Objective To study the pathological alterations,such as oxidative stress,cell proliferation and insulin resistance,especially autophagy,in Alzheimer' s disease (AD) complicated with type 2 diabetes (AD + T2DM).Methods The mouse models of T2DM,AD and AD + T2DM were used in the study,and totally 80 mice were divided into four groups:control group,T2DM group,AD group and AD + T2DM group.Morris water maze was applied to test the ability of learning and memory among the above mentioned groups.In the meantime,insulin resistance index,the expression of insulin receptor substrate 2,oxidative stress,cell proliferation and autophagy were observed with chemical analysis,immunofluorescent labeling,transmission electron microscopy and Western blotting.Results On day 4,the difference of time to find Morris water maze in control group,T2DM group,AD group and AD + T2DM group ((26.08 ±4.93) s,(38.46 ± 4.07) s,(47.32 ± 5.86) s,(53.01 ± 6.12) s,F =2.454,P =0.025) was statistically significant,and the time in AD + T2DM group was longer than that in AD group (t =-3.624,P =0.033).Compared with control group,insulin resistance occurred in T2DM group,AD group and AD + T2DM group (4.35 ± 0.48,16.12 ± 3.57,7.03 ± 3.11,18.78 ± 5.06,F =5.602,P =0.009),and the reduction of insulin receptor substrate 2 expression,the oxidative stress reaction,neural proliferative suppression and autophagy (F =418.344,222.514,436.250,113.934,23.772,35.469,all P ＜ 0.05) were induced in T2DM group,AD group and AD + T2DM group,which were more serious in AD + T2DM group than in AD group (t =-2.796,21.723,-8.041,9.037,-4.403,-32.011,-26.593,all P ＜0.05).Conclusion AD + T2DM mice suffered more serious cognitive impairment than AD and T2DM mice.The oxidative stress levels of AD + T2DM mice were upregulated,and thus led to the inhibition of cell proliferation,eventually leading to promotion of autophagy.

Objective To investigate the incidence of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) in Chengdu City in 2010 and summarize clinical characteristics of GEP-NEN.Methods The incidence of GEP-NEN was estimated with the data in 2010 from the databases of West China Hospital and Chengdu Health Information Centre.Results A total of 77 cases of GEP-NEN were diagnosed in West China Hospital in 2010.Ten cases from other hospitals or non-Chengdu citizenship were excluded,so a total of 67 cases were included in this study.In 2010,the incidence of GEP-NEN was 1.86/105 in Chengdu City.Among 67 GEP-NEN cases,most lesions were located in pancreas and rectum (38 cases,56.7％),followed by stomach (10 cases),esophagus (seven cases) and duodenum (four cases).Among 57 GEP-NEN cases which had pathotogial grading,26 cases (45.6 ％) had neuroendocrine carcinomas or mixed adenoneuroendocrine carcinomas when diagnosed.Conclusions In 2010,the incidence of GEP-NEN in Chengdu City is similar to the reports from other countries.Pancreas,rectum and upper gastrointestinal tract are predilection sites of GEP-NEN.The diagnosis rate of early GEP NEN needs to be raised.

Objective To investigate the effects of different dialysates on expression of protein kinase C-δ (PKCδ) and apoptosis of U937 cell line. Methods Different dialysates were added into culture fluid with U937 cell line at exponential phase of growth, and groups were divided: fluid A+fluid B group (dialysate A+dialysate B), fluid A+fluid B+rottlerin (PKCδ specific inhibitor)group, fluid A+powder B group (dialysate A+powder B) and fluid A+powder B + rottlerin group. Besides, blank control group and normal control group were established. Cells were harvested 24 h and 48 h after treatment, morphological changes were observed by Hoechst33258 fluorescence staining, cell apoptosis was measured by Annexin-V-FITC/PI double staining, and expression of PKCδ mRNA and protein was detected by RT-PCR and Western blotting, respectively. Results Cell apoptosis significantly increased in fluid A+powder B group, with typical morphology of apoptosis. After treatment for 24 h and 48 h, cell apoptosis rates in fluid A+powder B group were significantly higher than those at corresponding time points in blank control group , normal control group and fluid A+powder B+rottlerin group (P<0.05). Compared with normal control group, blank control group and fluid A+powder B+rottlerin group, the expression of PKCδ mRNA and protein of U937 cells in fluid A+powder B group were significantly increased (P<0.05). There was no significant difference in cell apoptosis rates and expression of PKCδ mRNA and protein between fluid A+fluid B group and blank control group, normal control group and fluid A+fluid B+rottlerin group (P＞0.05). Conclusion Fluid A+powder B can significantly increase apoptosis of U937 cell line, the mechanism of which may be associated with the up-regulation of expression of PKCδ. Compared with fluid A+powder B, fluid A+fluid B is superior in reducing apoptosis of peripheral blood monouclear cells.

Objective ToinvestigatethefeasibilityofassessingliverfunctiongradingbyIDEAL-IQsequenceon1.5T MR.Methods The patientswhowereclinicallydiagnosedaslivecirrhosisandunderwent1.5T MRIDEAL-IQsequenceinourhospitalfrom February 2016toDecember2017wereanalyzedretrospectively.TheyweredividedintoA,BandCgradesaccordingtotheChild-Pughgrading standardofliverfunction.Finally,therewere30patientsinChild-PughA,25patientsinChild-PughBand16patientsinChild-Pugh C.ThefatratiomapsandR2?relaxationratemapswereusedtomeasuretheliverfatcontentandironcontentbythetwoobservers onAW4.6workstation,respectively.ThemeanvaluesofthefatfractionsandtheR2?valuesweremeasuredandcomparedbyusing K ruskal-W allis H testamongthethreegroups.Then,thegroupAandBwerecombinedtoestablishthepredictivemodelindiagnosingthegroup Cbyusingthe L o g istic regressionanalysis,whichcombinedthefatfractionandR2?value.TheROCcurvewasdrawntoobtainedtheAUC,and calculatedthesensitivityandthespecificitywiththeoptimalthreshold.Results Thereweregoodconsistencyofmeasurementdata betweenthetwoobserves(ICC>0.8).ThefatfractionandR2?valueincreasedwiththedecreaseoftheliverfunction.Thefatfractionsofthe Child-PughA,BandCgroupwere(3.58±0.91)%,(3.64±1.20)%,(6.87±3.91)%,respectively.TheR2?valuesoftheChild-Pugh A,BandCgroupswere(33.31±11.80)Hz,(38.00±13.31)Hz,(58.98±44.54)Hz,respectively.TheAUCofwhichcombinedfat fractionandR2?valuediagnosingChild-PughCwas0.843.Thesensitivityandthespecificitywere81.8% and81.3%,respectively. Conclusion The1.5T MRIDEAL-IQsequencecanbeusedtoevaluatetheliverreserveunctionoflivercirrhosispatientsaccording ffatfractionandR2?value,especiallyfortheChild-PughCcirrhosis patientswithhighsensitivityandspecificity.

Objective To establish the method of predicting the vertical ground reaction force (vGRF) during treadmill running based on principal component analysis and wavelet neural network (PCA-WNN). Methods Nine rearfoot strikers were selected and participated in running experiment on an instrumented treadmill at the speed of 12, 14 and 16 km/h. The kinematics data and vGRF were collected using infrared motion capture system and dynamometer treadmill. A three-layer neural network framework was constructed, in which the activation function of the hidden layers was the Morlet function. Velocities of mass center of the thigh, shank and foot as well as joint angles of the hip, knee and ankle were input into the WNN model. The prediction accuracy of the model was evaluated by the coefficient of multiple correlation (CMC) and error. The consistencies between predicted and measured peak GRF were analyzed by Bland-Altman method. Results The CMC between the predicted and measured GRF at different speeds were all greater than 0.99; the root mean square error (RMSE) between the predicted and measured vGRF was 0.18-0.28 BW; and the normalized root mean square error (NRMSE) was 6.20%-8.42%; the NRMSE between the predicted and measured impact forces and propulsive forces were all smaller than 15%. Bland-Altman results showed that the predicted peak errors of propulsive force at 12 km/h and that of impact force and propulsive force at 14 km/h were within the 95% agreement interval. Conclusions The PCA-WNN model constructed in this study can accurately predict the vGRF during treadmill running. The results provide a new method to obtain kinetic data and perform real-time monitoring on a treadmill, which is of great significance for studying running injuries and rehabilitation treatment.

Objective Tostudy the influence of pipe structures on the mixing uniformity of airborne effluents from nuclear power plant chimneys. Methods We used the computational fluid dynamics (CFD) method to simulate the velocity distribution and gas mixing in long straight pipes (I type) with square section and circular section, 90° single-bend pipes (L type) with square section and circular section, and 90° double-bend pipes (S type and U type) with square section and circular section. Results For the long straight pipe, due to the lack of flow disturbance caused by structural changes, the mixing effect was not good; when the pipe section was circular, it might take mixing distance 20 times the hydraulic diameter to achieve the uniformity index required by the relevant standard; for the square pipe, the distance might be longer. In the single bend pipe with square section, the velocity uniformity was improved more greatly after the bend, and the tracer gas met the mixing uniformity at a shorter distance (11 times the hydraulic diameter), as compared with the single bend pipe with circular section. For the S-type double-bend pipe, the tracer gas appeared uniformly mixed after a distance 6 times the hydraulic diameter in the square pipe, and 7 times the hydraulic diameter in the circular pipe. For the U-type double-bend pipe, the gas in the square pipe also achieved uniform mixing ata shorter distance downstream, and the airflow showed greater disturbance when passing through the bend. Conclusion The CFD method can make an accurate prediction for the change patterns of gas mixing uniformity in pipes with different structures, and can partially replace physical experiments to study the factors affecting the mixing uniformity of airborne effluents from the chimney of nuclear power plants.

Objective : Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis (KOA) , this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression . Methods : The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected , and the percentage of M1 macrophages (CD80 , CD86) and M2 macrophages (CD163 , CD206) in the synovial fluid (M1 /M2 ratio) was measured to e- valuate the polarization of macrophage cytokines such as IL-1 , IL-6 , IL-10 , and tumor necrosis factor (TNF) -α, transforming growth factor ( TGF)-βExpression in KOA synovial fluid , and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K , AKT3 , mTORC1 , and inducible nitric oxide synthase ( iONS) in KOA synovial fluid . Results : Compared with the synovial fluid of normal individuals , the percentage of M1 macrophages (CD80 , CD86) in KOA patients increased (P < 0. 01) , and the M1 /M2 ratio increased ( P < 0. 001) ; The ex- pression of IL-1 , IL-6 , and TNF-αin the synovial fluid of the KOA group was also higher than that of the control group (P < 0. 01) , while the expression of IL-10 and TGF-βin the KOA group was significantly reduced ( P < 0. 01) ; The key proteins PI3K , AKT3 , mTORC1 , and downstream inflammatory factor iONS in the PI3K/AKT/ mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group (P < 0. 01) . Conclusion In KOA synovial fluid , M1 macrophage polarization plays a dominant role , and the inflam- matory response mediated by M1 macrophage polarization may be the cause of synovitis . At the same time , the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammato- ry response .

ObjectiveTo construct a cough model induced by chemical stimuli by whole-body plethysmography （WBP） for counting coughs based on cough waveforms， and use this model to explore the antitussive effect of GK-A. MethodDifferent chemical stimuli were used to induce coughs in mice or guinea pigs. Respiratory waveforms were monitored by WBP， and the recognizable and typical cough waveforms were selected for cough counting. Guinea pigs were induced to cough with different concentrations of citric acid or capsaicin， and cough waveforms were used to optimize the stimulation conditions. The optimized guinea pig model of cough was validated with dextromethorphan， and the optimized guinea pig model of capsaicin-induced cough was used to evaluate the antitussive effect of GK-A. ResultWBP could count the coughs induced by capsaicin and citric acid in guinea pigs by recognizable and typical respiratory waveforms. The optimized stimulation conditions were capsaicin concentration of 100 µmol·L^-1 and nebulization for 2 min. The validation results showed that compared with the model group， the dextromethorphan group of guinea pigs had reduced coughs （P<0.05） and prolonged cough latency （P<0.01）. GK-A prolonged the cough latency （P<0.05） and reduced coughs （P<0.05） in the mouse model of ammonia-induced cough. In the guinea pig model of capsaicin-induced cough， GK-A prolonged cough latency （P<0.05）， reduced coughs （P<0.05）， and decreased substance P （SP） content in the guinea pig serum （P<0.05， P<0.01）. ConclusionA guinea pig model of capsaicin-induced cough was successfully established based on cough waveform counting， which provided an objective and accurate cough counting method. GK-A has antitussive effects， possibly by inhibiting the neuropeptide SP.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.