Objective To observe effect of environmental enrichment on the learning and memory ability and the expressions of hypoxia inducible factor 1α (HIF-1a) and vascular endothelial growth factor (VEGF) in rats with chronic cerebral hypoperfusion.Methods A total of 40 rats were randomly divided into 3 groups: bilateral vascular occlusion (2VO) of the common carotid arteries group (n=14, 2VO group), 2VO + enriched environment (EE) group (n=14, 2VO+EE group) and sham group (n=12, SHAM group).Morris water maze, novel object recognition test, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR), immunohistochemistry methods and Western blotting were used to detect changes in learning and memory ability of rats and HIF-1α and VEGF expression levels in hippocampus.Results Morris water maze showed that the escape latency was longer in the 2VO group than in the SHAM group at 3, 4 and 5 day during the training (all P＜0.05), while the 2VO+EE group spent significantly less time in finding the platform as compared with the 2VO group at 4 and 5 day (both P＜0.05).The time for space exploration in target quadrant was less in 2VO group than in SHAM group (P＜0.05), while it was longer in 2VO +EE group than in 2VO group (P＜0.05).Novel object recognition test showed that the 2VO operation impaired the priority index (PI) of time spending at exploring the novel object (P＜0.05), and environmental enrichment could improve the PI in 2VO group (P＜0.05).The real-time RT-PCR and Western blotting showed that the HIF-1α mRNA expression was higher in 2VO group than in SHAM group (P＜0.05).The VEGF mRNA and protein expressions were higher in 2VO+EE group than in 2VO group (both P＜0.05).The expression of HIF-1α in hippocampal CA1 area was higher in 2VO group than in SHAM group (P＜0.05).Conclusions Environmental enrichment can alleviate the damages of spatial and non-spatial learning and memory ability which are caused by chronic cerebral hypoperfusion.And HIF-1α and its downstream gene VEGF may be involved in the restoration of cognitive function by enriched environment.

Objective To observe the effects of Radix Angelica Sinensis ( RAS) on depression be-havior and cytokines,TNF-αand IL-6,in the hippocampus and prefrontal cortex of depression model rats in-duced by chronic unpredictable mild stress ( CUMS) .Methods 32 adult male rats weighting 140-160 g were randomly divided into 4 groups: Control,CUMS,CUMS+fluoxetine and CUMS+RAS groups.CUMS procedure went on 5 consecutive weeks and during the last 3 weeks the rats in CUMS+fluoxetine and CUMS+RAS groups were taken RAS or fluoxetine via intragastric administration.After 5-week CUMS procedure, rats were subjected to sucrose preference test,forced swimming test and open field test.After behavioral tests were finished,all rats were anesthetized with 10%chloral hydrate (350 mg/kg,intraperitoneal injection) and then decapitated.The hippocampus and prefrontal cortex of rats were separated and ELISA was used to detect the expression of TNF-αand IL-6 in these regions.Results Comparing with control rats, rats exposed to CUMS showed decreased sucrose preference ratio((42±15)%),prolonged immobility time ((68.28±16.50) s),decreased crossing numbers (31.25±21.56) and increased TNF-α((206.14±30.53)pg/ml) and IL-6 ((369.51±103.81)pg/ml) expression in hippocampus and TNF-α((199.33±25.67)pg/ml) and IL-6 ((347.74±81.04) pg/ml) expression in prefrontal cortex ( P<0.01).However,RAS treated rats reversed the behavioral changes such as sucrose preference ratio((66±21)%),immobility time ((32.53±10.26)s) and crossing numbers ( 83.00 ±23.25 ) , meanwhile reduced TNF-α( ( 53.42 ±12.43 ) pg/ml ) and IL-6 ((93.84±13.19)pg/ml) expression in hippocampus,TNF-α((57.58±8.33)pg/ml) and IL-6((91.18± 17.37) pg/ml) expression in prefrontal cortex among stress rats ( P<0.01) .Conclusion RAS can amelio-rate CUMS induced depression behaviors of rats through regulating hippocampus and prefrontal cortex cyto-kines ( TNF-α,IL-6) .

Objective To explore the effect and molecular mechanism of CC chemokine ligand 2 (CCL2) on epithelial-mesenchymal transition in human breast cancer cells.Methods Breast cancer Michigan cancer foundation-7 (MCF-7) cells were treated with 50 ng/ml CCL2.The abilities of invasion were detected by Transwell assay.The expression of epithelial-mesenchymal transition (EMT)-associated markers,E-cadherin and vimentin were detected by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR).The expressions of Snail,protein kinase B (AKT),phosphorylated protein kinase B (p-AKT),phosphorylated glycogen synthase kinase 3β (p-GSK3β3) and GSK3β were detected by Western blot.Snail nuclear localization was detected by immunoflurescence staining.Results We found that CCL2 treatment could induce morphological alteration of MCF-7 cells from epithelial morphology to mesenchymal morphology.CCL2 significantly increased the migration of MCF-7 cells,and increased the expression of mesenchymal maker vimentin and decreased epithelial marker E-cadherin.More important,treatment of CCL2 significantly increased the expression of Snail,and promoted the nuclear localization of Snail.Knockdown of Snail significantly reverse the effects of CCL2 on the EMT in MCF-7 cells.Moreover,treatment of CCL2 significantly increased the phosphorylation levels of p-AKT and p-GSK3β,and AKT inhibitor LY294002 significantly inhibited CCL2-induced Snail and p-GSK3β expression.Conclusion CCL2 might induce EMT in MCF-7 cells,by which mechanism is related to activate AKT/GSK3β Snail pathway.

The residents who had lived for at least 5 years and aged over 20 years old were sampled from urban to rural districts of Jiangsu Province with a stratified cluster sampling technique. B mode ultrasonography and thyroid function determination were carried out in 6 128 persons. The location, diameter, number, boundary, and calcification in thyroid nodules were described by using 7.5 MHz/50 mm transducer of thyroid ultrasonography. TSH was measured by chemiluminescence immunoassay. Free triiodothyronine(FT3)and free thyroxin(FT4)were measured when TSH was abnormal. The crude prevalence of thyroid nodules was 21.12% in total population, 14.55% in male, and 25.24% in female. The standardized prevalence was 15.69%, 11.20%, and 20.40%, respectively. The prevalence was lower in male than in female, and increased with age(P＜0.05). Thyroid nodules in Jiangsu Province were highly prevalent and more attention should be paid to the follow-up, early diagnosis, and treatment.

Objective To investigate the prevalence and epidemiologic characteristics of hypothyroidism among community population in Jiangsu province. Methods The residents who had lived for at least five years and aged more than 20 years old were sampled from six layers in urban and rural districts of Jiangsu province by a stratified cluster sampling technique. Serum was sampled from 7 122 subjects and sTSH was measured by chemiluminescence immunoassay, and FT3 and FT4 were determined in the subjects with abnormal sTSH level. Results (1) The crude prevalences of overt hypothyroidism and subclinical hypothyroidism were 0.66% and 7.53% respectively in total population, with the respective standardized rates of 0.43% and 6.28%. (2)The prevalences of hypothyroidism and subclinical hypothyroidism were significantly higher in females than in males (both P <0.05). (3) The prevalence of subclinical hypothyroidism was significantly increased with advancing age in both female and males (P<0.05). Conclusion Comparing with hypothyroidism, subclinical hypothyroidism shows higher prevalence in Jiangsu province, and more attention should be paid to the follow-up and diagnosis of subclinical hypothyroidism.

Objective:To explore the value of radiomics model based on intratumoral and peritumoral early dynamic contrast-enhanced (DCE) MRI for identifying benign and malignant in breast imaging reporting and data system (BI-RADS) 4 tumors.Methods:A total of 191 patients diagnosed with BI-RADS 4 breast tumors by breast MRI examination with clear pathological diagnosis from January 2016 to December 2020 in the First Affiliated Hospital of Bengbu Medical College were analyzed retrospectively, including 77 benign and 114 malignant cases, aged 23-68 (46±10) years. The one-slice image with the largest area of the lesion of the second stage DCE-MRI images was selected to outline the region of interest, and automatically conformal extrapolated by 5 mm to extract the intra-tumoral and peritumoral radiomics features. The included cases were randomly divided into training and testing cohorts in the ratio of 8∶2. The statistical and machine learning methods were used for feature dimensionality reduction and selection of optimal radiomics features, and logistic regression was used as the classifier to establish the intratumoral, peritumoral, and intratumoral combined with peritumoral radiomics models. The independent risk factors that could predict the benignity and malignancy of breast tumors were retained as clinical-radiological characteristics by univariate and multivariate logistic regression to establish a clinical-radiological model. Finally, the intratumoral and peritumoral radiomics features were combined with clinical-radiological features to develop a combined model of the three. The receiver operating curve was used to analyze the predictive performance of each model and calculate the area under the curve (AUC),the AUC was compared by DeLong test. The stability of the three-component combined diagnostic model was tested by 10-fold cross-validation, and the model was visualized by plotting nomogram and calibration curves.Results:In the training cohort, the AUC of the three-component combined model for identifying benign and malignant BI-RADS 4 breast tumors was significantly higher than that of the intratumoral radiomics model ( Z=3.38, P<0.001), the peritumoral radiomics model ( Z=4.01, P<0.001), the intratumoral combined with peritumoral radiomics model ( Z=3.11, P=0.002), and the clinical-radiological model ( Z=3.24, P=0.001). And the AUC, sensitivity, specificity, accuracy, and F1-score of the three-component combined model were 0.932, 91.2%, 86.9%, 87.0% and 0.89, respectively. In the testing cohort, the three-component combined model also had the highest AUC value (0.875), and diagnostic sensitivity, specificity, accuracy and malignancy F1-score were 95.7%, 62.5%, 76.9%, and 0.89, respectively. The AUC calculated by 10-fold cross-validation was 0.90 (0.85-0.92), and the predicted curve of the three-component combined model in the calibration curve was in good agreement with the ideal curve. Conclusion:The three-component combined diagnostic model based on the intratumoral and peritumoral radiomics features and clinical-radiological features of early DCE-MRI has good performance and stability for identifying the benign and malignant in BI-RADS 4 breast tumors, and it can provide guidance for clinical decision non-invasively.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.