Autophagy is a “self-devouring” biological process of the degradation of organelles and proteins by lysosomes in eukaryotic cells. In the past few years, some results revealed that autophagy played an important role in the regulation of vascular calcification. This review summarized the recent studies on autophagy in the process of vascular calcification, and discussed the effects of electrolyte imbalance, matrix vesicle release, oxidative stress, inflammatory reaction of vascular endothelial cells, and lipid metabolism in autophagy. The research progress of β-catenin/AMPK/CREB/Nrf2-ARE/Erα signal transduction pathways in autophagy induction was reviewed.

Objective To investigate the hemodynamic changes in a tortuous coronary to elucidate the effects of tortuosity on coronary perfusion and wall shear stress (WSS). Methods A single tortuous and non-tortuous patient-specific left anterior descending (LAD) coronary artery cases were selected. Two LAD models with and without coronary tortuosity were reconstructed in Mimics software and then transferred to the ANSYS Fluent software for performing computational fluid dynamics (CFD) simulation. The hemodynamic characteristics of both the LAD models were compared. Results The vessel WSS of the tortuous coronary artery clearly decreased in the bend section where the maximum curvature was larger than 1 mm-1.Such a scenario could led to an inadequate blood supply in the downstream vessels. A low WSS (0-26 Pa) acted on the outer wall of the bend, whereas the inner wall of the bend had a high WSS (>100 Pa). The mean WSS of the non-tortuous and tortuous models was 10.79 Pa and 36.12 Pa, respectively. The overall WSS of the tortuous model was larger compared with that of the non-tortuous model. Conclusions Coronary tortuosity increased the overall WSS, which could delay the progress of coronary atherosclerosis.

Objective To investivate the effects of VocaStim?-Master electrical stimulation and pharyngeal muscles training on sleep breathing parameters, clinical symptoms and cognitive functions in stroke patients with obstructive sleep apnea syndrome (OSAS). Methods From December 1st, 2014 to November 30th, 2017, 50 stroke patients complicated with OSAS were divided into control group (n = 25) and research group (n = 25). All the patients received routine medicine and rehabilitation, while the research group accepted VocaStim?-Master electrical stimulation and pharyngeal muscles training in addition, for four weeks. Their symptoms were observed, and tested with polysomnography (PSG) and Mini-Mental State Examination (MMSE) before and after treatment.Results After treatment, the clinical symptoms improved (P < 0.05), while apnea hypopnea index (AHI) (t > 2.270, P < 0.05)and oxygen desaturation index (t > 3.044, P < 0.01) decreased, and average oxygen saturation (SaO2) and lowest SaO2 increased (t > 3.095, P < 0.01), in the research group, compared with those before treatment and those in the control group (P < 0.05), the scores of MMSE increased (t > 2.859, P < 0.01). There was no significant difference of AHI, averge SaO2, lowest SaO2 and oxygen desaturation index during the period of treatment in the control group (P > 0.05), nor for the score of MMSE.Conclusion VocaStim?-Master electrical stimulation combined with pharyngeal muscles training could effectively ameliorate nocturnal sleep apnea symptom and improve cognitive functions in stroke patients complicated with OSAS.

OBJECTIVE:To establish the method for the simultaneous determination of clopidogrel (CLO) and its active metabolites (CATM) and inactive metabolites (CCAM),and to conduct pharmacokinetic study. METHODS:The plasma sam-ple had been derivatized by 2-bromine-3′-methoxy acetophenone(MPB),and was precipitated by acetonitrile. Using carbam-azepine as internal standard,UPLC-MS/MS was adopted. The separation was performed on Waters ACQUITY UPLC HSS T3 column with mobile phase consisted of water(containing 0.1% formic acid)-acetonitrile(containing 0.1% formic acid)using a gradient elution program at the flow rate of 0.50 ml/min. The ESI was equipped and quantitative analysis was operated in posi-tive ion and MRM mode. The mass transition ion-pairs were followed as m/z 322.1→211.8(CLO),m/z 504.1→155.0(the alkyl-ation derivatives of CATM,CATMD),m/z 308.3→198.0(CCAM),m/z 273.2→194.3(internal standard). RESULTS:The lin-ear calibration curves for CLO,CATMD and CCAM were obtained in the concentration range of 0.03-20.00 ng/ml,0.30-200.00 ng/ml and 10.00-10 000.00 ng/ml in plasma,respectively;intra-day and inter-day RSD for them were all less than 15%,and relative error(RE)ranged from -3.5% to 5.7%. Main pharmacokinetic parameters of CLO,CATMD and CCAM in 5 healthy volunteers after oral administration of CLO 300 mg were as follows:cmax were(7.89±5.46),(15.58±8.08),(8 023.33± 1 047.39)ng/ml;tmax were(1.25 ± 0.43),(1.25 ± 0.43),(1.67 ± 0.29)h;t1/2 were (2.31 ± 0.61),(0.64 ± 0.08),(6.53 ± 2.55)h;AUC0-t were(17.19±14.59),(21.39±9.58),(30 648.85±8 026.63)ng·h/ml. CONCLUSIONS:The established method is sensi-tive,rapid and convenient,which is suitable for pharmacokinetic study and plasma concentration determination of CLO and its metabolites.

Objective To investigate induction effect of AGE on oxidative stress and type Ⅰ ,Ⅲcollagen synthesis in rat cardiac fibroblasts and interference effect of RGZ during the course. Methods Incubate rat cardiac fibroblasts with AGE of different concentration ,add RGZ to interfere for 48 h ,and then collect supernatant fluid .Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected by SOD kit and MDA kit separately ,and type Ⅰ ,Ⅲ collagen contents were measured by ELISA. Results When incubating cardiac fibroblasts with RGZ and 200 mg/L AGE together for 48 h , with the rise of RGZ concentration(0.1 ,1 and 10 mol/L) ,SOD activity in the supernatant fluid of cultured cardiac fibroblasts gradually increased [(21.564 ± 1.614) ,(22.323 ± 1.260) ,(23.661 ± 1.562) vs (19.320 ± 0.896) nU/ml ,P<0.05 or P<0.01] ,MDA content gradually decreased [(1.325 ± 0.048) ,(1.279 ± 0.032) ,(1.229 ± 0.045 ) vs (1.629 ± 0.043 ) nmol/ml ,P< 0.01 ] and type Ⅰ ,Ⅲ collagen Contents gradually decreased [(79.17 ± 3.25) ,(60.42 ± 3.58) ,(42.71 ± 5.11) vs (85.54 ± 2.28) ng/ml ,P<0.01 ;(37.52 ± 3.43) ,(27.09 ± 4.75) ,(20.81 ± 3.26) vs (40.75 ± 2.70) ng/ml ,P<0.01] as compared with 200 mg/L AGE group. Conclusion AGE can induce oxidative stress in cardiac fibroblasts and increase type Ⅰ ,Ⅲ collagen contents .RGZ can inhibit oxidative stress in cardiac fibroblasts and synthesis and secretion of type Ⅰ ,Ⅲ collagen induced by AGE. This finding indicates that RGZ may play an important role in the prevention of diabetic myocardial fibrosis.

Clinical internship is a key step for training qualified clinician. This article narrates the measures that the hospital have taken to improve administration of clinical internship and teaching quality on the aspect of clinical intern training, examination and quality control.

Objective To investigate the effects of rosiglitazone on the proliferation,connective tissue growth factor and Smad expression in cultured cardiac fibroblasts induced by advanced glycosylation end-products (AGEs).Methods After being treated with various amounts of rosiglitazone,the cultured neonatal rat cardiac fibroblasts were incubated with AGEs.The status of cardiac fibroblasts proliferation and cell cycle were detected by 3-(4,5-dimethyhhiazol-2-yl) -2,5-diphenyl tetrazolium bromide (MTI) assay and flow cytometry.Furthermore,ELISA technique was applied to identify the level of TGF-β1.The protein expressions of CTGF and Smad in cardiac fibroblasts of neonatal SD rats were detected with Western blotting.Results The exposure of cardiac fibroblasts to AGEs at doses of 0-200 mg/L induced a dose-dependent increase in cell proliferation.At the concentration of rosiglitazooe (0.1,1,and 10 μmol/L),the cell proliferation was reduced compared with 200 mg/L AGEs group by O.823±0.072,0.785±0.060,0.601±0.081 vs 0.981±0.049,respectively (P < 0.05).The increased levels of TGF-β1 in supematants of cultured cardiac fibroblasts stimulated by AGEs were inhibited by rosiglitazone at the concentrations of 0.1,1,10μmol/L by 257.77±9.09,230.29±6.56,200.84±10.26 vs 300.68±8.56,respectively (vs 200 mg/L AGEs,P<0.01).Western blot indicated that pretreatment with rosiglitazone (0.1,1,and 10 μmol/L) inhibited CTGF protein production in a dose-dependent by 0.769±0.108,0.590±0.095,0.534±0.115 vs 1.021±0.113,respectively (vs 200 mg/L AGEs,P<0.01).It was also demonstrated that pretreatment with rosiglitazone (1 and 10 μmol/L) inhibited Smad2 protein production by 0.424±0.059,0.396±O.080 vs 0.572±0.073,respectively (vs 200 mg/L AGEs,P < 0.05 or P < 0.01).Meanwhile pretreatment with rosiglitazone (1 and 10 μmol/L) inhibited Smad4 protein production by 0.580±0.063,0.556±0.051 vs 0.672±0.059,respectively (vs 200 mg/L AGEs,P < 0.05 or P < 0.01).Conclusions The findings suggest that AGEs promote the proliferation of cardiac fibroblasts and stimulate the protein production of Smad and CTGF of cardiac fibroblasts.Rosiglitazone inhibits the above reaction.These results indicate that CTGF/Smad pathway may play an important role in the protective effect of rosiglitazone on myocardial fibrosis.

BACKGROUND: A series of basic researches have confirmed that,the olfactory ensheathing cell transplantation can promote spinal cord regeneration and recover some neurological functions of spinal cord in animal models of spinal cord injury.Some clinical trials also prove that transplantation of olfactory ensheathing cells can indeed improve neurological function in patients with spinal cord injury,and then improve their quality of life.OBJECTIVE: To verify the effectiveness and safety of olfactory ensheathing cell transplantation in repair of neurological function of spinal cord injury patients.METHODS: The aborted embryonic olfactory bulb was collected and digested into single olfactory ensheathing cells.After they were cultured and purified 2 weeks,olfactory ensheathing cell suspension was prepared.A total of 213 cases of spinal cord injury were selected.Under general anesthesia,the prepared olfactory ensheathing cell suspension was injected through several target sites surrounding the injured spinal cord.ASIA scale was used to assay the patients before transplantation,3 weeks to 2 months after transplantation,so as to evaluate spinal cord recovery.RESULTS AND CONCLUSION: The spinal cord nerve function in all patients altered to different degrees at 3 weeks postoperation.Spinal cord function score,the sensory and motor functions were significantly increased compared with preoperation(P < 0.001),and showed a trend of continuous improvement with time; the patients were visited as follow-up for no more than 5 years,and no impairment of the restored nervous function or transplant adverse reactions were observed.It is confirmed that olfactory ensheathing cell transplantation can promote the recovery of nerve function in patients with spinal cord injury,it can restore and improve some spinal cord functions,and the treatment is safe.

Objective To explore the effect of advanced glycosylation end products (AGEs) on expression of connective tissue growth factor (CTGF) in cultured rat vascular smooth muscle cells (VSMCs) and the mechanism of accelerated atherosclerosis in diabetes. Methods VSMCs were isolated and cultured from the thoracic aorta of rat. Reverse transcription polymerase chain reaction (RT-PCR) and Western immunoblot analysis were used to detect the expression level of CTGF mRNA and protein. Results The expression of CTGF mRNA and protein were increased by AGE-BSA in the time- and dose-dependent manners(P<0.05). Conclusions AGEs may increase the expression activity of CTGF in cultured vascular smooth muscle cells.

The effect of rosiglitazone and advanced glycation end products (AGEs) on the expression of fractalkine in cultured human renal mesangial cells (HRMC) were investigated. Rosiglitazone inhibits the upregulation of fractalkine induced by AGEs in HRMC.