Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

Calcium phosphate cement (CPC) is considered as an important bone repairing materials due to its excellent biocompatibility, osteoconductivity and remodellability, the study about its performance is still a hot topic in the field of bone tissue engineering. Premixed calcium phosphate cements (PCPC) has advantages that can save operatiion time,be convenient to the operation and preservation compared with the traditional way of immediately mixing calcium phosphate cement. PCCP has overcome the shortcomings of uneven and inadequate mixing, and can be arbitrarily remodeled according to the shape of defect, thus researches on PCCP has also become more and more interested
Bone Cements ; chemistry ; Calcium Phosphates ; chemistry ; Humans ; Materials Testing ; Solubility

BACKGROUND:Cobalt chloride (CoCl2) may promote the proliferation of human umbilical cord-derived mesenchymal stem cels (hUC-MSCs) in a time- and concentration-dependent manner, and meanwhile, CoCl2 can regulate the expression of genes and proteins in hUC-MSCs. OBJECTIVE:To explore the effects of CoCl2 induced-hypoxia on the proliferation of hUC-MSCs and gene and protein expressions in hUC-MSCs, thereby establishing an effective method for MSCs culture and amplificationin vitro. METHODS: hUC-MSCs were extracted using tissue explant method. Under hypoxia conditions induced by CoCl2 (0, 100, 150, 200, 250 μmol/L) for different periods (0, 1, 2, 3, 4 days), flow cytometry was used to identify cel surface-associated antigens; cel counting kit-8 was used to detect cel proliferation; RT-PCR was used to determine levels of hypoxia inducible factor-1α, inducible nitric oxide synthase, stromal cel-derived factor-1, interleukin-6, transforming growth factor-β mRNA; western blot assay was used to detect protein expression of hypoxia inducible factor-1α. RESULTS AND CONCLUSION:The cels were positive for CD29, CD73, CD90, CD105, while negative for CD31, CD14, CD34, CD45, CD11b, HLA-DR. Moreover, the antigen expression was not affected by CoCl2 induced-hypoxia. CoCl2 induced-chemical hypoxia could promote the proliferation of hUC-MSCs in a time- and concentration-dependent manner. RT-PCR results showed thatunder hypoxia, hypoxia inducible factor 1α, inducible nitric oxide synthase and stromal cel-derived factor-1 mRNA expressions were significantly up-regulated, but interleukin-6 and transforming growth factor-β mRNA expressions were down-regulated significantly (P < 0.05). Additionaly, the protein expression of hypoxia inducible factor 1α was increased under hypoxia conditions. These findings indicate that CoCl2 induced-hypoxia environment may promote the proliferation of hUC-MSCs and the optimal concentration of CoCl2 is 200μmol/L. However, a higher concentration of CoCl2 (≥ 250μmol/L) inhibits the proliferation of hUC-MSCs, and the mechanism may be related to the increase of hypoxia inducible factor-1α at protein and mRNA levels.

ObjectiveTo provide the early diagnosis of Alzheimer\'s disease(AD), the memory in the patients with mild cognitive impairment(MCI) was detected under the functional magnetic resonance imaging(fMRI), combined with the behavioral experiment.Methods9 patients with MCI and 9 controls matched for the age, gender, level of education and handedness performed encoding and retrieval of nonsense line drawings, presented visually while the MR machine was scanning. ResultsCompared with the controls, the patients manifested longer reaction time and lower correct ratio. The patients\' brain activation showed: the first episode of encoding of nonsense line drawings elicited distributed activation in bilateral dorsal lateral frontal lobes, left parahippocampus, bilateral temporal-occipital conjunction, parietal lobes and visual cortex in the control subjects. While these activations decreased in the second episode of encoding of the same stimuli, much stronger activation was found in most same areas during the retrieval phase except for the right parietal lobe, in which the patients showed stronger activation. Moreover, activation in the anterior cingulate cortex was observed only in the retrieval phase. The patients showed weaker and smaller activation in almost all activation areas during all tasks in the normal subjects. ConclusionThe patients with MCI have the deficit in memory. The examination of encoding and retrieval of nonsense line drawings by means of the behavioral experiment and fMRI test can offer a powerful reference for the early diagnosis of AD.

Aim To investigate and compare the phar-macokinetics of doxapram injection in healthy subjects of different Chinese nationalities including Han, Mon-golian, Korean, Hui and Uigur, and the influence of gender,in order to provide instruction and help for the usage of doxapram for both clinic and remedy of battle wound. Methods An HPLC-UV method was used to determine the plasma concentration of doxapram. Fifty healthy subjects ( five males and five females of each nationality) were recruited for the study. A single dose of 50 mg doxapram was administered intravenously to the healthy subjects, and blood samples were collected at various predetermined time points. The pharmacoki-netic parameters were calculated by DAS software and were compared by SPSS 13. 0 software, in order to as-sess the influence of nationality or gender on pharmaco-kinetics of doxapram. Results The results indicated that the pharmacokinetic profile of doxapram in vivo could be described as two-compartment model. The main pharmacokinetic parameters for Han, Mongolian, Korean, Hui and Uygur were as follows: Cl ( 0. 25 ± 0. 11 ) , ( 0. 33 ± 0. 11 ) , ( 0. 27 ± 0. 07 ) , ( 0. 26 ± 0. 06) and (0. 39 ± 0. 25) L·h-1 ·kg-1 , while Cmax (1. 55 ± 0. 52 ) , ( 1. 02 ± 0. 30 ) , ( 1. 31 ± 0. 47 ) , (1. 48 ± 0. 46 ) and ( 0. 99 ± 0. 35 ) mg · L-1 . The AUC0-12. 5 , AUC0-∞ and Cmax of Chinese Han were sig-nificantly higher than those of Uigur and Mongolian ( P<0. 05 ) , while there was no significant difference in other parameters ( P>0. 05 ) . There were statistically significant differences in Vc , Vd and CL between young males and females ( P < 0. 05 ) . Conclusion The large inter-individual variation in the main pharmacoki-netics suggests the dosage of doxapram should be ad-justed for different nationalities for both clinic and rem-edy of battle wound.

BACKGROUNDThe lung functional status could be displayed on lung perfusion images. With the images, the radiotherapy plans of lung cancer could be guided to more optimized. This study aimed to assess quantitatively the impact of incorporating functional lung imaging into 3-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) planning for non-small cell lung cancer (NSCLC).

METHODSTen patients with NSCLC who had undergone radiotherapy were included in this study. Before radiotherapy, each patient underwent CT simulation and lung perfusion imaging with single photon emission computed tomography (SPECT). The SPECT images were registered with simulation planning CT and used to contour functional lung (lung-F) and non-functional lung (lung-NF). Two 3DCRT plans and two IMRT plans were designed and compared in each patient: two anatomic plans using simulation CT alone and two functional plans using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the four types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Total radiation dose was set at 66 Gy (2 Gy x 33 fractions).

RESULTSIn incorporating perfusion information in 3DCRT and IMRT planning, the reductions on average in the mean doses to the functional lung in the functional plan were 168 cGy and 89 cGy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with > 5 Gy, > 10 Gy, > 20 Gy, > 30 Gy and > 40 Gy for functional lung in the functional plans were 6.50%, 10.21%, 14.02%, 22.30% and 23.46% in 3DCRT planning, respectively, and 3.05%, 15.52%, 14.16%, 4.87%, and 3.33% in IMRT planning, respectively. No greater degree of sparing of the functional lung was achieved in functional IMRT than in 3DCRT.

CONCLUSIONFunction-guided 3DCRT and IMRT plannings both appear to be effective in preserving functional lung in NSCLC patients.

Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; pathology ; radiotherapy ; Humans ; Radiography ; Radiotherapy, Conformal ; methods ; Radiotherapy, Intensity-Modulated ; methods ; Tomography, Emission-Computed, Single-Photon ; methods

Objective To study the incidence of stroke among elderly people in China's longevity area and its association with diseases such as hypertension,diabetes and heart disease.The differences in the following common hematological indicators in subjects with stroke and non-hypertension,diabetes,heart disease and stroke were studied:superoxide dismutase (SOD),malondialdehyde (MDA),hypersensitive c-reactive protein (hsCRP),albumin (propagated) glucose (GLU),cholesterol (CHO),triglyceride (TG),high-density lipoprotein cholesterol (HDLC),glycosylated serum protein (GSP) urea nitrogen (BUN),creatinine (CREA) and uric acid (UA).Methods Residents who participated in the project of biomedical research of aging population conducted in 2014 were selected from 8 longevity Areas in China.2 315 people aged 40 and over attended the study,including 22 aged 40 and over,238 aged 60 and over,490 aged 70 and over,629 aged 80 and over,518 aged 90 and over,418 aged 100 and over.Using the self-designed questionnaire to collect information about the characteristics of social demographics,the clinical doctors used the unified inspection tool to examine the subjects.The fasting blood samples were collected by vacuum tube at early morning.The contents of plasma SOD,MDA,hsCRP,ALB,GLU,CHO,TG,HDLC,GSP,BUN,CREA and UA were detected and compared among these elderly who were classified into different genders and different age groups and different healthy groups.Results The prevalence of high blood pressure,diabetes,heart disease and stroke increased with age,reaching a peak and then slowly decreasing.The age of peak was 90 ～ 99,60 ～ 69,70～ 79 and 80～ 89.The prevalence of hypertension was 71.62 ％ and 60.54 ％ respectively for stroke subjects and non-cerebral apoplexy subjects,and the difference was statistically significant.The prevalence of diabetes was 18.92％ and 11.35％ respectively,and the difference was statistically significant.The prevalence of heart disease was 20.98％ and 5.26％,respectively,and the difference was statistically significant.The rates of non-hypertension,non diabetic and non-heart disease were 4.73％ and 33.41％ respectively,and the difference was statistically significant.In the groups of Stroke subjects and Non-high blood pressure,nomdiabetic,non-heart disease subjects the following indicators were Compared,values of SOD were 55.76±8.27 and 57.16±8.00 U/ml respectively,the difference between groups were not statistically significant (t=0.341,P=0.053),values of MDA were 5.81 ± 3.82 and 5.67± 3.16 μmol/L respectively,the difference between groups were not statistically significant (t=0.329,P =0.661),values of hsCRP were 4.15 ± 12.33 and 2.94 ± 6.25 mg/L,respectively,the difference between groups were not statistically significant (t=0.026,P=0.080),values of ALB were 41.60±4.51 and 42.08±3.94 g/L respectively,the difference between groups were not statistically significant (t=0.032,P=0.194),values of ALB were 41.60 ± 4.51 and 42.08± 3.94 g/L respectively,the difference between groups were not statistically significant (t =0.032,P=0.194),values of ALB were 41.60 ± 4.51 and 42.08 ± 3.94 g/L respectively,the difference between groups were not statistically significant (t =0.032,P=0.194),values of GLU were 5.89 ± 2.67 and 4.90 ± 0.90 mmol/L respectively,the difference between groups showed statistically significant (t=0.000,P=0.000)),values of CHO were 4.81 ± 1.00 and 4.71±1.02 mmol/L respectively,the difference between groups were not statistically significant (t =0.670,P=0.318),values of TG were1.33±0.69 and 1.14±0.57 mmol/L respectively,the difference between groups showed statistically significant (t=0.012,P=0.000),values of HDLC were 1.29±0.35 and 1.41±0.40 mmol/L respectively,the difference between groups showed statistically significant (t=0.004,P=0.001),values of GSP were 259.10±60.90 and 246.75±24.52 μmol/L respectively,the difference between groups showed statistically significant (t =0.000,P =0.000),values of BUN were 6.84±± 3.53 and 6.62 ± 2.20 mmol/L respectively,the difference between groups were not statistically significant (t=0.110,P=0.338),values of CREA were 84.92 ± 33.00 and 80.14 ± 24.64 μmol/L respectively,the difference between groups showed statistically significant (t=0.013,P=0.044),values of UA were 296.73±91.34 and 288.12±80.47 μmol/L respectively,the difference between groups were not statistically significant (t=0.123,P=0.247).Conclusion Diabetes,hypertension,and heart disease are risk factors for stroke.Abnormal blood glucose and lipid metabolism:the increase of GLU,TG and the decrease of HDLC are important common biochemical index of stroke.Patients with cerebral apoplexy have certain renal impairment.

[Objective]To investigate awareness of hepatitis B virus(HBV)infection and its mother to child transmis-sion(MTCT)among pregnant women attending their first prenatal visit.[Methods]Pregnant women who attended their first prenatal visit to obstetrics outpatient department of the third affiliated hospital of SUN Yat-sen University from May to Aug. 2014,were invited to participate this survey.The self-administered questionnaire about mother to child transmission of HBV was completed anonymously.Data were collected and using ANOVA and logistic analysis to assess the awareness of hepatitis B and its MTCT,and attitudes towards prevention of MTCT of HBV,and to analyze the effective factors of knowledge and at-titudes.[Results]①Of the 500 questionnaires,the effective response rate was 91.8%(459/500).② The total knowledge score of 11 knowledge questions was 11,and the mean score of participants was 6.09 ± 3.29(M±SD). Only about 50% of participants were aware of the complications of hepatitis B and increasing these complications if caused by MTCT. 65.3% of participants knew hepatitis B vaccine.The awareness about modes of HBV transmission including through blood,unprotected sexual intercourse,MTCT and unsafe needles or sharps were 72.0%,48.9%,75.9% and 66.3%,respectively.③The total attitudes score of 6 attitudes questions was 6,and the mean score of participants was 3.84±1.50(M±SD).More than 80% of pregnant women were willing to be screened for hepatitis B,and let neonate receive HBV vaccine.If diagnosed with hepatitis B,83.1% of pregnant women were willing to let neonate receive hepatitis B immunoglobulin,however,only 16.2% would take drugs to prevent MTCT of HBV.④Education with college or higher level was the independent effective factors associat-ed with better knowledge scores(OR=5.96,95%CI:2.95~12.06).Higher education level was the independent effective fac-tor associated with better attitude scores;when compared with junior high or below,the OR values of senior high and college or higher were 1.90(95%CI:1.01~3.55)and 2.50(95%CI:1.43~4.33),respectively.[Conclusion]Although education level is an independent effective factor associated with knowledge of hepatitis B and attitude towards prevention of MTCT of HBV,lack of knowledge about hepatitis B is common among first prenatal-visiting pregnant women,and more education about hepatitis B is necessary.

Acute pancreatitis(AP)is an inflammatory condition of the pancreas following the activationt of pancreatic enzymes induced by a variety of factors,with or without other organ dysfunction.The production and release of inflammatory factors is generally considered as a key link during pathogenesis.Non-steroidal anti-inflammatory drugs(NSAIDs)are the most commonly applied agents for inflammatory diseases.Many studies have proved that indomethacin can reduce the risk of pancreatitis after endoscopic retrograde cholangiopancreatography;however,few high-quality evidences have demonstrated the roles of NSAIDs in treating,rather than preventing AP.Most animal experiments have shown that NSAIDs can protect organs,although the currently available findings remained inconsistent.Randomized controlled trials with large sample sizes are warranted to elucidate the roles of NSAIDs in treating AP.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Cholangiopancreatography, Endoscopic Retrograde ; Humans ; Indomethacin ; therapeutic use ; Pancreatitis ; drug therapy

Objective To explore the influencing factors on mild cognitive impairment among the community-based elderly population.Methods A‘n:m'matched case-control study was conducted to analyze the risk factors.COx regression model of survival analysis was selected to deal with non-geometric proportional matched data which was difficult to analyze by logistic regression modeI.Results Four hundred and twenty-three cases together with nine hundred and twenty-five controls were interviewed with an uniformed questionnaire.Through univariate and multivariate cox regression analysis,the odds ratio and 95%CJ of these risk factors appeared to be:physieal labor as 1.396(1.092-1.785);smoking as 1.551 (1.021-2.359);higher level of blood glucose as 1.354(1.102-1.664);HDL-C in the serum as 1.543 (1.232-1.932);LDL-C in the serum as 1.299(1.060-1.592);lower level of estrogen in the serum as 1.263(1.031-1.547);hypertension as 1.967(1.438-2.689);diabete:1.381(1.139-1.675);depressive disorder:1.406(1.110-1.780);cerebral thrombosis as 1.593(1.307-1.943);higher SBP as 1.331(1.129-1.569)and ApoEe4 carrier as 1.462(1.140-1.873)respectively.Odds ratio and 95%CI on protection factors appeared to be:reading newspaper frequently as 0.610(0.503-0.740);frequently doing housework as 0.804(0.665-0.973);frequently engaging in social activities as 0.617(0.502-0.757);reemployment after formal retirement as 0.759(0.636-0.906);having acumen olfaction as 0.900(0.845-0.958);having extrovert personality as 0.829(0.699-0.984);being decisive as 0.811(0.662-0.993).Conclusion The major measures to prevent MCI seemed to be including the following factors as:being intellectuals,engaging in healthy life style and decreasing the risk in developing hypertension,diabetes,depressive disorder and cerebrovascular disease.However.olfactory hypoesthesia,cowardice and haring introvert character,ApoEε4 carrier etc could be treated as early indications to signify MCI.