AIMS:Glucokinase regulatory protein gene (GCKR) polymorphisms have been linked to progressive renal dysfunction in diabetic populations. However, their role in early renal injury of diabetic kidney disease (DKD) remains unclear. This study aimed to investigate the association between GCKR genetic variants and early renal impairment in newly diagnosed early-onset type 2 diabetes mellitus (T2DM). METHODS:A total of 337 newly diagnosed early-onset T2DM patients from a prospective cohort were enroled. Baseline characteristics, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR) were collected. Seven single nucleotide polymorphisms (SNPs) in GCKR were genotyped using ASAMD microarrays. Participants were divided into normal (UACR < 30 mg/g) and elevated albuminuria (UACR ≥ 30 mg/g) groups. Logistic regression and multivariate linear regression were performed to evaluate the relationship between GCKR genotypes and UACR. RESULTS:The patients had a mean age of 33.25 ± 5.38 years. Median eGFR was 119.33 mL/min/1.73 m2, and median UACR was 14.97 mg/g; 107 patients (31.8%) presented with elevated UACR. Carriers of the GCKR rs1260326 T/T genotype exhibited significantly higher median UACR compared with C/T + C/C carriers (22.85 vs. 13.53 mg/g, p = 0.021). The rs1260326 T allele was independently associated with increased UACR under the additive genetic model (p = 0.003) adjusted for sex, age, body mass index (BMI), glycated haemoglobin (HbA1c), and systolic blood pressure (SBP). CONCLUSIONS:The GCKR rs1260326 T allele is independently associated with early renal injury in newly diagnosed early-onset T2DM. This genetic variant may serve as a predictive marker for early DKD risk stratification in this high-risk population.

To evaluate the diagnostic yield and clinical value of a phenotype-driven genomic testing strategy in fetuses with central nervous system (CNS) abnormalities. In this retrospective single-center study, 966 fetuses with CNS abnormalities detected by prenatal ultrasound and/or fetal magnetic resonance imaging were included. All cases underwent copy number variation sequencing (CNV-seq), while karyotyping and trio exome sequencing (trio-ES) were performed based on clinical indications and parental preference. Fetuses were stratified into isolated-single, isolated-complex, and non-isolated subgroups according to CNS involvement and extracranial abnormalities. Diagnostic yields were compared across phenotypic subgroups and common CNS phenotypes. Among 966 fetuses with prenatal CNS abnormalities, pathogenic or likely pathogenic (P/LP) variants were identified in 12.63

Aim Monogenic diabetes is a group of disorders arising from single gene mutations with a clear pathophysiology, most of which present with impaired beta cell function rather than insulin resistance. This study aims to evaluate the ability of TyG index and polygenetic risk score (PRS) to identify multi-type beta cell monogenetic diabetes (beta-cell-MgD) in Chinese early-onset type 2 diabetes (EOD) population. Methods A prediction model for beta-cell-MgD was established by logistic regression analysis in Cohort 1 (92 beta-cell-MgD, 512 EOD). Model performance was evaluated by receiver operating characteristic curves (ROC) and validated in an independent case-control sample (Cohort 2, 35 beta-cell-MgD, 50 EOD) and a newly diagnosed drug-naive EOD cohort (Cohort 3, 7 beta-cell-MgD, 176 EOD). PRS was constructed based on Genome-wide genotyping data from participants in Cohort 3. The ability of PRS to identify beta-cell-MgD was tested by ROC. Results The TyG-MgD score based on age at diagnosis, BMI and TyG presented a good performance to distinguish beta-cell-MgD (AUC=0.769), and achieving AUCs of 0.966 and 0.754 respectively in validation cohorts. At the optimal cutoff point -16.19, the model achieved a sensitivity of 66.3% and a specificity of 75.39%, allowing one case of beta-cell-MgD identified among every three patients. -16.85 could be used as the screening threshold prioritizing 80% sensitivity (with 59% specificity). Models combining TyG-MgD with East Asian PRS and beta-cell dysfunction-high proinsulin partitioned polygenetic score showed AUCs of 0.842 and 0.834 respectively for indentifying beta-cell-MgD. Conclusion We developed a clinical prediction model as a simple screening tool for multi-type beta-cell-MgD, identifying who are most likely to benefit from next genetic sequencing in Chinese population. PRS might be helpful for further screening of MgD.

BackgroundDepression is a common mental health condition that can manifest at various stages of life, including the early stages such as childhood and adolescence. In particular, adolescence is a critical period where depression can present with numerous significant and severe symptoms, such as persistent sadness, behavioral changes, and difficulties in academic performance and social interactions. These symptoms, if left untreated, can have long-lasting effects and may recur in adulthood. Early identification and monitoring of depression are therefore essential to ensure timely intervention.The Short Mood and Feelings Questionnaire (SMFQ) is a widely used tool for measuring depression symptoms in adolescents. This study aimed to assess the SMFQ using Item Response Theory (IRT) in adolescents and determine optimal cutoff points for a revised version.MethodsUsing IRT and the Graded Response Model (GRM), we evaluated the SMFQ in 906 Chinese adolescents (average age 15 years). Items 1, 3, 4, and 6 were removed, resulting in the SMFQ-9. Reliability and validity were assessed using Cronbach’s alpha, and Receiver Operating Characteristic (ROC) analysis was conducted to determine cutoff points.ResultsWe validated the reliability and validity of the SMFQ-9, with the structure showing a Cronbach’s alpha as high as 0.86. It achieved significant correlations with three criterion questionnaires, and the correlation between SMFQ-9 and full version SMFQ reached 0.975. ROC analysis established an optimal cutoff value of 4.5, with an AUC of 0.985.ConclusionsThe SMFQ-9 retains the robustness of the original SMFQ, improves efficiency, reduces respondent burden, and is a reliable tool for assessing mood in adolescents in clinical and research settings.

OBJECTIVE:Tic disorders (TD) is a common neurodevelopmental disorder in children and adolescents, often co-occurring with psychiatric comorbidities and significantly impairing functioning. Symptom network analysis can identify key nodes for targeted interventions. METHODS:Children and adolescents diagnosed with TD at Beijing Children's Hospital (May 2024-Feb 2025) were assessed using nine standardized scales covering tic symptoms and eight related psychological dimensions. Network analysis was applied to examine the symptom structure. Subgroup analyses were performed to compare network characteristics by gender and developmental stage. RESULTS:715 TD patients were analyzed. In total sample, the tic symptoms (TIC) was directly linked to premonitory urges symptoms (PUT) and ADHD symptoms (ADH), and indirectly to depressive symptoms (DEP) and anxiety symptoms (ANX), with DEP as the central node (strength = 1.42). Centrality analysis highlighted DEP (strength = 1.42), neuroticism (NEU, strength = 1.27), and ANX (strength = 0.97) as key influencers. Gender-based analysis revealed stronger TIC-NSI (non-suicide self-injury, p = 0.020) and ANX-MPD (mobile-phone dependence, p = 0.041) connections in females. Developmental analysis revealed a stronger ADH-NEU link in children (p = 0.002), while TIC node (p = 0.024) and DEP node (p = 0.049) was more pronounced in adolescents. CONCLUSIONS:TD symptoms were closely associated with premonitory urges and ADHD symptoms, while depressive symptoms, anxiety symptoms, and neuroticism emerged as central nodes in the network. These findings highlight the importance of comprehensive intervention strategies for achieving more sustained therapeutic outcomes in TD.

BACKGROUND:Maturity-onset diabetes of the young resulting from mutations of the NEUROD1 gene (NEUROD1-MODY) is a rare form of diabetes and has not been well studied. We aimed to estimate its prevalence in Chinese patients with early-onset type 2 diabetes mellitus (EOD) and summarize its clinical and genetic characteristics. METHODS:We performed next-generation sequencing in 679 patients with EOD to screen rare variants in NEUROD1 exons and evaluated the effects of variants using in vitro experiments. All the reported NEUROD1-MODY cases were reviewed. Patients carrying pathogenic or likely pathogenic variants were diagnosed with NEUROD1-MODY according to the American College of Medical Genetics and Genomics guidelines. RESULTS:Four rare variants were identified in 679 patients with EOD, but only P197H decreased the transcriptional activity in in vitro functional assays to an extent comparable to the well-known mutation causing NEUROD1-MODY. Its frequency was pretty higher in the European population (0.024) than that in the East Asian population (0.00034) according to the gnomAD database. Twenty-eight previously reported patients could be confirmed as diagnosed. The patients in Asia had a lower body mass index and a higher rate of ketosis compared with Caucasians, and the mutations present in Asia often occurred in the transactivation domain. Neurological abnormalities were observed in 10.7% of the patients with NEUROD1-MODY. CONCLUSIONS:NEUROD1-MODY in Chinese patients with EOD is not common (≤ 0.15%). The P197H might account for MODY in Chinese with a higher penetrance than Caucasian and needs further exploration. The possible differences of phenotypes exist between the two ethnic populations.

OBJECTIVE:Gain-of-function (GOF) variants of KCNJ11 cause neonate diabetes and maturity-onset diabetes of the young (KCNJ11-MODY), while loss-of-function (LOF) variants lead to hyperinsulinemia hypoglycemia and subsequent diabetes. Given the limited research of KCNJ11-MODY, we aimed to analyse its phenotypic features and prevalence in Chinese patients with early-onset type 2 diabetes (EOD). DESIGN, PATIENTS AND MEASUREMENTS:We performed next-generation sequencing on 679 Chinese EOD patients to screen for KCNJ11 exons variants. Bioinformatics prediction and the American College of Medical Genetics and Genomics guidelines was used to determine the pathogenicity and diagnosed KCNJ11-MODY. A literature review was conducted to investigate the phenotypic features of KCNJ11-MODY. RESULTS:We identified six predicted deleterious rare variants in six EOD patients (0.88%). They were classified as uncertain significance (variant of uncertain significance [VUS]), but more common in this EOD cohort than a general Chinese population database, however, without significant difference (53/10,588, 0.50%) (p = .268). Among 80 previously reported patients with KCNJ11-MODY, 23.8% (19/80) carried 9 (32.1%) LOF variants, who had significantly older age at diagnosis, higher birthweight and higher fasting C-peptide compared to patients with GOF variants. Many patients carrying VUS were not correctly diagnosed. CONCLUSIONS:Some rare variants of KCNJ11 might contribute to the development of Chinese EOD, although available evidence has not enough power to support them as cause of KCNJ11-MODY. The clinical features of LOF variants were different from GOF variants in KCNJ11-MODY patients. It is necessary to evaluate the pathogenicity of VUS through function experiments.

Objective:This study explores the correlation between coping style, quality of life, and illness uncertainty in the family caregivers of patients with liver cancer.Methods:Employing convenience sampling, 210 family caregivers of patients with liver cancer who met the admission criteria were selected from a grade A infectious disease hospital in Beijing between January and December 2022. A cross-sectional survey was conducted using the Simplified Coping Style Questionnaire, Caregiver Quality of Life, and the Mishel Uncertainty in Illness Scale for Family Members. This study analysed the correlations between coping styles, quality of life, and illness uncertainty in these caregivers.Results:The study found that family caregivers of patients with liver cancer had average scores for illness uncertainty (83.44 ± 11.86), coping style (33.19 ± 9.79; both positive [23.02 ± 6.81] and negative [10.17 ± 5.05]), and quality of life (169.53 ± 32.46). A negative association was observed between illness uncertainty in these caregivers and positive coping style (r = -0.207, p = 0.003), physical status (r = -0.182, p = 0.008), psychological status (r = -0.200, p = 0.004), and social adaptation (r = -0.229, p = 0.001).Conclusion:The study concludes that illness uncertainty in family caregivers of patients with liver cancer is at a moderate level. Furthermore, there is a notable correlation between illness uncertainty, coping style, and quality of life in these caregivers.

BackgroundThe reported prevalence rate of anxiety disorder in the paediatric population varies widely between different counties. Currently, there is no national epidemiological surveyof childhoodanxiety disorder in China. This study aims to investigate the national prevalence of anxiety disorder, the distribution profiles of different subtypes and its comorbidity rates among school students.MethodsA nationwide epidemiological survey of mental disorders in school students aged 6–16 years was conducted. Participants were randomly recruited from five provinces in China. The Child Behavior Checklist was used to screen students at high risk for mental disorders. The final diagnosis was made based on the Diagnostic and Statistical Manual-IV. The point prevalence and comorbidity rate of anxiety disorder were calculated, and the difference between age, sex and socioeconomic status groups was also compared.ResultsGeneralised anxiety disorder (GAD) was the most common anxiety disorder in school-attending children and adolescents, with a prevalence rate of 1.3% (95% CI: 1.2 to 1.3). Separation anxiety and specific phobia were more common in children than in adolescents. Girls had a higher prevalence of panic disorder (0.3% vs 0.2%, χ2=14.6, p<0.001) and agoraphobia (0.9% vs 0.8%, χ2=4.3, p=0.03) than that of boys. We found no significant difference between developed and less developed areas. Girls were more likely to have panic disorder and GAD than boys, with ratios of 2.13:1 and 1.01:1, respectively. The co-occurrence of anxiety disorder and attention-deficit and disruptive behaviour disorder was very common, ranging from 40% to 85%.ConclusionsAnxiety disorder was prevalent among school students in China, and comorbidity with attention-deficit and disruptive disorder was very common. The data imply that screening for anxiety disorder is needed in school settings. Policies should be adapted to provide psychological services to children and adolescents. A comprehensive assessment is recommended in clinical practice.

The efficacy of probiotics, prebiotics, or synbiotics in children and adolescents with overweight or obesity remains uncertain. This systematic review evaluates their intervention effects through a network meta-analysis of randomized clinical trials (RCTs). Searches of 4 electronic databases until January 7, 2024, yielded 17 papers reporting on 15 RCTs involving 820 participants. Multiple-strain probiotics (MSP) showed significant efficacy in reducing BMI (Mean Difference (MD) -2.13 kg/m2, 95% credible interval (CrI) [-2.7, -1.57]), waist circumference (MD -1.34 cm, 95% CrI [-2.33, -0.35]), total cholesterol (MD -6.55 mg/dL, 95% CrI [-10.61, -2.45]), triglycerides (MD -3.71 mg/dL, 95% CrI [-5.76, -1.67]), leptin (MD -3.99 ng/mL, 95% CrI [-4.68, -3.3]), and hypersensitive C-reactive protein (Hs-CRP) (MD -1.21 mg/L, 95% CrI [-1.45, -0.97]). Synbiotics were effective in reducing BMI-z score (MD -0.07, 95% CrI [-0.10, -0.04]) and LDL-C (MD -1.54 mg/dL, 95% CrI [-1.98, -1.09]) but led to a slight increase in fasting glucose (MD 1.12 mg/dL, 95% CrI [0.75, 1.49]). Single-ingredient prebiotics and single-strain probiotics also had some beneficial effects on BMI and Hs-CRP, respectively. Moderate to low evidence suggests MSP may be a potential choice for improving BMI and reducing lipids, leptin, and Hs-CRP levels, implying that MSP could aid in managing pediatric obesity and related metabolic issues by modulating the gut microbiota. Although synbiotics show their favorable effects on body metrics and lipid control, their potential impact on blood glucose currently prevents them from being an alternative to MSP for treating pediatric obesity. Further large-scale, well-designed studies are needed to confirm these findings.

We report the clonal spread and evolution of high-risk Pseudomonas aeruginosa sequence type 463 co-producing KPC-2 and AFM-1 carbapenemases isolated from hospital patients in China during 2020-2022. Those strains pose a substantial public health threat and surveillance and stricter infection-control measures are essential to prevent further infections.

Context Maturity-onset diabetes of the young 4 (MODY4) is caused by mutations of PDX1; its prevalence and clinical features are not well known. Objective This study aimed to investigate the prevalence and clinical characteristics of MODY4 in Chinese people clinically diagnosed with early-onset type 2 diabetes (EOD), and to evaluate the relationship between the PDX1 genotype and the clinical phenotype. Method The study cohort consisted of 679 patients with EOD. PDX1 mutations were screened by DNA sequencing, and their pathogenicity was evaluated by functional experiments and American College of Medical Genetics and Genomics guidelines. MODY4 was diagnosed in individuals with diabetes who carry a pathogenic or likely pathogenic PDX1 variant. All reported cases were reviewed for analyzing the genotype-phenotype relationship. Result 4 patients with MODY4 were identified, representing 0.59% of this Chinese EOD cohort. All the patients were diagnosed before 35 years old, either obese or not obese. Combined with previously reported cases, the analysis revealed that the carriers of homeodomain variants were diagnosed earlier than those with transactivation domain variants (26.10 +/- 11.00 vs 41.85 +/- 14.66 years old, P < .001), and the proportions of overweight and obese individuals with missense mutation were higher than those with nonsense or frameshift mutations (27/34 [79.4%] vs 3/8 [37.5%], P = .031). Conclusion Our study suggested that MODY4 was prevalent in 0.59% of patients with EOD in a Chinese population. It was more difficult to identify clinically than other MODY subtypes owning to its clinical similarity to EOD. Also, this study revealed that there is some relationship between genotype and phenotype.

Early-onset polyhydramnios during pregnancy can be caused by X-linked transient antenatal Bartter syndrome. Most of the reported cases were molecularly diagnosed after birth, whereas few cases were diagnosed in the fetus period. We received a pregnant woman who had polyhydramnios detected by ultrasound imaging at 25 weeks of gestation, and treated with magnesium sulfate, indomethacin and an amnioreduction at 30 weeks of gestation, whereas amniotic fluid decreased spontaneously since 32 weeks of gestation. Prenatal molecular testing showed the fetus carried MAGED2 hemizygous variant c.967C>T [p. (Asp323*)] inherited from the mother. The preterm boy did not present with polyuria and electrolytes and acid-base imbalance in the early neonatal period, and had good development without polyuria at the age of 20 months. We presented the phenotypes of a Chinese case with a prenatal diagnosis of X-linked transient antenatal Bartter syndrome and his response to prenatal indomethacin treatment. Early identification of the condition helps to provide appropriate prenatal genetic counseling and postnatal management.

Background Life events and parenting styles might play an important role in children’s mental health. Aims This study aims to explore how life events and parenting styles influence children’s mental health based on a Chinese sample. Methods A total of 3535 participants had at least one mental disorder (positive group), while a total of 3561 participants had no mental disorders (negative group). The Child Behavior Checklist (CBCL), Adolescent Self-Rating Life Events Check List (ASLEC) and Egna Minnen Beträffande Uppfostran (EMBU) were used for screening these two groups. Results CBCL total scores differed significantly by sex in the Positive group according to the Mann–Whitney tests (Z = −5.40, p < 0.001). Multiple regression analyses showed that the dimensions of punishment ( p = 0.014) and other ( p = 0.048) in the ASLEC scale can significantly predict CBCL total scores in the Positive group. Sex, age and overprotection from the father were risk factors ( p < 0.001) according to binary logistic regression. Conclusions Life events and parenting styles may have impacts on mental health. Fathers play a very important role in children’s growth. Punitive education and fathers’ overprotection might be risk factors for children’s mental health. Impact It is a large sample (3535) study of Chinese children and adolescents It provides evidence that life events and parenting styles have impacts on mental health and that fathers play a very important role in children’s growth. It is conducive to the development of interventions for the mental health of children and adolescents.

Objective: To observe the clinical benefit of cluster nursing mode in RICU patients with acute exacerbation of Chronic Obstructive Pulmonary Disease (COPD) complicated with RF. Methods: From December 2020 to March 2022, 73 cases of patients with acute COPD and RF admitted to RICU Department of Respiratory Department were selected. According to the order before and after admission to RICU department of respiratory department, patients with inability to communicate due to disease were excluded and divided into two groups. Control group: Adoption of traditional nursing mode; Observation group: Cluster nursing mode was adopted. After nursing, blood gas analysis results and patients' satisfaction scores on nursing work were compared and observed between the two groups. Results: The blood gas analysis results of the observation group were significantly better than the control group, and their evaluation of nursing work was also higher than the control group. Conclusion: In the clinical operation of our department RICU, this cluster nursing mode alleviates the distress perception of patients with COPD acute attack combined with RF, which also alleviates the patients' mood, improves the patients' understanding and satisfaction of nursing work, and thus playing a promoting role in improving the nursery-patient relationship and nursery-patient harmony.

Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. Renal involvement was the most typical manifestation (95.5

Objective CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). Methods We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. Results In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. Conclusion CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.

ObjectiveFew studies reported the effects of growth hormone-secreting pituitary adenoma (GHPA) on uric acid (UA) metabolism and the relationship between growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels and UA are controversial. This study aimed to evaluate the relationship between IGF-1 and UA in patients with GHPA and to further clarify whether UA levels are associated with GHPA disease activity by follow-up.MethodsA longitudinal study of 424 GHPA patients presenting to Beijing Tiantan Hospital, Capital Medical University between January 2015 and January 2023 was conducted. Spearman’s correlation tests were performed to examine the relationship between IGF-1 and UA at baseline. Univariate and multivariate linear regression analysis was conducted to investigate the independent association between UA and IGF-1. Changes in postoperative IGF-1 and UA levels were followed prospectively, and the differences in UA levels between the biochemical remission and nonremission groups were compared.ResultsAt baseline, male patients, the lower the age, the higher the IGF-1 and body mass index (BMI), and the higher the UA levels. IGF-1 was significantly associated with UA after controlling for sex, age, and BMI (r = 0.122, P = 0.012). In adjusted multiple linear regression analysis, IGF-1 was independently associated with UA, and UA levels increased significantly with increasing IGF-1. During postoperative follow-up, UA decreased gradually as IGF-1 levels decreased. At 12 months postoperatively, UA levels were significantly lower in the biochemical remission group than in the nonremission group (P = 0.038).ConclusionsIn patients with GHPA, UA levels are associated with disease activity. Changes in UA levels should be taken into account in the comprehensive treatment of GHPA, patients presenting with HUA should be given lifestyle guidance and appropriate urate-lowering treatment according to their condition to better improve their prognosis.