[Purpose]To analyze the trends of cancer incidence and mortality from 1991 to 2020 in Jiashan County of Zhejiang Province,and to predict trends from 2021 to 2035.[Methods]Cancer cases and deaths from 1991 to 2020 in Jiashan County were collected.The crude inci-dence rate and mortality rate,age-standardized rate(ASR)were calculated.The annual percentage change(APC)and average annual percentage change(AAPC)were calculated by Joinpoint model to analyze the trend of cancer incidence and mortality.The age-period-cohort model was used to predict the trends of cancer incidence and mortality from 2021 to 2035 and the estimated annual percentage change(EAPC)was calculated.[Results]The age-standardized incidence rates by Chinese standard population(ASIRC)in Jiashan were 159.06/105,187.25/105,and 254.37/105 during 1991-2000,2001-2010,and 2011-2020,respectively.The trends in young and middle-aged women and people above 65 years old were more predominant.Lung,stomach,colorectal,liver and female breast cancers were major incident cancers for the period from 1991 to 2020.The cancer incidence showed an increasing trend from 1991 to 2020(AAPC=2.17％,P＜0.05)and is expect-ed to continue to increase over 2021 to 2035(EAPC=3.03％,P＜0.05).The age-standardized mor-tality rates by Chinese standard population(ASMRC)in Jiashan were 119.74/105,117.79/105,and 100.11/105 during 1991-2000,2001-2010,and 2011-2020,respectively.Lung,liver,stomach,colorectal,esophageal,and pancreatic cancers were leading causes of cancer deaths from 1991 to 2020.The cancer mortality showed a decreasing trend from 1991 to 2020(AAPC=-1.00％,P＜0.05)and is expected to continue to decline over 2021 to 2035(EAPC=-1.67％,P＜0.05).[Conclusion]The mortality rate from cancers has been gradually declined in Jiashan County,while the incidence rate has increased significantly and will continue to increase in the next 15 years.High incidence of lung cancer,liver cancer,gastric cancer and colorectal cancer makes it crucial to pay close attention to key groups and strengthen the control of risk factors of high inci-dence cancer.

[Purpose]To analyze the trends of cancer incidence and mortality from 1991 to 2020 in Jiashan County of Zhejiang Province,and to predict trends from 2021 to 2035.[Methods]Cancer cases and deaths from 1991 to 2020 in Jiashan County were collected.The crude inci-dence rate and mortality rate,age-standardized rate(ASR)were calculated.The annual percentage change(APC)and average annual percentage change(AAPC)were calculated by Joinpoint model to analyze the trend of cancer incidence and mortality.The age-period-cohort model was used to predict the trends of cancer incidence and mortality from 2021 to 2035 and the estimated annual percentage change(EAPC)was calculated.[Results]The age-standardized incidence rates by Chinese standard population(ASIRC)in Jiashan were 159.06/105,187.25/105,and 254.37/105 during 1991-2000,2001-2010,and 2011-2020,respectively.The trends in young and middle-aged women and people above 65 years old were more predominant.Lung,stomach,colorectal,liver and female breast cancers were major incident cancers for the period from 1991 to 2020.The cancer incidence showed an increasing trend from 1991 to 2020(AAPC=2.17％,P＜0.05)and is expect-ed to continue to increase over 2021 to 2035(EAPC=3.03％,P＜0.05).The age-standardized mor-tality rates by Chinese standard population(ASMRC)in Jiashan were 119.74/105,117.79/105,and 100.11/105 during 1991-2000,2001-2010,and 2011-2020,respectively.Lung,liver,stomach,colorectal,esophageal,and pancreatic cancers were leading causes of cancer deaths from 1991 to 2020.The cancer mortality showed a decreasing trend from 1991 to 2020(AAPC=-1.00％,P＜0.05)and is expected to continue to decline over 2021 to 2035(EAPC=-1.67％,P＜0.05).[Conclusion]The mortality rate from cancers has been gradually declined in Jiashan County,while the incidence rate has increased significantly and will continue to increase in the next 15 years.High incidence of lung cancer,liver cancer,gastric cancer and colorectal cancer makes it crucial to pay close attention to key groups and strengthen the control of risk factors of high inci-dence cancer.

Objective To learn the satisfaction and influencing factors of medical insurance for urban residents in Taiyuan city.Methods The multi-stage random sampling method was used to survey the satisfaction of medical insurance for urban residents so covered in 4 districts of Taiyuan city. The questionnaire covered basic personal information, and comments of the residents on the three dimensions of medical insurance regarding the stakeholders. The data solicited were subject to descriptive analysis, Kruskal-Wallis test and ordered multi-class logistic regression analysis. Results The rate of overall satisfaction of urban residents′ medical insurance in Taiyuan city was 44.6% , that of average satisfaction was 48.3% , and that of dissatisfaction was 7.1%.For residents of different family size and physical health status, the differences of their satisfaction were statistically different(P<0.05).Ordered multi-class logistic regression analysis showed that the proportion of reimbursement, the scope of drug treatment and the efficiency of treatment were top factors affecting their satisfaction ( OR > 1 ). Conclusions The rate of overall satisfaction of medical insurance by urban residents in Taiyuan city is low. To improve their satisfaction, it is important to increase the proportion of reimbursement, expand the scope of reimbursement for diagnosis and treatment along with drugs, simplify the reimbursement procedures, and improve the service attitude of the service agencies.

Objective To investigate microRNAs ( miRNAs) expression profiling of cardiomyocytes in rats with heart failure, and predict miRNAs-regulated target genes and their functions.Methods Total of 18 male SD rats weighing 200-220 g were randomly divided into 2 groups:the control group ( CON) and the heart failure group (HF).The rats in HF group were injected by adriamycin via tail vein to induce heart failure, meanwhile in CON group, rats were received an equal volume of 0.9% sodium chloride intravenously.The cardiomyocytes isolated from the rat hearts in two groups and cultured overnight.After that, total RNA was extracted and then subjected to miRNA microarray to screen differentially expressed miRNAs.The reults of microarray were further verified by quantitative real-time PCR ( qRT-PCR ) .The target genes regulated by differentially expressed miRNAs were predicted by the software of Targetscan and miRanda.Bioinformatics analysis was performed to predict the miRNAs-regulated target genes and analyze the enriched gene ontology ( GO) and signaling pathway ( KEGG Pathway) .Results The results of miRNA microarray showed that a total of 37 miRNAs were differentially expressed in HF group as compared to CON group, among which 22 miRNAs were up-regulated and 15 miRNAs were down-regulated (P<0.01, FDR<0.05).The expression of miR-133b-5p (t=14.56, P<0.01), miR-6216 (t=9.32, P<0.01) and let-7e-5p (t=13.92, P<0.01) which were detected by qRT-PCR exhibited the similar tendency of up or down regulation to those shown in microarray results.Bioinformatics analysis indicated that miRNAs-regulated target genes were significantly enriched in 31 GOs (P<0.01, FDR<0.05) and 12 signal pathways (P<0.05, FDR<0.05), among which ubiquitin-proteasome system, MAPK signaling pathway and Toll like siganling pathway exhibited a higher enrichment. Conclusion MiRNA expression profile on cardiomyocytes in rat with adriamycin-induced heart failure was significantly changed.These differentially expressed miRNAs might participate in the process of heart failing by regulating their target genes in rat cardiomyocytes.

Objective To evaluate the roles of 1-phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) signaling pathways in reduction of ischemia-reperfusion (I/R) injury to the isolated hearts by morphine preconditioning in the rats with chronic heart failure.Methods Adult male Sprague-Dawley rats,weighing 200-230 g,in which doxorubicin 2.0 mg/kg was injected via the tail vein once a week for 6 weeks to induce chronic heart failure,were studied.At the end of 8th week,42 rats with chronic heart failure were randomly divided into 7 groups (n =6 each) using a random number table:sham operation group (group S),I/R group,morphine preconditioning group (group MP),PD98059 (ERK inhibitor) + morphine preconditioning group (group PD + MP),wortmannin (PI3K inhibitor) + morphine preconditioning group (group WT + MP),PD98059 group (group PD) and wortmannin group (group WT).The hearts were quickly excised and passively perfused in a Langendorff apparatus and subjected to 30 min of occlusion of the left coronary artery followed by 2 h of reperfusion to establish the model of I/R injury.In group S,the hearts were only sutured,but not ligated and were continuously perfused with K-H solution for 195 min.In group I/R,the hearts were perfused with K-H solution for 45 min before ischemia.In group MP,the hearts were perfused with K-H solution for 15 min,with K-H solution containing morphine 1 μmol/L for 5 min and then with K-H solution for 5 min (3 cycles in total) before ischemia.In PD + MP and WT + MP groups,the hearts were perfused with K-H solution containing PD98059 (10 μmol/L) and wortmannin (100 nmol/L),respectively,starting from 10 min before morphine preconditioning until 5 min of ischemia.In PD and WT groups,the hearts were perfused with K-H solution containing PD98059 (10 μmol/L) and wortmannin (100 nmol/L),respectively,starting from 40 min before ischemia until 5 rin of ischemia.At 15 min of equilibration (baseline) and 5 and 10 min of reperfusion,the coronary flow was collected to detect the activity of lactate dehydrogenase (LDH).Infarct size (IS) and area at risk (AAR) were measured at the end of reperfusion and IS/AAR ratio was calculated.Results Compared with group S,LDH activity was significantly increased at 5 and 10 min of reperfusion,IS and IS/AAR ratio were also increased (P ＜ 0.05),and no significant change was found in AAR in group I/R (P ＞ 0.05).Compared with group I/R,LDH activity was significantly decreased at 5 min of reperfusion,IS and IS/AAR ratio were also decreased (P ＜ 0.05),and no significant change was found in AAR in group MP,and no significant change was found in LDH activity,IS,AAR and IS/AAR ratio in WT and PD groups (P ＞ 0.05).Compared with group MP,LDH activity was significantly increased at 5 and 10 min of reperfusion (P ＜ 0.05),and IS and IS/AAR ratio were decreased in group PD + MP,and no significant change was found in LDH activity,IS,AAR and IS/AAR ratio in group WT + MP (P ＞ 0.05).Conclusion Activation of ERK signaling pathway is involved in reduction of I/R injury to isolated hearts by morphine preconditioning in rats with chronic heart failure,however,PI3K signaling pathway has no such effect.

An ultrasensitive immunoassay was developed based on As3+ and Hg2+ labeled SiO2 @ Au nanoparticles signal tags and hydride generation-atomic fluorescence spectrometry (HG-AFS) for the detection of carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9 (CA 19-9) respectively. Firstly, amino SiO2@ Au NPs were synthesized for selective absorption of As3+ and Hg2+ ions respectively. Subsequently,the secondary antibody (Ab2) of CEA and CA 19-9 was respectively labeled on As3+ or Hg2+-SiO2 @ Au NPs to prepare the corresponding signal tags for CEA and CA 19-9. Based on the sandwich immunoassay scheme, the tags, two antigen and corresponding first antibodies were bio-conjugated on the bottom of 96-well plate at room temperature to form the immunocomplex. After it was dissolved in alkali solution, As3+ and Hg2+ ions were released in solution and detected by HG-AFS, which concentration was proportional with logarithms of CEA and CA 19-9. The reaction conditions were optimized and the tags were characterized. This assay was based on determination of the concentration of As3+ and Hg2+ for quantization of the corresponding CEA and CA 19-9 antigen. The assay showed a wide linear range from 0. 001 to 100. 0 μg / L for CEA and 0. 01-80 U/ mL for CA 19-9, and a lower detection limit of 0. 5 ng / L and 0. 005 U/ mL respectively. This proposed method was used in real serums samples, the results were consistence with that by ELISA. The immunoassay showed three orders of magnitude of sensitivity lower than that of ELISA, which provides a promising simultaneous immunoassay for the early diagnosis of cancer .

Aim To investigate the roles of mitogen-ac-tivated protein kinases ( MAPK ) pathways in the pro-tective effects of remifentanil preconditioning against is-chemia/reperfusion injury of isolated heart in rats with heart failure. Methods Adult male SD rats were injected with adriamycin via tail vein for 6 weeks to induce heart failure. The rats were confirmed chronic heart failure through echocardiography and randomly divided into 9 groups(n=6)as follows: sham group, ischemia/reperfusion group ( IR) , remifentanil precon-ditioning group( RPC) , ERK inhibitor PD98059+RPC group ( RPD ) , p38 inhibitor SB203580 +RPC group ( RSB ) , JNK inhibitor SP600125 + RPC group ( RSP ) , and the inhibitor control groups ( PD , SB and SP) . All hearts were linked to the Langendorff ap-paratus. The coronary effluent was collected to detect the activity of lactate dehydrogenase ( LDH ) at base-line, 5 min and 10 min after reperfusion, respectively. Infarct size ( IS) and area at risk ( AAR) were deter-mined by 2, 3, 5-triphenyl-tetrazolium (TTC) staining at the end of reperfusion. Left ventricular developed pressure ( LVDP), ± dp/dtmax and heart rate ( HR) were recorded to evaluate cardiac function in each group. Results When compared with IR group, RPC significantly reduced IS / AAR and decreased the ac-tivity of LDH at 5 min and 10 min after reperfusion. However, SP600125 almost thoroughly abolished the protective effects of RPC, as evidenced by the in-creased value of IS / AAR and the high activity of LDH. In addition, PD98059 also partly blocked the effects of RPC, while SB203580 showed no influence on RPC. Meanwhile, the hemodynamic parameters such as LVDP, HR and ± dp/dtmax were not signifi-cantly different in any group except sham group. Con-clusion JNK and ERK pathways may play an impor-tant role in cardioprotective effects of remifentanil pre-conditioning against ischemia/reperfusion injury in rats with heart failure.

Objective To evaluate the role of opioid receptors and phosphatidylinositol 3-kinase/proteinserine-threonine kinases (PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathways in reduction of hypoxia/reoxygenation (H/R)-induced injury to cardiomyocytes by remifentanil preconditioning in rats.Methods Primary cardiomyocytes were obtained from adult male Sprague-Dawley rats and cultured in DMEM culture medium.The cells were seeded in 48-well plates (density 2 × 104 cells/ml,500 μl/well) and randomly divided into 12 groups (n =9 each):control group (group C),group H/R,hypoxia preconditioning group (group HPC),remifentanil preconditioning (RPC) group,naltrindole (δ receptor antagonist) + RPC group,nor-binaltorphimine (κ receptor antagonist) + RPC group (BNI + RPC group),wortmannin (PI3K inhibitor) + RPC group (W+ RPC group),PD98059 (ERK inhibitor) + RPC group (PD + RPC group),NTD group,BNI group,W group and PD group.In group H/R,the cardiomyocytes were exposed to 90 min of hypoxia,followed by 120 min of reoxygenation.In group HPC,the cardiomyocytes were exposed to 10 min of hypoxia,followed by 30 min of reoxygenation before H/R.In group RPC,the cardiomyocytes were preconditioned with remifentanil with the final concentration of 1 μmol/L for 10 min,followed by 30 min routine culture before H/R.In NTD + RPC,BNI + RPC,W + RPC and PD + RPC groups,naltrindole 5μmol/L (final concentration),nor-binaltorphimine 5 μmol/L (final concentration),wortmannin 0.1 μmol/L (final concentration) and PD98059 30μmol/L (final concentration)were added,respectively,and then the cells were coincubated with remifentanil for 10 min,followed by 30 min routine culture before H/R.The viability of cardiomyocytes,cell apoptosis and activity of lactate dehydrogenase (LDH) in the culture medium were detected.The apoptosis rate (AR) was calculated.Results Compared with group C,the viability of cardiomyocytes,AR and activity of LDH in the culture medium were significantly increased in group H/R (P ＜ 0.05).Compared with group H/R,the viability of cardiomyocytes,AR and activity of LDH in the culture medium were significantly decreased in HPC,RPC and BNI + RPC groups (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in NTD + RPC,W + RPC,PD + RPC,NTD,BNI,W,and PD groups (P ＞ 0.05).The viability of cardiomyocytes was significantly lower,and the AR and activity of LDH in the culture medium were higher in NTD + RPC,BNI + RPC,W + RPC,and PD + RPC groups than in RPC group (P ＜ 0.05).Conclusion Remifentanil preconditioning activates PI3K/Akt and ERK signaling pathways possibly through activating δ opioid receptors thus attenuating H/R-induced injury to cardiomyocytes in rats.

Objective To evaluate the effects of morphine preconditioning on the expression of microRNAs (miRNAs) during hypoxia-reoxygenation (H/R) in isolated cardiomyocytes in rats with heart failure.Methods Healthy adult male Sprague Dawley rats,w eighing 200-220 g,were used in this study.Adriamycin 2.0 mg/kg was injected once a week for 6 weeks via the tail vein to induce heart failure.The cardiomyocytes were isolated from the failing hearts of rats and seeded in 24-well plates or in 60 mm diameter dishes.The cells were then randomly divided into 3 groups (n =16 each) using a random number table:control group (group C); group H/R;morphine preconditioning group (group MP).The cells were cultured in normal culture atmosphere in group C.After being exposed to hypoxic air (5％ CO2-95％ N2) for 90 min,the cells were returned to the high-glucose DMEM supplemented with 10％ newborn bovine serum and were then cultured for 120 min in H/R and MP groups.In group M,the cells were cultured in morphine culture medium (final concentration of morphine 0.3 μmol/L) for 10 min and then were returned to the culture medium without morphine and cultured for 30 min immediately before hypoxia.At 120 min of reoxygenation,the cells of 8 wells in each group were chosen to detect the cell viability and lactate dehydrogenase (LDH) activity (by Typan blue staining).All the RNAs were extracted from the cardiomyocytes of the left 8 wells in each group and subjected to miRNA microarray to screen differentially expressed miRNAs.Results The cell viability was significantly lower,the activity of LDH was higher,the expression of miR-6216 and let7e-5p was higher,and the expression of miR-133b-5p was lower in H/R and MP groups than in group C (P ＜ 0.05).Compared with H/R group,the cell viability was significantly increased,the activity of LDH was decreased,the expression of miR-133b-5p was up-regulated,and the expression of miR-6216 and let-7e-5p was down-regulated in MP group (P ＜ 0.05).Conclusion Morphine preconditioning reduces H/R injury to isolated cardiomyocytes in rats with heart failure through regulating the expression of miRNAs such as miR133b-5p,miR-6216 and let-7e-5p.

Aim To investigate whether pioglitazone has protective effect against glutamate induced neurotoxicity in cultured cortical neurons and its possible molecular mechanisms underlying pioglitazone's neuroprotective effects.Methods The cortical neurons were taken from newborn rats and used for experiments 7 days after culture.The neurons were randomly divided into control group;glutamate group; glutamate+piogli-tazone group;glutamate+SP600125 group;SP600125 group.Cell viability was determined by MTT.The morphology change of neurons was observed under a fluorescence microscope with fluorescence dye Hoechst 33258.Immunostaining was used to investigate the expression of phospho-ATF2 in neuronal cells.Western blot was performed to investigate the protein level of phospho-JNK1 and total JNK1.Results Pioglitazone markedly reduced the damage of cortical neurons caused by glutamate.Pioglitazone also significantly inhibited glutamate induced up-regulation of phospho-JNK1 protein level and phospho-ATF2 expression.SP600125, an inhibitor of JNK, antagonized the toxicity induced by glutamate.Conclusions Pioglitazone can protect cultured cortical neurons from glutamate induced damage.The protective effect of pioglitazone appears to be associated with inhibiting the c-Jun N-terminal protein kinase signaling pathway.