孟鲁司特治疗呼吸道合胞病毒毛细支气管炎症状及反复喘息疗效研究

背景　呼吸道合胞病毒（RSV）毛细支气管炎易出现反复喘息，且下呼吸道分泌物中半胱氨酸白三烯（CysLTs）水平升高。而孟鲁司特是一种白三烯受体拮抗剂，关于其治疗RSV毛细支气管炎症状的研究相对较少。目的　探讨孟鲁司特改善婴幼儿RSV毛细支气管炎后症状及减轻反复喘息发作的有效性和安全性。方法　2015年6月-2017年6月连续纳入在潍坊市妇幼保健院出院的RSV毛细支气管炎患儿，随机分为治疗组、对照组。Ⅰ期，治疗组：口服孟鲁司特颗粒（4 mg）12周，1次/d；对照组：口服安慰剂12周，1次/d。对两组无症状天数、个人日记评分进行评估。随访9个月（Ⅱ期），观察Ⅰ+Ⅱ期反复喘息人数和医疗资源应用情况等。依据意向性分析（ITT）原则，应用全分析集（FAS）分析数据。结果　共纳入研究对象186例，治疗组92例，对照组94例。治疗组完成Ⅰ期研究的患儿为89例，对照组为90例；治疗组完成Ⅰ+Ⅱ期的患儿为84例，对照组为86例。治疗组平均依从性为97.8%（7 560/7 728），对照组平均依从性为97.4%（7 690/7 896），两组患儿平均依从性比较，差异无统计学意义（χ2=3.16，P=0.07）。在Ⅰ期研究期间，两组无症状天数、日间无症状天数、夜间无症状天数、个人日记评分比较，差异均无统计学意义（P>0.05）。在整个研究过程中（Ⅰ+Ⅱ期），治疗组RSV毛细支气管炎喘息复发人数少于对照组（P<0.05），治疗组喘息患儿出现2次及以上喘息比例低于对照组（χ2=5.14，P=0.02）。Ⅰ+Ⅱ期研究期间治疗组医疗资源应用人数、β-受体激动剂应用人数、糖皮质激素应用人数、住院人数低于对照组（P<0.05）。在事后亚组分析中，治疗组有湿疹史与父母哮喘史的患儿中无症状天数〔（49.7±20.2）、（51.3±20.9）d〕多于对照组〔（36.3±20.4）、（37.8±19.3）d〕（t=2.19，P=0.03；t=2.24，P=0.03）。整个研究过程中没有患儿因不良反应退出研究，两组间胃肠道紊乱、皮疹、转氨酶升高发生率比较，差异均无统计学意义（χ2=0.23，P=0.63；χ2=0.03，P=0.86；χ2=0.15，P=0.69）。结论　口服孟鲁司特（4 mg）12周不能改善RSV毛细支气管炎患儿呼吸道症状，但能降低患儿反复喘息发作次数。口服孟鲁司特（4 mg）有一定效果且安全。     

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.     

PD-L1高表达晚期非小细胞肺癌患者单纯免疫治疗与免疫联合化疗疗效比较

背景与目的以免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）为代表的免疫治疗越来越广泛地应用于肺癌治疗。然而，对于程序性死亡受体配体1（programmed cell death-ligand 1, PD-L1）高表达，即肿瘤比例评分（tumor proportion score, TPS）≥50%的晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者，采用单纯免疫治疗还是免疫联合化疗在临床上仍存争议。本研究旨在评估PD-L1高表达的晚期NSCLC患者接受单纯免疫治疗与免疫联合化疗的疗效。方法本研究回顾性分析了49例PD-L1高表达晚期NSCLC患者的临床资料。PD-L1表达采用22C3抗体行免疫组化染色，按TPS判读PD-L1表达水平。比较不同临床特征分组患者的客观缓解率（objective response rate，ORR）和无进展生存时间（progression free survival, PFS）。结果免疫单药与免疫联合化疗组的ORR分别为47.1%（8/17）和43.8%（14/32），差异无统计学意义（P=0.825）。免疫单药与免疫联合化疗组的中位PFS分别为8.0个月和6.8个月，差异无统计学意义（P=0.502）。并对本组PD-L1高表达患者免疫治疗的预测因素进行了分析，结果显示，一线免疫治疗ORR（12/19, 63.2%）显著优于二线及以上免疫治疗（10/30, 33.3%），差异有统计学意义（P=0.041），二者间PFS无差异。年龄、性别、吸烟史、功能状态评分（performance status, PS）、病理类型、肿瘤大小、肿瘤淋巴结转移（tumor node metastasis, TNM）分期与ORR和PFS不相关。结论PD-L1高表达的晚期NSCLC患者接受免疫单药和免疫联合化疗的疗效相近。PD-L1高表达患者一线免疫治疗的ORR更佳。对此类人群的最佳治疗方案有待于前瞻性临床研究进一步探索。     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

Connectivity measures suggest a sub-cortical generator of myoclonus in Angelman syndrome

ObjectiveThe clinical and neurophysiological characteristics of myoclonus in Angelman syndrome (AS) have been evaluated in single case or small cohorts, with contrasting results. We evaluated the features of myoclonus in a wide cohort of AS patients.MethodsWe performed polygraphic EEG-EMG recording in 24 patients with genetically confirmed AS and myoclonus. Neurophysiological investigations included jerk-locked back-averaging (JLBA), cortico-muscular coherence (CMC) and generalised partial directed coherence (GPDC). CMC and GPDC analyses were compared to those obtained from 10 healthy controls (HC).ResultsTwenty-four patients (aged 3–35 years, median 20) were evaluated. Sequences of quasi-continuous rhythmic jerks mostly occurred at alpha frequency or just below (mean 8.4 ± 1.4 Hz), without EEG correlate. JLBA did not show any clear transient preceding the jerks. CMC showed bilateral over-threshold CMC in alpha band that was prominent on the contralateral hemisphere in the patient group as compared to HC group. GPDC showed a significantly higher alpha outflow from both hemispheres toward activated muscles in the patient group, and a significantly higher beta outflow from contralateral hemisphere in the HC group.ConclusionsThese neurophysiological findings suggest a subcortical generator of myoclonus in AS.SignificanceMyoclonus in AS has not a cortical origin as previously hypothesised.     

TACE 术前天冬氨酸氨基转移酶与淋巴细胞比值对原发性肝癌并门脉癌栓患者预后预测的价值

目的 探讨肝动脉化疗栓塞（transcatheter arterial chemoembolization，TACE）术前天冬氨酸氨基转移酶与淋巴细胞比值（aspartate aminotransferase to lymphocyte ratio index，ALRI）在原发性肝癌并门脉癌栓（primary liver cancer-portal vein tumor thrombosis，PLC-PVTT）患者预后预测中的价值。方法 选取2013年11月21日至2018年8月22日于广西医科大学附属肿瘤医院接受TACE治疗的175例PLC-PVTT患者为研究对象。采用时间依赖性ROC曲线确定ALRI的最佳临界值。采用Cox 回归模型分析总生存期（overall survival，OS）的独立预测因素，Kaplan-Meier法计算生存率。结果 ROC曲线显示，ALRI的最佳临界值为49.37，对应曲线下面积为0.71。Kaplan-Meier分析显示，ALRI>49.37的患者OS较ALRI≤49.37的患者短（P=0.003）。Cox 回归分析结果显示，ALRI>49.37、行1次以上TACE治疗、Child-Pugh分级B级、凝血酶原时间≥13 s是患者TACE术后OS的独立危险因素（均P＜0.05）。结论 TACE术前ALRI>49.37是PLC-PVTT患者OS的独立危险因素。     

PDCA循环在消化道肿瘤伴糖尿病患者营养全程管理中的效果观察

目的 探讨PDCA 循环在消化道肿瘤伴糖尿病患者营养全程管理中的效果观察。方法 运用PDCA循环对80例不同程度营养不良的消化道肿瘤伴糖尿病患者实施营养全程管理,比较干预前后患者的体重、BMI指数、糖化血红蛋白、血红蛋白、总蛋白、白蛋白及球蛋白水平。结果 患者血红蛋白、总蛋白、白蛋白及球蛋白水平均有提高,比较差异均有统计学意义(P＜0.05)。结论 PDCA循环管理在消化道肿瘤伴糖尿病患者营养全程管理中有较大的优势, 值得推广。     

99mTc-DTPA核素肾动态显像评价主动脉夹层患者术后肾功能受损研究

目的:应用99mTc-DTPA肾动脉显像评价Stanford不同分型主动脉夹层患者术后左、右侧肾功能及总体肾功能受损程度,帮助临床制定进一步的治疗方案,改善患者预后。方法:回顾性分析2018年3月8日至2019年7月19日,在本院核医学科行99mTc-DTPA肾动态显像的主动脉夹层术后患者48例,评价患者双肾血流灌注、总肾小球滤过率(GFR)和分肾的GFR,比较Stanford主动脉夹层A型(简称A型)患者和主动脉夹层B型(简称B型)患者之间总肾功能及分肾功能,血肌酐、血尿素氮及血尿酸水平的差异。结果:B型患者术后总GFR低于A型患者(67.5 vs.80.6 m L/min,P<0.05),其中以左肾功能受损为著(30.9 vs.40.3 m L/min,P<0.05),差异有统计学意义。结论:肾动态显像对主动脉夹层术后患者早期评价肾功能有重要价值。主动脉夹层B型患者GFR较A型减低,且左侧肾GFR减低更明显,临床可以早期采取干预措施,改善主动脉夹层患者预后。