2020年 · 第133卷第20期

2019年底，在湖北省武汉市的一组患者中报告了由新型冠状病毒引起的病毒性肺炎（2019年新型冠状病毒）。^[1]现在，冠状病毒疾病2019（新冠肺炎）对全球健康构成了重大威胁。截至2020年3月11日，中国经济大都市上海有344例确诊病例，320例康复，3例死亡，是新冠肺炎发病率较低的地区。^[2]在这项研究中，我们总结了新冠肺炎的控制策略和临床管理的几点，这些策略和管理对疾病的整体控制有很大影响。我们希望为世界其他地区的利益提供一些有价值的见解。

肺癌是对人类造成严重危害的最常见的恶性肿瘤之一。尽管化疗、放疗和靶向治疗取得了成功，但肺癌的预后仍然不令人满意。幸运的是，肺癌患者已经在免疫疗法中找到了希望，特别是在免疫检查点抑制剂（ICIs）中。ICIs是针对免疫检查点起作用的单克隆抗体，从而阻断T淋巴细胞的负性共刺激信号通路，恢复机体的抗肿瘤免疫反应，促进肿瘤细胞的清除。常见的ICI包括程序性细胞死亡（PD）-1抑制剂（纳武单抗和派姆单抗）、PD-配体1（PD-L1）抑制剂（阿特珠单抗和度伐鲁单抗）和细胞毒性T淋巴细胞相关抗原4（CTLA-4）抑制剂（伊匹木单抗和曲美木单抗）。

冠状病毒疾病2019（新冠肺炎）目前正在对全球人民的健康造成巨大损害。在2020年5月31日的新闻发布会上，世界卫生组织总干事谭德赛宣布，全球新冠肺炎病例已超过600万例。^[1]联合国经济和社会事务部的一项研究报告称，由于新冠肺炎疫情，2020年全球经济可能收缩近1%。^[2]面对这场史无前例的危机，包括科学家和普通公众在内的所有人都渴望收到关于新冠病毒的越来越详细的科学信息。为了及时分享最新的研究信息，无论是传统期刊还是非同行评议的预印本服务器都一直在孜孜不倦地发布关于这种疾病的最新研究，为临床医生和公共卫生官员提供支持和决策信息。

Due to development of magnetic resonance-based functional imaging, it is easier to detect micro-structural alterations of tumor tissues. The aim of this study was to conduct a preliminary evaluation of the correlation of non-Gaussian diffusion kurtosis imaging (DKI) parameters with expression of molecular markers (epidermal growth factor receptor [EGFR]; anaplastic lymphoma kinase [ALK]; Ki-67 protein) in patients with advanced lung adenocarcinoma, using routine diffusion-weighted imaging as the reference standard.

Data from patients with primary lung adenocarcinoma diagnosed at Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from 2016 to 2019 were collected for retrospective analysis. The pathologic and magnetic resonance imaging data of 96 patients who met the inclusion criteria were included in this study. Specifically, the K_app and D_app parameters measured from the DKI model; apparent diffusion coefficient (ADC) value from the diffusion-weighted imaging model; and the EGFR, ALK, and Ki-67 biomarkers detected by immunohistochemistry and/or molecular biology techniques after biopsy or surgery were evaluated. The relations between quantitative parameters (ADC, K_app, D_app) and pathologic outcomes (EGFR, ALK, and Ki-67 expression) were analyzed by Spearman correlation test.

Of the 96 lung adenocarcinoma lesions (from 96 patients), the number of EGFR- and ALK-positive and high Ki-67 expressing lesions were 53, 12, and 83, respectively. The K_app values were significantly higher among patients with EGFR-positive mutations (0.81 ± 0.12 vs. 0.66 ± 0.10, t = 6.41, P < 0.001), ALK rearrangement-negative (0.76 ± 0.12 vs. 0.60 ± 0.15, t = 4.09, P < 0.001), and high Ki-67 proliferative index (PI) (0.76 ± 0.12 vs. 0.58 ± 0.13, t = 4.88, P < 0.001). The D_app values were significantly lower among patients with high Ki-67 PI (3.19 ± 0.69 μm²/ms vs. 4.20 ± 0.83 μm²/ms, t = 4.80, P < 0.001) and EGFR-positive mutations (3.11 ± 0.73 μm²/ms vs. 3.59 ± 0.77 μm²/ms, t = 3.12, P = 0.002). The differences in mean D_app (3.73 ± 1.26 μm²/ms vs. 3.26 ± 0.68 μm²/ms, t = 1.96, P = 0.053) or ADC values ([1.34 ± 0.81] × 10^-3 mm²/s vs. [1.33 ± 0.41] × 10^-3 mm²/s, t = 0.07, P = 0.941) between the groups with or without ALK rearrangements were not statistically significant. The ADC values were significantly lower among patients with EGFR-positive mutation ([1.19 ± 0.37] × 10^-3 mm²/s vs. [1.50 ± 0.53] × 10^-3 mm²/s, t = 3.38, P = 0.001) and high Ki-67 PI ([1.28 ± 0.39] × 10^-3 mm²/s vs. [1.67 ± 0.77] × 10^-3 mm²/s, t = 2.88, P = 0.005). K_app was strongly positively correlated with EGFR mutations (r = 0.844, P = 0.008), strongly positively correlated with Ki-67 PI (r = 0.882, P = 0.001), and strongly negatively correlated with ALK rearrangements (r = -0.772, P = 0.001). D_app was moderately correlated with EGFR mutations (r = -0.650, P = 0.024) or Ki-67 PI (r = -0.734, P = 0.012). ADC was moderately correlated with Ki-67 PI (r = -0.679, P = 0.033).

The K_app value of DKI parameters was strongly correlated with different expression of EGFR, ALK, and Ki-67 in advanced lung adenocarcinoma. The results potentially indicate a surrogate measure of the status of different molecular markers assessed by non-invasive imaging tools.

The coronavirus disease 2019 (COVID-19) outbreak occurred during the flu season around the world. This study aimed to analyze the impact of influenza A virus (IAV) exposure on COVID-19.

Seventy COVID-19 patients admitted to the hospital during January and February 2020 in Wuhan, China were included in this retrospective study. Serum tests including respiratory pathogen immunoglobulin M (IgM) and inflammation biomarkers were performed upon admission. Patients were divided into common, severe, and critical types according to disease severity. Symptoms, inflammation indices, disease severity, and fatality rate were compared between anti-IAV IgM-positive and anti-IAV IgM-negative groups. The effects of the empirical use of oseltamivir were also analyzed in both groups. For comparison between groups, t tests and the Mann-Whitney U test were used according to data distribution. The Chi-squared test was used to compare disease severity and fatality between groups.

Thirty-two (45.71%) of the 70 patients had positive anti-IAV IgM. Compared with the IAV-negative group, the positive group showed significantly higher proportions of female patients (59.38% vs. 34.21%, χ² = 4.43, P = 0.035) and patients with fatigue (59.38% vs. 34.21%, χ² = 4.43, P = 0.035). The levels of soluble interleukin 2 receptor (median 791.00 vs. 1075.50 IU/mL, Z = -2.70, P = 0.007) and tumor necrosis factor α (median 10.75 vs. 11.50 pg/mL, Z = -2.18, P = 0.029) were significantly lower in the IAV-positive group. Furthermore, this group tended to have a higher proportion of critical patients (31.25% vs. 15.79%, P = 0.066) and a higher fatality rate (21.88% vs. 7.89%, P = 0.169). Notably, in the IAV-positive group, patients who received oseltamivir had a significantly lower fatality rate (0 vs. 36.84%, P = 0.025) compared with those not receiving oseltamivir.

The study suggests that during the flu season, close attention should be paid to the probability of IAV exposure in COVID-19 patients. Prospective studies with larger sample sizes are needed to clarify whether IAV increases the fatality rate of COVID-19 and to elucidate any benefits of empirical usage of oseltamivir.

Acute coronary syndromes mainly result from abrupt thrombotic occlusion caused by atherosclerotic vulnerable plaques (VPs) that suddenly rupture or erosion. Fibrous cap thickness (FCT) is a major determinant of the propensity of a VP to rupture and is recognized as a key factor. The intensive use of statins is known to have the ability to increase FCT; however, there is a risk of additional adverse effects. However, lower dose statin with ezetimibe is known to be tolerable by patients. The present study aimed to investigate the effect of intensive statin vs. low-dose stain + ezetimibe therapy on FCT, as evaluated using optical coherence tomography.

Patients who had VPs (minimum FCT <65 μm and lipid core >90°) and deferred from intervention in our single center from January 2014 to December 2018 were included in the trial. They were divided into the following two groups: intensive statin group (rosuvastatin 15-20 mg or atorvastatin 30-40 mg) and combination therapy group (rosuvastatin 5-10 mg or atorvastatin 10-20 mg + ezetimibe 10 mg). At the 12-month follow-up, we compared the change in the FCT (ΔFCT%) between the two groups and analyzed the association of ΔFCT% with risk factors. Fisher exact test was used for all categorical variables. Student’s t test or Mann-Whitney U-test was used for analyzing the continuous data. The relationship between ΔFCT% and risk factors was analyzed using linear regression analysis.

Total 53 patients were finally enrolled, including 26 patients who were in the intensive statin group and 27 who were in the combination therapy group. At the 12-month follow-up, the serum levels of total cholesterol (TC), total triglyceride, low-density lipoprotein (LDL-C), hypersensitive C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels were reduced in both the groups. The ΔTC%, ΔLDL-C%, and ΔLp-PLA2% were decreased further in the combination therapy group. FCT was increased in both the groups (combination treatment group vs. intensive statin group: 128.89 ± 7.64 vs. 110.19 ± 7.00 μm, t = -9.282, P < 0.001) at the 12-month follow-up. The increase in ΔFCT% was more in the combination therapy group (123.46% ± 14.05% vs. 91.14% ± 11.68%, t = -9.085, P < 0.001). Based on the multivariate linear regression analysis, only the serum Lp-PLA2 at the 12-month follow-up (B = -0.203, t = -2.701, P = 0.010), ΔTC% (B = -0.573, t = -2.048, P = 0.046), and Δhs-CRP% (B = -0.302, t = -2.963, P = 0.005) showed an independent association with ΔFCT%.

Low-dose statin combined with ezetimibe therapy maybe provide a profound and significant increase in FCT as compared to intensive statin monotherapy. The reductions in Lp-PLA2, ΔTC%, and Δhs-CRP% are independently associated with an increase in FCT.

Hasner valve incision has been recently introduced as a new treatment for ophthalmic patients with epiphora symptoms. The aim of this study was to examine whether surgical outcomes of Hasner valve incision for inferior nasolacrimal duct obstruction were different between pediatric and adult patients.

A total of 53 eyes of 52 patients who underwent Hasner valve incision in the Beijing Tongren Hospital from October 2016 to November 2019 were retrospectively observed. Patients were divided into two groups, including pediatric group (23 eyes of 22 patients, <18 years old) and adult group (30 eyes of 30 patients, ≥18 years old). Success rate of surgery was determined by both subjective measure (complete resolution of epiphora) and objective measure (lacrimal passage irrigation and tear meniscus height). Fisher exact test was conducted.

By conducting Fisher exact test and comparing complete resolution of epiphora (P = 0.627), lacrimal passage irrigation (P = 0.663), measurement of Tear Meniscus Height (P = 0.561), and appearance of complication (P = 0.339), there was no statistically significant difference of surgical outcomes between pediatric and adult patients (P > 0.05).

Hasner valve incision was effective for both adult and children with inferior nasolacrimal duct obstruction, with no difference in surgical outcomes between the two groups.

Endothelial cells play a key role in the cytokine storm caused by influenza A virus. MicroRNA-155 (miR-155) is an important regulator in inflammation. Its role in the inflammatory response to influenza A infection, however, has yet to be elucidated. In this study, we explored the role as well as the underlying mechanism of miR-155 in the cytokine production in influenza A-infected endothelial cells.

Human pulmonary microvascular endothelial cells (HPMECs) were infected with the influenza A virus strain H1N1. The efficiency of H1N1 infection was confirmed by immunofluorescence. The expression levels of proinflammatory cytokines and miR-155 were determined using real-time polymerase chain reaction. A dual-luciferase reporter assay characterized the interaction between miR-155 and sphingosine-1-phosphate receptor 1 (S1PR1). Changes in the target protein levels were determined using Western blot analysis.

MiR-155 was elevated in response to the H1N1 infection in HPMECs (24 h post-infection vs. 0 h post-infection, 3.875 ± 0.062 vs. 1.043 ± 0.013, P = 0.001). Over-expression of miR-155 enhanced inflammatory cytokine production (miR-155 mimic vs. negative control, all P < 0.05 in regard of cytokine levels) and activation of nuclear factor kappa B in infected HPMECs (miR-155 mimic vs. negative control, P = 0.004), and down-regulation of miR-155 had the opposite effect. In addition, S1PR1 was a direct target of miR-155 in the HPMECs. Inhibition of miR-155 enhanced the expression of the S1PR1 protein. Down-regulation of S1PR1 decreased the inhibitory effect of the miR-155 blockade on H1N1-induced cytokine production and nuclear factor kappa B activation in HPMECs.

MiR-155 maybe modulate influenza A-induced inflammatory response by targeting S1PR1.

Epithelial to mesenchymal transition (EMT) is strongly linked with tumor invasion and metastasis, which performs a vital role in carcinogenesis and cancer progression. Emerging evidence suggests that microRNAs (miRNAs) expression are closely associated to EMT by regulating targeted genes. MiR542 has been found to be involved in the EMT program and bound up with various cancers. However, the functions of miR542 and its underlying mechanism in glioblastoma multiforme (GBM) remain largely unknown. In the current study, we investigated the effect of astrocyte elevated gene-1 (AEG-1) on U251 cells aggressiveness, proliferation, apoptosis, and cell cycle.

The screening of targeted miRNAs was performed, as well as the functional roles and mechanisms of miR542 were explored.

MiR542 was selected as the target because of the most significantly differential expression and this high level of expression negatively correlated with cell migration and proliferation, which suggested that miR542 could be a novel tumor suppressor. Moreover, we confirmed that AEG-1 was a direct targeted gene of miR542 by luciferase activity assay, reverse transcription-polymerase chain reaction, and immunoblotting analysis. Furthermore, miR542 suppressed the expression of AEG-1, which upgraded the level of E-cadherin and degraded Vimentin expression contributing to retraining EMT.

The in vitro findings demonstrated that miR542 inhibited the migration and proliferation of U251 cells and suppressed EMT through targeting AEG-1, indicating that miR542 may be a potential anti-cancer target for GBM.

在过去的几十年中，在晚期非小细胞肺癌(NSCLC)方面取得了巨大的进展。致癌驱动因素的识别和靶向治疗的开发导致了“精准”医学的发展。另一方面，癌症免疫逃逸受到了更多的关注，并开发了一类新的免疫调节剂。探索两种途径的结合策略是非常有吸引力的，从免疫学的角度来看，这也可能是有意义的。

不同国家的特发性肺纤维化（IPF）发病率差异很大，在北美和欧洲为每年每100,000名居民3至9人，而在南美和亚洲，发病率较低，为每年每100,000名居民1.2至4.16人。^[1]随着IPF发病率的增加，IPF造成的经济负担也越来越重。美国一项关于IPF患者疾病负担的研究发现，总直接医疗费用（包括住院服务、门诊服务和药物索赔）为26,378美元。^[2]在西班牙，每位IPF患者的估计年费用为26,435欧元。^[3]然而，中国关于IPF患者经济负担的数据很少。本研究旨在检查IPF住院患者的直接医疗费用并确定影响因素。

重症急性呼吸窘迫综合征（ARDS）常见于重症监护病房（ICU）。其特征是毛细血管内皮和肺泡上皮损伤，导致毛细血管通透性和血管外肺水显著增加。使用常规成像很难准确量化肺水肿。脉搏指数连续心输出量（PiCCO）是一个基于经肺热稀释的参数，克服了这些缺点。可以连续且准确地确定源自PiCCO的几个测量值，包括血管外肺水指数(ELWI)和肺血管通透性指数(PVPI)。几项前瞻性研究表明，根据这些测量结果进行早期目标导向治疗（EGDT）有助于容量管理，并最终降低危重患者的住院死亡率。^[1]

冠状病毒病2019（新冠肺炎）是由严重急性呼吸综合征冠状病毒2（新型冠状病毒）引起的急性呼吸道传染病。^[1]要求综合医院发热门诊加强对这种高传染性疾病的监测。体温≥37.3°C的患者被要求首先到发热门诊就诊，在发热门诊实施分诊策略，由专家或专家小组确定可能或可能的病例，并送样本进行快速病毒检测。在此期间，流感等其他病因引起的肺炎在北京也和全国其他地区一样流行；对于医生来说，从发热患者，特别是各种病因的肺炎中识别疑似新冠肺炎是一个挑战。因此，在这种危急情况下，需要信息来帮助区分新冠肺炎和其他病因引起的肺炎。

冠状病毒疾病2019（新冠肺炎）是一场具有挑战性的健康危机，使全球医疗能力紧张。病例在家庭中聚集是新冠肺炎的一个特征。^[1]许多患者的家庭成员也感染了致病病毒严重急性呼吸综合征冠状病毒2（新型冠状病毒）。在这里，我们描述了患有新冠肺炎的家庭成员的伴侣及其对治疗该疾病的潜在益处。

致编辑：脊髓性肌萎缩症（SMA）是一种常染色体隐性疾病，由存活运动神经元1（SMN1）蛋白缺乏引起，导致脊髓前角运动神经元丢失。^[1]遗传相似基因、SMN2在其第7外显子的第6位具有翻译沉默的C-T转换，其通过选择性剪接仅导致10%正确剪接的全长和功能性SMN蛋白。但是在受SMA影响的个体中，SMN2是SMN蛋白的唯一来源，并且由于其拷贝数（1-8）与疾病严重程度之间的关系而被定义为疾病修饰基因。^[2]已经揭示了许多测定来定量SMN1和SMN2在DNA样本中。目前，多重连接依赖性探针扩增（MLPA）^[3]和一种新兴的方法液滴数字聚合酶链反应（ddPCR）^[4]是两种广泛使用的基因筛查方法。因此，比较了两种不同技术的再现性，以评估SMN1和SMN2.

致编辑：双侧丘脑病变并不常见，但不同类型的发病机制可分为代谢过程、毒性暴露、感染、血管病变和肿瘤。^[1]在可能的发病形式中，颅内硬脑膜动静脉瘘（dAVF）极为罕见。^[1]几篇文章报道了与DAVF相关的双侧丘脑病变的病例。然而，由于所涉及的供应动脉和引流静脉以及所使用的治疗方法的差异，DAVF会导致一系列临床结果。^[2,3]在此，我们报告一例罕见的复杂颅内dAVF病例，表现为痴呆样症状和双侧丘脑病变。我们描述了患者的症状、磁共振成像（MRI）、磁共振血管造影（MRA）和数字减影血管造影（DSA）的发现，以及血管内治疗的治疗过程和临床结果。

致编辑：高流量鼻插管（HFNC）的本质是无创呼吸机（NIVCFM）中的一种恒流模式。NIVCFM/HFNC的主要机制是死腔冲洗和低水平气道压力的产生，然而，需要在成人中进一步的证据。在这里，我们测量了呼气末二氧化碳压力（PetCO₂）、不同流速下鼻腔不同深度的呼气末压(EEP)和吸气末压(EIP)，以验证健康成人NIVCFM/HFNC的呼吸生理机制：二氧化碳(CO₂）洗涤机制的存在及其强度，以及NIVCFM/HFNC能产生多少EEP和EIP。

致编辑：一名70岁男性患者因严重主动脉瓣狭窄接受了经导管主动脉瓣植入术（TAVI）。超声心动图显示主动脉瓣内峰值速度为4.33 m/s，峰值压力梯度为75 mmHg，平均压力梯度为38 mmHg。左心室收缩末期尺寸和舒张末期尺寸分别为31.7和50.0 mm。主动脉环内径30.7 mm，主动脉窦直径37.3 mm。瓣膜面积0.87 cm²计算机断层扫描显示根据主动脉瓣环周长85.6 mm，直径为27.3 mm的二叶主动脉瓣，或根据569 mm，直径为27.4 mm的主动脉瓣²阀门孔口面积。植入26 mm Venus-A瓣膜（Venus Medtech，杭州，中国）。