Objective:To investigate the mechanisms underlying the effect of levocarnitine on myocardial cell fibrosis, proliferation, apoptosis and migration.Methods:Between June and December 2022, an overexpression vector for tissue inhibitor-1 of metalloproteinase(TIMP-1)and siRNA TIMP-1 were used to transfect rat H9c2 cardiomyocytes(from the cell bank of the Chinese Academy of Sciences), and transfection efficiency was measured using fluorescence reverse transcription quantitative PCR(RT-qPCR). After treating H9c2 cells with angiotensin Ⅱ(AngⅡ), the expression of the MMP3 and TIMP-1 genes in the cells was detected by RT-qPCR.A CCK8 kit was used to assess the effect of levocarnitine intervention on the proliferation of myofibroblasts after overexpression or knockdown of TIMP-1.The effects of levocarnitine on apoptosis and migration of myofibroblasts were detected by flow cytometry and Transwell assays.Results:The RT-qPCR results showed that the expression level of the MMP3 gene(1.38±0.05)in cardiomyocytes treated with AngⅡ for 24 hours exhibited an upward trend( P<0.01), while the expression level of the TIMP-1 gene(0.71±0.03)showed a downward trend( P<0.01). In addition, H9c2 cells with TIMP-1 overexpression(905.98±24.17)and knockdown(0.18±0.01)%, respectively, were successfully constructed.Based on CCK-8 detection results, knockdown of TIMP-1(86.56±7.98)% was able to promote the proliferation of H9c2 cells induced by levocarnitine( P<0.01). Apoptosis experiments showed that inhibition of TIMP-1 expression(23.22±2.69)significantly reduced the apoptosis level of H9c2 cells induced by levocarnitine( P<0.01). Migration experiments showed that inhibition of TIMP-1 expression(217.67±23.44)significantly promoted the migration ability of H9c2 cells induced by levocarnitine( P<0.01). Conclusions:After intervention to reduce TIMP-1 expression, levocarnitine can promote proliferation, inhibit apoptosis and promote migration of myofibroblasts and may therefore ameliorate myocardial fibrosis.

Sarcopenia is a progressive syndrome associated with aging, generalized loss of skeletal muscle mass, muscle strength and function.It is closely related to the occurrence of adverse events such as ambulatorydysfunction, falls and fractures in the elderly, and seriously affects the quality of life of the elderly.The etiology of sarcopenia has not been fully elucidated.Various pathophysiological mechanisms such as reduced exercise, genetic factors, age-related hormone changes, malnutrition and insufficient protein intake, decreased neuromuscular function, pro-inflammatory cytokines, and myocyte apoptosis are possible factors.Recent studies have found that intestinal microecological changes may be implicated in the occurrence and development of sarcopenia.In this article, we reviewed intestinal microecological changes and their possible role in the mechanisms underlying sarcopenia.

Objective:To investigate the role of Nogo-B in mitochondrial reactive oxygen species(m-ROS)production and vascular remodeling in vascular smooth muscle cells(VSMCs), and to further clarify the molecular mechanism for Nogo-B in m-ROS production via regulating ATP synthase expression.Methods:A mouse model of vascular remodeling was established.The expression of Nogo-B in mouse smooth muscle cells was detected.Forty mice were divided into the AAV-NC+ control, AAV-NC+ angiotensin Ⅱ(AngⅡ), AAV-Nogo-B+ control and AAV-Nogo-B+ AngⅡ groups(n=10 for each group). VSMCs cultured in vitro were divided into the control group and the Nogo-B overexpression group(Ad-Nogo-B). The expression of Nogo-B in VSMCs in vitro stimulated with AngⅡ was detected.Through experiments conducted in vivo, Nogo-B was overexpressed in VSMCs, then VSMCs were stimulated with AngⅡ, and m-ROS production, tissue fibrosis and mitochondrial function were examined.The regulatory effects of Nogo-B on m-ROS production were explored.Molecular mechanisms for NoGO-B in vascular remodeling via regulating ATP synthase/m-ROS production were examined. Results:Compared with the control group, the expression of Nogo-B was decreased in VSMCs treated with AngⅡ(0.36±0.13 vs.1.00±0.13, t=8.44, P<0.05). The production of m-ROS, fibrosis and mitochondrial dysfunction were increased in VSMCs during vascular remodeling( P<0.05), while overexpression of Nogo-B significantly reduced m-ROS production, fibrosis and mitochondrial dysfunction( P<0.05). ATP synthase expression in VSMCs was positively regulated by Nogo-B.ATP synthase expression was higher in the AAV-Nogo-B+ AngⅡ group than in the AAV-NC+ AngⅡ group(0.86±0.14 vs.0.49±0.17, t=-3.97, P<0.05). The production of m-ROS was reduced by Nogo-B and was lower in the AAV-Nogo-B+ AngⅡ group than in the AAV-NC+ AngⅡ group(1.28±0.34 vs.3.26±0.57, t=7.18, P<0.05). Meanwhile, the ability of Nogo-B to mitigate the deleterious effects of oxidative stress in VSMCs could be offset by oligomycin. Conclusions:Nogo-B participates in vascular remodeling by regulating ATP synthase-mediated m-ROS production.

Objective To investigate the health services use of hierarchical medical system in elderly patients with type 2 diabetes mellitus in the community and to provide information for improving hierarchical medical system.Methods A survey of 684 T2DM patients aged 60 years and older was conducted in the Hua Mu Community Health Service Center in Shanghai from September 2014 to August 2016.And the data about health services visits for T2DM and its complications were collected in the latest one year.Based on different habits for patients receiving medical service,all patients were divided into two groups:the hierarchical treatment group and control group.All clinical and follow-up data were compared between two groups.Results 368 patients (53.8 ％)took on a priority in clinical visits to community health service center.There were no significant differences in age,gender,education,marriage,income,health insurance and duration of diabetes between the two groups(all P＞0.05).The acquired written health information about diet and exercise were much more in hierarchical treatment group than in the control group during one year.Although the rate of screening of diabetic nephropathy was similar between the two groups (P ＞ 0.05),the rate for retinopathy,neuropathy,vascular and diabetic foot was lower in hierarchical treatment group than in control group (all P ＜ 0.05).Moreover,the levels of glycosylated hemoglobin,urine albumin-to-creatinine ratio,total cholesterol,triglyceride,low-density lipoprotein cholesterol were similar between the two groups (all P＞0.05),but the level of high-density lipoprotein cholesterol in hierarchical treatment group was lower(P＜0.05).Furthermore,the rates of emergency visiting and hospitalization were lower in hierarchical treatment group than in the control group(both P＜0.001),and there was no significant difference in the average length of hospital stay between two groups (P ＞ 0.05).Conclusions Hierarchical medical system is favourable for the rational use of medical resources,but it is not yet quite perfect.Further improvements are still needed.

Objective To explore the relationship between primary hypertension and benign prostatic hyperplasia (BPH) in the elderly.Methods From August 2010 to June 2012,135 consecutively referred patients with BPH were enrolled in this study,in which 70 cases were BPH with hypertension,65 cases were isolated benign prostatic hyperplasia.All patients were questioned in detail about history,body weight and height were measured to calculate the body mass index (BMI).Prostate specific antigen (PSA) and fasting plasma glucose (FPG) and lipids were assayed in the study.The international prostate symptom score (IPSS) were recorded.Prostate volume (PV) was detected by abdominal ultrasound.Results The levels of IPSS and PV were higher in BPH with hypertension than simple BPH group [(18.9±7.5)scores vs.(13.2±7.8) scores,P＜0.05 ;(43.0±15.4) ml vs.(39.2 ± 13.9) ml,P＜ 0.05].Pearson analysis showed that PV was positively correlated with age and the years of hypertension (r=0.34,0.29,P＜0.05).After adjustment for age,PV was significantly greater in hypertension group with more than 15 years compared to less than 15 years of hypertension group.Conclusions Hypertension,particularly long-term hypertension is related to BPH in the elderly.The long term of hypertension may accelerate the occurrence and clinical progression of BPH.

Objective To realize the clinical characteristics and treatment strategies in elderly patients with benign prostatic hyperplasia (BPH), and investigate the correlation between severity of BPH and cardiovascular diseases. Methods One hundred consecutively referred patients with BPH were enrolled in this study, and the international prostate symptom score (IPSS) and quality of life (QOL) scores were recorded. All patients were queried in detail about history of cardiovascular disease, and underwent detection of prostate specific antigen (PSA) levels, prostate volume (PV)measurement by abdominal ultrasound. Results PV and serum PSA level increased with age.Forty-eight percent of patients had a moderately enlarged prostate (IPSS 8-19). Patients with BPH had higher incidence of hypertension, diabetes, as well as coronary artery disease (P＜0.05). The most common medical treatments were 5α-reductase inhibitors and a-receptor blockers in our hospital and most patients had good compliance. Conclusions The severity of BPH is correlated with age and morbidity of coronary artery disease. For the drug intervention therapy, 5a-reductase inhibitors have the highest utilization rate.

Objective To explore the distribution characteristics of high density lipoprotein (HDL) subclasses in elderly patients with type 2 diabetes mellitus (T2DM), and to evaluate the relationships of them with oxidative stress and carotid atherosclerosis. Methods The serum levels of HDL subclasses and 8-iso-prostaglandin (PG) F2α were assayed, the carotid ultrasound examinations were executed in 56 elderly patients with T2DM (male: 40, female: 16) and 41 elderly healthy controls (male: 31, female: 10). Results Compared with control group, the serum level of HDL3 was significantly lower in T2DM group [(0.51±0.21) mmol/L vs. (0.59±0.15) mmol/L,t=1.991, P＜ 0.05], and the serum levels of HDL and HDL2 were also decreased [(1.07±0.36)mmol/L vs. (1.18±0.32) mmol/L; (0.56±0.25) mmol/L vs. (0.64±0.33) mmol/L], but there were no statistical significances (t= 1.611 and 0.614 both P＞0.05). The HDL3 was negatively correlated with HbA1C (r=-0.503, P=0.005). The values of absorbance of serum 8-iso-PG F2αwere significantly decreased in T2DM group than in control group (0.017±0. 004 vs. 0. 021±0. 008,t=2.245, P＜0.05). The mean carotid intima-media thickness (IMT) was higher in T2DM group,but there was no statistically significance. The detection rate of carotid atherosclerotic plaques was significantly higher in T2DM group than in control group (63.3% vs. 36.0%, x2=4.076, P＜0.05). Conclusions The low level of small particles HDL3 as well as elevated oxidative stress may contribute to the development of atherosclerosis in elderly patients with T2DM.

Objective To investigate the relationship between brain natriuretic peptide ( BNP)/ N-terminal pro-brain natriuretic peptide ( NT-proBNP) and New York Heart Association ( NYHA) classification, left ventricular structure and function, and explore the value of BNP/ NT-proBNP in the diagnosis of heart failure in the elderly. Methods Fifty-five elder patients with heart failure were selected (NYHA II, n = 15; NYHA III, n = 25; NYHA IV, n = 15) (heart failure group), and another 16 elder people with NYHA I were served as control group. The plasma mass concentrations of NT-proBNP and BNP were detected by electrochemiluminescence immunoassay and immunofluorescence method, respectively, and the structure and function of left ventricle were examined by echocardiography. Results The levels of plasma BNP and NT-proBNP increased with NYHA grades, were negatively correlated with LVEF (P <0.001), and were positively correlated with LVST, LVEDD, LAD and LVMI( P < 0.05). The area under the curve of BNP in diagnosis of heat failure was 0. 879 (P < 0.001), and that of NT-proBNP was 0.914(P < 0.001). Conclusion Both plasma BNP and NT-proBNP can be used to evaluate the heart function of patients with heart failure, and are useful tools for diagnosis of HF in the elderly.

ObjectiveTo investigate the protein expression of ERK1/2,p-ERK1/2,HIF-1α and α-enolase in hypertrophic cardiomyocytes induced by ET-1 and explore the regulation mechanism of overexpression of α-enolase in hypertrophic cardiomyocytes.MethodsET-1-induced abnormal cardiomyocytes were used as model of cardiac hypertrophy.Cellsurface area, [<'3>H]-leucine incorporation and the actin staining were measured to determine the extent of hypertrophy. Cultured cardiomyocytes were divided into 4 groups at random, control group, PD98059 treated group, ET-1 treated group and PD980594- ET-1 treated group. The protein expressions of ERK1/2, p-ERK1/2,HIF-1α and α-enolase were detected by immunoblotting analysis.ResultsCompared with the control group , cell surface area and [<'3>H] leucine incorporation were increased in ET-1 treated group ((1350.7±107.5)μtm<'2> vs. (896.1±70. 2)μtm<'2> , P<0.05; (1387.9±14.8) dpm vs. (787.7±10.2)dpm,P<0.013. Actin staining showed that ET-1-treated cardiomyoeytes had more intense actin staining and clear cross-striations than did control group, which suggested that myocardial cell hypertrophy could be induced by ET-1 in WKY neonatal cardiomyocytes. After MEK 1/2 inhibitor PD98059 was used, the cell surface area and [<'3>H] leucine incorporation were decreased in PD980594-ET-1 treated group compared with ET-1 treated group[(907.0±92.5)μm<'2> vs. (1350.7±107.5)μm<'2>;(841.5±10. 5)dpm vs. (1387.9±14.8)dpm, both P<0.05], which suggested that myocardial cell hypertrophy could be regulated by ERK1/2 signal pathway. Immunoblotting analysis showed that the protein expressions of p-ERK1/2, HIF-1α and α-enolase increased after ET-1 treatment,while PD98059 as an inhibitor of the upstream kinase of ERK1/2 was used, the protein expressions of HIF-1α and α-enolase were partially inhibited.ConclusionsET-1 induces hypertrophic cardiomyocytes through ERK1/2 phosphorylation in cultured neonatal rat cardiac myocytes.ERK1/2 and HIF-1α signal pathway may play an important role in the overexpression of α-enolase in the hypertrophic cardiomyocytes.

Objective To evaluate the relationship between hepatocyte growth factor (HGF) and myocardial fibrosis in the process of hypertension, and the therapeutic effect of losartan, an angiotension Ⅱ (Ang Ⅱ ) receptor antagonist. Methods Spontaneously hypertensive rats (SHR)were used as experimental model of myocardial fibrosis, and Wistar-Kyoto (WKY) rats were selected as control group. The therapeutic group was given losartan. Cardiac collagen was detected by Masson staining and HGF was determined by immunohistochemistry. All the pictures were analysed by Leica Qwin image disposal and analysis system. Results The cardiac collagen volume fraction (CVF) in SHR increased with aging and had a negative correlation with myocardium HGF. Losartan therapy increased the myocardium HGF expression but decreased the CVF. Conclusions Myocardium HGF may play a robe in hypertensive myocardial fibrosis due to its anti-fibotic effect reducing. Ang 1I AT1 receptor antagonist attenuates cardiac fibrosis by increasing myocardium HGF expression.