Objective:To explore the value of diffusion tensor imaging (DTI) in evaluating the effects of hyperbaric oxygen therapy (HOT) in treating spinal cord injury.Methods:The modified Allen′s method was used to induce a traumatic spinal cord injury in 30 rats who were then divided randomly into an injured group and a treatment group, each of 15. The treatment group was given HOT twice a day for 3 days, then once a day for a total of 4 weeks. The injured group did not receive HOT. DTI was performed (along with Basso-Beattie-Bresnahan (BBB) evaluation) at 0h, 6h, 24h, as well as 3, 7, 14, 21 and 28 days after the operation. Two-factor repeated measures ANOVA was conducted to analyze any differences in the DTI results: the fractional anisotropy, mean apparent diffusivity, radial diffusivity and axial diffusivity, as well as the BBB scores. LSD t-tests were performed to analyze the significance of the differences at different time points.Results:At each time point after 24h the average FA value of the treatment group was significantly higher than the injured group′s average, while its average MD and RD values were significantly lower. Beyond 14 days the average AD value of the treatment group was significantly higher than that of the injured group. The treatment group′s average BBB score was also significantly higher at all the time points beyond 3 days.Conclusions:DTI results can evaluate spinal cord function and provide valuable information for the dynamic assessment of hyperbaric oxygen therapy after a traumatic spinal cord injury, and the therapy promotes the recovery of motor function, at least in rats.

OBJECTIVE: To investigate the therapeutic mechanism of resveratrol (RES) for Alzheimer's disease (AD) in light of network pharmacology. METHODS: We searched PubChem, BATMAN-TCM, Genecards, AD, TTD, String 11.0, AlzData, SwissTargetPrediction, Metascape and other databases for the therapeutic targets of RES and human AD-related targets. The intersection was determined using Venny 2.1 to obtain the therapeutic targets of RES for AD. The protein-protein interaction (PPI) network was constructed, the gene ontology (GO) was enriched and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) were analyzed. Cytoscape 3.7.1 software was used to construct a target-signaling pathway network of RES in the treatment of AD. Molecular docking verification was carried out on SwissDock (http://www.swissdock.ch/docking). We examined a 293Tau cell model of AD for changes in protein levels of pS396, pS199, Tau5, CDK5, glycogen synthase kinase 3β (GSK3β) and p-GSK3β in response to RES treatment using Western blotting. RESULTS: We obtained 182 targets of RES, 525 targets related to AD, and 36 targets of RES for AD treatment, among which 34.6% of the targets were protein-modifying enzymes, 27.7% were metabolite invertase, 13.8% were gene-specific transcriptional regulators, and 10.3% were transporters. The core key targets of RES in the treatment of AD included INS, APP, ESR1, MMP9, IGF1R, CACNA1C, MAPT (microtubule- associated protein Tau), MMP2, TGFB1 and GSK3B. Enrichment analysis of GO biological process suggested that the biological function of RES in AD treatment mainly involved the response to β-amyloid protein, positive regulation of transferase activity, the transmembrane receptor protein tyrosine kinase signaling pathway, regulation of behavior, learning or memory, aging, and transmembrane transport. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathways were AD pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and MAPK signaling pathway. Molecular docking results showed that RES had strong binding with ESR1, GSK3B, MMP9, IGF1R, APP and INS. In the cell model of AD, treatment with 50 μmol/L RES for 12 h significantly reduced the levels of pS396 and pS199 by regulating CDK5 and GSK3β activity ( CONCLUSIONS RES produces therapeutic effects on AD by acting on multiple targets and affecting multiple signaling pathways and improves AD-associated pathologies
Alzheimer Disease/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Resveratrol/pharmacology*

Objective To explore the value of DTI quantitative parameters in evaluating neurological function changes of acute traumatic spinal cord injury (TSCI)in rat models.Methods The modified Allen's dropping weight technique was used to establish TSCI rat models.Then the rats were divided into mild injury group,moderate injury group and severe injury group (each n=10).DTI examination and Basso-Beattie-Bresnahan (BBB) score were performed pre-TSCI and 0 h,6 h,24 h,3 day,7 day and 14 day post-TSCI,respectively.The BBB scores and DTI parameters,including FA,mean apparent diffusivity (MD),radial diffusivity (RD) and axial diffusivity (AD) were measured and compared among groups.The correlation between BBB scores and the parameters was evaluated.Results The differences of FA,MD and RD value were statistically significant among varying injury degree groups and different time points after TSCI (all P＜0.05).AD value had statistical difference among different time points (F=12.720,P＜0.001),whereas no difference was found among varying injury degree groups (F=0.469,P=0.630).FA and MD values decreased while RD increased 0 h post-TSCI.Then RD and MD increased continuously,whereas FA decreased continuously until 24 h post TSCI (all P＜0.05),and the parameters kept stable after 24 h post-TSCI (all P＞ 0.05).The BBB scores were lowest on 0 h post-TSCI,then maintained increasing (all P＜0.05).In addition,the BBB scores and MD values had good correlation (r=0.958,P＜ 0.01).Conclusion DTI can quantitatively evaluate function changes of TSCI in rat models.Moreover,treatment within 24 h post-TSCI might be recommended for TSCI therapy.

Objective·To compare the clinical features between different subtype bipolar patients with first mania episode, and to contribute to early identification of bipolar disorder. Methods·This study was based on the database named as National Bipolar Mania Pathway Survey (BIPAS). From November 2012 to January 2013, bipolar patients from 26 mental health facilities in China were enrolled in current study. The clinical features were compared between mania patients of different subtypes, including hypomania (groupⅠ), mania without psychotic symptoms (groupⅡ), mania with psychotic symptoms (group Ⅲ) and mixed state (group Ⅳ). Results·There was significant difference in the percentage of clinical symptoms between different subtype bipolar patients with first mania episode, especially the mania and anxiety related symptoms. Group Ⅰ, Ⅲ , Ⅳ were further compared with groupⅡ, which was considered as the typical bipolar disorder. The results showed that the mania related symptoms was significantly higher in group Ⅱ, but anxiety related symptoms was significantly higher in group Ⅰ, Ⅲ, Ⅳ. Moreover, Logistic regression analysis revealed that more eloquent or humor and unusually restless could be in favor of the diagnosis of hypomania; younger and mania or hypomania as first episode might be in favor of the diagnosis of mania with psychotic symptoms; older, national minorities and unusually restless could be in favor of the diagnosis of mixed state. Conclusion·The clinical features between different subtype bipolar patients with first mania episode are various, and analysis of the clinical features can contribute to early identification of bipolar disorder.

Objective To observe the efifcacy and safety of ticagrelor in patients received percutaneous coronary intervention (PCI). Methods 50 patients with non-responding platelet aggregation rate and CYPC219 gene after clopidogrel treatment were given ticagrelor and enrolled in the study. All enrolled patients received aspirin loading dosage 300 mg, followed by maintenance dosage 100 mg, once daily and ticagrelor maintenance dosage 90 mg twice daily, for 1 year. The primary endpoint for the study were the incidence of major cardiovascular events (including death, stent thrombosis, stent restenosis, nonfatal myocardial infarction, target vessel revascularization) and stroke after followed up for a month. The secondary endpoint were the incidence of general events (including minor bleeding, allergies, breathing dififculties) and platelet count changes. Results No occur major cardiovascular and stroke events record after 1 month of ticagrelor treatment. The general events rates included 2 cases of dyspnen, 1 case of epitaxis and 1 case of subcutaneous bleeding. The platelet aggregation with ticagrelor was signiifcantly lower than clopidogrel without signiifcant decrease in platelets count. Conclusions Using ticagrelor for antiplatelet in patients with coronary artery stenting in clopidogrel resistance cases is safe and effective.

Gastric cancer (GC) is one of the most frequent malignant tumors. In order to systematically characterize the cellular and molecular mechanisms of intestinal GC development, in this study, we used 22 K oligonucleotide microarrays and bioinformatics analysis to evaluate the gene expression profiles of GC in 45 tissue samples, including 20 intestinal GC tissue samples,20 normal appearing tissues (NATs) adjacent to tumors and 5 noncancerous gastric mucosa tissue samples. These profiles allowed us to explore the transcriptional characteristics of GC and determine the change patterns in gene expression that may be of clinical significance. 1519 and 1255 differentially- expressed genes (DEGs) were identified in intestinal GC tissues and NATs, respectively, as determined by Bayesian analysis (P < 0.001). These genes were associated with diverse functions such as mucosa secretion, metabolism, proliferation, signaling and development, which occur at different stages of GC development.

OBJECTIVETo study the changes in diaphragmatic function and gene expressions of calcium regulatory proteins in diabetic rats and explore the mechanism of diaphragm dysfunction in diabetes mellitus.

METHODSSD rats were randomly divided into normal control group and diabetic (induced by intraperitoneal STZ injection) group. After 4 and 8 weeks, the body weight and diaphragm to body weight ratio were measured, and the activities of succinic dehydrogenase (SDH) in the diaphragm and blood glucose were assayed. The diaphragm contractility was assessed and the alterations of diaphragm ultrastructure were observed. RT-PCR was used to detect the changes in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLB) mRNA expressions in the diaphragm.

RESULTSThe diabetic rats showed a significant weight loss with a lowered diaphragm to body weight ratio (P<0.01) and SDH activity (P<0.01). The peak twitch tension and maximum tetanic tension of the diaphragm were significantly lowered and the time to peak contraction and half relaxation time significantly prolonged (P<0.01) in the diabetic rats, which also exhibited a lowered tetanic force in response to stimulus (P<0.01). Transmission electron microscopy revealed obvious ultrastructural changes of the diaphragm in diabetic rats. RT-PCR showed significantly decreased SERCA and increased PLB mRNA expressions in diabetic rat diaphragm (P<0.01), and these changes intensified with time (P<0.01).

CONCLUSIONDiabetes can cause impairment of diaphragmatic ultrastructure, mitochondrial injuries, and lowered SDH activity and ATP production. Decreased SERCA and increased PLB mRNA expressions in diabetes result in reduced Ca(2+) uptake by the diaphragm sarcoplasmic reticulum to induce diaphragm dysfunction.

Animals ; Body Weight ; Calcium ; metabolism ; Calcium-Binding Proteins ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; physiopathology ; Diaphragm ; metabolism ; physiopathology ; Glucose ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Sarcoplasmic Reticulum ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Succinate Dehydrogenase ; metabolism

OBJECTIVETo investigate the molecular mechanisms of diaphragm injury in rats with liver cirrhosis.

METHODSThirty adult male Sprague-Dawley rats were randomized into control group (n=10) and carbon tetrachloride-induced liver cirrhosis group (LC group, n=20). In the 9th week, the rat body weight and diaphragm to body weight ratio were measured, and the parameters of diaphragm contractility including peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT), and force-frequency curve were assessed using a Medlab-U/4C biological signal collecting system. The activities of superoxide dismutase (SOD), succinic dehydrogenase (SDH) and myeloperoxidase (MPO) and malondiadehyde (MDA) content in the diaphragm were detected. The mRNA expression levels of sarcoplasmic reticulum calcium ATPase (SERCA) and cytoskeletal proteins (titin and nebulin) in the diaphragm were detected by RT-PCR, and the diaphragm ultrastructure was examined with electron microscopy.

RESULTSCompared with those in the control group, body weight, diaphragm to body weight ratio, Pt, Po, and tetanic force under the stimulus frequency of 10, 20, 40, 60, 100 Hz were all significantly decreased (P<0.01), while CT and 1/2RT were significantly prolonged in LC group (P<0.01). SOD and SDH activities were significantly lowered (P<0.01) while the contents of MDA and MPO activity were significantly increased in LC group (P<0.01) with significantly decreased SERCA, titin and nebulin mRNA expressions in the diaphragm (P<0.01). Electron microscopy of the diaphragm in LC group revealed myofibrillar degeneration, absence of the Z line, and mitochondria swelling and edema.

CONCLUSIONLiver cirrhosis increases free radicals and aggravates inflammatory response and lipid peroxidation in the diaphragm, thus leading to mitochondrial damages and decreased expressions of cytoskeletal proteins and SERCA to cause diaphragmatic dysfunction.

Animals ; Body Weight ; Carbon Tetrachloride ; Connectin ; metabolism ; Diaphragm ; metabolism ; Lipid Peroxidation ; Liver ; enzymology ; pathology ; Liver Cirrhosis ; metabolism ; Male ; Muscle Contraction ; Muscle Proteins ; metabolism ; Oxidation-Reduction ; Rats ; Rats, Sprague-Dawley ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism

Objective To investigate the molecular mechanisms of diaphragm injury in rats with liver cirrhosis. Methods Thirty adult male Sprague-Dawley rats were randomized into control group (n=10) and carbon tetrachloride-induced liver cirrhosis group (LC group, n=20). In the 9th week, the rat body weight and diaphragm to body weight ratio were measured, and the parameters of diaphragm contractility including peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT), and force-frequency curve were assessed using a Medlab-U/4C biological signal collecting system. The activities of superoxide dismutase (SOD), succinic dehydrogenase (SDH) and myeloperoxidase (MPO) and malondiadehyde (MDA) content in the diaphragm were detected. The mRNA expression levels of sarcoplasmic reticulum calcium ATPase (SERCA) and cytoskeletal proteins (titin and nebulin) in the diaphragm were detected by RT-PCR, and the diaphragm ultrastructure was examined with electron microscopy. Results Compared with those in the control group, body weight, diaphragm to body weight ratio, Pt, Po, and tetanic force under the stimulus frequency of 10, 20, 40, 60, 100 Hz were all significantly decreased (P<0.01), while CT and 1/2RT were significantly prolonged in LC group (P<0.01). SOD and SDH activities were significantly lowered (P<0.01) while the contents of MDA and MPO activity were significantly increased in LC group (P<0.01) with significantly decreased SERCA, titin and nebulin mRNA expressions in the diaphragm (P<0.01). Electron microscopy of the diaphragm in LC group revealed myofibrillar degeneration, absence of the Z line, and mitochondria swelling and edema. Conclusions Liver cirrhosis increases free radicals and aggravates inflammatory response and lipid peroxidation in the diaphragm, thus leading to mitochondrial damages and decreased expressions of cytoskeletal proteins and SERCA to cause diaphragmatic dysfunction.

Objective To investigate the molecular mechanisms of diaphragm injury in rats with liver cirrhosis. Methods Thirty adult male Sprague-Dawley rats were randomized into control group (n=10) and carbon tetrachloride-induced liver cirrhosis group (LC group, n=20). In the 9th week, the rat body weight and diaphragm to body weight ratio were measured, and the parameters of diaphragm contractility including peak twitch tension (Pt), maximum tetanic tension (Po), time to peak contraction (CT), half relaxation time (1/2RT), and force-frequency curve were assessed using a Medlab-U/4C biological signal collecting system. The activities of superoxide dismutase (SOD), succinic dehydrogenase (SDH) and myeloperoxidase (MPO) and malondiadehyde (MDA) content in the diaphragm were detected. The mRNA expression levels of sarcoplasmic reticulum calcium ATPase (SERCA) and cytoskeletal proteins (titin and nebulin) in the diaphragm were detected by RT-PCR, and the diaphragm ultrastructure was examined with electron microscopy. Results Compared with those in the control group, body weight, diaphragm to body weight ratio, Pt, Po, and tetanic force under the stimulus frequency of 10, 20, 40, 60, 100 Hz were all significantly decreased (P<0.01), while CT and 1/2RT were significantly prolonged in LC group (P<0.01). SOD and SDH activities were significantly lowered (P<0.01) while the contents of MDA and MPO activity were significantly increased in LC group (P<0.01) with significantly decreased SERCA, titin and nebulin mRNA expressions in the diaphragm (P<0.01). Electron microscopy of the diaphragm in LC group revealed myofibrillar degeneration, absence of the Z line, and mitochondria swelling and edema. Conclusions Liver cirrhosis increases free radicals and aggravates inflammatory response and lipid peroxidation in the diaphragm, thus leading to mitochondrial damages and decreased expressions of cytoskeletal proteins and SERCA to cause diaphragmatic dysfunction.