ObjectiveTo explore the sequential effects of hypoxic exercising on miR-27/PPARγ and lipid metabolism target gene and protein expression levels in the obesity rats’ liver. Methods13-week-old male diet-induced obesity rats were randomly divided into three groups (n＝10): normal oxygen concentration quiet group (N), hypoxia quiet group (H), hypoxic exercise group (HE). Exercise training on the horizontal animal treadmill for 1 h/d, 5 d/week for a total of 4 week, and the intensity of horizontal treadmill training was 20 m/min (hypoxic concentration was 13.6%). Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done. And the serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were detected. RT-PCR and Western Blot were used to detect the levels of miR-27, PPARγ, CYP7A1 and CD36. ResultsHypoxic exercise decreased the expression levels of miR-27 in the obese rats’ liver, however, the expression level of PPARγ was gradually increased. The expression levels of miR-27 in HE group were significantly lower than N group (P<0.05). The expression levels of PPARγ mRNA in N group were significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The protein expression of PPARγ protein in N group was significantly lower than that other groups (P<0.01). The expression of lipid metabolism-related genes and proteins increased in the obese rats’ liver. The expression of CYP7A1 mRNA in N group was significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The expression of CYP7A1 protein in the obese rats’ liver in N group was extremely lower than H group and HE group (P<0.01). The protein expression of CD36 in N group was significantly lower than that in HE group (P<0.05). Hypoxia exercise improved the related physiological and biochemical indexes of lipid metabolism disorder. The perirenal fat weight of obese rats in HE group was extremely lower than N group and H group (P<0.01), and the perirenal fat weight in N group was significantly higher than H group (P<0.05). The epididymal fat weight in N group was significantly higher than H group (P<0.05), and extremely higher than HE group (P<0.01). The Lee’s index in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TC in obese rats in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TG in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of LDL-C in N group was extremely higher than HE group (P<0.01). The serum concentration of HDL-C in N group was extremely lower than H group (P<0.01). ConclusionHypoxia and hypoxia exercise may negatively regulate the levels of PPARγ by inhibiting miR-27 in the obese rats’ liver, thereby affecting the expression of downstream target genes CYP7A1 and CD36, and promoting cholesterol, fatty acid oxidation and HDL-C transport in the liver, and ultimately the lipid levels in obese rats were improved. The effect of hypoxia exercise on improving blood lipid is better than simple hypoxia intervention.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Objective: To analyze the status and correlation between screen time, screen behavior type, and anxiety, depression among children and adolescents in Jiangxi Province, so as to provide a basis for effective intervention measures. Methods: Using the method of stratified random sampling, 8 851 primary and secondary school students in 11 districts of Jiangxi Province were investigated by questionnaire during September to December in 2020. Anxiety and depression status were investigated using the State Trait Anxiety Inventory (STAI) and the Center for Epidemiological Studies Depression Scale for Children(CES-DC), respectively. Single factor analysis using χ 2-test, t-test,analysis of variance,and multivariate analysis using generalized linear models. Results: On school days and weekends, 4.7% and 20.4% of primary and secondary school students in Jiangxi Province had a total screen time of over 2 hours per day, respectively. The weighted scores of the total screen time (primary school students: 1.88± 0.68, junior middle school students: 1.96±0.71, high school students: 2.03±0.80) and time spent for playing video games (primary school students: 1.51±0.64, junior middle school students: 1.62±0.69, high school students: 1.68±0.75) daily showed an upward trend with the increase of educational stage ( F =31.48, 42.13), and with significantly higher in boys (1.97±0.74, 1.66± 0.72) than girls (1.93±0.72, 1.53±0.66)( t =2.48, 9.07)( P <0.05). The average scores of state anxiety and trait anxiety were (42.20±9.05) and (40.65±9.85), which showed an upward trend with the increase of educational stage ( F =168.12, 241.98 ), and were higher in girls than boys ( t =6.63, 8.48)( P <0.01). The average score of depression was (11.99±11.00), which was lower in elementary school students than middle school students and high school students ( F =136.42), with significantly higher in girls ( t =6.85)( P <0.01). On school days, with the increase of total screen time and time spent for playing video games daily, the risk of state anxiety, trait anxiety, and depression among primary and secondary school students significantly increased ( OR = 6.70- 818.98, P <0.01). On weekends, among primary and secondary school students, the total screen time of >1-2 hours daily reduced the risk of state anxiety ( OR =0.30). The risk of developing trait anxiety among students playing video games for more than 2 hours daily was 2.50 times higher than those without screen behavior ( OR =2.50). The risk of developing depression with a total screen time of more than 2 hours daily was 3.15 times higher those whithout screen behavior ( OR =3.15). The risk of developing depression among students playing video games >0-1, >1-2, >2 h daily was 2.14, 2.50, 4.90 times that of those without screen behaviors ( OR =2.14, 2.50, 4.90), and showed an upward trend with the increase of educational stage ( P <0.05). Conclusions Screen behaviors of primary and middle school students in Jiangxi Province are positively associated with the risk of anxiety and depression, but the total daily video time of >1-2 h on weekends was negatively associated with state anxiety. It is necessary to control the screen time as much as possible and reduce the risk of anxiety and depression.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

Lung cancer remains one of the leading cause of global cancer-related mortality, posing a significant burden of disease. Tobacco exposure stands as the foremost risk factor for lung cancer. Since the 1960, global efforts have gradually been implemented to control tobacco exposure, consequently reducing tobacco exposure levels within populations. This shift in exposure levels may have altered the epidemiological characteristics of lung cancer globally. This study aims to describe global lung cancer incidence data across five dimensions: age, gender, region, stage at diagnosis, and survival status, using global cancer registry data and relevant research findings. The objective is to elucidate the current epidemiological features of lung cancer worldwide, providing a scientific basis for lung cancer prevention and control. Furthermore, this study offers corresponding measures and recommendations for lung cancer prevention and control, aligning with the three-tiered cancer prevention strategy. Findings indicate that the incidence and mortality burden of lung cancer is significantly higher among the elderly population (aged 65 years and above) compared to the working-age population (aged 15-64 years). The aged-standardized incidence rate of lung cancer remains higher in males than in females, but the overall aged-standardized incidence rate of lung cancer in males shows a declining trend, while that in females shows an increasing trend. Regions with high and very high human development index (HDI) exhibit a substantially higher incidence and mortality burden of lung cancer compared to regions with low and very low HDI. Japan ranks highest in the diagnosis of stage Ⅰ lung cancer, with a diagnosis rate of 38.6%. Its age-standardized 5-year net survival rate is relatively high at 32.9%. Despite improvements in the survival status of lung cancer in certain countries like China and Japan, the overall prognosis for lung cancer remains pessimistic. Given the current epidemiological characteristics of lung cancer, reinforcing tobacco control measures and reducing female-specific lung cancer risk factors stand as significant goals for primary prevention. Promoting low-dose computed tomography screening for high-risk population, minimizing false-positive rates in lung cancer screening, and promoting medical system reforms and standardized treatment constitute principal measures for secondary and tertiary lung cancer prevention, respectively.

Objective:To analyze the incidence, mortality, and survival status and trends of lung cancer in China.Methods:The data of incidence, mortality, disability-adjusted life year (DALY), and survival status and trends of lung cancer in China were collected from GLOBOCAN 2020, Global Burden of Disease Study in 2019 (GBD2019) databases, and the CONCORD-3 project report. Joinpoint 5.0 software was used to analyze the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of lung cancer in China from 1990 to 2019. Data management was conducted by using Excel 2016, and relevant graphical representations were generated using the ggplot2 package in software R 4.2.1.Results:In 2020, a total of 815 563 lung cancer cases were newly reported in China with the ASIR of 34.8/100 000, in which 539 181 cases were reported in men, with the ASIR of 47.8/100 000, and 276 382 cases were reported in women, with the ASIR of 22.8/100 000. A total of 714 699 lung cancer deaths were reported in 2020, with the ASMR of 30.2/100 000. Among these deaths, there were 471 546 deaths in men with the ASMR of 41.8/100 000, and 243 153 deaths in women with the ASMR of 19.7/100 000. From 1990 to 2019, the ASIR and ASMR of lung cancer in both men and women showed increasing trends ( P<0.05). However, from 2010 to 2019, the ASIR and ASMR of lung cancer in men showed decreasing trends, with annual percent of change (APC) of -0.17% (95% CI: -0.24% - -0.09%) and -0.69% (95% CI: -0.79% - -0.59%), respectively. The ASIR and ASMR of lung cancer in women showed increasing trends from 2016 to 2019, with APC of 3.33% (95% CI: 2.73% - 3.88%) and 2.61% (95% CI: 1.99% - 3.28%), respectively. The five-year net survival rate for lung cancer was 19.8% in China (95% CI:19.4% - 20.2%) from 2010 to 2014. Conclusions:The morbidity and mortality of lung cancer in China remain at high levels, the prognosis of lung cancer was poor, and the disease burden of lung cancer would become more serious in the context of population aging, so three-level prevention of lung cancer should be implemented to address this problem. In addition, attention should be paid to the increasing trends of ASIR and ASMR of lung cancer in women in recent years. Further investigation of risk factors and targeted prevention are needed to curb the rising trend in the incidence of lung cancer in women.

Objective To explore the mediating effect of maternal childbirth self-efficacy between reproductive health literacy during pregnancy and expected mode of delivery,in order to provide a reference for obstetric care providers to carry out scientific and reasonable childbirth decision support interventions.Methods A questionnaire survey was conducted among pregnant women in late pregnancy seeing doctors in Obstetric Clinic of Obstetrics and Gynecology Hospital,Fudan University from Oct 2020 to Feb 2021 using convenience sampling.A general information questionnaire,the Reproductive Health Literacy Scale,and Childbirth Self-efficacy Scale were used in the survey.Linear regression and Logistic regression analyses were used to assess the associations between reproductive health literacy during pregnancy and childbirth self-efficacy and expected mode of delivery,respectively,and to assess the significance of the mediating effect of childbirth self-efficacy between productive health literacy during pregnancy and expected mode of delivery.The MacKinnon's product-of-coefficients method was used to assess the mediating effect of maternal childbirth self-efficacy.Results A total of 343 participants were included in the study.Regression analysis results of factors influencing expected mode of delivery showed that reproductive health literacy during pregnancy(c'=1.644,95%CI:2.223-12.059)and childbirth self-efficacy(β=2.211,95%CI:6.300-13.215)were associated with expected mode of delivery(P<0.001);childbirth self-efficacy was significantly and positively associated with reproductive health literacy during pregnancy(β=1.280,95%CI:0.102-0.165,P<0.01).Childbirth self-efficacy was a mediating variable for health literacy during pregnancy and expected mode of delivery with an effect size of 24.8%.Conclusion Childbirth self-efficacy mediated the association between reproductive health literacy during pregnancy and expected mode of delivery.Obstetric care providers should focus on strengthening maternal care and childbirth education,improving pregnant women's childbirth self-efficacy and reproductive health literacy during pregnancy,thereby enabling women to make scientific decisions on expected mode of delivery in order to promote normal childbirth.