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[New Horizon in Clinical Examination -Chairmen's Introductory Remarks -]. [临床检查新视野-主席导言-]。
Kaname Nakatani, Takashi Ishikawa

Translational research is leading to new technology and generating in practical diagnostic tests with clinical utility. This paper introduces three cutting-edge technologies: liquid biopsy, amino acid profiling, and con- tinuous glucose monitoring (CGM). Liquid biopsy was reviewed as one of the "10 Breakthrough Technologies in 2015" by MIT. This technol- ogy is based on fast DNA-sequencing machines or high-sensitivity PCR and non-invasive tests that detect fragments of DNA or cells in blood or other bodily fluids. Cell-free DNA refers to segments of DNA that are mainly derived from apoptotic and necrotic cells, and it is used for the detection and monitoring of cancer. Profiling of plasma-free amino acid is a promising approach because amino acid profiling links all organ sys- tems and amino acids have important roles in metabolism. Furthermore, amino acid profiles are known to be influenced by specific diseases, including cancers. CGM systems use a tiny sensor inserted under the skin to continuously check glucose levels in tissue fluid and convert blood glucose levels. CGM can provide valuable information at any points during the day and facilitate better treatment decisions and glucose control. [Review].

转化研究正在引领新技术并产生具有临床效用的实际诊断测试。本文介绍了三种前沿技术:液体活检、氨基酸谱分析和连续血糖监测(CGM)。液体活检被麻省理工学院评为“2015年十大突破性技术”之一。这项技术是基于快速DNA测序仪或高灵敏度PCR和非侵入性检测,检测血液或其他体液中的DNA片段或细胞。无细胞DNA是指主要来源于凋亡和坏死细胞的DNA片段,用于癌症的检测和监测。血浆游离氨基酸谱分析是一种很有前途的方法,因为氨基酸谱分析连接了所有器官系统,氨基酸在代谢中具有重要作用。此外,氨基酸谱已知会受到特定疾病的影响,包括癌症。CGM系统使用一个插入皮肤下的微小传感器来连续检查组织液中的葡萄糖水平并转换血糖水平。CGM可以在一天中的任何时间点提供有价值的信息,促进更好的治疗决策和血糖控制。(审查)。
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引用次数: 0
[Functional Residual Capacity Measurement Based on Lung Structure Model Analysis Using the Helium Gas Dilution Technique]. [基于氦气稀释技术肺结构模型分析的功能剩余容量测定]。
Hiroyasu Oe, Yusuke Nakade, Masako Nakata, Yuko Nanbu, Mikio Nagahara, Mika Mori

In the helium gas dilution method, functional residual capacity (FRC) is calculated from a helium concentra- tion equilibrium curve. In this study, we analyzed the helium concentration equilibrium curves of healthy patients, clarified the determinants of the equilibrium concentration, and studied the effects of an uneven lung distribution. We collected data from 200 patients (92 males and 108 females) whose FRC values had been measured at our institution over the past 6 years. Their FRC values ranged from 80% to 120%, and theit other pulmo- nary function values were within the normal range. In the compartmental model analysis, we discovered that the helium concentration equilibrium curve was composed of one compartment, and that it did not have a polyphasic structure. Each 0.25-minute (15-second) segment of the helium concentration equilibrium curve obtained from the patients was evaluated using univariate and multivariate regression analyses. The helium concentration equilibrium curve decreased exponentially over the time course of the analysis, and the multiple correlation coefficient for the relationship between the 0.25-minute to 0.75-minute segments and the 1.00-minute to 1.50-minute segments in the final model was 0.949. Finally, we examined the influence of an uneven peripheral lung distribution. A model based on the con- centration change seen between the initial and middle periods during at rest ventilation indicated that the latter parameter was not affected by the ventilation volume of the peripheral lung. [Original].

在氦气稀释法中,从氦气浓度平衡曲线计算功能剩余容量(FRC)。在本研究中,我们分析了健康患者的氦浓度平衡曲线,澄清了平衡浓度的决定因素,并研究了肺分布不均匀的影响。我们收集了200名患者(92名男性和108名女性)的数据,这些患者在过去6年中在我们的机构测量了FRC值。FRC值为80% ~ 120%,其他肺功能值均在正常范围内。在室室模型分析中,我们发现氦浓度平衡曲线由一个室室组成,而不具有多相结构。每0.25分钟(15秒)的氦浓度平衡曲线段通过单变量和多变量回归分析进行评估。在分析过程中,氦浓度平衡曲线呈指数递减,最终模型中0.25 ~ 0.75分钟段与1.00 ~ 1.50分钟段关系的多重相关系数为0.949。最后,我们检查了周围肺分布不均匀的影响。基于静息通气初期和中期浓度变化的模型表明,后一参数不受周围肺通气量的影响。(最初的)。
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引用次数: 0
[Clinical Use of Presepsin Compared with That of Procalcitonin in Children with Sepsis]. [Presepsin与降钙素原在脓毒症患儿中的临床应用比较]。
Kaori Nakanishi, Satomi Kasashima, Yuko Ishii, Hirokazu Shimoeda, Atsuhiro Kawashima

Diagnosing sepsis can be very difficult and without prompt treatment, sepsis frequently results in death. No definitive biomarker for diagnosing sepsis currently exists, although the use of various biomarkers, includ- ing procalcitonin (PCT), as diagnostic indicators has been considered valuable. The biomarker presepsin (P- SEP) has gained attention as a diagnostic tool for sepsis since health insurance coverage approval in Japan in 2014. In this study, we categorized 156 children into five groups based on the presence or absence of sys- temic inflammatory response syndrome and infection, and compared the levels of P-SEP and PCT among these groups. Furthermore, they were categorized into five groups based on the diagnosed disease, and the P-SEP and PCT levels were compared among these groups. The P-SEP levels exceeded the cut-off value in all patients with sepsis, and patients of other groups hardly exceeded the cut-off value. In contrast, the PCT levels increased in patients with sepsis, but those in other groups, particularly in local infection, also exceed- ed the cut-off value. Similarly, during the diagnosed disease classification, PCT levels also increased in Ka- wasaki disease. In conclusion, P-SEP could be a useful biomarker for the diagnosis of sepsis in children and should be studied further. [Short Communication].

诊断败血症非常困难,如果不及时治疗,败血症往往会导致死亡。目前还没有诊断败血症的明确生物标志物,尽管使用各种生物标志物,包括降钙素原(PCT),作为诊断指标被认为是有价值的。自2014年日本批准健康保险覆盖以来,生物标志物presepsin (P- SEP)作为败血症的诊断工具受到了关注。在这项研究中,我们根据是否存在系统性炎症反应综合征和感染将156名儿童分为五组,并比较了这些组的P-SEP和PCT水平。并根据诊断的疾病分为5组,比较各组间P-SEP和PCT水平。脓毒症患者P-SEP水平均超过临界值,其他组患者P-SEP水平几乎不超过临界值。相比之下,脓毒症患者的PCT水平升高,但其他组,特别是局部感染患者的PCT水平也超过了临界值。同样,在诊断疾病的分类过程中,卡wasaki病的PCT水平也升高。综上所述,P-SEP可作为诊断儿童脓毒症的一种有用的生物标志物,值得进一步研究。简短的沟通。
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引用次数: 0
[Discussion of Routine Laboratory Data of a Patient Complaining of Back Pain and General Fatigue]. 【对1例主诉背部疼痛和全身疲劳患者的常规实验室资料的讨论】。
Naotake Satoh, Mitsuru Yanai, Masahiro Ebashi, Yuta Hayashi, Akiko Masuda, Junko Murakami, Naoto Hosokawa

Conventional reversed clinicopathological conference (RCPC) is an educational method to interpret labora- tory data. In this RCPC, physicians and several specialists in laboratory medicine discussed laboratory data of a patient with tuberculous spondylitis who complained of back pain and general fatigue. Then, they and the moderators held a question-and-answer session with an audience in a hall, and they tried to understand the detailed state of the patient. This discussion revealed the usefulness of RCPC to elucidate the clinical state of patient. At the same time, we can understand the limits of laboratory data analysis. [Review].

常规反向临床病理会议(RCPC)是一种解释实验室数据的教育方法。在这个RCPC中,医生和几位检验医学专家讨论了一位结核性脊柱炎患者的实验室数据,该患者主诉背部疼痛和全身疲劳。然后,他们和主持人在大厅里与观众进行了问答环节,他们试图了解病人的详细状态。这一讨论揭示了RCPC对阐明患者临床状态的有用性。同时,我们可以理解实验室数据分析的局限性。(审查)。
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引用次数: 0
[Usefulness of Glycemic Control Utilizing CGM and Future Prospects]. [利用CGM控制血糖的有效性及未来展望]。
Daisuke Tsuriya, Masato Maekawa

The maintenance of the QOL by preventing the onset and progression of arteriosclerosis-related complica- tions such as a stroke and myocardial infarction is very important in the treatment of diabetes. However, recent large clinical trials reported that aggressively reducing the HbAlc level by the use of insulin or oral antidiabetic agents increased severe hypoglycemia, resulting in cardiovascular events and deaths. A "good quality of glycemic control" that improves postprandial hyperglycemia without hypoglycemia is required for the treatment of diabetes, and confirmation of the fluctuations in blood glucose for 24 hours using CGM (continuous glucose-monitoring) is now attracting marked attention. The introduction of CGM is use- ful for the patient to understand the effect of drugs and get more motivated for the treatment. Furthermore, real-time CGM provides a value of blood glucose on the spot, resulting in strict glycemic control. A sensor- augmented pump (SAP) was released last year in Japan, and patients have been able to confirm their blood glucose level in real time and adjust the amount of insulin timely. Such a new glucose-monitoring system is emerging. It does not need the drawing of blood from the finger- tip by a puncture needle, requiring only the attachment of a sensor to the outside of the upper arm, and linking a hand-held reader to the sensor could provide cumulative data with a frequency of every 15 min for up to 8 h. We expect such new devices to provide the level of blood glucose in real time to improve therapy. [Review].

通过预防动脉硬化相关并发症如中风和心肌梗死的发生和发展来维持生活质量在糖尿病的治疗中是非常重要的。然而,最近的大型临床试验报告,通过使用胰岛素或口服降糖药来积极降低HbAlc水平会增加严重低血糖,导致心血管事件和死亡。糖尿病的治疗需要“高质量的血糖控制”,即改善餐后高血糖而不出现低血糖,使用连续血糖监测(CGM)确认24小时的血糖波动正引起人们的极大关注。CGM的引入有助于患者了解药物的效果,并更积极地进行治疗。此外,实时CGM提供了一个现场血糖值,从而实现严格的血糖控制。日本去年推出了传感器增强泵(SAP),患者可以实时确认自己的血糖水平,并及时调整胰岛素量。这样一种新的血糖监测系统正在出现。它不需要用穿刺针从指尖抽血,只需要将传感器连接到上臂外部,并将手持式读取器连接到传感器上,可以以每15分钟的频率提供累积数据,最长可达8小时。我们期望这种新设备能够实时提供血糖水平,以改善治疗。(审查)。
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引用次数: 0
Relationship between Pericardial Adipose Tissue Thickness and Early Impairment of Left Ventricular Function, Both Evaluated on Echocardiography. 超声心动图评价心包脂肪组织厚度与早期左心室功能损害的关系。
Aeka Fujino, Tomonori Kishino, Keiko Watanabe, Kumiko Sekiguchi, Yasushi Takagi, Satsuki Matsushima, Kouki Ohtsuka, Masayuki Yotsukura, Hiroaki Ohnishi, Takashi Watanabe

Epicardial adipose tissue (EAT) is metabolically bioactive, and accumulation of this tissue is related to early impairment of left ventricular (LV) systolic function as well as diastolic function. However, pericardial adi- pose tissue (PAT), located outside the EAT, has recently been demonstrated to be more closely associated with metabolic risk factors than EAT. The present study aimed to clarify whether PAT thickness is related to early impairment of LV function in a similar manner to EAT thickness, with both evaluated echocardio- graphically. Subjects were 49 women (mean age, 68ill years) composed of both patients with metabolic diseases and those with other diseases, and ejection fraction (EF) >55%. Systolic function was assessed by measuring EF, systolic mitral annular velocity (S'), and tissue mitral annular displacement percentage (TMAD%). Diastolic function was assessed by measuring early rapid filling wave velocity (E)/late filling wave velocity due to atrial contraction (A) ratio (E/A), peak early diastolic mitral annular velocity (e'), and E/e' ratio. Correlations between EAT or PAT thickness and LV systolic or diastolic function were assessed. EAT thickness correlated with S' and TMAD%(r=-0.399, p=0.005 and r=-0.570, p<0.001, respective- ly), but not with EF. However, PAT thickness was not correlated with any of these. EAT thickness corre- lated with E/A, e' and E/e'(r=-0.382, p=0.007; r=-0.493, p<0.001; and r=0.331, p=0.020, respective- ly). Again, PAT thickness was not correlated with any of these. PAT thickness appears unrelated to early impairment of LV function.

心外膜脂肪组织(EAT)具有代谢生物活性,该组织的积累与左心室(LV)收缩功能和舒张功能的早期损害有关。然而,位于EAT外的心包脂肪组织(PAT)最近被证明与代谢危险因素的关系比EAT更密切。本研究旨在通过超声心动图评估PAT厚度是否与早期左室功能损害相关,其方式与EAT厚度相似。受试者为49名女性,平均年龄68岁,既有代谢性疾病患者,也有其他疾病患者,射血分数(EF) >55%。通过测量EF、收缩二尖瓣环速度(S')和组织二尖瓣环位移百分比(TMAD%)来评估收缩功能。通过测量心房收缩引起的早期快速充盈波速度(E)/晚期充盈波速度(A)比(E/A)、舒张早期尖峰二尖瓣环速度(E′)和E/ E′比来评估舒张功能。评估EAT或PAT厚度与左室收缩或舒张功能的相关性。EAT厚度与S′和TMAD%相关(r=-0.399, p=0.005和r=-0.570, p= 0.05)
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引用次数: 0
[Effects of Aging and Sex Differences on the Median Nerve: Relationship Between Nerve Conduction Study and Ultrasonographic Cross-Sectional Nerve Area]. [年龄和性别差异对正中神经的影响:神经传导研究与超声横断神经面积的关系]。
Daisuke Ito, Tsuneo Watanabe, Akihiro Hirakawa, Ako Ito, Yuzuru Nohisa, Nobuyuki Furuta, Mitsuru Seishima

Objective: The aim of this study was to evaluate the relationship between nerve conduction and sonographic measurements of the median nerve, and to investigate the effects of aging and sex on nerve structure.

Methods: Measurements from both hands of 82 healthy volunteers were included in this study (45 men and 37 women, 38.9 ?17.7 years). The cross-sectional area(CSA) of the median nerve was evaluated at the carpal tunnel inlet (MA) and at the midpoint of the forearm (MB).

Results: The CSA of the median nerve at the MA was significantly correlated with age (r=0.501, P< 0.001), and distal motor latency (r=0.269, P<0.001). Although this study demonstrated the effects of the sex dif- ferences and aging on the CSA of the median nerve at MA, there was no significant effect at the MB.

Conclusions: Our study suggests that aging could affect median nerve structure, especially at the anatomical entrapment point. [Original].

目的:探讨正中神经超声测量与神经传导的关系,探讨年龄和性别对正中神经结构的影响。方法:82例健康志愿者(男性45例,女性37例,年龄38.9 ~ 17.7岁)双手测量数据纳入本研究。在腕管入口(MA)和前臂中点(MB)处评估正中神经的横截面积(CSA)。结果:MA处正中神经CSA与年龄(r=0.501, P< 0.001)和远端运动潜伏期(r=0.269, P)显著相关。结论:我们的研究表明,年龄会影响正中神经结构,特别是在解剖夹持点。(最初的)。
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引用次数: 0
[Clinical Application of Cancer Molecular Diagnostics with Liquid Biopsy]. 【液体活检在肿瘤分子诊断中的临床应用】。
Mamoru Kubota

"Liquid biopsy" is one of the hottest topics in the cancer molecular diagnostics field because of its potential to replace conventional tissue biopsy. "BEAMing" is one of the digital PCR platform technologies for liquid biopsy samples, and it features a high enough sensitivity to detect a very low concentration of mutation frag- ments in circulating tumor DNA from the plasma of cancer patients. In this article, some of the promising clinical applications of BEAMing technology and its future possibilities as an advanced cancer diagnostic will be briefly summarized. [Review].

“液体活检”是癌症分子诊断领域最热门的话题之一,因为它有可能取代传统的组织活检。“BEAMing”是液体活检样本的数字PCR平台技术之一,它具有足够高的灵敏度,可以检测癌症患者血浆中循环肿瘤DNA中极低浓度的突变片段。在本文中,简要总结了一些有前景的临床应用,以及它作为晚期癌症诊断的未来可能性。(审查)。
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引用次数: 0
Can Plasma Free Amino Acid Profiling Be Used to Assess Cancer Risk?. 血浆游离氨基酸谱分析可用于评估癌症风险吗?
Toshihiko Ando

Amino acids are present in the blood. In healthy people, the concentrations of these amino acids in the blood are maintained at stable levels. However, different diseases disturb the balance of amino acids in the blood in different ways. AminoIndex® is a service that uses the latest medical technology to measure the concentration of amino acids in the blood to check a person's health and detect various diseases. It is now possible to conduct an AminoIndex® Cancer Screening (AICS®) test that can detect cancer from early stages. The AICS® measures the concentrations of amino acids in the blood and statistically analyzes the differ- ences in the balance of amino acid concentrations between healthy people and those with cancer. As a result, we can simultaneously screen for certain types of cancer. Currently, the test can screen for gastric cancer, lung cancer, colorectal cancer, prostate cancer (in males), breast cancer (in females), and uterine/ovarian cancer* (in females). The application of AminoIndex® technology will spread through the fields of medicine, such as in the treat- ment of metabolic syndrome. (*The uterine/ovarian cancer test determines the overall risk of having any of the three cancers: cervical cancer, endometrial cancer, and ovarian cancer, and can not determine the individual risk of having each cancer.) [Review].

氨基酸存在于血液中。在健康人群中,这些氨基酸在血液中的浓度保持在稳定的水平。然而,不同的疾病会以不同的方式扰乱血液中氨基酸的平衡。AminoIndex®是一项使用最新医疗技术测量血液中氨基酸浓度的服务,以检查一个人的健康状况并检测各种疾病。现在有可能进行AminoIndex®癌症筛查(AICS®)测试,可以从早期阶段检测癌症。AICS®测量血液中氨基酸的浓度,并统计分析健康人与癌症患者之间氨基酸浓度平衡的差异。因此,我们可以同时筛查某些类型的癌症。目前,该检测可筛查胃癌、肺癌、结直肠癌、前列腺癌(男性)、乳腺癌(女性)和子宫/卵巢癌*(女性)。AminoIndex®技术的应用将遍及医学领域,如代谢综合征的治疗。(*子宫癌/卵巢癌检查确定罹患宫颈癌、子宫内膜癌和卵巢癌这三种癌症中的任何一种的总体风险,但不能确定罹患每种癌症的个体风险。)[回顾]。
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引用次数: 0
[Contribution of In- Vitro Diagnostics to Effective Use of Therapeutic Drugs -Perspectives from IVD Industry-]. 体外诊断对有效使用治疗药物的贡献——来自体外诊断行业的观点——。
Shinichi Eda

The recent development of innovative therapeutic drugs has changed the relationship between diagnostics and therapeutic drugs. One of the major changes is personalized healthcare and companion diagnostics; many of innovative drugs such as Herceptin, Alectinib, and Atezolizumab have been developed and launched together with their corresponding companion diagnostics. Another aspect of the recent innovative drugs is the utilization of high-level biotechnology and develop- ment of antibody-based therapeutic drugs. Antibody-based drugs often induce heterophilic antibodies such as human anti-mouse antibody (HAMA). Taking this into account, the interference of HAMA is investigated intensively during the development of in-vitro diagnostics, and it is eliminated by employing countermeasures such as the addition of quench proteins, and utilization of fragmented antibodies as well as chimera-antibodies. With those measures, the incidence of interference can be reduced to acceptable levels and the assays can generate reliable results, which contribute to beneficial therapy. On the other hand, the recent development of innovative unique therapeutic drugs sometimes leads to interference in diagnostic assays, which were not expected during development. One example is interference observed in the BNP assay induced by a new drug for heart failure: angiotensin receptor-neprilysin inhibitor (ARNI). When patients take ARNI, BNP values increase instead of the improved condition of heart failure. Due to this observation, NT-proBNP, which is unaffected by ARNI, is usually used for monitoring the effect of the drug. The issue of drug-resistant bacteria is also discussed in conjunction with the potential contribution of diag- nostics for the effective use of antimicrobial agents. [Review].

近年来创新治疗药物的发展改变了诊断学与治疗药物之间的关系。其中一个主要变化是个性化医疗保健和伴随诊断;许多创新药物,如赫赛汀(Herceptin)、阿勒替尼(Alectinib)和阿特唑单抗(Atezolizumab),已与相应的伴随诊断一起开发和推出。近年来创新药物的另一个方面是利用高水平的生物技术和开发基于抗体的治疗药物。以抗体为基础的药物通常会诱导异亲性抗体,如人抗小鼠抗体(HAMA)。考虑到这一点,在体外诊断的发展过程中,对HAMA的干扰进行了深入的研究,并通过采用诸如添加猝灭蛋白、利用碎片化抗体和嵌合体抗体等对策来消除HAMA。有了这些措施,干扰的发生率可以降低到可接受的水平,检测可以产生可靠的结果,这有助于有益的治疗。另一方面,最近创新独特治疗药物的发展有时会导致诊断分析的干扰,这是在开发过程中没有预料到的。一个例子是在一种治疗心力衰竭的新药——血管紧张素受体-neprilysin抑制剂(ARNI)诱导的BNP检测中观察到的干扰。当患者服用ARNI时,BNP值升高而不是心力衰竭的改善。由于这一观察结果,NT-proBNP不受ARNI影响,通常用于监测药物的效果。本文还讨论了耐药细菌的问题,以及诊断对抗菌药物有效使用的潜在贡献。(审查)。
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引用次数: 0
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Rinsho byori. The Japanese journal of clinical pathology
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