Objective:To evaluate the role of miR-146a in hippocampal inflammatory responses in postoperative cognitive dysfunction (POCD) in mice.Methods:One hundred and sixty clean-grade male C57BL/6 mice, aged 12-16 weeks, weighing 22-28 g, were divided into 5 groups ( n=32 each) using a random number table method: control group (group C), group POCD, miR-146a agomir group (group Ag), miR-146a antagomir group (group At) and negative control group (group NC). The mice were subjected to an intramedullary fixation for tibial fracture under 1.5% isoflurane anesthesia to establish POCD model.At 2 days before operation, miR-146a agomir 0.5 nmol (0.1 nmol/μl) was injected into bilateral hippocampi in group Ag, miR-146a antagomir 2.5 nmol (0.5 nmol/μl) was injected in group At, miR-146a negative control solution 2.5 nmol (0.5 nmol/μl) was given in group NC, and the animals in group C did not receive any treatment.At 1 day before operation and at 1, 3 and 7 days after operation, open-field test was performed to evaluate spontaneous motor activity, and contextual fear conditioning test was performed to evaluate cognitive ability 15 min later.At 1 and 3 days after operation, the animals were sacrificed and hippocampi was removed for determination of expression of CD11b (a marker for activation of microglia) in hippocampal CA1 region by immunofluorescence staining.At 6, 12 and 24 h after operation, the expression of miR-146a was detected by quantitative real-time polymerase chain reaction, the expression of interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B p65 (NF-κB p65) and tumor necrosis factor-alpha (TNF-α) was determined by Western blot and interleukin-1beta (IL-1β) and IL-6 contents were determined by enzyme-linked immunosorbent assay. Results:There was no significant difference in the total exploring distance in the open-field test or percentage of freezing time in tone-fear conditioning test at each time point among the five groups( P>0.05). Compared with group C, the percentage of freezing time in the contextual fear conditioning test was significantly decreased at 1, 3 and 7 days after operation, the expression of CD11b at 1 and 3 days after surgery and expression of miR-146a, IRAK1, TRAF6, NF-κB p65 and TNF-α were up-regulated and the contents of IL-1 β and IL-6 were increased at 6, 12 and 24 h after operation in group POCD ( P<0.05). Compared with group NC, the percentage of freezing time in the contextual fear conditioning test was significantly increased at 1, 3 and 7 days after operation, and the expression of CD11b was down-regulated at 1 and 3 days after surgery, and the expression of miR-146a, IRAK1, TRAF6, NF-κB p65 and TNF-α was up-regulated and IL-1β and IL-6 contents were decreased at 6, 12 and 24 h after operation in group Ag, and the percentage of freezing time in the contextual fear conditioning test was decreased at 1, 3 and 7 days after operation, the expression of CD11b at 1 and 3 days after surgery was up-regulated, the expression of miR-146a was down-regulated and IRAK1, TRAF6, NF-κB p65 expression was up-regulated at 6, 12 and 24 h after operation, TNF-α expression was up-regulated and IL-1β and IL-6 contents were increased at 12 and 24 h after operation in group At ( P<0.05). Conclusion:miR-146a is involved in the process of hippocampal inflammatory responses, and the mechanism may be related to the inhibition of IRAK1-TRAF6-NF-κB signaling pathway in mice.

Objective To investigate the changes of miR-146a expression in serum,hippocam-pus and prefrontal cortex in postoperative cognitive dysfunction (POCD) mice.Methods Fifty healthy male C57BL/6 mice,aged 12-14 weeks,weighing 25-30 g,were randomly divided into two groups (n =25 each)using a random number table:control group (group C)and anesthesia plus sur-gery group (group AS).Mice in group AS underwent open tibial fracture of the left hind paw with in-tramedullary fixation in aseptic conditions under general anesthesia with 2.1% isoflurne.Ten mice in each group received the fear conditioning test (FCT)on the 1,3 and 7 days after anesthesia/surgery. The rest of mice were sacrificed 24 h before (baseline),and 6,12,24,48 h after anesthesia/surgery, and then the serum,prefrontal cortex and hippocampus were collected or removed for detection of the expression of miR-146a using quantitative reverse transcription polymerase chain reaction (qRT-PCR).Results Compared with group C,the percentage of freezing time in contextual FCT was sig-nificantly decreased (P <0.05)in group AS,while no significant change in freezing time percentage was found in tone-cued FCT.In serum,compared with group C,miR-146a expression at 6,12,24, 48 h after anesthesia/surgery was significantly up-regulated in group AS (P < 0.05 );and in group AS,the expression of miR-146a was significantly decreased 6,24,48 h as compared to that at 12 h after anesthesia/surgery (P <0.05).In hippocampus,compared with group C,miR-146a expression at 6,12,24,48 h after surgery was significantly up-regulated in group AS (P <0.05);and in group AS,the expression of miR-146a at 6,48 h after surgery was significantly decreased as compared to that at 12 h after anesthesia/surgery (P <0.05).In prefrontal cortex,compared with group C,miR-146a expression at 24,48 h after surgery was significantly up-regulated in group AS (P <0.05);and in group AS,the expression of miR-146a was significantly increased at 48 h as compared to that at 24 h after anesthesia/surgery (P <0.05).Conclusion The expression of miR-146a in serum,hippocam-pus and prefrontal cortex in POCD mice was up-regulated,and changes of miR-146a expression may be related to the development of POCD.

Objective To investigate the role of hippocampal cannabinoid receptor 2 (CB2R) in postoperative cognitive dysfunction (POCD) in mice.Methods Fifty-four healthy male C57BL/6 mice,aged 12-16 weeks,weighing 20-30 g,were divided into 3 groups (n=18 each) using a random number table:control group (group C),group POCD and POCD plus CB2R agonist JWH133 group (group POCD+J).The mice were subjected to an intramedullary fixation for tibial fracture under 1.5％ isoflurane anesthesia to establish POCD model.In group POCD+J,2 mg/kg JWH133 was injected intraperitoneally at a total volume of 10 ml/kg after emergence from anesthesia and then the injection was repeated once a day until the 7th day after surgery.Open field test was carried out on 1 day before surgery and 1,3 and 7 days after surgery to evaluate the locomotor activity.Fear conditioning test was carried out at 15 min after completion of open field test.Mice were sacrificed at 2 h after the end of behavioral test,and the hippocampus was harvested for determination of the expression of tumor necrosis factor-alpha (TNF-α),interleukin-1beta (IL-1β),monocyte chemotactic protein-1 (MCP-1) and CB2R (by Western blot) and expression of CD11b in hippocampal tissues (by immunofluorescence).Results There was no significant difference in the total exploring distance in open field test,percentage of freezing time in contextual fear conditioning test or percentage of freezing time in tone-fear conditioning text at each time point among the three groups (P＞0.05).Compared with group C,the percentage of freezing time in contextual fear conditioning test was significantly decreased,and the expression of TNF-α,IL-1β,MCP-1,CD11b and CB2R was up-regulated after surgery in group S (P＜0.05).Compared with group S,the percentage of freezing time in contextual fear conditioning test was significantly increased,and the expression of TNF-α,IL-1β,MCP-1,CD11band CB2R was down-regulated after surgery in group S+J (P＜ 0.05).Conclusion Activation of hippocampal CB2R may be involved in the endogenous protective mechanism of POCD in mice,and the mechanism is related to inhibiting activation of hippocampal microglia and attenuating central inflammatory responses.

Objective To understand the treatment circumstance of ST-elevation myocardial Infarction (STEMI) patients at public hospitals in Shenzhen.Methods Directed by Public Hospital Administration at Shenzhen Municipality (PHASM) and led by Chest Pain Treatment Quality Control Center at Shenzhen People's Hospital (CPTQCC-SZ),25 public hospitals in Shenzhen, including 15 PCI-capable hospitals and 10 non-PCI-capable hospitals,we investigated on the overall treatment conditions and the STEMI patient treatment situations from October to December 2015 in these hospitals. A regression analysis was performed between a few factors and the success rate of STEMI treatment was reviewed. Results 383 STEMI cases twere registered between October to December 2015 in the 25 public hospitals in Shenzhen,with 324 case treated in PCI-capable hospitals and 59 cases in non-PCI-capable hospitals. There were statistical differences between the PCI-capable hospitals and non-PCI-capable hospital in fields of total number of senior cardiologists (work year ≥ 3 year),total number of beds in general cardiology beds and number of beds in cccu(all P<0.01). There was no difference in the time of obtaining the first ECG at patient arrival between hospitals(P=0.052).Time for laboratory results availability for troporin was significantly shorter in PCI-capable hospital[(25.0±4.2)min vs.(58.0±2.8)min,P=0.002] .Among the PCI-capable hospitals,the mean D-to-B time was 320 minutes, and mean F-to-B time was 380 minutes. In non-PCI-capable hospitals,D-to-N time ranged from 20 to 350 minutes and F-to-N time ranged from 25 to 380 minutes. Conclusions There are gaps among the overall conditions of the public hospitals in Shenzhen. The overall conditions and chest pain treatment conditions of non-PCI-capable hospitals had bigger gaps with PCI-capable hospitals.

Objective To involve informatized measures into medical equipment maintenance to enhance their clinical quality and safety.Methods A medical equipment maintenance management system was developed with C/S and B/S to establish the architecture,PowerBuilder language for programming and SQL Server 2008 database for data storage and inquiry.Results 2-a clinical trial proved the system had high stability,which facilitated maintenance application as well as inquiry and statistical analysis on maintenance records through network.Concinsion The system realizes informatized medical equipment maintenance management and promotes medical equipment maintenance management.

Objective:To investigate the correlation between exposure to famine in early life and later risk of type 2 diabetes in adulthood.Methods:A cluster sampling method was used to include 8 868 residents who were lived in the Jiading community of Shanghai during the Great Famine from 1959 to 1962 in China. Subjects were divided into non-exposed group, fetal exposure group, childhood exposure group, and adolescent exposure group. Logistic regression model was used to analyze the relationship between famine exposure in early life and the risk of type 2 diabetes in adulthood. Results:Famine exposure during childhood and adolescent both increased the risk of developing type 2 diabetes in adulthood in women. No significant correlation was observed in men. In subjects with less physical activity and lower education level, the risk of developing type 2 diabetes mellitus in adulthood was significantly higher in the famine-exposed group than that of non-exposed groupand the interactions were statistically significant.Conclusion:Early life famine exposure increases the risk of developing type 2 diabetes in adults, especially in women.

OBJECTIVE: The association between lipoprotein (a) [Lp(a)] levels and metabolic syndrome (MetS) remains uncertain, especially in the Asian population. The purpose of this study was to demonstrate the association between Lp(a) levels and MetS in a middle-aged and elderly Chinese cohort. METHODS: A cross-sectional study of 10,336 Chinese adults aged 40 years or older was conducted in Jiading District, Shanghai, China. Logistic regression analysis was used to evaluate the association between serum Lp(a) levels and MetS. RESULTS: In the overall population, 37.5% of participants had MetS. Compared with individuals in the lowest quartile of serum Lp(a) levels, those in the highest quartile had a lower prevalence of MetS (30.9% vs. 46.9%, P for trend < 0.0001). Multivariate logistic regression analyses showed that compared with participants in the bottom quartile of serum Lp(a) levels, those in the top quartile had decreased odds ratio (OR) for prevalent MetS [multivariate-adjusted OR 0.45 (95% confidence interval 0.39-0.51); P < 0.0001]. Additionally, Lp(a) level was conversely associated with the risk of central obesity, high fasting glucose, high triglycerides, and low HDL cholesterol, but not with hypertension. Stratified analyses suggested that increasing levels of Lp(a) was associated with decreased risk of MetS in all the subgroups. CONCLUSION Serum Lp(a) level was inversely associated with the risk of prevalent MetS in a middle-aged and elderly Chinese cohort.
Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Lipoprotein(a) ; blood ; Male ; Metabolic Syndrome ; blood ; epidemiology ; Middle Aged

OBJECTIVE: To explore the effect of dihydromyricetin on the expression of miR-98-5p and its mechanism in the development of Herceptin resistance in SKBR3 cells. METHODS: The expression of IGF2 and miR-98-5p and their interaction relationship were analyzed by bioinformatics analysis through TargetScan online databases. SKBR3 cells and drug-resistant SKBR3-R cells were cultured in cell experiments. Xenograft tumor mice were constructed by SKBR3 and SKBR3-R cells. Proteins were detected by western blotting and immunohistochemistry. Transfected cells were constructed by shRNA lentivirus vectors. RT-QPCR was used to detect RNA. Cell proliferation was detected by MTS method. Cell jnvasion was detected by Transwell assay. Luciferase reporting assays were used to verify RNA interactions. IGF-1R/HER2 heterodimer was determined by immunocoprecipitation. RESULTS: The expression of IGF2, p-IGF1R, p-Akt and p-S6K in SKBR3-R cells were significantly higher than those in SKBR3 cells, while the expression of PTEN protein was lower in SKBR3-R cells (P < 0.05). IGF1R/HER2 heterodimer in SKBR3-R cells was significantly increased (P < 0.01).The expression of IGF2 and invasion ability were significantly reduced while transfected with miR-98-5p in SKBR3-R cells (P < 0.05), but the IGF2 mRNA were no difference in both cells (P > 0.05). The expression of miR-98-5p was up-regulated and IGF2 was decreased in drug-resistant xenograft tumor mice after feeding with dihydromyricetin, and the tumor became more sensitivity to Herceptin (P < 0.05). CONCLUSION Dihydromyricetin could induce the expression of miR-98-5p, which binds to IGF2 mRNA to reduce IGF2 expression, inhibit the IGF-1R/HER2 formation, thereby reversing cell resistance to Herceptin in SKBR3-R cells.
Animals ; Cell Line, Tumor ; Flavonols/pharmacology* ; Humans ; Mice ; MicroRNAs/metabolism* ; Receptor, IGF Type 1 ; Trastuzumab

OBJECTIVE: Ideal cardiovascular health (CVH) could predict a lower risk of developing cardiovascular diseases. This study was conducted to investigate the association between ideal CVH and subclinical atherosclerosis in a population cohort of Chinese adults aged ⪖ 40 years. METHODS: This study was designed as a cross-sectional analysis of 8,395 participants who had complete data at baseline and a prospective analysis of 4,879 participants who had complete data at 4.3 years of follow-up. Ideal CVH metrics were defined according to the American Heart Association. Subclinical atherosclerosis was evaluated by plaques in carotid arteries, carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), and urinary albumin-to-creatinine ratio (UACR). RESULTS: Both the prevalence and incidence of atherosclerosis measures were found to be decreased with increasing numbers of ideal CVH metrics at baseline (all P values for trend < 0.01). The levels of CIMT and UACR at follow-up showed an inverse and significant association with the numbers of ideal CVH metrics at baseline (both P values for trend < 0.05) but a borderline significant association with baPWV (P for trend = 0.0505). Taking participants with 0-1 ideal metric as reference, we found that participants with 5-6 ideal metrics had significantly lower risks of developing carotid plaques (odds ratio, OR = 0.46; 95% confidence interval, CI 0.27-0.79), increased CIMT (OR = 0.60; 95% CI 0.42-0.84), and increased baPWV (OR = 0.57; 95% CI 0.34-0.97) after full adjustments. A significant interactive effect of age and CVH was detected on CIMT and baPWV progression (both P values for interaction < 0.05). CONCLUSION The numbers of ideal CVH metrics showed a significant and inverse association with the risk of developing subclinical atherosclerosis in middle-aged and elderly Chinese adults, whereas its dose-response effect was attenuated in individuals aged ≥ 60 years and partially weakened in male participants.
Aged ; Atherosclerosis ; epidemiology ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Health Status ; Humans ; Male ; Middle Aged ; Prospective Studies

OBJECTIVETo explore the effects of aptamer-siRNA nucleic acid compound on growth and apoptosis in myeloid leukemia cell line K562.

METHODSthe changes of cellular morphology and structure were observed by using fluorescence microscope, laser confocal microscope, JEM-4000EX transmission electron microscopy; MTT assay were performed to evaluate the sensibility of K562 cells to aptamer-siRNA compound, the apoptosis was detected by DNA gel electro-phoresis.

RESULTSThe remarkably changes of morphology and structure of K562 cells treated with 200 µmol/L aptamer-siRNA were observed under fluorescence microscopy and electromicroscopy. As compared with control, the aptamer-siRNA compound showed more inhibitory effect on K562 cells and there was significant difference (P<0.05). The MTT assay showed that the IC50 value of aptamer-siRNA compound for K562 cells was 150 µmol/L. According to agarose gel electrophoresis observation, when the aptamer-siRNA compound showed effect on K562 cells, the typical DNA lader could be observed.

CONCLUSIONThe aptamer-siRNA compound can significantly induce K562 cell apoptosis, and provide reference for gene therapy of patients with chronic myelocytic lenkemia.