Objective:To evaluate the effect of berberine on acute kidney injury (AKI) in rats undergoing liver transplantation and the role of AMP-activated protein kinase (AMPK).Methods:Twenty-four SPF-grade adult male Sprague-Dawley rats, aged 12 weeks, weighing 210-230 g, were divided into 4 groups ( n=6 each) using the random number table method: sham operation group (S group), AKI group, berberine group (BBR group), and berberine + AMPK inhibitor Compound C group (BBR-Comp C group). In BBR group, berberine 200 mg/kg was given by gavage starting from 2 weeks before surgery, once a day for 14 consecutive days. In BBR-Comp C group, Compound C 1 mg/kg was injected into the tail vein at 30 min before surgery. The rat AKI model was prepared by in situ liver transplantation in AKI group, BBR group and BBR-Comp C group. Blood specimens were taken from the inferior vena cava at 24 h postoperatively, and serum BUN and Cr concentrations were determined by enzyme-linked immunosorbent assay. Then the rats were sacrificed, and the kidney tissues were taken for microscopic examination of the pathological changes (with the light microscope after HE staining) and for determination of the expression of phosphorylated AMPK (p-AMPK), receptor-interacting protein kinase-1 (RIPK-1), receptor-interacting protein kinase-3 (RIPK-3) and mixed lineage kinase domain-like protein (MLKL) (by Western blot). Results:Compared with S group, the serum BUN and Cr concentrations were significantly increased, the p-AMPK expression was down-regulated, the expression of RIPK-1, RIPK-3 and MLKL was up-regulated ( P<0.05), and the pathological damage to renal tissues occurred in AKI group. Compared with AKI group, the serum BUN and Cr concentrations were significantly decreased, the p-AMPK expression was up-regulated, the expression of RIPK-1, RIPK-3 and MLKL was down-regulated ( P<0.05), and the pathological changes of renal tissues were significantly attenuated in BBR group. Compared with BBR group, the serum BUN and Cr concentrations were significantly increased, the p-AMPK expression was down-regulated, and the expression of RIPK-1, RIPK-3 and MLKL was up-regulated in BBR-Comp C group ( P<0.05). Conclusions:Berberine can attenuate AKI in rats undergoing liver transplantation, and the mechanism may be related to the promotion of AMPK phosphorylation and inhibition of programmed necrosis.

Objective: To discuss the clinical value of neck circumference in screening for overweight and obesity in children and adolescents, so as to provide a theoretical basis and new ideas for overweight and obesity screening. Methods: From May to July 2023, a total of 2 493 children and adolescents aged 3 to 16 were sampled from three schools by the cluster random sampling method. General data, neck circumference, body mass index (BMI), waisttoheight ratio, and other information were collected. Mann-Whitney ranksum test, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis were used to statistically analyze the data. Results: The prevalence of overweight and obesity in children and adolescents aged 3 to 16 was 33.05%, and the prevalence of abdominal obesity was 28.33%.The neck circumferences of boys and girls in the overweight and obese group showed statistically significant differences from the normal weight group during the preschool, schoolage, and adolescence periods (Z=-16.69--4.54, P<0.05). The neck circumferences of children of different genders were moderately positively correlated with BMI (r=0.50-0.79, P<0.01). ROC curve analysis showed that neck circumference had good accuracy in assisting the screening for the occurrence of overweight and obesity in boys and girls during the preschool, schoolage, and adolescence periods [the AUC for boys:0.80(0.71-0.89), 0.89(0.86-0.91), 0.84(0.81-0.87); the AUC for girls:0.76(0.67-0.86), 0.81(0.74-0.88), 0.73(0.68-0.77), P<0.01], the optimal neck circumference cutoff values for boys were 26.95, 28.95, 33.55 cm, and for girls were 25.05, 26.55, 28.35 cm respectively. The neck circumferences of boys and girls were moderately positively correlated with the waisttoheight ratio during the schoolage and adolescence periods (r=0.41-0.70, P<0.01). ROC curves showed that neck circumferences had good accuracy in assisting the screening for the occurrence of abdominal obesity in boys and girls during the schoolage and adolescence periods [the AUC for boys:0.89(0.86-0.92), 0.82(0.78-0.85); the AUC for girls:0.84(0.75-0.93), 0.87(0.75-0.93)], the optimal cutoff values for boys were 28.95, 32.75 cm; for girls were 26.45, 31.85 cm respectively. Conclusion The neck circumference can be applied to screen for overweight and abdominal obesity in children and adolescents, and can provide new ideas for the prevention and control of overweight and obesity in children and adolescents.

Objective:To analyze the neurocognitive abnormalities and related emotional and behavioral problems in 410 adolescent patients with Turner syndrome (TS) managed in Henan Children′s Hospital in the past 5 years, and to explore the relationship between neurocognitive abnormalities and chromosome karyotype, pubertal development, hormone replacement therapy.Methods:A retrospective case series study.A total of 410 adolescent patients who were diagnosed with TS by karyotype or fluorescence in situ hybridization in the outpatient or inpatient Department of Endocrinology, Genetics and Metabolism at Henan Children′s Hospital from June 2018 to June 2023 were selected and divided into 2 groups according to age: < 12 years old and 12-18 years old.Neurocognitive assessments were performed based on the results of the Wechsler Intelligence Scale (4 th edition) for children and behavior scales for children, SPSS 22.0 software was used for data processing and statistical analysis, and chi-square test was used to analyze the correlation between chromosome karyotype, intelligence development level, pubertal development status, hormone therapy status and the occurrence of neuropsychiatric diseases. Results:Among the 410 TS patients, 207 cases had the karyotype of 45, X0/46, XX, accounting for 50.49%, 94 cases had the monosomic karyotype of 45, X0, accounting for 22.93%.Forty-six patients completed the Wechsler intelligence test, with the intelligence quotient (IQ) score ranging from 70 to 105, with high verbal comprehension and perceptual reasoning scores and low processing speed and working memory scores on all assessments.Fifty-two patients completed the hyperactivity scale assessment, and 43 cases had a predisposition to attention deficit hyperactivity disorder (ADHD).There were no significant differences in total IQ, perceptual reasoning and processing speed among the children with karyotype 45, X0, chimeric, and X chromosome structural abnormalities ( H=3.161, 1.955, 5.890, all P>0.05), while there were significant differences in verbal comprehension and working memory among the three groups ( H=7.697, 9.694, all P<0.05).Among TS patients 12-18 years old, 68 cases completed the depression scale self-assessment, of which 23 cases had depressive tendencies.There was no correlation between depressive tendency and chromosome karyotype, pubertal development and hormone replacement therapy ( P>0.05). Conclusions:TS patients generally have low intelligence levels and tend to have ADHD in childhood.TS patients in the pubertal development have a high incidence of depression.Pubertal development status and hormone replacement therapy show no correlation with the occurrence of neuropsychiatric diseases in TS patients.

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.
Humans ; Child ; Glucocorticoids/therapeutic use* ; Receptor, Melanocortin, Type 2/genetics* ; Retrospective Studies ; Adrenal Insufficiency/genetics* ; Mutation

Objective:To study the expression of serum microRNA-122 (miR-122) in children with non-alcoholic fatty liver disease (NAFLD) .Methods:35 NAFLD children aged 7-14 years from the department of Endocrinology and Inherited Metabolic disease, Children’s Hospital Affiliated to Zhengzhou University were collected, and 43 healthy children healthy children matched with the gender and age as the control group. The height, weight, body mass index (BMI) , waist-hip ratio (WHR) , triglyceride (TG) , cholesterol (TC) , alanine transaminase (ALT) , aspartate aminotransferase (AST) and miR-122 levels of the children in the two groups were detected and recorded.Results:There was no significant difference in age between NAFLD group (9.97±1.93 years) and control group (10.28±1.68 years) ( P=0.455) . Body weight (65.91±15.94kg) , BMI (29.93±3.77kg/m2) , WHR (0.97±0.04) , TG (1.49±0.46mmol/L) , TC (3.96±0.67mmol/L) , ALT (32.7±15.65U/L) and the level of miR-122 (2.33±1.75) in the NAFLD group was higher than that in the control group (36.93±7.54kg, 17.75±1.60kg/m 2, 0.83±0.04, 0.94±0.18mmol/L, 3.55±0.53mmol/L, 19.77±4.3U/L) , the differences were statistically significant ( P<0.05) . The levels of miR-122 in the NAFLD group were positively correlated with ALT and AST (r=0.618, 0.487, P < 0.05) . The ROC curve was used to evaluate the efficacy of miR-122 in diagnosing NAFLD, and the area under the curve of miR-122, ALT and ALT+ miR-122 in diagnosing NAFLD was 0.824, 0.727 and 0.839, respectively. MiR-122 combined with ALT had an advantage in diagnosing NAFLD. Conclusion:The levels of miR-122 in children with NAFLD were positively correlated with ALT. MiR-122 combined with ALT has clinical value in diagnosing NAFLD.

Objective: To investigate the changing trends in the burden of cardiovascular diseases (CVD) in Zhejiang Province from 1990 to 2019, so as to provide insights into CVD control in the province. Methods: Based on the data of the Global Burden of Disease Study (GBD) 2019 (GBD 2019), the years lived with disability (YLD), years of life lost (YLL), disability-adjusted life years (DALY), YLD rate, YLL rate and DALY rate due to CVD were estimated to assess the burden of CVD in Zhejiang Province from 1990 to 2019. The changing trends in the burden of CVD were using annual percent change (APC) in Zhejiang Province from 1990 to 2019, and compared to China and global regions with different socio-demographic indexes (SDI). Results: The YLL rate (APC=-0.50%, F=22.366, P<0.001) and DALY rate due to CVD (APC=-0.20%, F=5.212, P=0.030) appeared a tendency towards a decline in Zhejiang Province from 1990 to 2019, while the YLD rate showed a tendency towards a rise (APC=1.92%, F=1 117.891, P<0.001). The YLL rate (APC=-1.09%, F=56.871, P<0.001), YLD rate (APC=1.92%, F=922.541, P<0.001) and DALY rate (APC=-0.60%, F=28.974, P<0.001) appeared the same tendency among women relative to among the whole populations, while only the YLD rate showed a clear-cut change among men, appearing a tendency towards a rise (APC=1.82%, F=1 238.423, P<0.001). Both the YLL rate and DALY rate appeared a tendency towards a decline among subjects at all age groups, with the most significant reduction among subjects at ages of 50 to 69 years (YLL rate: APC=-4.40%, F=1 443.608, P<0.001; DALY rate: APC=-3.82%, F=1 519.452, P<0.001). Among all types of CVD, the highest burden was measured in cerebrovascular diseases, with a standardized DALY rate of 1 359.7/105, and the most remarkable reduction in the standardized DALY rate was seen in rheumatic heart diseases. The burden of CVD in Zhejiang Province was lower than that in China and the majority of the world, with consistent changing trends with that in China and global regions with different SDI. Conclusions The overall burden of CVD appeared a tendency towards a decline in Zhejiang Province from 1990 to 2019, which was in agreement with that in China and global regions with different SDI. A remarkable reduction in the burden of CVD was seen among women, residents at ages of 50 to 69 years and cases with rheumatic heart diseases.

Objective:To establish the mouse model with radiation-induced pulmonary fibrosis, and to identify and analyze it from the aspects of function, imaging and pathology.Methods:Thirty C57BL/6 mice were randomly divided into the control group, 16 Gy irradiation group and 20Gy irradiation group. The mice in the irradiation groups received a single 16 Gy or 20 Gy chest X-ray irradiation, and underwent functional examination, imaging examination and pathological examination at 3 and 6 months after irradiation.Results:At 6 months after irradiation, hair on the chest and back of the mice turned white and fell off, and the airway resistance was increased significantly. CT images showed extensive patch shadows and consolidation in the lung. Three dimensional reconstruction suggested that the lung of mice was distorted and deformed, and the volume was decreased significantly. Pathological examination confirmed that there was extensive pulmonary fibrosis.Conclusions:Significant pulmonary fibrosis occurs after 6 months of chest irradiation in mice. The animal model of radiation-induced pulmonary fibrosis in C57BL/6 mice was successfully established.

Objective:To analyze the clinical features and CBS gene variants of 13 patients with classic homocystinuria, and the strategies of individual treatment and prevention were explored.Methods:The general information, clinical manifestations, laboratory tests, cranial images, CBS gene variants, diagnosis and therapeutic strategies of 13 patients with classic homocystinuria admitted to the Department of Pediatrics of Children′s Hospital Affiliated to Zhengzhou University and Peking University First Hospital from November 2013 to June 2021 were analyzed retrospectively.Results:There were 13 patients diagnosed at the age of 10 days to 14 years, 6 were male and 7 were female. There were 3 patients detected by newborn screening and received treatment at the asymptomatic stage. There were 10 patients clinically diagnosed at the age of 5 to 14 years. Their symptoms appeared at age of 1 to 6 years. The major clinical manifestations were marfanoid features, lens dislocation and (or) myopia, developmental delay, osteoporosis, and cardiovascular diseases. Brain magnetic resonance imaging showed asymmetric infarcts in 4 patients and hypomyelination in 1 case. Increased blood methionine, plasma total homocysteine and urinary total homocysteine with normal urinary methylmalonic acid were found in 13 patients. The biochemical features were consistent with classic homocystinuria. Totally 18 variants were identified in CBS gene of 13 patients, 10 variants were novel and 8 were reported. only 1 patient was partially responsive to vitamin B 6 treatment, while 12 cases were non-responsive. They were mainly treated with low methionine diet and betaine supplement. Three vitamin B 6 non-responsive cases received liver transplantation at age of 3, 8 and 8 years, respectively. Their blood methionine and total homocysteine returned to normal within a week after liver transplantation. One patient died. Prenatal diagnosis was performed for a fetus when the mother was pregnant again. Two pathogenic CBS gene variants were identified from the amniocytes as same as the proband. Conclusions:The clinical manifestations of classic homocystinuria are complex and variable. Blood amino acid analysis, serum or urine total homocysteine assay and gene analysis are critical for its diagnosis. There were 10 novel CBS gene varients were identified expanding the CBS gene varient spectrum. Liver transplantation is an effective treatment. Prenatal diagnosis is important to prevent classic homocysteinuria.

Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:To investigate the risk factors of proteinuria in patients with hypertension in Qinghai-Tibet Plateau.Methods:From March 2019 to June 2020, prospective design was used to collect data of Qinghai-Tibet Plateau hypertension patients who were eligible for continuous enrollment in the Department of Cardiovascular Medicine in Hospital of Chengdu Office of People's Government of Tibet Autonomous Region. Questionnaire survey, physical examination and blood pressure measurement were performed on the selected patients. Fasting venous blood samples were collected for liver function test, blood lipid test, blood glucose test, and hemoglobin test, etc. Three times of morning urine samples were taken on different days, and urine protein creatinine ratio (UACR) was measured, UACR < 30 mg/g was negative for urinary protein, and UACR≥30 mg/g was positive for urinary protein. At the same time, the selected patients were examined by carotid artery color ultrasound and heart color ultrasound. The risk factors of proteinuria were analyzed.Results:A total of 588 patients with hypertension met the inclusion criteria, including 472 patients (80.3%) who received antihypertensive drug therapy, 239 patients (40.6%) had antihypertensive treatment compliance, and 252 patients (42.9%) reached the standard blood pressure after theropy. Hypertension was associated with diabetes mellitus in 150 patients (25.5%), and urinary protein was positive in 126 patients (21.4%). In univariate analysis, ethnic composition, systolic blood pressure [(138.19 ± 19.65) vs (133.16 ± 18.45) mmHg, 1 mmHg = 0.133 kPa], diastolic blood pressure [(85.80 ± 13.51) vs (83.17 ± 12.19) mmHg], uric acid [(411.79 ± 101.54) vs (379.96 ± 102.18) μmol/L], hemoglobin [(152.86 ± 30.70) vs (143.49 ± 21.15) g/L], pulmonary artery trunk width [(21.76 ± 3.94) vs (20.98 ± 3.34) mm], and ventricular septal thickness [(9.90 ± 1.70) vs (9.47 ± 1.60) mm] in the positive group ( n = 126) were significantly higher than those in the negative group ( n = 462, P < 0.01 or < 0.05). In multivariate logistic regression analysis, increased systolic blood pressure [odds ratio ( OR) = 1.015, 95% confidence interval (95% CI): 1.005 - 1.026], uric acid ( OR = 1.003, 95% CI: 1.001 - 1.005), and pulmonary artery trunk width ( OR = 1.058, 95% CI: 1.001 - 1.118) were risk factors for proteinuria; Tibetans had a decreased risk of proteinuria compared with Han ( OR = 0.505, 95% CI: 0.317 - 0.805), but increased hemoglobin had an increased risk of proteinuria compared with normal hemoglobin ( OR = 1.890, 95% CI: 1.231 - 2.903). Conclusion:In patients with hypertension at high altitude, increased hemoglobin, systolic blood pressure, uric acid, pulmonary artery trunk width, and Han nationality are risk factors for proteinuria.