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1.
目的 探讨耳穴贴压对腹部术后胃肠功能紊乱家兔模型的作用机制,为耳穴贴压治疗腹部术后胃肠功能紊乱提供参考。 方法 将30只SD清洁型家兔采用随机数字表法分为空白组、模型组、耳穴组各10只。耳穴组于造模成功后耳穴贴压胃、大肠、耳中穴,每日按压3次,每次每穴30 s,连续干预7 d;模型组进行造模手术未进行耳穴贴压;空白组不给予任何处理。 结果 耳穴组术后首次排便时间及肠鸣音恢复时间显著早于模型组(均P<0.05)。三组术后6 h、3 d及7 d血清皮质醇浓度的干预效应、时间效应、交互效应显著,模型组及耳穴组术后6 h及3 d血清皮质醇浓度显著高于空白组,且术后3 d耳穴组显著低于模型组(均P<0.05)。干预后,三组小肠推进率、C-kit蛋白阳性表达、iNOS活性有显著差异,其中耳穴组、空白组小肠推进率、C-kit蛋白阳性表达显著高于模型组,但iNOS活性显著低于模型组,耳穴组的C-kit蛋白阳性表达显著低于空白组(均P<0.05)。 结论 耳穴贴压可缩短腹部术后家兔首次排便及肠鸣音恢复时间,降低血清皮质醇浓度及应激反应,有助于提升小肠推进率及结肠组织中C-kit蛋白阳性表达,促进腹部术后胃肠蠕动恢复。  相似文献   
2.
尽管嵌合抗原受体(CAR)T细胞治疗在血液系统恶性肿瘤患者中取得了显著的临床疗效,但需要进一步优化。脂质纳米粒(LNP)-信使核糖核酸(mRNA)递送系统作为一种非病毒性基因载体运用于CAR-T细胞治疗研究中,一方面通过LNP将密封蛋白-6 mRNA靶向递送至抗原提呈细胞,从而实现抗原提呈细胞辅助性增强密封蛋白-6靶向的CAR-T细胞的功能,以进一步诱导对实体瘤的清除;另一方面,通过LNP将成纤维细胞激活蛋白(FAP)CARmRNA靶向递送至T细胞,实现体内FAP靶向的CAR-T细胞的制备,以通过阻断心脏纤维化过程达到治疗急性心肌损伤的目的。在CAR-T细胞研究和治疗中,LNP-mRNA递送系统具有不与细胞基因组整合、价格便宜、毒副作用小及可修饰等优点,亦存在蛋白瞬时表达导致调控细胞功能的持久性不足及制备等方面的技术局限性。本文综述了LNP-mRNA递送系统及其在CAR-T细胞治疗中的应用研究。  相似文献   
3.
《Clinical neurophysiology》2021,132(6):1312-1320
ObjectiveTo investigate the additional value of EEG functional connectivity features, in addition to non-coupling EEG features, for outcome prediction of comatose patients after cardiac arrest.MethodsProspective, multicenter cohort study. Coherence, phase locking value, and mutual information were calculated in 19-channel EEGs at 12 h, 24 h and 48 h after cardiac arrest. Three sets of machine learning classification models were trained and validated with functional connectivity, EEG non-coupling features, and a combination of these. Neurological outcome was assessed at six months and categorized as “good” (Cerebral Performance Category [CPC] 1–2) or “poor” (CPC 3–5).ResultsWe included 594 patients (46% good outcome). A sensitivity of 51% (95% CI: 34–56%) at 100% specificity in predicting poor outcome was achieved by the best functional connectivity-based classifier at 12 h after cardiac arrest, while the best non-coupling-based model reached a sensitivity of 32% (0–54%) at 100% specificity using data at 12 h and 48 h. Combination of both sets of features achieved a sensitivity of 73% (50–77%) at 100% specificity.ConclusionFunctional connectivity measures improve EEG based prediction models for poor outcome of postanoxic coma.SignificanceFunctional connectivity features derived from early EEG hold potential to improve outcome prediction of coma after cardiac arrest.  相似文献   
4.
Implant wear and corrosion have been associated with adverse tissue reactions that can lead to implant failure. Wear and corrosion products are therefore of great clinical concern. For example, Co2+ and Cr3+ originating from CoCrMo‐based implants have been shown to induce a proinflammatory response in macrophages in vitro. Previous studies have also shown that the polarization of macrophages by some proinflammatory stimuli is associated with a hypoxia‐inducible factor‐1α (HIF‐1α)‐dependent metabolic shift from oxidative phosphorylation (OXPHOS) towards glycolysis. However, the potential of Co2+ and Cr3+ to induce this metabolic shift, which plays a determining role in the proinflammatory response of macrophages, remains largely unexplored. We recently demonstrated that Co2+, but not Cr3+, increased oxidative stress and decreased OXPHOS in RAW 264.7 murine macrophages. In the present study, we analyzed the effects of Co2+ and Cr3+ on glycolytic flux and HIF‐1α stabilization in the same experimental model. Cells were exposed to 6 to 24 ppm Co2+ or 50 to 250 ppm Cr3+. Glycolytic flux was determined by analyzing extracellular flux and lactate production, while HIF‐1α stabilization was analyzed by immunoblotting. Results showed that Co2+, and to a lesser extent Cr3+, increased glycolytic flux; however, only Co2+ acted through HIF‐1α stabilization. Overall, these results, together with our previous results showing that Co2+ increases oxidative stress and decreases OXPHOS, suggest that Co2+ (but not Cr3+) can induce a HIF‐1α‐dependent metabolic shift from OXPHOS towards glycolysis in macrophages. This metabolic shift may play an early and pivotal role in the inflammatory response induced by Co2+ in the periprosthetic environment.  相似文献   
5.
PurposeMachine-learning (ML) approaches have been repeatedly coupled with raw accelerometry to classify physical activity classes, but the features required to optimize their predictive performance are still unknown. Our aim was to identify appropriate combination of feature subsets and prediction algorithms for activity class prediction from hip-based raw acceleration data.MethodsThe hip-based raw acceleration data collected from 27 participants was split into training (70 %) and validation (30 %) subsets. A total of 206 time- (TD) and frequencydomain (FD) features were extracted from 6-second non-overlapping windows of the signal. Feature selection was done using seven filter-based, two wrapper-based, and one embedded algorithm, and classification was performed with artificial neural network (ANN), support vector machine (SVM), and random forest (RF). For every combination between the feature selection method and the classifiers, the most appropriate feature subsets were found and used for model training within the training set. These models were then validated with the left-out validation set.ResultsThe appropriate number of features for the ANN, SVM, and RF ranged from 20 to 45. Overall, the accuracy of all the three classifiers was higher when trained with feature subsets generated using filter-based methods compared with when they were trained with wrapper-based methods (range: 78.1 %–88 % vs. 66 %–83.5 %). TD features that reflect how signals vary around the mean, how they differ with one another, and how much and how often they change were more frequently selected via the feature selection methods.ConclusionsA subset of TD features from raw accelerometry could be sufficient for ML-based activity classification if properly selected from different axes.  相似文献   
6.
AimSkin tears are traumatic wounds characterised by separation of the skin layers. Severity evaluation is important in the management of skin tears. To support the assessment and management of skin tears, this study aimed to develop an algorithm to estimate a category of the Skin Tear Audit Research classification system (STAR classification) using digital images via machine learning. This was achieved by introducing shape features representing complicated shape of the skin tears.MethodsA skin tear image was separated into small segments, and features of each segment were estimated. The segments were then classified into different classes by machine learning algorithms, namely support vector machine and random forest. Their performance in classifying wound segments and STAR categories was evaluated with 31 images using the leave-one-out cross validation.ResultsSupport vector machine showed an accuracy of 74% and 69% in classifying wound segments and STAR categories, respectively. The corresponding accuracy using random forest were 71% and 63%.ConclusionMachine learning algorithms revealed capable of classifying categories of skin tears. This could offer the potential to aid nurses in their management of skin tears, even if they are not specialised in wound care.  相似文献   
7.
目的:探讨干细胞标志物醛脱氢酶1A1(ALDH1A1)对乳腺癌细胞血管生成因子表达的影响,以及对与乳腺癌细胞共培养的HUVEC细胞小管形成和侵袭能力的影响。方法:采用免疫组化检测了乳腺癌组织和乳腺增生组织中ALDH1A1的表达。使用ALDH1A1 shRNA或过表达ALDH1A1的pcDNA3.1质粒转染乳腺癌细胞(MCF-7和MDA-MB-231),通过qRT-PCR和Western blot检测敲低或过表达ALDH1A1对乳腺癌细胞中血管内皮生长因子(VEGF)、缺氧诱导因子-1α(HIF-1α)和白细胞介素-12(IL-12)表达的影响。通过用1 μmol/L 的外源性RA和RAR阻断剂(AGN 193109)处理乳腺癌细胞48 h来考察视黄酸信号通路是否参与ALDH1A1对VEGF和HIF-1α的调控过程。将乳腺癌细胞(MCF-7和MDA-MB-231)和HUVEC细胞共培养来模拟肿瘤形成的微环境,并检测HUVEC的小管形成能力和细胞侵袭能力。结果:乳腺癌组织的ALDH1A1染色平均光密度显著高于乳腺增生组织,并且淋巴结转移的乳腺癌组织显著高于未淋巴结转移的乳腺癌组织(P<0.05)。敲低ALDH1A1可显著降低MCF-7和MDA-MB-231细胞中VEGF和HIF-1α蛋白表达,并上调IL-12蛋白表达。然而,上调ALDH1A1表达则可逆转上述变化。外源性RA处理可显著上调MCF-7和MDA-MB-231细胞中VEGF和HIF-1α的表达,然而,RAR阻断剂处理可抑制MCF-7和MDA-MB-231细胞中VEGF和HIF-1α的上调。敲低乳腺癌细胞中ALDH1A1的表达可导致共培养的HUVEC细胞的小管形成能力和侵袭能力显著降低。而上调乳腺癌细胞中ALDH1A1的表达则可显著促进共培养的HUVEC细胞的小管形成能力和侵袭能力。结论:在乳腺癌细胞中,ALDH1A1通过激活HIF-1α和视黄酸信号通路来上调血管生成因子的表达并提高共培养的内皮细胞的血管生成能力,从而增加肿瘤的侵袭性。  相似文献   
8.
目的 肝纤维化是一种由于反复肝损伤而导致肝组织细胞外基质过多沉积导致的疾病。缺氧损伤为肝损伤的一部分,缺氧诱导因子-1α(HIF-1α)是响应缺氧应激的关键转录因子,在肝纤维化组织和活化的肝星状细胞(HSC)表达显著增加。目前,通过对大量HIF-1α依赖性基因和信号通路的研究,确认这些基因及其通路的变化参与肝纤维化发展过程,并可能在肝纤维化发生发展过程中起关键作用。本文综述了HIF-1α相关的信号通路参与肝纤维化发展的相关机制,并对上游影响HIF-1α合成和降解的相关信号通路进行了阐述,为其作为新型治疗靶点的可能潜力提供依据。  相似文献   
9.
目的 探讨HIF-1α、CYPJ在舌鳞癌细胞(TSCC)中的作用及意义,并进一步研究热疗对HIF-1α、CYPJ的调控作用。方法 收集TSCC患者癌组织及癌旁正常组织标本80例,采用免疫组化、蛋白印迹、荧光定量PCR检测各标本中HIF-1α、CYPJ的表达及其与临床病理特征之间的关系。采用qPCR、蛋白印迹检测Cal-27细胞在常氧及乏氧状态下以及用42℃热疗、化疗及热化疗处理时HIF-1α、CYPJ的表达情况。细胞划痕检测细胞迁移,流式细胞术检测细胞凋亡。结果 HIF-1α、CYPJ蛋白在TSCC患者肿瘤组织中的表达水平高于相应的癌旁组织;且二者表达升高与TSCC患者肿瘤大小、TNM分期、分化程度、淋巴结转移等相关(均P<0.05),与性别、年龄无关(均P>0.05)。Cal-27细胞中HIF-1α、CYPJ表达水平在乏氧微环境中升高(均P<0.05),且单独热疗也促进其表达(均P<0.05)。相比于单独热疗及化疗,热化疗联合使用在明显抑制二者的表达的同时抑制细胞迁移并促进细胞凋亡(均P<0.05)。结论 HIF-1α、CYPJ是TSCC肿瘤发生和预后的一个潜在生物标志物,且热疗后肿瘤复发可能源于热疗触发了HIF-1α表达,其通过激活下游靶基因促使适应热处理的肿瘤细胞生长存活,而热疗联合化疗可能是治疗TSCC一种比较有前景的治疗方案。  相似文献   
10.
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