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.

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

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.

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.

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.

Objective:To explore the team construction and treatment strategy of the Diabetic Foot-Multidisciplinary Team.Methods:The clinical data of 19 patients with severe ischemic diabetic foot treated by our Diabetic Foot-Multidisciplinary Team Center from Apr 2021 to Mar 2022 were collected, and the overall amputation rate, above-ankle major amputation rate, minor amputation rate and mortality, Diabetic Foot-Multidisciplinary Team consultation discipline participation rate and treatment participation degree were retrospectively analyzed.Results:Nineteen patients (15 males and 4 females) were enrolled, aged 26 to 94 (68.6±14.2). All were with severe ischemic diabetic foot ulcer:Rutherford grade 5 or up and dysfunction in 2 or more organs. Complications included arteriosclerosis obliterans of the lower extremities in 18 cases, heart diseases in 18, hypertension in 15, and renal insufficiencies in 10. The overall amputation rate was 36.8%, major amputation rate in 21.1%, minor amputation rate in 15.8%, and mortality rate was 15.8%. A total of 16 disciplines participated in Diabetic Foot-Multidisciplinary Team; the main participating disciplines were vascular surgery (19 times), endocrinology (12 times), and cardiology (11 times). The main treatment disciplines were vascular surgery (14 times), plastic surgery (3 times), and cardiology (2 times).Conclusion:For the diagnosis and treatment of diabetic foot, it is necessary to set up a multidisciplinary team as early as possible to control the causes of diabetic foot ulcer, prevent the recurrence of diabetic foot ulcer, reduce the mortality and amputation rate, and improve the quality of life of patients.

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.
Humans ; Alzheimer Disease/diagnostic imaging* ; Neurodegenerative Diseases ; Magnetic Resonance Imaging/methods* ; Neural Networks, Computer ; Neuroimaging/methods* ; Cognitive Dysfunction/diagnosis*

Statistics show that 76.74% (4 688) of 6 109 patients with chronic wounds are those over 50 years of age; the proportion of patients with underlying diseases in all age groups above 50 years ranges from 78.25% to 100.00%; among the underlying diseases of chronic wound patients, the top four diseases are diabetes mellitus , cardiovascular and cerebrovascular diseases, hypertension, and respiratory diseases. The above underlying diseases and ages of patients are the susceptibility factors of corona virus disease 2019 released by National Health Commission of China. It is an unavoidable fact that patients with chronic wounds have to go to the hospital for treatment prescribed by the physician. At the same time, we found that there were not a few patients who go far afield because of various reasons when go to the hospital for treatment. During the period of epidemic prevention and control, this kind of "go far afield" style of seeking medical treatment may increase the exposure risk during transportation. Accordingly, we convened 36 wound care clinics in different regions in Shanghai to implement the "Five Measures" to encourage patients with chronic wounds to seek medical treatment proximately. The principle of this operation is that when seeking medical treatment, trying our best to reduce as much as possible the transportation distance for patients with chronic wounds to minimize the exposure risk during the epidemic period and eventually support the epidemic prevention and control campaign.