Abstract Third-generation cutaneous growth factor receptor tyrosine kinase inhibitors have led to impressive advances in the treatment of non-small cell lung cancer. However, acquired resistance significantly limits the clinical application of these agents, with the epidermal growth factor receptor (EGFR)C797S mutation being the primary resistance mechanism. In this study, a series of novel EGFR kinase inhibitors was designed and synthesized for the treatment of the EGFRC797S mutation in non-small cell lung cancer. Structure activity relationship screening revealed that compound 5d was the most effective inhibitor of the C797S mutation. It strongly inhibited Baf3-EGFRL858R/T790M/C797S and Baf3-EGFR 19del/T790M/C797S cell lines, with IC50 values of 0.01836±0.0065 and 0.025±0.005 μM, respectively. Molecular docking studies showed that 5d binds to the EGFRL858R/T790M/C797S and EGFR19del/T790M/C797S proteins effectively. A mechanistic study showed that 5d induced cell cycle arrest in the G2/M phase. Compound 5d caused cell apoptosis in a dose-dependent manner, accompanied by a significant increase in the level of the apoptotic protein cleaved caspase-3. An in vivo xenograft assay of mice with Baf3-EGFR19del/T790M/C797S cells showed that 5d effectively inhibited tumor growth, with inhibition rates of 45.2% (70 mg/kg) and 55.7% (100 mg/kg) being observed. Therefore, 5d is worthy of further investigation as a fourth-generation EGFR inhibitor.

目的:了解护士对乳腺癌相关淋巴水肿运动康复的知信行现状,探讨其影响因素,旨在为临床开展相关教学、培训提供依据.方法:采取便利抽样法,用自行设计的问卷对698名护士进行问卷调查,分析其影响因素.问卷包括一般资料和运动康复知识、态度、行为4个部分.结果:护士对乳腺癌相关淋巴水肿运动康复知信行总分、知识、态度、行为维度得分分别为(137.47±16.32)分、(40.87±7.36)分、(50.11±5.18)分和(46.50±7.77)分.多元线性回归分析结果显示,护士对乳腺癌相关淋巴水肿运动康复知识的主要影响因素为医院级别,态度的主要影响因素为职称,行为的主要影响因素为医院级别.结论:护士对乳腺癌相关淋巴水肿运动康复态度较积极,但知识和行为水平有待提高.三级医院护士对乳腺癌相关淋巴水肿运动康复的知识水平和行为水平较高,高职称护士对乳腺癌相关淋巴水肿运动康复的态度较好.提示今后应进一步提高护士,尤其是基层医院护士对淋巴水肿运动康复的知识和行为水平,加大对低职称护士的培训,提升其淋巴水肿运动康复的专业水平.

目的 通过随机对照临床试验,验证新型国产膝关节假体临床应用的安全性和有效性.方法 本研究采用多中心、随机、单盲、阳性平行对照设计,自2017年3月至2019年3月在全国6家医院共招募72例受试者,试验组和对照组各36例.试验组使用新型国产膝关节假体,对照组使用成熟的膝关节假体.所有受试者在术前和术后3个月、6个月、1年、2年进行随访评估,评价记录术后主要疗效指标HSS评分和不良事件发生率,确认试验产品的临床应用价值.结果 本研究72例受试者均完成了2年的随访.试验组术前和术后3个月、6个月、1年、2年的HSS评分分别为:(56.95±13.07)分、(76.85±9.88)分、(82.80±7.15)分、(88.22±5.95)分、(88.94±4.38)分,对照组HSS评分分别为:(55.25±9.47)分、(77.09±6.41)分、(83.77±6.04)分、(88.96±5.37)分、(89.23±5.06)分.试验组和对照组的HSS评分术后均较术前明显提高,但术后各随访时间点两组HSS评分比较,差异无统计学意义(P>0.05).试验组和对照组术后不良事件发生率比较,差异无统计学意义(P>0.05).结论 与对照组相比,试验组新型国产膝关节假体在主要疗效指标HSS评分、安全性评价指标方面均无明显差异.因此,试验组新型国产膝关节假体在术后早期可获得满意效果,远期疗效待进一步观察随访.

目的 通过随机对照临床试验,评价一种新型国产髋关节假体用于人工全髋关节置换术(total hip arthroplasty,THA)的临床疗效和安全性.方法 本研究采用多中心、随机、单盲、阳性平行对照设计,在全国5家医院共招募72例受试者,分别纳入试验组和对照组,各36例.试验组使用新型国产髋关节假体,对照组使用成熟的髋关节假体.所有受试者在术前及术后3个月、6个月、1年、2年进行随访评估,评价记录髋关节Harris评分和不良事件的发生情况,评估产品的临床应用价值.结果 共有3例受试者退出研究,其中试验组1例,对照组2例.试验组和对照组的髋关节Harris评分均较术前明显提高(P<0.05),但各随访时间点的数据进行组间比较,差异无统计学意义(P>0.05).两组间的不良事件发生率比较,差异无统计学意义(P>0.05).结论 新型国产髋关节假体用于THA,可显著改善病人髋关节功能,其临床疗效和安全性与成熟假体相近.

Abstract Background Gliomas are highly invasive and lack of effective targeted therapy. GRK5 is involved in several pathologic conditions including cancer. GRK5 phosphorylated MSN on T66 and regulated the subcellular distribution of MSN, which was a glioma progression marker that induces proliferation via interaction with CD44. Therefore, targeting GRK5-MSN-CD44 may provide a novel approach for the treatment of gliomas. Materials and methods GRK5-knockdown and GRK5-upregulated glioma cell lines were generated by using the lentivirus transfection method. The GRK5 and MSN expression and the association with the malignant characters in glioma were determined by Western blot and qRT-PCR. By using double-immunofluorescence and triple immunofluorescence analysis, the subcellular localization and distribution characteristics of GRK5-MSN-CD44 in gliomas were detected. The cell proliferation, migration, invasion and apoptosis were determined by CCK-8 assay, wound healing assay, transwell assay and flow cytometry respectively. Results GRK5 expression was up-regulated in human gliomas and positively correlated with MSN expression. GRK5-MSN and MSN-CD44 were found co-expressed in gliomas respectively. GRK5-MSN-CD44 were co-localized in the membrane of glioma cell and abundant in glioma stem cell niches. VEGF and N-cadherin expressions were increased/decreased according to the up-regulation/down-regulation of GRK5. And Bax expression showed decreased/increased according to GRK5 over-expression/low-expression. The proliferation, migration and invasion of glioma cells were improved due to the upregulation of GRK5. And the apoptosis of glioma cells was decreased/increased due to the up-regulation/down-regulation of GRK5. Conclusion Ectopic overexpression of GRK5 promoted the malignant progression of glioma and is closely related to MSN-CD44 interaction. GRK5-MSN-CD44 provides a new idea for gene targeted therapy of glioma.

目的:探讨基于冠状动脉CT血管成像(CCTA)的人工智能(AI)软件在检出冠状动脉病变及评估其CAD-RADS分级中的价值.方法:回顾性分析2018年11月-2020年12月本院临床疑诊为冠心病且行CCTA和冠状动脉血管造影(ICA)检查的175例患者的病例资料.由AI软件及3位不同年资影像诊断医师基于CCTA图像分别进行CAD-RADS分级,以ICA为金标准,计算AI软件和不同年资医师对阻塞性冠脉病变(冠脉狭窄程度≥50％)的诊断效能.采用Kappa检验分别评价AI软件与高、中、低年资医师基于CCTA对冠脉病变CAD-RADS分级评估的一致性.结果:(1)AI及高、中、低年资诊断医师评估冠脉狭窄≥50％ 的A U C值分别为0.764、0.858、0.747和0.731.其中,在钙化积分≥400组,相应的A U C值分别为0.608、0.750、0.625和0.625;在钙化积分<400组,相应的A U C值分别为0.801、0.884、0.776和0.756.A I软件及各年资医师A U C值的差异无统计学意义(P>0.05).(2)AI软件与高年资医师基于CCTA的CAD-RADS分级一致性良好(Kappa值为0.677,P<0.001),与中、低年资医师的分级一致性中等(Kappa值分别为0.466和0.428;P值均<0.001).结论:AI系统对冠脉狭窄≥50％ 具有良好的诊断效能,兼具时间效率.AI软件基于CCTA的CAD-RADS分级与诊断医师之间具有良好的一致性,可在临床影像诊断工作中推广使用.

RSNA2020腹部影像学对腹部多个脏器(肝脏、胆囊、胰腺、肾脏、前列腺、结直肠)从诊断及治疗方面进行研究,其中基于机器学习的影像学研究为肿瘤治疗相关的影像学组学及肿瘤预后等热门研究领域的有力分析工具.

Objective:To investigate clinical effects of lumbopelvic fixation and triangular osteosynthesis using sacral ala-iliac screws for the treatment of sacral fractures.Methods:The data of 12 patients with sacral fractures treated with lumbopelvic fixation and triangular osteosynthesis using sacral ala-iliac screws from December 2019 to June 2020 were retrospectively analyzed. There were 3 males and 9 females with an average age of 32.6±15.0 years (range, 13-52 years); causes of injury: 11 fall injuries and 1 traffic injury. The Denis classification of sacrum fracture: 4 cases of type II and 8 cases of type III. AO (Tile-Muller) classification: 4 cases of type C1.3, 8 cases of type C3.3; of the 8 cases of C3.3 fractures, Roy-Camille and Strange-Vognsen classification: 2 cases of type II, 6 cases of type III. According to the scoring system of Gibbons sacral nerve injury, there were 6 cases of scored 3 and 2 cases of scored 4; 4 cases of C1.3 fractures had no nerve injury. The time from injury to operation was 6 to 32 days, with an average of 19.3±9.2 days. After the vital signs were stabilized, laminectomy and decompression of sacral nerve roots, fracture reduction, lumbopelvic fixation and triangular osteosynthesis using sacral ala-ilac screws were performed. The fixation method of the anterior ring was determined according to the injury. The postoperative fracture reduction quality was evaluated according to Matta criteria. The clinical function and neurological function were evaluated according to the Majeed scoring system and Gibbons sacral nerve injury scoring system at the last follow-up.Results:Twelve patients were operated smoothly. 8 cases of C3.3 fractures were fixed by lumbopelvic fixation, of which 6 cases of U-shaped fractures were fixed by transverse rods due tolongitudinal separation displacement; Four cases of C1.3 used triangular osteosynthesis and transverse fixation in 3 cases with sacroiliac screws, and 1 case with sacral local plate. Six patients with anterior ring injury were fixed with steel plate in 4 cases, INFIX in 1 case and pubic branch screw in 1 case. All patients were followed up for 6 to 12 months, with an average of 7.3±1.7 months. Postoperative Matta standard evaluation: excellent in 7 cases; good in 4 cases; fair in 1 case. Majeed score at the last follow-up: excellent in 6 cases, good in 5 cases, and fair in 1 case. One of 2 cases of rectal and bladder dysfunction patients completely recovered, the other was found partial rupture of the nerve roots of sacrum 1 and 2 during operation, whose muscle strength below the calf was still reduced; 6 cases of preoperative muscle strength loss below the calf were significantly improved, among which 4 patients recovered completely, and 2 patients had lower limb sensory impairment; the Gibbons score improved by an average of 1.8±0.7 points (preoperative average 3.2 points, postoperative average 1.4 points). X-ray examinations were performed 3 to 6 months after the operation showed that the fractures were all healed. During the follow-up period, no complications such as fat liquefaction, infection, wound healing, and screw protrusion discomfort were found.1 case of S 2AI screw penetrated the outer plate of the ilium, and there was no pelvic tilt and unequal length deformity of the lower limbs. One patient took out the internal fixation 6 months after the operation due to lower back discomfort. At the last follow-up, all patients had no internal fractures or loss of fracture reduction. Conclusion:Lumbopelvic fixation and triangular osteosynthesis using sacral ala-iliac screws for the treatment of sacral fractures are reliable, with less trauma and lower incidence of complications; and the clinical results are satisfactory.

文章分析护理管理反馈中的问题,并总结出给予建设性反馈的新方法,即辨识情境(identifying settings)、描述行为(behavior description)、表达关心(expressing concerns)、征询根源(asking for root causes)、建构改进(constructing improvement strategies)、提供帮助(offering help)、留意变化(noticing changes).7个环节的英文首字母组成"I BEACON",意为"我点亮或被点亮",整个过程体现管理者主导作用和护士主体作用.该方法不仅为管理者给予建设性反馈提供一个指引,也引导护士反思和自我发现,促进管理双方的学习和成长.

骨盆骨折多为高能量损伤，常合并其他损伤，如血管、神经、尿道损伤，容易漏诊。对于血流动力学不稳定的骨盆骨折患者，急救过程中大量液体复苏往往会引起腹腔内压增高，甚至引发腹腔高压(IAH)/腹腔间隙综合征(ACS)，容易漏诊、误诊，故常规监测腹腔内压显得尤为重要。笔者介绍1例骨盆骨折合并髂外动脉损伤和ACS患者，探讨该类损伤的诊治要点，供临床医师鉴别并避免误诊漏诊。

2019年RSNA腹部影像学内容丰富,热点问题包括人工智能(AI)及其对肝脏、直肠的诊断、疗效评估等,为腹部影像学临床和科研工作的进一步开展提供了多角度的思路.

新型冠状病毒肺炎疫情作为突发的公共卫生事件,使抗疫一线的护理人员出现心理应激的风险增加.本文结合我院在抗疫过程中对护理人员心理干预的经验,对护理人员心理健康防护长效机制建设进行探讨,提出在日常、疫中和疫后三个阶段对护士进行心理干预的策略.日常心理建设包括职业心理训练、心理支持网络搭建、职业健康护士储备;疫中心理支持包括强有力的领导、规范化的培训、充足的物资保障、正向的激励和及时的疏导;疫后心理康复包含全面支持以预防创伤后应激障碍和反思总结经验教训.

Objective:To analyze the health empowerment level of elderly patients with chronic diseases and its influencing factors, so as to provide references for further improving the health empowerment level of elderly patients with chronic diseases.Methods:A total of 414 elderly patients with chronic diseases in hospitals and nursing homes in Wuhan city were investigated by self-designed general data questionnaire and health empowerment scale for elderly patients.Results:The health empowerment score of elderly patients with chronic diseases was (3.71±0.54), and the factors influencing the health empowerment level of elderly patients were their cohabitants, education level, proportion of medical reimbursement and place of residence (P＜0.05).Conclusions:The health empowerment level of elderly patients with chronic diseases was affected by a variety of factors.Family members and the society should provide personalized help and empowerment education to the elderly, stimulate their belief in responsibility, encourage them to seek support and acquire knowledge, encourage them to participate in treatment, and ultimately achieve self-reconstruction and improve their health empowerment level.

Background Dysfunction of oxalate synthesis can cause calcium oxalate stone disease and inherited primary hyperoxaluria (PH) disorders. PH type I (PH1) is one of the most severe hyperoxaluria disorders, which results in urolithiasis, nephrocalcinosis, and end-stage renal disease. Here, we sought to determine the role of microRNAs in regulating AGXT to contribute to the pathogenesis of mutation-negative idiopathic oxalosis. Methods We conducted bioinformatics to search for microRNAs binding to AGXT , and examined the expression of the highest hit (miR-4660) in serum samples of patients with oxalosis, liver tissue samples, and determined the correlation and regulation between the microRNA and AGXT in vitro. Results MiR-4660 expression was downregulated in patients with oxalosis compared with healthy controls (84.03 copies/µL vs 33.02 copies/µL, P < 0.0001). Moreover, miR-4660 epigenetically decreased the expression of AGT in human liver tissues (Rho = − 0543, P = 0.037). Overexpression of miR-4660 in HepG2 and L02 cell lines led to dysregulation of AGXT at both the mRNA (by 71% and 81%, respectively; P < 0.001) and protein (by 49% and 42%, respectively; P < 0.0001) levels. We confirmed the direct target site of miR-4660 binding to the 3′UTR of AGXT by a luciferase assay. Conclusion MiR-4660 is probably a new biomarker for mutation-negative idiopathic oxalosis by regulating the post-transcription of AGXT , providing a potential treatment target of mutation-negative idiopathic oxalosis.

2018年RSNA年会上腹部影像学方面的研究热点主要包括人工智能、影像组学/纹理分析和能谱CT的基础研究和临床应用,为今后的临床和科研工作开拓了新的思路.

病例资料 关节外色素沉着绒毛结节性滑膜囊炎(PVNB)是一种罕见的关节外滑膜增生性疾病,罕有影像学文献报道,极易误诊为肿瘤性病变.本文收集了2例经病理证实为髋关节周围 PVNB 的病例资料,现报道如下,并结合文献,对其影像学及临床病理学特征进行分析,旨在提高对该病的认识,减少误诊率.

目的 了解老年人养老机构入住体验现状及其影响因素,为养老机构照护服务改进以提升照护质量和老年人生活质量提供依据.方法 采用横断面调查方法,方便抽取5家医养结合型养老机构的老年人202人,采用自行设计的老年人养老机构入住体验问卷进行调查.结果 医养结合型养老机构老年人入住体验总得分为73～150(123.82±17.39)分,各维度得分由高到低依次为可靠性、有形性、保证性、关怀性、连续性.年龄、月收入、亲人支持程度、子女个数对老年人入住体验有显著影响(P＜0.05,P＜0.01).结论 老年人对养老机构入住体验评价较好,但在人文关怀性和医疗连续性上有待加强.亲人支持程度能在很大程度上提升老年人的入住体验,养老机构需提供条件促进子女与老年人的联系,以提升老年人的生活质量.

目的 探讨基于CCTA数据建立的校正后冠状动脉血管密度梯度参数对有显著性收缩期压迫的心肌桥的预测价值.方法 回顾性分析107例行CCTA和ICA检查的左前降支心肌桥病例,以ICA为金标准,测量冠状动脉腔内强化梯度(TAG)及其校正值(TAGstandard1zed)、壁冠状动脉血管密度差异(MCA-COD)、心肌桥长度,比较收缩期无压迫、轻度压迫、显著性压迫心肌桥组间差异,ROC分析TAG、TAGstandardized、MCA-COD对收缩期压迫的心肌桥的诊断价值.结果 (1)收缩期无压迫、轻度压迫、显著性压迫心肌桥组TAG(HU/10 mm)分别为(-14.0±4.8)HU、(-17.7±5.6)HU和(-22.8±8.3)HU;TAGstandardized(10-2/10 mm)分别为-3.8±1.2、-4.4±1.4和-6.3±2.0;MCA-COD(10-2/10mm)分别为9.5 ±10.2、12.6±10.0和29.1 ±10.6;TAGatandardized和MCA-COD显著压迫组与轻或无压迫组有显著性差异(P＜0.05),无压迫组与轻度压迫组无显著性差异(P＞0.05);(2)显著收缩压迫心肌桥,MCA-COD(AUC 0.89)比TAGstandardized(AUC 0.83)及心肌桥长度(AUC 0.76)具有更高的诊断价值;MCA-COD和TAGstandardized(AUC 0.94)联合显著高于单一指标(P＜0.01).结论 MCA-COD和TAGstandardized联合作为一种无创性的冠状动脉检查CCTA指标,能够较准确地预测收缩期有显著压迫的心肌桥.

Objective To develop a health empowerment assessment tool complying with Chinese cultural background for elderly patients with chronic disease.Methods A draft scale assessing health empowerment for elderly patients with chronic disease was formulated using literature review,qualitative interviews,expert consultation,etc,then 326 elderly patients with chronic disease were investigated to test its reliability and validity.Results The final scale included 26 items consisting of responsibility belief,support acquisition,knowledge acquisition,treatment participation and self-construction 5 dimensions,which explained 68.513％ of the total variance.The Cronbach's α coefficient of the scale was 0.927,and the split-half reliability was 0.842.The Cronbach's α coefficient of the 5 dimensions was 0.832 to 0.899,and the split-half reliability was 0.842 to 0.904.The item content validity index (CVI) ranged from 0.80 to 1.Conclusion The health empowerment scale for elderly patients with chronic disease has good reliability and validity,and it can provide reference to assess the health empowerment status for this population.

Objective To deeply explore the concept of health empowerment from the perspectives of elderly people with chronic disease in China,and to provide a theoretical basis for intervention and evaluation of empowerment.Methods Semi-structured interviews were conducted among 22 elderly people with chronic diseases.Then Colaizzi's 7-step analysis method was used to analyze the recording material.Results Six themes were extracted from the health empowerment concept in elderly people with chronic diseases,respectively:responsibility beliefs,support system,knowledge and skills,self-management,empowering others and selfreconstruction.Conclusion Nurses should endeavor to inspire elderly people's faith in health empowerment,and encourage them to empower others and themselves,in an effort to enhance the level of empowerment in elderly patients.