Objective To know the condition and feature of water-born endemic arsenism in Shaanxi province, and to provide scientific evidences for prevention and treatment of the disease. Methods In 2009, 8 villages of Duhe, Miaogou, Sanhe, Caiyuan in Shanyang county and Shuanglong, Guangming, Donghekou in Zhen'an county and Guojiawan in Mian county as monitoring sites from both the found water-born arsenic poisoning areas and potential ones of drinking water arsenic ＞ 0.15 mg/L were selected. The disease conditions of residents who lived for more than six months of continuous residence, were investigated according to "Endemic Arsenism Diagnostic Criteria" (WS/T 211-2001 ) and arsenic level in the drinking water were determined. Results Seven thousand six hundred and ninety-three individuals were investigated and 612 cases of arsenism were diagnosed in the 8 villages, the prevalence rate was 7.96%(612/7693). Mild patients accounted for 33.17%(203/612), moderate patients accounted for 50.16%(307/612), and severe patients accounted for 16.67%(102/612). The detection rate for male was 9.99%(408/4085), for female was 5.65%(204/3608), the former was higher than the latter(x2 = 49.138,P ＜ 0.01 ). The older the age was, the higher the rate was(x2 = 770.708, P ＜ 0.01 ). Main clinical manifestation of the patients was depigmentation and pigmentation in skin. Patients with one symptom accounted for 43.30% (265/612), with two symptoms accounted for 56.70% (347/612). Three hundred and seventy drinking water samples were detected, the median of arsenism content was 0.005 mg/L, ranged 0 - 1.660 mg/L. The over-limit rate of arsenic level in the drinking water were 11.62% (43/370). Conclusion Water-born endemic arsenism is mildly prevailing in Shaanxi province, however, great attention should be given to control and monitoring of the disease.

Objective To investigate the current situation of endemic fluorosis associated with drinking water in Shaanxi province in 2008, providing prevention and control work with scientific evidence. Methods According to data of drinking water endemic fluorosis in Shaanxi, 15 counties in Yulin, Weinan and Xianyang city were divided into mild, moderate and severe diseased areas according to fuoride level in the drinking water or the fluorosis severity, and 12,39,45 endemic fluorosis villages were selected respectively from each area. Dental fluorosis for all the children aged 8 - 12 years old and clinical skeletal fluorosis for the people over the age of 16 were examined. In mild, moderate and severe areas, 30% of the survey villages received X-ray to examine skeletal fuorosis. Five water samples were collected from villages with unimproved water respectively from the east, the west, the south, the north, the middle; if there was less than 5 that could be sampled, then all were collected, moreover 3 peripheral and 1 central water samples were collected from villages with improved water. Also in mild, moderate and severe illness areas, 50% of the surveyed villages were selected; in each village, 30 urine samples of the children aged 8 - 12 were collected, 6 portions in each age group. If Less than 30 children in all the age groups or less than 6 in each age group, all their urine samples were collected to determine fluoride. Results Totally 3652 children aged 8 - 12 years old were examined and 1930 cases of dental fluorosis were diagnosed, the rate was 52.85% and the index was 1.22. The rates in Dinghian, Jingbian and Pucheng village were higher, being 90.43% (170/188) ,82.89%(126/152),80.65% (325/403) respectively. A total of 40 543 adults over the age of 16 were examined and 5935 cases of skeletal fluorosis were diagnosed, in a rate of 14.64%. The rates of the mild, moderate, severe skeletal fluorosis were respectively 9.17%(3717/40 543),4.36%(1769/40 543),1.11%(449/40 543).All 706 adults were taken X-ray films.and 280 cases of positive change were diagnosed,the positive rate was 39.66%. The rates of the mild,moderate,severe change were respectively 17.28%(122/706),17.00%(120/706),5.38%(38/706).All 427 water samples were collected,the fluoride content waS(2.22±1.41)ms/L,and the abnormal rate was 85.01%(363/427).All 1393 portions of urine sample were collected in children and the median of fuoride was 2.37 mg/L Conclusions The endemic fluorosis associated with drinking water is still comparatively serious in Shaanxi.The preventive measures for improving water must be improved.

Objective To investigate the status of the disease of the fluorosis and arsenism caused by coal-burning in Ankang city of Shaanxi. Methods Nine survey spots were chosen to carry out the epidemiological investigation of adult skeletal fluorosis and arsenism in the coal-polluted areas of Ankang, respectively using Determination of Fluorine in Coal (GB/T 4633-1997) to determine the coal fluorine and using hydride generation atomic fluorescence spectrophotometry(HCAFS) to determine coal arsenic. The diagnose of the adult skeletal fluorosis followed the Diagnosis of Clinical Classification for Endemic Skeletal Fluorosis Standard(GB 16396-1996), that of arsenism using Standard of Diagnosis for Endemic Arsensim (WS/T 211-2001). Results Totally 569 adults were investigated over the age of 16, among which 121 cases were skeletal fluorosis, with a total detection rate of 21.27%. Four cases of II degree and higher skeletal fluorosis patients were identified, accounting for 0.70% of the number of subjects. One hundred and thirty-two cases of arsenic poisonin were detected, in a rate of 23.20%. Ninety-five patients were identified with moderate or severe arsenic poisoning, accounting for 16.69% of subjects. A positive correlation was found between the detection rates of the skeletal fluorosis and the arsenism(r = 0.816, P < 0.01), as well as between the detection rate of skeletal fluorosis and fluoride content of coal(r = 0.775, P < 0.05). The detection rate of arsenism and arsenic content of coal also had close relationship (r = 0.761, P < 0.05). The detection rate of skeletal fluorosis in the group aged 40 - ,50 - , and 60 - [27.20%(34/125) ,29.27%(36/123), 28.13%(36/128)] was increased, compared the group of less than 40 years age[7.77%( 15/193), X~2 = 21.969,25.648,23.856,P<0.01].For the detection rate of arsenism,male[33.67%(99/294)]was obviously higher than female[12.00%(33/275),)(X~2=37.162,P<0.01].Conclusions A high detection rate of fhorosis is correlated with arsenic poisoning,but the probability of the two diseases simultaneously occurred in a person is not high.In this polluted area.when fluoride accumulates to a certain level as in aduh,the detection rates no longer varies obviously;however,that of arsenism increases along with the age.

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

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

PARP [poly(ADP-ribose)polymerase] represents a novel potential target in cancer therapy. It is involved in a DNA repair process by catalyzing the transfer of ADP-ribose units from NAD to a number of its substrate proteins. In this work, a series of novel azaindole derivatives was designed and synthesized. Moreover, 16 target molecules were screened and 8 compounds displayed inhibitory activity against PARP-1. It has been demonstrated that these azaindoles bearing cycloamine substituents at 2-position were active to both PARP-1 and PARP-2.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Aza Compounds ; chemical synthesis ; chemistry ; pharmacology ; Indoles ; chemical synthesis ; chemistry ; pharmacology ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism

Objective To study the role of hematopoietic growth factor(HGF)of placenta chorionic villus in fetal hematopoiesis during embryo ontogeny by observation of the appearance time and the content changes with the fetal growth, which was compared with HGF in cord blood. Methods Thirty embryo villus (2 g each) and 30 cord blood (2 mL each) were collected separately from early pregnant stage(6- 8 weeks), middle pregnant stage(16-22 weeks)and late pregnant stage (37-42 weeks). The levels of HGF were detected by enzyme - linked immunosorbent assay. Results HGF were produced on the early pregnant stage and the content of FL-T3,IL-3 increased gradually.There were significantly differences at different stages(P

1.0?10~7 copies/mL. The HBsAg IHC staining positive cells could be observed in 6 placental tissues and 3 fetus' liver tissues,and HBcAg was also positive in 1 case of fetus' liver tissue.After co-incubating the tropho- blastic cells and HBV DNA positive serum in vitro,HBsAg expression and HBV DNA could be detected.Apoptosis of HBV-infected trophoblastic cells increased,which was demonstrated by in vivo and in vitro experiments and the apoptosis of placental cells was correlated with the cord blood HBV DNA level.The results of in vitro experiments showed that the apoptosis of trophoblastic cells increased with the elongation of infection time.After 6 months,1 of 12 newborns was positive for HBsAg,HBeAg and anti-HBc,6 was positive for anti-HBs.Conclusions The mechanism of HBV intra-uterine infection may be that HBV breaches the placental barrier and infects the fetus.The localization and replication of HBV in fetal tissues and organs are probably the important factors of chronic HBV infections in neonates.The apoptosis of trophoblastic cells may be the protective mecha- nism for the placental barrier to block the HBV intra-uterine transmission.

ObjectiveTo investigate the current situation of coal-burning borne endemic fluorosis in the infected area,the usage of defluoridation stove and the formation of related behavior; to evaluate the control effect,so as to provide a theoretical basis for superiors' policy-making.MethodsNine villages in three counties of Ankang city and Hanzhong city Shanxi province were monitored in 2010.Choose five disease infected villages with oven changed in the three monitoring counties,and 10 families were randomly selected in each of the nine monitoring points and every chosen village,and a survey on the stove using and related behavior changes was carried out.By using Dean method,the dental fluorosis of every child aged 8 - 12 in the monitoring villages was examined.Meanwhile 10 copies of urine samples were randomly collected in each age group in the above-mentioned villages.The content of fluoride in urine was determined by F-ion selective electrode(WS/T 30-1996) and evaluated according to “The Normal Concentration of Urinary Fluoride of Population” (WS/T 256-2005).Twenty men over 25years old in the monitoring counties were randomly selected in each age group to be examined skeletal fluorosis by X-rays,and diagnosis was based on “The Endemic Skeletal Fluorosis Standard”(WS 192-2007).ResultsThe proper utilization rate and the qualified households of iron stoves and improved stoves,the correct drying rate and the correct storage rate of peppers and coms were all low.The washing rate of corns and peppers before eating was higher than 95％.Of the 350 children being examined of dental fluorosis in the 9 monitoring villages,the detection rate of dental fluorosis was 59.71％ (209/350).A total of 871 adults over the age of 25 were examined,and the detection rate of skeletal fluorosis was 17.22％ (150/871).A total of 350 copies of children urine samples were tested and the fluoride content were between 0.07 - 2.02 mg/L,the geometric mean value of fluoride content was 0.66 mg/L.ConclusionsThe coal-burning borne endemic fluorosis in Shanxi is in a growth phase,many defluoridation stoves are out of order,and the formation of healthy behaviors is low.To strengthen the disease surveillance,health education and management of defluoridation stoves are keys to prevent coal-burning borne endemic fluorosis in the future.

Objective To investigate the running conditions of the water improvement projects and the role of these projects in reducing fluoride in drinking-water type of fluorosis in Shaanxi province, and provide a scientific basis for prevention and control of the disease. Methods Forty-eight villages of 16 counties in Xi'an, Baoji, and Yulin cities of Shaanxi province were monitored in 2009. Five water samples were collected randomly in water unimproved monitoring villages by the position of east, west, south, north, and center parts. In water improved monitoring villages, 3 tap water and one source water samples were collected. Water fluoride was tested using fluoride ion selective electrode method according to the "Standard Testing Methods for Drinking Water" (GB/T 5750-2006). All school children aged 8 to 12 in monitored villages were examined their dental fluorosis using Dean criteria. All people over 16 years old were examined clinical skeletal fluorosis, and 30% of the project counties were randomly selected, then randomly selected one village among these counties, clinically diagnosed patients with skeletal fluorosis were examined again by X-ray using "Diagnostic Criteria of Endemic Skeletal Fluorosis"(WS 192-2007). Urine samples of 30 children aged 8 to 12 and of 20 adults over the age of 16 were randomly collected, urinary fluoride was tested according to "the Determination of Urinary Fluoride by Ion Selective Electrode Method" (WS/T 89-19%). Results Of the 22 water improvement projects that in normal operation, fluoride level of 8 source waters exceeded the standard, accounting for 36.36%(8/22), and projects scrapped 5. Two hundred and two water samples were tested. In water improved historical diseased areas, the median of water fluoride of source water and tap water were 0.72,0.62 mg/L, respectively, and the average rate of water fluoride exceeded the standard ere 36.36%(8/22) and 31.94%(23/72), respectively. In water unimproved historical diseased areas, the median of water fluoride was 1.00 mg/L, and the average rate of water fluoride exceeded the standard was 39.81%(43/108). Detection rate of dental fluorosis among children aged 8 to 12 was 16.06% (367/2285), dental fluorosis index was 0.30, and the prevalence was negative. Detection rate of clinical skeletal fluorosis among adults over 16 years old was 5.09%(1542/30 272), a totally of 198 people had X-ray film taken, positive 68, the positive detection rate was 34.34%(68/198). One thousand and fifty-one copies of children's urine samples were tested, geometric mean of urinary fluoride was 0.95 mg/L; nine hundred and fourteen copies of adults urine samples were tested, geometric mean of urinary fluoride was 1.16 mg/L Conclusions Drinking-water type of fluorosis affects a large area in Shaanxi province, the disease is still serious, and the task of prevention remains very arduous. Further intensify the water improvement project in diseased areas, and strengthen disease monitoring, health education and water improvement project management is the key to prevention and control of endemic fluorosis.