OBJECTIVE To clarify out the network pharmacology mechanism of Polygala tenuifolia against Alzheimer disease(AD).METHODS Firstly,we collected the chemical constituents from Polyg-ala tenuifolia and key targets toward AD.Machine learning algorithms were applied to construct classifi-ers for predicting the effective constituents. Secondly, docking models were utilized for further evalua-tion.Finally,we built constituent-target,target-target network and target-biology pathway network.RE-SULTS 104 chemical constituents Polygala tenuifolia from were collected.Through prediction of blood-brain penetration and validation,36 chemical constituents were selected among 100 chemical constitu-ents,their action targets mainly focused on AChE,COX-2,TNF-α,insulin-degrading enzyme and APP. Their main structure types include Polygala saponins, Polygala glycosides, Polygala shrubby ketones, polygala xanthones and sterols,which acted on AchE,APP,M-TAU,GSK3β and 5HT1A with high fre-quency.Gene-Ontology and KEGG enrichment analysis showed that the main pathways of these con-stituents involve in neurotransmitter release,synaptic conduction and synaptic plasticity,apoptosis reg-ulation,phosphorylation pathway,Ca2+signaling pathway,and so on.CONCLUSION This study uncov-ered a network mechanism of Polygala tenuifolia against Alzheimer disease,which may provide impor-tant information for the further study and new drug development.

We investigated inhibition of Moloney leukemia virus 10 (MOV10) upon xenotropic murine leukemia virus-related virus (XMRV) and made a preliminary study of the mechanism of action. Using transfection, infection, western blotting and real-time polymerase chain reaction, we found that MOV10 inhibited XMRV replication. Using MOV10 overexpressed in viral producer cells, MOV10 was shown to reduce the infectivity of XMRV. MOV10 could be incorporated into XMRV, suggesting that MOV10 could undergo encapsidation by XMRV during viral assembly. MOV10 could also restrict the DNA production of XMRV in target cells. We found that the putative RNA-helicase domain of MOV10 maintained most of its XMRV inhibition. These results suggest that MOV10 could be required during the retroviral lifecycle. Perturbation of MOV10 disrupts the generation of infectious viral particles, suggesting that MOV10 has broad antiretroviral activity. Hence, MOV10 could be actively involved in host defense against retroviral infection.
Humans ; Moloney murine leukemia virus ; physiology ; RNA Helicases ; physiology ; Virus Replication

BST-2 plays an important role in host innate immune response via inhibiting the release of HIV-1. HIV-1 accessory protein Vpu can interact with BST-2 through its transmembrane domains, degrade BST-2, and decrease BST-2 that are transported to the cell surface, thus anti-virus function of BST-2 is antagonized. In our study, we constructed plasmid RB connecting Rluc to the N-termimal of BST-2, and plasmid VE connecting EYFP to the C-terminal of Vpu. The two fusion proteins were co-expressed in 293 cells, and the interaction between the two proteins was detected via BRET method. And we further established a stable 293 cell line of dual-expression. By using BRET method, and the interaction between BST-2 and Vpu transmembrane domain as the target, a high-throughput screening assay was created that was expected to seek novel interaction inhibitors.
Antigens, CD ; chemistry ; genetics ; metabolism ; Cell Line ; GPI-Linked Proteins ; chemistry ; genetics ; metabolism ; HIV Infections ; genetics ; metabolism ; virology ; HIV-1 ; genetics ; metabolism ; High-Throughput Screening Assays ; methods ; Human Immunodeficiency Virus Proteins ; genetics ; metabolism ; Humans ; Protein Binding ; Protein Structure, Tertiary ; Viral Regulatory and Accessory Proteins ; genetics ; metabolism

Objective To evaluate the value of measuring ankle brachial index (ABI) for diagnosing peripheral arterial disease(PAD)compared with conventional digital subtraction angiography (DSA) as the reference standard.Methotis A total of 383 consecutive inpatients (245 male.mean age 64.1 ±11.7 years) underwent both conventional DSA and ABI measurements.Results The rate of statin intervention was 90.9%,ACEI 69.2%,antiplatelet 96.6% and β-blockers 67.9%.The intravascular stenosis was classified into six degrees:normal,<30%,30%-49%,50%-69%,70%-89% and≥90%.Compared to the traditional gold standard (DSA) in diagnosis PDA.the ABI value decreased in proportion to the sevefity of PAD (the ABI value was 1.08±0.11,1.05±0.16,0.99±0.17,0.66±0.24,0.55±0.28 and 0.54±0.00 respectively in the six ranks).There was a significant correlation between DSA and ABI in diagnosis PAD.Conclusion ABI measurement is an accurate and reliable non-invasive altemative to conventional DSA in the assessment of lower extremity arteries in patients with peripheral arterial disease.

Purpose/Significance Taking Jiashan county's chronic disease management mode based on blockchain as an example,new strategies for chronic disease management under the integrated county medical community mode are discussed.Method/Process U-sing the PEST-SWOT analysis method,the paper analyzes the strengths,weaknesses,opportunities and threats of the chronic disease management mode based on blockchain in Jiashan county from 4 aspects:politics,economy,society,and technology.Result/Conclu-sion The chronic disease management mode based on blockchain technology can ensure seamless connection and sharing of data,guaran-tee the security and traceability of patients'personal information and health records,and promote the common development of blockchain technology and chronic disease management in Jiashan county.

Larp4b is a member of the LARP family, which can interact with RNA and generally stimulate the translation of mRNA. Abnormal expression of Larp4b can be found in leukemia patients in our previous study. This study was purposed to detect the relative expression of Larp4b mRNA in different subpopulations of mouse hematopoietic cells, to construct lentivirus vector containing shLarp4b targeting mouse gene Larp4b and to explore its effects on mouse Lin(-) cells infected with shLarp4b by lentivirus. SF-LV-shLarP4b-EGFP and control vectors were constructed and two-plasmid lentivirus packing system was used to transfect 293T cells. After 48 h and 72 h, lentivirus SF-LV-shLarp4b-EGFP was harvested and was used to infect Lin(-) cells. After 48 h, EGFP(+) cells was sorted by flow cytometry (FCM). Meanwhile, semi-quantitative real time-PCR, AnnexinV-PE/7-AAD staining, PI staining and colony forming cell assay (CFC) were performed to determine the expression of Larp4b and its effect on the proliferation of hematopoietic progenitor cells. The results showed that Larp4b was highly expressed in myeloid cells. SF-LV-shLarp4b-EGFP was successfully constructed according to the restriction endonuclease digestion assay. RT-PCR confirmed that Larp4b was efficiently knockdown in mouse Lin(-) cells. The low expression of Larp4b did not affect the colony forming number, the apoptosis and cell cycle of Lin(-) cells. It is concluded that knockdown of Larp4b in mouse Lin(-) cells do not contribute to the colony forming ability and the growth of Lin(-) cells in vitro. This useful knockdown system will be used to study in vivo Larp4b in future.
Animals ; Autoantigens ; metabolism ; Cells, Cultured ; Flow Cytometry ; Gene Knockdown Techniques ; Genetic Vectors ; Hematopoietic Stem Cells ; cytology ; Humans ; Lentivirus ; genetics ; Mice ; Plasmids ; Ribonucleoproteins ; metabolism ; Transfection

BACKGROUNDStudies have suggested that use of prolonged dual antiplatelet therapy (DAPT) following new generation drug-eluting stent implantation may increase costs and potential bleeding events. This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization) at 2-year follow-up.

METHODSThe SEEDS study is a prospective, multicenter study, where patients (n = 1900) with small vessel, long lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days. The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and major bleeding (Bleeding Academic Research Consortium II-V)) were investigated according to the DAPT status at 2-year follow-up.

RESULTSDAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST (0.7%). DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096-4.980, P = 0.715) and NACE (HR: 1.041, 95% CI: 0.145-7.454, P = 0.968). Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1- and 2-year (1.4%). There was a high frequency of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT treatment.

CONCLUSIONSProlonged DAPT use was not associated with improved clinical safety. The study emphasized that duration of DAPT needs to be shortened in Chinese patients following EES implantation (ClinicalTrials.gov identifier: NCT 01157455).

Adolescent ; Adult ; Aged ; Aspirin ; therapeutic use ; Drug-Eluting Stents ; Everolimus ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Prospective Studies ; Sirolimus ; analogs & derivatives ; therapeutic use ; Thrombosis ; drug therapy ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Treatment Outcome ; Young Adult

Objective: To analyze the morbidity, clinical characteristics, therapeutic outcomes and prognosis of cardiac lymphoma. Methods: Individual patient data were obtained from pathology defined 10 cases of cardiac lymphoma from Jan 2000 to Jun 2016. The patient’s general information, clinical manifestation, pathological diagnosis, laboratory examination, cardiac involvement feature, cardiac complications, treatment, therapeutic effect and prognosis were analyzed. Results: Of 3 918 cases of lymphoma patients, 10 cases of cardiac involvement were identified, including primary cardiac lymphoma (PCL) in 1 case, secondary cardiac lymphoma (SCL) in 9 cases. Of the 10 patients in our analysis, the male-to-female ratio was 3∶2, with a median age of 55 (19-88) years old. The most presenting complaints were dyspnea in 7 cases, followed by chest pain in 5 cases, fatigue in 2 patients and edema in 2 cases. Pathological types included diffuse large B cell lymphoma (DLBCL) in 7 cases, T cell lymphoma (T-LBL) in 1 case, Hodgkin’s lymphoma (HL) in 1 case, and Burkitt lymphoma (BL) in 1 case. The sites of the heart affected by lymphoma in the PCL patient were right and left atriums with multiple nodules; and for SCL, the sites were mainly pericardium associated with a pericardial effusion in 5 cases, a pericardial mass in 2 cases. Congestive heart failure affects 7 patients and cardiac arrhythmias were identified in 4 cases mainly sinus tachycardia, atrial fibrillation and atrioventricular block. Except one untreated because of old age and poor performance, the rest of 9 patients were treated by either chemotherapy in 4 cases or chemotherapy combined radiotherapy (including the extracardiac sites) in 5 patients. With the median follow-up of 9 months, the one PCL patient achieved partial response (PR) , progress free survival (PFS) for 6 months and the overall survival (OS) for 21 months; in the cohort of 6 SCL patients cardiac involved at diagnosis, complete response (CR) was achieved in 1 case (16.7%) , PR in 3 cases, progressing disease (PD) in 2 cases, with the median PFS for 5 months and the median OS for 19 months; and for the other 3 SCL patients cardiac involved at progression, PR was achieved in 2 case and death in 1 case, with the median PFS for 4 months and the median OS unavailable because of censored data. Conclusion Cardiac lymphoma represents a rare subset of lymphoma, the most common type is DLBCL, and the main clinical manifestations are dyspnea and chest pain, always combined by arrhythmia and congestive heart failure. The main therapeutic regimen for cardiac lymphoma includes combined chemotherapy and the prognosis for patients with either PCL or SCL is usually poor.

Objective:To explore the value of 18F-FDG PET/CT in preoperative assessment of patients with gallbladder carcinoma.Methods:The clinical data of 59 patients who were preliminarily diagnosed as gallbladder cancer and who accepted PET/CT preoperatively in Zhongshan hospital, Fudan university were retrospectively analyzed.The diagnostic value of PET/CT in the identification of tumor, lymph node metastasis and distant metastasis of gallbladder cancer was statistically analyzed.Results:Of the 59 patients, 55 patients were postoperatively pathologically confirmed as gallbladder cancer, 1 patient as cholangiocarcinoma and 3 patients as inflammatory disease of gallbladder.The sensitivity of PET/CT in tumor identification was 90.9%,while the sensitivity and specificity of PET/CT in the diagnosis of lymph node metastasis and distant metastasis were 61.5% and 72.3%, 66.7% and 91.1%, respectively.SUVmax value showed no statistical difference in tumor staging, lymph node metastasis and distant metastasis.Conclusions:PET/CT is of important value in the preoperative evaluation of gallbladder cancer, especially in the assessment of lymph node metastasis and distant metastasis.However, its value in tumor staging remains to be further evaluated.

Objective To enhance the efficiency of health education, to avoid the risk factors of community patients with pre-diabetes, and to prevent the occurrence of diabetes. Methods Health education and lifestyle intervention were applied in pre-diabetes and high-risk groups at subordinate community hospitals. Results After the intervention, the body mass index, fasting blood glucose, blood glucose 2 h after meals obviously decreased compared to those before the intervention (P <0.01). The diastolic blood pressure, systolic blood pressure and triglyceride also had some decrease (P<0.05). The knowledge rate of diabetes after the intervention had an obvious increase. Conclusions Health education and lifestyle intervention of pre-diabetes are practicable, and delay the development of diabetes. Health education and lifestyle intervention have crucial effects on the procedure of IGT developing to diabetes.