Prognostic CpG Methylation Biomarkers Identified by Methylation Array in Esophageal Squamous Cell Carcinoma Patients

Background: Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with poor prognosis. We aimed to identify a panel of CpG methylation biomarkers for prognosis prediction of ESCC patients.Methods: Illumina''s GoldenGate methylation array, supervised principal components, Kaplan-Meier survival analyses and Cox regression model were conducted on dissected tumor tissues from a training cohort of 40 ESCC patients to identify potential CpG methylation biomarkers. Pyrosequencing quantitative methylation assay were performed to validate prognostic CpG methylation biomarkers in 61 ESCC patients. The correlation between DNA methylation and RNA expression of a validated marker, SOX17, was examined in a validation cohort of 61 ESCC patients.Results: We identified a panel of nine CpG methylation probes located at promoter or exon1 region of eight genes including DDIT3, FES, FLT3, NTRK3, SEPT5, SEPT9, SOX1, and SOX17, for prognosis prediction in ESCC patients. Risk score calculated using the eight-gene panel statistically predicted poor outcome for patients with high risk score. These eight-gene also showed a significantly higher methylation level in tumor tissues than their corresponding normal samples in all patients analyzed. In addition, we also detected an inverse correlation between CpG hypermethylation and the mRNA expression level of SOX17 gene in ESCC patients, indicating that DNA hypermethylation was responsible for decreased expression of SOX17.Conclusions: This study established a proof-of-concept CpG methylation biomarker panel for ESCC prognosis that can be further validated by multiple cohort studies. Functional characterization of the eight prognostic methylation genes in our biomarker panel could help to dissect the mechanism of ESCC tumorigenesis.     

Cervical Arthroplasty for Moderate to Severe Disc Degeneration: Clinical and Radiological Assessments after a Minimum Follow-Up of 18 Months: Pfirrmann Grade and Cervical Arthroplasty

Purpose

Clinical outcomes and radiologic results after cervical arthroplasty have been reported in many articles, yet relatively few studies after cervical arthroplasty have been conducted in severe degenerative cervical disc disease.

Materials and Methods

Sixty patients who underwent cervical arthroplasty (Mobi-C®) between April 2006 and November 2011 with a minimum follow-up of 18 months were enrolled in this study. Patients were divided into two groups according to Pfirrmann classification on preoperative cervical MR images: group A (Pfirrmann disc grade III, n=38) and group B (Pfirrmann disc grades IV or V, n=22). Visual analogue scale (VAS) scores of neck and arm pain, modified Oswestry Disability Index (mODI) score, and radiological results including cervical range of motion (ROM) were assessed before and after surgery.

Results

VAS and mean mODI scores decreased after surgery from 5.1 and 57.6 to 2.7 and 31.5 in group A and from 6.1 and 59.9 to 3.7 and 38.4 in group B, respectively. In both groups, VAS and mODI scores significantly improved postoperatively (p<0.001), although no significant intergroup differences were found. Also, cervical dynamic ROM was preserved or gradually improved up to 18 months after cervical arthroplasty in both groups. Global, segmental and adjacent ROM was similar for both groups during follow-up. No cases of device subsidence or extrusion were recorded.

Conclusion

Clinical and radiological results following cervical arthroplasty in patients with severe degenerative cervical disc disease were no different from those in patients with mild degenerative cervical disc disease after 18 months of follow-up.     

Prevalence of Osteoporosis in Female Patients with Advanced Knee Osteoarthritis Undergoing Total Knee Arthroplasty

This study sought to demonstrate bone mineral density (BMD) conditions in elderly female patients with knee osteoarthritis (OA) undergoing total knee arthroplasty (TKA). In addition, we sought to determine whether their BMD conditions differ from those of community-based females without knee OA. Finally we sought to determine whether clinical statuses are related to BMD in the knee OA patients. BMD conditions in 347 female patients undergoing TKA and 273 community-based females were evaluated. Additionally, comparative analyses of BMD between age and body mass index-matched knee OA groups (n=212) and the control groups (n=212) were performed. In the pre-matched knee OA group, regression analyses were performed to determine whether preoperative clinical statuses were related to BMD. Considerable prevalence of coexistent osteoporosis (31%) was found in the pre-matched knee OA patients undergoing TKA. We found no significant differences of the BMD T-scores and the prevalence of osteoporosis between the age and body mass index-matched knee OA and control groups. In the pre-matched knee OA patients, poorer preoperative clinical scores were related to poorer BMD T-scores in the proximal femur and/or lumbar spine. Our study suggests that more attention should be paid to identify and treat osteoporosis in elderly female patients with advanced knee OA undergoing TKA.

Graphical Abstract

相似文献   

白细胞介素7和15对肺结核患者Th1/Th2平衡的调节作用

目的探讨白细胞介素7(IL7)、IL15对肺结核病患者外周血单个核细胞(PBMC)分泌Th1型细胞因子γ干扰素(IFNγ)、肿瘤坏死因子α(TNFα)和Th2型细胞因子IL4、IL10的影响。方法选择2003年1至9月入院的60例肺结核患者和25名健康对照者,用葡聚糖泛影葡胺密度梯度离心法分离PBMC。按加入刺激物的不同,将每份标本分为6组:RPMI1640组、纯化蛋白衍生物(PPD组)、PPD+IL7组、PPD+IL7抗体组、PPD+IL15组、PPD+IL15抗体组。加入相应刺激物后培养72h,收集上清液,采用酶联免疫吸附法(ELISA)检测各组培养上清液中IFNγ、TNFα、IL4、IL10的水平。结果与PPD组相比,加入IL7的患者组PBMC分泌IFNγ和TNFα显著增高,分别为(107±42)～(157±74)ng/L、(460±128)～(887±242)ng/L;显著抑制IL4和IL10的合成,分别为(58±15)～(31±9)ng/L、(153±40)～(112±32)ng/L。健康对照组PBMC分泌IFNγ和TNFα显著增高,分别为(211±57)～(292±92)ng/L、(1203±390)～(1722±503)ng/L;显著抑制IL4和IL10的合成,分别为(43±13)～(36±11)ng/L、(135±37)～(96±36)ng/L。加入IL15患者组PBMC分泌IFNγ和TNFα显著增高,分别为(107±42)～(231±62)ng/L、(460±128)～(843±208)ng/L;显著抑制IL4和IL10的合成,分别为(58±15)～(37±9)ng/L、(153±40)～(116±41)ng/L。健康对照组PBMC分泌IFNγ和TNFα显著增高,分别为(211±57)～(343±108)ng/L、(1203±390)～(1468±235)ng/L;显著抑制IL4和IL10的合成,分别为(43±13)～(36±8)ng/L、(135±37)～(90±35)ng/L。加入IL7抗体或IL15抗体均可抑制IFNγ和TNFα的分泌,促进IL4和IL10的合成。肺结核患者各组IFNγ、TNFα水平均低于健康对照各组,而IL4、IL10水平比较差异无统计学意义。结论IL7和IL15可作为免疫调节剂,诱导IFNγ及TNFα分泌,抑制IL4及IL10合成,从而调节Th1/Th2平衡,发挥对结核分枝杆菌感染患者的免疫保护作用。     

丹参对胃和十二指肠粘膜微循环血流和胃液分泌的影响

采用幽门结扎灌流法及氢气清除技术连续动态地观察了丹参注入前后,大鼠胃液分泌量、胃总酸度和胃及十二指肠粘膜血流量的改变,以深入探讨丹参的抗消化性溃疡,保护胃肠粘膜的作用机制。结果表明:丹参注入后40min左右,胃泌素刺激引起的胃液分泌亢进和胃酸排出增多均受到明显的抑制,效应持续120min以上;丹参注入20min左右,胃体和十二指肠粘膜的血流量分别增加了29.8%和43.7%(P<0.01)。在胃泌素引起最大胃液分泌亢进的同时,可伴有粘膜血流增多的趋势,但无统计学意义;上述结果提示,丹参能减少胃液的分泌和H~+的分泌,但其对胃肠粘膜的保护作用主要是借助改善粘膜的血液灌流而完成的。     

IL-6、IL-1及TNF对人类骨髓瘤细胞系KM_2、KM_3增殖的影响

细胞因子的异常表达对骨髓瘤细胞的恶性增殖起重要作用。本文研究了IL-6、IL-1及TNF 对人骨髓瘤细胞系增殖的影响。KM_2、KM,均能分泌IL-6,以维持自身的增殖。培养体系中加入抗IL-6抗体可抑制瘤细胞的增殖,这种抑制作用可通过加入重组IL-6而逆转.在培养体系中加入重组IL-6和TNF 均可促进KM_2、KM_3的增殖,而IL-1无此作用。培养体系中加入TNF 培养后,上清中IL-6活性增高。我们的结果提示,人骨髓瘤细胞系KM_2、KM_3存在IL-6自分泌增殖机制,而TNF 可加强这种自分泌作用。     

5-氮胞苷对培养兔骨髓基质细胞心房利钠肽表达的影响

目的研究5-氮胞苷(5-azacytidine,5-aza)对体外培养兔骨髓基质细胞中心肌特异性心房利钠肽(atrialnatriureticpolypeptide,ANP)表达的影响,探讨骨髓基质细胞向心肌样细胞分化的条件。方法体外分离培养兔骨髓基质细胞用不同浓度5-aza诱导培养,以RT-PCR方法测定诱导前后ANP的表达。结果正常培养兔骨髓基质细胞不表达ANP。经5-aza诱导并继续培养24h后,骨髓基质细胞表达ANP,在一定时间、浓度范围内ANP含量逐渐增加。结论5-aza诱导体外培养兔骨髓基质细胞表达心肌特异性ANP,与诱导时间及浓度呈正相关,提示可诱导兔骨髓基质细胞向心肌样细胞分化。     

Association between inflammatory markers and frailty in institutionalized older men

Objectives

To determine whether higher serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (CRP) were associated with frailty in the older institutionalized men.

Participants

The study enrolled 386 residents from a veterans care home in northern Taiwan in 2007. All participants were men. Residents younger than 65 years or with acute illness were excluded.

Methods

Frailty status was determined based on the frailty phenotype (indicators include weight loss, exhaustion, and low grip strength, slow walking speed). Participants with 3 or more of the indicators were defined as frail, with 1 or 2 as intermediate frail, with no as non-frail. Serum IL-6, TNF-α, and hsCRP levels were measured using enzyme-linked immunosorbent assay and modeled as tertile for severely skewed distributions.

Results

The mean age of the participants was 81.5 ± 4.9 years. The percentages of frail were 33.2%, intermediate frail 59.1% and nonfrail 7.8%. Higher IL-6 level was positively associated with the frail status. Adjusting for age, body mass index, smoking status, and comorbid conditions, serum IL-6 showed significant trend across frailty categories (P = 0.03 [95% CI 1.40–5.24]). No significant associations of TNF-α, and CRP level with frailty were observed. An IL-6 level of 1.79 pg/mL had the optimal predictive value for frailty, with an area under the receiver operating characteristic (ROC) curve of 0.66 (P = 0.01 [95% CI 0.53–0.78]).

Conclusion

Higher serum levels of IL-6 were associated with frailty status in the older institutionalized men with multiple comorbidities.     

Psychometric assessment of female overactive bladder syndrome and antimuscarinics-related effects

Objectives

To investigate the characteristics of psychological distress (PD), personality traits, and family support in women with overactive bladder syndrome (OAB), and the effects of antimuscarinic treatment.

Study design

Women with and without OAB (age- and body mass index [BMI]-matched control group) were prospectively enrolled; they recorded bladder diaries, underwent urodynamic studies, and completed PD, personality traits, and filled family support questionnaires before and after antimuscarinic treatment. OAB women underwent treatment with tolterodine or solifenacin for 12 weeks. The control group completed questionnaires.

Main outcome measures

The differences in PD, personality traits, and family support scores between both groups, and the changes after antimuscarinic treatment in OAB women.

Results

Eighty-five women with OAB (tolterodine, n = 42; solifenacin, n = 43) and 65 without OAB completed the studies. Linear regression analysis with age and BMI adjustment revealed: coefficients of OAB were significant (all P < 0.05) for somatic complaints (mean: 0.87 vs. 0.63, coefficient = 0.21), obsessive–compulsive symptoms (0.69 vs. 0.44, coefficient = 0.25), anxiety symptoms (0.42 vs. 0.27, coefficient = 0.14), General Symptom Index (GSI, 0.48 vs. 0.33, coefficient = 0.14), neuroticism (9.23 vs. 5.17, coefficient = 3.73), and extroversion–introversion (13.64 vs. 15.25, coefficient = −1.73). Anxiety symptoms (0.42 vs. 0.36) and GSI (0.48 vs. 0.39) improved after antimuscarinics (all P < 0.05). High Overactive Bladder Symptom Score questionnaire score (coefficient = −0.39), low hostility score (coefficient = 2.11), and high additional symptoms score (coefficient = −1.46) were associated with good therapeutic effect (all P < 0.05).

Conclusions

OAB women experience more PD, neuroticism, and introversion than asymptomatic women, and antimuscarinics could improve PD.