Research progress of PCSK9 in the mechanism of atherosclerotic cardiovascular disease / 中国医师杂志

Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitor has become a new drug for the treatment of hypercholesterolemia and atherosclerotic cardiovascular disease. Recent studies have shown that the mechanism of PCSK9 in atherosclerotic cardiovascular disease is very complex, which is closely related to the increase of plasma low-density lipoprotein cholesterol level, apoptosis, autophagy, inflammation, foam cell formation and vascular smooth muscle cell calcification, which will help us better understand the " multiple effects" of PCSK9 inhibitors. This review aims to analyze the research status of PCSK9 in molecular structure, cell function and cardiovascular disease treatment, which will further consolidate the success of new treatment strategies for atherosclerosis.

Development of Plantar Force Assessment Model for Patients with Patellofemoral Pain / 医用生物力学

Objective To develop plantar force model of patellofemoral pain (PFP), so as to provide theoretical references for the assessment of PFP rehabilitation. Methods The case-control study was conducted, and a total of 126 patients with PFP and 126 healthy controls matched by gender and age were enrolled in the study. The participants were tested for plantar force and pressure during level walking, and twelve plantar regions were divided and recorded. Whether the participants suffered PFP was analyzed as dependent variable, meanwhile the peak force and peak pressure in 12 plantar regions of participants at selected speed during level walking were analyzed as independent variables. Conditional logistic regression (CLR) equations of peak force and peak pressure with PFP were established, respectively. The receiver-operating characteristic (ROC) curve of the corresponding equations was derived, and the area under ROC curve was calculated to analyzed the validity of different equations on PFP assessment. Results The CLC equation of peak force in 12 plantar regions of the participants with FFP was constructed, and only peak force of lateral heel was in the equation. The CLC equation of peak pressure in each plantar region included medial heel, midfoot, 1st and 2nd metatarsals. Meanwhile, the area under ROC curve of the pressure equation was larger than that of the force equation. Conclusions Peak force and pressure at different plantar regions can be used to assess PFP during level walking, and peak pressure is more effective for assessment.

Calcium homeostasis during hibernation and in mechanical environments disrupting calcium homeostasis.

To maintain calcium homeostasis during physical inactivity, precise coordination is necessary between different organs of the body. There are a number of factors which alter an organism's calcium balance, such as growth, aging, physical inactivity and acquired or inherited disorders which ultimately lead to bone loss. In non-hibernating mammals, physical inactivity causes bone loss which may not be completely recoverable during the lifespan of an individual despite a resumption of activity. Extreme physical inactivity and nutritional deprivation are two other important factors that lead to bone loss in non-hibernating mammals. The mechanism of bone loss is still poorly understood, however, there is some evidence which shows that during hibernation, smaller mammals (ground squirrels, bats, and hamsters) undergo bone loss. While on the other hand, hibernating bears do not show any sign of bone loss and retain their bone structure and strength. This may be due to differences in their hibernation patterns, as smaller mammals may excrete calcium throughout the hibernation period, which ultimately leads to bone loss, whereas bears seem to have a more developed and advanced mechanism to prevent calcium loss and maintain their bone structure. In this review, we summarize calcium homeostasis and its adaptive mechanisms with reference to bone loss in hibernating as compared to non-hibernating mammals. We also review the effect of microgravity and simulated microgravity on bone physiology and subsequent adaptation.

Cardiac protective effect of the autoantibody against β3-adrenoceptor in rats with experimental heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the effect of the autoantibody against the β3-adrenoceptor on rats with experimental heart failure.</p><p><b>METHOD</b>The peptide corresponding to the sequence of β3 adrenoceptor was synthesized to actively immunize the rats, ELISA was used to detect the serum level of autoantibody against the β3-adrenoceptor (β3AA). Total IgGs were extracted from the serum containing β3AA in immunized rats. Aortic banding surgery was used to establish the heart failure model in male Wistar rats and rats were divided into the sham group (n = 8), heart failure group(n = 8),β3AA-immunized heart failure group (HF+β3AA, n = 8) and corresponding negative IgG-immunized heart failure group (HF+ IgG, n = 8).In 6 weeks and 8 weeks after aortic banding surgery, the serum levels of NT-pro brain natriuretic peptide (NT-proBNP) were assayed with ELISA assay and cardiac function was assessed by echocardiography.</p><p><b>RESULTS</b>β3AA was used to immunize rat with heart failure, the serum level of β3AA was stable at 50 days post immunization. At 8 weeks after aortic banding surgery, heart failure group showed significantly increased LVEDD [(6.92 ± 0.22) mm vs.(5.62 ± 0.19) mm, P < 0.001], LVESD [(4.63 ± 0.23) mm vs.(3.50 ± 0.20) mm, P < 0.01] and IVS [(2.44 ± 0.06) mm vs.(2.28 ± 0.05) mm, P < 0.05], and decreased LVEF[(62.07 ± 3.99)% vs.(79.63 ± 3.02)%, P < 0.01] and LVFS [(31.46 ± 3.22)% vs.(43.65 ± 2.68) %, P < 0.05] compared with the sham group.HF+β3AA IgG group showed decreased LVEDD [(6.07 ± 0.30) mm vs.(6.92 ± 0.24) mm, P < 0.05] and LVESD [(3.92 ± 0.22) mm vs.(4.68 ± 0.23) mm, P < 0.05], and higher LVEF [(70.29 ± 1.78)% vs.(61.95 ± 3.03)%, P < 0.05] and LVFS [(38.08 ± 2.32)% vs.(30.50 ± 1.82)%, P < 0.05] compared to the HF+ IgG group.In addition, compared with the HF+ IgG group, HF+β3AA IgG group showed decreased serum levels of NT-proBNP [(196.43 ± 6.56) pg/ml vs.(242.13 ± 7.86) pg/ml, P < 0.01].</p><p><b>CONCLUSION</b>Our results demonstrate that β3AA can improve cardiac function and reduce the serum levels of NT-proBNP in rat with heart failure.</p>

Comparison of therapeutic efficacy between recombinant human brain natriuretic peptide and sodium nitroprusside in treatment of acute attack of chronic heart failure / 中华老年医学杂志

Objective To compare the curative effects between recombinant human brain natriuretic peptide (rhBNP) and sodium nitroprusside in treatment of the acute attack of elderly patients with chronic heart failure (CHF), and probe the impacts of rhBNP on the heart function,serum B-type natriuretic peptide (BNP), norepinephrine (NE), endothelin 1 (ET-1) and antidiuretic hormone (ADH) levels. Methods The 89 patients aged 65-85 years at acute attack stage of CHF were randomized into two therapy groups: rhBNP group (n= 47) and sodium nitroprusside group (n=42). The clinical effects, heart function, serum BNP, NE, ET-1 and ADH changes were observed before and after the treatment. Results After 24 hours of treatment, the efficacy rate and total effective rate were higher in rhBNP group than in sodium nitroprusside group (51.1% vs. 26.2 %,95.7% vs. 66. 7%, respectively, P＜0. 05 and P＜0. 01), and non-efficacy rate in rhBNP group was lower (4.3% vs. 33. 3%, P＜0. 01). There was one death case in rhBNP group and three in sodium nitroprusside group. In rhBNP group, left ventricular ejection fraction values increased after 2 weeks of treatment [(46.2± 9.5)% vs. (38.1 ±6.0)%], P＜0.05. Serum BNP level significantly decreased in rhlBNP group than in sodium nitroprusside group after 2 weeks of treatment (P＜0.05).In rhBNP group, serum BNP and NE levels decreased 24 hours and 2 weeks after treatment (P＜0. 01) and the levels furtherly reduced after 2 weeks (P＜0.01). Serum ET-1 level decreased in rhBNP group than in sodium nitroprusside group 2 weeks after treatment (P＜0.05). In rhBNP group, there was no significant difference in serum ET-1 level between baseline and 24 hours after treatment (P＞ 0. 05), but the ET-1 level decreased 2 weeks after treatment as compared with 24 hours after treatment (P＜0.01). There were no significant differences between the two groups before and after treatment (P＞0.05). Incidences of headache and hypotension were lower in rhBNP group than in sodium nitroprusside group (4.3% vs. 19.0%, 14.9% vs. 23.8%, both P＜0.05),Conclusions RhBNP can be safely and effectively used for acute attack of CHF.

Target therapy of gefitinib in advanced adenocarcinoma of the lung / 中国肺癌杂志

<p><b>BACKGROUND</b>Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which is used to treat advanced non-small cell lung cancer, especially adenocarcinoma. The aim of this study is to evaluate the efficacy, side effects and prognostic factors of gefitinib in adenocarcinoma of the lung.</p><p><b>METHODS</b>A total of 26 patients with advanced adenocarcinoma of the lung were enrolled in the study. Gefitinib was orally administered 250mg once daily until disease progression or the occurrence of intolerable toxicity. They were evaluated regularly and their survival was analyzed.</p><p><b>RESULTS</b>In 26 patients, there was 1 with complete regression (3.8%), 11 with partial response (42.3%), 9 with stable disease (34.6%) and 5 with progression of disease (19.2%). The objective response rate was 46.2% and the disease control rate was 80.8%. The median progression-free survival time was 8.2 months and the median overall survival time was 10.4 months. The 1-year survival rate was 31.6%. Age ( < 70 years old), skin rash and CEA decrease were significantly related to longer survival, however, times of prior chemotherapy and gefitinib treatment stage did not influence the survival. Mean PS (ECOG) was 3.0 before treatment, and 1.8 after treatment. Mean symptom relief time was 5.2 days.</p><p><b>CONCLUSIONS</b>Gefitinib is an effective target drug with slight side effect. It can significantly improve quality of life of patients with adenocarcinoma. It can be used as first-line therapy to patients who are not suitable for chemotherapy.</p>

Effect of Long-term Smoking on Structure and Protein Expression of P53 and VEGF in Pericancer and Surrounding Lung Tissue / 医学研究杂志

Objective To investigate the effect of expressions of P53 and VEGF in smoking lung cancer and surrounding lung tissue,and to offer us with theorial evidence of early diagnosing smoking-related lung carcinoma clinically.Methods126 lung cancer patients were recruited,including 96 long-term smoking and 30 nonsmoking patients.All clinical data was integrity and the patients had clear smoking history.None of patients underwent chemotherapy,radiotherapy and other tumor treatment.The bronchial epithelium,cancer tissues,pericancer lung tissues,surrounding lung tissues were observed by light microscopy,and the expressions of P53 and VEGF of lung cancer tissues,pericancer lung tissues and surrounding lung tissues were detected by Immunohistochemical methed in smoking and non-smoking group.The experimental data was analyzed by SAS statistical software and the degree of difference between the groups was compared accordingly.ResultsThere were different levels of expansion of alveolar wall in lung tissues of smokers,and alveolar wall became capsular to expand.Respiratory bronchioles were cystic expansion and small bronchial wall becomed thickening,with severe bronchial epithelial membrane ranking nuts-chaos and peeling.Goblet cells and the cell surface of the cavity mucous secretions and suppositories were more than those of non-smokers.The P53 protein was expressed in cell nucleus and VEGF expressed in the cytoplasm and endothelial cells of neovascularization.Both their positive behavior was granular brown.Either for smoking or for non-smoking lung cancer,the expressions of P53 and VEGF were higher in tumor tissues than that of in the pericancer and surrounding lung tissue(P

Probucol and pravastatin in the prevention of restenosis after percutaneous coronary intervention / 中国介入心脏病学杂志

0.05).Repeat angiography performed 24 weeks after PCI,showed that the restenosis rate was 22.5% in the probucol group and 36.8% in the pravastatin group(P0.05).Conclusion Administration of probucol 4 weeks before PCI can reduce the rate of restenosis of BMS in a more extent when compared with pravastatin.