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991.
目的探讨肺癌化疗后发生化疗相关性白细胞减少(CIL)的危险因素。方法采用回顾性病例对照研究的方法,将192例肺癌化疗后发生CIL患者(CIL组)和100例无CIL患者(对照组)的临床指标进行单因素和多因素分析。结果在292例肺癌化疗患者中,共192例出现CIL,发生率为65.8%,其中28例(14.6%)为Ⅲ-Ⅳ级CIL。两组的性别(P=0.691)、年龄(P=0.245)、基础疾病(P=0.670)差异无统计学意义。CIL组的体质量下降率、PS评分、治疗前白细胞计数、治疗前血小板计数、曾接受化疗次数与对照组比较差异有统计学意义(P〈0.05)。多因素分析显示治疗前白细胞减低(OR=11.852)、体质量下降率≥5%(OR=0.324)、曾接受化疗次数≥3(OR=2.709)是肺癌化疗后发生CIL的独立危险因素。结论治疗前白细胞减低、体质量下降率≥5%、曾接受化疗次数≥3是肺癌化疗后发生CIL的独立危险因素。 相似文献
992.
目的通过比较机械通气患者容量-时间曲线指导的气囊充气法(以下简称容量-时间曲线法)与最小闭合容量(minimalocclusivevolume,MOV)法的气囊充气量及气囊压力,探讨两种气囊压力管理方法的优劣。方法80例患者纳入研究。在相同的机械通气模式、参数条件下,每例患者在研究开始时完全消气囊,在先后用MOV法及容量-时间曲线法重新充气直至完全闭合气道。两次气囊充气间相隔20min,分别记录并比较两者方法的气囊充气量及压力值。结果容量一时间曲线法的气囊充气量及气囊压力明显小于MOV法(PdO.01),12.5%(10/80)患者用MOV法充气后从容量-时间曲线观察仍存在漏气。结论容量一时间曲线指导的气管导管气囊法较MOV法精确、客观,是一种更可靠的指导气囊压力管理的方法。 相似文献
993.
Yuanyuan Zheng Limin Wang Zhixiang Zhu Xinxin YanLane Zhang Pingxiang XuDali Luo 《Thrombosis research》2014
Introduction
Downregulation of calsequestrin (CSQ), a major Ca2 + storage protein, may contribute significantly to the hyperactivity of internal Ca2 + ([Ca2 +]i) in diabetic platelets. Here, we investigated changes in CSQ-1 abundance, Ca2 + signaling and aggregation responses to stimulation with the progression of diabetes, especially the mechanism(s) underlying the exaggerated Ca2 + influx in diabetic platelets.Materials and methods
Type 1 diabetes was induced by streptozotocin in rats. Platelet [Ca2 +]i and aggregation responses upon ADP stimulation were assessed by fluorescence spectrophotometry and aggregometry, respectively. CSQ-1 expression was evaluated using western blotting.Results
During the 12-week course of diabetes, the abundance of CSQ-1, basal [Ca2 +]i and ADP-induced Ca2 + release were progressively altered in diabetic platelets, while the elevated Ca2 + influx and platelet aggregation were not correlated with diabetes development. 2-Aminoethoxydiphenyl borate, the store-operated Ca2 + channel blocker, almost completely abolished ADP-induced Ca2 + influx in normal and diabetic platelets, whereas nifedipine, an inhibitor of the nicotinic acid adenine dinucleotide phosphate receptor, showed no effect. Additionally, inhibition of Na+/Ca2 + exchange induced much slower Ca2 + extrusion and more Ca2 + influx in normal platelets than in diabetic platelets. Furthermore, under the condition of Ca2 +-ATPase inhibition, ionomycin caused greater Ca2 + mobilization and Ca2 + influx in diabetic platelets than in normal platelets.Conclusions
These data demonstrate that platelet hyperactivity in diabetes is caused by several integrated factors. Besides the downregulation of CSQ-1 that mainly disrupts basal Ca2 + homeostasis, insufficient Na+/Ca2 + exchange also contributes, at least in part, to the hyperactive Ca2 + response to stimulation in diabetic platelets. 相似文献994.
995.
996.
Celestino-Soper PB Violante S Crawford EL Luo R Lionel AC Delaby E Cai G Sadikovic B Lee K Lo C Gao K Person RE Moss TJ German JR Huang N Shinawi M Treadwell-Deering D Szatmari P Roberts W Fernandez B Schroer RJ Stevenson RE Buxbaum JD Betancur C Scherer SW Sanders SJ Geschwind DH Sutcliffe JS Hurles ME Wanders RJ Shaw CA Leal SM Cook EH Goin-Kochel RP Vaz FM Beaudet AL 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(21):7974-7981
We recently reported a deletion of exon 2 of the trimethyllysine hydroxylase epsilon (TMLHE) gene in a proband with autism. TMLHE maps to the X chromosome and encodes the first enzyme in carnitine biosynthesis, 6-N-trimethyllysine dioxygenase. Deletion of exon 2 of TMLHE causes enzyme deficiency, resulting in increased substrate concentration (6-N-trimethyllysine) and decreased product levels (3-hydroxy-6-N-trimethyllysine and γ-butyrobetaine) in plasma and urine. TMLHE deficiency is common in control males (24 in 8,787 or 1 in 366) and was not significantly increased in frequency in probands from simplex autism families (9 in 2,904 or 1 in 323). However, it was 2.82-fold more frequent in probands from male-male multiplex autism families compared with controls (7 in 909 or 1 in 130; P = 0.023). Additionally, six of seven autistic male siblings of probands in male-male multiplex families had the deletion, suggesting that TMLHE deficiency is a risk factor for autism (metaanalysis Z-score = 2.90 and P = 0.0037), although with low penetrance (2-4%). These data suggest that dysregulation of carnitine metabolism may be important in nondysmorphic autism; that abnormalities of carnitine intake, loss, transport, or synthesis may be important in a larger fraction of nondysmorphic autism cases; and that the carnitine pathway may provide a novel target for therapy or prevention of autism. 相似文献
997.
Yan KS Chia LA Li X Ootani A Su J Lee JY Su N Luo Y Heilshorn SC Amieva MR Sangiorgi E Capecchi MR Kuo CJ 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(2):466-471
The small intestine epithelium undergoes rapid and continuous regeneration supported by crypt intestinal stem cells (ISCs). Bmi1 and Lgr5 have been independently identified to mark long-lived multipotent ISCs by lineage tracing in mice; however, the functional distinctions between these two populations remain undefined. Here, we demonstrate that Bmi1 and Lgr5 mark two functionally distinct ISCs in vivo. Lgr5 marks mitotically active ISCs that exhibit exquisite sensitivity to canonical Wnt modulation, contribute robustly to homeostatic regeneration, and are quantitatively ablated by irradiation. In contrast, Bmi1 marks quiescent ISCs that are insensitive to Wnt perturbations, contribute weakly to homeostatic regeneration, and are resistant to high-dose radiation injury. After irradiation, however, the normally quiescent Bmi1(+) ISCs dramatically proliferate to clonally repopulate multiple contiguous crypts and villi. Clonogenic culture of isolated single Bmi1(+) ISCs yields long-lived self-renewing spheroids of intestinal epithelium that produce Lgr5-expressing cells, thereby establishing a lineage relationship between these two populations in vitro. Taken together, these data provide direct evidence that Bmi1 marks quiescent, injury-inducible reserve ISCs that exhibit striking functional distinctions from Lgr5(+) ISCs and support a model whereby distinct ISC populations facilitate homeostatic vs. injury-induced regeneration. 相似文献
998.
PX Shaw L Zhang M Zhang H Du L Zhao C Lee S Grob SL Lim G Hughes J Lee M Bedell MH Nelson F Lu M Krupa J Luo H Ouyang Z Tu Z Su J Zhu X Wei Z Feng Y Duan Z Yang H Ferreyra DU Bartsch I Kozak L Zhang F Lin H Sun H Feng K Zhang 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(34):13757-13762
The rs1061170T/C variant encoding the Y402H change in complement factor H (CFH) has been identified by genome-wide association studies as being significantly associated with age-related macular degeneration (AMD). However, the precise mechanism by which this CFH variant impacts the risk of AMD remains largely unknown. Oxidative stress plays an important role in many aging diseases, including cardiovascular disease and AMD. A large amount of oxidized phospholipids (oxPLs) are generated in the eye because of sunlight exposure and high oxygen content. OxPLs bind to the retinal pigment epithelium and macrophages and strongly activate downstream inflammatory cascades. We hypothesize that CFH may impact the risk of AMD by modulating oxidative stress. Here we demonstrate that CFH binds to oxPLs. The CFH 402Y variant of the protective rs1061170 genotype binds oxPLs with a higher affinity and exhibits a stronger inhibitory effect on the binding of oxPLs to retinal pigment epithelium and macrophages. In addition, plasma from non-AMD subjects with the protective genotype has a lower level of systemic oxidative stress measured by oxPLs per apolipoprotein B (oxPLs/apoB). We also show that oxPL stimulation increases expression of genes involved in macrophage infiltration, inflammation, and neovascularization in the eye. OxPLs colocalize with CFH in drusen in the human AMD eye. Subretinal injection of oxPLs induces choroidal neovascularization in mice. In addition, we show that the CFH risk allele confers higher complement activation and cell lysis activity. Together, these findings suggest that CFH influences AMD risk by modulating oxidative stress, inflammation, and abnormal angiogenesis. 相似文献
999.
Few studies to date have reported on the development and application of a nanobiosensor based on localized surface plasmon resonance (LSPR) for detecting gene mutations. This study aimed to develop a novel LSPR biosensor used for detecting p53 mutation. Nanosphere lithography was used to fabricate the silver nanoparticles. The DNA probe was designed to recognize the target sequence and immobilized on the chip surface by a covalent-coupling method using amine-group ligands. Synthetic oligonucleotides or PCR products were amplified from genomic DNA taken from blood samples and hybridized with the immobilized probe. Wild-type and mutant p53 was detected by measuring shifts in peak of LSPR extinction spectra. The low detection limit of the sensor for target sequence was 10 nM, and detection occurred over a wide dynamic range (10 nM - 10 μM). Importantly, the differences in measuring signal between wild-type and mismatched p53 DNA was significant, allowing for this sensor to effectively discriminate against single base mutations. In conclusion, we developed a biosensor with potential as a rapid, label-free, sensitive, and low-cost method for detecting p53 mutation. Our results suggest that such an LSPR-based biosensor provides an attractive alternative for clinical detection of genetic mutation. 相似文献
1000.