Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms

Ischemic stroke is a global disease with high disability and mortality rates. Cognitive impairment is one of the major clinical features of ischemic stroke, and microglia‐mediated inflammation has been shown to be an important contributor to the pathogenesis of ischemic stroke. Kellerin, extracted from Ferula sinkiangensis, was previously shown to inhibit microglial activation and exert a strong anti‐neuroinflammatory effect. However, there is no report of the potential therapeutic effect of kellerin on ischemic stroke by targeting microglial cells. In this study, we wanted to examine the effects of kellerin on ischemic stroke in the bilateral common carotid artery occlusion (BCCAO) model and the lipopolysaccharide (LPS)‐activated microglia model. We found that kellerin alleviated cognitive impairment, decreased neuronal loss, suppressed microglial activation, and transformed microglia from the pro‐inflammatory M1 phenotype to the anti‐inflammatory M2 phenotype in BCCAO mice. Moreover, in in vitro studies, we found that kellerin regulated microglial polarization and inhibited the NLRP3 and MAPK signaling pathways after LPS treatment. These findings provide a new understanding of the function of kellerin in ischemic stroke, and suggest that kellerin could be a potential therapeutic agent for the treatment of ischemic stroke.     

针对目前已注册的上市中成药治疗新型冠状病毒肺炎临床研究分析＊

本研究系统分析了中成药治疗新型冠状病毒肺炎临床研究方案注册信息，以提高相关临床研究设计质量，以及为中成药上市后评价提供参考和建议。对中国临床试验注册中心网站（www.chictr.org.cn）和美国临床试验注册中心网站（clinicaltrials.gov）进行检索，以新型肺炎、COVID-19、中成药等为检索词，检索新型冠状病毒肺炎中成药相关临床研究方案。按照纳排标准筛选临床研究，并提取注册号、研究题目、研究设计及类型、干预措施等数据，采用描述性分析方法对纳入研究的注册信息进行分析。共纳入新型冠状病毒肺炎中成药相关研究方案35个，其中涉及的8种中成药是新冠肺炎诊疗方案（第七版）中所推荐使用的药物。评价的干预措施共涉及23种中成药（如血必净注射液、喜炎平注射液、连花清瘟胶囊/颗粒等）。主要疗效指标以退热时间、疾病痊愈时间/有效率等为主。结果显示：中成药治疗新冠肺炎的临床研究响应快速，目前已注册多个临床研究，包括疾病诊治、预防全过程。但也存在问题，如研究人群不明确、评价指标代表性差等，相关研究设计和实施尚有待优化，以进一步提高临床试验研究的可行性，以期为当前和后续更多的临床研究方案提供参考。     

婴幼儿多发性大动脉炎14例临床特点分析

目的通过分析总结14例婴幼儿多发性大动脉炎(TA)的临床特点,并结合文献复习总结,以提高对该病的认识及诊疗水平。方法回顾性分析2016年7月至2019年5月在首都儿科研究所附属儿童医院住院的TA婴幼儿的临床资料及随访情况,并结合文献,分析总结该病的临床特点。结果14例患儿年龄为1个月23 d^28个月,男6例,女8例。临床表现中最常见的是发热[10例(71.4%)],高血压9例(64.3%),脉弱或无脉5例(35.7%)。按照病变血管部位的临床分型,广泛型11例(78.5%),头臂动脉型3例(21.4%),本组患儿无胸腹主动脉及单纯肺动脉型。14例TA患儿中,12例有颈总动脉、颈动脉、锁骨下动脉及冠状动脉及其分支(前降支、回旋支)受累(85.7%);11例肾动脉受累(78.6%);9例腋动脉受累(64.2%);8例腹主动脉受累(57.1%);6例降主动脉受累(42.9%);6例胸主动脉受累(42.9%);6例肠系膜上动脉受累(42.9%);5例股动脉受累(35.7%);5例肺动脉受累(35.7%);4例肱动脉受累(28.6%)。14例患儿中,误诊11例,诊断不清3例,误诊时间为18 d^2个月。误诊病例中,8例误诊为不典型川崎病。14例患儿中,7例治疗后大部分病变血管范围逐渐减少,受累较轻血管甚至可以完全恢复正常血管状态。4例患儿血管影像学检查较前无明显加重或好转。9例出现高血压患儿应用降压药血压能控制在正常范围,但不能停用降压药。5例查体发现脉弱或无脉患儿均未改善。14例患儿中7例生长发育同正常同龄儿,7例落后于正常同龄儿身高体质量第25百分位。14例患儿随访2~22个月,均规律治疗,未出现复发。结论3岁以内TA累及血管较多,病情严重,误诊率高,经过治疗病情很快能够控制,但容易遗留血管病变,部分患儿预后不佳。     

Emotional disorder syndrome after cosmetic facial injection

There are a number of patients who develop severe anxiety or depression after receiving facial cosmetic injections. We presented a 32‐year‐old woman who developed frequent panic, tension headache, tachycardia, shortness of breath, and sleep disorder for a year after the injection of hyaluronic acid on her forehead and glabella. Brain magnetic resonance imaging (MRI) showed multiple flaky and slightly longer T1, slightly longer T2 signals on the anterior frontal white matter. However, the patient's brain MRI scan 5 months before the injection showed no such performance. The patient was asked to consult the psychiatrist and was diagnosed with anxiety disorder. We name such phenomenon by Emotional disorder syndrome after cosmetic facial injection and assume that there are three major reasons for the emergence of this syndrome. One reason may be that emotional disorder is caused by the mental state of the patient. The second reason to explain the emotional disorder might be the frontal lobe syndrome caused by the frontal embolism during the filler injection. Another reason may be leukoaraiosis, a brain white matter change which may cause depression and anxiety.     

Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model(MCAO) and paired associated magnetic stimulation(PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments—the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m~2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval No. 201802173 S) on March 3, 2018.     

The third-generation retinoid adapalene triggered DNA damage to induce S-phase arrest in HaCat cells

Epidermal proliferative diseases consisted of a series of common skin diseases, most of which were recurrent chronic skin diseases, and had greatly negative influence on the life quality of patient. Retinoids exhibited vital roles in the treatment of many skin diseases. Our recent study demonstrated that adapalene significantly inhibited the growth of HaCat cells, and the inhibitory activity was stronger than other retinoids, such as all-trans-retinoic acid, acitretin, isotretinoin, tazarotene, and bexarotene. Further study showed that adapalene suppressed the colony formation of HaCat cells, and it dramatically triggered S-phase arrest and apoptosis, rather than G1 phase arrest which was reported in other retinoids in several studies. Additionally, adapalene treatment greatly upregulated the protein expression of DNA damage marker γ-H2AX, which was in accord with the results of the elongation of tail moment by comet electrophoresis analysis. Moreover, DNA damage was triggered and DNA repair was suppressed synchronously with adapalene treatment, which accounted for the mechanism of S-phase arrest induced by adapalene. In summary, our recent work demonstrated that adapalene showed strong anti-proliferation activity in HaCat cells and could be an alternative agent for the epidermal proliferative disease.     

四川省首例COVID-19婴儿病例分析及文献复习

目的探讨1例输入性、家庭聚集性严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的2^＋个月龄新型冠状病毒疾病(COVID-19)婴儿的临床流行病学资料及影像学资料特点，并进行文献复习。 方法选择2020年2月7日，四川省金堂县第一人民医院收治的2^＋个月龄COVID-19婴儿为研究对象。采用回顾性分析方法，收集该例婴儿的临床病例资料，对其临床流行病学特点、影像学资料、诊断、治疗方案及预后进行分析。本研究对报道COVID-19婴儿的相关文献进行复习，设定检索策略为：以"婴儿""新型冠状病毒肺炎""新型冠状病毒疾病""2019-nCoV""NCP""SARS-CoV-2""COVID-19""infant"等为关键词，在PubMed、Medline、中国知网、维普中文科技期刊数据库、万方数据知识服务平台，以及"医学界儿科频道"等公众平台及新闻网站中，检索相关文献，检索时间设定为2019年12月1日至2020年2月21日。总结符合本研究纳入、排除标准的文献中报道的COVID-19婴儿临床特点及其诊断、治疗方案与预后。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。 结果①病史采集、诊断、治疗结果：患儿，男性，生后2个月＋29 d；2020年1月18日，患儿姨妈自武汉返蓉，密切接触后，患儿出现气促、轻微咳嗽、腹泻等症状。入院后，患儿检查结果显示，肺炎支原体及衣原体、甲型及乙型流感病毒抗原均呈阴性。胸部CT检查结果显示，患儿双肺胸膜下多发性浅淡磨玻璃病灶。2次鼻咽拭子SARS-CoV-2核酸检测均呈阳性。根据流行病学史、临床与影像学表现及核酸检测结果，确诊为普通型COVID-19患儿。经过对症治疗后，患儿气促、咳嗽临床症状消失，胸部影像学检查结果显示，肺部炎症病灶吸收，SARS-CoV-2核酸检测呈阴性。目前，患儿继续观察中，等候出院。②文献复习结果：按照本研究设定的文献检索策略，共计检索出5篇国内有关婴儿COVID-19文献及2篇婴儿COVID-19新闻报道，涉及18例COVID-19婴儿的临床特点、诊断、治疗方案及预后等研究。这18例COVID-19婴儿，均具有家庭聚集性、输入性感染特点(武汉COVID-19患者接触史)。其中，3例新生儿及其母亲均为SARS-CoV-2感染者。出生后，对2例新生儿进行有效隔离，无感染者接触史。这18例COVID-19婴儿的首发症状为：发热5例(27.8%)、咳嗽及下呼吸道症状3例(16.7%)、打喷嚏及吐奶1例(5.6%)、无症状3例(16.7%)、病史不详6例(33.3%)。其中，7例婴儿文献报道胸部CT检查结果，并且均存在异常，表现为双肺或单侧肺纹理增粗、磨玻璃影和(或)实变影。除2例婴儿未报道预后情况外，其余16例婴儿均预后良好，无死亡病例报道。 结论文献报道的COVID-19婴儿及纳入本研究的1例婴儿，均具有输入性、家庭聚集性感染特点，而且对新生儿患者，目前尚不能排除母婴垂直传播可能性。对于临床症状相对较轻，肺部病变范围相对较小且局限的COVID-19婴儿，一般预后较好。在COVID-19暴发流行期，应尽可能加强儿童，特别是婴儿的防护，避免输入性、家庭聚集性SARS-CoV-2感染。     

HPV检测原发灶不明颈淋巴结转移癌的诊断作用初探(附6例报告)

目的 初步探讨HPV检测在诊断原发灶不明的颈淋巴结转移性鳞癌中的价值。方法 收集复旦大学附属肿瘤医院6例首诊为原发灶不明的颈淋巴结转移性鳞癌,最终确诊为HPV相关口咽鳞癌,分析确诊过程。结果 首诊时6例患者均被确诊为颈淋巴结转移性鳞癌,且p16表达阳性和HPV-16亚型阳性,而EBER表达阴性。经全面检查均未发现明显的原发病灶。随后对其中4例予同侧扁桃体盲检(2例)和切除(2例),病理均证实为扁桃体鳞癌。另2例分别在随访第149天、545天MRI检查发现同侧口咽侧壁和舌根增厚伴强化,经活检分别证实为扁桃体鳞癌、舌根鳞癌。结论 对于原发灶不明的HPV阳性颈淋巴结转移性鳞癌,应高度怀疑原发病灶来源于口咽部位的可能性,特别是扁桃体和舌根部位。     

The Comprehensive Analysis of Efficacy and Safety of CalliSpheres^® Drug-Eluting Beads Transarterial Chemoembolization in 367 Liver Cancer Patients: A Multiple-Center,Cohort Study

This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres^® DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375–393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size 5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1–3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres^® DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.