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1.
Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T2-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T2-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T2-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T2 relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T2 was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T2 relaxation time was derived (R2 = 0.98): T2 (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T2-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T2-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis.  相似文献   
2.
目的:探讨基于脉压变异度(PPV)的目标导向液体治疗(GDFT)在腹膜后巨大恶性肿瘤切除术患儿中的应用。方法:择期行腹膜后巨大恶性肿瘤切除术患儿64例,年龄0.5~3岁,ASA Ⅱ-Ⅲ级。随机将患儿分为目标导向液体治疗组(G组)和常规液体治疗组(C组),每组32例。G组以PPV为指导,根据GDFT方案进行液体管理,C组采用常规液体管理。记录手术开始(T1)、手术开始后1 h(T2)、手术结束(T3)的MAP、CVP、PPV、Lac值、TNF-α、IL-6浓度。记录术中输注晶体液量、胶体液量、液体总量、出血量、尿量、手术时间、多巴胺使用率以及排气时间、术后住院时间和恶心呕吐发生率。结果:G组输注晶体液量显著少于C组(P<0.05),而输注胶体液量显著多于C组(P<0.05)。两组术中输注液体总量、出血量、尿量与多巴胺使用率方面差异无统计学意义。T2、T3时刻,G组PPV、TNF-α、IL-6显著低于C组(P<0.05),而两组间MAP、CVP、Lac在各时点差异无统计学意义。G组术后排气时间明显短于C组(P<0.05),而在术后恶心呕吐发生率和住院时间方面两组差异无统计学意义。结论:PPV指导的GDFT可以应用于腹膜后巨大恶性肿瘤切除术患儿,能维持其血流动力学稳定,减少炎症因子IL-6、TNF-α释放,促进胃肠功能恢复,但对术后转归无明显影响。  相似文献   
3.
《Vaccine》2022,40(15):2274-2281
We evaluated compliance to the ACIP pneumococcal vaccination recommendations issued in 2014 for adults aged ≥ 65 years and in 2012 for adults with high-risk (HR) conditions. The MarketScan® Commercial and Medicare Supplemental databases (January 2007-June 2019) were used to identify the cohorts of interest. Analyses for adults aged ≥ 65 years were adjusted to account for missing vaccination history. Two HR cohorts were identified. The HR1 cohort included patients with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leak, or cochlear implant. The HR2 cohort included patients with chronic heart, lung, or liver disease; diabetes mellitus; alcoholism; cirrhosis; or cigarette smoking. Full compliance for those aged ≥ 65 years or in the HR1 cohort was defined as receipt of PCV13 and PPSV23, and partial compliance was defined as receipt of PCV13 or PPSV23. For those in the HR2 cohort, full compliance was defined as receipt of PPSV23. Annual compliance rates were estimated using the Kaplan–Meier method.Among those aged ≥ 65 years, partial compliance at 4 years post index was 53% and full compliance was 17% in adjusted analyses. In subjects ≥ 65 years receiving the first vaccination, 42% received the second vaccination by year 4. For the HR1 cohort, partial compliance was 19% and full compliance was 5% at 6 years post index date. For the HR2 cohort, full compliance was 20% at 6 years, with the highest rate in patients with diabetes (27%) and the lowest rate in patients with alcoholism (8%).Additional efforts are needed to maximize compliance to the ACIP pneumococcal vaccine recommendations among adults ≥ 65 years of age and adults with HR conditions including streamlined recommendations and single-dose vaccines. These efforts may subsequently reduce the incidence and burden of pneumococcal disease.  相似文献   
4.
目的:通过给小鼠腹腔注射右旋糖酐铁,建立小鼠铁过载干眼模型并初步探索其可能的机制。

方法:将40只雄性C57BL/6小鼠(取右眼为实验眼)用随机数字表法将小鼠分为4组:对照组10只,每次腹腔注射生理盐水0.2mL; 低剂量组、中剂量组、高剂量组各10只为模型组,每次分别腹腔注射浓度为12.5、25、50mg/mL的右旋糖酐铁溶液0.2mL。每3d注射1次,共注射28d。注药后第7、14、28d观察各组小鼠眼表炎症指数、角膜荧光素染色、泪膜破裂时间(BUT)及泪液分泌量(SⅠt),评估干眼及眼表炎症程度。28d后处死小鼠,取角膜、结膜及泪腺组织,进行HE染色、普鲁士蓝染色以及组织铁检测,评估小鼠炎症反应及铁过载情况; 采用酶联免疫吸附试验(ELISA)检测炎症因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)的表达情况。

结果:与对照组相比,模型组小鼠出现一系列干眼症状,小鼠眼表炎症指数增高,角膜荧光素染色评分增加,BUT缩短,泪液分泌量减少(均P<0.05); 模型组小鼠角膜、结膜及泪腺组织均受到不同程度的损伤,各组织眼表铁沉积情况较对照组加重,组织铁含量明显增加(均P<0.01); 模型组小鼠角膜、结膜及泪腺组织中炎症因子(IL-1β、TNF-α、MMP-9)的含量均高于对照组(均P<0.01),随着右旋糖酐铁注药时间及浓度增加,小鼠干眼及眼表炎症程度逐渐加重。

结论:腹腔注射右旋糖酐铁可成功建立小鼠铁过载干眼模型,其机制可能与铁过载加重眼表炎症反应有关。  相似文献   

5.
目的:对食管胃结合部腺癌近端胃切除术(PG)人工三角瓣成形后残胃食糜进行流体动力学数值模拟,并计算不同性质胃内食糜的流动特征。方法:构建常规PG和人工三角瓣成形术术后胃仿真模型,运用Fluent软件对不同粘度胃内食糜反流问题进行数值模拟。结果:站立位姿态时,相对常规PG方案,人工三角瓣成形手术方案表现出较好的抗反流作用;卧位姿态时,当胃内食糜粘度大于0.145 2 Pa[?s,且胃内食糜不超过人工三角瓣情况下,人工三角瓣成形抗反流手术表现出较好的抗反流效果;人工三角瓣抗反流成形手术方案数值模拟结果与临床上患者表现一致。结论:本研究仿真分析为人工三角瓣成形抗反流手术方案的有效性机理分析、临床患者术后饮食及手术方案的进一步改进提供理论及数值依据。 【关键词】食管胃结合部腺癌;抗反流;人工三角瓣;计算流体力学  相似文献   
6.
We evaluated the diagnostic utility of sonication of antibiotic loaded cement spacers comparing with periprosthetic tissue cultures for the detection of persisting infection in 14 patients undergoing staged procedures. Sonication improved microbial detection of intraoperative cultures from 14.2% to 28.5% (P = 0.481). Routine sonication of spacers is recommended.  相似文献   
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9.
Purpose: Hazelnut and birch pollen are known to destroy tear film components and attack ocular surface cells. We investigated further pollen species from different plant families, whether they show similar effects on human tear fluid and an epithelial cell line in vitro, to provide a broad basis for further research on pollen reactions affecting the tear film and ocular surface.

Materials and methods: Regional pollen species from different plant families (Adoxaceae, Betulaceae, Fagaceae, Juglandaceae, Malvaceae, Oleaceae, Pinaceae, Plantaginaceae, Poaceae, Salicaceae, Sapindaceae) were collected. Their proteolytic activity was evaluated by Zymography. Human tear fluid and cells of an epithelial cell line were incubated with pollen extracts. Tear fluid was analyzed by Polyacrylamide gel electrophoresis (PAGE). Cytomorphology was assessed microscopically and cell viability by proliferation (MTS), water-soluble tetrazolium (WST-1) assay and the impedance-based xCELLigence real-time analysis (RTCA).

Results: Zymography revealed significant protease activity and PAGE showed the degradation of tear proteins by different pollen species. Cells incubated with pollen extracts presented dose- and time-dependent cytomorphological changes. MTS, WST-1, and RTCA revealed cytostatic as well as cytotoxic effects of pollen extracts.

Conclusions: Pollen species from different plant families exert proteolytic activity and degrade human tear fluid as well as epithelial cells, which may play a crucial role in the pathogenesis of allergic and non-allergic reactions affecting the ocular surface.  相似文献   

10.
In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders.  相似文献   
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