ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI/CLA-1) are the key proteins in reverse cholesterol transport (RCT). The high expression of ABCA1 and SR-BI/CLA-1 can decrease the danger of atherosclerosis. The purpose of the study is to find ABCA1 and CLA-1up-regulators for treating atherosclerosis by using cell-based high throughput screening models. Among 20 000 compounds screened, E0869 [1-(3, 4-dimethylphenyl)-1-oxopropan-2-yll4-((methylsulfonyl)methyl)benzoate] was found as the positive hit. The up-regulated activities of E0869 in ABCAl1-LUC and bCA-l1-LUC HepG2 cell were 160% and 175%, respectively. The EC50 values of E0869 in ABCAl1-LUC and CLA-l1-LUC HepG2 cell were 3.79 and 1.42 pμol- x ,(-1) respectively. E0869 could upregulate the mRNA and protein levels of ABCA1, SR-BI/CLA-1 and ABCGJ1genes in HepG2 and RAW264.7 cells by Real-Time Quantitative PCR and Western blotting analysis, but could not influence the expression of FAS, SREBP-l1 and CD36. Foam cell assay showed that E0869 could inhibit lipids accumulation in mouse peritoneal macrophages RAW264.7. Cholesterol efflux assay showed that E0869 could induce HDL-mediated cholesterol efflux in mouse peritoneal macrophages RAW264.7. In conclusion, E0869 could up-regulate ABCA1 and CLA-1 activity, and had good anti-atherosclerotic activity in vitro.

In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti-atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9 [hCD36] and CHO [hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC50 of 2.80 and 8.79 micromol x L(-1) in Sf9[hCD36] and CHO [hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce DiI-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.

Objective:To detect the expression of acetaldehyde dehydrogenase (ALDH) 2 and microRNA (miR)-135b-3p in endometrial cancer (EC) tissues, and to explore their correlation with clinical characteristics.Methods:94 endometrial cancer tissue specimens (EC group) and 60 normal endometrial specimens (control group) were selected from Northwest Women′s and Children′s Hospital from February 2019 to February 2022. Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression changes of ALDH2 mRNA and miR-135b-3p in endometrial tissue of two groups, and immunohistochemistry was used to detect the positive expression rate of ALDH2 protein. The relationship between the expression levels of ALDH2 and miR-135b-3p and the clinicopathological characteristics was analyzed.Results:The expression of ALDH2 mRNA in the EC group (0.67±0.15) was lower than that in the control group (1.05±0.12), and the expression level of miR-135b-3p (1.52±0.26) was higher than that in the control group (1.01±0.06). The positive expression rate of ALDH2 in cancer tissue of EC group was 30.85%(29/94), which was lower than 51.67%(31/60) in normal endometrial tissue of the control group ( P<0.05). The expression levels of ALDH2 mRNA and miR-135b-3p in EC patients were related to International Federation of Obstetrics and Gynecology (FIGO) stage, lymph node metastasis, differentiation and myometrium invasion (all P<0.05), but not to age, pathological type, menopause, HPV infection, menarche age, parity, tumor length and BMI (all P>0.05). Conclusions:In EC tissues, the expression of ALDH2 is down-regulated and the expression of miR-135b-3p is up-regulated, which may be involved in the occurrence and development of EC.

Objective:To investigate the value of whole-lesion histogram parameters of apparent diffusion coefficient (ADC) in evaluating and predicting the pathological complete response(PCR) to neoadjuvant chemotherapy (NAC) in different subtypes of breast cancer.Methods:This retrospective study included 117 patients with breast cancer who underwent MRI examination before NAC prior to surgery from January 2016 to December 2017 in the First Affiliated Hospital of Nanjing University. All cases were divided into Luminal B, HER2 positive ( n=21) and triple negative ( n=26) groups. The surgical pathology after chemotherapy was evaluated by Miller-Payne (M-P) system and the patients were divided into PCR group and non-PCR (nPCR) group. Firevoxel software was used to generate the whole-lesion ADC histogram. The parameters included mean (ADC mean), skewness, kurtosis, the minimum (ADC min), the maximum (ADC max), 10th percentile(ADC 10%), 50th percentile (ADC 50%) and 90th percentile (ADC 90%). The two independent samples t test or Mann-Whitney U test was used to compare the differences between PCR and nPCR groups in each subtype. The diagnostic performance of statistically different ADC parameters for predicting PCR was evaluated by receiver operating characteristic (ROC) curve. Results:Kurtosis was significantly higher in PCR group than that in nPCR group in HER2 positive subtype ( P=0.039). It achieved an area under the curve (AUC) of 0.813 with sensitivity of 100% and specificity of 68.7% at the optimal cutoff value (1.861) for differentiating PCR from nPCR cases. In triple negative subtype, ADC mean and ADC 50% were smaller in PCR group than those in nPCR group ( P=0.028,0.013). They achieved AUCs of 0.800, 0.842, respectively. When ADC mean of 1.030×10 -3 mm 2/s and ADC 50% of 0.976×10 -3 mm 2/s were used as cutoff value to differentiate PCR from nPCR, the sensitivities were 75.0%, 80.0% and the specificities were 83.3%, 83.3%, respectively. Conclusion:Kurtosis can predict post-NAC PCR in patients with HER2 positive breast cancer, while ADC 50% has a high value in predicting post NAC PCR of triple negative breast cancer patients.

OBJECTIVE: To investigate the prevalence status and the influential factors for smokers of undergraduates in Huaihua. METHODS: The undergraduates from different grades and different professions in Huaihua were selected randomly and investigated using a self-developed questionnaire. The influential factors for smokers of students were analyzed using a Chi-square test and a logistic regression. RESULTS: A total of 1 050 undergraduates were surveyed in our study. Among them, 973 were valid. The rate for students with a habit of smoking was 21.17%. 53.7% of smokers began to smoke at the stage of primary and high schools. The main reason for smoking was due to curious (47.1%) or depressive (45.2%). The male students were more likely to smoke than female students (OR=6.730). The attitudes of parents on smoking, such as no intervention, were important risk factors that affect the children's behavior on smoking (OR=1.866). CONCLUSION The periods in primary and high school are the most possible time for student to begin smoking. The curiosity and depression are the most risk factors, and the gender and family education are also the important factors that affect the behavior of undergraduates on smoking.
China ; epidemiology ; Female ; Humans ; Logistic Models ; Male ; Parents ; Prevalence ; Risk Factors ; Smoking ; epidemiology ; Students ; statistics & numerical data ; Surveys and Questionnaires ; Universities

Objective To establish an HPLC fingerprint of Dingdang Qigui Decoction and analyze and evaluate it using chemical pattern recognition technology;To determine the contents of 5 effective chemical components in Dingdang Qigui Decoction;To provide a basis for its quality control.Methods The analysis was performed on Agilent 5 TC-C18(2)column(250 mm×4.6 mm).The mobile phase comprised of acetonitrile-0.1%phosphoric acid aqueous solution with the gradient elution at a flow rate of 1.0 mL/min.The detection wavelength was set at 260 nm.The column temperature was maintained at 30℃and the injection volume was 10 μL.SPSS 26.0 and SIMCA 14.1 were used to perform clustering analysis and principal component analysis on the 10 batches of Didang Qigui Decoction.The landmark components for inter batch differences were selected through orthogonal partial least squares discriminant analysis(OPLS-DA).Results The HPLC fingerprint with eighteen common peaks of Didang Qigui Decoction in 10 batches of sample was established,and the similarities of samples were between 0.828 and 0.989.Five indicative components were identified and quantitatively analyzed by comparing with the reference substances,which were paeoniflorin,mauroisoflavone glucoside,hesperidin,cinnamaldehyde and aloe rhodopsin.The linear ranges was 10.000 0-320.000 0 μg/mL,2.500 0-80.000 0 μg/mL,10.000 0-320.000 0 μg/mL,10.000 0-320.000 0 μg/mL,0.078 1-5.000 0 μg/mL,respectively,and their mean recovery ranged from 100.30%to 104.09%.Clustering analysis and principal component analysis divided 10 batches of samples from Didang Qigui Decoction into 2 categories.Through OPLS-DA screening,hairy pistil isoflavone glycosides,paeoniflorin,and hesperidin were selected as landmark components for quality differences.Conclusion The quality evaluation method for Didang Qigui Decoction established in this study is simple,sensitive,accurate,and reproducible,which can provide a basis for the quality evaluation of Didang Qigui Decoction.

Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.

COVID-19 has brought a significant impact to the global health system, and also opportunities and challenges to epidemiological researches. Theoretical epidemiological models can simulate the process of epidemic in scenarios under different conditions. Therefore, modeling researches can analyze the epidemical trend of COVID-19, predict epidemical risks, and evaluate effects of different control measures and vaccine policies. Theoretical epidemiological modeling researches provide scientific advice for the prevention and control of infectious diseases, and play a crucial role in containing COVID-19 over the past year. In this study, we review the theoretical epidemiological modeling researches on COVID-19 and summarize the role of theoretical epidemiological models in the prevention and control of COVID-19, in order to provide reference for the combination of mathematical modeling and epidemic control.
COVID-19 ; Communicable Diseases/epidemiology* ; Humans ; Models, Theoretical ; SARS-CoV-2

Liver X receptor (LXR) plays an important role in reverse cholesterol transport (RCT), and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXRβ agonists. A novel benzofuran-2-carboxylate derivative was identified with LXRβ agonist activity: E17110 showed a significant activation effect on LXRβ with an EC50 value of 0.72 μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXRβ ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXRβ agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound.

【Objective】 To investigate the expression of optineurin (OPTN) in multiple myeloma (MM) and explore the mechanism and clinical value of OPTN gene in the occurrence and development of MM. 【Methods】 In this study, three gene expression omnibus (GEO) data sets were used to analyze the expression level of OPTN in MM. Clinical bone marrow samples of MM patients were collected. qRT-PCR was used to further verify the expression of OPTN in MM patients. The Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to analyze the value of OPTN in the prognosis and diagnosis of MM. At the same time, MM transcriptome data were downloaded from the Cancer Genome Atlas (TCGA) database. According to the median boundary of OPTN mRNA expression level, the MM patients were divided into OPTN high- and low-expression groups. In order to investigate the possible molecular mechanisms of OPTN in MM, gene set enrichment analysis (GSEA) was made after the differentially expressed genes were filtered using the limma package of the R language. 【Results】 The expression level of OPTN was significantly lower in MM tissues than in normal tissues (P<0.05). OPTN expression level was significantly correlated with International Staging System (ISS) in MM patients (P<0.05). ROC results showed that the expression level of OPTN could distinguish between normal and MM patients. Survival analysis showed that the overall survival (OS) of patients with low OPTN expression was significantly lower than that of patients with high OPTN expression (P<0.05). GO, KEGG and GSEA enrichment analyses indicated that OPTN might affect apoptosis and autophagy, and regulate cellular immune response by regulating Nod-like receptors, NF-κB, TNF and RAS/MAPK pathways. 【Conclusion】 Low expression of OPTN in MM is associated with poor prognosis of patients, and thus may be an important potential biomarker for the diagnosis and treatment of MM.