Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

AIM:To investigate the effects of Shaoyao-Gancao decoction(SGD)on inflammation and mucosal barrier damage in rats with 2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced inflammatory bowel disease(IBD).METHODS:Forty-eight male SD rats were randomly divided into normal group,model group,high-dose(500 mg/kg),medium-dose(250 mg/kg)and low-dose(125 mg/kg)SGD groups,and balsalazide sodium(1 g/kg)group.All rats were pre-administered for 3 d,and on the 4th day of the experiment,they were fasted for 24 h.Except for the normal group,the rats in the other 5 groups were given enema mixed with TNBS(100 mg/kg)and 50％ethanol,and continued to be adminis-tered for 5 d after modeling.After modeling,the disease activity index(DAI)was evaluated.After the experiment,the levels of nitric oxide(NO)and myeloperoxidase(MPO)in serum and colonic tissues of rats were determined.RT-qPCR and Western blot were used to determine tumor necrosis factor-α(TNF-α),cyclooxygenase-2(COX-2),inducible nitric oxide synthase(iNOS)and nuclear factor-κB(NF-κB)in the colon of rats.The expression of tight junction proteins zonu-la occludens-1(ZO-1)and claudin 2 in rat colon tissues was determined by immunofluorescence staining.RESULTS:Compared with normal group,the weight of rats in model group was decreased,the colon was shortened,DAI and colon tissue macroscopic scores were significantly increased(P<0.05),colon pathological injury was serious,and NO and MPO levels in serum and colon tissues of the rats in model group were significantly increased(P<0.05).The mRNA and pro-tein expression levels of TNF-α,COX-2,iNOS and NF-κB in colon tissues were significantly increased(P<0.01),while the expression levels of ZO-1 and claudin 2 were significantly decreased(P<0.01).Compared with model group,the body weight and colon shortening of rats in SGD groups were alleviated,DAI and macroscopic scores of colon tissues were significantly decreased(P<0.05),the pathological damage of colon was improved,and the levels of NO and MPO in se-rum and colon tissues of rats were significantly decreased(P<0.05).The mRNA and protein expression levels of TNF-α,COX-2,iNOS and NF-κB in colon tissues were significantly decreased(P<0.05),while the expression levels of ZO-1 and claudin 2 were significantly increased(P<0.05).CONCLUSION:Treatment with SGD effectively attenuates the inflam-matory response and intestinal mucosal barrier damage caused by TNBS-induced IBD in rats.

Objective:To investigate the protective effect of quercetin(QUE)on acute lung injury(ALI)rats with sepsis.Methods:Sixty male SD rats were randomly divided into 6 groups(n=10):Sham operation group(Sham),model group(CLP),QUE 25 mg/kg group,QUE 50 mg/kg group,QUE 100 mg/kg group and positive drug dexamethasone(DEX)group.Rats in each group were continuously treated for 7 days,and the survival rate was calculated;HE staining and lung wet-to-dry weight ratio(W/D)were used to evaluate the severity of lung injury;TUNEL staining was used to detect lung tissue apoptosis;levels of inflammatory factors,SOD and MDA were detected by the kits;Western blot was used to detect expressions of apoptosis-related proteins and phosphoryla-tion levels of PTEN,β-catenin,protein kinase B(AKT)and glycogen synthase kinase-3β(GSK-3β)in rat lung tissue.Results:Com-pared with CLP group,after QUE 50 mg/kg and 100 mg/kg treatment,survival rate of rats was significantly increased(P<0.05),the degree of inflammatory cell infiltration in lung tissue was reduced,lung injury score and W/D were reduced(P<0.05),apoptosis rate of lung tissue cells and expressions of apoptosis-related proteins were significantly decreased(P<0.05),levels of inflammatory factors were decreased(P<0.05),while the antioxidant capacity was enhanced(P<0.05),phosphorylation levels of PTEN and β-catenin were decreased,while phosphorylation levels of AKT and GSK-3β were increased(P<0.05).Conclusion:QUE protects rats from ALI with sepsis by inhibiting apoptosis,reducing inflammation and antioxidance,which mechanism may be related to PTEN/β-catenin and AKT/GSK-3β pathways.

Objective:To prepare nanoprobes by using polydopamine (PDA) as a carrier which is modified with the sonosensitizer protoporphyrin Ⅸ (PpⅨ) and labeled with 131I, 99Tc m or 177Lu, and to explore the value of these new nanoprobes in diagnosis and combination therapy of breast cancer. Methods:PDA particles were synthesized by aqueous oxidation, and a layer of polyethylene glycol (PEG) and PpⅨ were modified on the surface to product PDA-PEG-PpⅨ. Then the nuclides 131I, 99Tc m and 177Lu were labeled on PDA, respectively, and the labeling yield and stability were determined. The cytotoxicity test was conducted by comparing the viabilities of 4T1 tumor cells in free 131I group and 131I-PDA-PEG-PpⅨ group. The 4T1 cells were divided into 7 groups according to different treatment methods: PDA-PEG-PpⅨ group, PDA-PEG-PpⅨ+ photothermal therapy (PTT) group, PDA-PEG-PpⅨ+ sonodynamic therapy (SDT) group, 131I-PDA-PEG-PpⅨ+ PTT group, 131I-PDA-PEG-PpⅨ+ SDT group, 131I-PDA-PEG-PpⅨ+ PTT+ SDT group (100 μg/ml PDA-PEG-PpⅨ, 925 kBq/ml 131I), and the control group (DMEM culture medium). The cell viabilities of those groups were compared to evaluate the therapeutic effect. 4T1 tumor bearing mouse models were established, then 99Tc m-PDA-PEG-PpⅨ was injected through the tail vein (29.6 MBq) or intratumorally (14.8 MBq) to perform gamma imaging. The independent-sample t test and one-way analysis of variance were used for data analysis. Results:The PDA particles were uniform in size, with a particle size of (160.0±1.5) nm. They had a good photothermal conversion effect. A characteristic peak consistent with PpⅨ (400 nm) appeared in the UV-Vis absorption spectrum of PDA-PEG-PpIX. In the cytotoxicity test, when the radioactivity was 1.850 or 3.700 or 7.400 MBq/ml, the cell viabilities of free 131I group and 131I-PDA-PEG-PpⅨ group were significantly different ((72.18±6.57)% vs (86.07±5.17)%, (59.31±9.06)% vs (80.85±4.21)%, (42.90±1.30)% vs (72.99±5.73)%; t values: 3.71, 4.82, 11.46, P values: 0.006, 0.001, <0.001). The 131I-PDA-PEG-PpⅨ+ PTT+ SDT combination therapy had a better killing effect on 4T1 tumor cells than the combination of 131I-PDA-PEG-PpⅨ+ PTT and 131I-PDA-PEG-PpⅨ+ SDT (cell viabilities: (10.09±2.50)% vs (16.04±2.63)%, (28.65±4.72)%; F=351.66, P<0.001). In vivo imaging showed that 99Tc m-PDA-PEG-PpⅨ was stable in mouse models and could be effectively enriched in tumors. Conclusions:A multifunctional nanoprobe based on PDA is successfully prepared. The radionuclide labeling method is simple and effective, with a good stability. 131I-PDA-PEG-PpⅨ can kill 4T1 cells efficiently. 99Tc m-PDA-PEG-PpⅨ has an obvious tumor concentration effect in mouse models.

Dyslipidemia is an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Statins delay the occurrence and development of ASCVD, and reduce the risk of cardiovascular events and death. Due to safety concerns, there exist insufficient use of lipid-lowering agents and a high withdrawal rate of the agents in the elderly. To promote the prevention and treatment of ASCVD, this expert consensus is issued and focuses on the management of dyslipidemia of Chinese elderly basing on the clinical evidence of the use of lipid-lowering drugs by the elderly, and the lipid management guidelines and expert consensus recommendations at home and abroad.

Capsule endoscopy is one of the main diagnostic methods of small bowel diseases. In small bowel capsule endoscopy, the main factors that influence the diagnostic rate of diseases include gastrointestinal examination completion rate and intestinal preparation, etc. The upper gastrointestinal transit time is one of the main influence factors of examination completion rate. This article reviewed risk factors and clinical management of prolonged upper gastrointestinal transit time in capsule endoscopy.

Objective: To evaluate the left ventricular systolic synchrony and investigate the early diagnostic value of left ventricular systolic dyssynchrony on cardiotoxicity caused by anthracyclines in patients with diffuse large B-cell lymphoma (DLBCL). Methods: Thirty-two patients (22 males, 10 females, age: 22-73(54.4±14.2) years) from June 2016 to January 2019 with confirmed DLBCL and normal gated myocardial perfusion imaging (GMPI) before anthracyclines chemotherapy were enrolled prospectively. GMPI was performed after 6 cycles or more of chemotherapy. Changes of myocardial markers, electrocardiogram (ECG) indicators, left ventricular function indicators including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), peak filling rate (PFR), summed motion score (SMS) and summed thickening score (STS) as well as left ventricular systolic synchrony indicators including phase bandwidth (BW), phase standard deviation (SD) and entropy before and after anthracyclines chemotherapy were analyzed. Paired t test, Wilcoxon signed rank test and χ² test were used for data analysis. Results: Compared with pre-chemotherapy, the left ventricular systolic synchrony indicators were significantly higher than those before chemotherapy (BW: (42.81±11.37)° vs (29.28±8.68)°; SD: (11.65±4.64)° vs (8.79±3.14)°; entropy: (39.84±5.51)% vs (36.19±5.94)%; t values: -9.132 to -3.173, all P<0.05). There were no significant differences in other indicators (t values: -1.161 to 1.750, z values: -1.633 to -0.096, all P>0.05). Of 32 patients, 13 patients (40.62%) had left ventricular systolic dyssynchrony, and the rate of chemotherapy-induced left ventricular systolic dyssynchrony was significantly higher than that of left ventricular dysfunction (15.62%, 5/32; χ²=4.947, P=0.025). All 5 patients with left ventricular dysfunction caused by chemotherapy had left ventricular systolic dyssynchrony. The LVEF of the chemotherapy-induced left ventricular systolic dyssynchrony group was significantly lower than that of the left ventricular systolic synchronization group ((54.54±9.25)% vs (66.79±7.65)%; t=4.087, P<0.01). Conclusion Left ventricular systolic dyssynchrony can be appeared in DLBCL patients after chemotherapy and is significantly earlier than left ventricular dysfunction, which can be an early indicator of cardiotoxicity caused by anthracycline chemotherapy.

Objective To understand the distribution and antimicrobial resistance of pathogens isolated from patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)in Ordos area,so as to provide guidance for rational antimicrobial use.Methods Sputum culture and antimicrobial susceptibility testing results of 372 patients with AECOPD in Ordos area in 2013-2015 were analyzed,and the quality of life before acute exacerbation was assessed.Results A total of 296 strains of pathogens were isolated from 372 patients,252(85.14%)of which were gram-negative bacteria,the major were Pseudomonas aeruginosa(n=58,19.59%),Klebsiella pneumoniae(n=51,17.23%),Acinetobacter baumannii(n=50,16.89%),Stenotrophomonas maltophilia(n=22,7.43%),Escherichia coli(n=19,6.42%),and Enterobacter cloacae(n=16,5.41%);27(9.12%)were fungi,the major was Candida albicans(n=19,6.42%);17(5.74%)were gram-positive bacteria,the predominant species was Staphylococcus aureus.Patients with CAT(COPD assement test)score≥10 had higher proportion of isolating Pseudomonas aeruginosa and Acinetobacter baumannii than those with CAT score<10.Conclusion The main pathogens from patients with AECOPD are gram-negative strains,CAT score prior to exacerbation may be related to the emergence of pathogens at AECOPD.

Objective Few studies are reported on the construction of a finite element model of human complex knee joint using multimodality CT and MRI images.In this study, we developed a finite element model of the knee joint for total knee arthroplasty (TKA) using matched and fused CT and MRI data, hoping to provide a useful tool for the simulation study of knee joint biomechanics of TKA.Methods The CT and MRI image data about an intact knee of a 26-year-old male volunteer were imported into the Mimics software for the establishment of 3D models of bony and soft-tissue structures.A complete knee model was developed following the registration and fusion of the constructed 3D models based on the external landmarks.After the simulated implantation of TKA components, a finite element model of the TKA knee was constructed with the Hypermesh software.Then the finite element model was analyzed following the definition of its material behavior, boundary conditions and loading.Results The finite element model of the TKA knee, which was composed of bones, ligaments, components, polyethylene insert and bone cement, was developed from CT-MRI image registration and fusion and maintained its important spatial relationship among different structures in the TKA knee.The results obtained from the finite element analysis showed the characteristics of stress distribution in the TKA knee.Conclusion The finite element model of the knee joint for TKA can be established by matching and fusing CT and MRI image data, which can be employed as a useful tool for the study of knee joint biomechanics of TKA.

Objective To observe the effects of creatine phosphate sodium on heart function and B -type natriuretic peptide in patients combination with ischemic cardiomyopathy and intractable heart failure .Methods 70 cases of coronary heart disease combined with ischemic cardiomyopathy and intractable heart failure were randomly ( with the random number table ) divided into the control group ( n=33) and the creatine phosphate sodium treatment group (n=37).The control group treated with conventional therapy (digitalis,diuretics,vasodilator,ACEI,et al) ten days;the treatment group with creatine phosphate sodium treatment on the basis of conventional therapy .The symp-tom,sign of the heart failure patients of the two groups before and after treatment were observed .NYHA cardiac func-tional grading were estimated.Echocardiography was used to detect left ventricular end -systolic diameter(LVESD), left ventricular end diastolic diameter ( LVEDD ) and left ventricular ejection fraction ( LVEF ); amino terminal pro brain natriuretic peptide (NT-proBNP) tested by laboratory of the two groups.Drug treatment for 10 days,the chan-ges of the indicators before and after treatment were observed .Results After treatment , compared with the control group[(50.63 ±4.67) mm,(61.30 ±4.58) mm].LVESD,LVEDD of the creatine phosphate sodium treatment [(47.16 ±4.30)mm,(57.92 ±4.30)mm]significantly decreased(t=5.73,4.96,all P<0.01),LVEF[(40.57 ± 4.51)%,(37.63 ±4.53)%]increased significantly(t =5.53,P<0.01).After ten days of treatment levels of NT-proBNP decreased in both two groups [(1 659.±248.18) pg/mL,1 899.3 ±205.45] than before treatment [2 043.46 ±217.04,(2 105.46 ±239.09)pg/mL](t=3.23,3.64,all P<0.05),and the decrease degree of the creatine phosphate sodium treatment group was more obvious than those of the control group (t=4.11,P<0.05). Conclusion Creatine phosphate sodium can improve the cardiac function and left ventricular ejection fraction of ischemic cardiomyopathy and intractable heart failurepatients ,enhance the clinical symptoms of patients .