静吸复合麻醉对特重度烧伤患者凝血功能障碍的影响

目的收集特重度烧伤(总TBSA50%以上或三度TBSA20%以上或伴有严重并发症者)患者围术期凝血指标(APTT、PT、FIB、DD和PLT)，分析静吸复合麻醉对患者凝血功能的影响及其临床意义。 方法选取近3年内蒙古医科大学第三附属医院烧伤外科收治的特重度烧伤患者148例，根据入院14 d内的预后分为死亡组和生存组，生存组男性129例，女性9例；年龄24~59岁，平均(43.30±12.90)岁。死亡组男性8例，女性2例；年龄26~63岁，平均(46.19±15.41)岁。收集入院时(T0)，术前(早晨入手术室前，T1)，术毕(送至PACU未拔除气管导管前，T2)及术后2 d(T3)4个时间点的凝血指标，比较两组凝血指标动态差异。 结果死亡组休克期输液量、累计血浆、红细胞输入量显著高于生存组(P<0.01)。T0时，生存组的FIB(1.78±0.32)显著高于死亡组(1.26±0.07)(P<0.05)；T2时，两组APTT、PT均显著缩短(P<0.05)，生存组的FIB(3.86±0.40)显著高于死亡组(2.45±1.02)(P<0.05)；T3时，死亡组PLT显著低于生存组(P<0.01)。 结论特重度烧伤患者在围手术期易出现高凝状态，并且这可能导致患者死亡。静吸复合麻醉和围术期大量液体复苏会促进患者的高凝状态。     

COX20基因变异线粒体复合物Ⅳ缺乏症相关的遗传性周围神经病4例病例系列报告及文献复习

背景：原发性线粒体病具有高度的临床和遗传异质性，其中周围神经是线粒体病的常见受累器官之一。 目的：总结COX20基因变异相关周围神经病的临床表型及遗传学特征。 设计：病例系列报告。 方法：回顾性收集2018年5月至2020年5月复旦大学附属儿科医院诊治的COX20基因变异相关周围神经病患儿的临床资料，总结其临床表现、基因检测结果及治疗效果，并以“COX20”、“线粒体复合物Ⅳ缺乏症（Complex Ⅳ deficiency）”为关键词检索中英文数据库。检索时间均为从建库至2021年12月。总结已报道COX20基因变异与临床表型的关系。 主要结局指标：临床表型和COX20基因变异位点。 结果：4例患儿纳入分析，男、女各2例，其中3例自幼运动发育落后。4例均在儿童期起病，均以行走不稳为首发症状。肌电图均提示多发性周围神经损害改变，感觉神经轴索受累为主。4例患儿均携带COX20基因复合杂合变异，包括错义变异2个，无义变异和移码变异各1个，其中移码变异c.262delG(p.E88Kfs*35)尚未见报道。文献复习目前共报道COX基因变异18个家系22例患儿（包括本文病例）,起病中位年龄为5（1.0~17）岁，22例均以行走困难或步态不稳起病，11例（50.0%）有精神运动发育迟滞，病程中14例(63.6%)出现构音障碍，14例(63.6%)出现肌力下降和/或足部畸形，8例（36.4%）出现共济失调，6例(27.3%)出现肌张力障碍，5例（22.7%）存在认知倒退等。21例患儿行神经传导及肌电图检查，19例(90.5%)提示多发性周围神经病变。头颅（18例）及脊髓（10例）MR检查提示，脊髓萎缩4例（40%），小脑萎缩4例（22.2%）。9例患儿已无法独立行走，丧失独立行走能力中位年龄为10（7~21）岁。目前共报道9个变异位点，4种变异类型，其中错义变异5个，剪切变异2个，无义变异和移码变异各1个。 结论：COX20基因变异患者多早期起病，以周围神经系统病变为主要表现，可合并构音障碍、共济失调、肌张力障碍、认知倒退等，病情逐渐进展，致残率高。COX20基因变异类型以错义变异最常见。     

Resiniferatoxin reduces cardiac sympathetic nerve activation to exert a cardioprotective effect during myocardial infarction

Background and objective: Myocardial infarction (MI) is a common critical disease of the cardiovascular system. The process of MI is often accompanied by the excessive activation of cardiac sympathetic nerves, which leads to arrhythmia. Resiniferatoxin (RTX) is a transient receptor potential vanilloid 1 (TRPV1), involved in the cardiac sympathetic afferent reflex. However, whether RTX can reduce the occurrence of arrhythmia and exert a cardioprotective effect by inhibiting the sympathetic reflex during MI is still unknown. Methods: The left anterior descending artery of cardiac was clamped to construct a model of MI. RTX (50 μg/ml) was used by epicardial application in MI rats. Ventricular electrophysiologic properties were continuously monitored by a body surface ECG. Yrosine hydroxylase (TH) and growth associated protein 43 (GAP43) were detected by Immunofluorescence staining. Connexin43 and transforming growth factor beta receptor 1 (TGF-β1) were detected by western blot. Norepinephrine (NE) and BNP levels in blood and tissue were determined by ELISA. Cardiac function was assessed by echocardiography. Results: The ERP, APD90, QRS, QT and the Tend-Tpeak intervals in MI rats were all prolonged, but decreased after RTX treatment (n = 3, P<0.05). In contrast, the RR interval was shortened in the MI group, but prolonged in the MI+RTX group (n = 3, P<0.05). RTX treatment significantly reduced ventricular arrhythmias after MI. TH- and GAP43-positive nerve densities and TGF-β1, and cx-43 protein expression were up-regulated in the MI group compared to the sham group, and they were decreased in the MI+RTX group compared to the MI group (n = 3, P<0.05). RTX can decrease serum and tissue NE and BNP levels (n = 3, P<0.05). RTX pretreatment significantly decreased heart rate, HW/BW ratio and LVIDS, and increased LVEF andLVFS values (n = 3, P<0.05). Conclusion: RTX improved cardiac dysfunction, ventricular electrophysiologic properties, and sympathetic nerve remodeling in rats with MI by inhibiting the excessive cardiac sympathetic drive.     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

国外动物智能军事应用情报研究

目的：阐述动物智能在军事学的应用及意义。方法：以学术论文、新闻、报纸、智库报告等作为信息源，综合研究国外动物智能军事应用实例及内在关联，描述动物智能在未来战场应用场景。结果：动物智能军事应用主要是动物特殊能力的军事应用和动物智能的仿生武器应用。结论：动物部队、仿生作战部队和动物战术是未来战争不可忽视的重要组成部分，动物智能的隐匿、灵活、多变等特点正逐渐被广泛应用于战场。     

三阴性乳腺癌治疗的研究进展

三阴性乳腺癌（triple negative breast cancer，TNBC）是雌激素受体(estrogen receptor，ER)、孕激素受体（progesterone receptor，PR）及人类表皮生长因子受体（human epidermal growth factor-2,HER-2）均不表达的乳腺癌。按其功能特征可归纳为5类分子分型:以DNA修复缺陷或生长因子为途径的基底细胞样三阴性乳腺癌；以上皮-间充质转化和肿瘤干细胞为特征的间质样三阴性乳腺癌；免疫调节型三阴性乳腺癌；雄激素受体过表达的管腔／分泌型三阴性乳腺癌；HER-2富集型三阴性乳腺癌。三阴性乳腺癌恶性程度高且异型性较大，其治疗困难且预后较差，内分泌治疗及靶向治疗不敏感。目前很多学者对于三阴性乳腺癌的治疗各有研究，并有临床试验证实下述治疗有效。     

A basal‐enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer‐enriched miRNA is required for prostate tumorigenesis. We identify miR‐205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR‐205 is not required for normal prostate development and homeostasis, genetic deletion of miR‐205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR‐205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR‐205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR‐205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR‐205 in the progression of Pten null‐induced prostate cancer.     

疏血通脉汤联合傍针刺对中风后肩手综合征患者肢体痉挛、血液流变学及活动能力的影响

目的:探讨疏血通脉汤联合傍针刺治疗中风后肩手综合征(shoulder-hand syndrome after stroke,SHSAS)的临床疗效,并观察其对患者上肢肢体痉挛程度、血液流变学以及上肢活动能力的影响。方法:110例痰瘀阻络型SHSAS患者按照随机数字表法分为对照组与联合组,每组55例。两组患者均给予神经内科常规药物和肢体功能康复训练治疗。对照组联合傍针刺法治疗,联合组在对照组治疗基础上给予疏血通脉汤。两组患者均以4周为1个疗程,治疗1个疗程。记录比较两组患者治疗前后上肢肢体痉挛程度(Ashworth)、上肢活动能力(FMA)、肩手综合征量表(shoulder hand syndrome scale,SHSS)、视觉模拟评分(visual simulation scoring,VAS)、中医证候评分,高切全血黏度、低切全血黏度、血浆黏度和血小板聚集率等血液流变学指标,并比较治疗效果。结果:联合组有效率为96.36%,对照组有效率为83.64%,两组患者有效率比较,差异有统计学意义(P0.05)。治疗后,联合组高切全血黏度、低切全血黏度、血浆黏度与血小板聚集率水平均低于对照组,差异有统计学意义(P0.05);联合组Ashworth评分低于对照组、上肢FMA评分高于对照组,差异有统计学意义(P0.05);联合组SHSS评分和中医证候评分均低于对照组,差异有统计学意义(P0.05);联合组VAS评分低于对照组,差异有统计学意义(P0.05)。结论:疏血通脉汤联合傍针刺治疗SHSAS患者疗效显著,能有效改善患者血液流变学,缓解疼痛程度和上肢痉挛,提高上肢活动能力。     

儿童新型冠状病毒感染诊断、治疗和预防专家共识(第二版)

自2019年12月新型冠状病毒感染暴发以来,我国政府采取了严格的防控措施,国内疫情已得到初步控制,但形势依然严峻,境外多个国家也相继出现疫情。根据世界卫生组织的报告:截至2020年3月5日,全球共报告95333例确诊病例(其中我国累计报告确诊病例80565例),85个国家有确诊病例报告,中国将面临输入性病例的传播风险,这为防治我国儿童的疾病疫情提出了新的挑战[1]。在这次疫情中,与成人病例相比,儿童病例相对较少、症状轻、预后较好。目前国内病例数据显示,18岁以下儿童占所有报告病例的2.4%,尚无死亡病例报告[2]。