简介：AbstractAntiphospholipid syndrome (APS) is a thromboinflammatory disease with a variety of clinical phenotypes. Primary thrombosis prophylaxis should take an individualized risk stratification approach. Moderate-intensity vitamin K antagonist such as warfarin remains the primary strategy for secondary thrombosis prophylaxis among APS patients, especially for patients with predominantly venous disease. For now, direct oral anti-coagulants should be avoided in most APS patients, especially those with history of arterial manifestations. Obstetric APS management should be tailored based on an individual patient’s antiphospholipid antibody profile, and obstetric and thrombotic history. Pharmacological agents beyond anticoagulants may be considered for the management of microthrombotic and nonthrombotic manifestations of APS, although more data are needed. A relatively recent discovery in the area of APS pathogenesis is the implication of neutrophil extracellular traps in thrombin generation and initiation of inflammatory cascades. APS is a complex thromboinflammatory disease with a broad clinical spectrum. Personalized therapy according to an individual’s unique thrombosis and obstetric risk should be advocated.

简介：AbstractAntiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is important to clarify how to evaluate efficacy and safety of antiviral agents in treatment of COVID-19 during the pandemic of this disease. We need to answer the following questions: do we still need to use rigorously designed randomized controlled clinical trials (RCTs)? Or, will it be enough if we use loosened criteria, observational studies or even retrospective case series and case reports? The answer is "No, we still need to use the strictly designed preferably blinded multicenter RCTs to evaluate the antiviral agents." In this article, we reviewed almost all the RCT reports on monotherapies and combined therapies with antiviral agents for COVID-19, and found that among the reports on monotherapies, only remdesivir, and among combined antiviral agents, only the combined regimen with interferon-β1b, lopinavir-ritonavir and ribavirin were effective and safe based on evidences from RCTs. The results of five RCTs for chloroquine or hydroxychloroquine consistently showed that they were ineffective and unsafe in the treatment of COVID-19, especially at larger doses. Many aspects in the design of the clinical trials may be related to success or failure of a trial and the relevant factors need to be analyzed, discussed and emphasized from the specific requirements and considerations of antiviral therapies. We hope such discussions be of certain use in designing clinical trials for pediatric antiviral therapies.

简介：AbstractDesmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.

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简介：AbstractAlthough whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders, about half of the patients still do not receive a molecular diagnosis. The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing (RNA-seq) in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence. RNA-seq data can be used to identify aberrantly spliced genes, detect allele-specific expression, and identify gene expression outliers. Amongst eight studies utilizing RNA-seq, a mean diagnostic uplift of 15% has been reported. Here, we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.

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简介：AbstractThe auditory brainstem implant (ABI) was originally developed to provide rehabilitation of retrocochlear deafness caused by neurofibromatosis type 2 (NF2). Recent studies of the ABI have investigated outcomes in non-NF2 cohorts, such as patients with cochlear nerve aplasia or cochlear ossification and more recently, intractable tinnitus. New technologies that improve the ABI-neural tissue interface are being explored as means to improve performance and decrease side effects. Innovative discoveries in optogenetics and bioengineering present opportunities to continually evolve this technology into the future, enhancing spatial selectivity of neuronal activation in the cochlear nucleus and preventing side effects through reduction in activation of non-target neuronal circuitry. These advances will improve surgical planning and ultimately improve patients’ audiological capabilities. ABI research has rapidly increased in the 21st century and applications of this technology are likely to continually evolve. Herein, we aim to characterize ongoing clinical, basic science, and bioengineering advances in ABIs and discuss future directions of this technology.

简介：AbstractPurpose:Liver is the most frequently injured organ in abdominal trauma. Today non-operative management (NOM) is considered as the standard of care in hemodynamically stable patients, with or without the adjunct of angioembolisation (AE). This systematic review assesses the incidence of complications in patients who sustained liver injuries and were treated with simple clinical observation. Given the differences in indications of treatment and severity of liver trauma and acknowledging the limitations of this study, an analysis of the results has been done in reference to the complications in patients who were treated with AE.Methods:A systematic literature review searched "liver trauma" , "hepatic trauma" , "conservative management" , "non operative management" on MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials databases, EMBASE, and Google Scholar, to identify studies published on the conservative management of traumatic liver injuries between January 1990 and June 2020. Patients with traumatic liver injuries (blunt and penetrating) treated by NOM, described at least one outcome of interests and provided morbidity outcomes from NOM were included in this study. Studies reported the outcome of NOM without separating liver from other solid organs; studies reported NOM complications together with those post-intervention; case reports; studies including less than 5 cases; studies not written in English; and studies including patients who had NOM with AE as primary management were excluded. Efficacy of NOM and overall morbidity and mortality were assessed, the specific causes of morbidity were investigated, and the American Association for the Surgery of Trauma classification was used in all the studies analysed. Statistical significance has been calculated using the Chi-square test.Results:A total of 19 studies qualified for inclusion criteria were in this review. The NOM success rate ranged from 85% to 99%. The most commonly reported complications were hepatic collection (3.1%), followed by bile leak (1.5%), with variability between the studies. Other complications included hepatic haematoma, bleeding, fistula, pseudoaneurysm, compartment syndrome, peritonitis, and gallbladder ischemia, all with an incidence below 1%.Conclusion:NOM with simple clinical observation showed an overall low incidence of complications, but higher for bile leak and collections. In patients with grade III and above injuries, the incidence of bile leak, collections and compartment syndrome did not show a statistically significant difference with the AE group. However, the latter result is limited by the small number of studies available and it requires further investigations.

简介：AbstractPlatelet-rich fibrin (PRF) is a second-generation platelet concentrate obtained from autologous blood. PRF is composed of abundant platelets, leucocytes, and a high concentration of various growth factors and fibrinogen. The composition and three-dimensional structure of PRF enable it to effectively make cells migrate and proliferate, playing an important role in tissue repair. Furthermore, the easy preparation and low cost of PRF make it a good treatment option. Numerous articles have been published about the application of PRF in clinical practice, however, the application of PRF in dermatology has not been comprehensively reviewed. The objective of this review article was to discuss various applications of PRF in dermatology, including healing chronic wounds, treating androgenic alopecia, skin rejuvenation, autologous fat transplantation, and treating vitiligo. PRF is a promising dermatologic treatment, but lacks a standardized protocol regarding its methods of attainment and use, which needs more investigations.

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简介：AbstractNucleic acid therapeutics, which involve transferring exogenous genes inside target cells, are a promising clinical treatment option that can regulate gene expression at the transcriptional or post-transcriptional level. Ideally, this kind of treatment modality will not lead to an unwanted immune response. Compared with traditional treatment methods, nucleic acid therapeutics can achieve prolonged and stable curative effects. As an emerging treatment method, nucleic acid therapeutics have played an increasingly important role in clinical settings for the treatment of various conditions, including infectious diseases, cancer, immune-related diseases, and monogenetic diseases. To date, a large number of clinical trials have been conducted, and more than 30 nucleic acid drugs have been approved, highlighting the strong potential of this approach in clinical practice. Diverse carriers are used to protect nucleic acids from being degraded and to help them reach their targets accurately. However, some carriers are known to cause negative effects on the release and expression of nucleic acid drugs as well as adverse effects such as allergic reactions and accumulation in the liver. Therefore, biosafety assessment of delivery systems before their application in clinical settings is critical. In this review, we describe different delivery systems for nucleic acid drugs and discuss their biosafety in both preclinical and clinical studies, with particular focus on the carriers themselves, drug administration method, and overall treatment of the disease.