Aim To investigate the protection of ramipril,BQ-123 and their combination against myocardial ischemia/reperfusion(I/R)injury in vivo in anesthetized rats,and to explore the mechanism of action of drugs on myocardial oxidation-antioxidation system.Methods Healthy male Wistar rats were divided into 5 groups randomly,sham operated(Sham)group,I/R group,ramipril(RAM)group,BQ-123(BQ)group and ramipril and BQ-123(R&B)group.All groups but not sham were subjected to I/R procedure.Twenty four hours before ligation,ramipril(1 mg·kg~(-1))was intragastrically administered to rats in RAM and R&B groups.The equal volume of normal saline was given to rats in other groups.BQ-123(10 μg·kg~(-1)· min-1)was infused intravenously from 10 min before ligation to the end of 30 min ischemia to rats in BQ and R&B groups.The equal volume of normal saline was given to other groups.HR,MAP and the change of ST-segment were observed;ventricular arrhythmias were monitored during ischemia;the infarct size was examined by TTC staining;the activity of myocardial T-SOD,Mn-SOD,CAT and the content of MDA were detected by spectrophotometer.Results Compared with I/R group,the elevation of ST-segment was decreased,onset of VPC and VT was delayed,duration of VPC and VT was shortened,incidence of VPC,VT and VF was decreased,IS and IS/AAR were improved,activity of T-SOD,Mn-SOD and CAT was increased,the content of MDA was decreased in RAM,BQ and R&B groups.Compared with RAM and BQ alone group,onset of VPC and VT,duration of VPC and VT,size,activity of T-SOD and Mn-SOD and content of MDA were changed dramatically in R&B group.Conclusions Ramipril,BQ-123 and the combined use of these two agents protected myocardium from I/R injury in vivo.The protective effects of the combination on delaying onset of VA,shortening duration of VA,decreasing infarct size and content of MDA,and increasing activity of SOD are better than those of using ramipril or BQ-123 alone.

Aim To construct a lentiviral low expres-sion of miR-139-5 p vector and validate its expression efficiency in H9c2 cells. Method Target sequence was designed according to the sequence of rat miR-139-5p. Oligonucleotide duplex was synthesized and cloned into the lentiviral vector pGC-LV. The recombi-nant lentiviral vector, pHelper 1. 0, and pHelper 2. 0 were co-transfected into 293T cells, packaging virus. Then H9 c2 cells were infected with the supernatant containing lentiviral particles, and its infection effi-ciency and miR-139-5 p expression were determined by fluorescent microscope and real-time quantitative PCR, respectively. Results A lentiviral low expression of miR-139-5p vector was successfully constructed. The infection efficiency in H9c2 cells reached over 95%, and the relative expression of miR-139-5p was significantly down-regulated. Conclusion The lentiviral low expression of miR-139-5p vector is successfully constructed, and the expression of miR-139-5p in infected H9c2 cells is inhibited effectively.

Objective To assess the role of Matrix Metalloproteinase-9 (MMP-9)in rheumatoid arthritis (RA).Methods Peripheral blood from 45 RA patients and 28 healthy individuals (HV)were collected to detect RF and hs-CRP by immuno-turbidimetry,ESR by westergren method and MMP-9 by ELISA.The correlation was analysed between MMP-9 and RF, ESR or hs-CRP,respectively,by pearson correlation analysis.Results Levels of RF,ESR,hs-CRP and MMP-9 were signifi-cantly higher in RA patients than HV group (t=3.93~5.96,P<0.001),respectively.RF high titer patients or patients with a high inflammation response showed a higher MMP-9 levels than the RF low titer or slight inflammation patients (P<0.05).MMP-9 was positively correlated to RF,ESR and hs-CRP in RA patients(P<0.05),respectively.Conclusion MMP-9 maybe a sensitive tool in the diagnosis and management of RA patients.

Objective To observe the response of left ventricular (LV)function and structure to chronic intermittent hypoxia (CIH)early stage in New Zealand white rabbits by echocardiography.Methods The New Zealand white rabbits were placed in the CIH chamber and exposed to hypoxia for 8 weeks (6 hours/day,6 days/week).The flow of nitrogen and oxygen were regulated into the customized chambers by the gas control delivery system.The fraction of inspired oxygen was changed from 21 % to 8% for 25 s of every 1 70 s.LV structure and function was assessed by echocardiography at CIH 0,1 ,2,4,6,8 weeks and histopathology was done by HE staining simultaneously.Results ①LV structural variables:compared with 0 week,LV posterior wall and interventricular septum thickness thickened at 6 week.LV end diastolic increased at 8 week (P < 0.05 ).② LV systolic function variables:compared with 0 week,LV ejection fraction increased at 2 week and 4 week,decreased at 6 week and 8 week,but it was higher than 0 week (P < 0.05).Isovolumic contraction time (IVCT)decreased at 1 week,2 week,4 week (P <0.05 ).③LV diastolic function variables:compared with 0 week,Peak velocity of early diastolic period increased at 2 week and 4 week,decreased at 6 week and 8 week with E/A>1 .Isovolumic relaxation time (IVRT)decreased at 1 week and 2 week,but increased at 8 week (P < 0.05 ).④ The myocardial pathology showed that myocardial fibers disordered slightly,cardiomyocytes swelled,nuclei increased and intracellular edema when exposed to CIH for 2 week and 4 week.Vacuolar degeneration,edema and congestion were found in intercellular substance at 6 week and 8 week.Conclusions ① LV systolic and diastolic function compensation started at CIH early stage then LV structure abnormality advent later.②IVCT and IVRT are sensitive indicators of LV systolic and diastolic function compensation.

ObjectiveTo observe right ventricle (RV) structure and function of New Zealand rabbits with chronic intermittent hypoxia (CIH) for short-term (0-8 weeks) by echocardiography. MethodsTwenty-four healthy male New Zealand rabbits were set up CIH animal model for 8 weeks. RV structure?s systolic and diastolic function were measured by conventional and tissue Doppler echocardiography at 0, 1, 2, 4, 6 and 8 week and one rabbit was sacriifced randomly for RV myocytes and pulmonary tissue pathology examination. RV structure and function parameters at 0, 1, 2, 4, 6 and 8 week were analyzed by mixed effects model analysis.ResultsRV structure variables: RV, RA at 8 week increased compared with those at 0 week, but had no signiifcant difference (P>0.05); RV systolic function variables:RVFAC at 8 week increased compared with those at 0 week (F=3.45, P<0.05), TAPSE at 4, 6, 8 week increased compared with that at 0 week (F=3.11, 3.41 and 3.86, all P<0.05), RVMPI at 4 week decreased compared with that at 0 week (F=3.46, P<0.05), recovered to baseline at 6, 8 week. Isovolumetric relaxation time (IRTc) corrected by heart rate at 1, 2, 4 week decreased compared with that at 0 week (F=3.15, 3.31 and 3.17, all P<0.05), recovered to baseline at 8 week, ET of PA at 1, 2 week decreased compared with that at 0 week (F=3.01 and 3.15, both P<0.05), recovered to baseline at 4, 6, 8 week, AT of PA at 1, 2, 4 week decreased compared with that at 0 week (F=3.13, 3.15 and 3.32, all P<0.05), recovered to baseline at 6, 8 week. RV diastolic function variables: isovolumetric contraction time (ICTc) corrected by heart rate at 2, 4 week decreased compared with that at 0 week (F=3.13 and 3.33,both P<0.05), E/E? at 1, 2 week decreased compared with that at 0 week (F=3.13 and 3.44,bothP<0.05), recovered to baseline at 4, 6, 8 week, E/A at 4, 6, 8 week increased compared with that at 0 week (F=4.01, 3.82 and 3.37, all P<0.05), E?/A? at 8 week increased compared with that at 0 week (F=3.81, P<0.05). The myocardial pathology showed that RV myocardial cell structure was normal at 4 week. Nuclei enlarged, stain darkened and some cytoplasms loosed when exposed to CIH for 8 weeks. The structure of lung tissues was normal when exposed to CIH for 4 weeks. Inflammatory cell inifltrated, capillary engorged as well as the wall of pulmonary arterioles thickened slightly at 8 week.ConclusionsRV diastolic and systolic function showed compensatory and structure was normal in early CIH (0-8 week). RV diastolic function compensated earlier than systolic function. IRT and ICT were sensitive indicators of RV systolic and diastolic function compensation.

Bone metastasis-caused pain （BMP） is a common complication of cancer， and the incidence has been on the rise with the increase in the overall prevalence of cancer， threatening the survival and quality of life of patients. BMP is a kind of special pain with the characteristics of inflammatory pain and neuropathic pain， but is different from the two. Therefore， its pathogenesis is very complicated， and it is of great significance to understand the pathogenesis. The currently available studies mainly focused on osteoclast activation， changes in the bone microenvironment， glial cell activation， spinal cord neuron activation， and miRNA dysregulation. Modern therapies include the three-step analgesics， bisphosphonates， palliative radiotherapy， and interventional therapy for bone metastases， which show definite efficacy in short term. However， the long-term effect is unsatisfactory due to the adverse reactions， addiction， and drug resistance. Studies have shown that traditional Chinese medicine （TCM） has definite curative effect on BMP， which is safe， enhances efficacy， reduces toxicity， and boosts immunity. Moreover， it exerts the effect through multiple components， multiple targets， and multiple pathways. As a result， it has unique advantages in the prevention and treatment of BMP and has become a research focus. This paper summarizes the research on the pathogenesis of BMP， the intervention of TCM （compound Chinese medicine prescriptions， Chinese medicinals， and monomers from Chinese medicinals）， and the mechanisms of TCM， such as inhibiting osteoclast activation， glial cell activation， and spinal cord neuron activation， regulating pain mediators and abnormal expression of microRNA， and anti-tumor， which is expected to further clarify the pathogenesis of BMP and provide ideas and methods for the effective prevention and treatment of BMP with TCM.

ObjectiveTo analyze the quality changes of Platycladi Semen before and after the deterioration of moth-eaten and rancidity during storage. MethodFour types samples of Platycladi Semen， including normal， moth-eaten， oxidative rancidity and hydrolytic rancidity， were determined for volatile components， odor， and taste based on headspace solid phase microextraction/gas chromatography-mass spectrometry （HS-SPME/GC-MS） and electronic sensory techniques such as electronic nose and electronic tongue. Volatile components were identified by searching the database and manual comparison， the odor and taste were determined by the response values of the electronic nose and electronic tongue sensors， and the difference between samples before and after deterioration was studied by multivariate statistical analysis. ResultA total of 85 compounds were identified in Platycladi Semen samples. Compared with the normal samples， the number of volatile compounds in samples after hydrolytic rancidity decreased by 5， the number of volatile compounds in samples after moth-eaten and oxidative rancidity increased by 1 and 21， respectively. Aldehydes and acids accounted for majority of types. Among them， the contents of N-hexanoic acid， hexanal and propionic acid in the samples of oxidative rancidity reached 11.49%， 10.21% and 7.52%， which became the key indicators of rancidity. There was significant variance among the odor components corresponding to W1W， W2W and W1S sensors by electronic nose analysis. It was indicated that the value of sourness in deteriorated samples generally increased by mean of electronic tongue analysis. Compared with normal samples， the moth-eaten samples had changed slightly and rancidity samples had changed significantly especially oxidative rancidity samples of volatile components， odor and taste by multivariate statistical analysis. ConclusionIn terms of Platycladi Semen， the oxidative rancidity caused by nature storage for 12 months has the greatest impact on the quality. Therefore， it should be mainly to prevent oxidative rancidity to ensure the quality of Platycladi Semen.

OBJECTIVE：To know about the research status of health utility value obtained by mapping method in pharmacoeconomic evaluation ，and to provide reference for bibliometric study in pharmacoeconomic evaluation . METHODS ： Using“Mapping method ”“Health utility value ”“Cost-utility”“Utility point system ”as Chinese and English keywords ，retrieved from CNKI ，Wanfang database ，PubMed，Medline，Ebsco，Ovid and Wiley database ，empirical journal documents published from the inception to Dec. 31st，2018 about using mapping method to obtain health utility value were collected. The bibliometrics was used to statistically analyze basic information of included literature ，the construction and test of the model ，the type of the best model and so on. RESULTS ：The 124 included documents were all published in English journal. In the construction and testing of the mapping model ，the most frequently used econometric methods ，performance evaluation indicators and model testing methods were ordinary least squares （OLS），mean absolute error （MAE）and residual normality test ，application frequency of which were 97 times（31.60％），89 times（24.93％）and 62 times（21.09％）. There are 117 articles that define the best mapping model ，of which 101 articles（86.32％）have the best direct mapping effect. Most of the non-utility measurement scales adopted specific scales （92 articles，77.97％），and a few literatures adopted the universal scale （26 articles，22.03％）. The most utility measurement scales were 3-level European 5-dimensional health scale （79 articles，66.95％）. CONCLUSIONS ：The domestic empirical researches that use the mapping method to obtain health utility values need to be developed yet. A series of mapping models successfully developed by foreign scholars not only provide the feasibility of using non-utility measurement scales for cost-utility analysis ，but also provide more ideas for China to choose the corresponding econometric methods ，evaluation indicators and mapping methods in the empirical research of the mapping method in the future.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*