Objective To explore the effects of arsenite on the expression of estrogen receptor (ER) mRNA,ER protein and the ER signaling pathway in rats.Methods Random grouping experiment design was used to evaluate the effects of arsenite on the expression of ER mRNA,ER protein and the ER signaling pathway (24 rats were divided into 4 groups:control,Aslow,Asmiddle,Ashigh groups;6 rats in each group).Female rats were exposed to NaAsO2 (0.625,2.500,10.000 mg/kg) by oral perfusion at gradient doses for three months respectively.The expression of ER mRNA as effect biomarker was observed through RT-PCR.The concentration of ER,vascular endothelial growth factor (VEGF),cyclin D1 (CYC-D1),and progesterone receptor (PR) in serum was determined as effect biomarkers using enzyme-linked immunosorbent assay (ELISA).Results The levels of ER mRNA,VEGF,PR,CYC-D1,and ER in control,Aslow,Asmiddle,and Ashigh groups were statistically different (F =204.13,227.14,256.13,179.23,167.34,all P ＜ 0.01).With increasing of arsenic,the expression of ER mRNA,VEGF,and PR gradually decreased (all P ＜ 0.01);the dose effect relationship was obvious;the expression of CYC-D1 and ER in Asmiddle [(25.45 ± 9.29) U/L,(22.16 ± 9.16) ng/L] was higher than that in Ashigh [(2.60 ± 0.23) U/L,(9.06 t 2.06) ng,/L,all P ＜ 0.01].Arsenic was negatively associated with ER mRNA,ER,VEGF,CYC-D1 and PR (r =-0.689,-0.515,-0.675,-0.456,-0.397,P ＜ 0.01 or ＜ 0.05).ER mRNA was positively associated with ER,VEGF,CYC-D1 and PR (r =0.894,0.662,0.713,0.699,P ＜ 0.01 or ＜ 0.05).Conclusions The expression of ER mRNA and ER protein are inhibited by arsenic,ER may be served as a sensitive biomarker of reproductive system damage after exposed to arsenic.The ER-VEGF,CYC-D1 and PR pathway participate in the process of reproductive system damage caused by arsenic.Arsenic is probably a environmental estrogen.

Aceclofenac is a non-steroidal anti-inflammatory drug (NSAIDs) for inflammatory diseases. In this report, we report a serious adverse event (AE) occurred during the phase I clinical trial for a new sustained-release (SR) formulation of aceclofenac. There was a serious adverse event (AE), agranulocytosis, induced by aceclofenac SR form. An open-labeled, repeated-doses, randomized, crossover study was conducted at Kyung Hee University Hospital and 26 Korean healthy male volunteers were enrolled. All subjects received both aceclofenac SR 200 mg once daily and aceclofenac IR 100 mg twice daily for 4 days with 11 days washout period. After 11 days washout period, one subject showed a serious decrease in the segment neutrophil (267/mm3) on a laboratory test prior to the reference drug administration in period 2. We first report a case of agranulocytosis, during a phase I clinical trial.
Agranulocytosis* ; Cross-Over Studies ; Humans ; Male ; Neutrophils ; Volunteers

Objective To investigate the level and proportional relationship of free fluorine and soluble fluoride in different brands of toothpaste,and analyze possible risk factors.Methods A total of 54 samples of commercially available toothpastes of domestic,joint venture and imported in Guiyang City were collected,and the levels of free fluoride and soluble fluorine were determined,respectively,using fluorideion selective electrode.method (GB 8372-2008).Results The number of the toothpaste was 32,12,10,respectively,in domestic,joint venture and imported.The levels of free fluorine ranged from 0.98 to 1 603.50 mg/kg,3.22 to 617.50 mg/kg and 306.80 to 1 590.80 mg/kg,respectively,in toothpastes of domestic,joint venture and imported; the number of exceeding the standard free fluorine was 3,0 and 1,respectively,in toothpastes of domestic,joint venture and imported; the rate of exceeding the standard free fluorine was 9.4％,0.0％ and 10.0％,respectively,in toothpastes of domestic,joint venture and imported.The levels of soluble fluorine ranged from 3.06 to 4 302.50 mg/kg,9.02 to 1 667.30 mg/kg and 9.18 to 4 013.20 mg/kg,respectively,in toothpastes of domestic,joint venture and imported; the number of exceeding the standard soluble fluorine was 9,2 and 3,respectively,in toothpastes of domestic,joint venture and imported; the rate of exceeding the standard soluble fluorine was 34.4％,16.7％ and 30.0％,respectively,in toothpastes of domestic,joint venture and imported.The proportion of free fluorine and soluble fluoride was:domestic 1.0 ∶ 2.7,joint venture 1.0 ∶ 2.7,imported 1.0 ∶ 2.5,respectively.The confidence limit (R/d) was 0.98.Conclusion The fluoride level in different brands of toothpaste has exceeded the standard,the content and proportion of soluble fluoride are obviously higher than those of free fluoride,and there is a risk on tooth damage from fluoride,and factories should strengthen quality control in adding fluoride.

Objective To explore the applied value of the super-short exposure time of the DR adjustable control in radiography of infant chest.Methods 100 chest radiographic films of infant in adjustable control group and fixed control group respectively were selected randomly.The quality of all films was evaluated by 4 technicians in charge in 4 grades(A,B,C and waste)and the detective rate of the tiny parts of the images was also evaluated.Results DR adjustable control:the rate of grade A,B,C and waste was 70%,20%,10% and 0% respectively.DR fixed control:the rate of grade A,B,C and waste was 42%,41%,15% and 2% respectively.The detective rate of tiny parts was 100% and 90% in DR adjustable control group and DR fixed control group respectively.Conclusion DR adjustable control chest film in infant is better than DR fixed control in image quality.DR adjustable control system is good for radiographic diagnosis.

Objective To investigate the accuracy for absolute quantification of brain creatine (Cr) concentration using long time echo (TE) point resolved spectroscopy (PRESS) sequence performed with an external standard and postprocessed with the linear combination of model spectra (LCModel).Methods Ten swine (3.1±0.6 kg) and an external standard phantom containing detectable compounds of known concentration were investigated in this study by using 1.5 T GE Signa scanner and a standard head coil. The single-voxel proton magnetic resonance spectroscopy (1H-MRS) data were acquired from the two ROIs (2 cm×2 cm×2 cm) placed in swine brain and external standard solution using PRESS sequence with TE 135 ms,TR 1500 ms,and 128 scan averages.The in vivo quantification of Cr was accomplished by LCModel.After 1H-MRS examination,each animal was sacrificed immediately.In vitro Cr concentration was analyzed by high performance liquid chromatography (HPLC).Results In the 1H-MRS group,the Cr concentration was (9.37±0.14)mmol/kg.In the HPLC group,the Cr concentration was (8.91±0.13)mmol/kg.Good agreement was obtained between these two methods (t=9.038,P=0.491).Conclusion The long echo time PRESS sequence performed with an external standard and processed with LCModel iS proven to be an accurate technique to detect the in vivo brain Cr concentration.

Objective To discuss the effects of pressure control (PC) and positive end-expiratory pressure (PEEP) incremental method lung recruitment maneuver (RM) on haemodynamics in piglets with acute lung injury (ALI) induced by paraquat (PQ) poisoning. Methods The ALI/acute respiratory distress syndrome (ARDS) model was reproduced by intraperitoneal injection of 20% PQ (20 mL) in 10 healthy female piglets, and they were randomly divided into PC lung RM group (RM1 group) and PEEP incremental method lung RM group (RM2 group), with 5 piglets in each group. Heart rate (HR), mean arterial pressure (MAP), and cardiac index (CI) were monitored by pulse-indicated continuous cardiac output (PiCCO) monitoring before model reproduction (baseline), on the time of successfully set up of model and at 5, 15 and 30 minutes after RM. At the same time the arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) were recorded, and oxygenation index was calculated. Lung tissues were collected before model reproduction, on the time of successfully set up of model, and at 30 minutes after RM respectively, and pulmonary pathology changes were observed after hematoxylin and eosin (HE) staining under light microscopy. Results The HR, MAP, and PaCO2 on the time of successfully set up of model in both groups were increased obviously while CI, PaO2, and oxygenation index were decreased obviously as compared with those at baseline, all of which conformed to the expression of ALI/ARDS. With RM time extended, the HR in both groups was declined while MAP and CI were increased gradually. The HR and MAP at 5 minutes after RM of RM1 group were significantly lower than those of the RM2 group [HR (bpm): 126.8±5.2 vs. 134.0±3.8, MAP (mmHg, 1 mmHg = 0.133 kPa): 98.4±3.3 vs. 102.8±2.6, both P < 0.05]. The CI at 5 minutes and 15 minutes after RM of RM1 group was significantly higher than that of the RM2 group (mL·s-1·m-2: 56.7±5.0 vs. 46.7±6.7, 65.0±5.0 vs. 56.7±5.0, both P < 0.05). PaO2 and oxygenation index at 5 minutes after RM in both groups were significantly higher than those on the time of sucessfully set up of model. The PaO2 and oxygenation index were gradually decreased, and PaCO2 was increased with RM time extended, but no statistically significant differences at all time points were found between the two groups (all P > 0.05). The lung tissue in both groups showed a variety of pathological changes at 30 minutes after RM. The main performances were the loss of alveolar epithelial cells, the further wideness of alveolar interval and the distension of alveolar, and the part breakage of alveolar interval. The wideness of alveolar interval was more significant in RM2 group than that of RM1 group, and alveolar cleft was more common too. Conclusion Both PC and PEEP incremental method lung RM can improve the oxygenation of the piglets with ALI/ARDS induced by PQ, and the PC lung RM has less impact on haemodynamics.

This study aimed to investigate the cognition-enhancing effect of Panax ginseng. A randomized, double-blind, placebo-controlled clinical trial was conducted to address the cognition-enhancing effects of Panax ginseng. A total of 90 Korean volunteers with mild cognitive impairment participated in this study. All subjects were allocated randomly into ‘Ginseng’ group or ‘Placebo’ group. All subjects were administered 3g of Panax ginseng powder or starch (placebo) for 6 months. The Korean version of the Mini-Mental Status Examination (K-MMSE), Korean version of Instrumental Activities of Daily Living (K-IADL), and Seoul Neuropsychological Screening Battery (SNSB) were used to assess the changes in cognitive function at the end of the 6 month study period. The subjects of the ‘Ginseng’ group improved significantly on the Rey Complex Figure Test (RCFT) immediate recall (P = 0.0405 and P = 0.0342 in per-protocol (PP) and intention-to-treat (ITT) analysis, respectively) and on the RCFT 20-min delayed recall (P = 0.0396 and P = 0.0355 in PP and ITT analysis, respectively) compared with ‘placebo’ group throughout the 6 months of Panax ginseng administration. There were no serious adverse events. These results suggest that Panax ginseng has a cognition-enhancing effect.
Activities of Daily Living ; Cognition ; Mass Screening ; Memory, Short-Term ; Mild Cognitive Impairment ; Panax ; Seoul ; Starch ; Volunteers

Objective:To investigate the role of cholinergic anti-inflammatory pathway in the regulation of peptide transporter 1 (PepT1) expression in small intestinal epithelium of septic rats by Ghrelin.Methods:One hundred adult male Sprague-Dawley (SD) rats were randomly divided into sham operation group, sepsis group, sepsis+vagotomy group, sepsis+Ghrelin group, and sepsis+vagotomy+Ghrelin group, with 20 rats in each group. In the sham operation group, the cecum was separated after laparotomy, without ligation and perforation. In the sepsis group, the rats received cecal ligation puncture (CLP). In the sepsis+vagotomy group, the rats received CLP and vagotomy after laparotomy. In the sepsis+Ghrelin group, 100 μmol/L Ghrelin was intravenously injected after CLP immediately. The rats in the sepsis+vagotomy+Ghrelin group received CLP and vagotomy at the same time, then the Ghrelin was intravenously injected immediately with the same dose as the sepsis+Ghrelin group. Ten rats in each group were taken to observe their survival within 7 days. The remaining 10 rats were sacrificed 20 hours after the operation to obtain venous blood and small intestinal tissue. The condition of the abdominal intestine was observed. The injury of intestinal epithelial cells was observed with transmission electron microscopy. The contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum and small intestinal tissue were detected by enzyme-linked immunosorbent assay (ELISA). The brush border membrane vesicle (BBMV) was prepared, the levels of mRNA and protein expression of PepT1 in the small intestinal epithelium were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting.Results:All rats in the sham operation group survived at 7 days after operation. The 7-day cumulative survival rate of rats in the sepsis group was significantly lower than that in the sham operation group (20% vs. 100%, P < 0.05). The cumulative survival rate of rats after Ghrelin intervention was improved (compared with sepsis group: 40% vs. 20%, P < 0.05), but the protective effect of Ghrelin was weakened after vagotomy (compared with sepsis+Ghrelin group: 10% vs. 40%, P < 0.05). Compared with the sham operation group, in the sepsis group, the small intestine and cecum were dull red, the intestinal tubules were swollen and filled with gas, the intestinal epithelial cells were seriously injured under transmission electron microscopy, the levels of TNF-α and IL-1β in serum and small intestinal were significantly increased, and the expression levels of PepT1 mRNA and protein in the small intestinal epithelium were significantly decreased. It indicated that the sepsis rat model was successfully prepared. After vagotomy, the intestinal swelling and gas accumulation became worse in septic rats, leading to the death of all rats. Compared with the sepsis group, the abdominal situation in the sepsis+Ghrelin group was improved, the injury of intestinal epithelial cells was alleviated, the serum and small intestinal TNF-α and IL-1β were significantly decreased [serum TNF-α (ng/L): 253.27±23.32 vs. 287.90±19.48, small intestinal TNF-α (ng/L): 95.27±11.47 vs. 153.89±18.15, serum IL-1β (ng/L): 39.16±4.47 vs. 54.26±7.27, small intestinal IL-1β (ng/L): 28.47±4.13 vs. 42.26±2.59, all P < 0.05], and the expressions of PepT1 mRNA and protein in the small intestinal epithelium were significantly increased [PepT1 mRNA (2 -ΔΔCt): 0.66±0.05 vs. 0.53±0.06, PepT1 protein (PepT1/GAPDH): 0.80±0.04 vs. 0.60±0.05, both P < 0.05]. Compared with the sepsis+Ghrelin group, after vagotomy in the sepsis+vagotomy+Ghrelin group, the effect of Ghrelin on reducing the release of inflammatory factors in sepsis rats was significantly reduced [serum TNF-α (ng/L): 276.58±19.88 vs. 253.27±23.32, small intestinal TNF-α (ng/L): 144.28±12.99 vs. 95.27±11.47, serum IL-1β (ng/L): 48.15±3.21 vs. 39.16±4.47, small intestinal IL-1β (ng/L): 38.75±4.49 vs. 28.47±4.13, all P < 0.05], the up-regulated effect on the expression of PepT1 in small intestinal epithelium was lost [PepT1 mRNA (2 -ΔΔCt): 0.58±0.03 vs. 0.66±0.05, PepT1 protein (PepT1/GAPDH): 0.70±0.02 vs. 0.80±0.04, both P < 0.05], and the injury of small intestinal epithelial cells was worse. Conclusion:Ghrelin plays a protective role in sepsis by promoting cholinergic neurons to inhibit the release of inflammatory factors, thereby promoting the transcription and translation of PepT1.