基于方剂构成信息的知识发现和关联网络构建挖掘海洋中药海马历代用药经验＊

目的 通过对含海马方剂构成信息进行数据挖掘和知识发现，构建关联网络，分析海马的历代应用情况，挖掘海马用药配伍经验，发现海马潜在功效和主治病症，为海马的临床应用和开发提供依据。方法 以《中医方剂大辞典》《中国药典》《中华医典》等多部著作为方源，收集含有海马的相关方剂，并进行频数分析、关联规则挖掘和关联网络的构建。结果 共筛选有文献记载的含海马方剂154首。从剂型看，大多为散剂，从方剂分布年代来看，海马的应用虽然有很长历史，但是古代应用并不广泛，现代应用较多。通过对配伍药物进行分析发现，与海马配伍频率较高的是“鹿茸”、“熟地黄”、“肉苁蓉”等补益药物。从功效主治方面看，大多数方剂具有“补肾”、“温阳”、“益精”等传统功效外，还具有健脑等功效；主治病症中，除“阳痿”、“癥瘕”、“疔疮”等《中国药典》所记载的疾病之外，还可治疗“虚劳”、“健忘”、“瘿病”、“不寐”、“痹证”、“小便淋沥或不通”等。对其进行关联关系分析发现，海马配伍补肾温阳的效果较为明显，多用于治疗阳痿，且腰痛、虚劳、遗精、健忘、不育等疾病的治疗与补肾关系密切；在治疗癥瘕时，多与醋、樗鸡、干漆、硇砂、斑蝥、水蛭、没药、当归配伍。结论 该研究不仅发现了含海马方剂的常用剂型、分布年代和药物配伍规律，发现了历代医家应用海马的临床经验，还探索了海马的潜在应用价值。海马作为一味海洋中药，具有温、补、托、消等特性，除常用于治疗阳痿外，还可用于治疗腰痛、健忘、瘿病、不寐、痹证等病症，这些研究结果可为拓展海马的临床应用提供理论基础及依据。     

逆行髓内钉辅助在儿童股骨延长中的应用

目的采用髓内钉辅助延长技术进行儿童股骨大段延长,评估其可行性,并对比同期矫正和分期手术的技术要点,明确此技术在儿童患儿中的应用价值。方法自2014年7月7日至2018年1月16日共规划完成逆行髓内钉辅助延长手术10例,其中男9例,女1例;年龄(13.10±2.18)岁。所有患儿延长截骨点均位于股骨远端干骺端,初诊至末次随访记录内容包括:性别、出生日期、不等长病因及治疗史、术时年龄、延长长度、带架时间、延长段愈合时间、屈膝角度、并发症等。比较同期延长和分期矫正的愈合时间,采用SPSS 22.0软件进行统计分析,提出合理的治疗策略。结果10例患儿患肢平均延长(7.07±1.01)cm,中位带架时间为8.5(4,16)个月,中位随访时间为39(34,54)个月。所有病例均获得了良好的临床和影像学愈合,并全部恢复正常行走功能,无延长后骨折发生。同期矫正与分期手术间在愈合速度为[(1.70±1.10)月/cm vs.(1.16±0.54)月/cm],膝关节功能(136.67°±20.82°vs.125.71°±26.37°)和并发症率方面的差异均无统计学意义。结论外固定架辅助逆行髓内钉技术进行股骨延长治疗儿童股骨短缩畸形是可行的,是股骨延长的有效手术方式之一;较轻的角度畸形和延长手术可同期进行;干骺端截骨延长成骨质量更佳,可有效减少带架时间;内生软骨瘤患儿的病变区延长是安全的。     

Epilepsy and pregnancy: What should the neurologists do?

Epilepsy is one of the most common chronic disorders affecting women of childbearing age. Unfortunately, many women with epilepsy (WWE) still report not receiving key information about pregnancy. They obviously need information about epilepsy and pregnancy prior to conception with a particular emphasis on effective birth control (i.e. contraception), necessity to plan pregnancy, antiepileptic drugs optimization, and folate supplementation. The risks associated with use of antiepileptic drugs during pregnancy have to be balanced against fetal and maternal risks associated with uncontrolled seizures. This report reviews evidence-based counseling and management strategies concerning maternal and fetal risks associated with seizures, teratogenic risks associated with antiepileptic drug exposure with a special emphasis on developmental and behavioural outcomes of children exposed to intra utero antiepileptic drugs.     

中西医一体化防治增生性瘢痕的研究现状

皮肤瘢痕是一个巨大的医学问题,每年约有1亿患者产生瘢痕。瘢痕的预防/治疗在很大程度上还没有得到满足的临床需求。瘢痕的形成通常是皮肤创伤的病理结果。而增生性瘢痕(hypertrophic scar,HTS)常发生在人深部损伤后。HTS通常被认为是组织收缩和过度的细胞外基质沉积的结果。肌成纤维细胞作为主要由成纤维细胞分化而来的效应细胞,在HTS的病理生理中起着至关重要的作用。多种生长因子、炎症因子参与了HTS发生的过程。目前,随着对HTS的深入探索和临床研究,各种创造性和有效的治疗方法正在萌芽。本文就HTS中西医形成机制研究进展进行综述,并针对其病理生理特点,对现有的中西医综合治疗方法进行综述。此外,我们进一步展望更适合的HTS中西医综合治疗的特色与方法。     

Metastasis of oral squamous cell carcinoma to the parotid lymph nodes

Parotid lymph node (PLN) metastasis greatly worsens the prognosis of patients with oral squamous cell carcinoma (OSCC) and poses a great challenge for further treatment of OSCC. The clinicopathological characteristics and treatment strategies for PLN metastasis from OSCC need to be comprehensively elucidated. A retrospective review of OSCC patients who experienced postoperative PLN metastasis in our department between 2000 and 2018 was performed in this study. A total of 47 OSCC patients with postoperative PLN metastasis were identified. PLN with metastasis were divided into three groups based on the location: parotid tail (PLN-t), superficial lobe (PLN-sl), and deep lobe (PLN-dl). Most of the patients experienced PLN metastasis within less than 12 months after the primary surgery for OSCC. Comparatively, patients with PLN-sl metastasis were more prone to have infiltration of the facial nerve. The tongue and buccal mucosa were the most frequent primary sites associated with PLN metastasis from OSCC. PLNs in the parotid tail were most commonly affected by the metastasized OSCC. Consequently, we recommend a series of strategies for the prevention and treatment of PLN metastasis for OSCC patients. In conclusion, PLNs should not be overlooked during preoperative evaluation and postoperative follow-up examinations for OSCC patients.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

Identification of two pathogenic mutations in SORL1 in early-onset Alzheimer’s disease

The sortilin-related receptor 1 (SORL1) gene has been the subject of many studies focusing on frequent polymorphisms, which is associated with increased risk for Alzheimer’s Disease (AD). By whole-exome sequencing (WES), we identified two pathogenic missense mutations c.579C > G (p.F193L) and c.1397A > G (p.N466S) in SORL1. The two mutations were located in the same protein domain, and the two unrelated probands both had an onset of memory problems at less than 65 years of age, but their clinical manifestations and cranial imaging are different. The protein structure and function affected by these mutations were predicted using bioinformatics analysis, which suggested they were pathogenic. 3D protein structural analysis revealed that these amino acid substitutions might result in instability of protein structure and adverse intramolecular interactions. These findings suggest that both F193L and N466S should be thought as potential causative mutations in early-onset Alzheimer’s disease (EOAD) patients. Further functional studies are warranted to evaluate their roles in the pathogenesis of AD.     

Differentiating ictal/subclinical spikes and waves in childhood absence epilepsy by spectral and network analyses: A pilot study

ObjectiveChildhood absence epilepsy (CAE) is a disease with distinct seizure semiology and electroencephalographic (EEG) features. Differentiating ictal and subclinical generalized spikes and waves discharges (GSWDs) in the EEG is challenging, since they appear to be identical upon visual inspection. Here, spectral and functional connectivity (FC) analyses were applied to routine EEG data of CAE patients, to differentiate ictal and subclinical GSWDs.MethodsTwelve CAE patients with both ictal and subclinical GSWDs were retrospectively selected for this study. The selected EEG epochs were subjected to frequency analysis in the range of 1–30 Hz. Further, FC analysis based on the imaginary part of coherency was used to determine sensor level networks.ResultsDelta, alpha and beta band frequencies during ictal GSWDs showed significantly higher power compared to subclinical GSWDs. FC showed significant network differences for all frequency bands, demonstrating weaker connectivity between channels during ictal GSWDs.ConclusionUsing spectral and FC analyses significant differences between ictal and subclinical GSWDs in CAE patients were detected, suggesting that these features could be used for machine learning classification purposes to improve EEG monitoring.SignificanceIdentifying differences between ictal and subclinical GSWDs using routine EEG, may improve understanding of this syndrome and the management of patients with CAE.