients wore the sensor for 14 days; sensor scans were performed immediately and at 5, 10, and 15 min after capillary blood glucose (BG) measurements to evaluate the effectiveness of the device and the lag effect. RESULTS: The consensus error grid showed that 96.40% of values fell within zone A (no clinical impact) and 3.60% within zone B (little/no clinical impact). Overall, the mean absolute relative difference (MARD) was 9.34%, and was higher in the capillary BG <4.0 mmol/L group (15.18%) than in the 4-10 mmol/L (9.63%) and >10 mmol/L (7.17%) groups. The MARD increased gradually with scanning time extension, indicating a short lag effect. Regression analysis showed that a higher BG level was associated with a greater difference in FreeStyle®Libre System measurements. CONCLUSIONS: The use of the FreeStyle®Libre System in children aged 1-4 years is accurate and safe, and may be accurate down to 4 months, independent of patient characteristics.

Polyethylene glycol recombinant human growth hormone in Chinese prepubertal slow-growing short children: doses reported in a multicenter real-world study.

BACKGROUND: To evaluate the effectiveness of individualized-dose polyethylene glycol recombinant human growth hormone (PEG-rhGH) for short stature. METHODS: This real-world study enrolled children with short stature in 19 hospitals throughout China. They were treated with PEG-rhGH for 6 months. The starting dosage ranged from 0.10 to 0.20 mg/kg/week. The primary outcome was the change in height standard deviation score (ΔHt SDS). RESULTS: Five hundred and ten patients were included and grouped based on dosage as A (0.10-0.14 mg/kg/week), B (0.15-0.16 mg/kg/week), C (0.17-0.19 mg/kg/week), and D (0.20 mg/kg/week). The mean 6-month ΔHt SDS for the total cohort was 0.49 ± 0.27, and the means differed among the four dose groups (P = 0.002). The ΔHt SDS was lower in group A than in groups B (LSM difference [95%CI], -0.09 [-0.17, -0.01]), C (LSM difference [95%CI], -0.10 [-0.18, -0.02]), and D (LSM difference [95%CI], -0.13 [-0.21, -0.05]) after adjusting baseline covariates. There were no significant differences among groups B, C, and D. When the baseline IGF-1 was < -2 SDS or > 0 SDS, the △Ht SDS was not different among the four groups (P = 0.931 and P = 0.400). In children with baseline IGF-1 SDS of -2 ~ 0 SDS, a higher dosage was associated with a better treatment effect (P = 0.003), and the △Ht SDS was lower in older children than in younger ones (P < 0.001). CONCLUSIONS: PEG-rhGH could effectively increase height in prepubertal short children. When the baseline IGF-1 was < -2 SDS, 0.10 mg/kg/week could be a starting dose. In other IGF-1 statuses, 0.15-0.20 mg/kg/week might be preferred. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03249480 , retrospectively registered.

Pediatric Continuous Reference Intervals of Serum Insulin-like Growth Factor 1 Levels in a Healthy Chinese Children Population - Based on PRINCE Study.

OBJECTIVES: We aimed to establish age- and sex-dependent reference intervals for insulin-like growth factor 1 (IGF-1) based on the measurements of healthy Chinese children from the pediatric reference intervals in China study and to investigate whether body mass index (BMI) and height affect IGF-1 levels. METHODS: A total of 3753 individuals with eligible blood specimens resampled from the pediatric reference intervals in China population were enrolled as reference individuals. IGF-1 levels were measured using a chemiluminescent immunoassay kit. The lower limit and upper limit values of the reference individuals were calculated by defining the 2.5th and 97.5th percentiles. The skewness-median-coefficient of variation method was used to calculate the standard deviation score (SDS) of serum IGF-1, and cubic spline curves were applied to depict a smoothed curve for each age- and sex-specific stratification of the L, M, and S parameters. RESULTS: Serum IGF-1 levels increased with age from the age of 1 year, peaking at around the age of 13 years in girls and 15 years in boys and then began to decline (both P <.001). Before 14 years, IGF-1 levels were higher in girls than in boys at the same age, and the difference was statistically significant (P < .05), but there was no significant difference in the IGF-1 levels between girls and boys aged 14 to 16 and 18 years. The Spearman correlation coefficients of height SDS, weight SDS, and BMI SDS with IGF-1 SDS were 0.29, 0.33, and 0.20, respectively (P < .001). CONCLUSION: This study established age- and sex-specific normative IGF-1 data for Chinese children and adolescents between the ages of 1 and 19 years. The BMI and height SDS had no effect on IGF-1 levels in healthy children.

A cross-sectional survey of adrenal steroid hormones among overweight/obese boys according to puberty stage.

BACKGROUND: Obesity is associated with many chronic diseases including cortisol rhythm disorder and low testosterone. Furthermore, studies on obese children are quite limited and no concordance results have been obtained, especially for boys in puberty. Moreover, the sample sizes of previous studies were small, and were not representative. METHODS: We conducted a cross-sectional survey including 1148 boys aged 6-14 years, they were divided into overweight/obesity (OW/OB) group and normal weight (NW) group. Puberty status was assessed according to Tanner scale and testicular volume. Serum levels of pregnenolone, 17-OH progesterone, corticosterone, dehydroepiandrosterone (DHEA), and androstenedione were detected by LC-MS. Serum free testosterone and sex hormone-binding globulin (SHBG) levels were measured by chemiluminescence immunoassay. RESULTS: The 17-OH progesterone, DHEA, androstenedione and free testosterone levels of OW/OB boys at prepubertal stage or at the age 6 = < 10 years group were higher than those of the NW boys (all the P values were < 0.01). Furthermore, androstenedione and free testosterone levels were lower in OW/OB boys at late puberty, and the trend continued at the post pubertal stage for FT (P < 0.01-0.05). DHEA, androstenedione, and FT levels persisted to be higher at the 10~ < 12 years in OW/OB boys but not for 17-OH progesterone. FT level was lower in the OW/OB group at the 12~ < 15 years group. The SHBG levels in the OW/OB boys were lower than those in the NW ones at the 6~12 years group, and prepubertal to early pubertal stage. CONCLUSIONS: Premature adrenarche is more likely in OW/OB boys. More attention should be given to the lower androgen levels of OW/OB boys at late pubertal and post pubertal stages.

Influence of initial insulin dosage on blood glucose dynamics of children and adolescents with newly diagnosed type 1 diabetes mellitus.

OBJECTIVE: To investigate the effect of initial insulin dosage on blood glucose (BG) dynamics, ß-cell protection, and oxidative stress in type 1 diabetes mellitus. METHODS: Sixty newly diagnosed type 1 diabetes mellitus patients were randomly assigned to continuous subcutaneous insulin infusions of 0.6 ± 0.2 IU/kg/d (group 1), 1.0 ± 0.2 IU/kg/d (group 2), or 1.4 ± 0.2 IU/kg/d (group 3) for 3 wk. BG was monitored continuously for the first 10 d and the last 2 d of wk 2 and 3. A total of 24-hour urinary 8-iso-PGF2α was assayed on days 8, 9, and 10. The occurrence and duration of the honeymoon period were recorded. Fasting C-peptide and glycosylated hemoglobin (HbA1c) were assayed after 1, 6, and 12 months of insulin treatment. RESULTS: BG decreased to the target range by the end of wk 3 (group 1), wk 2 (group 2), or wk 1 (group 3). The actual insulin dosage over the 3 wk, frequency of hypoglycemia on wk 1 and 2, and median BG at the end of wk 1 differed significantly, but not 8-iso-PGF2α and the honeymoon period in the three groups. No severe hypoglycemia event was observed in any patient, but there was significant difference in the first occurrence of hypoglycemia. CONCLUSIONS: Differences in initial insulin dosage produced different BG dynamics in wk 1, equivalent BG dynamics on wk 2 and 3, but had no influence on short- and long-term BG control and honeymoon phase. The wide range of initial insulin dosage could be chosen if guided by BG monitoring.

Acupuncture for Primary Dysmenorrhea: A Meta-analysis of Randomized Controlled Trials.

Context • Primary dysmenorrhea (PD) is one of the most common complaints among young women. Acupuncture has been widely applied as a therapeutic modality in China and abroad for PD; however, the evidence for its benefits is still not convincing. Objective • The study intended to conduct a systematic review of randomized, controlled trials (RCTs) to evaluate the evidence regarding the use of acupuncture in treating PD. Design • The research team retrieved reports for RCTs published in 7 databases from their inception to March 2016, with no language restrictions: PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure database, the Chinese Biomedical database, and the Wanfang database. Setting • The study was conducted at the Beijing University of Traditional Chinese Medicine (Beijing, China). Participants • Participants in the reviewed studies were women aged 14 to 49 y who had received a diagnosis of PD in the absence of any visible pelvic pathology. Interventions • The types of acupuncture included traditional acupuncture, electroacupuncture, ear acupuncture, scalp acupuncture, superficial acupuncture, electrosuperficial acupuncture, wrist-ankle acupuncture, and abdominal acupuncture. Outcome Measures • The primary outcome was pain relief measured using a visual analogue scale (VAS), a verbal rating scale (VRS), or a numerical rating scale (NRS). The secondary outcomes included (1) overall improvement as measured by the short-form McGill pain questionnaire or symptom scale based on the Clinical Study Guideline for New Developed Chinese Medicine, (2) menstrual distress as measured by the Menstrual Distress Questionnaire, (3) quality of life as measured by a validated scale (eg, the short-form 36), and (4) adverse effects. Results • Twenty-three trials enrolling a total of 2770 patients were included in the review. Overall, most trials were of poor quality. Among the trials, only 6 were evaluated as having a low risk of bias, 3 of which indicated that acupuncture was statistically more effective than sham acupuncture-mean difference (MD), -3.51; 95% confidence interval (CI), -5.27 to -1.75; P < .0001; I², 0%-or no treatment-MD, -21.95; 95% CI, -25.45 to -18.45; P < .00001; I², 0%-on the VAS (0 to 100 mm). Acupuncture also showed superiority to the control arms on the VRS, the NRS, and the McGill pain questionnaire, but those findings had been influenced by methodological flaws. Conclusions • The available evidence suggests that acupuncture may be effective for PD and justifies future high-quality studies.

Congenital hyperinsulinism in Chinese patients: 5-yr treatment outcome of 95 clinical cases with genetic analysis of 55 cases.

AIM: The aim of this study is to investigate the clinical features, therapeutic outcomes, and genetic mutations of congenital hyperinsulinism (CHI) in Chinese patients. METHODS: The clinical features and therapeutic outcomes of 95 CHI cases were recorded, and genetic analyses were conducted to identify mutations in ABCC8 and KCNJ11 in 55 cases. Direct sequencing was carried out in 25 of the cases with ABCC8 and KCNJ11 mutations. Additionally, 16 samples with no mutations and the remaining 30 samples were sequenced using Ion Torrent platform. RESULTS: Clinical misdiagnosis occurred in 36/95 (38%) of the cases. Most (82/95; 84%) of the patients were given diazoxide therapy combined with age-dependent frequent feeding, which was effective in 54/95 (66%) cases. The side effects of diazoxide included sodium and water retention, gastrointestinal reactions, polytrichia, and thrombocytopenia. Five patients were treated with octreotide for 1-4 months, of which 80% (4/5) showed a positive response. Non-surgical therapy was effective in 71/95 (75%) cases. Of the four children who received subtotal pancreatectomy, only one had a good outcome. The remission rate of hypoglycemia was 59% for children over 2-yr-old. The CHI-related gene mutation rate was 38% for potassium channel-related genes. Early onset of CHI and a lower diazoxide response rate were associated with potassium-ATP channel gene mutations. CONCLUSION: Age-dependent frequent feeding is an acceptable therapy for CHI. Non-surgical therapy may be highly effective, in part, due to the low rate of potassium channel gene mutations. Surgical outcomes are unreliable without 18F-fluoro-L-DOPA positron emission tomography. Therefore, we do not recommend operation without definitive identification of the pathologic type.

Effect on glycemia in rats with type 2 diabetes induced by streptozotocin: low-frequency electro-pulse needling stimulated Weiwanxiashu (EX-B 3) and Zusanli (ST 36).

OBJECTIVE: To investigate the effect of low frequency electro-pulse acupuncture (EA) on blood glucose in rats with streptozotocin-induced type 2 diabetes, and the possible mechanism underlying the action. METHODS: Rat models were established with high fat feeding and intraperitoneal injection of streptozotocin (STZ) (30 mg/kg). Rats with a random blood glucose > 16.7 mmol/L and blood glucose at 2 h-point of oral glucose tolerance test (OGTT) > 11.1 mmol/L were included as diabetic rats, and randomly divided into model group, EA Weiwanxiashu (EX-B 3) group, EA Zusanli (ST 36) group, glimepiride group, and EA non-acupoint group (n = 12). EA (2 Hz continuous wave, 2 mA, 20 min/day, 6 days/week, 4 weeks) and intra-gastric administration of glimepiride were applied as interventions. With fasting blood glucose and OGTT tested at the end of the intervention, the study observed the patterns of hypoglycemic effects. For mechanism study, it observes hematoxylin and eosin staining and Masson staining of pancreas paraffin sections, protein expression of glucagon- like peptide 1 receptor (GLP-1R) in the pancreas and skeletal muscle, glucose transporter 4 (GLUT4) protein expression in skeletal muscle membrane, to detect whether EA controls blood glucose via regulation of GLP-1R. RESULTS: EA Weiwanxiashu (EX-B 3) significantly increased model rats' pancreas GLP-1R, and GLUT4 of skeletal muscle membrane; the therapy significantly decreased model rats' skeletal muscle GLP-1R, restored pancreas morphology, and reduced fasting blood glucose and insulin resistance indices. CONCLUSION: EA Weiwanxiashu (EX-B 3) alone has significant effect on glycemia. EA Weiwanxiashu (EX-B 3) plus glimepiride further strengthen the effect. The regulation of the GLP-1R in pancreas and skeletal muscle might be mechanism underpinning the effect.

Effect of miniscalpel-needle on relieving the pain of myofascial pain syndrome: a systematic review.

OBJECTIVE: To evaluate the effect and safety of miniscalpel-needle (MSN) on reducing the pain of myofascial pain syndrome (MPS). METHODS: We reviewed the available literatures inception up to February 2014 using Pubmed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Database and Wanfang Database. RESULTS: Eight randomized controlled trials were finally identified. The main controls involved acupuncture, medications, injection, massage and cupping. We found that all of the studies agreed on the potential benefit of MSN as a strategy for MPS and the superiority compared to the controls, however, randomized methods applied in most of the trials could be criticized for their high or unclear risk of bias. Further research is also needed to clarify questions around the appropriate frequency and number of treatment sessions of MSN. CONCLUSION: This review shows that MSN might have the effect on MPS, even though there were some limitations in the studies included in the review. Studies with robust methodology are warranted to further test its pain-relieving effect on MPS.

Association between obesity and anemia in an nationally representative sample of United States adults: a cross-sectional study.

Introduction: Few studies are about the relationship between anemia and obesity, and previous studies have only paid attention to BMI. Methods and Results: We first included body fat percentage (BF%) as an assessment indicator and divided it into quartiles, grouped participants into obesity and non-obesity used data from NHANES database. After adjustment for age, gender, ethnicity, education and family income, the level of soluble transferrin receptor (sTfR), and incidence of elevated CRP or HsCRP were progressively higher with increased BF%, whereas mean cell volume (MCV), natural logarithm (Ln) serum ferritin (SF), and Ln SF/sTfR were progressively reduced. Although a higher prevalence of anemia and lower hemoglobin was observed with increased BF%, but there was no statistical difference. Women in the highest BF% group demonstrated a significantly higher risk of iron deficiency compared to those in the lowest BF% group. Discussion: BF% should be given more attention, and women with high BF% should pay attention to iron deficiency.

Relationship of Glucagon-like Peptide 1 and Peptide YY with Catch-up Growth in Children Born Small for Gestational Age

Objective: Children born small for gestational age (SGA) are at a greater risk of developing insulin resistance, type 2 diabetes, and cardiovascular disease in adulthood. Gastrointestinal peptides, some secreted by intestinal L cells, regulate glucose and lipid metabolism and act on the hypothalamus to regulate energy homeostasis. The aim of this study was to explore whether gastrointestinal peptides are involved in metabolic disorders in SGA, which remains unclear. Methods: The secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were investigated in prepubertal children born SGA, the differences between catch-up growth and persistent short stature were compared, and correlation with glucose and lipid metabolism was analyzed. GLP-1, PYY, insulin-like growth factor 1, glucose, insulin, and lipid concentrations were analyzed in prepubertal children aged 4-10 years, stratified into three groups: short-SGA (SGA-s), catch-up growth SGA, and normal growth appropriate for gestational age (AGA). Results: Fasting GLP-1 and PYY concentrations were significantly lower in the SGA group than in the AGA group (p<0.05), and the GLP-1 level in infants born SGA with catch-up growth was lower than that in the SGA-s group (p<0.05). In the SGA population, GLP-1 showed a weak negative correlation with catch-up growth (r=-0.326) and positive correlation with fasting insulin (r=0.331). Conclusion: Lower GLP-1 concentrations may be associated with abnormal glucose metabolism in prepubertal children born SGA with catch-up growth. This is indirect evidence that impaired intestinal L cell function may be involved in the development of metabolic complications in SGA children.

Analysis of genetic and clinical characteristics of androgen insensitivity syndrome: a cohort study including 12 families.

CONTEXT: Androgen insensitivity syndrome (AIS) manifests itself as variable symptoms of under-virilization in patients with 46,XY disorders caused by androgen receptor (AR) gene variants. This large-sample study aimed to correlate the genotypes and phenotypes to the fertility of individuals. METHODS: This was a cohort study that analyzed the genetic and clinical characteristics of patients with AIS from a single center in China. RESULTS: The 117 patients were divided into 53 with complete AIS (CAIS) and 64 with partial AIS (PAIS). At their first visit, the median age was 1.83 years (0.92-4.17), and the external masculinization score was 3.0 (2.0-6.0). At the last follow-up, 92% (49/53) of patients with CAIS maintained their female gender, and 94% (60/64) of patients with PAIS were raised as males. No gender anxiety was observed in this study. Eighty-eight AR variants were identified, with 31 (35%) being unreported. Moreover, 24% (21/88) occurred more than once. The variants that appeared most frequently were located at amino acid 841, including p.R841H (n = 5) and p.R841C (n = 2). Variants p.N706S, p.R856H, and p.A871V were each observed 4 times. In terms of inheritance, 83% of patients with parental verification inherited variants from their mothers. We also observed that the variants from 1 case were inherited from his maternal grandfather who had hypospadias. CONCLUSION: Most children with PAIS were raised as males. The abundance of maternally inheritable variants and the presence of case of preserved fertility indicate the fertility potential in patients with AIS. Hence, we recommend a careful evaluation of gonadectomy when fertility preservation is being considered.

A Gender-, Age-, and Weight Status-Specific Analysis of the High Prevalence of Hyperuricemia Among Chinese Children and Adolescents with Obesity.

Objective: To explore the gender-, age-, and weight status-specific prevalence of hyperuricemia (HUA) and its associated risk factors among Chinese children and adolescents with obesity. Methods: A total of 1329 children aged 2-17 years, who were diagnosed with obesity and hospitalized in our center from January 2016 to December 2022 were recruited. They were divided into mild obesity, moderate obesity, and severe obesity groups. HUA was defined as fasting serum uric acid level >420 µmol/L for boys and >360 µmol/L for girls. Multivariate logistic regression analyses were performed to identify risk factors for HUA. Results: The highest proportion of hospitalized obese children was aged 10-13 years comprising 677 (50.9%) followed by those aged 6-9 years comprising 348 (26.2%) whereas the least proportion was aged 2-5 years comprising 76 (5.7%). The above differences in age distribution were still present in subgroup analyses according to weight status. Most hospitalized obese children were boys (64.7%), especially in the severe obesity group (75.0%). The overall estimated prevalence of HUA in obese children was 54.8%. It presented a gradual increase trend over the last 7 years, with more rapidly in boys than in girls. Subgroup analysis by weight status showed that the prevalence of HUA was higher in children with moderate obesity (64.3%) and severe obesity (64.2%) when compared with mild obesity (48.2%) (P all<0.01). Boys reached a relatively high HUA incidence level (≥60%) at age 12, which occurred about 2 years later than in girls (age 10). With 12 years as the cut-off point, a high prevalence of HUA (≥60%) was observed in both genders. Multivariable logistic regression analyses showed that boy (OR=2.844, 95% CI 2.024-3.998), age (OR=1.253, 95% CI 1.155-1.360), BMI-Z score (OR=2.132, 95% CI 1.438-3.162), fasting blood glucose (OR=0.907, 95% CI 0.860-0.956), phosphorus (OR=4.123, 95% CI 2.349-7.239), alkaline phosphatase (OR=1.002, 95% CI 1.001-1.004), creatinine (OR=1.067, 95% CI 1.037-1.098), urea nitrogen (OR=1.193, 95% CI 1.032-1.378), aspartate aminotransferase (OR=1.016, 95% CI 1.002-1.030), triglycerides (OR=1.339, 95% CI 1.075-1.667), and high-density lipoprotein cholesterol (OR=0.381, 95% CI 0.160-0.910) were independently associated with odds of HUA (P all<0.05). Conclusion: The prevalence of HUA in Chinese obese children and adolescents is unexpectedly high. Childhood HUA was significantly associated with obesity. Gender and age differences were observed in the association between childhood obesity and HUA. Obese children aged ≥12 years should be focused on screening the risk of HUA.

Role of intestinal flora in the development of nonalcoholic fatty liver disease in children.

In China, 45% of adolescents with obesity develop fatty liver disease, a condition that increases the long-term risk of developing cirrhosis and liver cancer. Although the factors triggering nonalcoholic fatty liver disease (NAFLD) vary in children, the composition of intestinal microflora has been found to play an increasingly important role. However, evidence is limited on the prevalence of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) in Chinese children. Therefore, this study aimed to evaluate the fecal microbiome of Chinese children with NAFLD and further analyze the potential of flora in regulating NAFLD-related symptoms and metabolic functions. Specifically, the study applied a 16S rRNA and metagenomic sequencing to the fecal samples of pediatric patients with NAFLD, NASH, and NAFL, as well as healthy controls, to explore the correlation among NAFLD-related indexes, metabolic pathways, and gut flora. The findings showed that some fecal microbiota had a negative correlation with body mass index, and various NAFLD-related bacteria, including Lachnoclostridium, Escherichia-Shigella, and Faecalibacterium prausnitzii, were detected. Consequently, the study concluded that the variation in gut microbiota might be more important in improving NAFLD/NASH compared with single species, providing a microbiota diagnostic profile of NAFLD/NASH.IMPORTANCEThis study aims to characterize the gut microbiota in Chinese children with nonalcoholic fatty liver disease (NAFLD) through 16S rRNA and metagenomic sequencing. The results highlight the association between fecal microbiota and NAFLD in Chinese children, demonstrating distinct characteristics compared to adults and children from other countries. Based on the sequencing data from our cohort's fecal samples, we propose a microbiota model with a high area under the curve for distinguishing between NAFLD and healthy individuals. Furthermore, our follow-up study reveals that changes in the relative abundance of microbial biomarkers in this model are consistent with variations in patients' body mass index. These findings suggest the potential utility of the microbiota model and microbial biomarkers for diagnosing and treating NAFLD in children.

The Mechanical Properties and Degradation Behavior of 3D-Printed Cellulose Nanofiber/Polylactic Acid Composites.

Polylactic acid (PLA) has been widely used in many fields because of its good biodegradability, biocompatibility, and renewability. This work studied the degradation behavior and mechanical properties of cellulose nanofiber (CNF)/PLA composites. In vitro degradation experiments of 3D-printed samples were conducted at elevated temperatures, and the degradation characteristics were evaluated by mechanical tests, gel permeation chromatography (GPC), differential scanning calorimetric (DSC), and scanning electron microscope (SEM). The results indicated that the addition of CNF (0.5 wt%) accelerated the degradation rate of PLA. The decreases in number average molecular weight (Mn) and weight average molecular weight (Mw) of composites were 7.96% and 4.91% higher than that of neat PLA, respectively. Furthermore, the tensile modulus of composites was 18.4% higher than that of neat PLA, while the strength was 7.4% lower due to poor interfacial bonding between CNF and PLA. A mapping relationship between accelerated and normal degradation showed that the degradation experienced during 60 days at 37 °C was equivalent to that undergone during 14 days at 50 °C; this was achieved by examining the alteration in Mn. Moreover, the degradation process caused a notable deformation in the samples due to residual stress generated during the 3D printing process. This study provided valuable insights for investigating the in vitro degradation behavior of 3D-printed products.