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Clinical and genetic aspects of Charcot-Marie-Tooth disease subtypes 腓骨肌萎缩症亚型的临床和遗传方面
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2019-03-05 DOI: 10.23838/PFM.2018.00163
S. H. Nam, Byung-Ok Choi
Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neuropathies and is both genetically and clinically heterogeneous, with variable inheritance modes. With regard to clinical and genetic aspects, CMT is divided into several subtypes, including CMT1, CMT2, CMT3, CMT4, CMT5, CMT6, X-linked CMT, and intermediate CMT. Up to date, more than 90 causative genes for CMT have been identified. Furthermore, previous animal studies reported some molecules to have therapeutic effects on specific CMT subtypes, depending on the underlying genetic cause. Therefore, accurate genetic diagnosis is of crucial importance when performing customized therapy. Finally, recent investigations on induced pluripotent stem cells expanded the possibility of both patient-specific cell therapy and drug discovery. The current review focuses on the latest classification updates for accurate CMT diagnosis.
Charcot-Marie Tooth病(CMT)是最常见的遗传性神经病之一,在遗传和临床上都是异质性的,具有可变的遗传模式。就临床和遗传方面而言,CMT分为几个亚型,包括CMT1、CMT2、CMT3、CMT4、CMT5、CMT6、X-连锁CMT和中间型CMT。到目前为止,已经鉴定出90多个CMT的致病基因。此外,先前的动物研究报告称,根据潜在的遗传原因,一些分子对特定的CMT亚型具有治疗作用。因此,在进行定制治疗时,准确的基因诊断至关重要。最后,最近对诱导多能干细胞的研究扩大了患者特异性细胞治疗和药物发现的可能性。目前的综述集中在准确诊断CMT的最新分类更新上。
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引用次数: 8
Implication of hepatocyte dedifferentiation in pathogenesis and treatment of hepatocellular carcinoma 肝细胞去分化在肝癌发病及治疗中的意义
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2019-01-21 DOI: 10.23838/PFM.2018.00135
Hyunsoo Kim, Eun-Ji Park, Chang-Woo Lee
Liver cancer is the fifth most common malignancy worldwide and the third most common cause of cancer-related death. Five hundred million individuals are infected by hepatitis B or C virus. Of these cases, some will progress to liver failure and cancer. Systemic treatments against liver cancer show poor efficacy mainly because of high resistance and poor response to therapeutics and high degree of tumor heterogeneity. Although progress has been made in combinational treatment of liver cancer, no effective disease-modifying therapies for hepatocellular carcinoma (HCC) have been developed to date. A comprehensive understanding of HCC pathogenesis will enable identification of biomarkers and therapeutic targets and provide insights into mechanism-based strategies for HCC treatment. However, the identification of cellular origins of liver cancer remains a challenging issue. This review focuses on HCC heterogeneity that escapes current treatment strategies and causes disease recurrence to provide a better understanding for the biology of liver cancer.
癌症是全球第五大常见恶性肿瘤,也是癌症相关死亡的第三大常见原因。五亿人感染了乙型或丙型肝炎病毒。在这些病例中,有些会发展为肝衰竭和癌症。对癌症的系统治疗显示出较差的疗效,主要是因为对治疗的高耐药性和不良反应以及高度的肿瘤异质性。尽管癌症的联合治疗取得了进展,但迄今为止还没有开发出有效的肝细胞癌(HCC)的疾病改良疗法。对HCC发病机制的全面了解将有助于识别生物标志物和治疗靶点,并为基于机制的HCC治疗策略提供见解。然而,癌症细胞起源的鉴定仍然是一个具有挑战性的问题。这篇综述的重点是HCC异质性,它逃避了当前的治疗策略并导致疾病复发,以更好地了解癌症的生物学。
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引用次数: 1
Reversible cerebral vasoconstriction syndrome without typical thunderclap headache: highresolution magnetic resonance imaging features 无典型雷击性头痛的可逆性脑血管收缩综合征:高分辨率磁共振成像特征
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2018-12-31 DOI: 10.23838/PFM.2018.00170
Eun‐Hyeok Choi, Inwu Yu, Jaehong Park, C. Yoon, O. Bang
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by sudden onset severe headache with or without focal neurologic deficits and is accompanied by segmental or multifocal intracranial arterial vasospasms that resolve within 3 months. The typical RCVS has thunderclap headache but patients with RCVS without this type of headache have been reported. Herein we introduce an unusual case of RCVS without thunderclap headache, together with typical high-resolution magnetic resonance imaging (HR-MRI) features of RCVS showing the possible mechanisms of this condition. The present case suggests that HR-MRI features like dynamic negative remodeling but no enhancement may be a suspicious sign for RCVS, especially in cases with atypical presentation. HR-MRI can be helpful in direct visualization of the vasoconstriction of RCVS and differential diagnosis of other diseases, possibly even without serial examinations. Further research should be performed to test the diagnostic accuracy of HR-MRI in patients with RCVS.
可逆性脑血管收缩综合征(RCVS)的特征是伴有或不伴有局灶性神经功能缺损的突然发作的严重头痛,并伴有节段性或多局灶性颅内动脉血管痉挛,并在3个月内消退。典型的RCVS有雷击性头痛,但没有这种头痛的RCVS患者也有报道。本文介绍一例罕见的无雷击性头痛的RCVS病例,以及RCVS典型的高分辨率磁共振成像(HR-MRI)特征,显示该疾病的可能机制。本病例提示HR-MRI表现为动态负重构但无强化可能是RCVS的可疑征象,特别是在表现不典型的病例中。HR-MRI可以直接显示RCVS血管收缩和其他疾病的鉴别诊断,甚至可能不需要进行系列检查。需要进一步的研究来检验HR-MRI对RCVS患者的诊断准确性。
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引用次数: 1
Investigative strategies on lymphatic vessel modulation for treating lymphedema in future medicine 淋巴管调节治疗淋巴水肿在未来医学中的研究策略
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2018-11-06 DOI: 10.23838/PFM.2018.00142
Raghu P. Kataru, B. Mehrara, Honsoul Kim
Impairment of lymphatic drainage may result in the development of lymphedema, a life-long disorder that results in significant morbidity. However, although lymphedema is common, current treatments are palliative in nature aiming to decrease swelling and control symptoms rather than cure the underlying problem. However, as our understanding in lymphatic biology increases, recent translational studies have described strategies that induce lymphangiogenesis to correct the underlying pathologic problem. These strategies can be classified into three categories: Increase the prolymphangiogenic drive (exogenous vascular endothelial growth factor C [VEGF-C] protein administration or VEGF-C gene delivery); suppress inflammation and inhibit production of antilymphangiogenic molecules (tacrolimus topical administration or leukotriene B4 antagonism); or cell therapy. In this review, we will briefly discuss the mechanisms regulating lymphangiogenesis along with recent translational studies that adopt strategies to modulate these mechanisms. We consider these strategies as candidate therapeutic options that may be in the near future used for the clinical treatment of lymphedema.
淋巴引流受损可能导致淋巴水肿的发展,这是一种终身疾病,会导致显著的发病率。然而,尽管淋巴水肿很常见,但目前的治疗方法本质上是姑息性的,旨在减轻肿胀和控制症状,而不是治愈潜在的问题。然而,随着我们对淋巴生物学的理解不断加深,最近的转化研究描述了诱导淋巴管生成以纠正潜在病理问题的策略。这些策略可分为三类:增加促淋巴生成驱动(外源性血管内皮生长因子C[VEGF-C]蛋白给药或VEGF-C基因递送);抑制炎症并抑制抗淋巴管生成分子的产生(他克莫司局部给药或白三烯B4拮抗);或细胞治疗。在这篇综述中,我们将简要讨论调节淋巴管生成的机制,以及最近采用策略来调节这些机制的转化研究。我们认为这些策略是候选的治疗选择,可能在不久的将来用于淋巴水肿的临床治疗。
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引用次数: 1
Fast upper airway magnetic resonance imaging for assessment of speech production and sleep apnea 快速上呼吸道磁共振成像评估言语产生和睡眠呼吸暂停
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2018-10-10 DOI: 10.23838/PFM.2018.00100
Yoon-Chul Kim
The human upper airway is involved in various functions, including speech, swallowing, and respiration. Magnetic resonance imaging (MRI) can visualize the motion of the upper airway and has been used in scientific studies to understand the dynamics of vocal tract shaping during speech and for assessment of upper airway abnormalities related to obstructive sleep apnea and swallowing disorders. Acceleration technologies in MRI are crucial in improving spatiotemporal resolution or spatial coverage. Recent trends in technical aspects of upper airway MRI are to develop state-of-the-art image acquisition methods for improved dynamic imaging of the upper airway and develop automatic image analysis methods for efficient and accurate quantification of upper airway parameters of interest. This review covers the fast upper airway magnetic resonance (MR) acquisition and reconstruction, MR experimental issues, image analysis techniques, and applications, mainly with respect to studies of speech production and sleep apnea.
人类的上呼吸道涉及多种功能,包括言语、吞咽和呼吸。磁共振成像(MRI)可以可视化上呼吸道的运动,并已被用于科学研究,以了解语音过程中声道成形的动力学,并用于评估与阻塞性睡眠呼吸暂停和吞咽障碍相关的上呼吸道异常。MRI中的加速技术对于提高时空分辨率或空间覆盖率至关重要。上气道MRI的技术方面的最新趋势是开发用于改进上气道的动态成像的最先进的图像采集方法,以及开发用于有效和准确地量化感兴趣的上气道参数的自动图像分析方法。本文综述了快速上呼吸道磁共振(MR)的采集和重建、MR实验问题、图像分析技术及其应用,主要涉及语音产生和睡眠呼吸暂停的研究。
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引用次数: 3
Functional roles of heterogeneous nuclear ribonucleoprotein K in post-transcriptional gene regulation 异质核核糖核蛋白K在转录后基因调控中的功能作用
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2018-10-02 DOI: 10.23838/PFM.2018.00107
C. H. Shin, Hyeon-ho Kim
Since it is widely accepted that the accumulation of genetic alterations is the main cause of cancer, understanding how cancer-associated genes are regulated is crucial to the development of cancer therapies. As one of important RNA-binding proteins (RBPs), heterogeneous nuclear ribonucleoprotein K (hnRNPK), is known to regulate the expression of target genes involved in various pathways, such as transcription, splicing, and translation. HnRNPK is also closely associated with cancer progression, including the acquisition of metastatic potential. At the post-transcriptional level, gene expression is determined by competitive or cooperative interactions between trans-acting factors including RBPs and non-coding RNAs (ncRNAs) which are capable of binding to cis-elements in target genes. In this review, we discuss the roles of hnRNPK in post-transcriptional gene regulation. The regulation of cancer-associated genes (oncogenes and tumor suppressors) via crosstalk between hnRNPK and ncRNAs such as microRNAs and long ncRNAs is described in detail. This review highlights how hnRNPK may be a promising target for the development of cancer therapeutics.
由于人们普遍认为基因改变的积累是癌症的主要原因,因此了解癌症相关基因的调节对癌症疗法的发展至关重要。作为一种重要的RNA结合蛋白(RBPs),异质核核糖核蛋白K(hnRNPK)可以调节参与转录、剪接和翻译等多种途径的靶基因的表达。HnRNPK也与癌症进展密切相关,包括获得转移潜能。在转录后水平上,基因表达由反式作用因子(包括RBPs和能够与靶基因中的顺式元件结合的非编码RNA(ncRNA))之间的竞争或合作相互作用决定。在这篇综述中,我们讨论了hnRNPK在转录后基因调控中的作用。详细描述了通过hnRNPK和ncRNA(如微小RNA和长ncRNA)之间的串扰对癌症相关基因(致癌基因和肿瘤抑制剂)的调节。这篇综述强调了hnRNPK如何可能成为癌症治疗发展的一个有前途的靶点。
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引用次数: 6
Pneumonia in immunocompromised patients: updates in clinical and imaging features 免疫功能低下患者的肺炎:临床和影像学特征的更新
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2018-09-28 DOI: 10.23838/PFM.2018.00121
K. Peck, Tae Jung Kim, Min A Lee, K. Lee, Joungho Han
Pulmonary infection is a major cause of mortality in immunocompromised patients. Immunosuppression can be divided into neutropenia, humoral immunodeficiency, and cellular immunodeficiency. Pulmonary infection in these patients typically depends on the type, duration, and degree of immunodeficiency. Pulmonary infection in immunocompromised patients is often nonspecific, both clinically and radiologically, but a certain type of pulmonary infection may provide typical radiological features helpful for definitive diagnosis. Therefore, it is essential to incorporate clinical information into radiological features to narrow down the differential diagnosis and to potentially reduce the morbidity and mortality associated with pulmonary infections in immunocompromised patients.
肺部感染是免疫功能低下患者死亡的主要原因。免疫抑制可分为中性粒细胞减少症、体液免疫缺陷症和细胞免疫缺陷症。这些患者的肺部感染通常取决于免疫缺陷的类型、持续时间和程度。免疫功能低下患者的肺部感染通常在临床和影像学上都是非特异性的,但某些类型的肺部感染可能提供典型的影像学特征,有助于明确诊断。因此,必须将临床信息纳入影像学特征,以缩小鉴别诊断范围,并潜在地降低免疫功能低下患者与肺部感染相关的发病率和死亡率。
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引用次数: 10
The associations between bone mineral density and cerebral white matter hyperintensity in elderly stroke patients 老年脑卒中患者骨矿物质密度与脑白质高强度的关系
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2018-09-28 DOI: 10.23838/PFM.2018.00114
Ji Sun Kim, Minjik Kim, Sung Hoon Kang, Kyungmi Oh, S. Suh, W. Seo
Purpose: Osteoporosis is an important senile disease and has significant relationship with ischemic stroke and cerebral small vessel disease (SVD). Correlation between bone mineral density (BMD) and cerebral white matter hyperintensity on magnetic resonance imaging were analyzed to investigate the relationship between osteoporosis and cerebral SVD. Methods: Medical records of acute stroke patients with age ≥65 years were retrospectively collected from single center. Cerebral white matter hyperintensity was classified into two categories, periventricular white matter hyperintensity (PWMH) and deep white matter hyperintensity (DWMH), and the severity was graded according to maximal lesion size. Association between the clinical factors including BMD and the severity of cerebral white matter hyperintensity was analyzed. Results: Four hundred eight patients were included in the study. High severity grade of both MWMH and DWMH was independently correlated with low BMD. Additionally, high PWMH grade was correlated with old age and high serum homocysteine. High DWMH grade was correlated with old age, atrial fibrillation history and high serum total calcium. Conclusion: Low BMD was associated with a high severity of cerebral white matter hyperintensity in elderly Asian stroke patients, independent of other clinical factors.
目的:骨质疏松症是一种重要的老年性疾病,与缺血性脑卒中和脑小血管病(SVD)有密切关系。分析骨密度(BMD)与脑白质磁共振高信号的相关性,探讨骨质疏松症与脑SVD的关系。方法:回顾性收集年龄≥65岁急性脑卒中患者的单中心病历资料。脑白质高信号可分为室周白质高强度(PWMH)和深部白质高密度(DWMH)两类,并根据最大病变大小对其严重程度进行分级。分析了包括骨密度在内的临床因素与脑白质高信号严重程度之间的关系。结果:408名患者被纳入研究。MWMH和DWMH的高严重程度与低BMD独立相关。此外,高PWMH分级与老年和高血清同型半胱氨酸相关。高DWMH分级与老年、心房颤动史和高血清总钙相关。结论:低骨密度与老年亚洲脑卒中患者脑白质高信号的严重程度有关,与其他临床因素无关。
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引用次数: 0
Atypical clinical presentations in right hemispheric infarcts: complex stories beyond neurological examination and diffusion-weighted magnetic resonance imaging 右半球梗死的非典型临床表现:神经学检查和弥散加权磁共振成像之外的复杂故事
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2018-09-28 DOI: 10.23838/PFM.2018.00093
Jaeho Kim, Jaehong Park, H. Kang, O. Bang
Although, both neurological examination and neuroimaging represent the main methods for the anatomical localization of lesions in stroke patients, atypical anatomical-functional representation of cortical lateralized syndromes can occur. Herein, we introduce three cases of atypical representation of left hemispheric syndromes with right hemispheric lesions and we explore the possible mechanisms underlying such disorders and their clinical implications.
尽管神经学检查和神经影像学是脑卒中患者病变解剖定位的主要方法,但皮质侧化综合征的非典型解剖功能表征也可能发生。在此,我们介绍三例左半球综合征伴右半球病变的非典型表现,并探讨这些疾病的可能机制及其临床意义。
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引用次数: 0
Infectious pneumonia in immunocompetent patients: updates in clinical and imaging features 免疫活性患者感染性肺炎的临床和影像学特征更新
IF 0.5 Q2 MEDICINE, GENERAL & INTERNAL Pub Date : 2018-09-28 DOI: 10.23838/PFM.2018.00079
K. Lee, Tae Jung Kim, K. Peck, Joungho Han
Morphologically pneumonia is usually classified into lobar pneumonia, bronchopneumonia, and interstitial pneumonia. Chronic pneumonia is also a kind of pneumonia in immunocompetent and mildly immunocompromised patients. Specific organisms may be involved in community-acquired pneumonia (CAP) according to patients’ age or underlying conditions. The organisms involved in CAP are different from those in hospital-acquired pneumonia. Mixed pneumonia includes septic pneumonia, lung abscess, and focal organizing pneumonia. The role of imaging in pneumonia includes the detection or exclusion of the presence of pneumonia, narrowing down of differential diagnosis of the pneumonia from other lung conditions, planning of further diagnostic procedure, and the assessment of treatment response with follow-up studies. New drugs for pneumonia are expected to open a door widely for antibiotic treatment for various pneumonias.
形态学上的肺炎通常分为大叶性肺炎、支气管肺炎和间质性肺炎。慢性肺炎也是免疫功能低下和轻度免疫功能低下患者的一种肺炎。根据患者的年龄或潜在条件,特定生物体可能参与社区获得性肺炎(CAP)。CAP涉及的生物体与医院获得性肺炎不同。混合性肺炎包括感染性肺炎、肺脓肿和局灶性组织性肺炎。影像学在肺炎中的作用包括检测或排除肺炎的存在,缩小肺炎与其他肺部疾病的鉴别诊断范围,规划进一步的诊断程序,以及通过后续研究评估治疗反应。治疗肺炎的新药有望为各种肺炎的抗生素治疗打开广泛的大门。
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引用次数: 3
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Precision and Future Medicine
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