As a powerful endogenous protection,myocardial ischemic preconditioning and postconditioning have cardioprotection against ischemia reperfusion injury and cardiopretection against reperfusion injury respectively.They perhaps share some mechanisms during reperfusion,such as reduction of the production of oxygen free radical,activation of adenosine receptors,recruit of reperfusion injury salvage kinases,opening of the mitochondrial KATP channel,and inhibition of the mitochondrial permeability transition pore.These common targets may provide new strategy for development of drugs against reperfusion injury.

AIM : To prepare a phase-specific drug delivery system withfloating and pulsatile release of sinome-nine hydrochloride and evaluate in vitro drug release behavior. METHODS: The floating and pulsatile-release of coat-core tablets were prepared by press-coated technics. The effects of factors influencing release characteristic of the drug were investigated by dissolution test, and to elucidate the mechanism of drug releaseof the tablets with erosion and water-uptake test. RESULTS: The tablets had typical floating and pulsatile release properties with a lag time rapid release. The lag-time was shortened with the increase of expansion ratio of tablet core and rotation speed of stirrer. The lag-time was prolonged with the increase of pH and ionic strength of dissolution media.CONCLUSION: The tablet could float and rapidly release drug at the predetermined time.

AIM: To prepare a phase-specific drug delivery system with floating and pulsatile release of sinomenine hydrochloride and evaluate in vitro drug release behavior. METHODS: The floating and pulsatile-release of coat-core tablets were prepared by press-coated technics.The effects of factors influencing release characteristic of the drug were investigated by dissolution test,and to elucidate the mechanism of drug release of the tablets with erosion and water-uptake test. RESULTS: The tablets had typical floating and pulsatile release properties with a lag time rapid release.The lag-time was shortened with the increase of expansion ratio of tablet core and rotation speed of stirrer.The lag-time was prolonged with the increase of pH and ionic strength of dissolution media. CONCLUSION: The tablet could float and rapidly release drug at the predetermined time.

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 study the variation characteristics of peripheral blood β-catenin and DKK1 levels in patients with rheumatoid arthritis (RA) and the correlation with bone and joint damage.Methods One hundred and eight patients with RA (observation group) and 110 healthy individuals (control group) were selected.The bone mineral density(B MD) in the femur (femur neck,Ward area,greater trochanter,total femur area) and lumbar spine (L2,3,4) were measured by dual-energy X-ray absorptiometry instrument.X-ray for two hands were evaluated according to the Sharp score.The peripheral blood β-catenin and DKK1 levels were detected by enzyme-linked immunosorbent assay (ELISA).Multiple analysis was completed by multiple linear regression and Logistic regression.Results The peripheral blood DKK1 level in observation group was significantly higher than that in control group [(8.2 ±5.0) mg/L vs.(6.1 ±4.2)mg/L],there was statistical difference (t =2.452,P =0.025),but there was no statistical difference in β-catenin level between the 2 groups (t =15.947,P =0.142).Compared to control group,patients with RA had lower BMD at femur and lumbar spine (P ＜ 0.01).The incidence of osteoporosis in observation group was significantly higher than that in control group [31.5％ (34/108) vs.15.5％ (17/110)],there was statistical difference (x2 =9.289,P =0.005).The correlation analysis results showed that the peripheral blood DKK1 was positive correlation with erythrocyte sedimentation rate (ESR),28-jonit disease activity score (DAS28),alkaline phosphatase (AKP) and two hands X-ray joint narrowing space score in patient with RA (P ＜ 0.01 or ＜ 0.05) ;the peripheral blood β-catenin level was positively correlated with ESR and AKP (P ＜ 0.01 or ＜ 0.05).The multiple linear regression results showed that the disease duration,health assessment questionnaires (HAQ),DKK1 influenced two hands X-ray joint narrowing space score; but the age,disease duration,HAQ influenced two hands X-ray bony erosion score.The multiple Logistic regression results showed that the two hands X-ray Sharp score was the risk factor of osteoporosis at femur in patients with RA; but the age was the risk factor of osteoporosis at lumbar in patients with RA.Conclusions Peripheral blood DKK1 level in patients with RA increases significantly,while there is no apparent alteration in β-catenin level.Peripheral blood DKK1 level is correlated with disease activity and joint space narrow score.

Objective: To investigate the prevalence and influencing factors of poor eyesight among primary and middle school students in Tongzhou District, Beijing Municipality, so as to provide the evidence for developing control strategies for poor eyesight among primary and middle school students. Methods: Grades 3 to 6 students in district- and township-level primary schools, grades 1 to 3 students in district- and township-level junior high schools, and grades 1 to 3 district- and township-level high schools were sampled in Tongzhou District using the stratified cluster sampling method from 2020 to 2021. Basic information, daily activity, sleep duration and eye-using habits were collected using the specific questionnaires for poor eyesight and influencing factors among students in the 2018 national program for common diseases and health risk factors surveillance program among Chinese students, and the height and body weight were measured. Factors affecting poor eyesight were among primary and middle school students identified using a multivariable logistic regression model. Results: A total of 771 valid questionnaires were recovered, and the respondents included 392 male students (50.84%) and 379 female students (49.16%), and 321 primary school students (41.63%), 228 junior high school students (29.57%) and 222 high school students (28.79%). The prevalence of poor eyesight was 73.54% among the respondents. Multivariable logistic regression analysis showed that education phase (junior high school, OR=2.940, 95%CI: 1.931-4.476; high school, OR=5.998, 95%CI: 3.701-9.723) , obesity (OR=1.989, 95%CI: 1.258-3.146), daily exercise duration of less than 1 h (OR=1.931, 95%CI: 1.351-2.760), daily sleep duration of less than 8 h (OR=1.719, 95%CI: 1.193-2.477), at least 33 cm distance between a reading book and eyes (sometimes, OR=2.165, 95%CI: 1.320-3.550; never, OR=2.634, 95%CI: 1.767-3.928) and continuous short-distance eye use duration of 1 h and longer (OR=1.455, 95%CI: 1.020-2.078) were associated with poor eyesight among primary and middle school students. Conclusions The prevalence of poor eyesight is high among primary and middle school students in Tongzhou District. Higher grade, obesity, inadequate exercise and sleep duration and poor eye-using habits may increase the risk of poor eyesight.

Aim To study the protective effects of sphingosine 1-phosphate (S1P) postconditioning on rat myocardial cells injured by hypoxia/reoxygenation in reperfusion injury salvage kinase ( RISK ) signal path-way. Methods The cultured rat H9c2 cells were ran-domly divided into seven groups: ( 1 ) control group;(2) hypoxia/reoxygenation (H/R) group; (3) S1P group;(4) S1P+LY294002 group(S1P+LY); (5) LY group; ( 6 ) S1 P +PD98059 group ( S1 P +PD );(7) PD group. The viability of H9c2 cells was detec-ted using MTT method. The content of MDA in the cultured medium and the activity of T-SOD and Mn-SOD were measured with colorimetry. The concentra-tion of intracellular free calcium ion was detected by confocal microscopy. The rate of cell apoptosis was de-termined by flow cytometric analysis. Western blot was used to assess phosphorylation of Akt and ERK1/2 in H9c2 cells. Results Compared with the H/R group, S1P significantly increased vaibility of cells, lowered the rate of apoptosis, decreased the content of MDA in the culture medium, increased the activity of T-SOD and Mn-SOD, reduced concentration of intracellular calcium and increased the phosphorylation of Akt and ERK1/2 . When added LY294002 or PD98059 , the effects of S1P above were inhibited. Conclusion S1P protects H9 c2 cells against hypoxia/reoxygenation inju-ry. The protection of S1P was inhibited by LY294002, the inhibitor of PI3 K/Akt and PD98059 , the inhibitor of ERK1/2 . S1 P protects H9 c2 cells against hypoxia/reoxygenation injury via RISK pathway.

Aim To investigate the protective effects of nicorandil, glutamine and metoprolol used in single and combination on the antiapoptosis ability of cardio-cytes and the expression of HSP70 after myocardial is-chemia/reperfusion injury in rats. Methods Male Wistar rats were divided randomly into seven groups:( 1 ) Sham group:in which the coronary artery was not roped;(2) I/R group:in which only 30 min ischemia and 120 min reperfusion of LAD was executed; ( 3 ) Nicorandil group; ( 4 ) Glutamine group; ( 5 ) Meto-prolol group; ( 6 ) Nic + Glu + Met ( NGM ) group;(7) low dose of Nic+Glu+Met ( NGML) group. In the pharmacological precondition groups, correspond-ing drugs were administered 30 min before I/R proto-col, and the initial drug dose in each group was 1 mg ·kg-1 . Myocardial apoptotic rates were measured with TUNEL ( terminal dexynucleotidyl transferase-mediated dUTP nick end labeling) , and the expression of apop-tosis related proteins-Bcl-2/Bax and protective pro-tein-HSP70 was detected by Western blot. ResultsIn I/R group, the apoptotic rate in ischemic region was very high ( 36.9% ± 10.3%) , and Bcl-2/Bax was very low ( 0.14 ±0.08 ) . Compared with I/R group, the apoptotic rate of pharmacological precondition groups was decreased significantly ( P <0.01 ) , and the ratio of Bcl-2 to Bax was raised ( P<0.01 ) . Com-pared with Sham group, the expression of HSP70 in-creased significantly ( P<0.01 ) in I/R group. Com-pared with IR group, the expression of HSP70 of phar-macological precondition groups was elevated ( P <0.01 ) , and the expression in NGM group was higher than in the single drug group ( P<0.01 ) . Conclusion Compared with single therapy after I/R in rat, the combination therapy of nicorandil, glutamine, meto-prolol can decrease the apoptotic rate, and the expres-sion of apoptosis related proteins is developed. In the mean time, the expression of protective protein HSP70 is elevated.

Aims To investigate the protective effects of noninvasive limb ischemic preconditioning (LIPC) on myocardial ischemia-reperfusion (I /R)injury,and to explore the mechanism.Methods Healthy male Wistar rats were divided randomly into I /R,I /R +LIPC,I /R +5-Hydroxydecanoate (5-HD)and I /R +LIPC +5-HD groups.The I /R +LIPC and I /R +LIPC-5-HD groups of rats were subjected to three cy-cles of LIPC induction per day with 5 min of reperfu-sion after occlusion for 5 min at the left hind limb for 3 days.All rats were subjected to myocardial I /R injury on the fourth day.The I /R +5-HD and I /R +LIPC-5-HD groups of rats were given the inhibitor of ATP-sen-sitive potassium channel 5-HD before and during myo-cardial I /R injury. Results Compared with I /R group,LIPC reduced myocardial infarct size (P <0.05),lowered cardiocyte apoptosis index and Fas, FasL positive cell number (P <0.01 ),increased the reduced nitric oxide (NO)/endothelin (ET)-1 ratio (P <0.05)in serum in I /R +LIPC group.5-HD a-bolished the protective effects induced by LIPC in I /R+LIPC-5-HD group.Compared with normal myocardi-al tissue,expression of mir-30a-3p was increased in I /R group (P <0.01 )and was decreased in LIPC group (P <0.01 ).Conclusion LIPC alleviates myocardial I /R injury and improves endothelial function. The mechanism may be related with the opening of ATP-sensitive potassium channel,regulating the balance be-tween NO and ET-1 and decreasing the expression of myocardial mir-30a-3p.