Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

Objective To observe the effect of omeprazole enteric-coated capsules on clinical symptoms and serum inflammatory factor levels in children with chronic gastritis and peptic ulcer.Methods Children with chronic gastritis and peptic ulcer were divided into treatment group and control group by random number table method.The control group was given triple therapy of ranitidine hydrochloride tablets,amoxicillin and clarithromycin,while the treatment group was treated with omeprazole enteric-coated capsules combined with amoxicillin and clarithromycin.Clinical efficacy,symptom relief time,and changes in serum motilin(MOT),gastrin(GAS)and inflammatory factors[interlrukin-6(IL-6)and interlrukin-8(IL-8)]were compared between the two groups.Results There were 48 cases in treatment group and 48 cases in control group.After treatment,the total effective rates in treatment group and control group were 93.74％(45 cases/48 cases)and 85.42％(41 cases/48 cases),with significant difference(P＜0.05).After treatment,the disappearance time of ulcer induced pain in treatment group and control group were(1.51±0.26)and(2.08±0.42)d;the disappearance time of acid regurgitation were(2.29±0.40)and(2.93±0.33)d;the disappearance time of burning sensation were(2.37±0.21)and(2.85±0.54)d;the length of hospital stay were(6.21±1.07)and(6.94±1.25)d;serum MOT levels were(298.48±35.15)and(273.58±31.25)pg·mL-1;serum GAS levels were(167.28±19.46)and(128.32±18.61)ng·L-1;IL-6 levels were(58.67±5.39)and(76.14±6.63)mg·mL-1;IL-8 levels were(50.08±5.16)and(58.68±5.49)mg·mL-1.The above indexes were significantly different between control group and treatment group(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 8.33％and 12.50％,with no statistical significance(P＞0.05).Conclusion Omeprazole enteric-coated capsules in the treatment of children with chronic gastritis and peptic ulcer can effectively alleviate various clinical symptoms and improve clinical efficacy.At the same time,it can lower serum levels of inflammatory factors and improve inflammation,with good effect.

Objective·To analyze the progression of children with severe coronary artery lesions due to Kawasaki disease by coronary artery angiography,and evaluate the diagnostic value of echocardiography in these children.Methods·A retrospective analysis was performed to enroll children with Kawasaki disease whose coronary artery lesions were graded Ⅳ or above from Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,from January 2013 to January 2023.The subjects were required to have received at least 2 times of coronary angiogram,and their clinical and imaging data were collected to analyze the progression of the lesions.Echocardiography results were compared with the results of the coronary angiogram.Results·A total of 21 children were included,including 15 males and 6 females,with a median age at onset of 3 years and 6 months,a median age at initial coronary angiography of 7 years and 11 months,a median interval of 4 years and 5 months between the time of onset and initial angiography,a median age at angiographic review of 9 years and 2 months,and a median interval of 1 year and 3 months between the time of initial angiography and review.Coronary stenosis or occlusion was detected in 13 children in the initial angiography,of whom 6 underwent coronary artery bypass grafting(CABG)and had their angiography reviews 1 year later.The review results showed that the bridging vessels were unobstructed and no obvious stenosis was observed.Fifteen children had progression of the lesions detected by echocardiography in the subsequent follow-up and had their angiogram reviews,of whom 8 had significant progression of the coronary lesions.Intracoronary balloon dilatation was performed in 1 case,and CABG was performed in another case.Sixteen lesions of coronary stenosis or occlusion were detected in the initial angiography in 21 children,while only 1 lesion of coronary stenosis was detected by echocardiography during the same period of time.Twenty-eight medium-to large-sized coronary aneurysms were detected in the initial angiography in the 21 children,and the diameters of the 28 aneurysms measured by echocardiography and coronary angiogram were subjected to the Bland-Altman analysis.The Bland-Altman analysis showed that the difference in maximum diameter between 2 methods was(1.63±2.33)mm,with 95％CI of-2.95-6.21 mm.Conclusion·Coronary artery lesions due to Kawasaki disease may be progressive;in the children with severe lesions,coronary artery stenosis or occlusion may be missed or misdiagnosed and some errors may exist in the measurement of diameters of aneurysms by echocardiography.Regular review of coronary angiography is needed.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective: To understand the influence of meteorological factors on the morbidity of influenza in northern cities of China and explore the differences in the influence of meteorological factors on the morbidity of influenza in 15 cities. Methods: The monthly reported morbidity of influenza and monthly meteorological data from 2008 to 2020 were collected in 15 provincial capital cities, including Xi 'an, Lanzhou, Xining, Yinchuan and Urumqi (5 northwestern cities), Beijing, Tianjin, Shijiazhuang, Taiyuan, Hohhot, Ji'nan, Zhengzhou (7 northern cities), Shenyang, Changchun and Harbin (3 northeastern cities). The panel data regression model was applied to conduct quantitative analyze on the influence of meteorological factors on influenza morbidity. Results: The univariate and multivariate panel regression analysis showed that after controlling the population density and other meteorological factors, for each 5 ℃ drop of monthly average temperature, the morbidity change percentage (MCP) of influenza was 11.35%, 34.04% and 25.04% in the 3 northeastern cities, 7 northern cities and 5 northwestern cities, respectively, and the best lag period months was 1, 0 and 1 month; When the monthly average relative humidity decreased by 10%, the MCP was 15.84% in 3 cities in northeastern China and 14.80% in 7 cities in northern China respectively, and the best lag period months was 2 and 1 months respectively; The MCP of 5 cities in northwestern China was 4.50% for each 10 mm reduction of monthly accumulated precipitation, and the best lag period months was 1 month; The MCPs of 3 cities in northeastern China and 5 cities in northwestern China were 4.19% and 5.97% respectively when the accumulated sunshine duration of each month decreased by 10 hours, the best lag period months was 1 month. Conclusions: In northern cities of China from 2008 to 2020, the temperature, relative humidity, precipitation and sunshine duration all had negatively impact on the morbidity of influenza, and temperature and relative humidity were the main sensitive meteorological factors. Temperature had a strong direct impact on the morbidity of influenza in 7 cities in northern China, and relative humidity had a strong lag effect on the morbidity of influenza in 3 cities in northeastern China. The duration of sunshine in 5 cities in northwestern China had a greater impact on the morbidity of influenza compared with 3 cities in northeastern China.
Humans ; Cities ; Influenza, Human ; China ; Beijing ; Meteorological Concepts

OBJECTIVE: To analyze the association between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years, and to provide suggestions for the prevention and control of metabolic syndrome in Chinese children and adolescents. METHODS: Data were collected from the research project "Development and Application of Technology and Related Standards for Prevention and Control of Major Diseases among Students" of public health industry in 2012. This project is a cross-sectional study design. A total of 65 347 students from 93 primary and secondary schools in 7 provinces including Guangdong were selected by stratified cluster random sampling method. Given the budget, 25% of the students were randomly selected to collect blood samples. In this study, 10 176 primary and middle school students aged 7 to 17 years with complete physical measurements and blood biochemical indicators were selected as research objects. Chi-square test was used to compare the distribution differences of growth patterns under different demographic characteristics. Birth weight, waist circumference and blood biochemical indexes were expressed in the form of mean ± standard deviation, and the differences among different groups were compared by variance analysis. Binary Logistic regression model was used to analyze the relationship between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years. RESULTS: The prevalence of metabolic syndrome in children and adolescents was 6.56%, 7.18% in boys and 5.97% in girls. The risk of metabolic syndrome was higher in the catch-down growth group than in the normal growth group (OR=1.417, 95%CI: 1.19-1.69), and lower in the catch-up growth group(OR=0.66, 95%CI: 0.53-0.82). After adjusting for gender, age and so on, the risk of developing metabolic syndrome in the catch-down growth group was higher than that in the normal growth group (OR=1.25, 95%CI: 1.02-1.52), but there was no significant difference between the catch-up growth group and the normal growth group (OR=0.79, 95%CI: 0.62-1.01). Stratified analysis showed that the association between different growth patterns and metabolic syndrome was statistically significant in the 7-12 years group, urban population, and Han Chinese student population. CONCLUSION There is a correlation between different growth patterns and metabolic syndrome in children and adolescents. The risk of developing metabolic syndrome in children and adolescents with catch-down growth is higher than that in the normal growth group, which suggests that attention should be paid to the growth and development of children and adolescents, timely correction of delayed growth and prevention of adverse health outcomes.
Male ; Female ; Humans ; Child ; Adolescent ; Metabolic Syndrome/epidemiology* ; Cross-Sectional Studies ; Students ; Urban Population ; Asian People ; China/epidemiology* ; Prevalence

OBJECTIVE: To investigate the status of depression and social anxiety in children and adolescents, and to analyze the association between body fat distribution and depression, social anxiety in children and adolescents. METHODS: A total of 1 412 children aged 7 to 18 years in Beijing were included by stratified cluster random sampling method. Body fat distribution, including total body fat percentage (total BF%), Android BF%, Gynoid BF% and Android-to-Gynoid fat ratio (AOI), were obtained by dual-energy X-ray absorption method. Depression and social anxiety were evaluated by Children Depression Inventory and Social Anxiety Scale for Children. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non-linear correlation between body fat distribution and depression and social anxiety. RESULTS: 13.1% and 31.1% of the children and adolescents had depressive symptoms and social anxiety symptoms respectively, and the detection rate of depression and social anxiety in the boys and young groups was significantly lower than those in the girls and old groups. There was no significant linear correlation between total BF%, Android BF%, Gynoid BF%, AOI and depression and social anxiety in the children and adolescents. However, total BF% and Gynoid BF% had significant nonlinear correlation with depression, showing an inverted U-shaped curve relationship with the tangent points of 26.8% and 30.9%, respectively. In terms of the nonlinear association of total BF%, Android BF%, Gynoid BF% and AOI with depression and social anxiety, the change trends of the boys and girls, low age group and high age group were consistent. The overall anxiety risk HR of body fat distribution in the boys was significantly higher than that in the girls, and the risk HR of depression and social anxiety were significantly higher in the high age group than those in the low age group. CONCLUSION There was no significant linear correlation between body fat distribution and depression and social anxiety in children and adolescents. Total BF% and depression showed an inverted U-shaped curve, mainly manifested in Gynoid BF%, and this trend was consistent in different genders and different age groups. Maintaining children and adolescents' body fat distribution at an appropriate level is the future direction of the prevention and control of depression and social anxiety in children and adolescents.
Humans ; Female ; Child ; Male ; Adolescent ; Cross-Sectional Studies ; X-Rays ; Depression/epidemiology* ; Absorptiometry, Photon/methods* ; Body Mass Index ; Body Fat Distribution ; Anxiety/epidemiology* ; Adipose Tissue ; Body Composition

Objective:To analyze the coronary angiographic (CAG) characteristics of coronary artery lesion (CAL) in children with Kawasaki disease (KD), and to clarify the necessity of CAG in the diagnosis and treatment of KD combined with CAL in children.Methods:It was a retrospective study to analyze the clinical data, electrocardiogram, echocardiography, time and findings of CAG in children with KD and CAL who underwent CAG in Shanghai Children′s Medical Center of Shanghai Jiao Tong University School of Medicine from January 2013 to August 2022.The distribution, type, severity, and prognosis of CAL were analyzed.Results:A total of 117 children with KD and CAL were included in the analysis.The onset age of KD was from 2 months to 12.8 years old, and the age of performing CAG was from 8 months to 18.1 years old.A total of 234 coronary artery lesions were detected in 117 cases.Among them, CAL in the right coronary artery (RCA), left anterior descending branch (LAD), left main coronary artery and left circumflex artery were detected in 96 branches(41.1%), 78 branches(33.3%), 44 branches(18.8%), and 16 branches(6.8%), respectively.Unilateral coronary artery involvement was detected in 43 cases (36.8%), of which LAD was the dominant; while bilateral involvement was detected in 74 cases (63.2%), among which, LAD and RCA were the most involved arteries.Stratified by the degree of coronary involvement, large coronary aneurysms and severe coronary stenosis were most frequently occurred in the RCA and LAD.In contrast, 10 cases (13.6%), 20 cases (24.3%), 55 cases (45.8%) and 37 cases (67.3%) of intraluminal lesions were found in small, medium and large coronary aneurysms, and stenosis or occlusion, respectively.The incidence of intraluminal lesions tended to be higher in the site of severe lesions.CAG showed stenosis or occlusion in a total of 55 cases, and collateral circulation at varying degrees was found in cases of severe stenosis or occlusion.Conclusions:CAL in children with KD are complex and varied.Although clinical symptoms, routine electrocardiogram and cardiac ultrasound may indicate severe CAL.Their applications are limited by the diagnosis of the type (especially stenosis), degree, and extent of CAL, as well as the detection of extracoronary lesions.CAG is of great significance to identify vascular lesions and guide clinical management of KD combined with CAL in children.