多发性骨髓瘤中表观遗传学修饰的研究进展北大核心

多发性骨髓瘤(multiple myeloma,MM)是一种病因不明,目前仍无法治愈的恶性血液系统性疾病。研究显示MM是一种复杂的表观遗传学修饰所驱动的恶性肿瘤,表观遗传学修饰是改变MM发病进展的重要机制,并影响治疗及预后。本文将对表观遗传学异常调控在MM的发生发展过程中的作用及相关耐药机制和治疗的现状进行综述。     

Molecular imaging in oncology: Current impact and future directions

The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging—particularly when combined with liquid biopsy for screening purposes—promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology.     

基于生物信息学的肥厚型心肌病易感基因TNNC1单核苷酸多态性致病表型分析

肥厚型心肌病(HCM)是一种常见的遗传性心脏病,是青少年及年轻运动员心源性猝死的最主要原因之一,其分子遗传学基础为基因突变。TNNC1是HCM的重要致病基因之一,目前仅发现其少量非同义单核苷酸多态性(nsSNPs)位点与HCM发病相关,但该基因其他nsSNPs数量较多,结合临床进行实验遗传检测其基因型与表型的关系,工作量巨大,尚不可行。因此,采用生物信息学方法,从dbSNP数据库中筛选出TNNC1基因全部的nsSNPs,联合4款(Mutation Taster、PolyPhen-2、PhD-SNP和MutPred)专业软件,进行有害性分级筛选和致病关联预测,最后进行突变蛋白三维结构建模及可视化分析。结果显示,首次从TNNC1基因102个nsSNPs位点中预测出疾病相关的18个(G159D、S69R、P52R、D149G、D3V、G140E、N51K、D151V、M47R、G110C、A23D、G140R、K158N、C35Y、R147C、L48P、F74C和V44G)高风险nsSNPs。基于生物信息学方法,以TNNC1基因的nsSNPs为示范,分析其nsSNPs与疾病表型的关系,这为其他遗传疾病致病基因nsSNPs的关联分析打下理论研究基础,具有重要的参考价值。     

Artificial intelligence and clinical data suggest the T cell-mediated SARS-CoV-2 nonstructural protein intranasal vaccines for global COVID-19 immunity

Advanced computational methodologies suggested SARS-CoV-2, nonstructural proteins ORF1AB, ORF3a, as the source of immunodominant peptides for T cell presentation. T cell immunity is long-lasting and compatible with COVID-19 pathology. Based on the supporting clinical data, nonstructural SARS-CoV-2 protein vaccines could provide global immunity against COVID-19.     

Rehabilitation in long COVID-19: A mini-review

We have been experiencing multiple waves of the coronavirus disease 2019 (COVID-19) pandemic. With these unprecedented waves, we have entered into an era of ‘new normal’. This pandemic has enforced us to rethink the very basics of childhood learning: Habits, health etiquette, and hygiene. Rehabilitation has immense importance during this pandemic considering a few aspects. Multidisciplinary COVID-19 rehabilitation clinics are essential to address the demand. The equitable distribution of COVID-19 rehabilitation services for differently-abled individuals during the pandemic is an important aspect. Rehabilitation needs identification and further studies on various rehabilitation interventions are among the key unmet future research needs.     

Dissection of Capsid Protein HPV 52 to Rationalize Vaccine Designs Using Computational Approaches Immunoinformatics and Molecular Docking

Background: Human Papillomavirus type 52 (HPV 52) is considered one of the threatening HPV types inducing cervical cancer worldwide. This study was conducted to address strategies of an effective vaccine against cervical cancer using computational approaches immuno-informatics and molecular docking. Methods: Major capsid protein L1 and L2 HPV 52 (L1 and L2 HPV 52) sequences were investigated by multiple analyses including B and T cell epitope, toxicity, allergenicity, Immunogenicity, epitope conservancy, population coverage, and molecular docking. Results: L1 and L2 HPV 52 showed a conserved sequence among amino acid levels. Q307K, S383D/N, and D473E are found as major mutations in L1, while mutations in L2 are S122T, Q247H, L247S, and E365D. Multiple epitopes were identified and elicited strong immune responses against cross types of HPV in various HLA populations. To enhance vaccine effectiveness that allows having cross-protection over HPV types, N terminus HPV L2 was analyzed suggesting multi-candidates chimeric L1/L2 vaccine design. Conclusion: This study shed a light on a useful pipeline with robust analysis for effective vaccine production.     

Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

Preoperative comprehensive malignancy risk estimation for thyroid nodules: Development and verification of a network-based prediction model

BackgroundIn order to avoid excessive treatment of thyroid nodules in the clinic, it is necessary to find a simple and practical analysis method to comprehensively and accurately reflect benign or malignant thyroid nodules. This study aimed to construct and validate a comprehensive and reliable network-based predictive model using a variety of imaging and laboratory criteria for thyroid nodules to stratify the risk of malignancy prior to surgery.MethodsWe retrospectively analyzed data from patients who underwent surgical treatment for thyroid nodules at the Thyroid and Breast Diagnosis and Treatment Center of Weifang Hospital of Traditional Chinese Medicine between January 2018 and December 2020. Binary logical regression analysis was performed to predict whether nodules were malignant or benign. The developmental dataset included 457 patients (January 2018–December 2020). The validation set included separate data points (n = 225, January 2018–December 2020).ResultsIn this study, criteria that showed significant predictive value for malignant nodules included TI-RADS: 4b (p = 0.065); Bethesda IV, Bethesda V, Bethesda VI (P < 0.0001); BRAF^V600E mutation (P < 0.0001); Calcitonin>5 pg/ml (p = 0.0037); and FNA-Tg>30 ng/ml (p = 0.0003). A 10-grade risk scoring system was developed. The risk of malignancy risk ranged from 2.06% to 100% and was positively associated with increasing risk grade. The areas under the receiver-operating characteristic curve of the development and validation sets were 0.972 and 0.946, respectively.ConclusionA simple, comprehensive and reliable web-based predictive model was designed using a variety of imaging and laboratory criteria to stratify thyroid nodules by probability of malignancy.