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Background@#Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. @*Methods@#β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. @*Results@#Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. @*Conclusion@#These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.
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Stroke is one of the main causes of death in the world, of which more than 85% are acute ischemic stroke, and reperfusion therapy is its main treatment. Studies have shown that the neutrophil to lymphocyte ratio (NLR) is associated with the efficacy, safety and outcome of the reperfusion therapy. This article reviews the predictive role of NLR in patients with ischemic stroke receiving reperfusion therapy.
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Objective:To analyze the clinical characteristics of ischemic colitis(IC) and further improve the diagnosis and treatment of the disease.Methods:The clinical manifestations, risk factors, colonoscopy and abdominal CT examination results of 35 patients with IC confirmed from January 2014 to December 2018 in the Second Hospital of Jilin University were retrospectively analyzed, and their clinical characteristics were summarized.Results:The sudden manifestation of abdominal pain and blood in 31 cases of the 35 patients were the main manifestations.Ten patients who underwent abdominal CT scan showed a thickened bowel wall with a thickness of (7.92±1.41)mm.The CT value of the thickened bowel wall decreased significantly to (21.20±2.27)Hu.In 35 cases of colonoscopy, 42.86%, 31.42%, 20.00%, 2.86% and 2.86% were involved in the descending colon, sigmoid colon, transverse colon, ascending colon and whole colon, respectively.The left colon was the main part, with clusters and bands Mucosa-like erythema, ecchymosis, erosion, and even ulcers.No rectum was involved in 35 patients.Conclusion:The typical manifestation of IC is sudden abdominal pain and bloody stool.Abdominal CT in emergency department has obvious suggestive value for early diagnosis of this disease.Colonoscopy is the main diagnostic method for this disease.
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Lacunar stroke is one of the most common ischemic stroke types in clinical practice at present. Its prognosis is generally better. However, studies have shown that about 20％ ～30％ of patients with lacunar stroke may have early neurological deterioration. This article reviews the pathophysiological mechanisms and predictors of early neurological deterioration in patients with lacunar stroke.
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Objective To understand the epidemiological characteristic of bacterial food-poisoning in Zhuhai City to provide a scientific basis for the judgment ,control and prevention of bacterial food-poisoning .Methods The samples of bacterial food-poison-ing in the Zhuhai Municipal Bacterial Food-Poisoning Laboratory during 2011-2015 were detected according to two version of Mi-crobiological Examination of Food (implementation on 2004-01-01 and 2016-06-01 respectively ) ,and the detection results were sta-tistically analyzed .Results Thirty-seven cases of bacterial food-poisoning(430 samples) occurred in Zhuhai City in the recent five years ,among which 22 cases(124 strains of pathogenic bacteria) were detected ,the cause detection rate of bacterial food-poisoning events was 59 .46% .The pathogenic bacteria causing bacterial food-poisoning were mainly vibrio parahaemolyticus (97 strains , 78 .23% ) and Staphyloccocus aureus (12 strains ,9 .68% ) .The sample detection rate of anal swabs was highest (77 strains ,62 . 10% ) ,followed by feces samples(17 strains ,13 .71% ) .The seasonality distribution was obviously concentrated in the third quarter (99 strains of pathogenic bacteria ,79 .84% ) and second quarter o (16 strains ,12 .90% ) .Conclusion Vibrio parahaemolyticus and Staphyloccocus aureus were the main pathogenic bacteria causing bacterial food-poisoning in Zhuhai City during these recent five years ,and the seasonality distribution was mainly concentrated in the second and third quarter .It is important to improve health awareness of the whole people and strengthen the surveillance and supervision and management work of food-borne pathogenic bac-teria during the food production ,processing and storage process in order to reduce the occurrence of food-poisoning .
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Objective: To establish an HPLC-fluorescence detection method for the determination of thioguanosine-monophosphate (TGMP), thioguanosine-diphosphate (TGDP) and thioguanosine-triphosphate (TGTP) in red blood cells (RBC), as well as quantify the individual thioguanine nucleotides metabolites in kidney transplant recipients with azathioprine (AZA) therapy.Methods: The individual thioguanosine phosphates were extracted from RBC by dichloromethane and subsequently oxidized by potassium permanganate.The separation was achieved on a Nucleosil C18 column (150 mm×4.6 mm,5 μm) with an ion pairing reagent and detected by a fluorescence detector (excitation at 315 nm, emission at 390 nm).The mobile phase consisted of 20 mmol·L-1 potassium phosphate buffer (pH was adjusted to 6.8 by 5 mmol·L-1 tetrabutylammonium hydrogensulfate)-acetonitril (80:20) with the flow rate of 1.0 ml·min-1.Results: TGMP, TGDP and TGTP were quantified from RBC within the range of 50-500, 50-1000 and 100-5 000 pmol·ml-1, respectively.The limit of quantification (LOQ) was 50, 50 and 100 pmol·ml-1 RBC for TGMP, TGDP and TGTP, respectively.The intra-and inter-day RSDs were below 7.0% with the method recovery between 95.0% and 103.6%.The mean extraction recovery was above 90%.The assay was applied in the blood samples of 30 kidney transplant recipients with AZA therapy, and the results indicated that TGTP was the predominant phosphate metabolite in RBC.Conclusion: The method is simple, rapid, sensitive and specific, and it can quantitatively determine the individual thioguanosine phosphates in RBC of kidney transplant recipients with AZA therapy.
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Objective:To study the association of RAC1 gene polymorphisms with protein expression levels of Rac1-GTP. Methods:A total of 182 healthy Hans population in Hubei were recruited. The 4 tag-SNPs in RAC1 gene were genotyped by Real time TaqMan-MGB genotyping assay. And the Rac1-GTP protein levels in plasma samples from all participants were determined by enzyme linked immunosorbent assays ( ELISA ) . The distribution characteristics of Rac1-GTP expression levels were also analyzed. Furthermore,the expression levels of Rac1-GTP were compared among different genotypes of the 4 tag-SNPs in RAC1 gene. Results:The distribution of Rac1-GTP expression levels was positive skewed in healthy Chinese Hans population. The expression levels were significantly higher in females than in males (P0. 05). Different expression levels of Rac1-GTP were observed in different genotypes for rs702482 and rs10951982 (P0. 05). Conclusion:RAC1 genetic polymorphisms can potentially affect the expression levels of Rac1-GTP protein in healthy Chinese Hans population.
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Objective:To develop a method for the detection of 10 single nucleotide polymorphisms(SNPs) of Nm23 gene,and to explore the genotypic and allelic distributions of the 10 SNPs in Chinese Hans population in Wuhan.Methods: Two hundreds healthy subjects ,115 men and 85 women included ,were enrolled as DNA sample donors.The real time TaqMan-MGB genotyping assay was used for the determination of the 10 SNPs selected ,and the results were validated by direct gene sequencing.Results:The method established could accurately and quickly screen the genotypes of the 10 SNPs of Nm23/NDPK gene.Distribution frequencies of the 10 SNPs were similar to these in other researches as well as these of HCB.All the loci follow the Hardy-Weinberg equilibrium.Highly linkage disequilibriums were found between rs 16949649 and rs7207370 , rs16949649 and rs34214448 , rs2159359 and rs2302254 , rs2159359 and rs8075231 ,rs2159359 and rs2041296 ,as well as rs2159359 and rs8071647 ,respectively.Four Tag SNPs:rs34214448 , rs2302254 ,rs11868380 and rs2318785 were initially selected by Heploview software.Conclusion:The method established for SNP gen-otyping can meet the needs for rapid analysis of Nm 23 gene polymorphisms ,and may have great values in investigating the association between gene polymorphisms and diseases as well as adverse drug reactions.
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mGlu5 (Metabotropic glutamate receptor 5) does not only exist in nervous system , but also in many pe-ripheric organs and tissues .The vital role that mGlu5 plays in both nervous and non-nervous system diseases , which will be important for further studying the pathogenesis of diseases .Moreover, it can provide us with new ide-as and methods for precaution and cure of illness with mGluRs .
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Objective:To establish a method for the detection of 8 single nucleotide polymorphisms (SNPs) of RAC1 gene,and to analyze the genotypic and allelic distributions of the 8 SNPs in healthy Chinese Han population.Methods:The real-time fluorescence TaqMan-MGB probes allele classification technology was used for the determination of the 8 SNPs in 150 cases of healthy volunteers in Hubei China ,and the results were validated by direct gene sequencing.Results: The method established in this study can accurately screen the genotypes of the 8 SNPs of human RAC1 gene.Highly linkage disequilibriums were found between rs 10951982 and rs9374 , rs702482 and 836488 ,respectively.All the 8 sits were in accordance with Hardy-Weinberg equilibrium.Six Tag-SNPs were selected by Heploview software:rs10951982 ,rs6954996 ,rs6951997 ,r1s2977 ,rs702482 and rs702483.The MAFs of the 8 SNPs in our study were close to the MAFs in CHB and Asian in Hap Map database .Significant distribution differences were also observed in different races.Conclusion:No significant differences are observed in this study in healthy Chinese Han population.But differences are found when compared with the data of other races in Hap Map.
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Objective To investigate the correlation between neuronal injury and the expression of caspase-3 and caspase-activated deoxyribonuclease (CAD) after focal cerebral ischemia-reperfusion in rats, also to study the effect of caspase-3 particular inhibitor. Methods The focal cerebral ischemia model (occluding middle cerebral artery of the rats) was made by using modified inserting thread method and reperfusion after embolizing for one hour. Using HE staining, TUNEL staining and microscopy to observe the morphological changes of ischemic neurons at six different time points including 6,12,24,48 and 72 h, using immunohistochemistry to observe the changes of caspase-3 and CAD protein in two groups (model group and interfere group). Results There was no significant difference between the two groups using HE staining and microscopy. While there was difference of TUNEL staining positive cells in all time points, except 6 h time point; Both the two groups reached the expression peak of caspase-3 in 24 h, and the number was 2. 360± 0. 318 and 0. 804 ± 0. 206 respectively(t' = 10. 039, P < 0. 01), there was statistical significance from 12 h to 48 h between the two groups ; The expression peak time of CAD protein in two groups was 48 h, and the number was 3.061 ± 0. 567 and 0. 812 ± 0. 240 respectively (t' = 8. 960, P < 0. 01), there was statistical significance from 12 to 72 h between two groups. Conclusions Caspase-3-CAD-DNA degradation is one important way of neuronal injury in cerebral ischemia-reperfusion of rats, caspase-3 inhibitor can protect neuron in a certain degree.
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Interleukin-17 (IL-17) is a newly discovered proinflammatory cytokine in recent years. It has wide biological activities; therefore it may be one of the important factors in the occurrence and development of certain diseases. The article mainly reviews the current situation of the study on the related roles of IL-17 in nervous system diseases.
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Aim To investigate the effects of cholecys-tokinin octapeptide(CCK-8)on the withdrawal symp-toms of morphinistic rats by the observation of praxiology,and change of expression of proto-oncogene c-jun in caudate nucleus(Cd) after CCK-8 injected by immunohistochemistry.Methods Animal praxiology evaluation and immunohistochemistry were used.The influence of CCK-8(10 mg?L-1,1 ?l) on the withdrawal symptoms and the expression of c-jun of morphinistic rats was observed.Results Morphinistic rats had obvious praxiological changes in the withdrawal symptoms compared with normal saline rats;the scores of withdrawal symptoms decreased most obviously at withdrawal 40 h after Cd injection of CCK-8;the expression of c-jun protein in Cd decreased in morphinistic rats,but increased after Cd injection of CCK-8.Conclusions Models of morphinomania rats were successfully built.The Cd injection of CCK-8 could decrease the withdrawal symptoms of morphinomania rats.The CCK-8 could increase the expression of c-jun protein in Cd.These findings suggested that CCK-8 could regulate the production of withdrawal symptoms and the expression of c-jun protein in Cd of morphinomania rats.
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Objective To investigate the association between the mutations in the ALOX5AP gene and ischemic stroke.Methods In 26 patients with acute cerebral infarction and 23 normal controls,the mononucleoside polymorphism(SNPs)in the ALOX5AP was analysised by the single strand conformation polymorphism analysis of polymerase chain reaction products(PCR-SSCP)and Sanger's dideoxy chain termination.Results The frequency of SG13S100(A/G)in the ALOX5AP gene in group of cerebrall infarction(18/26,69.2%)was significantly higher than that in normal controls(8/23,34.8%)(P
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Objective To explore the possible mechanism of over expression of P-glycoprotein(Pgp) in brain tissue and peripheral blood in refractory epileptic rats with amygdale kindled by electricity and kainic acid,and compare the expression tendency of Pgp in brain tissue and peripheral blood of the different ways to establish refractory epileptic rats models.Methods The models of refractory epileptic rats were made by electrical kindling and kainic kindling in amygdale.Group A was for amygdale-electrical-kindling rats(n=12),group B was for amygdale-kainic-kindling rats(n=12),group C was implanted electrode without kindling and Carbamazepine was given by gavage(n=8),group D was injected saline in amygdale and Carbamazepine was given by gavage(n=8),group E was implanted electrode without kindling and saline was given by gavage(n=8) and group F was injected saline in amygdale and saline was given by gavage(n=8).The expression of Pgp in brain tissue and peripheral blood was detected by immunohistochemistry in each group.Results The expression of Pgp in brain tissue and peripheral blood of rats in group A and B were both much higher than those in the other groups and there were statistical differences(all P