Objective To evaluate the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in diabetes mellitus-induced reduction of hypoxic postconditioning (HPO)-induced protection of cardiomyocytes and the relationship with glycogen synthase kinase-3β (GSK-3β)-mediated mitochondrial apoptotic pathway.Methods H9c2 cells incubated in high-glucose (30 mmol/L) medium for 24 h were divided into 6 groups (n =5 each) using a random number table:normoxia group (group N),hypoxia-reoxygenation (H/R) group,group HPO,PTEN gene silencing normoxia group (group P-N),PTEN gene silencing H/R group (group P-H/R),and PTEN gene silencing HPO group (group P-HPO).H9c2 cells were exposed to 95％ N2-5％ CO2 for 4 h followed by 2 h reoxygenation with 90％ O2-10％ CO2.HPO was induced by 3 cycles of 5 min reoxygenation followed by 5 min hypoxia before reoxygenation.At the end of reoxygenation,the level of lactate dehydrogenase (LDH) in the supernatant was detected by enzyme-linked immunosorbent assay,the changes in mitochondrial membrane potential (MMP were assessed by JC-1 fluorescence assay,the cell apoptosis was detected by AnnexinV-FITC/PI flow cytometry,and the expression of PTEN and phosphorylated GSK-3β (p-GSK-3β) was determined by Western blot.The JC-1 monomer/polymer ratio and apoptosis rate were calculated.Results Compared with group N,the amount of LDH released,JC-1 monomer/polymer ratio and apoptosis rate were significantly increased,and the expression of PTEN was up-regulated in H/R and HPO groups (P＜0.05).There was no significant difference in the parameters mentioned above between group H/R and group HPO (P＞0.05).Compared with group HPO,the amount of LDH released,JC-1 monomer/polymer ratio and apoptosis rate were significantly decreased,PTEN expression was down-regulated,and the expression of p-GSK-3β was up-regulated in group P-HPO (P＜0.05).Compared with group N,the expression of PTEN was significantly down-regulated,and no significant changes were found in the other parameters mentioned above in group P-N (P＞0.05).Compared with group H/R,the expression of PTEN was significantly down-regulated,and no significant changes were found in the other parameters mentioned above in group P-H/R (P＞0.05).Conclusion PTEN is involved in diabetes mellitus-induced reduction of HPO-induced protection of cardiomyocytes,and the mechanism is associated with PTEN-induced activation of GSK-3β-modulated mitochondrial apoptotic pathway.

Objective To investigate the relationship between high-sensitivity C-reactive protein(hsCRP), pulse pressure(PP) and microalbuminuria(MAU) in patients with essential hypertension.Methods Consecutive 60 patients with essential hypertension were classified based on the MAU level:patients with MAU(n=30) and the group of patients with normoalbuminuria(NMAU,n=30) with 30 healthy subjects as control.MAU,hsCRP,PP were determined.Results The level of hsCRP and pulse pressure in MAU group were higher than those in NMAU patients and healthy subjects (P

Abstract: Objective - - To establish a pre column derivatization high performance liquid chromatography method for detecting Methods dimethyl sulfate (DMS) in workplace air. DMS in workplace air was collected with mercaptopyridine impregnated （ silicone tube. The derivative of DMS and mercaptopyridine was eluted by mobile phase phase A: water, phase B: acetonitrile, ∶ the volume ratio was 40 60) , and separated with a C18 column, then detected with diode array detector and quantitated by a Results - standard curve. The linear range of DMS was 0.17 40.00 mg/L, with the correlation coefficient of 0.999 95. The detection limit and the lower limit of quantitation were 0.05 and 0.17 mg/L respectively. The minimum detection concentration and minimum quantitation concentration were 0.02 and 0.04 mg/m³, respectively (air sample volume of 4.5 L, 1.0 mL sample - - - solution). The average desorption efficiency was 98.40% 102.00%. The within run and between run relative standard deviations - - were 0.61% 3.92% and 1.71% 6.00%, respectively. The samples could be stored at room temperature for at least 14 days. Conclusion This method can be used to detect DMS in workplace air.

Abstract: Nitrobenzene compounds (NBCs) are widely used in the world. It has 40 isomers such as nitrobenzene, dinitrobenzene and nitrotoluene, that are highly toxic and difficult to degrade and can cause harm to human health in different degrees. At pres⁃ ent, there is no unified standard method and occupational exposure limit for the detection of NBCs in the air. In terms of sampling medium, solid adsorption tube is mostly used for trapping vapor state NBCs, and filter membrane and solid adsorption tube are mostly used in series for sampling coexist NBCs in vapor state and aerosol state. In the detection methods, gas chromatography and liquid chromatography are common, and ultraviolet spectrophotometry, Raman spectroscopy, ion migration spectrometry and some other rapid response methods and technologies are also used in the detection of NBCs. In the detection of NBCs by gas chro⁃ matography, capillary column separation is commonly used, and the main detectors are flame ionization detector, electron capture detector and mass spectrometry detector. It is of practical significance to establish a method with high sensitivity, strong practica⁃ bility, convenient operation, and can simultaneously collect and detect a variety of NBCs in different states.

This study is to report the study of protective effects of myricitrin against oxidative stress-induced apoptosis of vascular endothelial cells and the investigation of the possible mechanisms of action of myricitrin. The model of H2O2-induced apoptosis of vascular endothelial cells was used to determine the protective effects of myricitrin. The levels of LDH, MDA and the activities of SOD, NO were measured using the respective kits. The H2O2-induced apoptosis of vascular endothelial cells was detected using MTT reduction, TUNEL assay, JC-1 and ROS staining. The activation of Caspase-3 was also measured by fluorometry. The expression of apoptosis-related proteins was determined with Western blotting assay. Myricitrin had significant protective effects against H2O2-induced apoptosis of vascular endothelial cells in a time- and dose-dependent manner. The results show that myricitrin could attenuate H2O2-induced decrease in the activities of SOD (P < 0.01). Myricitrin could decrease the levels of LDH, MDA and increase cell viability and the mitochondrial membrane potential (P < 0.01). Myricitrin had protective effects in a dose-dependent manner between 32 micromol x L(-1) to 64 micromol x L(-1). Myricitrin pretreatment could attenuate H2O2-induced increase of p-ERK. Moreover, myricitrin pretreatment could up-regulate the expression of the anti-apoptotic protein Bcl-2, down-regulate the expression of the pro-apoptotic protein Bax, and decrease the expression of Caspase-3, 9. In conclusion, myricitrin had significant protective effects against H2O2-induced apoptosis of vascular endothelial cells. Myricitrin can enhance the activities of anti-oxidative enzymes and decrease the production of free radicals. The possible mechanisms of action of myricitrin are due to myricitrin-mediated inhibition of phosphorylation of the apoptosis signaling pathways-related kinase ERK, up-regulation of the expression of the anti-apoptotic protein, and down-regulation of the expression of the pro-apoptotic protein.
Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Endothelial Cells ; cytology ; Flavonoids ; administration & dosage ; pharmacology ; Humans ; Hydrogen Peroxide ; toxicity ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Membrane Potential, Mitochondrial ; drug effects ; Nitric Oxide ; metabolism ; Oxidative Stress ; drug effects ; Protective Agents ; administration & dosage ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Reactive Oxygen Species ; metabolism ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism

In this paper, duloxetine was chosen as the lead compound. The pharmacophores with 5-HT(1A) antagonism activity were used to replace the naphthyl of duloxetine. A series of duloxetine derivatives had been designed and synthesized and whose structures were confirmed with elemental analysis, MS and H NMR. All synthesized compounds were tested by tail suspension test and forced swimming test in vivo. The test results revealed that most of the compounds have shown better activity than duloxetine at the same dosage. Some of them are worth to be studied further.
Animals ; Antidepressive Agents ; chemical synthesis ; chemistry ; pharmacology ; Duloxetine Hydrochloride ; Hindlimb Suspension ; Male ; Mice ; Mice, Inbred ICR ; Molecular Structure ; Serotonin 5-HT1 Receptor Antagonists ; pharmacology ; Structure-Activity Relationship ; Swimming ; Thiophenes ; chemical synthesis ; chemistry ; pharmacology

OBJECTIVETo evaluate the value of (18)F-FDG PET-CT for assessment of therapeutic response and prediction of patient outcome after concurrent chemoradiotherapy (CCRT) of non-small cell lung cancer (NSCLC).

METHODSForty six patients with histologically proven stage III NSCLC had two repeated (18)F-FDG PET-CT scans either one week before therapy and at the dose of 40 ∼ 50 Gy. The SUV(max) and changes of the two groups were compared with (1) the therapeutic response and (2) treatment results and long-term survival.

RESULTSOf the 46 eligible cases, the pretreatment SUV(max) of the responding and non-responding groups was 7.59 ± 3.14 and 14.72 ± 4.67, respectively. The midtreatment SUV(max) of the two groups was 2.89 ± 1.39 and 9.82 ± 3.31, respectively. Significant difference(t = 4.74, P = 0.001;t = 7.23, P = 0.001) in SUV(max) was observed both before and during treatment. Furthermore, the percentage change of pretreatment and midtreatment SUV(max) was ΔSUV(max) = 61.9% ± 8.7% and ΔSUV(max) = 33.6% ± 9.0%, also with a significant difference between the two groups (t = 2.83, P = 0.007). In addition, the 1-year survival rate of the the responding and non-responding groups was 68.0% and 38.1%, respectively. The 2-year survival rate of the two groups was 64.0% and 33.3%, respectively, with a significant difference between the two groups (P = 0.043, P = 0.038).

CONCLUSION(18)F-FDG PET-CT is highly effective in detecting therapeutic response in stage III NSCLC patients. The analysis of percentage change of SUV(max) provides incremental value in early prediction of therapeutic response and patient outcome.

Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; diagnostic imaging ; metabolism ; pathology ; therapy ; Cisplatin ; administration & dosage ; Combined Modality Therapy ; Female ; Fluorodeoxyglucose F18 ; pharmacokinetics ; Humans ; Lung Neoplasms ; diagnostic imaging ; metabolism ; pathology ; therapy ; Male ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Positron-Emission Tomography ; Prognosis ; Radiopharmaceuticals ; pharmacokinetics ; Radiotherapy, Conformal ; Tomography, X-Ray Computed ; Vinblastine ; administration & dosage ; analogs & derivatives

OBJECTIVETo observe clinical characteristics of herb-induced liver injury (HILI).

METHODSGeneral conditions, medical history, clinical manifestations, biochemical indices, prognosis, and Roussed Uclaf Causality Assessment Method (RUCAM) scores were retrospectively analyzed in 595 inpatients at 302 Military Hospital between January 2009 and January 2014.

RESULTSThere were 423 cases (accounting for 71.1%) were females with multiple onset age ranging 41 to 50 years old. The median time from starting Chinese herbs to the occurrence of liver injury (LI) was 30 days (15-75 days), and 511 cases (85.9%) were classified as hepatocellular injury. Chinese herbs inducing HILI were mainly used for skin disease (102 cases, 17.1%), osteoarticular disease (57 cases, 9.6%), and gastrointestinal disease (49 cases, 8.2%), covering 207 kinds of Chinese patent medicines. Polygonum multiflorum, Psoralea corylifolia, and Corydalis ambigua were often seen in Chinese prescriptions. In RUCAM scoring, 451 HILI patients (accounting for 74.1%) were very possibly associated with Chinese herbs. Liver failure occurred in 47 HILI patients (accounting for 7.9%), cirrhosis in 45 patients (accounting for 7.6%), chronic HILI in 80 patients (accounting for 13.4%), 27 (4.5%) died, and only 2 (0.3%) underwent liver transplantation.

CONCLUSIONSChinese herbs could cause LI or even death. Attention should be paid to herbal hepatotoxicity and improving monitoring system of HILI.

Chemical and Drug Induced Liver Injury ; diagnosis ; Female ; Humans ; Prognosis ; Retrospective Studies

Because of irregular shapes of Chinese herbal pieces, we simplified the previously deduced general extraction kinetic model for TCMs, and integrated particle diameters of Chinese herbs that had been hard to be determined in the final parameter "a". The reduction of the direct determination of particle diameters of Chinese herbs was conducive to increase the accuracy of the model, expand the application scope of the model, and get closer to the actual production conditions. Finally, a simplified model was established, with its corresponding experimental methods and data processing methods determined. With total flavonoids in Scutellariae Radix as the determination index, we conducted a study on the adaptability of total flavonoids extracted from Scutellariae Radix with the water decoction method in the model. The results showed a good linear correlation among the natural logarithm value of the mass concentration of total flavonoids in Scutellariae Radix, the time and the changes in the natural logarithm of solvent multiple. Through calculating and fitting, efforts were made to establish the kinetic model of extracting total flavonoids from Scutellariae Radix with the water decoction method, and verify the model, with a good degree of fitting and deviation within the range of the industrial production requirements. This indicated that the model established by the method has a good adaptability.
Chemical Fractionation ; methods ; Drugs, Chinese Herbal ; isolation & purification ; Flavonoids ; isolation & purification ; Kinetics ; Models, Theoretical ; Scutellaria baicalensis ; chemistry ; Water ; chemistry

OBJECTIVE To explore the mechanism of Gαiand Gβγsubunits on dexmedetomidine (DMED)-induced sedation.METHODS Kunming mice were randomly placed into three groups(DMED group, DMED+dbcAMP/rolipram/gallein/M119 group, dbcAMP/rolipram/gallein/M119 group) to explore the regulation of dbcAMP/rolipram/gallein/M119 on DMED-induced sedation by establishing loss of righting reflex (LORR) model. DbcAMP/rolipram was intracerebroventricular injected and gallein/M119 was intraperitoneal injected 15 min before DMED intravenous injection. In CHO-α2A-AR cells, after administration of DMED/gallein/M119, the regulation on the cAMP accumulation stimulated by Forskolin (FSK) was detected, so was the intracellular calcium ion concentration ([Ca2+]i. The levels of pERK/pCREB were detected by Western Blot to explore the key signal molecules involved in DMED-induced sedation. RESULTS The ED50of DMED-induced LORR (200.0 nmol·kg-1) was increased to 375.0 or 433.3 nmol·kg-1by pre-treatment with cAMP analog dbcAMP(50 nmol/5μl per mouse)or phosphodies-terase 4 inhibitor rolipram(100 nmol/5μl per mouse).In addition,the ED50of DMED-induced LORR was decreased to 113.6 or 136.5 nmol·kg-1when pre-treated with Gβγsubunits inhibitor M119(100 mg·kg-1) or gallein(100 mg·kg-1)respectively.Administration of dbcAMP,rolipram,gallein or M119 alone had little effect on LORR of mice.Gallein(10 μmol·L-1)significantly inhibited forskolin-stimulated cAMP accumu-lation in CHO-α2A-AR cells.Compared with Gβγsubunits inhibitors or DMED alone,[Ca2+]iand pERK1/2 significantly increased after co-administration of Gβγsubunits inhibitors with DMED.DbcAMP(5 μmol·L-1) or rolipram (5 μmol·L- 1) alone had little effect on ERK1/2 phosphorylation, but decreased DMED-induced ERK1/2 phosphorylation after co-administration with DMED. Gβγsubunit inhibitors treatment increased DMED-induced phosphorylation of CREB, whereas dbcAMP or rolipram had little effect on pCREB induced by DMED.CONCLUSION Gβγsubunits might inhibit DMED-induced sedation through cAMP and pERK1/2 pathway,which was opposite to Gαisubuint.