Research on classification method of multimodal magnetic resonance images of Alzheimer's disease based on generalized convolutional neural networks / 生物医学工程学杂志

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Neuroimaging based on magnetic resonance imaging (MRI) is one of the most intuitive and reliable methods to perform AD screening and diagnosis. Clinical head MRI detection generates multimodal image data, and to solve the problem of multimodal MRI processing and information fusion, this paper proposes a structural and functional MRI feature extraction and fusion method based on generalized convolutional neural networks (gCNN). The method includes a three-dimensional residual U-shaped network based on hybrid attention mechanism (3D HA-ResUNet) for feature representation and classification for structural MRI, and a U-shaped graph convolutional neural network (U-GCN) for node feature representation and classification of brain functional networks for functional MRI. Based on the fusion of the two types of image features, the optimal feature subset is selected based on discrete binary particle swarm optimization, and the prediction results are output by a machine learning classifier. The validation results of multimodal dataset from the AD Neuroimaging Initiative (ADNI) open-source database show that the proposed models have superior performance in their respective data domains. The gCNN framework combines the advantages of these two models and further improves the performance of the methods using single-modal MRI, improving the classification accuracy and sensitivity by 5.56% and 11.11%, respectively. In conclusion, the gCNN-based multimodal MRI classification method proposed in this paper can provide a technical basis for the auxiliary diagnosis of Alzheimer's disease.

Potent anti-inflammatory activity of tetramethylpyrazine is mediated through suppression of NF-k

The purpose of the current study was to evaluate the anti-inflammatory activity of tetramethlpyrazine on oxazolone-induced colitis mice. Spleen mononuclear cells [SMC], lamina propria mononuclear cells [LPMC] and peripheral blood mononuclear cells [PBMC] were isolated from oxazolone-induced colitis and normal mice. The colitis cells treated by oxazolone were randomly divided into model, low dose, middle dose and high dose groups treated with 0, 0.5, 1.0 and 2.0 g/L tetramethlpyrazine, respectively. The apoptotic rate of SMC and LPMC in the oxazolone-induced group was lower than that in the normal group. Compared with model group, apoptotic rate of SMC was significantly increased in the high dose group, while the apoptotic rate of LPMC in the middle dose group was increased. Compared with SMC, LPMC and PBMC of normal group, the mRNA level of nuclear factor kappa B [NF-kB], transcription factor-activated protein-1 [AP-1] and nuclear factor of activated T cells [NF-AT] were higher in model group. Tetramethylpyrazine inhibited the increase of NF-kB, AP-1 and NF-AT mRNA induced by oxazolone. For SMC, LPMC and PBMC there was significant difference in the mRNA level of AP-1 among the three different doses of tetramethylpyrazine treated groups. However, no significant difference was observed in the mRNA levels of NF-AT and NF-kB between normal and middle groups. Tetramethylpyrazine promoted the apoptotic rate of SMC and LPMC in-vitro, and suppressed the expression of transcription factors in SMC, LPMC and PBMC isolated from oxazolone-induced colitis mice. The study provides a novel insight into the mechanism behind the effect of etramethylpyrazine on colitis

Role and mechanism of sinomenine and sulfasalazine in experimental colitis of mice model / 中华消化杂志

Objective To investigate the role and mechanism of sinomenine and sulfasalazine (SASP) in experimental colitis of mice.Methods Seventy SPF grade Kunming mice were evenly divided into seven groups.Except control group,all mice were treated with oxazolone to create experimental colitis model.After modeling,the model group,low dose sinomenine group,high dose sinomenine group,low dose sinomenine combined group,high dose sinomenine combined group and SASP group was gavaged once daily with 0.9％ NaC1 solution 1 mL,40 mg/kg sinomenine,120 mg/kg sinomenine,40 mg/kg sinomenine and 400 mg/kg SASP,120 mg/kg sinomenine and 400 mg/kg SASP and 400 mg/kg SASP alone for seven days.The mouse stool characters,changes in body weight and fecal occult blood were recorded and disease activity index (DAI) was scored.The next day after the end of the intervention,all mice were sacrificed and specimens of the colon were obtained aud injury was scored.The specimens of inflammation part and ulcer site of colon were taken for histological examination and injury scoring.The expression of mitogen-activated protein kinase kinase 5 (MKK5),extracellular signal-regulated kinase 5 (ERK5),mitogen-activated protein kinase kinase 7 (MKK7),Jun N-terminal kinase (JNK),nuclear factor κB (NF-κB) at mRNA level were detected by reverse transcription-polymerase chain reaction (RT-PCR).The t-test was performed for comparison between groups.Results The DAI of low dose sinomenine group,high dose sinomenine group,low dose sinomenine combined group,high dose sinomenine combined group and SASP group was 2.33±0.77,1.03±0.73,2.70±0.67,1.60±0.66 and 2.03±0.79,respectively,the score of injury was 5.50±1.43,4.00±1.49,6.80±1.75,4.80±1.32 and 5.40±1.58,respectively,all were lower than those of model group (3.40±0.66 and 11.40±1.71) and the differences were statistically significant (tDA1 =3.33,7.61,2.34,6.08 and 4.18,t score of injury =8.35,10.31,5.94,9.66 and 8.15 ; all P＜0.05).The score of injury of high dose sinomenine group,high dose sinomenine combined group and SASP group was 1.40 ±± 1.26,1.70 ± 1.06 and 1.80 ± 1.32,respectively,which were lower than that of model group (3.00 ± 1.05) and the differences were statistically significant (t ＝ 3.07,2.75 and 2.25,all P＜0.05).The expression of MKK5,ERKS,MKK7,JNK and NF-κB at mRNA level of SASP group was 24.29±3.40,34.74±3.05,21.34±3.74,18.71±4.12 and 21.68±2.96,respectively,all were lower than those of low dose sinomenine group (51.94±9.16,50.71±11.09,57.98±17.22,55.99±9.65 and 67.41±10.21) and low dose sinomenine combined group (72.03±17.44,119.91±47.26,74.09±21.24,71.83±16.91 and 86.51±18.61).However,those of SASP group were higher than those of high dose sinomenine group (6.53±0.85,17.87±2.74,13.52±2.56,10.41±2.62 and 13.79± 1.43) and high dose sinomenine combined group (16.80±7.15,21.09±3.92,15.81±1.35,14.11±3.10 and 16.62±3.15).All of low dose sinomenine group were higher than those of high dose sinomenine group,all of low dose sinomenine combined group were higher than those of high dose sinomenine combined group,all of low dose sinomenine combined group were higher than those of low dose sinomenine group and all of high dose sinomenine combined group were higher than those of high dose sinomenine group and the differences were statistically significant (tMKK5=8.95,8.49,16.01,2.99,15.61,9.26,3.22 and 4.51,tERK5=4.41,5.69,13.02,12.81,7.82,6.78,4.50 and 2.13,tMKK7 =6.58,7.73,5.80,4.40,8.11,6.32,1.86 and 2.94,tJNK=10.59,7.57,5.37,2.82,13.21,7.57,2.57 and 2.88,tNF-κB =13.60,10.88,7.60,3.70,16.44,11.71,2.85 and 2.59 ; all P＜0.05).Conclusions Sinomenine can efficiently improve the inflammatory reaction in the mouse model of colitis and the mechanism may be related with ERK5,JNK and NF-κB signaling pathways.The higher the dose,the more significant the efficacy.The antagonism may exist between sinomenine and SASP.

Effects of interleukin-10 in epithelial-mesenchymal transition and endoplasmic reticulum stress on intestinal fibrosis / 中华消化杂志

Objective To investigate the effects of interleukin-10 on mice intestinal fibrosis and epithelial-mesenchymal transition(EMT),and the relation between these effects and endoplasmic reticulum stress(ERS).Methods Forty-two IL-10 knockout(IL-10-/-)mice were divided into fibrosis model group(n=18),IL-10 treatment group(n=12)and solvent control group(n =12),another 18 wild-type mice were taken as negative control group.IL-10 and 0.9％ NaCl were intraperitonealy injected in IL-10 treatment group and solvent control group respectively since 12th week,and mice were sacrificed at week 14th and 16th,and no treatment to fibrosis model group and negative control group.The injury and fibrosis in mice colon tissue were detected with HE staining and Masson collagen staining.The expressions of collagen Ⅰ,glucose-regulated protein78(GRP78),C/EBP homologous protein(CHOP)and a-smooth muscle actin(α-SMA)and E-cadherin(E-cad)at mRNA level were determined by realtime PCR.The expression of α-SMA and E-cad in mice colon tissue was examined by immunohistochemical staining.Results At 16th week,the colonic tissue injury scores(7.00±0.90,7.17±1.17)and collagen area ratio(17.78％±4.15％,18.56％±3.81％)of fibrosis model group and solvent control group significantly increased compared with negative control group(1.50±1.38 and 9.11％±2.99％)and IL-10 treatment qroup(4.33±0.82 and 12.56％±1.39％)(F=36.150,F=11.280； P=0.000).At week 12th,14th and 16th,the expressions of GRP78,α-SMA,collagen Ⅰ in fibrosis model group and solvent control group significantly increased compared with negative control group(all P＜0.05),however the expression of E-cad significantly decreased(P＜0.05).The expression of CHOP mRNA in fibrosis model group(0.95％ ±0.12％)significantly increased compared with negative control group(0.21％ ± 0.12％)at week 12th(t=5.188,P=0.000),however there was no statistical significant difference in groups at week 14th and 16th(P＞0.05).At week 14th and 16th,the expressions of GRP78,α-SMA and collagen Ⅰ(at week 14th:0.73％±0.31％,1.18％±0.11％ and 1.10％±0.49％； at week 16th:0.57％±0.16％,0.81％ ±0.50 ％ and 0.76 ％ ± 0.25 ％)in IL-10 treatment group were significantly lower than that of fibrosis model group(P＜0.05).The expression of E-cad(at week 14th:0.73％ ±0.29％ ； at week 16th:0.97％ ±0.25％)significantly increased compared with fibrosis model group(at week 14th:0.37％±0.17％； at week 16th:0.35％±0.20％)(F=6.524,P=0.003； F=17.493,P=0.000).However at week 16th,the expression of α-SMA in IL-10 treatment group was lower than that of solvent control group(1.82±0.22)％(F=9.842,P=0.000),and the expression of E-cad significantly increased than in solvent control group(0.47 ± 0.25)％(F=17.493,P =0.000).Conclusion IL-10 may have a role in inhibiting EMT and reducing intestinal fibrosis in mice,which may be related to the regulation of ERS by IL-10.

Effects of curcumin in intestinal fibrosis of rats and its mechanism / 中华消化杂志

Objective To investigate the anti-fibrotic effects of curcumin in trinitrobenzene sulphonic acid (TNBS) induced intestinal fibrosis in rats and its mechanism. Methods Forty SD rats were randomly divided into model group, treatment group, control group and normal group with 10each. Except the normal group, the other three groups were given 10, 15, 20, 25 and 30 mg of TNBS enema on the 1st, 8 th, 15th, 22nd and 29th days,respectively. The rats in treatment group were intraperitonealy injected with 30 mg/kg of curcumin daily. Control group was injected with 0. 9%NaCl solution and normal group received an equal volume of 50% ethanol enema without any treatment. The damage and fibrosis of colon were detected with HE staining and Masson collagen staining, respectively. The contents of interleukin (IL) -2, tumor necrosis factor (TNF) -α, IL-4 and IL-17 in colon were measured by enzyme-link immunosorbent analysis (ELISA). The expressions of intestinal fibrosis related cytokines such as transforming growth factor (TGF) -β1, connective tissue growth factor (CTGF), Smad3, collagen Ⅰ and collagen Ⅲ mRNA were determined by FQ-PCR.Results The macroscopic and micrpscopic colonic damage scores and collagen area were significantly higher in model group (6.14 ± 1.07, 8. 42 ± 1.40 and 36. 59% ± 4.07%, respectively) and control group (6.17 ± 1.47, 8. 17 ±1.47 and 37.18 %±4.05 %, respectively) than those in normal group (2.13±0.64, 2.25±1.28 and 25.43%±5.39% ,respectively)(P＜0.05). Contents of IL2, TNF-α, IL-17, as well as expressions of intestinal fibrosis related cytokines including TGF-β1, CTGF,Smad3, collagen Ⅰ and Ⅲ mRNA were also higher in model group [(378. 25±29. 90) ng/L,(87.11±23.85) ng/L, (47.80±5.62) ng/L, 4.71%±2.71%,10.33%±6.99%,9.35%±7.32%,1.52% ± 1.11% and 3.04% ±1.33%, respectively] and control group [(410. 06 ± 64.74) ng/L,(100.41±12.59) ng/L, (41.45±2. 12) ng/L, 4. 12%±3.01%,11.46%±4.72%,10. 11%±3.80%,1. 57% ± 1. 35% and 3. 03% ± 3. 53%, respectively] in comparision with normal group [(179.74±20. 73) ng/L, (35. 47±7. 13) ng/L, (14. 48±7. 52) ng/L and 0. 90%± 1. 13%,0.53%±0.47%, 0. 62%±0. 44%, 0. 16%±0. 09% and 0. 18%±0. 10%, respectively] (P＜0.05). While in treatment group, the macroscopic (4.00 ± 1.07 ) and micrpscopic (5. 13 ± 1.46)colonic damage scores, collagen area (30.01%±7.56%), contents of IL-2 [(223.91±28.04) ng/L],TNF-α [(44.19±4. 77) ng/L] and IL-17 [(14.89±4. 31) ng/L], expressions of TGF-β1 (0.85%±0.76%), CTGF (1.56%±1.13%), Smad3 (3.62%±3.03%), collagen Ⅰ (0.40%±0.31%) and Ⅲ (0.60 % ± 1.02 % ) mRNA were much lower than those in model group and control group (P＜0.05 ), but similar to those in normal group (P＞ 0.05 ). Conclusions Curcumin can inhibit intestinal fibrosis caused by excessive "wound-healing" reaction via reducing the overexpression of cytokines in colonic mucosa and attenuating the inflammation of colon.

The expressions of nuclear factor-κB and activator protein-1 in oxazolone induced colitis in mice / 中华消化杂志

Objective To investigate the expression changes of nuclear factor(NF)-κB and activator protein (AP)-1 in oxazolone induced colitis in mice and their mechanisms. Methods Twenty-four mice were randomly divided into normal group and model group with 12 each. Experimental colitis was induced with skin sensitization of 3% oxazolone for 5 days, then rectal administration of 0.15 ml of 0. 5% oxazolone solution in mice. All mice were sacrificed on day 3. Peripheral blood mononuclear cells (PBMC), spleen mononuclear cells (SMC) and lamina propria mononuclear cells (LPMC) were isolated from the colon tissues. Expression of NF-κB and AP-1 in SMC, LPMC and PBMC were determined by fluorescence quantitative polymerase chain reaction (PCR). The colitis was evaluated histologically. Results The expressions of NF-κB and AP-1 in SMC, LPMC,PBMC of model groupwere significantly higher than those in normal group(NF-κB : 5.62±0.78 vs. 3.16±0.59,5.46±0.38 vs. 3.18±0.58, 5.65±0.56 vs. 3.36±0.59, P＜0.01; AP-1; 5.61±0.54 vs. 3.22±0.50, 5.50±0.69 vs. 3.19± 0.40,5.67±0.44 vs. 3. 27±0.41, P＜0.01). Conclusion The activation of NF-κB and AP-1 are involved in the mechanisms of ulcerative colitis.

A Preliminary Study of Hemorheological Parameters of Patients with Silent Myocardial Ischemia / 第三军医大学学报

Fifty-two patients with silient myocardial ishcemia (SMI) were categorized into Type Ⅰ SMI group (n=21) and Type HI SMI group (n=31).22 normal subjects were also observed to serve as the control.It was found that the apparent viscosity of whole blood at different shear rate of 192.0 s-1,30.72s-1,and 3.84 s-1,the plasma viscosity,and the inter-viscosity of erythrocytes,and the duration of total myocardial ischemia on Holter monitoring electrocardiogram were higher and longer in Type Ⅲ SMI patients than in Type Ⅰ SMI ones and the normal controls (P