IL-6、ESR、CRP和常规生化检测用于诊断新型冠状病毒肺炎的临床价值分析

目的探讨白细胞介素-6(IL-6)、红细胞沉降率(ESR)和C反应蛋白(CRP)和常规生化指标在新型冠状病毒肺炎(COVID-19)诊断中的应用价值。方法收集2020年1-2月湖南中医药大学第一附属医院和厦门大学附属第一医院44例COVID-19确诊患者作为新冠肺炎组,30例体检健康者作为健康对照组。采集研究对象的血液标本,检测其IL-6、ESR、CRP和常规生化指标的水平,对IL-6、ESR、CRP作受试者工作特性曲线(ROC曲线),分析灵敏度和特异度,并且对IL-6、ESR、CRP和常规生化指标的结果进行综合比较。结果新冠肺炎组的IL-6水平为4.12(1.53~14.16)pg/mL,高于健康对照组,但差异无统计学意义(P>0.05);新冠肺炎组ESR和CRP的水平分别为61.50(19.75~85.00)mm/h、16.16(8.30~37.33)mg/L,显著高于健康对照组,差异有统计学意义(P<0.05)。IL-6、ESR和CRP单项检测诊断COVID-19的ROC曲线下面积(AUC)依次分别为0.577、0.872、0.905,灵敏度依次分别为38.6%、75.0%、72.7%,特异度依次分别为100.0%、96.7%、100.0%。CRP对COVID-19的诊断效能要优于ESR、IL-6,ESR对COVID-19的诊断效能要优于IL-6。而IL-6、ESR和CRP三项联合检测诊断COVID-19的AUC为0.939,灵敏度为86.4%,特异度为96.7%,要优于IL-6+ESR、IL-6+CRP、ESR+CRP两项联合检测及IL-6、ESR和CRP单项检测的诊断效能。同时40.91%的患者IL-6升高,79.55%的患者ESR升高,68.19%的患者CRP升高,93.18%的患者肌酸激酶(CK)正常,95.45%的患者肌酸激酶同工酶(CK-Mb)正常,48.00%的患者白细胞计数(WBC)正常,44.00%的患者WBC下降,64.00%的患者淋巴细胞百分率(LYMPH%)下降,52.00%的患者淋巴细胞计数(LYMPH)下降。结论IL-6、CRP和ESR三项指标联合检测的诊断效能优于IL-6、CRP、ESR单项检测和其他两项指标联合检测的诊断效能,所以IL-6、ESR和CRP对COVID-19有一定的诊断价值。     

1 203例泌尿生殖道衣原体和支原体感染检测及药敏分析

目的回顾本地区泌尿生殖道患者感染沙眼衣原体(CT)和解脲脲原体(Uu)、人型支原体(MH)的分布状况;了解支原体对12种抗生素体外药物敏感试验的现状。方法对1203例泌尿生殖道感染患者标本进行沙眼衣原体(CT)检测、支原体(Uu、MH)培养及药敏试验。结果1203例检测标本中,CT、Uu、MH三种病原体,总感染率为61.9%(745例),男性44.3%(221例),女性70.9%(524例)。其中CT总检出率13.7%(165例);单纯Uu感染女性(46.4%)大于男性(28.1%),Uu MH混合感染女性(12.55%)大于男性(2.4%),两者均有显著性差异。Uu对强力霉素、美满霉素、交沙霉素、环脂红霉素、克拉霉素敏感率大于90%,而对喹诺酮类的敏感率均小于50%;Uu MH混合感染对罗红霉素、红霉素、环丙沙星100%不敏感,其对药物的敏感性比单纯Uu感染存在差异。结论泌尿生殖道感染以Uu为主,其次为CT及Uu MH混合感染,女性感染率比男性高。Uu、Uu MH对抗生素的敏感性不同。对泌尿生殖道感染患者及时进行Uu和MH培养及耐药性监测,指导临床合理使用抗生素具有重要意义。     

Systemic treatment of patients with gastrointestinal stromal tumor: Current status and future opportunities

Imatinib mesylate is considered the standard first-line systemic treatment for patients with advanced gastrointestinal stromal tumor (GIST). Results from recent research have expanded the knowledge of tyrosine kinase inhibitors in management of GIST. In the setting of unresectable and metastatic GIST, long-term follow-up of the B2222 study showed that imatinib 400 and 600 mg/d produced objective responses in 68% of patients and clinical benefit in 84%; it also extended median survival from 19 months in historical controls to 57 months. The MetaGIST analysis in two large phase 3 trials consisting of more than 1600 patients with metastatic and/or unresectable GIST showed that imatinib 800 mg/d compared with the standard 400-mg/d dose conferred a progression-free survival advantage in patients with KIT exon 9 mutations but not in other subpopulations. The higher starting dose does not significantly improve overall survival. The BFR14 trial demonstrated that interrupting imatinib is associated with a high risk of rapid disease progression. For patients with imatinib-intolerant or imatinib-resistant GIST, sunitinib or a variety of investigational agents, including the next-generation kinase inhibitor nilotinib, may be viable options for achieving disease control. In the setting of primary localized GIST, function- sparing surgical resection is the standard treatment approach, but some patients may be at substantial risk of disease recurrence and metastasis depending on tumor size, mitotic count, and possibly other factors. Initial results from ACOSOG Z9001 indicate that adjuvant imatinib for 1 year prolongs recurrence-free survival following surgical resection of larger (at least 3 cm) KIT-expressing GIST. Other ongoing studies are further exploring the role of imatinib in both adjuvant and neoadjuvant therapy. Recent updates to clinical practice guidelines and recommendations now incorporate some of these new findings.     

吸烟及HPV16/18 感染对低度宫颈上皮内瘤自然消退的影响

目的宫颈上皮内瘤变(cervical intraepithelial neoplasias,CIN)是一组与宫颈浸润癌密切相关的癌前期病变的统称,包括宫颈不典型增生和宫颈原位癌,反映了宫颈癌发生中连续发展的过程,本研究探讨吸烟及HPV16/18感染与宫颈上皮内瘤变自然消退之间的关系。方法追踪2009年1月～2010年12月在长沙市三医院及长沙市妇幼保健院确诊为宫颈上皮内瘤变Ⅰ、Ⅱ期患者并在1年后复检者共385例,其中吸烟者98例,不吸烟者287例,高危HPV16/18感染者242例,无高危HPV16/18感染者143例。1年后复检385例患者中166例宫颈上皮内瘤变自然消退。对HPV16/18及吸烟对宫颈上皮瘤变转归的关系进行统计学分析。结果一年后385例CIN中166自然消退,非HPV16/18感染患者较HPV16/18感染患者有更高的宫颈上皮内瘤变自然消退率(60.8%vs32.6%),而其中吸烟的HPV16/18感染者宫颈上皮内瘤变自然消退率最低(27.1%)。结论Ⅰ、Ⅱ期宫颈上皮内瘤变在12月内可自然消退,HPV感染(HPV16/18)是宫颈上皮内瘤变持续的重要因素,吸烟可能促进HPV感染患者宫颈上皮内瘤变的持续存在。     

活血通脉利水明目法治疗非缺血型视网膜静脉阻塞的随机对照试验：对眼底荧光血管造影结果的影响

背景：活血通脉利水明目法能明显改善实验性视网膜静脉阻塞后眼底出血情况,作为一种中医治疗非缺血型视网膜静脉阻塞的治疗方法,显效率高,可有效改善中医症状,其作用机制可能与降低血浆黏度,减少无灌注区,建立有效侧枝循环有关。 目的：观察活血通脉利水明目法（散血明目片）对非缺血型视网膜静脉阻塞患者眼底荧光血管造影结果的影响。 设计、场所、对象和干预措施：纳入2005年4月至2007年4月在湖南中医药大学第一附属医院眼科门诊及病房就诊的34例非缺血型视网膜静脉阻塞患者。所有患者分为气滞血瘀和肝阳上亢两种证型。将该34例患者随机分为治疗组与对照组,治疗组给予散血明目片联合中西医常规治疗方法,对照组给予血栓通片联合中西医常规治疗方法。2个月为1个疗程。 主要结局指标：治疗1个疗程后,行眼底照相与眼底荧光血管造影,并进行评价。 结果：治疗组总有效率较对照组高,但差异无统计学意义,而治疗组总显效率与治疗组比较,差异有统计学意义（P〈0.01）;治疗组视网膜循环时间优于对照组,另外治疗组无灌注区、眼底新生血管和侧枝循环建立的改善程度均优于对照组。 结论：活血通脉利水明目法（散血明目片）是治疗非缺血型视网膜静脉阻塞的有效方法,能改善患者视功能,可反映在眼底荧光血管造影的多项指标上。     

护心通络方通过干预CETP介导脂质代谢抗兔动脉粥样硬化的实验研究

目的 探究护心通络方通过调控胆固醇脂转运蛋白（CETP）抗兔动脉粥样硬化（AS）的效果及作用机制。方法 将40只雄性新西兰兔按照随机数字表法分为空白对照组、AS模型组、辛伐他汀组[0.33 mg/（kg·d）]、护心通络方组[0.34 g/（kg·d）],每组10只。空白对照组予普通饲料喂养22周,其他3组予高脂饲料喂...     

Decoding the Evolutionary Response to Ensartinib in Patients With ALK-Positive NSCLC by Dynamic Circulating Tumor DNA Sequencing

IntroductionBy implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.MethodsIn a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.ResultsA total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p < 0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p < 0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.ConclusionsOur study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.     

Safety but Limited Efficacy of Ensartinib in ROS1-Positive NSCLC: A Single-Arm,Multicenter Phase 2 Study

IntroductionSome ALK inhibitors with good inhibition of ROS1 in preclinical studies have been reported to be possibly beneficial in ROS1-positive NSCLC. In this work, we studied the efficacy and safety of ensartinib in the treatment of patients with ROS1-positive NSCLC.MethodsThe exploratory study was a phase 2, single-arm, multicenter design (NCT03608007). Patients with ROS1-positive NSCLC with a previous chemotherapy line number of less than or equal to 1 who received ensartinib at the dose of 225 mg once daily were enrolled. The primary end point was objective response rate evaluated by an investigator per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom June 2018 to July 2019, a total of 59 patients were enrolled at 23 centers in the People’s Republic of China. At the time of data cutoff, the median follow-up was 19.8 months (range: 0.8–22.5). The median objective response rate was 27.0 % (95 % confidence interval [CI]: 13.8–44.1) with 10 partial responses. Median duration of response was 4.8 months (95 % CI: 1.8–10.8). The median progression-free survival was 4.6 months (95 % CI: 4.0–6.4). The median overall survival was not estimable (95 % CI: 14.9–not estimable). Of four patients with brain metastases, intracranial disease control was reported in three (75.0 %, 95 % CI: 19.4–99.4). The most common treatment-related adverse events (TRAEs) were rash and liver enzyme abnormalities, with good prognosis after adjustment for dosage and concomitant medication. Most of the TRAEs were of grades 1 to 2, and incidence of grade greater than or equal to 3 TRAEs was 25.4 %.ConclusionsEnsartinib had a modest efficacy in patients with ROS1-positive NSCLC with an acceptable safety profile.