Objective To provide reference for focusing and improving policy efficiency in China by establishing the conceptual model and index system of effectiveness of Township and Village Health Services Integration Policy(TVI).Methods The conceptual model and index system of TVI effectiveness were established by literature review and Delphi method.Comprehensive Index Method and Weighted TOPSIS Method were used in index consistency check.Results The conceptual model and index system of TVI effectiveness contain four conceptual modules,8 policy goals and 27 evaluation indexes.The positive coefficient of experts is 0.95 and authoritative grades of experts are more than 0.90.Conclusion Based on SPO Model,the conceptual model and index system of TVI effectiveness in China have been established,which consists three aspects:construction of organization system,health services and satisfaction.

OBJECTIVETo investigate the effects of ethyl acetate extract of Huanglian Jiedu decoction (EAHD) on hyphae development of Candida albicans.

METHODInverted microscope, fluorescence microscope, SEM were applied to inspect the Morphological change of C. albicans treated by EAHD at different concentrations. Solid agar plate was utilized to evaluate the colony morphology. Quantitative Real-ime PCR(qRT-PCR) was adopted to observe the expression of hyphae-specific genes such as HWP1, ALS3, UME6, CSH1, SUN41, CaPDE2.

RESULTEAHD with concentration of 312 and 1 250 mg . L-1 could inhibit formation of hyphae and colony morphology. The expression of HWP1, ALS3, UME6, CSH1 were downregulated 4. 13, 3. 64, 2. 46, 2. 75 folds ,while the expression of SUN41 were upregulated 7. 26 folds, CaPDE2 keep unchanged.

CONCLUSIONEAHD could inhibit formation of hyphae and colony morphologies of C. albicans through downregulating HWP1, ALS3, UME6 and CSH1.

Acetates ; Biofilms ; drug effects ; growth & development ; Candida albicans ; cytology ; drug effects ; genetics ; growth & development ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Fungal Proteins ; genetics ; Gene Expression Regulation, Fungal ; drug effects ; Hyphae ; Medicine, Chinese Traditional ; Microscopy, Fluorescence ; Reverse Transcriptase Polymerase Chain Reaction

Along with the increase in fungal infections, Candida albicans prevention and control become the focus of anti-fungal infection at present. This study aims to discuss the effect monomer andrographolide (AG) on C. albicans biofilm dispersion. In the experiment, micro-well plates and medical catheter pieces were used to establish the C. albicans biofilm model. It was discovered by XTT assay and flat band method that 1 000, 500, 250 mg x L(-1) AG could impact the activity of C. albicans biofilm dispersion cells. The morphological structures of residual biofilms on catheter pieces were observed with scanning electron microscopy, which showed that 1 000, 500, 250 mg x L(-1) AG could induce C. albicans biofilm dispersion in a dose-dependent manner, and the dispersed cells were dominated by the yeast phase. According to the real-time fluorescence quantification PCR (qRT-PCR) test, AG could up-regulate HSP90 expression and down-regulate UME6 and PES1 expressions. This study demonstrates that AG could induce C. albicans biofilm dispersion to some extent.
Anti-Inflammatory Agents ; pharmacology ; Biofilms ; drug effects ; Candida albicans ; genetics ; physiology ; ultrastructure ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Fungal Proteins ; genetics ; Gene Expression Regulation, Fungal ; drug effects ; HSP90 Heat-Shock Proteins ; genetics ; Microscopy, Electron, Scanning ; Reverse Transcriptase Polymerase Chain Reaction ; Time Factors

OBJECTIVETo investigate the effect of andrographolide derivative Yanhuning (YHN) on Candida albicans biofilms in rats.

METHODThe rat C. albicans biofilms subcutaneous catheter model was established by intraperitoneally injecting YHN (40, 20, 10, 5, 2.5 mg x kg (-1)), with the FLC (80 mg x kg(-1)) positive group as the control group. After 7 d, CFU counting and XTT assay were used to evaluate the effect of YHN on C. albicans biofllms in vivo. Scanning electron microscopy (SEM) was applied to observe the morphological changes in rat biofilms intervened by YHN. The real-time fluorescence quantification PCR was adopted to detect expressions of C. albicans adhesion-related genes, such as ALS1, ALS3, HWP1, EAP1 and MP65.

RESULTThe YHN group showed much less CFUs on catheter pieces and lower XTT metabolic activity than the blank group, with dosage dependence. SEM also showed that YHN could obviously decrease C. albicans adhesion on subcutaneous catheters in rats. According to qRT-PCR's results, YHN can down-regulate expressions of ALS1, ALS3, HWP1, EAP1 and MP65.

CONCLUSIONYHN could inhibit C. albicans biofilms in rats.

Animals ; Biofilms ; drug effects ; growth & development ; Candida albicans ; cytology ; drug effects ; physiology ; Catheters ; microbiology ; Cell Adhesion ; drug effects ; Diterpenes ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Rats

OBJECTIVETo investigate the effects of ethyl acetate extract of Huanglian Jiedu decoction (EAHD) , alone and in combination with fluconazole (FLZ) on FLZ-resistant Candida albicans.

METHODThe minimum inhibitory concentrations (MIC) and sessile MIC80 (SMIC80) of EAHD and FLZ to FLZ-resistant C. albicans were determined by CLSI M27-A3 microdilution method, and the synergy of EAHD combined with FLZ were examined by the checkerboard microdilution assay. Agar plate-method was adopted to observe the rate of antifungal activity according to time-kill curve. HPLC and qRT-PCR were utilized to evaluate the changes of ergosterol content and expressions of related genes, respectively.

RESULTMICs of EAHD ranged from 156 to 1,250 mg · L(-1), those of FLZ from 256 to above 2,048 mg · L(-1) with FICI approximate 0.066 in combination; SMIC80 of EAHD were higher than 1,250 mg · L(-1), SMIC80 of FLZ were higher than 512 mg · L(-1) and up to above 2,048 mg · L(-1). Combination group also showed synergy effect except one group showing addition effect. The results of T-K experiment also confirmed obviously fungicidal effect when treated for 12 h. When compared with control groups, the ergosterol was reduced 85% and 50% in the treatments of combination and EAHD alone by HPLC, respective- ly. The expressions of ERG1, ERG2, ERG6, ERG7 and ERG11 were upregulated, and ACS1, ACS2, MET6 were downregulated when exposed to FLZ. The expressions of the above genes were downregulated by treatment of EAHD. The expressions of ERG2, ERG6, ERG11 were upregulated, while ERG1, ERG7, ACS1, ACS2, MET6 were downregulated in combination group.

CONCLUSIONThe combination of EAHD and FLZ exhibited synergy against FLZ-resistant C. albicans through decreasing the synthesis of ergosterol, and resulting in the breakage of cell membrane.

Antifungal Agents ; pharmacology ; Candida albicans ; drug effects ; growth & development ; metabolism ; Drug Resistance, Fungal ; drug effects ; Drug Synergism ; Drugs, Chinese Herbal ; pharmacology ; Ergosterol ; biosynthesis ; Fluconazole ; pharmacology ; Microbial Sensitivity Tests

OBJECTIVETo investigate anti-attachment effect of ethyl acetate extract of Huanglian Jiedu decoction (EAHD) on Candida glabrata.

METHODSerial 2-fold dilution assay was used to determine the minimum inhibitory concentrations MICs of EAHD to C. glabrata. XTT assay was used to evaluate the effect of EAHD against adhesion of C. glabrata. Inverted microscope, scanning electron microscope (SEM) and fluorescein diacetate (FDA) staining were applied to observe the morphological changes of C. glabrata in adhesion. PCR was adopted to inspect the expression of attachment-related genes such as EPA1, EPA6 and EPA7.

RESULTThe MIC of EAHD and fluconazole to C. glabrata were 320 mg · L(-1) and 1 mg · L(-1) respectively. The total cells including budding cells decreased in a dose-dependent manner following EAHD treatment. The expressions of EPA1, EPA6 and EPA7 were downregulated dramatically after EAHD treatment.

CONCLUSIONEAHD could effectively inhibit adherence of C. glabrata.

Acetates ; Candida glabrata ; drug effects ; physiology ; Drugs, Chinese Herbal ; pharmacology ; Fungal Proteins ; genetics ; Lectins ; genetics ; Plant Extracts ; pharmacology

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

Objective To explore the DNA damage in peripheral blood lymphocytes of rats exposed to sodium arsenite. Methods Thirty-two Wistar rats, weighing 180 - 200 g, equal male and female, were randomly divided into 4 groups, 8 in each group. Sodium arsenite 0(control) ,0.05,0.15,0.45 mg/L were given through drinking water for 30 days. Body weight and drinking water consumption were measured every day. Blood were collected and DNA damage in peripheral blood lymphocytes was examined by single cell gel electrophoresis.Results The increase of body mass[( 121.00 ± 38.57), ( 120.62 ± 42.80), ( 125.38 ± 48.68)g]and water intake [(36.9 ± 6.2), (37.9 ± 5.8), (39.3 ± 4.2)ml/d]in 0.05,0.15,0.45 mg/L sodium arsenite groups were compared with the control group[( 119.25 ± 47.27)g, (38.4 ± 5.1 )ml/d], and the difference were not significant (F = 0.040,0.828, all P ＞ 0.05). The tail ratios[46.25%(185/400) ,57.00%(228/400),64.00%(256/400)], tail lengths [(32.89 ± 17.18), (58.74 ± 36.28), (77.55 ± 35.73 ) μm]and tail moments [(6.29 ± 3.74), ( 11.20 ± 9.64),(17.30 ± 12.60)μm]in 0.05,0.15,0.45 mg/L sodium arsenite groups were significantly higher than those of the control group[39.25%(157/400), (18.73 ± 15.83),(2.61 ± 1.05)μm, all P ＜ 0.01], and the tail ratios,tail lengths and tail moments in lymphocytes increased with increased doses of arsenic concentration. Conclusions Low doses of arsenic exposure can induce DNA damage in peripheral blood lymphocytes of rats.

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

OBJECTIVETo investigate the effect of propofol on brain regions at different sedation levels and the association between changes in brain region activity and loss of consciousness using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) and bispectral index (BIS) monitoring.

METHODSForty-eight participants were enrolled at Peking Union Medical College Hospital from October 2011 to March 2012 and randomly assigned to a mild or a deep sedation group using computer- generated random numbers. Preliminary tests were performed a week prior to scanning to determine target effect site concentrations based on BIS and concomitant Observer's Assessment of Alertness/Sedation scores while under propofol. Within one week of the preliminary tests where propofol dose-response was established, BOLD-fMRI was conducted to examine brain activation with the subject awake, and with propofol infusion at the sedation level.

RESULTSMild propofol sedation inhibited left inferior parietal lobe activation. Deep sedation inhibited activation of the left insula, left superior temporal gyrus, and right middle temporal gyrus. Compared with mild sedation, deep propofol sedation inhibited activation of the left thalamus, precentral gyrus, anterior cingulate, and right basal nuclei.

CONCLUSIONMild and deep propofol sedation are associated with inhibition of different brain regions, possibly explaining differences in the respective loss of consciousness processes.

Adult ; Brain ; drug effects ; Consciousness Monitors ; Deep Sedation ; Dose-Response Relationship, Drug ; Humans ; Hypnotics and Sedatives ; pharmacology ; Male ; Propofol ; pharmacology