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11.
Electroacupuncture has been widely used to treat cognitive impairment after cerebral ischemia, but the underlying mechanism has not yet been fully elucidated. Studies have shown that autophagy plays an important role in the formation and development of cognitive impairment, and the phosphoinositide 3-kinase(PI3 K)/Akt signaling pathway plays an important role in autophagy regulation. To investigate the role played by the PI3 K/Akt signaling pathway in the electroacupuncture treatment of cerebral ischemia/reperfusion rat models, we first established a rat model of cerebral ischemia/reperfusion through the occlusion of the middle cerebral artery using the suture method. Starting at 2 hours after modeling, electroacupuncture was delivered at the Shenting(GV24) and Baihui(GV20) acupoints, with a dilatational wave(1–20 Hz frequency, 2 mA intensity, 6 V peak voltage), for 30 minutes/day over 8 consecutive days. Our results showed that electroacupuncture reduced the infarct volume in a rat model of cerebral ischemia/reperfusion injury, increased the mRNA expression levels of the PI3 K/Akt signaling pathwayrelated factors Beclin-1, mammalian target of rapamycin(mTOR), and PI3 K, increased the protein expression levels of phosphorylated Akt, Beclin-1, PI3 K, and mTOR in the ischemic cerebral cortex, and simultaneously reduced p53 mRNA and protein expression levels. In the Morris water maze test, the latency to find the hidden platform was significantly shortened among rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. In the spatial probe test, the number of times that a rat crossed the target quadrant was increased in rats subjected to electroacupuncture stimulation compared with rats without electroacupuncture stimulation. Electroacupuncture stimulation applied to the Shenting(GV24) and Baihui(GV20) acupoints activated the PI3 K/Akt signaling pathway and improved rat learning and memory impairment. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, China(approval No. 8150150901) on March 10, 2016.  相似文献   
12.
13.

Objective

To compare perioperative and long-term outcomes in patients undergoing hemiarch and aggressive arch replacement for acute type A aortic dissection (ATAAD).

Methods

From 1996 to 2017, we compared outcomes of hemiarch (n = 322) versus aggressive arch replacements (zones 2 and 3 arch replacement with implantation of 2-4 arch branches, n = 150) in ATAAD. Indications for aggressive arch were arch aneurysm >4 cm or intimal tear in the aortic arch that was not resectable by hemiarch replacement, or dissection of arch branches with malperfusion.

Results

Patients in the aggressive arch group were significantly younger (mean age: 57 vs 61 years old) and had significantly longer hypothermic circulatory arrest, cardiopulmonary bypass, and aortic crossclamp times. There were no significant differences in perioperative outcomes between hemiarch and aggressive arch groups, including 30-day mortality (5.3% vs 7.3%, P = .38) and postoperative stroke rate (7% vs 7%, P = .96). Over 15 years, Kaplan–Meier survival was similar between hemiarch and aggressive arch groups (log-rank P = .55, 10-year survival 70% vs 72%). Given death as a competing factor, incidence rates of reoperation over 15 years (2.1% vs 2.0% per year, P = 1) and 10-year cumulative incidence of reoperation (14% vs 12%, P = .89) for arch and distal aorta pathology were similar between the 2 groups.

Conclusions

Both hemiarch and aggressive arch replacement are appropriate approaches for select patients with ATAAD. Aggressive arch replacement should be considered for an arch aneurysm >4 cm or an intimal tear at the arch unable to be resected by hemiarch replacement, or dissection of the arch branches with malperfusion.  相似文献   
14.
Objective: The main pathological change of Parkinson’s disease (PD) is progressive degeneration and necrosis of dopaminergic neurons in the midbrain, forming a Lewy body in many of the remaining neurons. Studies have found that in transgenic Drosophila, mutations in the PTEN-inducible kinase 1 (PINK1) gene may cause indirect flight muscle defects in Drosophila, and mitochondrial structural dysfunction as well.

Methods: In this study, Wnt4 gene overexpression and knockdown were performed in PINK1 mutant PD transgenic Drosophila, and the protective effect of Wnt4 gene on PD transgenic Drosophila and its possible mechanism were explored. The Wnt4 gene was screened in the previous experiment; And by using the PD transgenic Drosophila model of the MHC-Gal4/UAS system, the PINK1 gene could be specifically activated in the Drosophila muscle tissue.

Results: In PINK1 mutation transgenic fruit flies, the Wnt4 gene to study its implication on PD transgenic fruit flies’ wing normality and flight ability. We found that overexpression of Wnt4 gene significantly reduced abnormality rate of PD transgenic Drosophila and improved its flight ability, and then, increased ATP concentration, enhanced mitochondrial membrane potential and normalized mitochondrial morphology were found. All of these findings suggested Wnt4 gene may have a protective effect on PD transgenic fruit flies. Furthermore, in Wnt4 gene overexpression PD transgenic Drosophila, down-regulation autophagy and apoptosis-related proteins Ref(2)P, Pro-Caspase3, and up-regulation of Beclin1, Atg8a, Bcl2 protein were confirmed by Western Blotting.

Conclusion: The results imply that the restoring of mitochondrial function though Wnt4 gene overexpression in the PINK1 mutant transgenic Drosophila may be related to autophagy and/or apoptosis.  相似文献   

15.

Background and aims

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

Methods and results

The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.

Conclusion

The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall.  相似文献   
16.

Introduction

There are limited randomized data comparing radical cystectomy (RC) with bladder-sparing tri-modality therapy (TMT) in the treatment of muscle-invasive bladder cancer (MIBC). Both strategies are thought to have similar survival outcomes with different morbidity profiles. We compare the effectiveness of TMT and RC using decision-analytic modeling and the endpoint of quality-adjusted life years (QALYs).

Patients and Methods

Using a Markov model, we simulated the lifetime outcomes after TMT versus RC ± neoadjuvant chemotherapy for 67-year-old patients with clinical stage T2-T4aN0M0 MIBC. Model probabilities and utilities were extracted from the literature. The incremental effectiveness was reported in QALYs and sensitivity analyses were performed.

Results

For all patients with MIBC, although the model showed identical survival, TMT was the most effective strategy with an incremental gain of 0.59 QALYs over RC (7.83 vs. 7.24 QALYs, respectively). When limiting the model to favorable, contemporary cohorts in both the TMT and RC strategies, TMT remained more effective with an incremental gain of 1.61 QALYs (9.37 vs. 7.76 QALYs, respectively). One-way sensitivity analyses demonstrated the model was sensitive to the quality of life parameters (ie, the utilities) for RC and TMT. When testing the 95% confidence interval of the RC utility parameter the model demonstrated an incremental gain with TMT from ?0.54 to 4.23 QALYs. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC for 63% of model iterations.

Conclusions

This modeling study found that treatment of MIBC with organ-sparing TMT in appropriately-selected patients may result in a gain of QALYs relative to RC.  相似文献   
17.
目的总结分析胃癌D2根治术后发生大出血的原因及治疗方法并探讨其对生存预后的影响。方法回顾性分析广东省中医院2012年1月至2016年3月258例行胃癌D2根治术患者的临床资料,根据术后是否发生大出血分为出血组和非出血组。结果14例患者(5.4%)术后发生大出血;吻合口出血、十二指肠残端瘘或破裂是出血的主要原因;二次手术和胃镜止血是主要治疗措施。两组的短期总生存期有统计学意义(1年:P=0.017,3年:P=0.011)。结论吻合口出血、十二指肠残端瘘或破裂是胃癌D2根治术后出血的主要原因,及时诊断和治疗能有效降低病死率。胃癌D2根治术后大出血会降低患者的短期总生存期。  相似文献   
18.
Objective To prove the efficacy of peritoneal dialysis on shock wave-induced acute lung injury of rats, and analyze its mechanisms. Methods Forty-five adult Sprague-Dawley rats were randomly divided into three groups: control group, sham operation (Sham) group and peritoneal dialysis (PD) group. Sham group and PD group did abdominal catheterization before blast injury. The 55 kg shock wave (bst-I) was used to induce lung blast injury. After one hour of blast injury, PD group was given 2.5% peritoneal dialysate 20 ml to stay abdomen, which was released 30 min posted, repeated 12 cycles. After 6 hours of peritoneal dialysis, all of the rats were sacrificed. Partial damaged tissues in lung were used to evaluate the pathomorphologic changes by HE staining, and the remnants were used to measure the lung water content. Lung function was detected by blood gas analyzer and small animal detector from the arterial blood gas. The levels of serum inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and monocyte chemoattractant protein-1 (MCP-1) were tested by ELISA. Results The relative integrity of alveolar structure, interstitial edema and inflammatory cell infiltration in PD group were significantly improved than those in control group. The lung water content of PD group was significantly lower than that of control group (P<0.05). The levels of TNF-α, IL-1β, IL-6 and MCP-1 in serum of PD group were significantly lower than those in control group (all P<0.05). The blood oxygen saturation, oxygen partial pressure, oxygenation index, vital capacity, functional residual volume and maximum mid-expiratory flow rate in PD group were significantly higher than those in control group (all P<0.05). Conclusions Through reducing pulmonary edema and inflammatory factors, peritoneal dialysis can improve lung function in shock wave -induced acute lung injury of rats.  相似文献   
19.
In the previous research, we found that anticancer agent LS-1-2F could cause the vacuolation of tumor cells. Herein we investigated the effect of compound LS-1-2F on the endocytosis of macromolecules, including fluorescence quantum dots, human serum albumin, single-stranded RNA, and monoclonal antibody, into tumor cells. We found that LS-1-2F could accelerate the endocytosis of these large molecules by laser confocal microscope and flow cytometry. The effect of LS-1-2F on the improvement of the internalization efficiency of Herceptin biosimilar was particularly significant. Promoting endocytosis will help increase the efficiency of liquid-phase drug uptake in drug-resistant cancer cells and could potentially facilitate the use of drugs in nanoparticle delivery vehicles.  相似文献   
20.
目的探讨无创产前检测(NIPT)联合孕妇血清可溶性转铁蛋白受体(sTfR)、生长分化因子(GDF)-15、红细胞体积分布宽度变异系数(RDW-CV)检测,对胎儿β-地中海贫血的诊断价值。 方法选择2017年1月至2018年6月,于自贡市妇幼保健院接受羊膜腔穿刺术确诊胎儿为β-地中海贫血的120例孕妇为研究对象。根据其妊娠胎儿的β-地中海贫血轻、中、重型,将其分别纳入轻型组(n=48)、中型组(n=40)与重型组(n=32)。选取同期于本院建卡进行常规产前检查,并且妊娠胎儿发育正常的100例健康孕妇作为对照,纳入对照组。采集4组孕妇空腹肘静脉血,提取孕妇外周血浆中胎儿细胞外游离DNA(cfDNA),采用2次PCR方法扩增后,采用反向斑点杂交方法检测胎儿β-地中海贫血基因。采用酶联免疫吸附测定法,测定4组孕妇血清sTfR、GDF-15、RDW-CV水平。对4组孕妇血清sTfR、GDF-15与RDW-CV水平分别总体比较,采用单因素方差分析,进一步两两比较,采用最小显著性差异(LSD)-t检验。与胎儿β-地中海贫血诊断"金标准"比较,计算NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平及这4项指标单独检测,对于胎儿β-地中海贫血诊断的敏感度、特异度、粗符合率、阳性预测值、阴性预测值。本研究严格按照2013年修订的《世界医学协会赫尔辛基宣言》要求进行。4组孕妇年龄及其妊娠胎儿的胎龄等一般临床资料比较,差异均无统计学意义(P>0.05)。 结果①夫妻双方β-地中海贫血基因型相同的40例孕妇中,NIPT与羊膜腔穿刺术对于胎儿β-地中海贫血诊断的符合率为90.0%(36/40);夫妻双方β-地中海贫血基因型不同的80例孕妇中,上述2种方法对于胎儿β-地中海贫血诊断的符合率亦为90. 0%(72/80)。②4组孕妇血清sTfR、GDF-15、RDW-CV水平分别总体比较,差异均有统计学意义(F=2 283.445、323.181、45.900,P均<0.001),进一步两两比较,任意2组孕妇血清sTfR、GDF-15、RDW-CV水平比较,差异均有统计学意义(P<0.05),并且孕妇血清sTfR、GDF-15、RDW-CV水平随着β-地中海贫血胎儿严重程度增加而逐渐升高。③NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平检测,对于胎儿β-地中海贫血诊断的敏感度、特异度、粗符合率、阳性预测值与阴性预测值,分别为86.7%、88.0%、87.3%、86.7%与84.6%,其特异度与阳性预测值,均显著高于单独检测孕妇血清sTfR、GDF-15、RDW-CV水平,并且差异均有统计学意义(与孕妇血清sTfR水平比较:χ2=8.866、5.301,P=0.003、0.021;与孕妇血清GDF-15水平比较:χ2=9.765、5.929,P=0.002、0.015;与孕妇血清RDW-CV水平比较:χ2=7.167、4.327,P=0.007、0.038)。 结论孕妇血清sTfR、GDF-15、RDW-CV可能成为诊断胎儿β-地中海贫血的生物标志物,NIPT联合这3项指标检测,可提高诊断胎儿β-地中海贫血的特异度与阳性预测值。由于本研究纳入样本量相对较小,NIPT联合孕妇血清sTfR、GDF-15、RDW-CV水平,对胎儿β-地中海贫血的诊断价值,仍然有待进一步研究、证实。  相似文献   
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