Objective To study that puerarin can prevent the renal glucose reabsorbtion process and promote urinary glucose excretion by inhibiting sodium-dependent glucose cotransporters 2 (SGLT2) to reduce plasma glucose in diabetes rats.Methods Molecular docking was carried out on puerarin and the obtained SGLT2 complexes through homology modeling method with dapagliflozin as positive control.Chinese hamster ovary (CHO) cells stably expressing human SGLT2 and [14C]-MethylD-glucopyranoside ([14C]-AMG) as the substrate were used in vitro for the transport assays and IC50 for SGLT2.The antihyperglycemic activity ofpuerarin was operated by oral glucose tolerance test (OGTT) and urinary glucose excretion (UGE) test in rats.Results Puerarin was identified as the substrate of SGLT2 through molecular docking,but the overall effect was not as strong asdapagliflozin.In vitro experiments showed that puerarin can strongly inhibit hSGLT2,the maximum effect was about 84％ with the half inhibitory concentration (IC50) of 0.40 mol/L.OGTT results showed that glucose inhibition rates of puerarin 10,30,60 and 120 mg/kg doses were 5.1％,6.5％,16％,and 22％ respectively,in a dose-dependent manner.In the UGE experiment,the urine sugar increased with the increase of puerarin dose.Compared with model group,the 30,60,and 120 mg/kg dose groups had significant difference (P ＜ 0.05 and 0.01).Conclusion Puerarin exhibited antiglycemic activity through inhibiting SGLT2 and was considered to be a new lead compound of SGLT2 inhibitors.

Objective To explore the distribution of water with high level arsenic and prevalence of arsenism along Huai'he River and the surrounding area of Hong'ze lake in Huai'an of Jiangsu. Methods Wate rsamples were collected and tested in 2008 from 18 villages of 6 towns according to history data in 3 counties like Xuyi,Jinhu and Hongze. Samples having arsenic level higher than 0.05 mg/L were investigated by epidemiological method and the patients were diagnosed by Standard of Diagnosis for Endemic Arsenism. Results All 5199 water samples were determined,and 260 water samples were exceeding the national drinking water quality level (0.05 mg/L) in 3 counties,the rates of exceeding diagnosis were 5.6%(247/4454),0.7%(4/597),6.0%(9/148) respectively. Total detected rate of endemic arsenic disease was 5.94%(128/2155). The detected rates of age group of 0 ～ ,20 ～,30 ～ ,40 ～ ,50 ～ ,60 ～ ,70 ～ ,80 ～ were 2.86%(1/35),2.11%(2/95),1.26%(3/239),3.10%(16/516),5.53% (32/579),10.07%(41/407),11.84%(27/228),10.71%(6/56) respectively. The detected rate of male (9.10%,78/857) was higher than that of female(3.85%,50/1298,χ~2 = 25.46,P < 0.01). Conclusions Huai'he River and the surrounding areas of Hong'ze lake like Xuyi,Jinhu and Hongze are identified existing endemic arsenic disease area. The prevention of arsenism should be strengthened in these areas.

Objective We aimed to assess the association between urinary bisphenol A(BPA)concentrations and gestational age in pregnant women. Methods A total of 248 pregnant women were recruited from a maternal and child care hospital in Shanghai. A questionnaire survey was completed to collect socio-demographic information and spot urine samples were collected during pregnancy. Gas chromatography-tandem mass spectrometry(GC-MS/MS)was used to measure BPA concentrations in urine samples. Linear relationship between urinary BPA level and gestational age was assessed by using generalized additive models. Multivariate regression model was used to evaluate associations of prenatal BPA exposure with gestational age. Results BPA was detected in all the urine samples. Median value and geometric mean of urinary BPA levels were 0.85 μg/L and 1.21 μg/L, respectively. Linear relationship between urinary BPA concentration and gestational weeks was confirmed(non-linear P > 0.05). Positive association between urinary BPA level and gestational age was indicated(regression coefficient, β = 0.19;95%CI:0.04-0.35;P = 0.016). However, it was only observed in girls, stratified by sex of newborns(β = 0.18;95%CI:0.03-0.34;P = 0.020). After stratification by trimester, no significant association was found in the second or the third trimesters. Conclusion Pregnant women are extensively exposed to BPA. Urinary BPA exposure during pregnancy may extend gestational age, especially in girls.

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2'-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the functional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony formation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.
Adenocarcinoma ; genetics ; metabolism ; Apoptosis ; genetics ; Cell Line, Tumor ; Colorectal Neoplasms ; genetics ; metabolism ; DNA Methylation ; Exons ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Insulin-Like Growth Factor Binding Proteins ; genetics ; metabolism ; Transfection ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo identify the volatile organic compounds (VOCs) in lung cancer tissue and lung cancer cell lines.

METHODSThe lung cancer tissue samples from 18 patients were cultured and 4 lung cell lines (A549, NCI-H446, SK-MES-1, BEAS-2B) were also included in the study. Air samples in the headspace of culture flasks were analyzed for VOCs with solid-phase micro-extraction and gas chromatography-mass spectroscopy technique (SPME-GC/MS).

RESULTTwo kinds of VOCs 2-pentadecanone and nonadecane were detected in lung cancer cell lines A549, NCI-H446 and SK-MES-1. The concentration of 2-pentadecanone were (1.382 + or -0.171) X 10(-5)mg/L, (1.681 + or - 0.190) X 10(-4)mg/L and (2.835 + or - 0.401) X 10(-6)mg/L, respectively; the concentrations of nonadecane were (8.382 + or - 0.606 ) X 10(-6)mg/L, (1.845 + or - 0.130) X 10(-5)mg/L and (6.220 + or - 0.362) X 10(-6)mg/L), respectively. The eicosane was detected in A549 and NCI-H446 with the concentration of (8.313 + or - 1.130) X 10(-6)mg/L and (1.020 + or - 0.141) X 10(-5)mg/L), respectively. All the 3 VOCs were not detected in cell line BEAS-2B. The concentrations of 12 VOCs including decane, 2- pentadecanone, nonadecane and eicosane were high in 18 lung cancer tissue samples; the concentrations of 2-pentadecanone were 5.421 X 10(-6)mg/L-3.621 X 10(-5)mg/L,those of nonadecane were 5.805 X 10(-6)mg/L-1.830 X 10(-5)mg/L, those of eicosane were 2.730 X 10(-6)mg/L-2.343 X 10(-5)mg/L. There were no differences of VOCs levels among patients with different cancer differentiation (P>0.05). The concentration of eicosane in the non-squamous carcinoma was higher than that in squamous carcinoma, the same results were confirmed in the lung cancer cell lines.

CONCLUSIONThis study has identified VOCs produced by lung cancer tissue, which may support to use breath test as a complementary noninvasive diagnostic method for lung cancer.

Adult ; Aged ; Alkanes ; metabolism ; Biomarkers, Tumor ; metabolism ; Cell Line, Tumor ; Female ; Humans ; Lung Neoplasms ; diagnosis ; metabolism ; Male ; Middle Aged ; Tumor Cells, Cultured ; Volatile Organic Compounds ; metabolism

OBJECTIVETo investigate the coverage rate of primary immunization of measles containing vaccine (MCV1) among migrant children in Yiwu,Zhejiang province.

METHODSHousehold cluster sampling survey and probability proportion to size sampling method were adopted. A total of 967 migrant children born from 1st July 2007 to 1st July 2010 and their caregivers were selected as target population. Standard face-to-face interviews were conducted to investigate the subjects' knowledge, attitude, practice (KAP) of immunization, MCV1 vaccination and determinants. Multi-variable weighted average score method was adopted to evaluate the result of our survey on KAP. Kaplan-Meier analysis was adopted to assess the coverage of MCV1 and Cox regression analysis was adopted to explore the influencing factors associated with the coverage of MCV1.

RESULTSOut of the 967 children, 104 were born in 2007, accounting for 10.8%; 301 were born in 2008, accounting for 31.1%; 343 were born in 2009, accounting for 35.5% and 219 were born in 2010, accounting for 22.6%. Among the surveyed caregivers, 71.9% (695/967) were mothers and 90.2% (872/976) were migrant from other provinces. According to the result of survey on KAP among caregivers, 56.2% (543/967) scored ≥ 4 points on knowledge, 75.8% (734/967) scored ≥ 4 points on attitude and 48.7% (471/967) scored ≥ 4 points on behavior. 86.6% (838/967) of surveyed caregivers' education levels were under junior middle school.85.9% (831/967) of the migrant children were born in hospitals.36.3% (351/967) of the surveyed families' household income were under 2000 yuan per month.32.7% (316/967) of surveyed caregivers waited less than 15 min for immunization for each time. Coverage rate of MCV1 was 85.9% (831/967; 95%CI: 83.7%-88.1%). The timely coverage rates at 8 months, 12 months, and 24 months were 58.8% (569/967; 95%CI: 55.5%-62.1%), 88.2% (853/967; 95%CI: 86.0%-90.4%) and 98.6% (953/967; 95%CI: 97.8%-99.4%), respectively. The average age of MCV1 immunization for each birth cohort between 2007 and 2010 were 10.4, 10.1, 10.1 and 9.3 month, respectively; without statistical significance (χ(2) = 0.722, P = 0.398). According to the analysis by Cox regression, the caregivers aged ≤ 25 years (24.3% (235/967), RR = 1.520 (95%CI: 1.280-1.800)), the caregivers' education level above college (2.8% (27/967), RR = 3.841 (95%CI: 2.287-6.451)), delivered in county-level hospital (49.4% (478/967), RR = 6.048 (95%CI: 4.311-8.485)), household income > 4000 yuan per month (21.7% (210/967), RR = 1.366 (95%CI:1.163-1.604)), the average score of attitude towards immunization ≥ 4 points (75.9%(734/967), RR = 2.613 (95%CI: 1.026-6.655)), the average waiting time for each vaccination ≤ 15 min (32.7% (316/967), RR = 2.116 (95%CI: 1.341-3.339)) were the important factors to improve the timely immunization coverage rate of MCV1 among migrant children.

CONCLUSIONThe coverage of MCV1 were obviously delayed among migrant children in Yiwu, Zhejiang province. We suggest that the investigation of migrant children should be strengthened and remind or recall mechanism for immunization should be established. Increasing the open days for immunization clinics and reducing the waiting time for vaccination could also improve the coverage and timeliness of the MCV vaccination.

Child ; Child, Preschool ; China ; Family Characteristics ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Measles Vaccine ; Regression Analysis ; Transients and Migrants ; Vaccination ; statistics & numerical data

Aldehyde Dehydrogenase ; immunology ; Animals ; Antibodies, Monoclonal ; biosynthesis ; immunology ; Humans ; Liver ; cytology ; Liver Extracts ; immunology ; Mice ; Mice, Inbred BALB C

The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III (P<0.01), and raised the resting membrane potentials (E(m)) in all these three types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for type I, II, III cells, respectively. These results suggest that acute hypoxia suppresses the potassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction/relaxation response to acute hypoxia.
4-Aminopyridine ; pharmacology ; Animals ; Calcium ; metabolism ; Cell Hypoxia ; Male ; Membrane Potentials ; drug effects ; Muscle, Smooth, Vascular ; cytology ; physiology ; Myocytes, Smooth Muscle ; physiology ; Peptides ; pharmacology ; Potassium Channels ; physiology ; Pulmonary Artery ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Ulnar osteotomy is firstly recommended for the therapy of Monteggia fracture in children. But,there is still a lack of biomechanical evidence to confirm its efficacy and safety. OBJECTIVE: To analyze the stress distribution on the humeroradial joint after ulnar osteotomy and to provide evidence for confirming the angular size and mechanism for ulnar osteotomy. METHODS: Nine elbow joints were subjected to different positions of physiological, posterior 15° and posterior 30° osteotomy, followed by loaded at different flexion angles in the neutral, pronation and supination positions, respectively, and then the detailed stress distribution and area in the humeroradial joint were obtained using I-Scan Stress Distribution Test system. One elbow joint was scanned by three-dimensional reconstruction CT and the three-dimensional finite element model was established by ANSYS software. The model was loaded with the same conditions based on the I-Scan Test RESULTS AND CONCLUSION: (1) I-Scan Test system showed that the stress concentration area was in the medial side of humeroradial joint when elbow joint extended after the posterior osteotomy. Following the buckling angle of elbows increased, the area of stress concentration was changed to posterior and stress and contact area of humeroradial joint decreased correspondingly. An increase of stress and decrease of contact area appeared after posterior osteotomy compared with physiological osteotomy. (2) According to the finite element analysis, after posterior 15° and 30° osteotomy, pressure of humeroradial joint concentrated in medial-posterior region and the stress was increased. (3) To conclude, ulnar posterior 30° osteotomy is superior to 15° in reducing the incidence of radial head redislocation of Monteggia fracture, but may induce osteoarthritis of humeroradial joint.

AIM To study the effects of Elemene Injection (ELE) on the kinetics of intracellular transport of Gefitinib (GEF) in PC-9/GR cells and to probe the role of ELE in reversing oncological multidrug resistance.METHODS The intracellular pharmacokinetic behavior of D-luciferin potassium salt,a substrate of an ATP-binding cassette (ABC) protein,was investigated in PC-9/GRFluc cells using real-time bioluminescence imaging.The resistance of PC-9/GR cells to GEF was determined by MTT assay.Compusyn software was used to analyze the synergistic effect of GEF and ELE,and HPLC to detect the uptake of GEF in PC-9/GR cells.RESULTS The respective GEF IC50 values of 0.01 μg/mL in PC-9 cells and 1.50 μg/mL in PC-9/GR cells revealed the 150 times drug resistance of PC-9/GR to PC-9 cells.The significantly enhanced intracellular fluorescence intensity of D-fluorescein potassium salt by the intervention of ELE also indicated remarkable GEF uptake increase in PC-9/GR cell line (P ＜ 0.05) due to the synergistic result.CONCLUSION Partly as the mechanism in reversing oncological multidrug resistance,ELE,a booster for the fluorescence intensity of D-luciferin potassium salt,promotes cellular uptake of GEF by inhibiting efflux function of ABC proteins.