Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.

Objective:To investigate impact of leonurine(Leo)on necrotic apoptosis in rats with myocardial ischemia/reperfu-sion(MIR)injury by regulating receptor interacting protein 1(RIP1)-receptor interacting protein 3(RIP3)-mixed lineage kinase domain-like protein(MLKL)pathway.Methods:Fifteen rats were randomly selected as sham surgery group(Sham),left anterior descending coronary artery of remaining rats were ligated to construct MIR model,and randomly grouped into MIR group,Leo group(15 mg/kg),Compound 6i group(1 mg/kg RIP1-RIP3-MLKL pathway activator Compound 6i)and Leo+Compound 6i group(15 mg/kg Leo+1 mg/kg Compound 6i),with 15 rats in each group.MIR group and Sham group were injected with equal amounts of physiological saline.Cardiac function indicators were observed through ultrasound electrocardiogram;ELISA was applied to detect myocardial injury indicators and inflammatory factor levels;HE staining was applied to observe pathological damage of heart;TTC staining was applied to detect myocardial infarction area;TUNEL staining was applied to detect cell apoptosis;Western blot was applied to detect expres-sions of RIP1-RIP3-MLKL pathway proteins.Results:Myocardial cells in Sham group were intact and arranged in an orderly manner;arrangement of myocardial cells was disordered and swollen,myofibril contracted,and sarcolemma was destroyed in MIR group,ejec-tion fraction(EF)and cardiac output(CO)level were obviously lower than Sham group(P<0.05),Mb,cTnⅠ,CK-Mb contents,IL-6,IL-18 levels,myocardial infarction area,myocardial cell apoptosis rate,RIP1,RIP3 and MLKL protein levels were obviously increased(P<0.05);compared with MIR group,Leo group had improved cell arrangement disorder and edema,and obviously increased EF and CO levels(P<0.05),Mb,cTnⅠ,CK-Mb contents,IL-6,IL-18 levels,myocardial infarction area,myocardial cell apoptosis rate,RIP1,RIP3 and MLKL protein levels were obviously reduced(P<0.05),trend of Compound 6i group was opposite;myocardial tissue structure of Leo+Compound 6i group was similar to MIR group,and Compound 6i eliminated cardioprotective effect of Leo on MIR rats.Conclusion:Leo may alleviate myocardial necrosis apoptosis in MIR rats by down-regulating RIP1-RIP3-MLKL pathway,thus playing a therapeutic role in MIR.

Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.

Objective:To investigate impact of leonurine(Leo)on necrotic apoptosis in rats with myocardial ischemia/reperfu-sion(MIR)injury by regulating receptor interacting protein 1(RIP1)-receptor interacting protein 3(RIP3)-mixed lineage kinase domain-like protein(MLKL)pathway.Methods:Fifteen rats were randomly selected as sham surgery group(Sham),left anterior descending coronary artery of remaining rats were ligated to construct MIR model,and randomly grouped into MIR group,Leo group(15 mg/kg),Compound 6i group(1 mg/kg RIP1-RIP3-MLKL pathway activator Compound 6i)and Leo+Compound 6i group(15 mg/kg Leo+1 mg/kg Compound 6i),with 15 rats in each group.MIR group and Sham group were injected with equal amounts of physiological saline.Cardiac function indicators were observed through ultrasound electrocardiogram;ELISA was applied to detect myocardial injury indicators and inflammatory factor levels;HE staining was applied to observe pathological damage of heart;TTC staining was applied to detect myocardial infarction area;TUNEL staining was applied to detect cell apoptosis;Western blot was applied to detect expres-sions of RIP1-RIP3-MLKL pathway proteins.Results:Myocardial cells in Sham group were intact and arranged in an orderly manner;arrangement of myocardial cells was disordered and swollen,myofibril contracted,and sarcolemma was destroyed in MIR group,ejec-tion fraction(EF)and cardiac output(CO)level were obviously lower than Sham group(P<0.05),Mb,cTnⅠ,CK-Mb contents,IL-6,IL-18 levels,myocardial infarction area,myocardial cell apoptosis rate,RIP1,RIP3 and MLKL protein levels were obviously increased(P<0.05);compared with MIR group,Leo group had improved cell arrangement disorder and edema,and obviously increased EF and CO levels(P<0.05),Mb,cTnⅠ,CK-Mb contents,IL-6,IL-18 levels,myocardial infarction area,myocardial cell apoptosis rate,RIP1,RIP3 and MLKL protein levels were obviously reduced(P<0.05),trend of Compound 6i group was opposite;myocardial tissue structure of Leo+Compound 6i group was similar to MIR group,and Compound 6i eliminated cardioprotective effect of Leo on MIR rats.Conclusion:Leo may alleviate myocardial necrosis apoptosis in MIR rats by down-regulating RIP1-RIP3-MLKL pathway,thus playing a therapeutic role in MIR.

Damage to organelles plays a significant role in myocardial ischemia/reperfusion injury,which results in the dysfunction of mitochondria and other related organelles.The communication between mitochondria and other organ-elles can also affect the development of myocardial ischemia/reperfusion injury.For instance,the mitochondria-associated endoplasmic reticulum membrane provides a"seamless connection"and regulates the exchange of organelles and metabolites(such as ions,lipids and proteins)between the mitochondria and the endoplasmic reticulum,which subse-quently affects myocardial ischemia/reperfusion injury.However,there is a lack of studies regarding the interaction be-tween mitochondria and related organelles,which is a critical component in triggering myocardial ischemia/reperfusion inju-ry.Therefore,this article describes the role of mitochondrial crosstalk with endoplasmic reticulum,lysosomes and nuclei in myocardial ischemia/reperfusion injury,and aims to provide a theoretical basis for targeting mitochondrial crosstalk with other organelles in the treatment of myocardial ischemia/reperfusion injury.

Objective To investigate the prevalence of urine abnormalities for school children in Chengdu city and to evaluate the significance of urinary screening.Methods During January to December 2013,morning urine of 6 615 students were collected and screened by urine reagent paper.Two weeks later,the repeated screening was conducted in the children whose urine samples were positive for the first screening.Urine samples with positive testing results for twice were submitted to urine routine tests at local hospital,and the children with the urine positive results were defined as urine abnormalities.The children with urine abnormalities were transferred to a tertiary hospital and given treatment and follow-up.Results There were 6 615 cases receiving urine screening,including 2 624 cases (39.67 ％) of the grade I,and 3 991 cases(60.33％) at junior middle school.During the first screening,323 cases (4.83％) children had urinary occult blood positive,43 cases (0.65％) had urinary protein,20 cases (0.30％) had occult blood positive and proteinuria,and 103 cases (1.56％) had white cells in urine.During the second urine screening,62 cases (0.94％) had occult blood positive,6 cases (0.09％) had urinary protein,2 cases (0.03％) had proteinuria and occult blood positive,46 cases (0.70％) had white cells in urine.The incidence of urine abnormalities with occult blood positive,proteinuria,occult blood positive and proteinuria,and white cells in urine of children at junior middle school [1.38％ (55/3 991 cases),0.13％ (5/3 991 cases),0.05％ (2/3 991 cases),0.70％ (28/3 991 cases)] were significantly higher than those of children at primary school [0.27％ (7/2 624 cases),0.04％ (1/2 624 cases),0 (0/ 2 624 cases),0.69％ (18/2 624 cases)],and all the differences were statisticallysignificant (x2 =64.16,168.53,178.09,98.16,all P ＜ 0.05).In children transferred to a tertiary hospital for treatment,there were 4 cases with IgA nephropathy,1 case with minor glomerular abnormalities,and 12 cases with urinary tract infection.Conclusion Urinary screening is an effective way to find out kidney disease and urinary tract infection in children.Follow-ups should be strengthened.

Objective:To assay aflatoxin B1 in the oil as a pharmaceutical excipient in soft capsules by LC-MS/MS. Methods:Aflatoxin B1 was extracted from the peanut oil in soft capsules by the solvent composed of methanol and 0. 1% formic acid solution, and then centrifuged and the supernatant was purified by neutral alumina cartridges and tested after the concentration with the mobile phase consisting of methanol and 0. 1% formic acid solution with gradient elution at the flow rate of 0. 3 ml·min-1 . 25μl of the tested solu-tion was injected for the analysis at the column temperature of 30℃. Electrospray ionization ( ESI) source was applied and operated in the position ion mode. Multiple reactions monitoring ( MRM) mode was used to quantify the samples. Results:Aflatoxin B1 was in good linearity within the range of 0. 098-1. 960 μg·L-1(r=0. 999 5). The limit of detection was 0. 05 μg·L-1. The average sampling recovery was 97. 73% (n=6) with RSD of 4. 625%. Conclusion:The method is proved to be sensitive, accurate, specified and re-producible, which is referential for the assay of aflatoxin B1 in oily preparations.

Objective To determine the optimum dose of pentazocine when combined with propofol for gastroscopy in elderly patients.Methods One hundred and forty ASA physical status Ⅰ or Ⅱ patients,aged 6575 yr,scheduled for elective gastroscopy under general anesthesia,were randomly assigned into Ⅰ-Ⅳ groups (n =35 each) using a random number table.Before insertion of the gastroscope,pentazocine 0.2,0.4 and 0.8 mg/kg were injected intravenously in Ⅱ-Ⅳ groups,respectively,while the equal volume of normal saline was given in Ⅰ group.Propofol was then administered by target-controlled infusion (TCI).The half-effective concentration (EC50 of propofol was determined by up-and-down sequential trial.The target plasma concentration (Cp) was set at 3.5 μg/ml in the first patient.Gastroscopy was performed at 5 min after the target effect-site and plasma concentrations were balanced.The response to gastroscopy was defined as positive when body movement and/or bucking occurred during gastroscopy.Each time the Cp increased/decreased by 0.3 μg/ml in the next patient depending on whether or not the response to gastroscopy was positive.EC50 and 95 ％ confidence interval of propofol TCI inhibiting the response to gastroscopy were calculated using Probit analysis.The development of respiratory depression and hypotension was observed.Results EC50 (95 ％ confidence interval) of propofol TCI inhibiting the response to gastroscopy was 2.82 (2.63-3.02) μg/ml,2.78 (2.58-2.97) μg/ml,2.16 (2.00-2.32) μg/ml and 2.03 (1.88-2.19) μg/ml in Ⅰ-Ⅳ groups,respectively.Compared with group Ⅰ,EC50 was significantly decreased in Ⅲ and Ⅳ groups,and the incidence of respiratory depression was increased in Ⅳ group (P ＜ 0.05).Conclusion The optimum dose of pentazocine when combined with propofol is 0.4 mg/kg for gastroscopy in elderly patients.

ObjectiveTo investigate the role of platelet-derived growth factor(PDGF) and its receptor in the development of hypertrophic scar. MethodsThe expression of PDGF and its receptor were detected in biopsy specimens of 9 pieces of normal skin, 7 pieces of granulation tissue of burn wound and 34 pieces of hypertrophic scar by immunohistochemical staining using specific polyclonal antibodies.ResultsPDGF and its receptor markedly increased in granulation tissue and hypertrophic scars, reaching the peak in the hypertrophic scars within 6 months and then decreased after the peak, whereas PDGF and its receptor expressed weakly in only a few normal skin specimens, and the differences were significant(P<0.05).ConclusionsThe increasing expression of PDGF and its receptor may be related to the development of hypertrophic scar.

0.05).The sera levels of sCD40L in CHD were significantly and positively correlated with Jenkins score(r=0.524,P