Metabolic reprogramming plays a crucial role in the pathogenesis of cardiovascular diseases(CVD).Lactate,a metabolite of glycolysis,is now considered an important cellular signaling molecule involved in regulating various metabolic processes within the microenvironment.Recently discovered lactylation modifications have been found to play significant roles in CVD such as atherosclerosis(As),vascular or valve calcification,myocardial infarction,heart failure(HF),and pulmonary hypertension(PH).This review summarizes the regulatory mechanisms of lactate and lactylation modifications in these CVD,aiming to provide new insights for their precise prevention and treatment strategies.

Metabolic reprogramming plays a crucial role in the pathogenesis of cardiovascular diseases(CVD).Lactate,a metabolite of glycolysis,is now considered an important cellular signaling molecule involved in regulating various metabolic processes within the microenvironment.Recently discovered lactylation modifications have been found to play significant roles in CVD such as atherosclerosis(As),vascular or valve calcification,myocardial infarction,heart failure(HF),and pulmonary hypertension(PH).This review summarizes the regulatory mechanisms of lactate and lactylation modifications in these CVD,aiming to provide new insights for their precise prevention and treatment strategies.

Objective:To investigate the protective effect of moxibustion on joints and its influence on the expression levels of S100 calcium binding protein A8(S100A8),S100 calcium binding protein A9(S100A9),serum amyloid A1(SAA1),and related inflammatory factors in rats with adjuvant arthritis(AA).Methods:Forty Wistar rats were randomly divided into a normal group,a model group,a moxibustion group,and a medication group,with 10 rats in each group.Except for the normal group,AA models were established in the other three groups by exposing rats to wind-cold-dampness environmental conditions combined with complete Freund's adjuvant.After successful modeling,the moxibustion group received moxibustion intervention,while the medication group was administered tripterygium glycosides tablets via oral gavage.The normal and model groups underwent similar handling and fixation without additional interventions.After 15 d of intervention,hematoxylin-eosin staining was used to assess pathological changes in the knee joint synovial membrane.Western blotting was performed to detect the protein expression of S100A8,S100A9,and SAA1 in the synovial tissue.Enzyme-linked immunosorbent assay was used to measure the serum levels of interferon(IFN)-γ,interleukin(IL)-6,and IL-23.Results:Compared to the normal group,the model group exhibited significantly increased protein expression of S100A8,S100A9,and SAA1 in the knee joint synovial tissue,as well as elevated serum levels of IFN-γ,IL-6,and IL-23(P<0.01).Histopathological analysis revealed marked synovial hyperplasia and extensive infiltration of inflammatory cells in the model group.Compared to the model group,both the moxibustion and medication groups showed significant reductions in the protein expression of S100A8,S100A9,and SAA1 in the synovial tissue,as well as decreased serum levels of IFN-γ,IL-6,and IL-23(P<0.01).Additionally,synovial tissue in these two groups displayed minimal hyperplasia and only mild inflammatory cell infiltration.Notably,compared to the moxibustion group,the medication group exhibited significantly higher protein expression of S100A9 in the synovial tissue(P<0.05),while no significant differences were observed in the expression of S100A8,SAA1,or serum levels of IFN-γ,IL-6,and IL-23(P>0.05).Both intervention groups showed comparable degrees of synovial inflammation,clear tissue structure,and no obvious hyperplasia.Conclusion:Moxibustion can alleviate joint swelling and reduce inflammatory responses in AA rats.Its mechanism may involve regulating the protein expression of S100A8,S100A9,and SAA1 in the knee joint synovial tissue.

Objective:To investigate the protective effect of moxibustion on joints and its influence on the expression levels of S100 calcium binding protein A8(S100A8),S100 calcium binding protein A9(S100A9),serum amyloid A1(SAA1),and related inflammatory factors in rats with adjuvant arthritis(AA).Methods:Forty Wistar rats were randomly divided into a normal group,a model group,a moxibustion group,and a medication group,with 10 rats in each group.Except for the normal group,AA models were established in the other three groups by exposing rats to wind-cold-dampness environmental conditions combined with complete Freund's adjuvant.After successful modeling,the moxibustion group received moxibustion intervention,while the medication group was administered tripterygium glycosides tablets via oral gavage.The normal and model groups underwent similar handling and fixation without additional interventions.After 15 d of intervention,hematoxylin-eosin staining was used to assess pathological changes in the knee joint synovial membrane.Western blotting was performed to detect the protein expression of S100A8,S100A9,and SAA1 in the synovial tissue.Enzyme-linked immunosorbent assay was used to measure the serum levels of interferon(IFN)-γ,interleukin(IL)-6,and IL-23.Results:Compared to the normal group,the model group exhibited significantly increased protein expression of S100A8,S100A9,and SAA1 in the knee joint synovial tissue,as well as elevated serum levels of IFN-γ,IL-6,and IL-23(P<0.01).Histopathological analysis revealed marked synovial hyperplasia and extensive infiltration of inflammatory cells in the model group.Compared to the model group,both the moxibustion and medication groups showed significant reductions in the protein expression of S100A8,S100A9,and SAA1 in the synovial tissue,as well as decreased serum levels of IFN-γ,IL-6,and IL-23(P<0.01).Additionally,synovial tissue in these two groups displayed minimal hyperplasia and only mild inflammatory cell infiltration.Notably,compared to the moxibustion group,the medication group exhibited significantly higher protein expression of S100A9 in the synovial tissue(P<0.05),while no significant differences were observed in the expression of S100A8,SAA1,or serum levels of IFN-γ,IL-6,and IL-23(P>0.05).Both intervention groups showed comparable degrees of synovial inflammation,clear tissue structure,and no obvious hyperplasia.Conclusion:Moxibustion can alleviate joint swelling and reduce inflammatory responses in AA rats.Its mechanism may involve regulating the protein expression of S100A8,S100A9,and SAA1 in the knee joint synovial tissue.

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.

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 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.