循环肿瘤细胞分子鉴定与个体化肿瘤诊疗

肿瘤细胞表现的高度异质性严重困扰着肿瘤临床诊断和治疗.因此,肿瘤分子分型及其指导个体化治疗一直是肿瘤研究领域的热点.循环肿瘤细胞(circulating tumor cells,CTCs)作为具有肿瘤代表性的"液体活检"样本,允许多次、实时、非侵入性获取,是指导个体化肿瘤诊疗的绝佳标本.目前认为,基于分子鉴定检测少数更具存活力和侵袭性的CTCs比单独CTCs计数更有价值.而在肿瘤转移过程中C T C s表现的多种生物学特性及其分子机制都可被用于分型,并且可能成为个体化肿瘤诊疗的靶点.本文综述近年来关于CTCs分子鉴定的研究进展,以及CTCs分子分型指导个体化诊疗的研究现状,提出相关领域今后的研究方向.     

新生儿糖尿病的研究进展

新生儿糖尿病(NDM)是一种少见的特殊类型糖尿病,分为暂时性新生儿糖尿病(TNDM)和永久性新生儿糖尿病(PNDM)两种临床类型.过去NDM一直被误诊为1型糖尿病,终身给予胰岛素治疗.新近NDM的分子遗传学研究取得了突破性进展,其特殊基因突变类型正逐渐得以鉴定明确.对于某些基因突变如KCNJ11或ABCC8基因杂合子激活突变导致的NDM患者,胰岛素治疗并不是最佳选择,口服降糖药物可以更好地控制血糖并改善其相应临床症状.     

血清胱抑素C和γ-谷氨酰转移酶在糖尿病早期肾损伤的诊断价值

目的探讨血清胱抑素C(Cys C)和γ-谷氨酰转移酶(γ-GT)在糖尿病早期肾损伤的诊断价值。方法选取该院2014年4月—2016年4月收治的2型糖尿病早期肾损伤患者98例,将其设定为观察组。选取同期在该院接受健康体验者98例作为对照,将其设定为对照组。采用全自动生化分析仪检测两组受检者的血清Cys C、γ-GT、尿素氮(BUN)、肌酐(Cr),对两组测定值进行比较分析。比较联合检测血清Cys C、γ-GT与常规肾功检测早期肾损伤阳性率,并对患者的血清Cys C、γ-GT检测结果进行相关性分析。结果测定结果显示两组血清Cys C、γ-GT差异有统计学意义(P0.05),血清BUN、Cr差异无统计学意义(P0.05)。联合检测血清Cys C、γ-GT发现早期肾损伤呈阳性32例,阳性率为32.7%(32/98),常规肾功检测未发现阳性病例,差异有统计学意义(P0.05)。糖尿病早期肾损伤患者血清Cys C与γ-GT检测结果呈正相关(r=0.68,P0.01)。结论血清Cys C、γ-GT是糖尿病早期肾损伤诊断的良好指标,联合检测血清Cys C、γ-GT可提高糖尿病肾病的早期诊断率。     

MODY2的认识及诊疗进展

青少年发病的成年型糖尿病2型(MODY2)由葡萄糖激酶(GCK)基因突变所致,以空腹血糖及糖化血红蛋白水平轻度升高并保持稳定状态为主要表现,多不增加糖尿病并发症及相关代谢疾病的发生风险,无需降糖治疗.但对于妊娠期患者,若胎儿未携带突变基因,妊娠相关并发症及巨大儿发生风险增加,故此类患者需积极降糖治疗.     

降糖治疗影响糖尿病患者眼屈光度的相关因素分析

目的 分析降糖治疗对糖尿病患者眼屈光度的影响,探讨其发生机制.方法 选择20例新诊断的糖尿病患者,检测治疗前随机血糖、糖化血红蛋白(HbA1c)、空腹及餐后2 h C肽等生化指标.测定双眼屈光度、角膜曲率、前房深度、晶状体厚度等,并在降糖治疗的第1、2、3、4周分别复测以上眼部指标.分析屈光度改变与各生化指标的相关性及降糖治疗前后各眼部指标的变化.结果 降糖治疗后所有患者均出现远视性屈光改变,平均最大远视改变幅度1.6 D(0.50 D～3.20 D),改变幅度与HbA1c、治疗第1周的降糖速度呈正相关(r值分别为0.84,0.53;P值均＜0.05),与治疗前随机血糖、空腹及餐后2 h C肽无相关性,持续约2～4周逐渐恢复治疗前屈光水平.治疗前后角膜曲率、前房深度、晶状体厚度等眼部指标未见显著性变化.结论 降糖治疗导致糖尿病患者出现暂时性远视改变,改变幅度主要与治疗前HbA1c水平及治疗的前7天的降糖速度有关.其发生机制可能与晶状体水合化导致的屈光力降低有关,而非晶状体形态的改变.     

《中国成人住院患者高血糖管理目标》专家共识解读

住院患者中高血糖可增加其并发症的发生率、病死率及医疗费用开支,并延长住院时间。为安全、有效地控制住院患者的高血糖,中华医学会内分泌学分会组织相关专家制定了关于中国成人住院患者高血糖管理的共识原则：强调个体化原则,根据不同患者和不同病情制定分层血糖控制目标;糖尿病患者住院期间血糖不一定要求达标;一般不应该快速降糖;降糖治疗应尽量避免低血糖及超重和肥胖者体重增加;避免宽松血糖管理增加感染和高血糖危象的风险。     

《心脏离子通道病与心肌病基因检测专家共识》中的长QT综合征基因检测

2011年美国心律学会/欧洲心律学会发表了《心脏离子通道病与心肌病基因检测专家共识》,在有关长QT综合征(LQTS)的部分中推荐经心脏病专家诊断或高度怀疑的LQTS患者进行LQT1～3(KCNQ1、KCNH2、SCN5A)的基因检测;已在先证者发现LQTS致病基因突变者,推荐其直系亲属进行该特定突变的检测。如果基因检测、病史以及12导ECG均为阴性方可排除LQTS。通过对病人进行基因检测、综合评估及危险分层可帮助他们选择最适合的个体化治疗方案,并取得最佳的临床结果。     

胰岛素敏感性指数和胰岛β细胞功能指数指导2型糖尿病的治疗

目的　观察依据胰岛素敏感性指数 (ISI)和胰岛β细胞分泌胰岛素功能指数 (FBCI)检测直接选择降糖药物治疗 2型糖尿病 (T2DM )的疗效。方法　以T2DM常规治疗 1 0 9例病人为对照组 ,以ISI和FBCI指导治疗的 1 0 6例T2DM病人为观察组 ,比较两组住院治疗时间及治疗后糖尿病控制指标。结果　观察组住院时间 (1 4 55± 2 1 8)d,对照组 (2 5 67± 8 93)d(P <0 0 1 ) ;观察组FPG、PPG及GSP均接近糖尿病良好控制标准 ,优于对照组 (P <0 0 5 ,P <0 0 1 ,P <0 0 5)。结论　ISI和FBCI可具有针对性指导T2DM病人降糖药物的选择 ,为临床T2DM防治的基础工作提供了一个科学而有效的方法。     

MMP-9及PPARγ与2型糖尿病动脉粥样硬化

基质金属蛋白酶-9(MMP-9)是一种降解细胞外基质的蛋白酶,能促进动脉粥样硬化(AS)斑块的形成、发展及破裂,在AS病变时明显增高。已发现高糖可诱导其表达,在2型糖尿病合并AS中更是显著升高。抑制其生成,改善细胞外基质重构已成为2型糖尿病治疗的方向之一。过氧化物酶体增殖物活化受体(PPAR)γ是核受体超家族成员,可调控靶基因转录,从多方面发挥抗AS的作用,其中一个关键环节就是抑制MMP-9的表达。PPARγ激动剂(噻唑烷二酮类降糖药)应用于2型糖尿病合并AS,不仅有效降糖、降脂,改善胰岛素抵抗,而且抑制MMP-9表达,抑制AS的形成和进展。     

关注血糖达标与低血糖风险之间的平衡——谈糖尿病合并心血管疾病的降血糖治疗

糖尿病明显增加了心血管疾病的死亡率.出人意料的是更严格的血糖控制在某个大型临床试验中竟然增加了心血管病死亡,其间降糖治疗诱发的低血糖难辞其咎.为了减少低血糖的风险,在今后糖尿病合并心血管病患者的降糖治疗中至少有以下三点应予注意:(1)早期识别低血糖,包括不典型或表现怪异的低血糖;(2)强调血糖达标的个体化;(3)更精心地设计降糖治疗方案,特别要注意避免低血糖的发生.     

人工智能在内分泌代谢领域的应用及展望

人工智能(artificial intelligence,AI)是近年发展最快的科学之一,其在医学领域的发展带来了全新的概念,也对传统医学带来了巨大的冲击,是借势而为还是静观其变是对各学科和医学人的考验。AI在医学影像等领域已经取得了令人瞩目的效果。目前,AI在内分泌代谢领域的应用研发也日趋广泛,包括在糖尿病及其并发症的诊断和预测的应用,辅助治疗方案的选择和血糖管理,人工胰岛的开发与管理,在肥胖分类诊疗的探索,在减重手术的疗效和并发症预测的探索;在骨质疏松和骨折风险的预测,骨龄分析;脂肪肝的无创评估及纤维化预测;肢端肥大症的诊断;甲状腺和垂体肿瘤分子生物学与病理的智能诊断等。AI在临床上的应用仍处于初期和探索阶段,相信在不久的将来,随着AI技术的快速发展和临床认可,AI会在内分泌代谢领域发挥举足轻重的作用。面对AI时代的来临,对医学领域来讲是一场脱胎换骨的变革。在新生事物面前,只有积极接受,有机融合才能得以生存,取得共赢。     

Clinical implications of omics and systems medicine: focus on predictive and individualized treatment

Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High‐throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole‐genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples.     

Noninvasive Cardiovascular Imaging: Emergence of a Powerful Tool for Early Identification of Cardiovascular Risk in People Living With HIV

Antiretroviral therapy (ART) has been pivotal in prolonging the lifespan of people living with HIV (PLWH). However, this also simultaneously increases their risk of cardiovascular disease (CVD) either related to ART, aging, hypertension, immunosenescence, inflammation, immune activation, or other comorbidities. Although the use of risk markers has greatly enhanced the field of cardiovascular (CV) medicine and improved the prognosis and early diagnosis in the general population, this strategy has not been clearly elucidated in PLWH. Developing accurate risk algorithms for PLWH requires an innate understanding of mechanistic factors influencing their risks. Early identification of CV risk will significantly enhance the prospects of PLWH living longer and relatively healthily. Herein, we discuss the use of multimodality noninvasive CV imaging as robust markers for ameliorating CV risk. The ability to prognosticate CV risk and hence prevent CV events in PLWH would represent an important advance in CV medicine, allowing precise detection and early institution of preventative strategies. Using novel CV imaging modalities and strategies would have a positive impact on precision medicine in this patient cohort.     

Personalized Medicine for Diabetes: Circulating Biomarkers of Glycemia in Diabetes Management and Implications for Personalized Medicine

Personalized medicine represents a new model in how the medical community approaches disease management. Rather than managing those with a particular diagnosis according to an established guideline, the personalized medicine model seeks to identify unique characteristics within each patient that can serve as a basis for disease characterization and specialized treatment. This article reviews several circulating biomarkers of glycemia that are used in the medical management of diabetes, to include hemoglobin A1c, fructosamine, and 1,5-anhydroglucitol. Within the discussion, specific attention is paid to areas in which biomarker results do not correlate with anticipated results based on actual mean glycemia. Variability between actual and anticipated results of the various biomarker tests represents opportunities to identify previously undefined subcategories of diabetes and groups of patients that fit into these subcategories. Finally, research areas are proposed for these subcategories that would further promote the field of personalized medicine in diabetes.     

Non-invasive markers associated with liver fibrosis in non-alcoholic fatty liver disease

The diagnosis of fibrosis within liver disease is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. The rising incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) has driven the search for accurate non-invasive tools of liver fibrosis within this condition. With the aid of a systematic review, we explore how the field has evolved from the discovery of simple blood parameters to panel markers of liver fibrosis. We will discuss the biological plausibility, limitations, potential uses, and emerging diagnostic techniques of non-invasive markers in this rapidly expanding field.     

Diabetes coexistent with Charcot–Marie–Tooth disease presenting as a recurrent foot ulcer misdiagnosed as diabetic foot: A case report

Both diabetes mellitus and Charcot–Marie–Tooth disease (CMT) can lead to severe peripheral neuropathy. The differential diagnosis of peripheral neuropathy is difficult due to the similar clinical features. There are still some clues, such as unusual muscle atrophy, unmatched severity of peripheral neurogenic damage with nephropathy or retinopathy, which could alert clinicians to make differential diagnosis. Although diabetes mellitus is rarely concurrent with CMT, it will exacerbate clinical disorders in patients with CMT. To date, there is no specific medicine for CMT treatment. Offloading devices and desirable comprehensive management of diabetes mellitus might be beneficial to avoid plantar ulcer recurrence and anti-progression of CMT.     

冠状动脉粥样硬化精准诊治的分子影像研究进展

动脉粥样硬化斑块破裂具有隐匿性和突发性的特点，可诱发包括心源性猝死等严重心血管事件，但是目前临床常用的检查手段难以对易损斑块进行早期人群筛查。分子影像为斑块的早期诊断带来了新的契机，同时精准医学概念可指导斑块的精准诊治。本综述主要阐述了在精准医学的理念下，结合心血管疾病病理生理、生物医学工程和纳米技术对动脉粥样硬化斑块进行精准诊治的分子影像学进展。     

Glycated albumin as biomarker: Evidence and its outcomes

Glycemic control markers are important for the diagnosis and treatment of diabetes. Hemoglobin A1c (A1C) is an important marker that is mandatory in routine medical examinations; however, it is well known that it has some limitations. In this review, we focus on the limitation of A1C and introduce a relatively new marker, glycated albumin (GA), which can be used to complement A1C.First, for a better understanding of the characteristics of each marker, we sort the similarities and differences of glycemic control markers as well as the characteristics of each marker. Second, we point out the limitation of A1C, introduce GA as an alternative indicator, and discuss the limitations of GA. Finally, we summarize important evidence regarding the utility of GA. We hope that this review provides useful information that permits more effective usage of GA as well as other glycemic control markers.     

Molecular diagnosis of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinomas (iCCA) are primary intrahepatic malignancies originating from biliary epithelia. While both hepatocellular cancer and iCCA can present as mass lesions within the liver, these cancers are distinct in their morphology, etiology, pathology, natural history and response to therapy. There is a need for accurate and sensitive molecular markers for the diagnosis of iCCA. Recent advances in elucidating molecular and genetic characteristics of iCCA offer the potential of molecular‐based diagnosis of iCCA. Specific genetic mutations of IDH1/2, BAP1, p53, and KRAS, FGFR gene fusions and alterations in microRNA have all been described in iCCA. Although there are no accurate serum or biliary biomarkers currently available for diagnosis of iCCA, several potential candidates have been identified. Knowledge of specific genetic or molecular abnormalities offers potential for individualized approaches for the treatment of patients with iCCA in the future.     

糖尿病筛查与诊断方法的争议

及时筛查、正确诊断是糖尿病治疗的关键环节,近年来,不同国际组织美国糖尿病协会（ADA）,WHO以及日本糖尿病协会（JDS）等在糖尿病诊断和筛查方面如糖尿病及糖尿病前期诊断切点的设立,糖化血红蛋白（HbA1C）在筛查与诊断中的应用价值等都存在争议。根据糖尿病发展的病理生理机制和基于血糖范围和糖尿病并发症危险的大规模的流行病学研究结果,设置适合各国人群的糖尿病诊断和筛查标准是当前亟待解决的问题。