AIM: To establish an LC-MS/MS method for determination of evodiamine concentration in rat plasma and to study its pharmacokinetic profile in rats. METHODS: Six rats were administrated (i.g.) evodiamine at the dose of 100 mg/kg. Blood samples were collected from eye socket. Evodiamine concentration in rat plasma was determined by LC-MS/MS method. The pharmacokinetic parameters were calculated using DAS program. RESULTS: A good linear relationship was obtained in the concentration range (0.2-50.0 ng/mL) studied (r2=0.9997). Average recoveries ranged from 96.12% to 99.46%. Intra-and inter-day relative standard deviations were 4.61%-13.51% and 5.65%-11.49%, respectively. The main pharmacokinetic parameters of evodiamine were as follows: Cmax (5.3±1.5) ng/mL; tmax (22±8) min; t1/2 (451±176) min. CONCLUSION: A selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the quantification of evodiamine in rat plasma is developed and validated. This method is successfully applied for the pharmacokinetic studies of evodiamine in rats.

AIM: To determine the concentration of escitalopram in human plasma by HPLC-MS/MS and investigate the pharmacokinetics of escitalopram. METH-ODS: The method involved protein precipitation with methanol. The chromatographic separation was achieved within 6.0 min by using methanol-water with 15 mmol·L-1 ammonium acetate-formic acid (72:28:O.1, v/v/v) as mobile phase and a Lichrospher CN 150 mm×4.6 mm analytical column. The analytes were detected using an electrospray ionization tandem mass spectrometry in SRM mode. Detection of the ions was performed by monitoring the transitions of m/z 325.0 to 234.0 for escitalopram and m/z 409.1 to 238.1 for amlodipine (intemal standard), respectively. RESULTS:The standard curve was linear ( r = 0. 999) over the concentration range of 0.20 - 50.00 ng· ml- 1. Accuracy and precision were below the acceptance limits of 15%. The recoveries of escitalopram ranged from 96.0% to 103.6%. The lower limit of quantification for escitalopram was 0.20 ng· ml-1 using 200 μl plasma sample.The pharmacokinetic parameters of escitalopram after a single oral dosing of escitalopram oxalate tablet (10 rog)to ten healthy male volunteers were achieved. The Cmax, Tmax, AUC0-t, AUC0-∞, t1/2 and Ke of escitalopram were 9.21±2.10 ng·ml-1 , 3.75±1.04 h, 514.6±152.3 ng·h·ml-1 ,540.5±162.3 ng·h·ml-1 , 34.06±7.71 h and 0.021±0.004 h-1,respectively. CONCLUSION:The determination of concentration of escitalopram in human plasma by HPLC-MS/MS method was repid, sensitive and reliable. It can be used for clinical pharmacokinetic study of escitalopram.

Objective To investigate mental health literacy (MHL) of community medical staffs in district and town of Zhongshan city,and to provide data to improve MHL of community medical staffs.Methods Totally 352 medical staffs who were not psychiatric physician and 81 psychiatric physician were selected.The Chinese Mental Health Knowledge Awareness Questionnaire (published by Ministry of Health) was used to investigate the awareness rate of mental health knowledge.Five vignettes of two schizophrenia,one bipolar disorder,one depression and one obsessive compulsive disorder,each with 8 related questions,were used to investigate the recognition and response ability.Results The average awareness rate of the two groups was more than 80.0% (87.6%,91.6%).For the item 2(75.6%,88.6%),6(74.1%,62.6%),19(36.5%,65.6%),and 20(74.1%,86.2%),the awareness rates were lower than 80.0%,and there were significant differences between the two groups (x2=8.45,4.92,27.48,6.99,all P<0.05).In vignettes survey,the correct rate was lower in the staffs who did not engaged in the mental health work than those in the other group,the difference was statistically significant(64.6% vs.75.9%,P<0.001).For both of the two groups the correct rate of depression was the lowest(x2=44.46,P<0.001).There was statistically significant difference between the total (x2=141.17,P<0.001).Conclusion The awareness rate of mental health knowledge has reached the national standards for community medical staffs,but they have to improve for some knowledge point.Their recognition and response ability for mental illness should be improved.

A highly sensitive, rapid and selective liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for the quantitative determination of retinamido-ester in rat plasma was developed and validated. A simplified protein precipitation with acetonitrile was employed for the sample preparation.The separation was carried out on an Agilent TC C18 column ( 150 mm×4. 6 mm ID, 5 μm particle size)with the mobile phase consisted of methanol-water-formic acid (93 : 7 : 0.1). Simvastatin was used as internal standard. The detection was performed on a trap-quadrupele tandem mass spectrometer by selected reaction monitoring (SRM) scan mode via atmospheric pressure chemical ionization (APCI). The range of and inter-day precision values were between 95.97% and 104. 43%, and RSD was between 4. 63% and 10. 69%, respectively. This method was applied to determine the pharmacokinetic parameters. The main pharmacokinetic parameters of retinamido-ester after oral administration via gastric gavage of 2. 5, 5, 10mg·kg-1 were as follows,T1/2;(11.28±7.23),(8.90±3.82),(8.01±5.56)h; AUC0-∞:(103.41±61.46),(190.23±74.99),(421.66±299.20)ng·h·mL-1;MRT:(6.31±0.75),(5.98±0.71), (6.18±0.97) h; CL/F: (30. 10 ± 13.67), (29.58±10.59), (31.18 ±17.51)L·h-1·kg-1;Vd/F:(414.94±159.82),(356.16±139.85),(369.28±322.73)L·kg-1,respectively.

Objective To investigate the epidemiological features of 937 patients wounded in China Wenchuan earthquake. Methods An analysis was done on 937 patients treated in the city of Deyang in aspects fo their gender,age,injury causes,wound sites,complications and misdiagnosis.Results There were more wounded females than males,with ratio of male to female of 1:1.12.The main injury causes were crush injury and falling injury.The most frequent injury sites include head,chest,ankle and foot,tibia and fibula,spine and hip.The rate of misdiagnosis was as high as 15.5%,mainly brain injuries and chest iniuries. Conclusion The main causes are crush iniury and falling in-jury.Lower limb fractures account for the most.While close brain and thoracic injuries are likely to be misdiagnosed.

Objective:To explore the effect of coronary injection of recombinant human prourokinase (rhPro-UK) during PCI for ST-segment elevation acute myocardial infarction (STEMI) patients.Methods:A total of 124 STEMI patients treated in Tangshan Gongren Hospital, Hebei Province from November 2018 to November 2019 were selected as the research objects.They were simply randomized by random number table method into the observation group(63 cases) and the control group(61 cases). Thrombus aspiration was used.The control group was treated with 25 μg/kg tirofiban, and the observation group was injected with 20 mg rhPro-UK into the coronary arteries.After that, both groups underwent emergency PCI treatment.The bleeding degree, myocardial microcirculation indexes, plasma fibrinolytic factor changes, vascular recanalization, ST segment fall of electrocardiogram and changes in left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), cardiac index (CI) were recorded.Results:The peak value of creatine kinase isoenzymes MB (CK-MB) (184.64±21.47) U/L and the peak time of CK-MB (14.32±2.02) h in the observation group were significantly lower than those in the control group((258.94±31.64) U/L, (16.58±2.09) h), the differences were statistically significant ( t=15.345 and 6.123, all P<0.001). After treatment, human tissue plasminogen activator (t-PA) (0.85±0.28) kU/L in the observation group was significantly higher than that in the control group (0.74±0.24) kU/L, human plasminogen activator inhibitor (PAI-1) (0.16±0.05) kU/L.compared with the control group (0.32±0.08) kU/L significantly decreased ( t=2.345, P=0.021; t=13.401, P<0.001); 77.78% (49/63) of the ST-segment complete fall in observation group was significantly higher than 54.10% (33/61) of the control group ( Z=7.758; P=0.005), and 4.76% (3/63) in the observation group without a fall in ST segment was significantly lower than 19.67% (12/61) of the control group ( Z=6.480; P=0.011). The LVEDD at 7 days, 14 days and the LVESD at 7 days and 14 days in the observation group were (49.37±3.14) mm, (48.34±3.03) mm, (33.19±2.23) mm and (32.05±2.23) mm respectively, which were significantly lower than those in the control group at 7 days, (50.64±3.03) mm, (49.66±2.83) mm, (34.86±1.73) mm and 14 days, (33.74±1.97) mm respectively ( P<0.05 or P<0.001). The LVEF of 7 days and 14 days after treatment were (56.32±4.97)% and (59.23±5.11)%, which were significantly higher than those of the control group (54.46±4.87)% and (57.18±4.33)% ( P<0.05 or P<0.001). CI at 7 days and 14 days after treatment were (3.65±0.22) L/ (min·m 2) and (3.76±0.21) L/(min·m 2), which were significantly higher than those of the control group (3.48±0.25) L/(min·m 2) and (3.56±0.24) L/(min·m 2)( P<0.05 or P<0.001). Conclusion:STEMI patients treated by intraoperative coronary injection of Rhpro-UK versus tirofeban, can further improve the total bleeding rate and the vascular recanalculation rate, and also significantly improve plasma fibrinolysis factor, myocardial microcirculation and cardiac function.This provides an alternative to the treatment of myocardial infarction in patients with STEMI.

Objective To study the effect and mechanisms of chloride channel blocker 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) on thansforming growth factor β1 (TGF-β1) induced human conjunctival fibroblasts (HConF) fibrosis.Methods Cell counting kit (CCK-8) was used to screen out the optimal TGF-β1 treatment time and the optimal NPPB concentration.The cells were divided into control group,TGF-β1 treatment group and TGF-β1+NPPB group.Cell proliferation and cell cycle were detected by CCK-8 and flow cytometer,respectively.Cell migration ability were observed by scratch and transwell migration assays.Western blot and Real time-PCR were used to detect the expression of collagen Ⅰ (COL-Ⅰ),fibronectin (FN) and α-smooth muscle actin (α-SMA).The phosphorylation level of PI3K and Akt were measured by Western blot.Results TGF-β1 promotes cell proliferation in a time-dependent manner.There was no statistically significant difference in A values between 48 hours and 72 hours after TGF-β1 treatment (P =0.064).Forty-eight hours was selected as the most appropriate time for TGF-β1 treatment.NPPB inhibited HConF cell proliferation in a concentration-dependent manner.Compared with the control group,the proliferation A values of cells in the 50 mol/L and 100 mol/L NPPB groups were significantly reduced (P =0.020,0.000),and 100 mol/L was selected as the optimal concentration of NPPB.The cell proliferation A value,migration area and migration cell number of TGF-β1 +NPPB group were significantly lower than those of TGF-β1 treatment group (all at P＜0.05).Compared with the control group and TGF-β1 +NPPB group,the proportion of G1 phase cells in the TGF-β1 treatment group was reduced,and the proportion of cells in the S phase and G2/M phase were increased,with statistically significant differences between them (all at P ＜ 0.05).The protein and mRNA expression of α-SMA,COL-Ⅰ and FN in the TGF-β1 treatment group were higher than those in the control group and TGF-β1+NPPB group,with statistically significant differences between them(all at P＜0.05);the ratios of p-PI3K/PI3K and p-Akt/Akt in the TGF-β1 treatment group were significantly higher than those in the control group and TGF-β1 +NPPB group,with statistically significant differences between them (all at P＜0.05).Conclusions NPPB may inhibit TGF-β1 induced HConF fibrosis process by inhibiting phosphorylation of PI3K and Akt.

OBJECTIVETo design and manufacture a new custom-made artificial articular cartilage of femoral condyle based on rapid prototyping technique and explore a method to solve the necroses of allocartilage in hemi joint allotransplantation.

METHODSDesign the new custom-made artificial articular cartilage of femoral condyle. The allograft and the patient distal femurs were scanned with Picker 6000 spiral computed tomography (CT) with 1.0 slice thickness and pitch of 1.5, reconstructed the distal femurs in Voxel Q image workstation with volume rendering technique. Then downloaded the transaxial 2D image data to personal computer at 0.1 mm interval and converted it into 2D digitized contour data by using image processing software developed by our team. The 3D wire frame and solid images of femoral condyle could be reconstructed when the 2D digitized contour data were input into image processing software Surfacer 9.0 (Imageware Company, USA). Subsequently based on the clinical experience and the need of design, the 3D contour image of articular cartilage was extracted from the surrounding. Based on the extracted 3D contour image, the computer-aided design (CAD) of the custom-made artificial articular cartilage was accomplished in Surfacer software, converted the CAD model into RP data format. Standard triangularization language, imported into the LPS600 rapid prototyping machine (Hengtong Company, Xi'an Jiaotong University, China), and the resin prototype was achieved. Then the resin model was used as a positive mould to build up a silica gel negative mould, the negative mould was sent to the factory to manufacture Ti-6Al-4V alloy articular cartilage through ordinary mould-melted founding process. Finally, the whole metal cartilage was completed after melting two special cages on it. A patient was selected to clinical applying.

RESULTSA new custom-made artificial articular cartilage of femoral condyle was made. It was press-fit well to the subchondral bone of the allograft bone. The patient's one and half year follow-up result was excellent.

CONCLUSIONSWe design and manufacture a new custom-made artificial articular cartilage of femoral condyle based on rapid prototyping technique. The result shows that the manufacturing process has the advantage of rapidness and precision that are very important for individualized artificial implant manufacturing. The artificial articular cartilage is press-fit well and could be a good idea to solve the necroses of allocartilage in hemijoint allotransplantation.

Adolescent ; Arthroplasty, Replacement, Knee ; Bone Transplantation ; Cartilage, Articular ; Computer-Aided Design ; Femoral Neoplasms ; surgery ; Follow-Up Studies ; Humans ; Knee Prosthesis ; Male ; Neoplasm Recurrence, Local ; surgery ; Osteosarcoma ; surgery ; Prosthesis Design ; methods ; Transplantation, Homologous

A highly sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of retinamido-ester in rat plasma was developed and validated. A simplified protein precipitation with acetonitrile was employed for the sample preparation. The separation was carried out on an Agilent TC C18 column (150 mm x 4.6 mm ID, 5 microm particle size) with the mobile phase consisted of methanol-water-formic acid (93: 7: 0.1). Simvastatin was used as internal standard. The detection was performed on a trap-quadrupole tandem mass spectrometer by selected reaction monitoring (SRM) scan mode via atmospheric pressure chemical ionization (APCI). The range of calibration curve was 0.05-50 ng x mL(-1) and the limit of quantification was 10 pg x mL(-1). The intra- and inter-day precision values were between 95.97% and 104.43%, and RSD was between 4.63% and 10.69%, respectively. This method was applied to determine the pharmacokinetic parameters. The main pharmacokinetic parameters of retinamido-ester after oral administration via gastric gavage of 2.5, 5, 10 mg x kg(-1) were as follows, T(1/2): (11.28 +/- 7.23), (8.90 +/- 3.82), (8.01 +/- 5.65) h; AUC(0-infinity): (103.41 +/- 61.46), (190.23 +/- 74.99), (421.66 +/- 229.20) ng x h x mL(-1); MRT: (6.31 +/- 0.75), (5.98 +/- 0.71), (6.18 +/- 0.97) h; CL/F: (30.10 +/- 13.67), (29.58 +/- 10.59), (31.18 +/- 17.51) L x h(-1) x kg(-1); Vd/F: (414.94 +/- 159.82), (356.16 +/- 139.85), (369.28 +/- 322.72) L x kg(-1), respectively.
Administration, Oral ; Animals ; Antineoplastic Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, Liquid ; methods ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods ; Tretinoin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics

OBJECTIVETo compare the expressions of transforming growth factor alpha (TGFalpha), tumor necrosis factor alpha (TNFalpha), and vascular endothelial growth factor (VEGF) between pheochromocytoma (PHEO) tissues and normal adrenal medulla tissues.

METHODSThe mRNA expressions of TGFalpha, TNFalpha, and VEGF detected by RT-PCR, were compared between 22 PHEO tissues and 18 normal adrenal medulla tissues (according with the principle of medical ethnics). Immunohistochemistry staining was performed on 27 PHEO tissues and 14 normal adrenal medulla tissues. The comparisons of the protein expression of TGFalpha, TNFalpha, and VEGF were analyzed in both of PHEO tissues and normal adrenal medulla tissues.

RESULTSCompared with normal adrenal medulla tissues, the expressions of TGFalpha and TNFalpha mRNA and protein were higher in PHEO tissues, and VEGF145 mRNA expression was also higher in PHEO tissues, while there was no significant difference of the mRNA expression of VEGF121 and VEGF165 between these two tissues. Positive staining rates for VEGF of endothelial cells and tumor cells were higher in PHEO tissues than in normal adrenal medulla tissues. Expressions of the TGFalpha, TNFalpha, and VEGF protein were higher in extra-adrenal PHEO than in adrenal PHEO. The TNFalpha immunohistochemistry staining rate was higher in the malignant or multiple PHEO than in the benign or single PHEO.

CONCLUSIONSThe mRNA and protein expressions of TGFalpha, TNFalpha, and VEGF are higher in PHEO tissues than those in normal adrenal medulla tissues. Expressions of these cytokines vary in PHEO with different characteristic.

Adrenal Gland Neoplasms ; metabolism ; Adrenal Medulla ; metabolism ; Humans ; Pheochromocytoma ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Transforming Growth Factor alpha ; biosynthesis ; genetics ; Tumor Necrosis Factor-alpha ; biosynthesis ; genetics ; Vascular Endothelial Growth Factors ; biosynthesis ; genetics