Background::Asthma imposes a large healthcare burden in China and the United States (US). However, the trends of asthma mortality and the relative risk factors have not been comparatively analyzed between the countries. The aim of this study was to compare the mortality and risk factors between China and the US.Methods::The deaths, and mortality rates of asthma in China and the US during 1990–2019 were obtained from the Global Burden of Disease Study 2019. The age–period–cohort model was used to estimate these mortality rates based on a log-linear scale with additive age, period, and cohort effects. The population attributable fractions of risk factors for asthma were estimated.Results::In 1990–2019, the asthma mortality rate was higher in China than in the US. The crude and age-standardized asthma mortality rates trended downward in both China and the US from 1990 to 2019. The decline in mortality was more obvious in China. Mortality gap between the two countries was narrowing. A sex difference in asthma mortality was observed with higher mortality in males in China and females in the US. The age effects showed that mortality increased with age in adults older than 20 years, particularly in the elderly. Downward trends were generally observed in the period and cohort rate ratios in both countries, with China experiencing a more obvious decrease. Smoking and high body mass index (BMI) were the leading risk factors for asthma mortality in China and the US, respectively. Mortality attributable to occupational asthmagens and smoking decreased the most in China and the US, respectively.Conclusions::In 1990–2019, the asthma mortality rate was higher in China than in the US; however, the mortality gap has narrowed. Mortality increased with age in adults. The improvements in asthma death risk with period and birth cohort were more obvious in China than in the US. Smoking, high BMI, and aging are major health problems associated with asthma control. The role of occupational asthmagens in asthma mortality underscores the importance of management and prevention of occupational asthma.

Diabetic nephropathy （DN） is a chronic microvascular complication in diabetic patients and the main cause of end-stage renal disease （ESRD）. Studies have shown that nuclear factor kappa-B （NF-κB） signaling pathway is involved in the pathological process of DN by activating pathological mechanisms such as inflammation， oxidative stress， fibrosis， apoptosis， autophagy， and pyroptosis. Therefore， blocking the transduction of NF-κB signaling pathway can help prevent and treat DN. Currently， western medical treatment involves strategies such as lowering blood sugar， blood pressure， and lipids， as well as using endothelin receptor antagonists， mineralocorticoid receptor antagonists， aldosterone synthase inhibitors， and other drugs， but they still cannot block the pathological process of DN. Traditional Chinese medicine （TCM） offers a simpler and more cost-effective approach that addresses both the symptoms and underlying causes of DN. Recent research has shown promising results in managing DN with TCM， and NF-κB， as a key factor， plays an important role in the prevention and treatment of DN. This article summarized the research results of TCM based on the NF-κB signaling pathway for the treatment of DN in the past five years. It described a variety of TCM extracts， such as polysaccharides， terpenes， phenols， flavonoids， saponins， and alkaloids， as well as TCM compound prescriptions such as Huaiqihuang granules， Astragalus mongholicus Bunge and Panax notoginseng formula， and Danzhi Jiangtang capsules， which regulated the NF-κB signaling pathway and its upstream and downstream factors to block the pathological process of DN. This inhibition aims to prevent renal pathological damage caused by DN and slow down the deterioration of renal function. The article aims to provide new ideas and references for the research and development of drugs for the prevention and treatment of DN.

Objective To observe the effects of Renshen Yimai Prescription on oxidative stress and vascular aging in ApoE-/-mice;To explore its mechanism of intervention in vascular aging.Methods Forty ApoE-/-mice were divided into model group,Western medicine group(rosuvastatin,2.6 mg/kg),TCM low-and high-dosage group(Renshen Yimai Prescription,4.29,8.58 g/kg),with 10 mice in each group.Another 10 C57BL/6J mice were set as normal group.A vascular aging model was established by ApoE-/-mice fed with a Western diet.Each medication group was given corresponding drugs by gavage for 12 consecutive weeks,the normal group and model group were given equivalent volume of pure water.HE staining and Masson staining were used to observe the morphological changes of aortic tissue,and ox-LDL content in serum was detected by ELISA,the contents of ROS,GSH,GPX and NAD+in serum were detected by colorimetric method,the expressions of SIRT1,p53,p21 and NOX4 protein in aortic tissue were detected by Western blot.Results Compared with the normal group,the model group mice showed significant fat deposition in the aorta,thickening of the intima and media,a significant decrease in elastic fibers,and an increase in collagen fibers;the serum contents of ox-LDL and ROS significantly increased(P<0.01),while the contents of GSH,GPX and NAD+significantly decreased(P<0.01);the expression of SIRT1 protein in the aortic tissue significantly decreased(P<0.05),the expressions of p21 and p53 protein significantly increased(P<0.01,P<0.05).Compared with the model group,a small amount of lipid deposition was observed in the intima of aorta in each medication group,with clearer membrane structures in each layer and reduced collagen fiber;the serum contents of ox-LDL and ROS in each medication group were significantly decreased(P<0.01),while the GSH content significantly increased(P<0.05,P<0.01),the NAD+content in TCM low-dosage group significantly increased(P<0.05);the expressions of p21 and NOX4 protein in aortic tissue of the TCM high-dosage group significantly increased(P<0.05,P<0.01).Compared with the Western medicine group,the TCM high-dosage group showed a significant decrease in ROS content(P<0.01)and a significant decrease in p53 protein expression(P<0.05).Compared with the TCM low-dosage group,the TCM high-dosage group showed a significant decrease in p21 protein expression(P<0.01)and a significant increase in NOX4 protein expression(P<0.01).Conclusion Renshen Yimai Prescription may reduce vascular endothelial damage by regulating oxidative stress levels and related protein expression,thereby playing a role in improving vascular aging.

Objective To obtain the range of anatomical parameters of healthy knee joints in Chinese males and validate a statistical shape model(SSM)based on the geometric shape of a healthy knee to provide references for the design of knee SSM-based prostheses.Methods Computed tomography(CT)images of knee joints from 112 healthy males were acquired to build three-dimensional(3D)knee joint models.Each model was the target model separately,and the remaining models were used as the training set for principal component analysis(PCA).The obtained knee SSM was fitted to the target model to predict the SSM.The exact anatomical measurement points were marked on the sample and SSM prediction models,and 17 linear and 3 angular parameters were derived.The values of the anatomical parameters were statistically tested using an independent samples t-test and Mann-Whitney U-test,and the validity of the SSM in terms of geometric shape was demonstrated if the resulting P-values were all greater than 0.05.Results Qualitative and quantitative comparative analyses of anatomical parameters showed that the mean deviation of linear parameters was less than 6 mm,and that of angular parameters was less than 2.5°.The results of statistical tests showed P＞0.05 for all anatomical parameters,proving that the knee SSM prediction model was not statistically different from the true healthy model in terms of geometric shape.Conclusions This study derived a reference range of anatomical parameters for a healthy knee and demonstrated that the knee SSM model was consistent with the real healthy model in terms of shape.The results provide a reference for the design of knee SSM-based prostheses.

Objective To explore the value of shear wave elastography(SWE)in the early assessment of hepatic and renal fibrosis in patients with metabolic associated fatty liver disease(MAFLD).Methods A total of 52 MAFLD patients admitted to the Second Affiliated Hospital of Wenzhou Medical University from July 2023 to May 2024 were selected as MAFLD group,and 40 non-MAFLD patients treated during the same period were served as control group.General information,laboratory data and ultrasound data were collected and compared between two groups.The differences as well as the correlation of the indicators between two groups were compared.The value of SWE in hepatic fibrosis and renal fibrosis in MAFLD patients was assessed.Results Liver function indicators,uric acid and aspartate aminotransferase-to-platelet ratio index(APRI)in MAFLD group were higher than those in control group(P＜0.01);There were no statistically significant differences between two groups in fibrosis 4 index,estimated glomerular filtration rate,serum creatinine and blood urea nitrogen(P＞0.05).The brightness of the liver,liver-kidney ratio,and liver elasticity value were higher in MAFLD group than those in control group(P＜0.05);There was no significant difference in the elasticity value of the right renal cortex between two groups(P＞0.05).Liver elasticity values was positively correlated with alanine aminotransferase(ALT);The liver-kidney ratio was positively correlated with body mass index(BMI),ALT,aspartate aminotransferase,alkaline phosphatase,y-glutamyl transferase and APRI.No significant correlation was found between the right renal cortex elasticity and BMI,estimated glomerular filtration rate,serum creatinine,blood urea nitrogen,or serum uric acid.Conclusion SWE helps in early identification of liver hardness in the MAFLD patients.But the application of SWE in early renal fibrosis in the MAFLD patients needs further evaluation.

【Objective】 To explore the causal association between interleukin (IL) level and constipation by using two-sample Mendelian randomization. 【Methods】 Analyses were performed based on the data from gene-wide association studies (GWAS). Both interleukin and constipation data were obtained from European populations. IL as an exposure variable was obtained from two GWAS data sets: ⅰ. from a genetic map of the human plasma proteome containing 3 301 samples; ⅱ. from a GWAS data set on 90 circulating proteins, containing 30 931 samples. Constipation as an outcome variable was obtained from two GWAS data sets: ⅰ. from Finngene, containing 26919 cases and 282235 controls; ⅱ. from UKBiobank, containing a total of 3 328 cases and 459682 controls. Single nucleotide polymorphisms strongly associated with exposure variables were used as instrumental variables, with inverse variance weighted (IVW) as the main analysis method, MR-egger regression and weighted median method as supplementary evidence for IVW results, and horizontal pleiotropy and heterogeneity were tested to ensure the stability of the results. 【Results】 In both of the two different outcome variables GWAS data, IVW analysis results showed that decreased level of IL-17 receptor C was associated with an increased risk of constipation, with ORs of 0.956 (95% CI: 0.916-0.997, P=0.036‖Finngene) and 0.998 (95% CI: 0.997-0.999, P=0.040‖ukb). Increased level of IL-18 was associated with an increased risk of constipation, with ORs of 1.055 (95% CI: 1.008-1.104, P=0.022‖Finngene) and 1.001 (95% CI: 1.000-1.002, P=0.044‖ukb); while in the Finngene data, the IVW results also suggested that increased levels of IL-2 receptor alpha subunit α and decreased levels of IL-10 and IL-17 were associated with an increased risk of constipation, with ORs of 1.054 (95% CI: 1.001-1.110, P=0.049), 0.945 (95% CI: 0.896-0.996, P=0.035) and 0.934 (95% CI: 0.896-0.997, P=0.040). 【Conclusion】 IL-17 receptor C, IL-18, IL-2 receptor alpha subunit α, IL-10, and IL-17 were causally associated with the risk of constipation.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

Objective:To study the effect of eye-open/closed state on 40 Hz auditory steady state response (ASSR) in first-degree relatives of schizophrenia.Methods:Thirty-eight first-degree relatives of schizophrenic patients treated in Shanghai Mental Health Center from March 2010 to October 2011 were selected, and 31 healthy controls were recruited in the same period. All subjects were assessed with schizotypal personality questionnaire (SPQ). The 40 Hz EEG ASSR signals lasting for 3 min under open and closed eyes of all subjects were sequentially collected.Event-related spectrum perturbation (ERSP) and intertribal phase coherence (ITC) were used to evaluate ASSR. SPSS 22.0 software was used for statistical analysis. Two-way analysis of variance was used to compare ITC and ERSP between the two groups under open and closed eyes. Spearman correlation analysis was used to analyze the correlation between each measurement.Results:ITC in group main effect and group×the eye open/closed interaction effect were not significant (both P>0.05), but the main effect of eye-open and eye-closed was significant ( F(1, 67)=10.61, P=0.002). In the healthy control group, the ITC in eye-open state was significantly higher than that in eye-closed state ( P=0.014), and in the first-degree relatives group, the ITC in eye-open state was higher than that in eyes closed state ( P=0.039). ERSP in the main effect of eye-open and eye-closed ( F(1, 67)=0.195, P=0.660), group main effect ( F(1, 67) =0.627, P=0.431), group × the eye-open/closed interaction effect ( F(1, 67)= 1.034, P=0.313) was not significant. Spearman correlation analysis showed that there was no correlation between ERSP (eye open: r=-0.260, P=0.210; eye closed: r=-0.318, P=0.122), ITC (eye open: r=-0.248, P=0.232; eye closed: r=-0.260, P=0.209) and SPQ score in the healthy control group. There was also no correlation between ERSP (eye open: r=-0.387, P=0.226; eye closed: r=-0.363, P=0.238) or ITC (eye open: r=0.126, P=0.485; eye closed: r=0.096, P=0.595) and SPQ score in the first-degree relatives group of schizophrenia. Conclusion:The regulation pattern of 40 Hz ASSR in schizophrenic first-degree relatives is not significantly impaired in the eye-open/closed state, suggesting that the open/closed regulation pattern of 40 Hz ASSR may not be a potential marker for predicting the genetic high-risk prognosis of schizophrenia.

Objective : To investigate the role of hepatic long-chain non-coding RNA (lncRNA) H19 in key genes associated with glucose metabolism disorder induced by p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE). Methods: Human embryonic liver CCC-HEL-1 cells were divided into the DMSO group, 0.1 μmol/L p,p′-DDE group, 1 μmol/L p,p′-DDE group, 10 μmol/L p,p′-DDE group, small interference RNA (siRNA)+DMSO group and siRNA+10 μmol/L p,p′-DDE group. The promoter region methylation, mRNA expression and protein expression of hepatocyte nuclear factor 4α (HNF4α), forkhead box transcription factor O1 (FoxO1) and insulin-like growth factor (IGF2) were detected in CCC-HEL-1 cells using the bisulfite method, real-time fluorescence quantitative PCR (qPCR) assay and BCA assay, respectively. The changes in H19 mRNA expression, the methylation of associated genes in the promoter region and transcriptional expression were compared in CCC-HEL-1 among groups. Results: Exposure to p,p′-DDE alone at different doses resulted in an increase in H19 expression, and the H19 mRNA expression was higher in the 10 μmol/L p,p′-DDE group than in the DMSO group [(1.31±0.25) vs. (1.02±0.22); P<0.05]. Lower methylation of the HNF4α gene in the pro moter region [(38.59±32.77)% vs. (61.43±24.64)%; P<0.05] and higher HNF4α mRNA expression [(1.33±0.26) vs. (1.03±0.28); P<0.05] were detected in the 10 μmol/L p,p′-DDE group than in the DMSO group, while no significant differences were detected between the two groups in terms of the methylation of FoxO1 and IGF2 genes in the promoter region, FoxO1 and IGF2 mRNA and protein expression (P>0.05). Following siRNA-induced H19 knockdown, higher methylation of the HNF4α gene in the promoter region [(71.33±22.23)% vs. (38.59±32.78)%; P<0.05], lower HNF4α mRNA expression [(0.71±0.17) vs. (1.33±0.26); P<0.05], higher methylation of FoxO1 gene in the promoter region [(47.73±34.24)% vs. (25.09±25.35)%; P<0.05] and higher IGF2 mRNA [(1.39±0.25) vs. (0.80±0.20); P<0.05] were found in the siRNA+DMSO group than in the 10 μmol/L p,p′-DDE group, and higher IGF2 protein expression was detected in the siRNA+DMSO group than in the DMSO group [(1.03±0.11) vs. (0.74±0.12); P<0.05]. Conclusion Hepatic H19 may alter HNF4α, FoxO1 and IGF2 transcription and expression through mediating the methylation of genes in the promoter region, thereby playing a role in p,p′-DDE-induced glucose metabolism disorders.