非小细胞肺癌患者p53基因突变检测的临床意义

目的探讨非小细胞肺癌（NSCLC）患者呼出气冷凝液（EBC）中p53基因突变检测的临床意义。方法采用巢式PCR结合DNA测序法,检测53例NSCLC患者EBC中p53基因第5～8外显子的突变情况,并以32例健康体检者EBC标本作为对照。结果肺癌组53例EBC标本中扩增到1）53基因26例,其中10例检测到p53基因突变,突变率为38．5％（10／26）;正常对照组32例EBC标本中扩增到p53基因15例,但未检测到p53基因突变。结论p53基因突变可能参与NSCLC的发生发展,检测EBC中p53基因的突变对肺癌的早期诊断有一定的价值。     

可疑肺癌患者纤支镜后痰液标本的p53基因突变检测

目的：探讨纤支镜后痰液标本的p53基因突变检测用于肺癌早期诊断的可行性。方法：采用聚合酶链反应－单链构象多态性分析（PCR－SSCP）银染技术,对29例怀疑为肺癌患者的痰液标本行p53基因5－8号外显子突就检测。结果：8例患者有p53突变,突变率为27．6％,其中以6号外显子突变率最高（17．2％）。p53突变率明显高于相应细胞学阳性率（P＜0．05）。结论：纤支镜后痰标本p53突变检测对肺癌的早期诊断具有一定价值,可作为肺癌早期诊断的辅助方法之一。     

560例中国结直肠癌患者K-ras基因突变研究

目的探讨结直肠癌患者K-ras基因突变状态并为个体化治疗提供指导。方法采用嵌套和COLD-PCR的方法分析560例结直肠癌患者K-ras基因突变状态。结果 560例患者K-ras基因总体突变率27.08%,128例血浆标本突变率为0,432例组织标本突变率为27.08%。突变类型包括G12S、G12C、G12D、G12A、G12V、G13R、G13C、G13D、Q61K、Q61L,2种不同K-ras基因突变率比较,差异有统计学意义(P0.000 1)。362例男性患者的突变率为20.44%,包括G12S、G12C、G12D、G12V、G13R、G13C、G13D、Q61K、Q61L;198例女性患者的突变率为21.72%,包括G12S、G12C、G12D、G12A、G12V、G13R、G13D,不同性别间K-ras基因突变率比较,差异无统计学意义(P=0.722 7)。80例年轻患者的突变率为20%,包括G12S、G12C、G12D、G12V、G13D;127例中年患者的突变率为33.07%,包括G12S、G12D、G12A、G12V、G13R、G13C、G13D、Q61K、Q61L;353例老年患者的突变率为16.71%,包括G12C、G12D、G12V、G13R、G13D,不同年龄间K-ras基因突变率比较,差异有统计学意义(P=0.000 5)。结论 560例结直肠癌患者K-ras基因突变类型主要为G12D、G12V、G13D,K-ras基因突变在不同标本类型、不同年龄间存在差异,不同性别间无差异。     

新疆地区维吾尔族乳腺癌中职甜7基因突变及P53蛋白的表达

目的：了解新疆地区维吾尔族乳腺癌患者BRCA1基因突变及P53蛋白的表达情况。方法：选择2000-01/2004-06石河子大学医学院第一附属医院、喀什地区第一人民医院病理科收集的70例维吾尔族乳腺癌根治标本。其中维吾尔族早发性乳腺癌（≤35岁，即定为早发性乳腺癌）22例。51例患者淋巴结转移。2例为双侧乳腺癌。另选32例维吾尔族乳腺癌旁非癌组织及乳腺良性病变（纤维腺病及纤维腺瘤）作对照；上述标本为甲醛溶液固定石蜡包埋组织及少量新鲜冰冻组织。运用聚合酶链反应-单链构象多态性分析和DNA序列测定的方法检测BRCA1基因突变及用Evision二步法检测P53蛋白的表达。结果：①70例维吾尔族乳腺癌中发现9例BRCA1突变的12个新位点。②70例维吾尔族乳腺癌中BRCA1的突变率为12.86％（9／70）；其中22例维吾尔族早发性乳腺癌（≤35岁）BRCA1突变率为31.82％（7／22），高于维吾尔族晚发性乳腺癌（2／48），差异有显著性（χ^2=10．295，P〈0．01）。③2例双侧乳腺癌中均检测出BRCA1基因的突变。④70例维吾尔族乳腺癌中发现9例BRCA1基因核苷酸多态性位点。⑤BRCA1基因突变相关性乳腺癌中P53蛋白阳性表达率高于对照组，其淋巴结转移率高于对照组，其发病年龄小于对照组。结论：BRCA1基因突变与新疆维吾尔族早发性乳腺癌及双侧乳腺癌的发生密切相关，且BRCA1突变相关性乳腺癌具有P53阳性率高、发病午龄趋于年轻化、淋巴结转移率高的趋势，这些特点有可能为基因检测前的筛选提供参考依据。     

乳腺癌彩色多普勒超声表现与P53、Ki-67及p63表达的相关性及意义

目的：探讨乳腺癌P53、Ki-67及p63的表达与彩色多普勒超声表现的关系与意义。方法：回顾性分析经手术病理证实为乳腺癌的116例患者彩色多普勒超声表现,包括肿块大小、肿瘤彩色血流分级、有无腋窝淋巴结肿大及侵犯周边组织。全部患者术后肿瘤标本均采用免疫组化二步法检测P53、Ki-67及p63的表达情况,研究超声表现和基因表达的相关性。结果：在所有病例中,肿块直径≥2cm、彩色多普勒血流显像2~3级、腋窝淋巴结肿大及肿块侵犯周边组织者P53、Ki-67的表达明显高于肿块直径<2cm、血流显像0~1级、无腋窝淋巴结肿大及未侵犯周边组织者对应病例（P≤0.05）,而p63在肿块直径≥2cm、彩色多普勒血流显像2~3级、腋窝淋巴结肿大及肿块侵犯周边组织者肿瘤标本中的表达明显低于肿块直径<2cm、彩色多普勒血流显像0~1级、无腋窝淋巴结肿大及未侵犯周边组织者（P<0.05）。结论：乳腺癌彩色多普勒超声表现与P53、Ki-67及p63的表达具有相关性,二者联合能够更好地评价乳腺癌恶性程度和判定预后,从而能够在一定程度上指导临床治疗。     

358例肺癌患者K-ras基因的突变分析

目的分析358例肺癌患者K-ras基因突变的突变情况,为肺癌患者的个体化治疗提供指导。方法通过嵌套和低变性温度下的复合PCR(COLD-PCR)-测序法分析358例肺癌患者K-ras基因突变状态。结果在358例肺癌患者中,K-ras基因总体突变率为8.10%。94份血浆标本、250份肿瘤组织标本、14份胸腔积液及腹水标本中的突变率分别为2.13%、9.60%、7.14%。突变类型包括G12C、G12D、G12A、G12V、G13D、Q61H,3种不同标本之间K-ras基因的突变率比较,差异无统计学意义(P=0.064 8);男性与女性患者的突变率分别为6.96%、8.59%,差异无统计学意义(P=0.574 0);30~45岁、45~60岁、大于或等于60岁患者中的突变率分别为4.76%、5.34%、9.22%,不同年龄段患者K-ras基因的突变率比较,差异无统计学意义(P=0.250 3)。结论肺癌患者K-ras基因突变类型主要为G12C、G12D、G12V、G13D,K-ras基因在不同标本类型、不同性别、不同年龄之间的突变率无明显差异。     

基底细胞样型浸润性乳腺癌中PTEN、p53、Ki-67的表达及意义

目的探讨基底细胞样型浸润性乳腺癌中PTEN、p53、Ki-67的表达情况,并分析其意义。方法采用免疫组织化学方法检测57例基底细胞样型浸润性乳腺癌中PTEN、p53、Ki-67的表达水平。结果基底细胞样型浸润性乳腺癌中PTEN、p53、Ki-67的阳性表达率分别是38．6％（22／57）、56．1％（32／57）、82．5％（47／57）,与对照组非特殊类型浸润性导管癌中PTEN、p53、Ki-67的表达水平相比,差异有统计学意义（P〈0．05）。PTEN阳性标本中Ki-67的阳性率（68．2％,15／22）与PTEN阴性标本中Ki-67的阳性率（91．4％,32／35）相比差异显著,统计学分析显示PTEN表达与Ki-67表达呈负相关（P〈0．05）。结论抑癌基因PTEN、p53的异常表达与基底细胞样型浸润性乳腺癌的发生和发展有关,PTEN在一定程度上可以抑制肿瘤细胞的增殖。     

淋巴组织肿瘤中p53、p73基因改变和表达及其意义

目的：探讨淋巴组织肿瘤中p53、p73基因改变和异常表达情况及其意义.方法：采用PCR-SCP法、RT-CR法、REP法、免疫组化法分别检测26例急性淋巴细胞白血病（ALL）、12例多发性骨髓瘤（MM）及12例淋巴瘤（MLs）标本中p53、p73基因改变及异常表达情况.结果：（1）26例ALL中仅有3例检测到p53基因点突变,12例MM标本中2例p53基因突变.未发现p73基因突变;（2）p73mRNA在淋巴组织肿瘤中总的阴性表达率为24%;（3）10例ALL和3例NHL在p73基因外显子1启动子区的CpG岛高甲基化,而正常对照组和12例MM标本均无甲基化存在;（4）对照组p53蛋白均为阴性.26例ALL中,p53蛋白阳性者20例;7例中高度恶性NHL中6例p53蛋白阳性.结论： p53基因在淋巴组织肿瘤中的突变率较低;MLs中p53蛋白表达和恶性程度、临床分期相关;p73mRNA在ALL/NHL中存在较高的阴性表达,,而在MM为阳性表达;p73基因转录失活与p73基因外显子1CpG岛高甲基化有关,不存在基因的突变和缺失;p73基因异常可能在MM的发生、发展中不是一个重要的分子事件.     

新疆地区维吾尔族乳腺癌中BRCA1基因突变及P53蛋白的表达

目的:了解新疆地区维吾尔族乳腺癌患者BRCA1基因突变及P53蛋白的表达情况。方法:选择2000-01/2004-06石河子大学医学院第一附属医院、喀什地区第一人民医院病理科收集的70例维吾尔族乳腺癌根治标本。其中维吾尔族早发性乳腺癌(≤35岁,即定为早发性乳腺癌)22例。51例患者淋巴结转移。2例为双侧乳腺癌。另选32例维吾尔族乳腺癌旁非癌组织及乳腺良性病变(纤维腺病及纤维腺瘤)作对照;上述标本为甲醛溶液固定石蜡包埋组织及少量新鲜冰冻组织。运用聚合酶链反应-单链构象多态性分析和DNA序列测定的方法检测BRCA1基因突变及用Evision二步法检测P53蛋白的表达。结果:①70例维吾尔族乳腺癌中发现9例BRCA1突变的12个新位点。②70例维吾尔族乳腺癌中BRCA1的突变率为12.86%(9/70);其中22例维吾尔族早发性乳腺癌(≤35岁)BRCA1突变率为31.82%(7/22),高于维吾尔族晚发性乳腺癌(2/48),差异有显著性(χ2=10.295,P<0.01)。③2例双侧乳腺癌中均检测出BRCA1基因的突变。④70例维吾尔族乳腺癌中发现9例BRCA1基因核苷酸多态性位点。⑤BRCA1基因突变相关性乳腺癌中P53蛋白阳性表达率高于对照组,其淋巴结转移率高于对照组,其发病年龄小于对照组。结论:BRCA1基因突变与新疆维吾尔族早发性乳腺癌及双侧乳腺癌的发生密切相关,且BRCA1突变相关性乳腺癌具有P53阳性率高、发病年龄趋于年轻化、淋巴结转移率高的趋势,这些特点有可能为基因检测前的筛选提供参考依据。     

靶向高通量测序检测卵巢癌患者易感基因突变与临床特征的相关性研究

目的　探讨卵巢癌易感基因突变与临床特征的关系。方法　采用靶向高通量测序技术对35例卵巢癌患者的外周血进行BRCA1,BRCA2,CHEK2,PALB2,BRIP1,TP53,PTEN,STK11,CDH1,ATM,BARD1,MLH1,MRE11A,MSH2,MSH6,MUTYH,NBN,PMS1,PMS2,RAD50和RAD51C共21种易感基因进行测序,结合临床资料分析基因突变与卵巢癌的相关性。结果　卵巢癌患者多以高级别浆液性卵巢癌晚期为主。35例卵巢癌患者中共检出已知致病突变19例,突变率54.3%,其中BRCA1基因突变7例（20.0%）,BRCA2基因突变4例（11.4%）,RAD51C基因突变2例（5.7%）,CHEK2,ATM,RAD50,MSH2,MRE11A和TP53基因突变各1例。BRCA1/2基因突变和高级别浆液性卵巢癌相关（P=0.034）,和家族史显著相关（P=0.003）,与年龄、FIGO分期无显著相关性（P>0.05）。另外,发现两种新的基因突变,包括BRCA1基因c.438delC和RAD51C基因c.390_391delAA。结论　BRCA1和BRCA2是卵巢癌最主要的胚系突变基因,该基因突变与遗传性卵巢癌显著相关。高通量基因测序技术可有效检测卵巢癌胚系易感基因的突变情况,为卵巢癌的早期诊断和预防提供科学依据。     

Variables Associated with Anxiety and Depression in Children with Autism

Mothers of 627 children with autism (ages 1–17, IQs 16–146) completed the Pediatric Behavior Scale. Maternal ratings of anxiety and depression increased with age and IQ, but were unrelated to gender, parent occupation, and race. Anxiety and depression were highly correlated with each other and with autism severity, somatic complaints, mood disturbance, and social problems. Remaining correlations with behavior problems, attention deficit, hyperactivity, and sleep problems were small. The strongest combined predictors of anxiety and depression were autism severity, verbal IQ, and age, explaining 25% and 23% of the variance. Findings suggest that anxiety and depression have a direct link with autism (increasing with autism severity) and a developmental component (increasing with age and IQ). Anxiety is present in most children with autism and depression is present in about half. Therefore, all children with autism should be screened for anxiety and depression and treated if indicated. Controlled studies are needed to determine what interventions are effective in reducing anxiety and depression in autism.     

原发性高血压患者颈动脉内膜中层厚度及其与脑卒中的关系

【目的】探讨原发性高血压患者颈动脉内膜中层厚度（IMT）及颈动脉粥样斑块与脑卒中的关系。【方法】应用高频彩色多普勒超声检测100例原发性高血压患者与60例健康体检者IMT值,分析其变化,随访5年,了解高血压患者IMT与脑卒中的关系。【结果】原发性高血压患者IMT值明显高于健康体检者（P〈0．01）。不稳定性斑块患者发生脑卒中的比率显著高于硬斑患者（P〈0．01）。【结论】了解高血压患者IMT与颈动脉斑块性质对预测脑卒中发生及防治有重要意义。     

冠心病合并焦虑抑郁患者血清MPO和LXA水平的变化研究

目的观察冠心病合并焦虑抑郁患者体内血清髓过氧化物酶(MPO)以及脂氧素A4(LXA4)的变化及其临床意义。方法选择冠心病患者共156例,根据医院焦虑抑郁情绪评定表(HADS)得分将冠心病患者分为抑郁焦虑组(81例)和非抑郁焦虑组(75例),另匹配80例体检者为对照,检测MPO、LXA4及两者比值。结果冠心病患者血清MPO、LXA4及两者比值(M/L)显著高于对照组。抑郁焦虑组血清MPO水平、M/L显著高于非抑郁焦虑组,但LXA4在两组中无统计学差异(P0.05)。冠心病患者血清MPO、LXA4及两者比值与HADS亚量表得分均具有较好的相关性(r=0.439~0.581,P均0.05)。结论冠心病患者存在血清MPO、LXA4水平及其比值上升,对于合并焦虑抑郁之冠心病病人而言,炎症及其消退间的平衡失调更加明显。     

Satisfaction with and confidence in needle-free subcutaneous sumatriptan in patients currently treated with triptans

(Headache 2011;51:1202‐1211) Objective.— To evaluate patient satisfaction with and confidence in Sumavel^® DosePro^® (needle‐free subcutaneous sumatriptan) among current triptan users administering Sumavel DosePro for up to 4 migraine attacks. Background.— Sumavel DosePro is a needle‐free, single‐use device that facilitates subcutaneous injection of sumatriptan 6 mg and confers relief as early as 10 minutes after dosing. Design/Methods.— In this open‐label, multicenter study, Sumavel DosePro was self‐administered for ≤4 migraine attacks (over a ≤60‐day period) involving moderate or severe baseline pain by adult migraineurs who currently were using triptans (any form, any dosage) and reported being less than very satisfied with their current therapy (ie, baseline satisfaction ranging from satisfied to very dissatisfied). Treatment satisfaction was measured via the Patient Perception of Migraine Questionnaire, revised (PPMQ‐R). Results.— Among the 212 patients using Sumavel DosePro to treat ≥1 migraine attack, PPMQ‐R Overall Satisfaction (primary endpoint) increased significantly from baseline to the end of treatment (mean ± SD 65.7 ± 19.8 vs 73.7 ± 29.1, P = .0007), an improvement that met the criterion for clinical significance. From baseline to the end of treatment, PPMQ‐R scores also improved significantly for Efficacy (62.2 ± 17.6 vs 76.2 ± 23.7, P < .0001), Functionality (59.0 ± 22.3 vs 73.8 ± 25.3, P < .0001), and Tolerability (83.9 ± 13.1 vs 86.4 ± 15.0, P = .02), but declined for Ease of Use (82.6 ± 15.3 vs 67.8 ± 27.6, P < .0001). For all global satisfaction domains, the percentage of patients satisfied or very satisfied increased from baseline to the end of treatment (Overall Satisfaction 36.3% vs 64.0%, Satisfaction with Medication Effectiveness 40.1% vs 68.2%, Satisfaction with Side Effects 48.6% vs 67.3%). The percentage of patients who were confident or very confident in treating repeated migraine attacks also increased (baseline: 41.0%, 90% confidence interval [CI] 35.4, 46.9 vs end of treatment: 66.5%, 90% CI 58.9, 70.1). The efficacy results (pain relief, pain‐free response, sustained 24‐hour pain relief and pain‐free response) were consistent with those previously observed with needle‐based sumatriptan. Conclusion.— Patients currently treated with triptans and less than very satisfied with their acute migraine therapy experienced a statistically significant and clinically relevant increase in satisfaction with therapy and enhanced confidence in treatment after use of Sumavel DosePro for up to 4 migraine attacks.     

Student and professional attitudes and interests in working with people with complex communication needs

Speech-language pathology interest in working with people with complex communication needs was investigated in this study. Participants were third year speech-language pathology undergraduates and recent graduates who had participated in a unit on AAC. Undergraduates (n = 85) completed an Interaction with Disabled Persons attitudinal scale and a questionnaire about interest in various client groups before and after the unit. Some undergraduates (n = 34) repeated the attitudinal scale and completed another questionnaire 2 years after graduation. Recent graduates (n = 56) completed a questionnaire about working with people with complex communication needs and factors influencing work choices; 10 also participated in interviews or focus groups. We found a small but positive attitudinal shift for the undergraduates, but, along with previous disability experience, this was a weak predictor of working with this group. Working in developmental disability ranked low amongst undergraduate preferences. Most graduates were influenced in their job choices by a desire to work on a particular team and previous clinical placements. Questionnaires and interview/focus group data indicated the strong influence of clinical placements on later work choices. Participants who worked in disability appeared passionate about the work involved and offered suggestions for engaging more professionals with this group. Implications for speech-language pathology services in disability are discussed.     

非酒精性脂肪性肝病患者瘦素水平与胆石症及胰岛素抵抗关系的研究

目的探讨非酒精性脂肪性肝病(NAFLD)患者瘦素水平与胆石症及胰岛素抵抗关系。方法选择NAFLD伴胆石症患者共62例(研究组)和不伴胆石症患者共60例(对照组)。检测两组血清瘦素、空腹血糖(FBG)、空腹胰岛素(FINS)水平;计算胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR),观察瘦素水平与其他指标的相关性。结果研究组胰岛素水平、HOMA-IR、瘦素水平显著高于对照组。瘦素与HOMA-IR、FINS、FBG等存在较好的相关性。瘦素(OR=2.763)和胰岛素抵抗(OR=1.934)是NAFLD合并胆石症的最重要的预测指标。结论 NAFLD患者血清瘦素水平与胰岛素抵抗密切相关,是反映胆石症形成的一个预测指标。