This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.

Molecular imprinting is a biomimetic technique that simulates the specific recognition of biological macromolecules such as antibody. Based on molecular imprinting and high-specificity affinity analysis,the biomimetic imprinting affinity analysis (BIA) possesses many advantages such as high sensitivity,strong tolerance,good specificity and low cost,and thus,it has shown excellent prospects in food safety detection,pharmaceutical analysis and environmental pollution monitoring. In this review,the construction methods of recognition interfaces for BIA were summarized,including bulk polymerization,electro-polymerization and surface molecular imprinting. The application of molecularly imprinted polymers in different analysis methods,such as radiolabeled affinity analysis,enzyme-labeled affinity analysis,fluorescence-labeled affinity analysis,chemiluminescence affinity analysis and electrochemical immunosensor was mainly discussed. Furthermore,the challenges and future development trends of BIA in practical application were elucidated. This review might provide new reference ideas and technical supports for the further development of BIA technique.

Objective To determine the optimal conditions for CXCR4 upregulation by comparing the expression levels of chemokine(C-X-C motif)receptor 4(CXCR4)in MSCs cultured with varying concentrations of oxygen and hydrogen peroxide(H2O2).Methods MSCs were cultured with 0.1％,1％,or 3％O2 and 50 μmol/L H2O2 for different lengths of time(3,6,12,and 24 h).The mRNA and protein expressions of CXCR4 in MSCs were measured by real-time quantitative PCR(qPCR),Western blotting,and immunofluorescence staining.The viability and chemotactic ability of MSCs were measured using CCK-8,wound-healing and Transwell migration assays.Results Both hypoxia and H2O2 treatment were found to upregulate MSC expressions of CXCR4 to some extent.The mRNA and protein levels of CXCR4 were higher after 6-12 h of culture of MSCs with 3％O2,and significantly higher when treated with H2O2 for 6 h.Cell viability was significantly increased after culture with 3％O2 compared with the control group and both 3％O2 and H2O2 pretreatment could enhance chemotactic migration in MSCs.Conclusion Culture with 3％O2 and H2O2 pretreatment can upregulate CXCR4 expressions in MSCs and enhance migration in cells,with superior effects observed with 3％O2.Therefore,treatment with 3％O2 represents the best choice for upregulating the chemotactic ability of MSCs.

Objective: To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of ~12 weeks from community hospitals in Tianjin. Latent class growth modeling (LCGM) was used to model the blood pressure trajectories. Methods: This was a large prospective cohort study. The study enrolled pregnant women of ~12 weeks of gestation in 19 community hospitals in Tianjin from November 1, 2016 to May 30, 2018. We obtained related information during 5 antepartum examinations before gestational week 28, i.e., week 12, week 16, week 20, week 24 and week 28. LCGM was used to model longitudinal systolic (SBP) and diastolic blood pressure (DBP) trajectories. For the association study, the predictors were set as SBP and DBP trajectory membership (built separately), the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation. Results: A total of 5 809 cases with known pregnant outcomes were documented. After excluding 249 cases per exclusion criteria, 5 560 cases with singleton pregnancy were included for final analysis. There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort. Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia. Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for SBP latent classification trajectory_ 4 was 4.023 (95%CI: 2.368 to 6.835, P<0.001), and the OR for SBP latent classification trajectory_3 was 1.854 (95%CI: 1.223 to 2.811, P=0.004). Logistic regression showed that: using the DBP latent classification trajectory_1 as the reference group, the OR for DBP latent classification trajectory_4 was 4.100 (95%CI: 2.571 to 6.538, P<0.001), and 2.632 (95%CI: 1.570 to 4.414, P<0.001) for DBP latent classification trajectory_2. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for DBP_traj_4 was 2.527 (95%CI: 1.534 to 4.162, P<0.001), and the OR for DBP_traj_3 was 1.297 (95%CI: 0.790 to 2.128, P=0.303), and 2.238 (95%CI: 1.328 to 3.772, P=0.002) for DBP_traj_2. Therefore, BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia. Receiver operating characteristic (ROC) curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories. Conclusion: By applying LCGM, we for the first time identified distinctive BP trajectories from gestational week 12 to 28, which can independently predict the development of preeclampsia after 28 weeks of gestation.
Female ; Humans ; Pregnancy ; Infant ; Blood Pressure ; Pre-Eclampsia/diagnosis* ; Prospective Studies ; Gestational Age ; Alanine Transaminase ; Hemoglobins

Objective: To understand the associations between internet addiction, screen time (computer/mobile devices use and television watching time) and depressive symptoms in adults. Methods: A total of 6 932 adults aged <60 years from the Tianjin Chronic Low-grade Sgstemic Inflammation and Health (TCLSIH) Cohort of 2013-2019 were surveyed. The information about their computer/mobile devices use and television watching time were collected by using a self-reported questionnaire. The depressive symptoms were assessed using the self-rating depression scale (SDS). The adults surveyed were divided into two groups: non-depressive symptom group (SDS score <45) and depressive symptom group (SDS score ≥45). The associations between internet addiction, screen time and depressive symptoms were estimated using Cox proportional hazard regression models, with adjusting for multiple confounders. Results: After adjusting for confounding factors, the hazard ratios (HRs) of depressive symptom in the adults who had internet addiction before, had light internet addiction and had moderate or severe internet addiction were 0.83 (95%CI: 0.56-1.23) , 1.20 (95%CI: 1.03-1.41) for light and 1.48 (95%CI: 1.16-1.89), respectively, compared with those without internet addiction. The linear trend test results of the association between internet addiction and depressive symptoms was significant (trend P<0.001). Compared with the adults who used computer/mobile devices for <1 hour/day, the HRs of depressive symptoms in those who used computer/mobile devices for >1 hour, >3 hours, >5 hours and >10 hours were 0.59 (95%CI: 0.40-0.88), 0.58 (95%CI: 0.40-0.85), 0.52 (95%CI: 0.36-0.76) and 0.69 (95%CI: 0.45-1.05) respectively, a U-shaped association was found between computer/mobile devices use time and depressive symptoms (trend P<0.001). Compared with the adults who never watch TV, the HR of depressive symptoms was 1.36 (95%CI:1.09-1.69) for those watching TV for ≥3 hours/day in crude model and 1.34 (95%CI: 1.07-1.68) for those watching TV for ≥3 hours/day in adjusted model (trend P<0.001). Conclusion: Our findings suggested that internet addiction and television watching time were associated with an increased risk of depressive symptoms, while computer/mobile device use time was associated with a reduced risk of depressive symptoms.
Adult ; Humans ; Screen Time ; Internet Addiction Disorder ; Self Report

Objective: To explore the association between weight gain during the first half of pregnancy and the risk of hypertension disorder of pregnancy (HDP). Methods: This prospective cohort study recruited singleton pregnant women in the first trimester from November 2016 to March 2019 at 19 community hospitals in Tianjin. According to pre-pregnancy body mass index (BMI), the cohort was divided into 3 groups: underweight(BMI<18.5 kg/m²), normal-weight(18.5-24.9 kg/m²), and overweight/obese(≥25.0 kg/m²). The basic information of the participants was gathered through questionnaires, and the height, weight, and blood pressure of the participants were measured along with routine pregnancy examinations. The rate of gestational weight gain (rGWG) in the 3 periods (0-13⁺⁶, 14⁺⁰-20⁺⁶, and 0-20⁺⁶ weeks) of the participants was calculated. To observe the occurrence of HDP, the participants were followed up to 42 days postpartum. Using a generalized linear model, the association between rGWG at the 3 periods during the first half of pregnancy and HDP after 20 weeks of gestation was evaluated. Results: A total of 9 805 pregnant women were finally included, with the age of (30.6±3.8) years old, 9 418 (96.1%) Han ethnicity, and 6 845 (69.8%) primipara. There were 1 184 (12.1%), 6 831 (69.7%) and 1 790 (18.3%) participants in the underweight, normal-weight, and overweight/obese groups. Five hundreds and eight pregnant women were diagnosed with HDP (5.2%). The incidences of HDP were 1.8% (21/1 184), 3.9% (269/6 831), and 12.2% (218/1 790), respectively, in underweight, normal-weight, and overweight/obese groups. Adjusted for age, pre-pregnancy BMI, primipara, and family history of hypertension, women in the entire cohort with rGWG ≥ 0.18 kg/week before 13⁺⁶ weeks of pregnancy had a 28% higher HDP risk than those with rGWG ≤ 0.00 kg/week (RR=1.28, 95%CI 1.04-1.55, P=0.015), and the risk of HDP was increased by 39% in the overweight/obese group (RR=1.39, 95%CI 1.04-1.85, P=0.026), while no correlation was found between rGWG and HDP in underweight and normal-weight pregnant women (P>0.05). Weight gain during 14⁺⁰-20⁺⁶ weeks of pregnancy in any group was not related to the risk of HDP (P>0.05).In the entire cohort, compared to rGWG ≤0.14 kg/week, rGWG≥0.28 kg/week prior to 20⁺⁶ weeks increased HDP risk by 36% (RR=1.36, 95%CI 1.11-1.67, P=0.003). Normal-weight pregnant women with rGWG≥0.29 kg/week faced a 46% higher risk of HDP than those with rGWG≤0.15 kg/week (RR=1.46, 95%CI 1.11-1.93, P=0.008).In the overweight/obese group, excessive weight gain before 20⁺⁶ weeks seemed to increased risk of HDP, but the difference was not statistically significant (RR=1.35,95%CI 0.99-1.85, P=0.059), while the connection was nonexistent in underweight women. Conclusions: Except for pre-pregnancy underweight women, excessive weight gain during the first half of pregnancy is associated with increased risk of HDP among pregnant women.
Female ; Pregnancy ; Humans ; Infant, Newborn ; Adult ; Overweight/complications* ; Thinness/epidemiology* ; Prospective Studies ; Risk Factors ; Weight Gain ; Body Mass Index ; Obesity/complications* ; Hypertension, Pregnancy-Induced/etiology* ; Cohort Studies ; Pregnancy Complications

OBJECTIVE: To investigate the expression of CD56 in multiple myeloma (MM) cells and its relationship between extramedullary disease and extramedullary relapse. METHODS: Clinical data of 99 patients with MM treated in our hospital from January 2015 to December 2019 was retrospectively analyzed. The patients were divided into positive group and negative group according to the expression of CD56. The relationship between CD56 and multiple myeloma extramedullary disease, extramedullary relapse was analyzed. RESULTS: Among 99 newly diagnosed patients with MM, the positive rate of CD56 was 65%, and the incidence of extramedullary disease of patients in the CD56 positive group was lower than that in the CD56 negative group (17.19% vs 48.57%) (P<0.01). Meanwhile, the incidence of extramedullary relapse of patients in the CD56 positive group was lower than that in the CD56 negative group (1.56% vs 34.29%) (P<0.01). CONCLUSION CD56 is highly expressed in MM, and its low expression is associated with the occurrence of extramedullary disease and extramedullary relapse, which suggests that CD56 may be an important indicator for predicting the occurrence of extramedullary disease and extramedullary relapse.
CD56 Antigen ; Humans ; Multiple Myeloma ; Neoplasm Recurrence, Local ; Retrospective Studies

Thrombomodulin (TM) is a single-chain transmembrane glycoprotein that mainly exists in vascular endothelial cells, hematopoietic progenitor cells, monocytes and macrophages. TM is mainly composed of five structural regions: the N-terminal lectin-like domain which plays a role in anti-inflammatory, and the six epidermal growth factor-like repeats which function as coagulation and fibrinolysis as well as serine-rich threonine regions and transmembrane domains and cytoplasmic domains. TM exhibits anti-inflammatory and anticoagulant effects by binding to thrombin to activate protein C, and TM-thrombin complex can also activate fibrinolytic inhibitors to suppress fibrinolysis. Previous reports showed that inhibiting epithelial mesenchymal transformation, mitogen-activated protein kinase or activating protein C and fibrinolytic inhibitor are the major mechanisms by which TM exerts anti-tumor properties. In atherosclerosis, TM can prevent atherosclerosis by blocking the activation of thrombin-mediated PAR-1 and inhibiting autophagy and apoptosis of endothelial cells. TM lectin-like domains can also bind to thrombin to inhibit its activity and further inhibit pulmonary thrombosis, fibrosis and inflammation. Moreover, TM protein is also involved in the pathogenesis of diabetic nephropathy, preeclampsia and ischemia-reperfu-sion injury. At present, TM is only clinically used for the treatment of sepsis and disseminated intravascular coagulation. Its role and therapeutic potential in cardiovascular and cerebrovascular diseases, cancers and other diseases deserve further exploration.

Objective:Through phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR） signaling pathway， explore the effect of Zhigancao Tang on myocardial ischemia-reperfusion injury（MIRI）The role and mechanism of arrhythmia（ventricular tachycardia and ventricular fibrillation）. Method:The 72 SD rats were randomly divided into sham operation group，model group， Zhigancao Tang low，medium and high dose group（11.43，22.86，45.72 g·kg^-1），Wenxin granule group（2.43 g·kg^-1），continuous drug intervention for 10 days. Two hours after the last administration，the MIRI model of rat was prepared by ligating the left anterior descending coronary artery，and the changes of electrocardiogram were recorded. After successful modeling，blood and heart tissue were collected to detect the content of creatine creatine（CK），lactate dehydrogenase（LDH）and aspartate aminotransferase（AST）in the serum, the enzyme-linked immunoassay（ELISA） method was used to detect cardiac troponin（CtnI）content, immunohistochemical detection of myocardial PI3K，Akt，mTOR expression. Western blot was used to detect the myocardial autophagy-related protein microtubule-associated protein 1 light chain 3（LC-3），autophagy markers Beclin1 and PI3K/Akt/mTOR signaling pathway related protein expression and phosphorylated p-PI3K，p-Akt，p-mTOR levels. Result:In model group， 100% of ventricular tachycardia and 91.67% of ventricular fibrillation occurred. Compared with sham operation group， the serum levels of CK，LDH，AST，and CtnI in the model group were significantly increased（P<0.01），PI3K，Akt，mTOR AOD values in myocardial tissue were significantly increased （P<0.01），the relative expression of the ratio of LC3-Ⅱ/LC3-Ⅰ and Beclin1 was significantly increased（P<0.01），p-PI3K/PI3K，p-Akt/Akt，and p-mTOR/mTOR were significantly reduced （P<0.01）. Compared with model group， the incidence of ventricular tachycardia and ventricular fibrillation in the high-dose Zhigancao Tang group was significantly reduced （P<0.01），and the duration was the shortest compared with other administration groups（P<0.01）， CK，LDH，AST level and CtnI content were significantly reduced（P<0.01）， the expression of PI3K，Akt and mTOR of Zhigancao Tang group was significantly decreased with increasing dose（P<0.01）， the expression of LC-3 and Beclin1 was accompanied by Zhigancao Tang increase of each dose group of soup had different degrees of decrease （P<0.01），while the expression ratio of PI3K/Akt/mTOR-related protein was significantly increased （P<0.05，P<0.01）. Conclusion:Pretreatment of Zhigancao Tang can reduce the abusually elevated cardiac enzymes CK, LDH, AST and CtnI, inhibit excessive autophagy of cells, and up-regulate the expression of PI3K, Akt and mTOR, indicating that the anti-MIRI arrhythmia effect of Zhigancao Tang may be related to the PI3K/Akt/mTOR signaling pathway.