Objective·To explore the predictive capability of retinal vascular features in preeclampsia(PE)based on artificial intelligence(AI)models.Methods·This retrospective study enrolled 789 pregnant women who registered from June 2020 to January 2021 at Shanghai First Maternity and Infant Hospital of Tongji University in the first 16 weeks of gestation.These women underwent regular prenatal examinations,had retinal fundus images captured,and delivered singleton live births at the hospital.According to whether they developed hypertensive disorders of pregnancy(HDP),they were divided into unaffected group(n=685)and HDP group(n=104).Within the HDP group,pregnancies were further categorized into gestational hypertension(GH)group(n=36)and PE group(n=68)based on the occurrence of PE.Based on the gestational age at onset,the PE group was further divided into early-onset PE group(gestational age<34 weeks)and late-onset PE group(gestational age≥34 weeks).Fundus images of the pregnant women were obtained,and an AI algorithm was utilized to diagnose retinal lesions and quantify retinal vascular features.Comparative analyses were conducted on fundus features and retinal vascular features.Univariate Logistic regression model was employed to analyze the influencing factors of PE occurrence,and multivariate Logistic regression model was further utilized to assess the correlation between retinal vascular features and the occurrence of PE.The predictive capability of retinal vascular features for PE(both early-and late-onset PE)was analyzed by using area under the curve(AUC)of receiver operator characteristic curve(ROC curve).Results·The comparative analysis of fundus features and retinal vascular features demonstrated statistically significant differences between the unaffected group and PE group in terms of central retinal artery equivalent(CRAE),central retinal vein equivalent(CRVE),arteriole-to-venular ratio(AVR),retinal artery tortuosity and retinal artery fractal dimension(all P<0.05).Univariate Logistic regression analysis indicated that second-trimester mean arterial pressure(MAP),second-trimester estimated fetal weight(EFW),CRAE,CRVE,AVR,retinal artery tortuosity and retinal artery fractal dimension were the influencing factors for PE occurrence(all P<0.05).Multivariate Logistic regression analysis revealed that second-trimester EFW,CRAE,CRVE,AVR,retinal artery tortuosity and retinal artery fractal dimension were the protective factors for the occurrence of PE,while second-trimester MAP was the risk factor for PE(all P<0.05).The analysis of ROC curves revealed that maternal risk factors along with second-trimester prenatal examination data(including MAP and EFW)and retinal vascular features model had good predictive ability for PE[AUC(95%CI)=0.784(0.725-0.843),and this model exhibited better predictive capability for early-onset PE,with an AUC(95%CI)of 0.840(0.756-0.924).Conclusion·The integration of quantified retinal vascular features based on AI models with maternal risk factors and second-trimester prenatal examination data(including MAP and EFW)enables a more effective prediction of PE occurrence,particularly early-onset PE.

Protein kinase CK2 is a common, evolutionarily conserved and ubiquitous protein kinase. In recent years, increasing evidences have shown that CK2 has a variety of phosphorylated protein substrates, which play important roles in growth, development and various diseases. Therefore, CK2 may participate in these physiological processes by regulating the phosphorylation of these substrates. This article briefly reviewed the structural characteristics of protein kinase CK2 and its physiological functions in growth, development, immunity, formation of tumor and other diseases, in order to provide knowledge basis for further research on the regulatory mechanism of CK2 and potential applications of its inhibitors.
Casein Kinase II/metabolism* ; Phosphorylation ; Proteins

Objective: To investigate the cumulative and sensitive period effects of family adversity on the outcome of psychopathological symptoms,so as to provide evidence for the prevention and intervention of adverse events. Methods: A total of 710 adolescents were recruited from local schools in rural area of Fuyang,Anhui Province in Dec. 2017 by using the convenience sampling method. The Adverse Childhood Experiences Questionnaire was used to assess family adversity. The MacArthur Health & Behavior Questionnaire was used to assess internalizing and externalizing symptoms. Multiple linear regression model was used to analyze the association between number and time of family adversity and psychopathological symptoms. Results: Persistent family adversity was associated with increased internalizing symptoms [(β(95%CI)=0.35(0.15-0.54)] and increased externalizing symptoms [β(95%CI)=0.16(0.01-0.32)]. 2 and ≥3 family adversities were associated with increased internalizing symptoms[β(95%CI)=0.20(0.04-0.36),0.42(0.24-0.60)]and increased externalizing symptoms[β(95%CI)=0.14(0.01-0.26),0.23(0.09-0.37)]. In childhood family adversity group,2 and ≥3 family adversities were associated with increased internalizing symptoms [β(95%CI)=0.23(0.06-0.41),0.34(0.11-0.58)] and increased externalizing symptoms [β(95%CI)=0.17(0.02-0.31),0.21(0.02-0.39)]. In persistent family adversity group,≥3 family adversities were associated with increased internalizing symptoms[β(95%CI)=0.56(0.31-0.82)] and increased externalizing symptoms [β(95%CI)=0.24(0.02-0.45)]. Adolescence family adversity was not associated with psychopathological symptoms. Conclusion The cumulative family adversity may increase the risk of psychopathological symptoms,and that childhood may be the sensitive period for family adversity to cause psychopathological symptoms.

The neurotrophin-tyrosine receptor kinase B (TrkB) signaling pathway plays an important role in regulating the balance of excitation and inhibition in the primary visual cortex (V1). Previous studies have revealed its mechanism of regulating the level of cortical excitability by increasing the efficiency of excitatory transmission, but it has not been elucidated how TrkB receptors regulate the balance of excitation and inhibition through the inhibitory system, which in turn affects visual cortex function. Therefore, the objective of this study was to investigate how the TrkB signaling pathway specifically regulates the most important inhibitory neuron-PV neurons affects the visual cortex function of mice. The expression of TrkB receptor on PV neurons in the V1 region was specifically reduced by the virus, the functional changes of inhibitory and excitatory neurons in the primary visual cortex were recorded by multi-channel electrophysiological in vivo. The orientation discrimination ability of mice was tested by behavioral experiments, and altered orientation discrimination ability of mice was tested by behavioral experiments. The results showed that reduced expression of TrkB receptors on PV inhibitory neurons in primary visual cortex significantly increased the response intensity of excitatory neurons, reduced the orientation discrimination ability of inhibitory and excitatory neurons, and increased the signal-to-noise ratio, but the orientation discrimination ability at the individual level in mice showed a decrease. These results suggest that the TrkB signaling pathway does not modulate the function of PV neurons solely by increasing excitatory transmission targeting PV neurons, and its effect on neuronal signal-to-noise ratio is not due to enhancement of the inhibitory system.
Mice ; Animals ; Receptor, trkB/metabolism* ; Neurons/metabolism* ; Signal Transduction

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor β1 (TGF-β1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-β1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in Transwell^TM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-β1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-β1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. Transwell^TM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-β1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.
Humans ; Arthritis, Rheumatoid/genetics* ; Interleukin-23 ; Macrophages ; RNA, Messenger ; RNA, Small Interfering/genetics* ; Smad7 Protein/genetics* ; Transforming Growth Factor beta1/genetics* ; Smad3 Protein/genetics* ; Gene Silencing