Based on ninety three acetylcholinesterase inhibitors (AChEIs) which have the same mechanism of action but are different in structural characteristics, the pharmacophore model for acetylcholinesterase inhibitor was constructed by the CATALYST system. The optimal pharmacophore model with three hydrophobic units, a ring aromatic unit and a hydrogen-bond acceptor unit were confirmed (Weight=3.29, RMS=0.53, total cost-null cost=62.75, Correl=0.93, Config=19.05). This pharmacophore model will act on the double active site of acetylcholinesterase and is able to predict the activity of known acetylcholinesterase inhibitors that are used for clinical treatment of Alzheimer's disease (AD), and can be further used to identify structurally diverse compounds that have higher activity treating with Alzheimer's disease (AD) by virtual screening.

In 2015, American College of Endocrinology ( ACE), American Association of Clinical Endocrinologists ( AACE ) , European Association for the Study of Diabetes ( EASD ) , Chinese Society of Endocrinology, American Diabetes Association ( ADA ) , American Association of Diabetes Educators ( AADE ) , Academy of Nutrition and Dietetics(AND), etc. published several guidelines and statements on diabetes and its complications. The selection of hypoglycemic drugs, diabetes self-management education and support, the characteristics of blood pressure and blood lipid, the efficacy and adverse reaction of hypoglycemic drugs were also suggested and recommended. These guidelines and statements will play key roles in the clinical diagnosis and treatment of diabetes mellitus, which is reviewed in this article.

Objective To discuss the relationship between various T lymphocyte subsets apoptosis and disease progression in chronic antiretroviral-naive HIV/AIDS patients. Methods Thirty-six chronic antiretrovi-ral-naive HIV-infected individuals as well as 16 healthy HIV-negative controls were performed in this study. Ac-cording to the CD4~+ T cell counts, all the patients were divided three groups: < 200/μl, 200-350/μl and > 350/μl. After the peripheral blood mononuclear cells(PBMC) were isolated, T lymphocyte subpopulations were determined by the expression of CD45RO and CD27, and the apoptosis of different T cell subsets were measured by Annexin V staining, then analyzed by flow cytometry. To investigate whether the apoptosis of T cells varied with the culture time in vitro, 4 healthy controls and 4 patients were chosen as subjects, and the lev-els of cell apoptosis were analyzed at the culture time points of 0, 3, 6, 12, 24 h. Results (1)The percenta-ges of the AnnexinV expression on CD4~+ and CD8~+ T cells and all the subsets in HIV/AIDS patients were sig-nificantly higher than that in the healthy controls (P<0.05), but there were no significant differences among the three HIV-infected patient groups(P>0.05). (2) No significant correlations were observed between the levels of apoptosis of all the T cells and subsets and total CD4~+ T cell counts(P>0.05) ,nor with the HIV viral load (P>0.05). (3)As the culture time prolonged in vitro, the levels of apoptosis and necrosis of CD4~6 T cells in HIV/AIDS patients were significantly higher than those in the healthy conlrols, and the CD4~+ T cells were more susceptible to apoptosis and necrosis compared with CD8~+ T cells. Conclusion The levels of T cell apoptosis in HIV/AIDS patients was significantly higher than those in the healthy controls, at the same time, CD4~+ T cells were more susceptible to apoptosis and necrosis compared with CD8~+ T cells, but no correlation was found between the T cell apoptsis and disease progression.

Objective Collecting the loosening periprosthetic interface-membrane, to discuss the mechanism of hip arthroplasty loosening. Methods The periprosthetic interface tissues of 29 hip arthroplasty revision cases from February 1995 to December 2003 were collected. The retrieved periprosthetic interface tissues were detected by immunohistochemistry. Some of them were studied by electronic microscope. Results (1)Transmission electronic microscope examination: the mitochondria swell. There were some substantia like lipid in the plasm of macrophages. Wear particles could be seen under scaning electronic microscope.(2)Immunohistochemistry: there were 22 IL-1? positive cases in cells of interface membrane. There were 29 IL-6 positive cases in cells of interface membrane. There were no positive results in TNF-? test. Conclusion (1)The wear particles of arthroplasty are important factors which cause biological reaction.(2)The interface membranes contain cytokine IL-1? and IL-6, which may play an important role in periprosthetic osteolysis and arthroplasty loosening.

Objective: To evaluate the efficacy of paclitaxel-coated balloon for de novo coronary lesions with diameters ≥ 2.8 mm. Methods: This prospective study included 215 consecutive patients with 238 de novo lesions, who received paclitaxel-coated balloon angioplasty in Beijing Hospital from May 2014 to June 2016. According to the reference vessel diameter, the patients were divided into large vessel disease (LVD) group (reference vessel diameter≥2.8 mm, 85 patients and 90 lesions) and small vessel disease (SVD) group (reference vessel diameter<2.8 mm, 130 patients and 148 lesions). Clinical characteristics, interventional procedures and major adverse cardiovascular events (includingall-cause mortality, non-fatal myocardial infarction and target lesion revascularization) after procedure were compared between the 2 groups. Results: (1)Patients in LVD group were younger than SVD group ((60.1±11.1) years old vs. (65.0±10.6) years old, P<0.01), and less patients had diabetes (24.7% (21/85) vs. 43.1%(56/130), P<0.01).(2)Prevalence of three-vessel disease (35.5%(30/85) vs. 53.6%(67/130), P<0.05) and complex lesions (type B2/C,34.4% (31/90) vs. 50.0%(74/148), P<0.05) were significantly lower in LVD group than in SVD group.(3) During pre-dilation, the rate with plain balloons use was significantly higher in SVD group than in LVD group(76.4%(113/148) vs. 58.9%(53/90), P<0.01), while the proportion of additional use of non-compliant balloons was significantly higher in LVD groupthan in SVD group(20.0% (18/90) vs. 3.4% (5/148) , P<0.01). The ratio of paclitaxel-coated balloon diameter/RVD was significantly lower (0.87±0.12 vs. 0.96±0.15, P<0.01) and the duration of dilationwas significantly shorter ((41.5±9.5) seconds vs. (45.1±9.1) seconds, P<0.01) in LVD group than those in SVD group. Each group had 1 failure case that was bailout stented with drug-eluting stents. The success rate of paclitaxel-coated balloon treatment was similar in LVD group and SVD group (98.9% (89/90) vs. 99.3%(147/148), P>0.05).(4) At the fourth day of procedure, there was 1 acute myocardial infarction requiring emergent target lesion revascularization in SVD group. No major adverse cardiovascular event was observed in LVD group during hospitalization. Forty-two patients with 53 lesions, including 27 LVD lesions and 26 SVD lesions,underwent coronary angiography at (9.4±4.6) months after paclitaxel-coated balloon intervention. The quantitative coronary angiography analysis showed that minimal lumen diameter significantlyincreased during follow-up than that of post-procedurein SVD group ((1.71±0.36)mm vs. (1.52±0.30)mm, P<0.05) , while in LVD group the minimal lumen diameter was similar between during follow-up and post-procedure ((2.35±0.48)mm vs. (2.19±0.34)mm, P>0.05). Major adverse cardiovascular event rate was 0 in LVD group and 2.3%(3/130) in SVD group (P>0.05) during follow up. No death was observed in this patient cohort. Conclusion Treatment with paclitaxel-coated balloon for de novo coronary lesions with diameters≥2.8 mm is safe and effective.

Objective To analyze the effect of transport and storage conditions on the detection of pathogenic nucleic acid MHV, Reo-3, MNV in laboratory mouse cecal contents samples. Methods MHV, Reo-3 and MNV were mixed with mouse cecal contents and used as reference samples,respectively. They were placed in the lysis buffer of RNA extraction reagent(buffer AVL)or normal saline, and stored at 4℃ and room temperature(22℃-25℃). RNA of these samples was extracted at 1,2,3,7,and 14 days. Then the amount of nucleic acid in samples was detected by real-time fluorescence quantitative PCR. Results A greater decrease of the amount of nucleic acid was observed when the samples were placed in normal saline than that kept in buffer AVL. The amount of nucleic acid in samples stored at 4℃ was found to be higher than that stored at 25℃ room temperature. The amount of nucleic acid in the samples which were kept in buffer AVL at 4℃ for 3 days was higher than 50%,still detectable in the samples kept for 7 days,and undetectable at 14 days. Conclusions Mouse cecal content samples are preferably stored in the lysis buffer of RNA extraction reagent and transported at 4℃ for the detection of MHV, Reo-3, and MNV nucleic acid. It is better to complete the detection test within 3 days.

Animals ; Biocatalysis ; Cattle ; Enteropeptidase ; chemistry ; metabolism ; Humans ; Models, Molecular ; Oryzias ; metabolism ; Structure-Activity Relationship ; Substrate Specificity

Objective By comparing the physical properties (cell area, volume and elastic modulus) of red blood cells (RBCs) between newborn infants and the elderly over 80 years old, and correlation with the physiological and biochemical parameters such as total cholesterol and glycosylated hemoglobin, the effects of different ages and biochemical parameters on RBC physical properties were analyzed. Methods The mcropipette aspiration was used to measure the surface area, volume and elastic modulus of erythrocytes in newborn infants and the elderly over 80 years old, and the data were analyzed by statistical distribution analysis, correlation analysis and regression analysis. Results The mean values of RBC volume, surface area and elastic modulus in the elderly over 80 years old were smaller than those in newborn infants, and the mean values of RBC mechanical parameters in the same age group were not significantly different. The erythrocytes geometric parameter distribution of newborn infants was more concentrated than that of the elderly, while the elastic modulus distribution of newborn infants was more dispersed than that of the elderly. The mechanical properties of RBCs in newborn infants were highly correlated with the total cholesterol and gestational week; the mechanical properties of RBCs in the elderly were highly correlated with diastolic blood pressure and glycated hemoglobin. Conclusions There are significant differences in physical properties of RBCs between newborn infants and the elderly over 80 years old, and the biochemical parameters that affect physical properties of RBCs at different ages are also different.

Objective:To investigate an accurate and quantitative method to measure the eyeball morphological parameters of guinea pigs through a method that combines programmed digital techniques and mathematical geometric principles.Methods:Twenty-two three-week-old clean-grade male tricolor guinea pigs were selected and sacrificed by anesthesia overdose.Eyeballs were enucleated.The horizontal and sagittal images of the eyeball were taken with the high-speed photographic model of 13 million pixels macro meter, and the pictures were imported into pycharm programming software.Using the pre-written analysis program of Python 3.9, the conversion coefficient between the photo pixel and the actual length was obtained by a scale, and then the corneal surface was fitted by arc fitting and conic curve fitting.The results of arc fitting were converted to calculate the corneal radius of curvature.The corneal eccentricity was calculated according to the general conic equation (Ax 2+ Bxy+ Cy 2+ Dx+ Ey+ F=0). The corneal asphericity was evaluated by curve fitting between the central 3-mm and the whole cornea.The use and care of the animals complied with Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Shanghai Public Health Clinical Center (No.2022-A009-01). Results:The digital method of Python programming can show the corneal contour of guinea pigs completely and clearly.In the transverse plane, there was no significant difference in the corneal curvature measurements among the digital fitting in central 3-mm cornea, digital fitting in whole cornea and curvature meter ( F=1.693, P=0.190). In the sagittal plane, there was a significant difference in the corneal curvature measurements among the three methods ( F=3.500, P=0.030), and the corneal curvature measurements of the whole cornea measured by the curvature meter were significantly greater than those measured by the digital fitting ( P<0.05). There was no statistical significance in the measurements of corneal curvature radius among the three methods in the transverse plane and the sagittal plane ( F=1.817, P=0.170; F=2.050, P=0.133). The horizontal and sagittal corneal eccentricity measured by digital fitting in central 3-mm cornea were 0.55±0.15 and 0.53±0.17, which were lower than 0.66±0.10 and 0.64±0.14 measured by digital fitting in whole cornea, and the differences were statistically significant ( t=-4.860, -5.210; both at P<0.01). Conclusions:It is feasible to use Python programming digital method to measure the corneal curvature and eccentricity of guinea pigs.

OBJECTIVES: During the coronavirus disease 2019 (COVID-19) pandemic, a growing prevalence of racial and ethnic discrimination occurred when many Americans struggled to maintain healthy lifestyles. This study investigated the associations of racial and ethnic discrimination with changes in exercise and screen time during the pandemic in the United States. METHODS: We included 2,613 adults who self-identified as non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, or Hispanic from the Health, Ethnicity, and Pandemic study, a cross-sectional survey conducted among a nationally representative sample of United States adults between October and November 2020. We assessed self-reported racial and ethnic discrimination by measuring COVID-19-related racial and ethnic bias and examined its associations with changes in exercise and screen time using multivariable logistic regression models. We analyzed data between September 2021 and March 2022. RESULTS: COVID-19-related racial and ethnic bias was associated with decreased exercise time among non-Hispanic Asian (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.13 to 1.89) and Hispanic people (OR, 1.91; 95% CI, 1.32 to 2.77), and with increased screen time among non-Hispanic Black people (OR, 1.94; 95% CI, 1.33 to 2.85), adjusting for age, sex, education, marital status, annual household income, insurance, and employment status. CONCLUSIONS Racial and ethnic discrimination may have adversely influenced exercise and screen time changes among racial and ethnic minorities during the COVID-19 pandemic in the United States. Further studies are needed to investigate the mechanisms through which racial and ethnic discrimination can impact lifestyles and to develop potential strategies to address racial and ethnic discrimination as a barrier to healthy lifestyles.