Marker

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  • 文章类型: Journal Article
    海洋无脊椎动物干细胞(MISC)代表了一类不同的多能和全能细胞,具有自我更新和分化为多个胚层的显着能力,类似于脊椎动物。这些独特的细胞在生物体的成年生活中持续存在,并在各种成年海洋无脊椎动物门中观察到。MISC在许多生物过程中发挥关键作用,包括海洋无脊椎动物特有的发育生物学现象,比如衰老,延迟衰老,全身再生,和无性繁殖。此外,它们是研究干细胞生物学的有价值的模型。尽管意义重大,有关MISC的信息在科学文献中仍然很少且分散。在这次审查中,通过阅读研究和检测各种海洋无脊椎动物中MISC的文章,我们仔细收集和总结了有关MISC检测的有价值的信息。该综述首先定义了MISC,并突出了它们与脊椎动物相比的独特特征。然后讨论了无脊椎动物和脊椎动物研究中MISC检测和体外技术的常见标记。这篇全面的综述为研究人员和科学家提供了一个连贯而简洁的MISC特征概述,检测方法,以及海洋无脊椎动物生物中相关的生物现象。我们的目标是为对海洋无脊椎动物干细胞感兴趣的研究人员和科学家提供宝贵的资源,促进更好地理解它们在生物学中的更广泛含义。随着科学技术的不断进步和对海洋无脊椎动物物种的不断探索,我们预计进一步的发现将扩大我们对MISC的认识及其在生物学中的更广泛意义.
    Marine invertebrate stem cells (MISCs) represent a distinct category of pluripotent and totipotent cells with remarkable abilities for self-renewal and differentiation into multiple germ layers, akin to their vertebrate counterparts. These unique cells persist throughout an organism\'s adult life and have been observed in various adult marine invertebrate phyla. MISCs play crucial roles in numerous biological processes, including developmental biology phenomena specific to marine invertebrates, such as senescence, delayed senescence, whole-body regeneration, and asexual reproduction. Furthermore, they serve as valuable models for studying stem cell biology. Despite their significance, information about MISCs remains scarce and scattered in the scientific literature. In this review, we have carefully collected and summarized valuable information about MISC detection by perusing the articles that study and detect MISCs in various marine invertebrate organisms. The review begins by defining MISCs and highlighting their unique features compared to vertebrates. It then discusses the common markers for MISC detection and in vitro techniques employed in invertebrate and vertebrates investigation. This comprehensive review provides researchers and scientists with a cohesive and succinct overview of MISC characteristics, detection methods, and associated biological phenomena in marine invertebrate organisms. We aim to offer a valuable resource to researchers and scientists interested in marine invertebrate stem cells, fostering a better understanding of their broader implications in biology. With ongoing advancements in scientific techniques and the continued exploration of marine invertebrate species, we anticipate that further discoveries will expand our knowledge of MISCs and their broader implications in biology.
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  • 文章类型: Journal Article
    在生物医学发展领域,细胞外囊泡(EV)正在彻底改变我们的诊断能力,监视器,并预测疾病进展。然而,由于目前的分离技术,电动汽车的综合探索和临床应用面临着巨大的局限性。尺寸排阻色谱法,商业沉淀剂,经常使用超速离心,需要熟练的操作员,并带来与一致性相关的挑战,再现性,质量,和产量。值得注意的是,当处理可获得有限的临床样本时,细胞外囊泡分离的巨大挑战仍然存在.本研究通过旨在设计一种快速、用户友好,和为血液样本量身定制的高回收率电动汽车分离技术。与目前的方法相比,NTI-EXO沉淀法证明血清EV的回收率增加了5倍。重要的是,我们说明,仅仅两滴血液(~100µL)就足以回收富集的电动汽车。严格评估了这些孤立电动汽车的完整性和质量,纯度,和污染物。该方法通过从器官移植受者中成功分离EV以检测疾病特异性外泌体标志物得到验证,包括LKB1,SARS-CoV-2刺突蛋白,PD-L1总之,NTI-EXO方法可用于小的临床样本,从而推进以电动汽车为中心领域的发现,推动生物医学研究和临床应用的前沿。
    In the realm of biomedical advancement, extracellular vesicles (EVs) are revolutionizing our capacity to diagnose, monitor, and predict disease progression. However, the comprehensive exploration and clinical application of EVs face significant limitations due to the current isolation techniques. The size exclusion chromatography, commercial precipitation reagents, and ultracentrifugation are frequently employed, necessitating skilled operators and entailing challenges related to consistency, reproducibility, quality, and yields. Notably, the formidable challenge of extracellular vesicle isolation persists when dealing with clinical samples of limited availability. This study addresses these challenges by aiming to devise a rapid, user-friendly, and high-recovery EVs isolation technique tailored for blood samples. The NTI-EXO precipitation method demonstrated a 5-fold increase in the recovery of serum EVs compared to current methodologies. Importantly, we illustrate that a mere two drops of blood (∼100 µL) suffice for the recovery of enriched EVs. The integrity and quality of these isolated EVs were rigorously assessed for the size, purity, and contaminants. This method was validated through the successful isolation of EVs from organ transplant recipients to detect disease-specific exosomal markers, including LKB1, SARS-CoV-2 spike protein, and PD-L1. In conclusion, NTI-EXO method can be used for small clinical samples, thereby advancing discoveries in the EV-centric domain and propelling the frontiers of biomedical research and clinical applications.
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  • 文章类型: Journal Article
    据报道,IL1RL2在多种肿瘤类型中高表达,而其在膀胱癌(BLCA)中的作用尚不清楚。本研究旨在探讨Il1RL2在BLCA中的预后价值及其与临床病理特征的关系。癌症基因组图谱(TCGA)数据库用于评估BLCA组织和细胞中IL1RL2的表达水平,通过逆转录定量聚合酶链反应和蛋白质印迹进行验证。采用免疫组织化学方法分析IL1RL2基因在17对肿瘤和正常标本中的表达,以及112个不同阶段和等级的肿瘤样本。探讨Il1RL2在BLCA中的生物学功能,进行了共表达网络和功能富集分析。使用相互作用基因搜索工具构建了蛋白质-蛋白质相互作用网络。IL1RL2在BLCA细胞和组织中明确表达。在TCGA数据库中,IL1RL2扩增区分肿瘤和正常组织的曲线下面积为0.700(95%CI:0.579-0.821),在密云图数据库中为0.647(95%CI:0.497-0.797)。分别。此外,在我们的数据库中,单因素和多因素分析均表明IL1RL2表达是总生存期(OS)的独立危险因素.Kaplan-Meier生存分析揭示了高IL1RL2表达和低OS之间的关联。通路富集分析表明IL1RL2通过MAPK信号通路参与肿瘤进展的调控。IL1RL2的表达水平与分期有关,grade,淋巴结和BLCA的预后。
    IL1RL2 has been reported to be highly expressed in a variety of tumor types whereas its role in bladder cancer (BLCA) remains unclear. The aim of the present study was to explore the prognostic value of Il1RL2 in BLCA and its relationship with clinical pathological features. The Cancer Genome Atlas (TCGA) database was used to assess the levels of IL1RL2 expression in BLCA tissues and cells, which were validated by reverse transcription-quantitative polymerase chain reaction and western blotting. Immunohistochemistry was employed to analyze expression of the IL1RL2 gene in 17 pairs of tumor and normal specimens, as well as 112 samples with different stages and grades of tumors. To investigate the biological functions of Il1RL2 in BLCA, co-expression networks and functional enrichment analyses were conducted. A protein-protein interaction network was constructed using interaction gene search tools. IL1RL2 was revealed to be clearly expressed in BLCA cells and tissues. The area under the curve for amplification of IL1RL2 distinguishing between tumor and normal tissues was 0.700 (95% CI: 0.579-0.821) in the TCGA database and 0.647 (95% CI: 0.497-0.797) in Miyun chart database, respectively. Furthermore, in our database, both univariate and multivariate analyses indicated that IL1RL2 expression was an independent risk factor for overall survival (OS). Kaplan-Meier survival analysis revealed an association between high IL1RL2 expression and low OS. Pathway enrichment analysis suggested that IL1RL2 is involved in the regulation of tumor progression through the MAPK signaling pathway. The expression level of IL1RL2 was associated with the stage, grade, lymph node album and prognosis of BLCA.
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  • 文章类型: Journal Article
    超声检查更常用于动静脉瘘(AVF)狭窄患者。这项研究的目的是使用超声参数来预测接受超声引导的经皮腔内血管成形术(PTA)治疗的静脉瓣膜相关狭窄(VVRS)的血液透析患者的主要通畅性。
    共纳入在2017年1月至2021年12月期间接受PTA的229例VVRS患者。回顾性收集临床特征。在PTA之前和之后测量超声参数。进行单变量和多变量Cox分析以确定与原发性通畅率相关的独立因素。
    与PTA之前相比,PTA之后所有测得的超声图像参数都得到了改善。在PTA之前,VVRS的直径>1.0mm,年龄≤57岁,体重指数(BMI)>21.57kg/m2与更好的结局相关。而桡动脉的直径,靠近吻合口的近端桡动脉,肱动脉,肱动脉的流量,VVRS的长度和峰值速度(PV),VVRS后的直径和PV与主要通畅率无关。PTA之后,只有VVRS直径>4.0mm的患者有良好的预后.此外,PTA后VVRS直径增加>2.4mm的患者有更好的结局趋势.
    PTA前后VVRS的直径可以作为预测VVRS的AVF患者的初次通畅率和二次通畅率的指标。VVRS的直径增益也可以是潜在的标记。
    结论:使用简单的超声参数标记,我们可以快速识别再狭窄风险较高的患者.在早期再狭窄的情况下,应更密切地随访这些患者。它也有利于预防血栓形成。这些措施有助于为长期透析保留更有价值的血管。此外,医生应该更加注意这些危险患者的透析相关并发症,如血液透析相关的低血压。
    UNASSIGNED: Ultrasonography is more frequently used in patients with arteriovenous fistula (AVF) stenosis. The aim of this study is to use sonographic parameters for predicting primary patency in hemodialysis patients with venous valve-related stenosis (VVRS) who are treated by ultrasound-guided percutaneous transluminal angioplasty (PTA).
    UNASSIGNED: A total of 229 VVRS patients who underwent PTA between January 2017 and December 2021 were enrolled. Clinical characteristics were retrospectively collected. Sonographic parameters were measured both before and after PTA. Univariate and multivariate Cox analyses were performed to identify independent factors associated with primary patency rate.
    UNASSIGNED: All measured sonographic parameters improved after PTA compared to before PTA. Before PTA, the diameter of VVRS > 1.0 mm, age ≤ 57 years, and body mass index (BMI) > 21.57 kg/m2 were associated with better outcomes. While the diameter of radial artery, proximal radial artery close to the anastomosis, brachial artery, the flow volume of brachial artery, the length and peak velocity (PV) of the VVRS, and the diameter and PV after the VVRS had no association with the primary patency rate. After PTA, only patients with a diameter of VVRS > 4.0 mm had favorable outcome. In addition, patients with a gain of diameter of VVRS > 2.4 mm after PTA had a trend of better outcomes.
    UNASSIGNED: The diameter of VVRS before and after PTA could be served as markers to predict primary patency rate and second patency rate in AVF patients with VVRS. The gain of diameter of VVRS could also be a potential marker.
    CONCLUSIONS: Using simple markers of sonographic parameters, we could quickly identify patients with a higher risk of restenosis. These patients should be followed more closely in case of restenosis at early. It is also beneficial to the prevention of thrombosis. These measures help to preserve more valuable vascular for a long-term dialysis. Additionally, the physician should pay more attention on the dialysis-related complications in these risky patients, such as hemodialysis-related hypotension.
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  • 文章类型: Journal Article
    一些研究已经调查了血清乳酸脱氢酶与白蛋白比率(LAR)与癌症预后之间的关系。然而,尚无研究探讨血清LAR与口腔癌(OC)生存率之间的关系。本研究旨在确定血清LAR与OC总生存期(OS)的相关性。
    在2018年1月至2019年12月期间,有190例OC患者被纳入本研究。采用Logrank检验和Kaplan-Meier法比较低LAR组与高LAR组的OC生存率。通过单变量和多变量Cox回归分析确定血清LAR与OC患者生存率之间的关联。
    Kaplan-Meier分析和Log秩检验表明,低LAR组的OS率明显高于高LAR组(P<0.05)。单因素Cox分析显示TNMIII-IV期,血清LDH>162U/L,血清LAR>3.79与OC患者的OS显著相关。多变量Cox分析表明TNMIII-IV期(HR,2.317;95%CI,1.423-3.774,P=0.001),血清LAR>3.79(HR,5.138;95%CI,2.245~11.756,P=0.000)与OC患者OS差独立相关。
    高血清LAR(>3.79)是OC患者不良预后的独立预测因子。LAR可以作为预测OC患者OS的一个有希望的标志物。
    UNASSIGNED: Several studies have investigated the relationship between serum lactate dehydrogenase-to-albumin ratio (LAR) and the prognosis of cancers. However, no studies have explored the association between serum LAR and the survival of oral cancer (OC). This study was aimed to determine the association of serum LAR with the overall survival (OS) of OC.
    UNASSIGNED: One hundred and ninety patients with OC were included in this study between January 2018 and December 2019. Log rank test and Kaplan-Meier method were used to compare the survival rate of OC between the low LAR group and the high LAR group. The association between serum LAR and the survival of OC patients was determined via univariate and multivariate Cox regression analyses.
    UNASSIGNED: Kaplan-Meier analysis and Log rank test indicated that the OS rate in low LAR group was significantly higher than that in high LAR group (P < 0.05). Univariate cox analysis showed that TNM III-IV stage, serum LDH > 162 U/L, and serum LAR > 3.79 were significantly associated with the OS of OC patients. Multivariate Cox analysis suggested that the TNM III-IV stage (HR, 2.317; 95% CI, 1.423-3.774, P = 0.001) and serum LAR > 3.79 (HR, 5.138; 95% CI, 2.245-11.756, P = 0.000) were independently related with poor OS of OC patients.
    UNASSIGNED: High serum LAR (>3.79) is an independent predictor of adverse prognosis in OC patients. LAR could be used as a promising marker for predicting the OS of OC patients.
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  • 文章类型: Journal Article
    阻碍红色荧光蛋白在快速发展的线虫C.elegans中使用的一个问题是几代红色荧光团成熟的显著时间延迟。最近描述的mScarlet-I3蛋白具有可以克服该限制的性质。我们在这里比较了CRISPR/Cas9基因组工程化mScarlet表达的亮度和开始,mScarlet3、mScarlet-I3和GFP报告基因敲入。比较编码广泛表达的高尔基体常驻蛋白的C.elegansgorg-4的报告等位基因的表达的开始和亮度,我们发现胚胎中mScarlet-I3的检测开始比旧版本的mScarlet早几个小时,并且与GFP相当。通过比较mScarlet-I3和GFP报道等位基因pks-1,在CAN神经元和消化系统细胞中表达的基因,进一步支持了这些发现。以及泛神经元的报告等位基因,核标记UNC-75.因此,mScarlet-I3和GFP的相对特性不取决于细胞或亚细胞环境。在所有情况下,mScarlet-I3报道分子与GFP相比也显示出改善的信噪比。
    One problem that has hampered the use of red fluorescent proteins in the fast-developing nematode C. elegans has been the substantial time delay in maturation of several generations of red fluorophores. The recently described mScarlet-I3 protein has properties that may overcome this limitation. We compare here the brightness and onset of expression of CRISPR/Cas9 genome-engineered mScarlet, mScarlet3, mScarlet-I3 and GFP reporter knock-ins. Comparing the onset and brightness of expression of reporter alleles of C. elegans golg-4, encoding a broadly expressed Golgi resident protein, we found that the onset of detection of mScarlet-I3 in the embryo is several hours earlier than older versions of mScarlet and comparable to GFP. These findings were further supported by comparing mScarlet-I3 and GFP reporter alleles for pks-1, a gene expressed in the CAN neuron and cells of the alimentary system, as well as reporter alleles for the panneuronal, nuclear marker unc-75. Hence, the relative properties of mScarlet-I3 and GFP do not depend on cellular or subcellular context. In all cases, mScarlet-I3 reporters also show improved signal-to-noise ratio compared to GFP.
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  • 文章类型: Journal Article
    目的:炎症参与非酒精性脂肪性肝病(NAFLD)的发生和发展。单核细胞与高密度脂蛋白胆固醇之比(MHR)已成为各种炎症相关疾病的标志物。本研究的目的是调查儿童肥胖人群中MHR和NAFLD之间的关系。
    方法:基于肝脏超声,共有504名肥胖儿童(357名患有NAFLD的儿童和147名无NAFLD的儿童)被纳入研究.通过Pearson和Spearman分析评估MHR与NAFLD危险因素之间的相关性。进行多因素逐步logistic回归分析以探讨MHR与NAFLD风险之间的关系。
    结果:NAFLD患者的MHR明显高于非NAFLD患者[0.52(0.44-0.67)对0.44(0.34-0.57),P<0.001]。多因素逐步logistic回归分析表明,MHR[比值比(OR):1.033,95%置信区间(CI):1.015-1.051;P<0.001]是儿童肥胖患者NAFLD的独立预测因子。年龄(OR:1.205,95%CI:1.059-1.371;P=0.005],腰围[OR:1.037,95%CI:1.008-1.067;P=0.012],丙氨酸转氨酶[OR:1.067,95%CI:1.045-1.089;P<0.001]。此外,校正潜在混杂因素后,MHR四分位数与NAFLD的发生率呈显著正相关。
    结论:本研究表明,MHR可作为儿童肥胖患者NAFLD的有效指标。
    OBJECTIVE: Inflammation is involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). The monocyte to high-density lipoprotein cholesterol ratio (MHR) has emerged as a marker for various inflammation-related diseases. The aim of the present study was to investigate the association between the MHR and NAFLD in a population with childhood obesity.
    METHODS: Based on hepatic ultrasound, a total of 504 children with obesity (357 with NAFLD and 147 without NAFLD) were included in the study. The correlation between the MHR and NAFLD risk factors was assessed by Pearson\'s and Spearman\'s analyses. Multivariate stepwise logistic regression analyses were conducted to explore the association between the MHR and the risk of NAFLD.
    RESULTS: The MHR in patients with NAFLD was significantly greater than that in patients without NAFLD [0.52 (0.44-0.67) versus 0.44 (0.34-0.57), P<0.001]. Multivariate stepwise logistic regression analysis demonstrated that the MHR [odds ratio (OR): 1.033, 95% confidence interval (CI): 1.015-1.051; P<0.001] was an independent predictor of NAFLD in childhood obesity patients, as were age (OR: 1.205, 95% CI: 1.059-1.371; P=0.005], waist circumference [OR: 1.037, 95% CI: 1.008-1.067; P=0.012], and alanine transaminase [OR: 1.067, 95% CI: 1.045-1.089; P<0.001]. Additionally, MHR quartiles showed a significant positive association with the incidence of NAFLD after adjusting for potential confounding factors.
    CONCLUSIONS: The present study showed that the MHR may serve as an available and useful indicator of NAFLD in individuals with childhood obesity.
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  • 文章类型: Journal Article
    探讨前蛋白转换枯草杆菌蛋白酶kexin9型(PCSK9)水平在2型糖尿病(T2D)不同阶段的糖尿病视网膜病变(DR)患者中的价值,并将这些发现与没有糖尿病(DM)的健康对照组进行比较。
    总共135名患者,其中100名是T2D患者,35名是健康对照组,被纳入这项前瞻性研究。将T2D患者分为三组:第一组包括34名T2D患者,无DR,第二组有32例非增殖性DR(NPDR),第三组有34人患有增生性DR(PDR)。分析并比较各组之间的血清PCSK9水平。
    49%的参与者是女性,平均年龄为64±9.1岁,在年龄和性别方面,四组之间没有统计学意义的结果。当评估所有组时,平均血清PCSK9值存在显着差异(p=0.01),随着DR的进展,观察到有统计学意义的变化。当评估所有T2D患者(第1、2和3组)的血清PCSK9水平时,与低密度脂蛋白呈中等水平相关性(p<0.05).
    与对照组相比,糖尿病患者的血清PCSK9值存在显著差异。临床上应谨慎考虑循环PCSK9浓度作为糖尿病性视网膜病变风险指标的有效性。
    UNASSIGNED: To investigate the value of proprotein-converting subtilisin kexin type 9 (PCSK9) levels in type 2 diabetes mellitus (T2D) patients with different stages of diabetic retinopathy (DR) and to compare these findings with a healthy control group without diabetes mellitus (DM).
    UNASSIGNED: A total of 135 patients, 100 of whom were patients with T2D and 35 of whom were in the health control group, were included in this prospective study. T2D patients were divided into three groups: the first group included 34 people with T2D without DR, the second group had 32 people with non-proliferative DR (NPDR), and the third group had 34 people with proliferative DR (PDR). Serum PCSK9 levels were analyzed and compared between the groups.
    UNASSIGNED: Forty-nine percent of the participants were female, and the mean age was 64 ± 9.1 years, with no statistically significant results between the four groups in terms of age and sex. The mean serum PCSK9 value was significantly different (p = 0.01) when all groups were evaluated, and statistically significant change was observed with the progression of DR. When serum PCSK9 levels were evaluated in all T2D patients (groups 1, 2, and 3), a medium-level correlation was observed with low-density lipoprotein (p < 0.05).
    UNASSIGNED: Serum PCSK9 values differed significantly in diabetic patients compared to the control group. One should be clinically cautious about the usefulness of circulating PCSK9 concentrations as an indicator of the risk of diabetic retinopathy.
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  • 文章类型: Journal Article
    目的:在本研究中,我们旨在比较有和无子宫腺肌病患者的血清CK-MM水平,并研究CK-MM水平是否可以作为子宫腺肌病所致子宫肌层损伤的非侵入性标志物.
    方法:我们的研究是一项在三级中心进行的前瞻性病例对照研究,根据最近发表的子宫形态学超声评估(MUSA)标准,将40例临床/超声诊断为子宫腺肌病的患者和40例无临床/超声诊断为子宫腺肌病的患者作为对照组。我们的研究包括签署自愿同意书的年龄相似的个人。人口统计,临床,并记录两组患者的实验室检查结果.血清样品用于测定我们研究中参与者的血清CK-MM水平。通过使用人CK-MM酶联免疫吸附测定(ELISA)试剂盒分析样品。
    结果:在我们的研究中,子宫腺肌病患者的平均血清CK-MM水平为16.2±21.7(ng/dL),无子宫腺肌病患者的平均血清CK-MM水平为2.6±2.2(ng/dL)。子宫腺肌病患者组的血清CK-MM水平明显高于对照组(p<0.001)。CK-MM阈值为3.43ng/mL,灵敏度为82.5%,特异性为85%,已被发现是有和没有子宫腺肌病的患者的有价值的区分水平。
    结论:在这项研究中,我们证明血清CK-MM可作为子宫腺肌病患者的非侵入性诊断方法。由于文献中围绕这一主题的研究数量不足,需要更大规模的研究来使用CK-MM作为子宫腺肌病的诊断标志物。
    OBJECTIVE: In the present study, we aimed to compare serum CK-MM levels in patients with and without adenomyosis and to investigate whether CK-MM level can be a non-invasive marker for myometrial damage due to adenomyosis.
    METHODS: Our study was a prospective case-control study in a tertiary center and consisted of 40 patients with a clinical/ultrasonographic diagnosis of adenomyosis and 40 patients without a clinical/ultrasonographic diagnosis of adenomyosis as the control group based on recently published morphological uterus sonographic assessment (MUSA) criteria. Individuals of similar age who signed a voluntary consent form were included in our study. Demographic, clinical, and laboratory findings of the patients in both groups were recorded. Blood serum samples were used for the determination of serum CK-MM levels of the participants in our study. The samples were analyzed by using the human CK-MM enzyme-linked immunosorbent assay (ELISA) kit.
    RESULTS: In our study, the mean serum CK-MM level was 16.2 ± 21.7 (ng/dL) in patients with adenomyosis and 2.6 ± 2.2 (ng/dL) in patients without adenomyosis. Serum CK-MM level was statistically significantly higher in the patient group with adenomyosis than in the control group (p < 0.001). The CK-MM threshold value of 3.43 ng/mL, with a sensitivity of 82.5% and specificity of 85%, has been found to be a valuable distinguishing level in patients with and without adenomyosis.
    CONCLUSIONS: In this study, we demonstrated that serum CK-MM can be used as a non-invasive diagnostic method in patients with adenomyosis. As the number of studies around this subject in the literature is insufficient, larger studies are needed to use CK-MM as a diagnostic marker in adenomyosis.
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  • 文章类型: Journal Article
    胆汁酸稳态对于肝脏的正常生理功能至关重要。胆汁酸谱的破坏与胆汁淤积性肝损伤的发生密切相关。作为我们诊断和治疗方法的一部分,我们旨在研究胆汁淤积期间胆汁酸谱的紊乱及其与胆汁淤积性肝损伤的相关性。在肝损伤发生之前,胆汁酸谱的变化在8和16小时之间在血浆和肝脏中检测到,持续96小时。TCA,TCDCA,和等离子体中的TUDCA,以及TCA,TUDCA,TCDCA,TDCA,TLCA,和肝脏中的THDCA,在8-16h时成为诊断ANIT引起的胆汁淤积的早期敏感和潜在标志物。ANIT引起的肝损伤的显着特征如下:T-BA超过G-BA,血清生化指标超过游离胆汁酸。值得注意的是,等离子体T-BA,特别是TCA,与血清酶活性和肝组织病理学相比,对胆汁淤积性肝毒性的敏感性更高。进一步的研究表明,TCA通过提高肝功能酶活性来加剧ANIT诱导的肝损伤,炎症,并促进胆管上皮细胞的增殖和迁移。然而,在单独用TCA治疗的大鼠中未观察到指示肝损伤的形态学变化或转氨酶活性的改变。此外,在保持胆汁酸稳态的生理条件下,胆汁酸谱或炎症反应没有变化。总之,我们的研究结果表明,牛磺酸结合胆汁酸在血浆和肝脏,特别是TCA,可以作为预测肝内胆汁淤积药物的早期和敏感的标志物,并且可以作为胆汁淤积性肝损伤进展的有效标志物。然而,在维持胆汁酸稳态的生理条件下,外源性TCA不会诱导肝损伤。
    Bile acid homeostasis is crucial for the normal physiological functioning of the liver. Disruptions in bile acid profiles are closely linked to the occurrence of cholestatic liver injury. As part of our diagnostic and therapeutic approach, we aimed to investigate the disturbance in bile acid profiles during cholestasis and its correlation with cholestatic liver injury. Before the occurrence of liver injury, alterations in bile acid profiles were detected in both plasma and liver between 8 and 16 h, persisting up to 96 h. TCA, TCDCA, and TUDCA in the plasma, as well as TCA, TUDCA, TCDCA, TDCA, TLCA, and THDCA in the liver, emerged as early sensitive and potential markers for diagnosing ANIT-induced cholestasis at 8-16 h. The distinguishing features of ANIT-induced liver injury were as follows: T-BAs exceeding G-BAs and serum biochemical indicators surpassing free bile acids. Notably, plasma T-BAs, particularly TCA, exhibited higher sensitivity to cholestatic hepatotoxicity compared with serum enzyme activity and liver histopathology. Further investigation revealed that TCA exacerbated ANIT-induced liver injury by elevating liver function enzyme activity, inflammation, and bile duct proliferation and promoting the migration of bile duct epithelial cell. Nevertheless, no morphological changes or alterations in transaminase activity indicative of liver damage were observed in the rats treated with TCA alone. Additionally, there were no changes in bile acid profiles or inflammatory responses under physiological conditions with maintained bile acid homeostasis. In summary, our findings suggest that taurine-conjugated bile acids in both plasma and liver, particularly TCA, can serve as early and sensitive markers for predicting intrahepatic cholestatic drugs and can act as potent exacerbators of cholestatic liver injury progression. However, exogenous TCA does not induce liver injury under physiological conditions where bile acid homeostasis is maintained.
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