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Lingxu Jiang Yingwan Luo Shuanghong Zhu Lu Wang Liya Ma Hua Zhang Chuying Shen Wenli Yang Yanling Ren Xinping Zhou Chen Mei Li Ye Weilai Xu Haiyang Yang Chenxi Lu Jie Jin Hongyan Tong 《Cancer science》2020,111(2):580-591
Patients with lower‐risk myelodysplastic syndromes (LR‐MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter‐individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS‐relevant genes in 159 patients with LR‐MDS using next‐generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P = .001), RUNX1 (P = .031), EZH2 (P = .049), TP53 (P = .016), SRSF2 (P = .046), JAK2 (P = .040), and IDH2 (P = .035). We also found significantly shorter OS in patients with an adjusted TET2 variant allele frequency (VAF) ≥18% versus those with either an adjusted TET2 VAF <18% or without TET2 mutations (median: 20.4 vs 47.8 months; P = .020; HR = 2.183, 95%CI: 1.129‐4.224). After adjustment for IPSS, shorter OS was associated with mutation status of ASXL1 (P < .001; HR = 4.306, 95% CI: 2.144‐8.650), TP53 (P = .004; HR = 4.863, 95% CI: 1.662‐14.230) and JAK2 (P = .002; HR = 5.466, 95%CI: 1.848‐16.169), as well as adjusted TET2 VAF ≥18% (P = .008; HR = 2.492, 95% CI: 1.273‐4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P < .001). A novel prognostic scoring system incorporating the presence/absence of the four independent mutational factors into the IPSS further stratified LR‐MDS patients into three prognostically different groups (P < .001). The newly developed scoring system redefined 10.1% (16/159) of patients as a higher‐risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of the IPSS with mutation status/burden of certain MDS‐relevant genes may improve the prognostication of patients with LR‐MDS and could help identify those with worse‐than‐expected prognosis for more aggressive treatment. 相似文献
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目的:研究高频电针(100Hz)结合膝关节腔内注射臭氧对膝骨关节炎(KOA)患者血清IL-1及TNF-α水平的影响。方法:将195例KOA患者随机分为三组,100 Hz电针治疗组(A组,n=65); 膝关节腔内臭氧注射治疗组(B组,n=65); 100 Hz电针结合膝关节腔内臭氧注射治疗组(C组,n=65),疗程均为3周。分别于治疗前和治疗后检测患者血清IL-1及TNF-α水平,并进行WOMAC 指数评分。结果:治疗后,三组患者的血清IL-1、TNF-α含量均较治疗开始前有所降低; 且C 组改善水平优于A、B 组,B组改善水平优于A组,差异均具有统计学意义(P<0.05); 治疗后,三组患者WOMAC 指数评分均较治疗前有所降低; 且C 组WOMAC评分好于A和B 组,B 组WOMAC评分优于A 组,差异均有统计学意义(P<0.05)。结论:高频电针结合膝关节腔内注射臭氧可显著抑制KOA患者血清 IL-1、TNF-α的表达,改善患者WOMAC指数评分。 相似文献
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目的 通过检测胆囊癌患者β-纤维蛋白原(Fgβ)-455G/A基因,探讨Fgβ-455G/A基因多态性与胆囊癌的相关性。方法 采集50 例胆囊癌患者(胆囊癌组)和50 例胆囊结石伴慢性胆囊炎患者(胆囊炎组)的静脉血,应用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)方法对Fgβ-455进行基因分型。 结果 Fgβ-455 基因GA杂合型和AA纯合子在胆囊癌中的频率显著高于胆囊炎组,显著增加胆囊癌发生的危险性,OR值(95%CI)分别为2.526(1.052~6.068)和4.306(1.177~15.749)。结论 Fgβ-455G/A位点G/A单个碱基的改变可能在胆囊癌的发病中起着重要的作用。 相似文献
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Qingyang Xiao Yitian Zhou Stefan Winter Florian Büttner Elke Schaeffeler Matthias Schwab Volker M. Lauschke 《International journal of cancer. Journal international du cancer》2020,146(9):2475-2487
Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine. 相似文献
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《Clinical neurophysiology》2019,130(1):128-137
ObjectiveHigh frequency oscillations (HFO) between 80–500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting.MethodsSpikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed.Results24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome.ConclusionsScalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome.SignificanceAnalysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings. 相似文献
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