Volume 133 · Issue 21 · 2020

Secukinumab demonstrated sustained efficacy in patients with ankylosing spondylitis (AS) through 5 years in pivotal Phase III studies. Here, we present efficacy and safety results (52-week) of secukinumab in patients with AS from the MEASURE 5 study.

MEASURE 5 was a 52-week, Phase III, China-centric study. Eligible patients were randomly assigned (2:1) to receive subcutaneous secukinumab 150 mg or placebo weekly for the first five doses and then once every 4 weeks (q4w). All placebo patients switched to secukinumab 150 mg q4w starting at Week 16. Primary endpoint was Assessments of SpondyloArthritis international Society (ASAS) 20 at Week 16. Randomization was stratified by region (China vs. non-China).

Of 458 patients (secukinumab 150 mg, N= 305; placebo, N= 153) randomized, 327 (71.4%) were from China and 131 (28.6%) were not from China. Of these, 97.7% and 97.4% patients completed Week 16 and 91.1% and 95.3% (placebo-secukinumab) patients completed Week 52 of treatment. The primary endpoint was met; secukinumab significantly improved ASAS20 response at Week 16 vs. placebo (58.4% vs. 36.6%; P < 0.0001); corresponding rate in the Chinese population was 56.0% vs. 38.5% (P < 0.01). All secondary efficacy endpoints significantly improved with secukinumab 150 mg in the overall population at Week 16; responses were maintained with a trend toward increased efficacy from Week 16 to 52. No new or unexpected safety signals were reported up to Week 52.

Secukinumab 150 mg demonstrated rapid and significant improvement in signs and symptoms of AS. Secukinumab was well tolerated and the safety profile was consistent with previous reports. Efficacy and safety results were comparable between the overall and Chinese populations.

ClinicalTrials.gov, NCT02896127; https://clinicaltrials.gov/ct2/show/NCT02896127?term=NCT02896127&draw= 2&rank=1.

Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis.

The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays.

Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs.

The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.

Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC).

The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature.

Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease.

We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.

Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor prognosis and outcomes. This study aimed to investigate clinicopathological features, molecular characteristics, and treatments among Chinese patients diagnosed with IBC.

We collected data of 95 patients with IBC who were treated by members of the Chinese Society of Breast Surgery, from January 2017 to December 2018. The data, including demographic characteristics, pathological findings, surgical methods, systemic treatment plans, and follow-up, were obtained using a uniform electronic questionnaire. The clinicopathological features of different molecular types in patients without distant metastases were compared using the Kruskal-Wallis (H) test followed by post hoc analyses.

Lymph node metastasis was noted in 75.8% of all patients, while distant metastasis was noted in 21.4%. Pathological findings indicated invasive ductal and lobular carcinomas in 86.8% and 5.3% of cases, respectively. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) (41.5%) and HR-/HER2+ (20.1%) were the most common biologic subtypes, followed by HR+/HER2+ (19.1%) and HR-/HER2-(19.1%). Stage III IBC was treated via pre-operative neoadjuvant chemotherapy in 87.7% of the cases, predominantly using anthracycline and taxanes. A total of 91.9% of patients underwent surgical treatment. Among them, 77.0% of the patients underwent modified radical mastectomy, 8.1% of whom also underwent immediate breast reconstruction. The Kruskal-Wallis test revealed that the efficacy of chemotherapy significantly differed among those with HR+/HER2 -and HR-/HER2-tumors (adjusted P = 0.008), and Ki-67 expression significantly differed in HR-/HER2+ and HR+/HER2+ molecular subtypes (adjusted P = 0.008).

Our study provides novel insight into clinicopathological characteristics and treatment status among patients with IBC in China, and might provide a direction and basis for further studies.

chictr.org.cn, No. ChiCTR1900027179; http://www.chictr.org.cn/showprojen.aspx?proj=45030

Multifocal motor neuropathy (MMN), Lewis-Sumner syndrome (LSS), and many chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) are representative of acquired multifocal polyneuropathy and are characterized by conduction block (CB). This retrospective study aimed to investigate the demyelinating distribution and the selective vulnerability of MMN, LSS, and CIDP with CB (CIDP-CB) in nerves.

Fifteen LSS subjects (107 nerves), 24 MMN subjects (176 nerves), and 17 CIDP-CB subjects (110 nerves) were included. Their clinical information was recorded, blood and cerebrospinal fluid tests were conducted, and nerve conductions of the median, ulnar, radial, peroneal, and tibial nerves were evaluated. CB, temporal dispersion, distal motor latency (DML), and F-wave latency were recorded, and nerve conduction velocity, terminal latency index, and modified F-wave ratio were calculated.

CB was more likely to occur around the elbow in CIDP-CB than in MMN (78.6% vs. 6.8%, P < 0.01) but less likely to occur between the wrist and the elbow than in LSS (10.7% vs. 39.3%, P < 0.05). Tibial nerve CB was most frequently observed in MMN (47.4%, P < 0.05). CIDP-CB was characterized by a prolonged DML in all nerves, and slow motor nerve velocity of the upper limb was significant when CB nerves were excluded (P < 0.05).

We report the different distributions of segmental and diffuse demyelination of the ulnar and tibial nerves in LSS, MMN, and CIDP-CB. These distinct distributions could help in differentiating among these conditions.

Recent studies have reported circular RNA (circRNA) expression profiles in various tissue types; however, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. This work aimed to compare circRNA expression patterns in EAT between the heart failure (HF) and non-HF groups.

RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups. Quantitative real-time polymerase chain reaction was performed for validation. Comparisons of patient characteristics between the two groups were using t test, Mann-Whitney U test, and Chi-squared test.

A total of 141 circRNAs substantially different between the HF and non-HF groups (P < 0.05; fold change >2) were detected, including 56 up-regulated and 85 down-regulated. Among them, hsa_circ_0005565 stood out, for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including GSE1, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B, and SPECC1. The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance, respectively.

These data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.

Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses distinct clinical challenges due to extensively drug resistant (XDR) phenotype, and sequence type (ST) 11 is the most dominant bla_KPC-2-bearing CP-Kp clone in China. The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit (ICU) of a Chinese tertiary hospital.

Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination, polymerase chain reaction, and pyrosequencing. The six ST11 XDR CP-Kp, as well as three multi-drug resistant (MDR) and four susceptible strains, were sequenced using single-molecule real-time method. Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains.

We found that ST11 XDR bla_KPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital. Functionally, genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains, especially genes correlative with mobile genetic elements (MGEs) such as transposons and prophages. Structurally, eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons, integrons, prophages, genomic islands, and integrative and conjugative elements. Three of them were located on plasmids and eight on chromosomes; five of them were with antimicrobial resistance genes and eight with adaptation associated genes. Notably, a new bla_KPC-2-bearing ΔΔTn1721-bla_KPC-2 transposon, probably transposed and truncated from ΔTn1721-bla_KPC-2 by IS903D and ISKpn8, was identified in all six ST11 XDR CP-Kp strains.

Our findings suggested that together with clonal spread, MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability, which facilitated their widespread dissemination in hospital.

自体移植、同种异体移植和异种移植是最广泛使用的增强骨缺损有效重建的方法，但天然供体骨存在一些缺陷，如供应有限、移植供应部分过度损伤、生长受限和并发症发生率高。^[1]生物活性骨替代材料为骨缺损修复和再生提供了一种选择。增强可注射骨支架材料应用于骨科和牙科的骨替代治疗，在骨组织工程中用于骨缺损修复引起了广泛的讨论。目前临床使用和正在研究的可注射骨水泥材料可分为三大类：聚甲基丙烯酸甲酯（PMMA）、磷酸钙基骨水泥（CPCs）和硫酸钙基骨水泥（CSCs）。其中，CPCs的化学成分与骨的无机成分最相似。CPC模拟骨的矿物相，为骨组织形成天然晶格，以促进天然骨向内生长和重塑。^[2]此外，与最广泛使用的PMMA骨水泥相比，CPC具有较低的放热反应温度，并促进更好的骨整合。由于这些原因，它们已成为最有前途的骨修复材料之一。^[3]然而，CPCs也有一些局限性：（1）其降解速率慢，缺乏促进新骨形成的大孔隙率，使其骨诱导能力不足以满足临床需求。^[4]改性工作包括制造多孔/纳米结构和/或药物递送CPC复合材料以促进骨生长；（2）另一个缺点是CPCs的机械强度无法与人皮质骨的强度相匹配；因此，强度改性是另一个研究方向。

循环肿瘤DNA（ctDNA）是凋亡或坏死的肿瘤细胞释放到外周血中的DNA片段，携带基因突变后的基本遗传信息。ctDNA的检测和分析可以提供肿瘤大小和发展的基因组信息；因此，它被认为是一种新兴且有前途的肿瘤生物标志物，用于癌症进展、复发和术后常规监测。尽管由于ctDNA的稳定性，分离方法相对简单，但ctDNA的丰度极低，并且由于背景无细胞DNA(cfDNA)的高含量、个体之间的大差异以及需要预测的检测位点，因此有必要以综合的方式分析ctDNA。目前，以敏感性和特异性满足ctDNA检测需求的主要方法有扩增难治性突变系统PCR（ARMS-PCR）、数字PCR（dPCR）和高通量测序。其中，dPCR在实用性方面具有优势，可实现单分子DNA的绝对定量，检测和追踪DNA分子并进行定量分析，为临床监测肿瘤复发和微小残留病提供可靠依据。本文就ctDNA在妇科肿瘤中的检测及潜在价值作一综述。

甲状腺素运载蛋白相关家族性淀粉样多发性神经病（TTR-FAP）是一种常染色体显性、危及生命且可治疗的疾病，由TTR突变。其特征是外周神经和主要器官（包括心脏、肾脏和眼睛）中的淀粉样蛋白沉积。到目前为止，超过130TTR已经确定了突变，其中P.Val 30Met在流行国家最常见。TTR-FAP已在29个国家报告，包括欧洲、美国、日本、中国和印度的许多国家。TTR-FAP的临床和遗传学特征在欧洲和日本已经比较明确，然而，在中国仍需开展。在这里，我们报告了8个中国TTR-FAP家系的临床和遗传学特征。

多发性骨髓瘤（MM）是一种以浆细胞克隆性增殖为特征的血液恶性肿瘤，使血、尿中单克隆免疫球蛋白数量增加，引起靶器官损害。据报道，长非编码RNA（lncRNAs）具有高遗传异质性，并参与MM的恶性肿瘤形成、进展和转移。^[1]此外，lncRNAs和环状RNA（circRNAs）通过间接结合miRNA并影响靶基因表达的转录后调节而充当微小RNA（miRNA）海绵。这种现象被称为竞争内源性（ceRNA）关系，它可能是癌症中最重要的lncRNA机制之一。然而，唯一的lncRNA母体表达基因3（MEG3）被报道作为ceRNA通过海绵化MM中的miR-181a来调节同源盒基因A11 mRNA表达。^[2,3]因此，其他ceRNA关系，尤其是在新诊断的MM患者中，仍有待研究。

免疫抑制（IS）对于肝移植（LTx）患者控制主要由T细胞介导的不需要的同种免疫反应是不可或缺的。然而，T细胞的抗原非依赖性稳态对于维持长期T细胞介导的免疫至关重要，过量的IS可能增加机会性感染和恶性肿瘤的风险。因此，LTx患者的IS治疗应根据个体患者的免疫状态进行定制。^[1]胆道并发症（BC），包括胆道狭窄伴胆管炎，是LTx术后最常见的并发症。然而，这些患者的免疫学特征，尤其是T细胞介导的免疫尚不清楚。

报告表明，外周动脉损伤尤其具有挑战性，因为它们与肢体丧失的高风险相关。需要快速诊断和干预来提供肢体挽救，并且可以挽救生命。随着血管内技术和工具的不断发展，开放修复已经不是治疗创伤性血管损伤的唯一选择。类似地，微创经皮血管内治疗提供了一种有吸引力的治疗选择。由于血管内治疗几乎同时进行诊断评估和治疗干预，急性创伤性血管病变的保肢可能会得到改善。

致编辑：目前的指南建议急性冠状动脉综合征（ACS）患者如果没有禁忌症，应接受阿司匹林加P2Y12抑制剂（氯吡格雷、普拉格雷或替格瑞洛）的双重抗血小板治疗。到目前为止，关于强效抗血小板药物在老年ACS患者中的临床疗效和安全性的信息有限，尤其是在高龄人群（年龄≥75岁）中。我们搜索了2000年1月至2019年12月的PubMed、Cochrane图书馆、Web of Science、EMBASE（摘录医学数据库）。使用Stata软件12.0版（StataCorp LP，College Station，TX，USA）进行数据分析。总体调查结果记录为双侧风险比(RR)和95%置信区间(CI)P价值观。最后，本荟萃分析纳入了7项临床研究，包括8848名老年ACS患者（年龄≥65岁）口服强效P2Y12抑制剂与氯吡格雷的比较。^{[1,2,3,4,5,6,7]}纳入试验中65岁以上患者以阿司匹林联合替格瑞洛为主，75岁以上患者以阿司匹林联合普拉格雷为主。五千六百四十八名（63.8%）患者接受阿司匹林加普拉格雷治疗，3839名患者（43.4%）接受减少维持剂量的普拉格雷治疗（<10毫克）。纳入的7项研究均为高质量研究。

致编辑：在世界范围内，肺癌，特别是非小细胞肺癌(NSCLC)是肿瘤相关死亡的主要原因。成本效益分析显示，晚期非小细胞肺癌患者接受化疗无经济效益。^[1]此外，分别通过免疫组织化学方法和下一代测序评估的诸如程序性细胞死亡配体1(PD-L1)和肿瘤突变负荷(TMB)测试的测试被广泛用于筛选免疫检查点抑制剂(ICI)的潜在受益者。但这两种方法的预测值不同，使其综合评价成为当前争议的焦点。

致编辑：Charcot-Marie-Tooth病(CMT)包括一组遗传异质性遗传性神经病，其特征是进行性远端肌肉无力和萎缩、感觉缺陷、肌腱反射受损和足部畸形。^[1]迄今为止，已在CMT患者中鉴定出80多个致病基因，与常染色体显性或隐性遗传或X连锁传播相关。CMT的传统分类是基于周围神经病变类型，由神经传导速度确定。随着更多致病基因的鉴定和神经病变表型的重叠变得明显，传统的分类系统被证明是笨拙和不充分的。此外，CMT需要与包括具有神经病变的全身性疾病和其他类型的遗传性神经病变在内的几种实体相区别。在临床实践中，表型的重叠可能是达到正确诊断的主要挑战。本研究旨在调查中国CMT患者队列的遗传谱，并评估基因检测在CMT诊断和亚型分型中的作用。

致编辑：唤醒卒中(WUS)是主要在夜间睡眠期间发生的缺血性卒中的名称，约占所有急性缺血性卒中(AIS)病例的20%。流行病学研究表明，AIS呈昼夜节律分布，早晨频率较高，睡眠期间频率较低。^[1]目前尚不清楚WUS是否是一个随机事件，或者是否有一个独特的病理生理过程，如昼夜节律紊乱，将WUS与日间卒中（非WUS）区分开来。

致编辑：许多经过充分研究的超声特征已在临床上用于评估甲状腺结节的恶性肿瘤。美国放射学院甲状腺成像、报告和数据系统（TI-RADS）提出的超声灰度特征包括成分、回声、形状、边缘和回声病灶。^[1]其他特征，如血管成像，已逐渐被超声医师认识。在结构和生物学行为方面，与正常组织相比，持续的血管生成导致肿瘤特异性脉管系统。^[2]肿瘤新血管形成显示异常成熟，表现为不规则的发芽和血管生成血管的分支，周细胞的无序覆盖。因此，血管分布对于评估甲状腺结节的恶性肿瘤至关重要。

致编辑：颈椎前路椎间盘切除融合术（ACDF）是保守治疗失败的脊髓型颈椎病患者的“金标准”。^[1]zeroprofile独立设备（Zero P；Synthes GmbH，Zuchwil，Switzerland）比用于ACDF的传统板和笼更受欢迎。^[2]云等人^[3]表明Zero-P在椎间盘间隙的插入点可能是维持椎间盘前高度的重要因素。然而，对于与更好的临床和放射学结果相关的立场没有共识。

致编辑：心房颤动（AF）是在普通人群中观察到的最常见的心律失常之一。与AF相关的中风的主要原因是血栓形成在左心耳（LAA）中并从其脱落。超过90%的心源性血栓形成起源于LAA，因为LAA的囊状和复杂形态诱导血流停滞。^[1]在本研究中，我们旨在通过一般观察、生化和组织学研究以及超声心动图评估在犬模型中微创开胸植入改良LAA夹（LAAC）的可行性和有效性。