ObjectiveTo investigate the effects of modified Ditan tang on genes related to the transcription-translation feedback loop （TTFL） of biorhythm in the rat model of non-alcoholic fatty liver disease （NAFLD） and its mechanism for prevention and treatment of NAFLD. MethodsSixty-five healthy SPF male SD rats were randomly assigned into blank （n=20）， model （n=15）， and low-， medium-， and high-dose （2.68， 5.36， and 10.72 g·kg^-1·d^-1， respectively） modified Ditan tang （n=10） groups. Other groups except the blank group were fed a high-fat diet for 12 weeks. The modified Ditan tang groups were treated with the decoction at corresponding doses by gavage， and the blank and model groups were treated with an equal volume of normal saline from the 9th week for 4 weeks. The levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in the serum were measured by an automatic biochemical analyzer. TG and non-esterified fatty acid （NEFA） assay kits were used to measure the levels of TG and NEFA in the liver. The pathological changes in the hypothalamus and liver were observed by hematoxylin-eosin staining， and the lipid deposition in the liver was observed by oil red O staining. The levels of brain-muscle ARNT-like protein 1 （BMAL1/ARNTL） in the hypothalamus and liver were determined by immunohistochemical staining. The mRNA and protein levels of BMAL1， circadian locomotor output cycles kaput （CLOCK）， period circadian clock 2 （PER2）， and cryptochrome1 （Cry1） in the hypothalamus and liver were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the model group showed elevated levels of TG， TC， LDL-C， AST， and ALT （P<0.01） and a lowered level of HDL-C （P<0.05） in the serum， elevated levels of TG and NEFA in the liver （P<0.01）， pyknosis and deep staining of hypothalamic neuron cells， and a large number of vacuoles in the brain area. In addition， the model group showed lipid deposition in the liver， up-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.01）， and down-regulated mRNA and protein levels of Cry1 and PER2 （P<0.01） in the hypothalamus and liver. Compared with the model group， all the three modified Ditan tang groups showed lowered levels of TG， TC， LDL-C， ALT， and AST （P<0.05， P<0.01） and an elevated level of HDL-C （P<0.05） in the serum， and lowered levels of TG and NEFA （P<0.05， P<0.01） in the liver. Furthermore， the three groups showed alleviated pyknosis and deep staining of hypothalamic neuron cells， reduced lipid deposition in the liver， down-regulated mRNA and protein levels of CLOCK and BMAL1 （P<0.05， P<0.01）， and up-regulated mRNA and protein levels of Cry1 and PER2 （P<0.05， P<0.01） in the hypothalamus and liver. ConclusionModified Ditan tang can reduce lipid deposition in the liver and regulate the expression of CLOCK， BMAL1， Cry1， and PER2 in the TTFL of NAFLD rats.

Objective:To describe the population and area distribution differences in the prevalence of urinary incontinence in middle-aged and elderly adults in 10 areas in China.Methods:A total of 24 913 participants aged 45-95 years who completed the third resurvey of China Kadoorie Biobank during 2020-2021 were included. The prevalence of urinary incontinence was assessed by an interviewer-administered questionnaire, and urinary incontinence was classified as only stress urinary incontinence, only urgency urinary incontinence and mixed urinary incontinence. The prevalence of urinary incontinence and its subtypes were reported by sex, age and area, and the severity of urinary incontinence and treatment were described.Results:The average age of the participants was (65.4±9.1) years. According to the seventh national census data in 2020, the age-standardized prevalence rates of urinary incontinence was 25.4% in women and 7.0% in men. The age-standardized prevalence rates of only stress, only urgency and mixed incontinence were 1.7%, 4.2% and 1.2% in men and 13.5%, 5.8% and 6.1% in women, respectively. The prevalence rates of urinary incontinence and all subtypes in men and the prevalence of urinary incontinence and all subtypes except only stress urinary incontinence in women all increased with age ( P<0.001). After adjusting for age, the prevalence of urinary incontinence in both men and women were higher in rural area than in urban area ( P<0.001). The treatment rates in men and women with urinary incontinence were 15.4% and 8.5%, respectively. Conclusions:The prevalence of urinary incontinence was high in middle-aged and elderly adults in China, and the prevalence rate was higher in women than in men, but the treatment rate of urinary incontinence was low.

Objective:To analyze the association between waist circumference (WC) and ischemic stroke (IS).Methods:The data for the present study were from the prospective cohort study of China Kadoorie Biobank in Qingdao. Using baseline information and IS events of the participants, the Cox proportional hazard regression model and restricted cubic spline (RCS) were used to analyze the association between WC and IS.Results:A total of 33 355 participants were included in the study, with 302 008.88 person-years of follow-up. A total of 1 093 new cases of IS were observed. Multivariate Cox proportional hazard regression model analysis showed that compared to the respondents with normal WC (male <85.0 cm, female <80.0 cm), respondents with excessive WC (male ≥85.0 cm, female ≥80.0 cm) had a 78% higher risk of IS incidence [hazard ratio( HR)=1.78, 95% CI: 1.51-2.10], and the risk increased by 72% ( HR=1.72, 95% CI: 1.40-2.12) and 83% ( HR=1.83, 95% CI: 1.40-2.39) in men and women. According to the RCS, the increase in WC and the risk of IS showed an "S" trend of nonlinear dose-response relationship. Conclusions:The risk of IS would increase with the WC. Keeping a normal WC is important for preventing IS.

Objective:To explore the relationship between BMI and levels of plasma amino acids and acylcarnitines in Chinese adults.Methods:Based on 2 182 individuals with targeted mass spectrometry metabolomic measurements from the first resurvey of the China Kadoorie Biobank, we assessed the linear and nonlinear associations between BMI and plasma levels of 20 amino acids and 40 acylcarnitines using linear regression models and restricted cubic spline models, and identified BMI-related metabolic pathways. We conducted one-sample Mendelian randomization (MR) with BMI genetic risk scores as the instrumental variable further to explore the potential causal relationships between BMI and 20 amino acids and 40 acylcarnitines, and tested for horizontal pleiotropy using the MR-Egger method.Results:Observational analyses found that BMI was associated with increased plasma levels of 3 branched-chain amino acids (isoleucine, leucine, and valine), 2 aromatic amino acids (phenylalanine and tyrosine), 3 other amino acids (cysteine, glutamate, lysine), and 7 acylcarnitines (C3, C4, C5, C10, C10:1, C14, and C16), and with decreased circulating levels of asparagine, serine, and glycine. Pathway analysis identified 7 BMI-related amino acids metabolic pathways (false discovery rate corrected all P<0.05), including branched-chain amino acids and aromatic amino acids biosynthesis, glutathione metabolism, etc. BMI showed a nonlinear relationship with leucine, valine, and threonine, and a linear relationship with other amino acids and acylcarnitines. One-sample MR analyses revealed that BMI was associated with elevated levels of tyrosine and 4 acylcarnitines [C5-DC(C6-OH), C5-M-DC, C12-DC, and C14], with tyrosine and acylcarnitine C14 positively correlated with BMI in both observational [the β values (95% CIs) were 0.057 (0.044-0.070) and 0.018 (0.005-0.032), respectively] and One-sample MR analyses [the β values (95% CIs) were 0.102 (0.035-0.169) and 0.104 (0.036-0.173), respectively]. The MR analyses of the current study satisfied the 3 core assumptions of instrumental variable. Conclusions:BMI was associated with circulating 11 amino acids and 7 acylcarnitines in Chinese adults, involving several pathways such as branched-chain amino acid and aromatic amino acid metabolism, fatty acid metabolism, and oxidative stress. There may be a causal relationship between BMI and tyrosine and acylcarnitine C14.

Objective:To investigate the association between solid fuel use for heating, smoking, and respiratory diseases.Methods:This study is based on the Qingdao project of the China Kadoorie Biobank. After screening, 26 165 individuals were included in the study. We employed Cox proportional hazards regression models, stratified by risk age (in 5-year intervals) and sex while adjusting for confounding variables such as occupation and physical activity level to analyze the association between solid fuel use for heating, smoking, and increased risk of respiratory diseases.Results:Among the 26 165 participants, the average age of those using solid fuel for heating was (52.57±10.31) years, with females constituting 58.04% and former/current smokers accounting for 65.38%. The results indicated that both the solid fuel group and the former/current smoking group had a higher risk of respiratory diseases, with hazard ratios ( HR) (95% CI) of 1.21 (1.04-1.41) and 1.41 (1.16-1.71), respectively. For the duration of solid fuel use, the HR (95% CI) for 20 years or more, it was 1.27 (1.07-1.51). The multiplicative interaction term between solid fuel use and smoking was statistically significant. Conclusions:The use of solid fuel for heating and smoking significantly increases the risk of respiratory diseases, and there may be a multiplicative interaction between solid fuel use and smoking.

Objectives:To analyze the clinical prognosis stratification of fetal heart disease(FHD)and the mid-term follow-up results following integrated prenatal and postnatal management. Methods:Present retrospective analysis was performed on 817 fetuses diagnosed with FHD by fetal echocardiography in Fuwai Hospital,Chinese Academy of Medical Sciences(Fuwai Hospital)from the 8th February 2018 to 30th April 2022.According to the Chinese expert consensus on fetal prognosis score of congenital heart disease(CHD)and Fuwai Hospital Pediatric Center score,FHD was divided into grade Ⅰ(0 point),grade Ⅱ(1-3 points),grade Ⅲ(4-6 points)and grade Ⅳ(7-9 points).For FHD fetuses that need to be treated in the neonatal period,the whole closed-loop management and treatment were completed,including pregnancy,birth,neonatal monitoring,surgery,and follow-up.The clinical data and mid-term follow-up results of FHD fetuses were analyzed. Results:A total of 752 fetuses completed the mid-term follow-up.The mean follow-up time was(18.5±2.3)months.There were 111 cases(14.8%)of FHD grade Ⅰ,251 cases(33.4%)of FHD grade Ⅱ,275 cases(33.6%)of FHD grade Ⅲ and 115 cases(15.3%)of FHD grade Ⅳ.There were 393 cases(52.2%)of fetal preservation,1 case(0.2%)of intrauterine death,and 358 cases(47.6%)of induced abortion.Compared with the induced fetus,the pregnant women in the reserved fetus group were older,the gestational age was longer,the rate of receiving noninvasive DNA and amniocentesis was lower,the proportion of chromosomal abnormalities or genetic abnormalities was smaller,and the FHD prognostic score was lower(all P<0.05).One case(0.9%)of FHD grade Ⅰ fetus experienced intrauterine fetal death,and 110 cases(99.1%)were born and recovered.164 cases(65.3%)of grade Ⅱ fetuses were born,and all of them were cured by surgery or spontaneously.118 cases(42.9%)of grade Ⅲ fetuses were born,117 cases completed biventricular radical operation,and 1 case completed two-stage operation waiting for the second stage biventricular radical operation.One case(0.9%)of grade Ⅳ was born and completed the two-stage bidirectional Glenn procedure.Among the induced FHD grade Ⅱ fetuses,8(9.2%)had abnormal chromosomal or genetic testing results,and 8(9.2%)had other organ abnormalities.Among the induced FHD grade Ⅲ fetuses,5 cases(3.2%)had chromosomal abnormalities,5 cases(3.2%)had genetic abnormalities,and 9 cases(5.7%)had other organ abnormalities.There was only one case(0.9%)of FHD Ⅳ with hypoplastic left heart syndrome,which was retained as one of the twins and was born successfully.Norwood one-stage procedure was performed in the neonatal period,and two-stage bidirectional Greene procedure was performed at 6 months after birth.Other fetuses were induced following the choice of maternity and their family members. Conclusions:Hierarchical management based on clinical prognosis is helpful to scientifically guide the integrated treatment of FHD fetuses and improve the success rate of treatment of FHD fetuses with good prognosis.

Purpose To investigate the expression of TRPS1 in synovial sarcoma(SS)and its significance.Methods Twenty-one cases of synovial sarcoma diagnosed by SS1 8(18q11)(SYT)fluorescence in situ hybridization(FISH)or SS18-SSX immunohistochemistry were collected.The expression of TRPS1 was detected by immunohistochemistry EnVision two-step staining,and the relevant literature was reviewed.Results There were 21 cases of synovial sarcoma,including 9 females and 12 males,aged 17-79 years,with a median age of 50 years and an average age of 47.1 years.The tumors occurred in the lung(3 cases),legs(3 cases),kidney(3 cases),feet(2 cases),psoas major muscle(2 cases),rectum(1 case),tho-racic cavity(1 case),ankle canal(1 case),inguinal area(1 case),knee(1 case),palm(1 case),nasal cavity(1 case),and forearm(1 case).The maximum diameter of the tumor was 1.2-13 cm.Grossly,the tumor section was grayish-white,grayish-yellowish solid,and the lesion with hemorrhage was dark red.Microscopically,there were monophasic fibrous SS(16/21,76.2％),poorly differential SS(small cell)(3/21,14.3％),and biphasic SS(2/21,9.5％).Immunophenotypi-cally,tumor cells expressed SS18-SSX(18/18,100％),TLE1(12/12,100％),BCL2(18/18,100％),partially expressed EMA(10/16,62.5％),CK(12/18,66.7％),CD99(4/10,40.0％),SMA(3/16,18.6％),S-100(3/19,15.8％),and desmin(0/21).The proliferation index of Ki67 ranged from 3％-80％,with an average of 39.9％.FISH test showed that all 11 cases were positive for SS18(18q11)split-ting.All 21 cases of SS expressed TRPS1 to varying degrees and intensities(21/21,100％),of which 19 cases(19/21,90.5％)had a positive range of＞50％.There were 19 cases(19/21,90.5％)with a positive intensity of 2+or above.All the 21 patients underwent surgical resection of the tumor,and 20 patients received follow-up visits.3 patients treated with postop-erative combination of radiotherapy and chemotherapy,18 pa-tients treated with postoperative chemotherapy,and 7 patients showed different degrees of recurrence or metastasis,and 9 pa-tients who received follow-up visits died(45％,9/20).Con-clusion Although TRPS1 is regarded as a highly sensitive and specific marker of breast tumor origin,it is also highly expressed in synovial sarcoma,and it is necessary to be vigilant at its pit-falls in the pathological diagnosis.

BACKGROUND: Several studies have reported that polygenic risk scores (PRSs) can enhance risk prediction of coronary artery disease (CAD) in European populations. However, research on this topic is far from sufficient in non-European countries, including China. We aimed to evaluate the potential of PRS for predicting CAD for primary prevention in the Chinese population. METHODS: Participants with genome-wide genotypic data from the China Kadoorie Biobank were divided into training ( n = 28,490) and testing sets ( n = 72,150). Ten previously developed PRSs were evaluated, and new ones were developed using clumping and thresholding or LDpred method. The PRS showing the strongest association with CAD in the training set was selected to further evaluate its effects on improving the traditional CAD risk-prediction model in the testing set. Genetic risk was computed by summing the product of the weights and allele dosages across genome-wide single-nucleotide polymorphisms. Prediction of the 10-year first CAD events was assessed using hazard ratios (HRs) and measures of model discrimination, calibration, and net reclassification improvement (NRI). Hard CAD (nonfatal I21-I23 and fatal I20-I25) and soft CAD (all fatal or nonfatal I20-I25) were analyzed separately. RESULTS: In the testing set, 1214 hard and 7201 soft CAD cases were documented during a mean follow-up of 11.2 years. The HR per standard deviation of the optimal PRS was 1.26 (95% CI:1.19-1.33) for hard CAD. Based on a traditional CAD risk prediction model containing only non-laboratory-based information, the addition of PRS for hard CAD increased Harrell's C index by 0.001 (-0.001 to 0.003) in women and 0.003 (0.001 to 0.005) in men. Among the different high-risk thresholds ranging from 1% to 10%, the highest categorical NRI was 3.2% (95% CI: 0.4-6.0%) at a high-risk threshold of 10.0% in women. The association of the PRS with soft CAD was much weaker than with hard CAD, leading to minimal or no improvement in the soft CAD model. CONCLUSIONS In this Chinese population sample, the current PRSs minimally changed risk discrimination and offered little improvement in risk stratification for soft CAD. Therefore, this may not be suitable for promoting genetic screening in the general Chinese population to improve CAD risk prediction.
Male ; Humans ; Female ; Coronary Artery Disease/genetics* ; Biological Specimen Banks ; East Asian People ; Risk Assessment/methods* ; Genetic Predisposition to Disease/genetics* ; Risk Factors ; Genome-Wide Association Study

Accurate segmentation of pediatric echocardiograms is a challenging task, because significant heart-size changes with age and faster heart rate lead to more blurred boundaries on cardiac ultrasound images compared with adults. To address these problems, a dual decoder network model combining channel attention and scale attention is proposed in this paper. Firstly, an attention-guided decoder with deep supervision strategy is used to obtain attention maps for the ventricular regions. Then, the generated ventricular attention is fed back to multiple layers of the network through skip connections to adjust the feature weights generated by the encoder and highlight the left and right ventricular areas. Finally, a scale attention module and a channel attention module are utilized to enhance the edge features of the left and right ventricles. The experimental results demonstrate that the proposed method in this paper achieves an average Dice coefficient of 90.63% in acquired bilateral ventricular segmentation dataset, which is better than some conventional and state-of-the-art methods in the field of medical image segmentation. More importantly, the method has a more accurate effect in segmenting the edge of the ventricle. The results of this paper can provide a new solution for pediatric echocardiographic bilateral ventricular segmentation and subsequent auxiliary diagnosis of congenital heart disease.
Adult ; Humans ; Child ; Heart Ventricles/diagnostic imaging* ; Echocardiography ; Image Processing, Computer-Assisted

Objective: A Mendelian randomization (MR) analysis was performed to assess the relationship between tea consumption and cancer. Methods: There were 100 639 participants with the information of gene sequencing of whole genome in the China Kadoorie Biobank. After excluding those with cancer at baseline survey, a total of 100 218 participants were included in this study. The baseline information about tea consumption were analyzed, including daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption. We used the two-stage least square method to evaluate the associations between three tea consumption variables and incidence of cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer. Multivariable MR and analysis only among nondrinkers were used to control the impact of alcohol consumption. Sensitivity analyses were also performed, including inverse variance weighting, weighted median, and MR-Egger. Results: We used 54, 42, and 28 SNPs to construct non-weighted genetic risk scores as instrumental variables for daily tea consumption or not, cups of daily tea consumption, and grams of daily tea consumption, respectively. During an average of (11.4±3.0) years of follow-up, 6 886 cases of cancer were recorded. After adjusting for age, age², sex, region, array type, and the first 12 genetic principal components, there were no significant associations of three tea consumption variables with the incidence of cancer and cancer subtypes. Compared with non-daily tea drinkers, the HR (95%CI) of daily tea drinkers for cancer and some subtypes, including stomach cancer, liver and intrahepatic bile ducts cancer, colorectal cancer, tracheobronchial and lung cancer, and female breast cancer, are respectively 0.99 (0.78-1.26), 1.17 (0.58-2.36), 0.86 (0.40-1.84), 0.85 (0.42-1.73), 1.39 (0.85-2.26) and 0.63 (0.28-1.38). After controlling the impact of alcohol consumption and performing multiple sensitivity analyses, the results were similar. Conclusion: There is no causal relationship between tea consumption and risk of cancer in population in China.
Humans ; Female ; Stomach Neoplasms/epidemiology* ; Mendelian Randomization Analysis/methods* ; Tea ; Breast Neoplasms ; Lung Neoplasms ; Colorectal Neoplasms ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study