Objective To investigate the effects of simvastatin mediated adenylate activated protein kinase/peroxisome proliferator-activated receptor-γ-coactivator 1 α(AMPK/PGC-1α)pathway on neural function in rats with Parkinson's disease.Methods Parkinson's disease model was established in SD rats.After successful modeling,they were divided into model group,positive group(1.67 mg·kg-1 metoba),experimental-L group(10 mg·kg-1 simvastatin),experimental-H group(20 mg·kg-1 simvastatin),BML-275 group(20 mg·kg-1 simvastatin+0.25 mg·kg-1 AMPK inhibitor BML-275)and 10 normal rats were selected as control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect dopamine(DA),3,4 dihydroxyphenylacetic acid(DOPAC),homovanillic acid(HVA),5-hydroxyindoleacetic acid(5-HIAA),5-hydroxytryptamine(5-HT);Western blot was used to detect the expression of tyrosine hydroxylase(TH)and AMPK/PGC-1α pathway-related proteins;TH expression was detected by immunohistochemistry,malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were detected by kit.Results The DA of control group,model group,experimental-H group and BML-275 group were(495.63±34.30),(207.53±24.10),(429.39±44.89)and(285.55±20.79)pg·mL-1,respectively;DOPAC were(33.38±2.48),(17.70±1.31),(29.12±1.72)and(20.67±1.45)ng·mL-1,respectively;HVA were(58.75±6.25),(25.27±2.00),(46.16±2.83)and(30.58±1.91)ng·mL-1,respectively;5-HT were(5.62±0.45),(2.37±0.13),(4.42±0.26)and(3.23±0.29)ng·mL-1,respectively;5-HIAA were(11.11±1.08),(3.88±0.30),(7.99±0.63)and(6.04±0.51)ng·mL-1,respectively;p-AMPK protein expression were 0.98±0.06,0.35±0.04,0.80±0.05 and 0.21±0.02,respectively;PGC-1α protein expression were 1.12±0.11,0.40±0.04,0.90±0.08 and 0.58±0.05,respectively.There were statistically significant differences in the above indexes between control group and model group,and between model group and experimental-H group and inhibitor group(all P＜0.05).Conclusion Simvastatin can improve the neural function of Parkinson's disease rats by regulating AMPK/PGC-1α pathway.

OBJECTIVE: To predict the trends for fine-scale spread of Oncomelania hupensis based on supervised machine learning models in Shanghai Municipality, so as to provide insights into precision O. hupensis snail control. METHODS: Based on 2016 O. hupensis snail survey data in Shanghai Municipality and climatic, geographical, vegetation and socioeconomic data relating to O. hupensis snail distribution, seven supervised machine learning models were created to predict the risk of snail spread in Shanghai, including decision tree, random forest, generalized boosted model, support vector machine, naive Bayes, k-nearest neighbor and C5.0. The performance of seven models for predicting snail spread was evaluated with the area under the receiver operating characteristic curve (AUC), F1-score and accuracy, and optimal models were selected to identify the environmental variables affecting snail spread and predict the areas at risk of snail spread in Shanghai Municipality. RESULTS: Seven supervised machine learning models were successfully created to predict the risk of snail spread in Shanghai Municipality, and random forest (AUC = 0.901, F1-score = 0.840, ACC = 0.797) and generalized boosted model (AUC= 0.889, F1-score = 0.869, ACC = 0.835) showed higher predictive performance than other models. Random forest analysis showed that the three most important climatic variables contributing to snail spread in Shanghai included aridity (11.87%), ≥ 0 °C annual accumulated temperature (10.19%), moisture index (10.18%) and average annual precipitation (9.86%), the two most important vegetation variables included the vegetation index of the first quarter (8.30%) and vegetation index of the second quarter (7.69%). Snails were more likely to spread at aridity of < 0.87, ≥ 0 °C annual accumulated temperature of 5 550 to 5 675 °C, moisture index of > 39% and average annual precipitation of > 1 180 mm, and with the vegetation index of the first quarter of > 0.4 and the vegetation index of the first quarter of > 0.6. According to the water resource developments and township administrative maps, the areas at risk of snail spread were mainly predicted in 10 townships/subdistricts, covering the Xipian, Dongpian and Tainan sections of southern Shanghai. CONCLUSIONS Supervised machine learning models are effective to predict the risk of fine-scale O. hupensis snail spread and identify the environmental determinants relating to snail spread. The areas at risk of O. hupensis snail spread are mainly located in southwestern Songjiang District, northwestern Jinshan District and southeastern Qingpu District of Shanghai Municipality.
Animals ; Bayes Theorem ; China/epidemiology* ; Ecosystem ; Gastropoda ; Supervised Machine Learning

OBJECTIVE: To express and purify the antigenic peptide of adeno-associated virus (AAV) capsid conserved regions in prokaryotic cells and prepare its rabbit polyclonal antibody. METHODS: The DNA sequence encoding the conserved regions of AAV capsid protein was synthesized and cloned into the vector pET30a to obtain the plasmid pET30a-AAV-CR for prokaryotic expression and purification of the conserved peptides. Coomassie blue staining and Western blotting were used to identify the AAV conserved peptides. Japanese big ear white rabbits were immunized with AAV conserved region protein to prepare polyclonal antibody, with the rabbits injected with PBS as the control group. The antibody titer was determined with ELISA, and the performance of the antibody for recognizing capsid protein sequences of AAV1-AAV10 was assessed with Western blotting and immunofluorescence assay. RESULTS: The plasmid pET30a-AAV-CR was successfully constructed, and a recombinant protein with a relative molecular mass of 17000 was obtained. The purified protein induced the production of antibodies against the conserved regions of AAV capsid in rabbits, and the titer of the purified antibodies reached 1:320 000. The antibodies were capable of recognizing a wide range of capsid protein sequences of AAV1-AAV10. CONCLUSION We successfully obtained the polyclonal antibodies against AAV capsid conserved region protein from rabbits, which facilitate future studies of AAV vector development and the biological functions of AAV.
Animals ; Antibodies ; Capsid ; Capsid Proteins/genetics* ; Dependovirus/genetics* ; Prokaryotic Cells ; Rabbits ; Recombinant Proteins/genetics*

Objective:To analyze the status quo and development of the Hope Houses for individuals with spinal cord injury (SCI) in Shanghai. Methods:In June, 2018, the organizers and managers of Hope Houses from 16 districts in Shanghai were investigated with the self-designed questionnaires, which covered the personal characteristics, knowledge of related policy, development of projects and obstacles, and rehabilitation recognition. The descriptive analysis and correlational analyses were conducted. Results:Totally, eleven organizers and 16 managers were investigated. The knowledge of related policy for organizers was not good enough. Eight Hope Houses in 16 districts in Shanghai were operated by social organizations. The average implementation rate of projects in Hope Houses was 60.6%, and the highest was rehabilitation knowledge education (96.3%). There was insufficient provision in legal services, job skills training, rehabilitation nursing guidance, job referral, medical referral and education referral, etc. The main related factors limiting the development of the Hope Houses were lacks of budgets, social consensus and professionals. The rehabilitation cognition of organizers and managers was generally good, but the cognition of rehabilitation principles and rehabilitation value needed to be strengthened. Conclusion:The Hope Houses for individuals with SCI in Shanghai work well, and the rehabilitation cognition of organizers and managers is satisfactory. It should be strenghened in resource input, comprehensive rehabilitation and standard of management, to expand the service timely.

Objective:Preliminary study on rats with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) model intervention agent tBHQ before and after the nuclear factor E2-related factor 2(Nrf2) and its downstream target genes of heme oxygenase 1(HO-1) change in hippocampus associated,in order to further study the pathogenesis of DEACMP,at the same time for the targeted therapy of provide a certain experimental basis.Methods: One hundred and twenty rats were randomly divided into carbon monoxide poisoning group(CO group),air control group(AC group),carbon monoxide+3% ethanol group(EC group),carbon monoxide+tBHQ group(group TC),then the rats in exposure after 1 d,3 d,7 d,14 d,21 d,28 d,with the machine was divided into 6 sub groups,followed by the Morris water maze test to observe the behavior of rats,immunohistochemistry and protein Western blot method of chemical(Western blot) detecting expression of Nrf2 and HO-1 mploying intervention agent tBHQ before and after,and then TUNEL staining was detected cell apoptosis.Results: CO group,EC group,TC group Nrf2 in hippocampus of rats and the expression of HO-1 were increased in the first day and reach a peak at the third day,then gradually decreased,and at each time point in AC group were statistically significant,TC group and CO group Nrf2 and HO-1 were increased in each sub group and the deffirences were statistically meaning.Comparison apoptotic cells in CO group,EC group,TC group with AC group rats increased significantly over time,and showed higher peak(7-14 d)-decreased.TC group compared with CO group,the apoptotic cells(7-14 d) decreased,the difference was statistically significant.Conclusion: The Nrf2/ARE/HO-1 pathway plays an important role in the development of DEACMP,and the tBHQ specific activation of the Nrf2 pathway achieves early protection and is expected to reduce or mitigate DEACMP.

Increasingly accumulated results from randomized controlled trials and other clinical studies have demonstrated that male circumcision reduces the risks of acquisition and transmission of HIV, HPV, HSV-2, and other sexually transmitted infections, and thus has a potential role in preventing cervical cancer, penile cancer and prostate cancer. The prevalence of male circumcision in China is currently less than 5%. The clinical evaluation studies and randomized controlled trials of the Shang Ring device showed excellent safety profiles, extremely high acceptability, and satisfaction among the participants and service providers in Africa and China. Given the recent recommendations by the World Health Organization and the Joint United Nations Program on HIV/AIDS (UNAIDS), voluntary medical male circumcision should be promoted in China at the national level as an important alternative intervention to reduce reproductive tract infections and prevent both males and females from reproductive tract cancers. More emphasis is required on the studies of the long-term health benefits of male circumcision in uro-andrology.
China ; Circumcision, Male ; Female ; HIV Infections ; prevention & control ; Humans ; Male ; Penile Neoplasms ; prevention & control ; Prevalence ; Randomized Controlled Trials as Topic ; Sexually Transmitted Diseases ; prevention & control ; Urinary Tract Infections ; prevention & control ; Uterine Cervical Neoplasms ; prevention & control ; World Health Organization

BACKGROUNDMultidrug resistance (MDR) is a main reason for paclitaxel (TAX) treatment failure. Indirubin-3'-monoxime (IRO) and Matrine are traditional Chinese medicines, which may reverse the resistance of tumor cells to some chemotherapy drugs, but the relationship between paclitaxel resistance and Matrine is still unclear. The aim of this study was to explore the potential molecular mechanism of IRO and Matrine in reversal of TAX resistance.

METHODSIn this study, MTT assay was used to measure the non-cytotoxic dosage of IRO and Matrine on NCI-H520/TAX25 cells and determine the reversal extent of TAX resistance under non-toxic doses. In addition, RT-PCR and Western blotting were used to evaluate the mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 cells using semi-quantitative methods.

RESULTSThere was no obvious inhibition on sensitive cell strains and drug-resistant strains, when the final concentration was at lest 4 µmol/L for IRO and 100 µmol/L for Matrine. So 4 µmol/L of IRO and 100 µmol/L of Matrine were considered as the reversal dosage. When 4 µmol/L of IRO or 100 µmol/L of Matrine were used together with TAX, the sensitivity to TAX increased evidently in NCI-H520/TAX2 cells; the reversal rate of IRO and Matrine was about 1.92 (43.56/22.6 nmol/L) and 1.74 (43.56/25.0 nmol/L), respectively. The mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 decreased significantly (P < 0.05) after addition of IRO or Matrine in TAX treatment, compared to that of TAX treatment alone.

CONCLUSIONThe decrease in both mRNA expression and protein level of survivin, Oct-4, and Sox-2 might be the molecular mechanism, by which IRO and Matrine mediate the reversal of TAX resistance.

Alkaloids ; pharmacology ; Blotting, Western ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Humans ; Indoles ; pharmacology ; Inhibitor of Apoptosis Proteins ; genetics ; metabolism ; Octamer Transcription Factor-3 ; genetics ; metabolism ; Oximes ; pharmacology ; Paclitaxel ; pharmacology ; Quinolizines ; pharmacology ; SOXB1 Transcription Factors ; genetics ; metabolism

OBJECTIVETo investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC) on TIP30 gene expression and the relationship between TIP30 expression and the sensitivity to 5-fluouracil (5-Fu) in colorectal cancer cells.

METHODSThe methylation profile of TIP30 gene in HCT116 colorectal cancer cells was determined by methylation-specific PCR. The levels of TIP30 mRNA and protein were determined by RT-PCR and Western blot after the 5-Aza-dC treatment. MTT assay was used to detect the chemosensitivity of HCT116 cells to 5-Fu.

RESULTSTIP30 gene displayed complete DNA methylation in the HCT116 cells without 5-Aza-dC pretreatment. After the 5-Aza-dC treatment for 3 days, only demethylating PCR amplification product was detected and TIP30 gene showed DNA demethylation. With the prolongation of the time of removal of 5-Aza-dC treatment, methylated and demethylated PCR amplification products were observed and TIP30 gene displayed both DNA methylation and DNA demethylation in the colorectal cancer cells. At the day 10 after removal of 5-Aza-dC, methylating PCR amplification product appeared and TIP30 gene showed DNA methylation. No expressions of TIP30 mRNA and protein were detected in the HCT116 cells untreated with 5-Aza-dC. After the treatment of 5-Aza-dC for 3 d and then removed the 5-Aza-dC, the expressions of TIP30 mRNA and protein were increased obviously. With the prolonged time after 5-Aza-dC removal, the expressions of TIP30 mRNA and protein decreased and reached the lowest level on day 10. The IC50 values of 5-Fu were 41.62, 33.17 and 4.96 µg/ml in the HCT116 cells pretreated with 5-Aza-dC, d0 and d10 with the drug removal after drug treatment for 3 d, respectively.

CONCLUSIONSThe results of this study show that the expression of TIP30 gene may be associated with its DNA methylation status and may affect the sensitivity of colorectal cancer cells to 5-Fu.

Acetyltransferases ; genetics ; metabolism ; Antimetabolites, Antineoplastic ; pharmacology ; Azacitidine ; analogs & derivatives ; pharmacology ; Cell Proliferation ; drug effects ; CpG Islands ; genetics ; DNA Methylation ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Fluorouracil ; pharmacology ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; Humans ; Inhibitory Concentration 50 ; RNA, Messenger ; metabolism ; Transcription Factors ; genetics ; metabolism

OBJECTIVETo evaluate the effect of comprehensive control and prevention for chronic diseases in demonstration plot of Chongqing.

METHODSResidents were enrolled through multi-stage stratified random sampling method from 17 districts or counties which had successfully established demonstration plots and 21 districts or counties which had not established demonstration plots (non-demonstration plot for short) yet on May, 2012. Questionnaire was designed to survey awareness of health knowledge, health behaviors and utilization of health supportive tools. The results were analyzed by SPSS 15.0 software.

RESULTSWe investigated 15 108 residents, 6156 of which were in demonstration plot and others (8951) were not. The findings revealed the percentage of the people who were aware the national action of health lifestyle in demonstration plot and in non-demonstration plot were 44.4% (2734/6157) and 40.2% (3598/8951), respectively, and the awareness of the hypertension risk of too much sodium were 72.4% (4458/6156) and 67.5% (6042/8951), respectively, and the awareness of the cardinal vascular disease (CVD) risk of obesity and overweight were 77.2% (4753/6157) and 69.6% (6230/8951), respectively. About the residents' health behaviors in demonstration plot and in non-demonstration plot, the utilization rates of salt restriction scoop or pot were 23.5% (1447/6157) and 17.9% (1602/8951), and the utilization rates of oil restriction pot were 16.7% (1028/6157) and 11.8% (1064/8951), respectively. Totally, 33 of the 37 indexes were shown higher in demonstration plot than that in non-demonstration plot (P < 0.05).

CONCLUSIONThe chronic diseases comprehensive control and prevention in demonstration plot was more effective, and the remarkable improvement of health knowledge and behaviors level had been achieved in demonstration plot.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; Chronic Disease ; prevention & control ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Surveys and Questionnaires ; Universal Precautions ; Young Adult

The purpose of this study is to investigate the penetration effects and mechanism of N-arginine chitosan (ACS). This novel transdermal enhancer with a mimetic structure of cell-penetration peptides was synthesized by introducing hydrophilic arginine groups to the amino-group on chitosan's side chain. The structure of ACS was confirmed by FT-IR, 1H NMR and element analysis. In addition, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) was used to study the protein conformation and the water content of stratum corneum, and the result suggested that ACS can change the orderly arrangement of the molecules in the stratum corneum, making the stack structure of keratin become loose. And ACS can increase the water content of the stratum corneurn. Inverted fluorescence microscope and flow cytometry were used to examine penetration effect of ACS on Hacat cell. The result confirmed that the uptake of ACS was enhanced with increased substitution degree of arginine by 4-8 folds compared to chitosan. In vitro penetration studies on three electrical types of drugs were carried out using three model drugs of negatively charged aspirin, positively charged terazosin and neutral drug isosorbide mononitrate by the method of Franz diffusion cells. The results showed that ACS has obviously penetration of the negatively charged drug aspirin, and certain penetration of neutral drug issorbide mononitrate, but inhibition of positively charged terazosin. In vivo imaging technology research results show that the ACS can significantly enhance the fluorescence intensity of morin, which is the auto-fluorescence anionic drug. These obtained results suggested that ACS, as a promising transdermal enhancer, can change the structure of the keratinocytes and analog penetrating peptides promote absorption, but have certain selectivity for the drug.
Administration, Cutaneous ; Animals ; Arginine ; chemical synthesis ; chemistry ; pharmacology ; Aspirin ; administration & dosage ; pharmacokinetics ; Cell Line ; Cell Survival ; drug effects ; Cell-Penetrating Peptides ; chemical synthesis ; chemistry ; pharmacology ; Chitosan ; chemical synthesis ; chemistry ; pharmacology ; Drug Carriers ; Humans ; Isosorbide Dinitrate ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Keratinocytes ; cytology ; Male ; Mice ; Prazosin ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Skin Absorption ; drug effects