特发性肺纤维化急性加重期证候与血清生物标志物的相关性研究＊

目的 通过分析特发性肺纤维化急性加重期（AE-IPF）患者证候与血清生物标志物的关系，为中医辨证治疗提供参考。方法 采用观察性研究设计，收集2019年3月至2019年11月三个中心的AE-IPF患者76例，其中痰热壅肺证26例、痰浊阻肺证50例，并纳入健康志愿者10例作为对照。采用ELISA测定患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平，分析与中医证候的相关性。结果 AE-IPF患者血清CCL18、HMGB1、KL-6、MMP-7、SP-A和SP-D水平均显著高于健康对照组。血清CCL18、HMGB1、KL-6、MMP-7和SP-D水平在痰热壅肺证和痰浊阻肺证患者间无显著性差异（P＞0.05），而血清SP-A水平存在显著性差异（P＜0.05）。结论 血清SP-A与AE-IPF证候存在一定的相关性，血清SP-A的浓度升高，与痰热壅肺证关系越密切，反之，血清SP-A浓度降低，则与痰浊阻肺证关系越密切。AE-IPF痰热壅肺证患者的预后可能较痰浊阻肺证患者更差。     

中医药干预新型冠状病毒肺炎临床研究方案分析

对中医药防治新型冠状病毒肺炎临床研究方案注册情况进行分析,为提高相关研究设计质量提供参考和建议。检索中国临床试验注册中心网站(www.chictr.org.cn)以及美国临床试验注册中心网站(clinicaltrials.gov),以新型冠状病毒肺炎、2019-nCoV等为检索词,检索新型冠状病毒肺炎中医药相关临床研究方案。按照纳入排除标准筛选文献,并提取研究注册时间、研究目的、研究类型、申办单位、研究对象、样本量、干预措施、评价指标等数据,采用描述性分析方法。共纳入新型冠状病毒肺炎中医药相关研究方案49个,研究负责单位以湖北、北京、浙江等地医院或高等院校为主。研究具体实施单位属地集中在湖北、广东、浙江、河南等地医院。研究设计以干预性试验研究为主(共40个),其中随机平行对照研究30个,非随机对照试验7个,单臂研究2个,连续入组1个;观察性研究6个;卫生服务研究2个;预防性研究1个。总样本量30562例,单个研究样本量最大20000例,最小30例。49个方案的研究对象包括健康人群(3个)、隔离观察人群(1个)、疑似病例(10个)、确诊病例(31个)、康复期病例(4个)。31个拟纳入确诊病例的研究方案中,有16个研究未明确病情分级,3个研究明确排除危重症,4个研究纳入普通型,2个研究纳入轻型、普通型或重型,1个研究纳入轻型和普通型,1个研究纳入普通型或重型,3个研究纳入重型,1个研究纳入重症或危重症。评价的干预措施包括中成药(连花清瘟胶囊/颗粒、藿香正气滴丸/口服液、八宝丹、固表解毒灵、金蒿解热颗粒、复方鱼腥草合剂、金叶败毒颗粒、疏风解毒胶囊、双黄连口服液、痰热清注射液、血必净注射液、热毒宁注射液、喜炎平注射液)、汤药、太极拳疗法。主要疗效指标以退热时间、临床症状缓解、新型冠状病毒核酸转阴、重症转化率、胸部CT影像为主。结果表明中医药防治新冠肺炎的临床研究响应快速,当前注册方案涵盖了疾病预防、治疗和康复全过程。但存在人群定义不清,研究目标不明确,干预方案需要细化,疗效评价指标需要优化等问题;另外,需要考虑疫情救治的实际困难和工作负担,在符合医学伦理条件下,优化流程,提高研究方案的可操作性。     

中医药文献语义标注系统研究与开发

目的研究和开发支持中医和现代生物医学本体和术语集的语义标注系统。方法以MedPortal本体库和中医临床术语集等为术语资源库,设计语义标注系统工作流程和功能框架,并开发Web应用系统。结果构建了一个基于Web的中医药文献语义标注系统,支持语料库管理与维护、术语词典管理、语义标注和语义检索等功能,既可以为基于机器学习的信息抽取算法研究提供训练集,又能实现语义层面的多来源数据集成与知识融合。结论该中医药文献语义标注系统设计方案已经过实际项目验证,可为其他同类系统研发提供参考。     

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.     

Direct oral anticoagulants (DOACs) and neck of femur fractures: Standardising the perioperative management and time to surgery

Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC.     

中医药调控IL-1治疗肿瘤机制的研究进展

炎症已成为影响肿瘤细胞增殖转移的第七大因素,而白细胞介素-1(IL-1)是炎性微环境的重要因子之一。中医药在治疗肿瘤时具有多途径、多靶点的优势,同时炎性微环境致病特点与现代中医学"癌毒"的理论相吻合。查阅近年中医药调控IL-1家族分子治疗肿瘤机制的文献,对其进行梳理,并做出概括及评价,从中医药主要调控IL-1α、IL-1β和IL-18因子治疗肿瘤展开综述,为中医药更系统化治疗肿瘤提供参考。     

Clinical observation on the effect of Chinese medicine-“TCM formula” intervention on recurrence and metastasis of triple negative breast cancer

ObjectiveThis study used a prospective cohort study to observe the effect of triple-negative breast cancer on the 2-year disease-free survival rate with or without “TCM formula”.MethodsFrom November 1 st, 2016, the first patient was enrolled in the cohort study. A total of 356 patients were enrolled on January 30, 2019. Among them, 154 cases were followed up for 2 years. During the follow-up, there were 6 cases of shedding, so 6 cases were affected. A total of 148 cases were included in the analysis, including 73 in the exposed group and 75 in the non-exposed group. The exposed group was given “TCM formula” on the basis of standardized treatment, and the non-exposed group was treated with simple triple-negative breast cancer. The two groups visited each of the three months. The interview included safety examination (hematology and imaging). The endpoint was the difference in 2-year invasive disease-free survival between the exposed and non-exposed groups and the safety of the “TCM formula”.ResultsThere were 6 cases of shedding during the experiment and the shedding rate was 3.9 %. The 2-year rate of invasive disease-free survival in the exposed team was 88.7 % and the non-exposed group was 82.5 %. Logistic multivariate regression analysis predicted that “TCM formula” could reduce the disease-related recurrence and metastasis rate by 11 % (OR = 0.89, 95 % CI 0.37−0.956, P＜0.05). Through K–M survival analysis, TNBC patients with age ≤35 years and regional lymph node stage N1 may be the benefit group of “TCM formula”(P＜0.05). During the study, the incidence of total adverse events was 8.2 % in the exposed group, mainly manifested as stomach discomfort, diarrhea, and hepatocyte damage.Conclusion1. In the exposed group, the two-year rate of invasive disease-free survival increased by 6.2 % compared with the non-exposed group(P＞0.05). 2. According to K–M survival analysis, TNBC patients with age ≤35 years and regional lymph node metastasis to N1 may be potential beneficiaries of “TCM formula”. 3. “TCM Formula” is safe and tolerable to most patients.     

Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala University Hospital

Background. Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. HLH in adults is often secondary to autoimmune diseases, cancer, or infections in contrast to familial HLH. Treatment of secondary HLH is directed against the triggering disease in addition to immunosuppressive therapy, the latter commonly according to the HLH-2004 protocol.Methods. We conducted a retrospective study to identify triggering diseases, disease-specific and immunosuppressive therapy administered, and prognosis in adult patients with secondary HLH. Patient data were collected from October 2010 to January 2015.Results. Ten adult patients with secondary HLH were identified. Seven were men, and the median age at diagnosis was 62 years. Five cases were triggered by malignant disease and five by infection. The median patient fulfilled five of the eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever, cytopenia, and ferritin >500 µg/L. Median time from hospital admission to HLH diagnosis was 20 days. Four patients received immunosuppressive therapy according to the HLH-2004 protocol. The prognosis was dismal, especially for the patients with malignancy-associated HLH, of whom all died.Conclusion. HLH should be suspected in patients who present with fever, cytopenia, and ferritin >500 µg/L. Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by malignancy survived. Achieving remission of the triggering disease seems to be important for a favourable outcome as, in all surviving patients, the haemophagocytic syndrome resolved after remission of the underlying infection.