PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats / 药物分析学报

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

The influence of anxiety and depression on meaning in life in college students: the mediating role of boredom tendency / 中华行为医学与脑科学杂志

Objective:To explore the mediating role of boredom tendency in anxiety, depression and meaning in life in college students.Methods:Totally 590 college students in Shijiazhuang were selected to carry out a questionnaire survey, including general questionnaire, boredom proneness questionnaire (BPQ), meaning in life questionnaire (MLQ), patient health questionnaire (PHQ-9) and general anxiety disorder-7(GAD-7). Spearman correlation analysis and hierarchical regression analysis were conducted to analyze the data by using SPSS 20.0, and Amos 24.0 was used to analyze the mediating effect of boredom tendency on anxiety, depression and sense of life meaning in college students.Results:Correlation analysis found that the total score of boredom tendency was negatively correlated with meaning in life ( r=-0.260, P<0.05) and education ( r=-0.110, P<0.05). The total score of boredom tendency was positively correlated with depression ( r=0.649, P<0.05) and anxiety ( r=0.555, P<0.05). The mediating effect model fit well(χ 2/ df=0.582, GFI=1.000, AGFI=0.994, RMSEA=0.000). Boredom tendency played a partial mediating role between anxiety meaning in life(standard effect size=-0.054), a complete mediating role between depression and meaning in life(standard effect size=-0.175), and a complete mediating role between educational background and meaning in life(standard effect size=0.025). Conclusion:Boredom tendency plays a mediating role in the model between related factors and meaning in life, and attentions should be paid to the psychological development of college students.

Clinical analysis of 249 cases of children with foreign bodies in the nasal cavity and paranasal sinus / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#Insertion of a foreign body in the nasal cavity is a very common incident in children. It is easily diagnosed, but the type of foreign body varies and the extraction can sometimes be difficult with risk of complications. The present study reported nasal foreign bodies diagnosed in emergency in our ENT department, with an update on the state of knowledge.@*METHOD@#A prospective study between Feb 2013 to Sept 2015 included patients admitted to the ENT emergency unit for nasal foreign body. Data comprised age, gender, circumstances of discovery, symptoms, type of foreign body, extraction method and complications. Many patients required anterior rhinoscope for the diagnosis and removal (179/249, 71. 9%), and 170 cases were directly removed and 9 cases were into alimentary canal; Most irregularly shaped objects were removed by a endoscope under general anesthesia (70/249, 28.1%), including button batteries (n= 65), nasal calculi (n = 2) and chopsticks (n = 3).@*RESULT@#The main types of foreign body were vegetal forms (61.8%). The incident was discovered following nasal symptoms in 24.9% (n = 62). Extraction was easy by using forceps, micro-hooks or suction in 71.9% of qn:Nasal sinuses foreign body on prevention, detailed history and make the necessary inspection, can improve the correct diagnostic rate.

Clinical application evaluation of thrombus aspiration on emergency percutaneous coronary intervention of patients with ST-segment elevation type of myocardial infarction / 中国综合临床

Objective To investigate the influence of thrombus aspiration on ventricular remodeling of patients with ST?segment elevation type of myocardial infarction ( STEMI ) who underwent emergency percutaneous coronary intervention ( PCI) and its predicative value for patients′ prognosis. Methods Three hundred and eight patients who were diagnosed with STEMI line emergency PCI and hospitalized in the Cardiology Department of Jinghai Clinical College of Medical University of Tianjin from March 2011 to March 2014 were retrospective analyzed, including 152 patients received thrombus aspiration during primary PCI as thrombus aspiration group,and the remaining 156 patients without thrombus aspiration as control group. Indexes of myocardial perfusion levels such as ST?segment resolution 2 hours after PCI and TIMI myocardial perfusion grade were measured in all patients. All patients accepted echocardiography examinations to detect left ventricular end diastolic diameter(LVED) and left ventricular ejection fraction(LVEF) 10 days after PCI. The indexes differences of the two groups,secondary end points major cardiac adverse events(MACE) at 6 months were compared. Results There was no statistical difference between the ratio of two groups for ST segment fell more than 50%( 78. 9%( 120/152) vs. 71. 2%( 111/156) ,χ2=0. 428,P=0. 669) . But for ST segment fell more than 70%,the ratio of the thrombus aspiration group was significantly higher than that in the control group ( 73. 7%( 112/152 ) vs. 47. 4% ( 74/156 ) , χ2 = 4. 701, P = 0. 001 ) . Two groups of patients were treated by echocardiography 10 days after PCI,showed the LVED in the thrombus aspiration group was lower than that in the control group((50. 2±4. 7) mm vs. (51. 6±4. 6) mm,t=2. 642,P=0. 008),while the LVEF value was higher than that in the control group((56. 9±4. 9)% vs. (49. 4±4. 2)%,t=14. 434,P=0. 001). Recurrent angina pectoris decreased significantly in the thrombus aspiration group at 6 months ( 4. 61% ( 7/152 ) vs. 10. 90%(17/156),χ2=2. 056,P=0. 040). Conclusion STEMI patients adopt thrombus aspiration that undergoing emergency PCI,not only can improve myocardial reperfusion,especially microcirculation reperfusion, but also can improve the left ventricular systolic function and the prognosis of patients.

Expression and significance of NLRP3 inflammasome and its downstream factors IL-1β/IL-18 in rat model of allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To detect the expression and explore the role of the innate immune NLRP3 inflammasome and its downstream factors interleukin-1β (IL-1β)/ interleukin-18 (IL-18) in rat model of allergic rhinitis (AR).</p><p><b>METHODS</b>Forty Sprague Dawley (SD) rats were randomly divided into control group (A group), AR model group 1 (B group), AR model group 2(C group), AR model group 3 (D group). Every group contained 10 rats. After the rats in the model group were sensitized by ovalbumin (OVA) and alum, B, C and D groups were separately stimulated with 5% OVA for 10 days, 20 days and 30 days (once a day). The control group did not add OVA in the process of sensitization and excitation. All rats were executed after excitation.Eosinophil granulocyte (EOS) infiltration were observed in nasal mucosa by hematoxylin-eosin (HE) staining, the expression of NLRP3 and cysteinyl aspartate-specific protease-1 (Caspase-1) were observed in nasal mucosa by immunohistochemical staining. The concentrations of ovalbumin specific IgE (OVA-sIgE), IL-18 and IL-1β in peripheral blood and the concentrations of IL-18 and IL-1β in nasal fluid were tested by enzyme-linked immunosorbent assay (ELISA). The data were processed by SPSS 17.0 software.</p><p><b>RESULTS</b>EOS cell counted, the behavioral score and the concentrations of OVA-sIgE in AR model group were obviously higher than those in control group (P < 0.05), and the difference of which had statistical significance between the AR model groups (P < 0.05). The expression of NLRP3 in AR model group (The expression of NLRP3 in group of B, C and D were 48.80 ± 10.75, 71.80 ± 16.98 and 100.32 ± 13.91, respectively) were obviously higher than those in control group (17.47 ± 5.59), the difference of which had statistical significance (F = 78.399, P < 0.05). The expression of Caspase-1 in AR model group (The expression of Caspase-1 in group of B, C and D were 36.33 ± 4.71, 50.87 ± 11.18 and 73.10 ± 14.77, respectively) were obviously higher than those in control group (11.48 ± 2.70), the difference of which had statistical significance (F = 71.727, P < 0.05). The concentrations of IL-1β in AR model group [The concentrations of IL-1β in group of B, C and D were (56.46 ± 10.13), (82.37 ± 11.93), (112.01 ± 22.91) pg/ml, respectively] were obviously higher than those in control group [(38.26 ± 4.66) pg/ml], the difference of which had statistical significance (F = 51.981, P < 0.05). The concentrations of IL-18 in AR model group [The concentrations of IL-18 in group of B, C and D were (177.92 ± 23.63), (194.33 ± 20.78), (234.06 ± 31.70) pg/ml, respectively] were obviously higher than those in control group [(89.71 ± 5.56) pg/ml], the difference of which had statistical significance (F = 73.295, P < 0.05). And the difference of which had statistical significance between the AR model groups (P < 0.05). The expression of NLRP3 was significantly positively correlated with the behavioral score, the concentrations of OVA-sIgE and EOS cell counted in rat model of allergic rhinitis (r value were 0.833,0.873 and 0.868, respectively, all P < 0.01).</p><p><b>CONCLUSION</b>NLRP3 inflammasome and its downstream factors IL-1β/IL-18 play a role in the pathogenesis of allergic rhinitis, which may be correlated with the degree of inflammation.</p>

Clinical analysis of 12 cases of nasal surgery in patients with coronary heart disease after accepted PCI / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the perioperative treatments of endoscopic sinus surgery for nasal diseases in patients with coronary heart disease after PCI.@*METHOD@#Clinical data of 12 cases of endoscopie-assised surgery such as nasal tumors resection,functional sinus surgery,correction of deviated nasal septum,low-temperature plasma hemostasis in patients with coronary heart disease after PCI were analyzed retrospectively.@*RESULT@#Serious bleeding did not take place with the 12 cases during surgery, and surgery progressed smoothly; one of patients had heavy nosebleed after surgery, however her condition was stable when received active treatment. Follow-up 3 months to 2 years, nasal diseases of 12 patients recovered well and symptoms were relieved; cardiovascular events such as hemorrhage, thrombosis and so on did not occur.@*CONCLUSION@#Due to physiological function of the heart dysfunction in patients with coronary heart disease after PCI,they often accompany a number of trouble issues such as medical disorders, oral antiplatelet drugs, surgery affordability loss and increase surgical risk. Correct and effective perioperative treatments, strictly surgical indications are really necessary which can keep patients safe through perioperative period.

Relationship between cytomegalovirus infection and heart rate variability in elderly patients with atherosclerosis / 中华老年医学杂志

Objective To investigate the correlation between cytomegalovirus infection and heart rate variability (HRV) in elderly patients with atherosclerosis.Methods 160 patients with coronary heart disease who met World Health Organization diagnostic criteria for coronary heart disease in 1979 were collected.According to the IMTHCMV PP65 antigen test results,patients were divided into positive group (observation group,n=103) and negative group (control group,n=57).We detected the levels of of HRV,metalloprotease-9 (MMP 9) and tumor necrosis factor α (TNF-α) in the two groups in order to access the plaque stability.Results The all sinus standard deviation of RR interval (SDNN),standard deviation of the average NN interval (SDANNI),mean value of sinus standard deviation of RR interval (SDNNI) were lower in observation group than in control group (P ＜0.05).There were no significant differences in square root of the mean squared differences of successive NN intervals (RMSSD) level and percentage of differences exceeding 50ms between adjacent normal number of intervals (PNN50) between the two groups (P＞0.05).The levels of total cholesterol and low density lipoprotein were higher and the levels of MMP 9 AND TNF α were lower in observation group than in the control group (all P＜0.05).Compared with control group,the plaque stability was decreased in observation group [20.4％ (21/103) vs.61.4％ (35/57),x2=4.273,P=0.015].Conclusions Patients with atherosclerosis combined with cytomegalovirus infection have a greater heart rate variability and poorer plaque stability.

Expression and their significance of Jab1 p27kip1 in laryngeal squamous cell carcinoma and Hep-2 cells / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To discuss the expression and the significance of Jab1 p27kip1 in laryngeal squamous cell carcinoma and Hep-2 cells.@*METHOD@#Immunohistochemical method was used to examine the expressions of Jab1 and p27kip1 proteins in 50 cases laryngeal squamous cell carcinomas and 10 cases normal laryngeal tissues adjacent to laryngeal squamous cell carcinoma. Hep-2 cells were transfected with synthetic Jab1 siRNA by Lipofectamine 2000. RT-PCR method was adopted to examine the mRNA expression of the Jab1 and p27kip1 gene in Hep-2 cells which was treated with Jab1 siRNA II.@*RESULT@#Clearly brown staining restricted to nucleus was considered as positive expression of Jab1 and p27kip1 protein. The expression rate of Jab1 protein in laryngeal squamous cell carcinoma was significantly higher than that of normal laryngeal mucosa, and the expression rate of protein p27kip1 in laryngeal squamous cell carcinoma was significantly lower than that of normal laryngeal mucosa. There was a negative relationship between Jab1 and p27kip1 protein in laryngeal squamous cell carcinoma. The expression of Jab1 mRNA was suppressed markedly after transfected by Jab1 siRNA II. As the reaction time increased, the expression of Jab1 mRNA of Hep-2 cells decreased significantly, and the expression of p27kip1 mRNA remained unchanged.@*CONCLUSION@#The expression rate of Jab1 protein in laryngeal squamous cell carcinoma is significantly higher than that of normal laryngeal mucosa. There is a negative relationship between Jab1 and p27kiPl protein in laryngeal squamous cell carcinoma. After transfected by Jab1 siRNA II in the Hep-2 cells, the expression of Jab1 mRNA is suppressed markedly. Jab1 siRNA would be a good methodology for the further study.

Protective effect of high expression of glutathione peroxidase on cell model of Alzheimer disease / 中华老年医学杂志

Objective To study the effects of eliminating free radical and increasing antioxidative capacity of glutathione peroxidase 1(GPX1) on PC12 cells. MethodsGPX1 recombinant plasmid and Plncxplasmid were transfected into PC12 cells and PC12 cells highly-expressing GPX1 stably were sieved by G418 solution. PC12 ceils were treated with different concentrations of amyloid β-protein (Aβ25-35) for 48 h, to decide the optimal concentration of Aβ25-35 and construct ideal cell model. GPX1/pLNCX/PC12 group, pLNCX/ PC12 group and PC12 group were treated with optimal concentration of Aβ25-35 ,respectively for 48 h, and their absorbance (A) value by MTT conversion was compared among three groups.ResultsCell clone highly expressing GPX1 stably were obtained by G418 selection. The increment of cell inhibition ratio was 24.7 ％ after 20 μmol/L Aβ25-35 treatment for 48 h, compared with control group (P＜0.01). Thus the optimization concentration of Aβ25-35 was 20 μmol/L. After treatment with 20 μmol/L for 48 h, the A value was significantly higher in GPX1/pLNCX/PC12 group than in pLNCX/ PC12 group and in PC12 cells group(0.53±0. 02 vs. 0.44±0.02;0.53±0.02 vs. 0.39±0.07, P＜0.01). Conclusions Transfection of GPX1 recombinant plasmid may protect cell against injury from free radical and reverse the decrease of PC12 cell survival rate impaired by Aβ25-35.

Transplantation of corneal stem cells cultured on amniotic membrane for corneal burn: experimental and clinical study / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the proliferation and differentiation of cultured corneal stem cells and determine the effect of corneal stem cells cultured on amniotic membranes on the limbal area for treating corneal burns.</p><p><b>METHODS</b>The proliferation and differentiation of corneal stem cells in vitro had been examined using colony-forming efficiency and immunohistochemistry. The stem cells had been cultured on amniotic membranes and transplanted to the limbal area for treating corneal burns.</p><p><b>RESULTS</b>Corneal stem cells had a high proliferation capacity in primary and first passage, cytokeratin 3 was not expressed in primary culture but partly in first passage. The stem cells could proliferate to form cell layer on an amniotic membrane. When transplanted, stem cells could survive on limbus. After transplantation, ocular inflammation resolved, the cornea re-epithelialized, the stromal opacity reduced, the superficial neovascularity was lessened and the conjunctival fornix re-established.</p><p><b>CONCLUSIONS</b>Ocular surface conditions could be improved by allograft of corneal stem cells cultured on amniotic membranes.</p>