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81.
82.
在重大公共卫生事件新型冠状病毒肺炎的流行背景下,以中南大学湘雅医院八年制诊断学见习课程为实例,阐明如何整合“线上”+“线下”教学资源,组织和实施以学生为中心的混合式临床见习教学。该课程包括:基于数字课程云平台(ICC)的自主学习;基于“引导性反馈”的在线讨论学习;基于“案例教学(case based learning)”的在线讨论课;以及基于“练习视频反馈”的“在线实操”诊断技能教学。问卷调查结果显示,学生对在线混合式诊断学见习课整体满意度高,理论考试成绩优异,临床操作技能提高显著。如何运用资源整合的混合式教学进一步提高医学生临床思维能力和临床操作技能必将成为医学教育同行关注的热点和难点。  相似文献   
83.
目的:探讨六味地黄汤对慢性抑郁大鼠记忆障碍的改善作用,并探讨其可能的作用机制。方法:Wistar雌性大鼠随机分为正常组(生理盐水)、慢性不可预见性温和应激(CUMS)模型组(生理盐水)、六味地黄汤低、中、高剂量组(2. 60,7. 81,23. 50 g·kg~(-1)·d~(-1))。除正常组外,其余各组造成CUMS模型。每周称体质量,观察其行为学指标变化;实时荧光定量聚合酶链式反应(Real-time PCR)检测其海马G蛋白偶联雌激素受体(GPR30),胞内磷脂酰肌醇激酶(PI3K),环磷酸腺苷反应元件结合蛋白(CREB),脑源性神经营养因子(BDNF) mRNA的表达;酶联免疫吸附测定(ELISA)检测血清中雌激素含量。结果:与正常组比较,模型组体质量、活动能力、兴趣等明显降低(P 0. 05,P 0. 01);与模型组比较,六味地黄汤2. 60,7. 81,23. 50 g·kg~(-1)可明显提高CUMS大鼠糖水偏好度(P 0. 01)和旷场实验的站立次数(P 0. 01);7. 81,23. 50 g·kg~(-1)明显提高旷场实验的总距离(P 0. 05,P 0. 01);2. 60,7. 81 g·kg~(-1)可缩短水迷宫实验寻台潜伏期(P 0. 01);7. 81 g·kg~(-1)可增加血清中雌激素含量(P 0. 05);CUMS模型组大鼠海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达明显下降(P 0. 05,P 0. 01),六味地黄汤2. 60 g·kg~(-1)显著增加海马组织内的GPR30,CREB mRNA表达(P 0. 05,P 0. 01),7. 81 g·kg~(-1)明显增加海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达量(P 0. 05,P 0. 01)。结论:六味地黄汤具有抗抑郁作用,逆转CUMS大鼠抑郁样行为及学习记忆障碍,其中中剂量组药效最显著。其作用机制可能与增加血清中雌激素和提高大鼠海马GPR30,PI3K,CREB,BDNF mRNA表达有关。  相似文献   
84.
KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R). Patients received escalating doses of continuous or intermittent once daily (QD) orally administered lapatinib and trametinib, starting at 750 mg and 1 mg continuously, respectively. Thirty-four patients (16 CRC, 15 NSCLC, three pancreatic cancers) were enrolled across six dose levels and eight patients experienced dose-limiting toxicities, including grade 3 diarrhea (n = 2), rash (n = 2), nausea (n = 1), multiple grade 2 toxicities (n = 1), and aspartate aminotransferase elevation (n = 1), resulting in the inability to receive 75% of planned doses (n = 2) or treatment delay (n = 2). The RP2R with continuous dosing was 750 mg lapatinib QD plus 1 mg trametinib QD and with intermittent dosing 750 mg lapatinib QD and trametinib 1.5 mg QD 5 days on/2 days off. Regression of target lesions was seen in 6 of the 24 patients evaluable for response, with one confirmed partial response in NSCLC. Pharmacokinetic results were as expected. Lapatinib and trametinib could be combined in an intermittent dosing schedule in patients with manageable toxicity. Preliminary signs of anti-tumor activity in NSCLC have been observed and pharmacodynamic target engagement was demonstrated.  相似文献   
85.
目的探讨经皮注射对比增强超声(CEUS)在乳腺癌前哨淋巴结(SLN)术前定位及转移风险评估中的临床应用价值。 方法根据纳入及排除标准,选择2019年5~9月在江苏大学附属人民医院乳腺外科行手术治疗的21例女性乳腺癌患者进行前瞻性研究。术前根据经皮CEUS示踪结果,在皮肤表面标记SLN位置及数目,根据其增强模式评估SLN转移风险,并在术中联合亚甲蓝共同确认SLN的位置及数目。以亚甲蓝染色的病理检查结果为金标准,计算经皮CEUS预测SLN状态的敏感度、特异度、阳性预测值、阴性预测值及准确率。用Kappa一致性检验分析CEUS与SLN常规病理检查结果的一致性及2名超声科医师对SLN增强模式判读的一致性。用Fisher精确概率法分析不同临床病理特征患者CEUS评估SLN结果的差异。 结果21例患者中,经皮CEUS共检出32枚SLN,亚甲蓝染色共检出71枚。经皮CEUS体表定位的SLN均为术中亚甲蓝染色的SLN,患者经皮CEUS检出(1.6±0.9)枚SLN,低于亚甲蓝染色检出的(3.4±1.4)枚(t=5.017, P<0.001)。CEUS预测SLN转移风险:判定有SLN转移患者9例(病理证实SLN有转移7例,无转移2例),判定无转移患者12例(病理证实SLN无转移11例,有转移1例)。CEUS评估SLN状态的敏感度7/8,特异度11/13,阳性预测值7/9,阴性预测值11/12,准确率85.7%(18/21)。CEUS与病理诊断结果具有较高一致性(Kappa =0.704,P=0.001)。2名超声科医师对CEUS中32枚SLN增强模式的判读结果一致性较好(Kappa=0.829,P<0.001)。不同组织学分级的患者,其CEUS预测结果比较,差异有统计学意义(P=0.046)。 结论经皮CEUS是乳腺癌患者SLN术前定位及转移风险评估的一种有效方法。  相似文献   
86.
目的 探讨健康信念综合提醒系统对脑卒中患者出院后6个月健康知识、信念、行为、卫生服务利用情况及临床结局的效果。方法 2015年2月至2016年3月,方便抽样广州市3家综合医院高血压并发缺血性脑卒中出院患者174例,分为对照组(n = 87)和干预组(n = 87)。对照组予常规健康教育;干预组在此基础上采用“基于健康信念模式的综合提醒系统”进行健康教育和延续护理。出院6个月后,采用脑卒中健康知识问卷(SKQ)、脑卒中患者健康信念简表(SF-HBMS-SP)和脑卒中健康行为量表(HBS-SP)进行调查,并记录临床结局(急诊就诊、再住院、复发和死亡)。结果 对照组75例、干预组76例完成调查。干预组SKQ (U = 903.000)、SF-HBMS-SP (t = -9.099)和HBS-SP (t = -7.786)总分均显著高于对照组(P < 0.001)。干预组门诊复诊率(97.37%)显著高于对照组(76.00%) ( P <0.001);两组急诊就诊数和再住院数无显著性差异(P > 0.05),死亡和复发率无显著性差异( P > 0.05)。 结论 健康信念综合提醒系统能提高脑卒中患者出院后健康知识、信念、行为和门诊复诊率,但尚未对临床结局产生明显效果。  相似文献   
87.
88.

Background

There is evidence linking metformin to improved prostate cancer–related outcomes.

Patients and Methods

Twenty-five men with metastatic castration-resistant prostate cancer and prostate-specific antigen (PSA) progression while receiving treatment with abiraterone from 3 Swiss centers were included in this single-arm phase 2 trial between November 2013 and September 2016. Metformin was added to abiraterone continuously at 1000 mg twice daily in uninterrupted 4-week cycles. The primary end point was the absence of disease progression at 12 weeks (PFS12). The Fleming single-stage design was applied. With a 5% significance level and 80% power, 25 patients were required to test PFS12 ≤ 15% (H0) compared to ≥ 35% (H1). Secondary end points included toxicity and safety issues. The study was registered at ClinicalTrials.gov (NCT01677897).

Results

The primary end point PFS12 was 12% (3 of 25 patients) (95% confidence interval, 3-31). Most patients had PSA progression, almost half had radiographic progression, but only 1 patient had symptomatic progression. Eleven (44%) of 25 patients had grade 1 and 2 patients each grade 2 (8%) or grade 3 (8%) gastrointestinal toxicity (nausea, diarrhea, loss of appetite). One patient discontinued treatment at week 5 because of intolerable grade 3 diarrhea.

Conclusion

The addition of metformin to abiraterone for patients with metastatic castration-resistant prostate cancer and PSA progression while receiving abiraterone therapy does not affect further progression and has no meaningful clinical benefit. A higher-than-expected gastrointestinal toxicity attributed to metformin was observed.  相似文献   
89.
Journal of Neuro-Oncology - Understanding the molecular landscape of glioblastoma (GBM) is increasingly important in the age of targeted therapy. O-6-Methylguanine-DNA methyltransferase (MGMT)...  相似文献   
90.

Aims

Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.

Materials and methods

One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan–Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included.

Results

In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time.

Conclusion

Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.  相似文献   
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