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The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.
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The incidence of ulcerative colitis (UC) is increasing in recent years, and its pathogenesis is not completely clear. The extraintestinal manifestations (EIM) of UC are diverse and can involve multiple organ systems such as bone and joint, skin, liver and gallbladder, eye, etc. The incidence of one EIM increases the risk of development of other EIM. Cutaneous manifestations are important EIM of UC, and are usually classified into reactive, immunity-associated, malnutrition and treatment-induced manifestations. This article reviewed the clinical symptoms, diagnosis and treatment of cutaneous extraintestinal manifestations of UC.
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@#Objective To observe the effect of repetitive focal muscle stimulation on recovery of upper limb function after stroke.Methods From October, 2016 to February, 2018, 46 stroke patients at early stage were recruited and divided into control group (n=23) and observation group (n=23). Both groups received basic rehabilitation training. The observation group accepted additional repetitive focal muscle stimulation on palms, forearm extensor carpi radialis, biceps brachii and muscles around scapula. The control group received sound stimulation as placebo treatment. The treatment was implemented once a day, five days a week for four weeks totally. The scores of Fugl-Meyer Assessment -Upper Extremities (FMA-UE), the Motricity Index of Upper Extremities (MI-UE) and the Hong Kong version of Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) were compared before and four weeks after treatment. Results After treatment, the scores of FMA-UE, MI-UE and FTHUE-HK improved in both groups (F>2.577, P<0.05), and were higher in the observation group than in the control group (t>2.153, P<0.05).Conclusion Repetitive focal muscle stimulation could facilitate to recover the function of upper limb in early-stage stroke patients.
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Objective To investigate the cognitive behavioral characteristic longitudinally of the patients after subcortical infarction engaged in feature and binding working memory tasks.Methods The behavioral performances were recorded from 28 patients after subcortical infarction at the 1 st week (W1),3 rd moth (M3) and 6th month (M6) while performing color,location,and color-location binding delayed match-to-sample working memory task.25 healthy volunteers(controls) were investigated once using the same task protocol during the study period.Computer recorded the behavior reaction time and accuracy.Single factor variant analysis of repeated measurement was adopted.Results The accuracy of three memory tasks of M3 ((64.92 ± 5.47) ％ ; (92.88 ± 2.98) ％ ;(82.35 ±7.44)％) was improved than that of W1 ((61.06 ±7.78)％; (90.59 ±2.95)％; (77.06 ±5.58) ％) and the difference had statistically significant (P ＜ 0.05).But the reaction time of M3 ((868.31 ±118.91)ms; (833.37 ± 120.99) ms; (918.72 ± 101.28) ms) was shortened than that of W1 ((914.02 ±110.53) ms; (859.89 ± 139.94) ms; (1150.17 ± 92.02) ms) and the difference also had statistically significant (P ＜ 0.05).In the location-memory task,the correct rate of M6 ((93.91 ± 2.86) ％) was improved than that of M3 ((92.88 ± 2.98) ％) and the reaction time of M6 ((813.24 ± 119.54) ms) was shortened than M3 ((833.37 ±120.99) ms).M6 and M3 to be compared in the color memory task,the correct rate ((64.50 ± 4.49) ％ ; (64.92 ± 5.47) ％) and the reaction time ((866.47 ± 123.87) ms; (868.31 ± 118.91) ms) had no significant difference (P ＜ 0.05).But in the color-location binding task,the correct rate of M6 ((78.49 ± 7.85) ％) and M3 ((82.35 ± 7.44)％) to be compared had significant decreased nearly the level ((77.06 ± 5.58)％) of the stroke beginning.All behavioral performances of patients were worse than that of control subjects except the compare result of location-memory task in M6((93.91 ± 2.86) ％ ; (813.24 ± 119.54) ms).Conclusion Feature memory and binding memory had been damaged in different degrees in the patient after subcortical infarction.The binding memory had the secondary damage what might be related to the secondary nerve fiber degeneration after infarction.
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@#ObjectiveTo explore the effect of acupuncture combined with training of the modified rehabilitation apparatus on upper limb motor function of patients with ischemic stroke.Methods86 patients with ischemic stroke were divided randomly into the treatment group ( treated by acupuncture combined with training of the rehabilitation apparatus) and the control group (treated by simple acupuncture). The upper limb motor function of two groups was evaluated by Fugl-Meyer Assessment (FMA) before and after treatment.ResultsAfter 28 days treatment, scores of FMA of two groups were all raised significantly, but it was significantly greater for the treatment group than the control group (P<0.01).ConclusionIt is shown that acupuncture combined with training of the rehabilitation apparatus can improve the upper limb motor function and activity of daily living of patients with ischemic stroke.