基于网络药理学和分子对接探讨预防肺疾一号方预防新型冠状病毒肺炎（COVID-19）的作用机制＊

目的 从分子层面探讨预防肺疾一号方预防新型冠状病毒肺炎的作用机制，并探索预防肺疾一号方的潜在治疗靶点。方法 利用TCMSP数据库及BATMAN-TCM数据库筛选预防肺疾一号方的化合物成分，在PharmMapper数据库进行潜在靶点识别，然后使用David软件对靶点进行GO富集及KEGG通路富集分析，利用iGEMDOCK软件进行分子对接分析。结果 通过网络药理学方法分析预防肺疾一号方的6味中药，发现其有效化学成分有58个，对应47个作用靶点；通过GO分析靶点富集出81个生物学过程、26个细胞组成及31个分子功能；通过KEGG分析得出靶点显著富集的信号通路有35条；分子对接分析得出，靶点CAT和化合物Daidzein-4，7-diglucoside的结合度最高。结论 预防肺疾一号方具有多成分、多靶点的作用特点，并通过参与多种生物过程，调控多条信号通路以预防新型冠状病毒肺炎并发挥其药理疗效。     

Should we start integrating genetic data in decision-making on device-aided therapies in Parkinson disease? A point of view

Parkinson disease (PD) is a complex heterogeneous neurodegenerative disorder. Association studies have revealed numerous genetic risk loci and variants, and about 5–10% suffer from a monogenic form. Because the presentation and course of PD is unique to each patient, personalized symptomatic treatment should ideally be offered to treat the most disabling motor and non-motor symptoms. Indeed, clinical milestones and treatment complications that appear during disease progression are influenced by the genetic imprint. With recent advances in PD, more patients live longer to become eligible for device-aided therapies, such as apomorphine continuous subcutaneous infusion, levodopa duodenal gel infusion, and deep brain stimulation surgery, each with its own inclusion and exclusion criteria, advantages and disadvantages. Because genetic variants influence the expression of particular clinical profiles, factors for better or worse outcomes for device-aided therapies may then be proactively identified. For example, mutations in PRKN, LRRK2 and GBA express phenotypes that favor suitability for different device therapies, although with marked differences in the therapeutic window; whereas multiplications of SNCA express phenotypes that make them less desirable for device therapies.     

Respiratory syncytial virus and influenza hospitalizations in Danish children 2010–2016

ObjectiveTo pave the way for universal or risk factor-based vaccination strategies, the present study aimed to describe the epidemiology and compare risk factors for hospitalization associated with respiratory syncytial virus (RSV) and influenza virus infections in Danish children.MethodsNational register-based cohort study among 403,422 Danish children born 2010–2016.ResultsPrior asthma hospitalization, number of children in the household, chronic disease and maternal history of asthma hospitalization were the most important risk factors for both RSV and influenza hospitalization. The incidence of influenza increased at school start.ConclusionsOur findings enable targeted vaccination programs for high-risk children with asthma-like disease, chronic disease, siblings in the household, or maternal history of asthma hospitalization.     

从武汉抗疫看中医药文化认同与新的医学模式

从武汉抗疫中医药的投入使用情况,反思现代临床和国人所呈现出的中医药文化认同和就医习惯,探索其历史文化根源及社会因素与医学发展的内在关联。回顾历史,中医屡次临危受命,不负重托,如今大疫当前,中医药再次发挥了重要作用。故新时代探讨如何遵循中医药发展规律,传承精华、守正创新,坚持中医药原创优势,形成中医药学科优势整体化呈现的新模式医学,对提升全社会的中医药认知度具有重要意义。     

周亚滨教授运用六经辨证治疗心病证治经验

周亚滨教授从“伤寒最多心病”立意,通过总结《伤寒论》一书对于心病的脉证及遣方用药,指出六经辨证体系对于心病证治具有指导意义。六经辨证是涵盖了八纲以及脏腑经络辨证的学说,能够指导着脏腑经络生理、病理变化的辨证论治。文章整理周亚滨教授在基于六经病证分论的基础上,临证上运用六经辨证思维论治心病的辨证经验,用药上可概括以和、温、补、清、下法为多。     

The emerging role of ultrasound in detecting interstitial lung disease in patients with rheumatoid arthritis

ObjectiveTo investigate the potential role of US in the detection of ILD in a cohort of patients with RA.MethodsPatients with diagnosis of RA were consecutively enrolled. All patients underwent pulmonary examination, laboratory data, DLCO measure, chest HRCT and radiographs, and US examination. A healthy group was included as control group. US was performed according the 14-intercostal space scanning protocol using the following semiquantitative scale [0 = normal (≤ 5 B-lines); 1 = slight (≥ 6 and ≤ 15 B-lines); 2 = moderate, (≤ 16 and ≥ 30 B-lines); 3 = severe (≥ 30 B-lines)].ResultsA total of 74 RA patients and 74 healthy controls were included. Thirty of 74 patients (40.5%) showed US signs of ILD with respect to the healthy controls (3 subjects, 4.1%) (P < 0.001); whereas HRCT showed ILD in 27 (36.4%) of 74 patients. Among the 30 patients that showed US findings of ILD, 17 (56.6%) were asymptomatic from respiratory view-point. The sensitivity and specificity of US were 92% and 89% respectively. A positive correlation between US and HRCT findings were found (P < 0.001) whereas no correlation was found with chest radiographs and DLCO findings. Positive association between US findings and DAS28-ESR, anti-CCP and RF (P < 0.01 for each respectively) was found. Feasibility, represented by the mean time spent to perform the pulmonary US assessment was 7.8 minutes (± SD 1.2, range 6 to 10 minutes).ConclusionsOur results support the potential of US in detect accurately ILD in patients with RA and provide a rationale to consider it as a friendly screening tool to be implemented in early phases of the disease.     

Event-related potential changes due to early-onset Parkinson’s disease in parkin (PARK2) gene mutation carriers and non-carriers

ObjectiveTo investigate cognitive functions in non-demented patients with early-onset Parkinson's disease (PD), and to compare PARK2 gene mutation carriers and non-carriers by means of event-related brain potentials (ERPs).MethodsThe participants comprised patients with early-onset PD (EOPD) and healthy controls (HC). Patients with EOPD were divided into two groups as carriers of known pathogenic variants of PARK2 gene (EOPD-PC) and non-carriers of genes involved in familial PD (EOPD-NC). ERP data were collected during auditory oddball and visual continuous performance test (CPT).ResultsBoth EOPD groups (EOPD-PC and EOPD-NC) displayed reduced and delayed P3 in response to oddball target and CPT NoGo. CPT Go P3 was reduced in EOPD-NC but not in EOPD-PC. Oddball target N1 was reduced and P2 was enhanced in both EOPD-PC and EOPD-NC. In both cognitive tasks, RTs were prolonged and accuracy was lower in EOPD-PC and EOPD-NC.ConclusionsWe found several EOPD-related neurophysiologic changes, implying impairments in cognitive functions. Pairwise comparisons between EOPD-PC and EOPD-NC revealed no significant ERP marker.SignificanceIn this study, the confounding effect of normative aging was somewhat excluded compared with many previous studies. In contrast with the many oddball studies in non-demented PD, we clearly observed reduced and prolonged P3 in early-onset PD. Our NoGo P3 findings also contribute to the limited ERP research concerning response inhibition.     

Interstitial lung diseases in children

Interstitial lung disease (ILD) in children (chILD) is a heterogeneous group of rare respiratory disorders that are mostly chronic and associated with high morbidity and mortality. The pathogenesis of the various chILD is complex and the diseases share common features of inflammatory and fibrotic changes of the lung parenchyma that impair gas exchanges. The etiologies of chILD are numerous. In this review, we chose to classify them as ILD related to exposure/environment insults, ILD related to systemic and immunological diseases, ILD related to primary lung parenchyma dysfunctions and ILD specific to infancy. A growing part of the etiologic spectrum of chILD is being attributed to molecular defects. Currently, the main genetic mutations associated with chILD are identified in the surfactant genes SFTPA1, SFTPA2, SFTPB, SFTPC, ABCA3 and NKX2-1. Other genetic contributors include mutations in MARS, CSF2RA and CSF2RB in pulmonary alveolar proteinosis, and mutations in TMEM173 and COPA in specific auto-inflammatory forms of chILD. However, only few genotype-phenotype correlations could be identified so far. Herein, information is provided about the clinical presentation and the diagnosis approach of chILD. Despite improvements in patient management, the therapeutic strategies are still relying mostly on corticosteroids although specific therapies are emerging. Larger longitudinal cohorts of patients are being gathered through ongoing international collaborations to improve disease knowledge and targeted therapies. Thus, it is expected that children with ILD will be able to reach the adulthood transition in a better condition.     

Progressive muscle-strength protocol for the functionality of upper limbs and quality of life in individuals with Parkinson’s disease: Pilot study

The effects of physical-therapy intervention on the motor function of upper limbs and the quality of life in patients with Parkinson’s disease (PD) are not fully understood. We evaluated the effects of a progressive muscle-strengthening protocol for upper limbs on the functionality and quality of life. Patients were divided into two groups: Intervention (n = 6) and Control (n = 7). Assessment tools used were: Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire, Nine-Hole Peg Test (9HPT), Test d’Évaluation des Membres Supérieurs de Personnes Âgées (TEMPA), 10-Repetition Maximum (10-RM) and handgrip dynamometer, which were applied pre- and post-intervention, with follow-up for one month after the last training session. Only, the Intervention group (post-intervention) showed significant statistical differences, with the following outcomes: UPDRS III (p = 0.042); 9HPT, right (p = 0.028) and left side (p = 0.028); TEMPA for total right side (p = 0.028), left side (p = 0.028) and total bilateral tasks (p = 0.028); TEMPA task 2 – open a jar and take a spoonful of coffee (p = 0.028), task 3 – pick up a pitcher and pour water into a glass for right (p = 0.046) and left side (p = 0.028), task 5 – write on an envelope and stick on a stamp (p = 0.028), and task 6 – shuffle and deal playing cards (p = 0.028). We observed significant statistical differences between groups (post-intervention) for TEMPA task 6 (p = 0.032), total right side (p = 0.032), and total bilateral tasks (p = 0.032). An increase in the maximum load in the post-intervention stage, based on the 10-RM test, was observed on the right (p = 0.003) and left (p = 0.007) sides. Our results showed an improvement in upper-limb functionality in PD patients submitted to progressive muscle-strength training, although not in quality of life.