beta 2-Microglobulin

β 2 - 微球蛋白
  • 文章类型: Journal Article
    探讨新诊断的多发性骨髓瘤(MM)患者在不同阶段和不同M蛋白类型时凝血功能的变化,并分析凝血指标与β2-微球蛋白(β2-MG)的相关性。
    从2016年1月至2022年12月共选择371例新诊断的MM患者(n=371)和健康对照(n=48)。基线数据,收集β2-MG和凝血指数值。指标包括凝血酶原时间(PT),活化部分凝血活酶时间(APPT),纤维蛋白原(FIB),凝血酶时间(TT),纤维蛋白原降解产物(FDP),和D-二聚体(D-D)。根据Durie-Salmon分期系统(DS)将患者分为不同的组,国际分期系统(ISS)和疾病分类(M蛋白类型)。比较各组间6项指标水平,分析各指标与β2-MG的相关性。
    与正常对照组相比,PT的水平,FIB,TT,MM组FDP和D-D显著增高(均P<0.001)。随着DS和ISS分期的增加,PT的水平,TT,FDP和D-D也显著增加(均P<0.001)。β2-MG与PT呈正相关,TT,和FDP水平(Spearmanr分别为0.157、0.270、0.108;所有P<0.05),与FIB呈负相关(r=-0.220,P<0.001)。6项指标在不同M蛋白类型间存在显著差异(均P<0.001)。其中,IgA-κ组PT和APTT明显升高,FIB在λ轻链基团中增加,IgG-κ组TT升高,FDP在κ轻链基团中增加,IgG-λ组的D-D增加。
    MM患者的凝血功能障碍程度随疾病分期而加重,各种凝血指标的异常升高发生在不同的M蛋白类型中,与β2-MG密切相关。
    UNASSIGNED: To explore the changes in the coagulation function of patients newly diagnosed with multiple myeloma (MM) at different stages and with different M protein types, and to analyze the correlation between coagulation indexes and β2-microglobulin (β2-MG).
    UNASSIGNED: A total of 371 Patients with newly diagnosed MM (n = 371) and healthy controls (n = 48) were selected from January 2016 to December 2022. Baseline data, β2-MG and coagulation index values were collected. Indexes included prothrombin time (PT), activated partial thromboplastin time (APPT), fibrinogen (FIB), thrombin time (TT), fibrinogen degradation products (FDP), and D-dimer(D-D). Patients were divided into different groups according to the Durie-Salmon staging system (DS), the International Staging System (ISS) and disease classification (M protein type). The levels of these six indexes were compared among the groups and the correlation between each index and β2-MG was analyzed.
    UNASSIGNED: Compared to the normal control group, the levels of PT, FIB, TT, FDP and D-D in the MM group were significantly higher (all P < 0.001). As DS and ISS staging increased, the levels of PT, TT, FDP and D-D also increased significantly (all P < 0.001). β2-MG was positively correlated with PT, TT, and FDP levels (Spearman r = 0.157, 0.270, 0.108, respectively; all P < 0.05), and negatively correlated with FIB (r = -0.220, P < 0.001). Significant differences existed in the levels of these six indexes among different M protein types (all P < 0.001). Among them, PT and APTT increased significantly in the IgA-κ group, FIB increased in the λ light chain group, TT increased in the IgG-κ group, FDP increased in the κ light chain group, and D-D increased in the IgG-λ group.
    UNASSIGNED: The degree of coagulation dysfunction in MM patients increases with disease stage and abnormal increases of various coagulation indicators occur in different M protein types and are closely related to β2-MG.
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  • 文章类型: Journal Article
    背景:血液透析器应有效消除小分子和中分子尿毒症毒素,并具有特殊的血液相容性,以改善终末期肾病患者的健康状况。然而,由于血浆蛋白吸附到透析器膜,在治疗期间性能和血液相容性受到损害。增加的膜亲水性减少了蛋白质对膜的吸附,并在新型FXCorAL透析器中实施。本随机对照试验比较了FXCorAL透析器与血液透析滤过治疗中使用的其他常用透析器的性能和血液相容性。
    方法:这种前瞻性,打开,控制,多中心,介入,交叉研究将稀释后在线血液透析滤过(HDF)的稳定患者随机分为FXCorAL600,FXCorDiax600(包括FreseniusMedicalCare)和xevontaHi15(B.布劳恩)每人4周。主要结果是β2-微球蛋白去除率(β2-mRR)。检验了FXCorAL与比较者的非劣效性和优越性。次要终点是RR和/或小分子和中分子的清除,以及血液相容性标志物的透析内和透析间概况,关于补体激活,细胞活化/炎症,血小板活化和氧化应激。进一步的终点是患者报告的结果(PRO)和临床安全性。
    结果:82例患者被纳入,76例作为意向治疗(ITT)人群进行分析。FX珊瑚显示出最高的β2-mRR(76.28%),其次是FXCorDiax(75.69%)和xevonta(74.48%)。对两个比较者的非劣效性和对xevonta的优越性具有统计学意义。与中间分子相关的次要终点证实了这些结果;透析器之间小分子的性能相当。关于血液透析相容性,FX珊瑚显示补体较低,白细胞,和血小板活化。透析间血液相容性没有差异,PROs,或临床安全。
    结论:与临床实践中其他常用的透析器相比,具有增加的膜亲水性的新型FXCorAL显示出强大的性能和良好的血液相容性特征。进一步的长期调查应检查FXCorAL的益处是否会转化为改善的心血管和死亡率终点。
    背景:eMPORAIII于2021年1月19日在ClinicalTrials.gov(NCT04714281)注册。
    BACKGROUND: Hemodialyzers should efficiently eliminate small and middle molecular uremic toxins and possess exceptional hemocompatibility to improve well-being of patients with end-stage kidney disease. However, performance and hemocompatibility get compromised during treatment due to adsorption of plasma proteins to the dialyzer membrane. Increased membrane hydrophilicity reduces protein adsorption to the membrane and was implemented in the novel FX CorAL dialyzer. The present randomized controlled trial compares performance and hemocompatibility profiles of the FX CorAL dialyzer to other commonly used dialyzers applied in hemodiafiltration treatments.
    METHODS: This prospective, open, controlled, multicentric, interventional, crossover study randomized stable patients on post-dilution online hemodiafiltration (HDF) to FX CorAL 600, FX CorDiax 600 (both Fresenius Medical Care) and xevonta Hi 15 (B. Braun) each for 4 weeks. Primary outcome was β2-microglobulin removal rate (β2-m RR). Non-inferiority and superiority of FX CorAL versus comparators were tested. Secondary endpoints were RR and/or clearance of small and middle molecules, and intra- and interdialytic profiles of hemocompatibility markers, with regards to complement activation, cell activation/inflammation, platelet activation and oxidative stress. Further endpoints were patient reported outcomes (PROs) and clinical safety.
    RESULTS: 82 patients were included and 76 analyzed as intention-to-treat (ITT) population. FX CorAL showed the highest β2-m RR (76.28%), followed by FX CorDiax (75.69%) and xevonta (74.48%). Non-inferiority to both comparators and superiority to xevonta were statistically significant. Secondary endpoints related to middle molecules corroborated these results; performance for small molecules was comparable between dialyzers. Regarding intradialytic hemocompatibility, FX CorAL showed lower complement, white blood cell, and platelet activation. There were no differences in interdialytic hemocompatibility, PROs, or clinical safety.
    CONCLUSIONS: The novel FX CorAL with increased membrane hydrophilicity showed strong performance and a favorable hemocompatibility profile as compared to other commonly used dialyzers in clinical practice. Further long-term investigations should examine whether the benefits of FX CorAL will translate into improved cardiovascular and mortality endpoints.
    BACKGROUND: eMPORA III registration on 19/01/2021 at ClinicalTrials.gov (NCT04714281).
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  • 文章类型: Journal Article
    目的:调查9种尿液生物标志物在2型糖尿病(T2DM)患者中的分布,有或没有微血管并发症。
    方法:总共,从2021年到2022年,有407名T2DM患者注册。根据糖尿病视网膜病变(DR)和尿白蛋白-肌酐比值(UACR),407人分为四(4)组,DR(-)UACR(-),DR(+)UACR(-),DR(-)UACR(+),和DR(+)UACR(+)。此外,同期纳入112名健康志愿者。九(9)个尿液标记包括α1-微球蛋白(u-α1MG),免疫球蛋白G(u-IgG),中性粒细胞明胶酶相关脂质载体蛋白(u-NGAL),胱抑素C(u-CysC),视黄醇结合蛋白(u-RBP),β2-微球蛋白(u-β2MG),N-乙酰-β-D-氨基葡萄糖苷酶(u-NAG),转铁蛋白(u-Trf),和胶原IV型(u-Col)。对于每个标记,健康志愿者各自的97.5百分位数水平作为参考上限.
    结果:在407人中,248例(61%)为DR(-)UACR(-),100(25%)为DR(-)UACR(+),37(9%)为DR(+)UACR(-),DR(+)UACR(+)22例(5%)。u-NAG/Cr生物标志物水平显示健康参与者和T2DM患者之间存在显着差异。在DR(-)UACR(-)组中,u-Trf/Cr阳性率最高(21.37%),其次是u-IgG/Cr(14.52%);u-NAG/Cr(10.48%);u-β2MG/Cr(4.44%);u-CysC/Cr(4.03%);u-NGAL/Cr(4.03%);u-RBP/Cr(2.82%);u-α1MG/Cr(2.42%);17.34%的T2DM患者生物标志物≥2。在T2DM少于五(5)年的人群中,一种生物标志物(21.33%)和两种生物标志物(18.67%)的阳性率几乎接近DR(-)UACR(-)组(21.37%,12.10%,分别)。
    结论:肾小管生物标志物可作为糖尿病肾损伤的早期检测和监测指标。对于初次诊断的T2DM患者,应测量u-NAG生物标志物。
    OBJECTIVE: To investigate the distribution of nine (9) urine biomarkers in people living with type 2 diabetes mellitus (T2DM), with or without microvascular complications.
    METHODS: In total, 407 people with T2DM were enrolled from 2021 to 2022. According to diabetic retinopathy (DR) and urinary albumin-creatinine ratio (UACR), the 407 people were divided into four (4) groups, DR(-)UACR(-), DR(+)UACR(-), DR(-)UACR(+), and DR( + )UACR(+). In addition, 112 healthy volunteers were enrolled during the same period. The nine (9) urine markers included α1-microglobulin (u-α1MG), immunoglobulin G (u-IgG), neutrophil gelatinase-associated lipid carrier protein (u-NGAL), cystatin C (u-CysC), retinol-binding protein (u-RBP), β2-microglobulin (u-β2MG), N-acetyl-β-D-glucosaminidase (u-NAG), transferrin (u-Trf), and collagen type IV (u-Col). For each marker, the respective level of 97.5 percentile in healthy volunteers was taken as an upper reference limit.
    RESULTS: Among the 407 people, 248 individuals (61%) were DR(-)UACR(-), 100 (25%) were DR(-)UACR(+), 37 (9%) were DR(+)UACR(-), and 22 (5%) were DR(+)UACR(+). The u-NAG/Cr biomarker level showed a significant difference between healthy participants and people with T2DM. In the DR(-)UACR(-)group, u-Trf/Cr showed the highest positive rate (21.37%), followed by u-IgG/Cr (14.52%); u-NAG/Cr (10.48%); u-β2MG/Cr (4.44%); u-CysC/Cr (4.03%); u-NGAL/Cr (4.03%); u-RBP/Cr (2.82%); u-α1MG/Cr (2.42%); 17.34% of people with T2DM showed multiple biomarkers positive (≥2 biomarkers). The positive rates of one biomarker (21.33%) and two biomarkers (18.67%) in people who have less than five (5) years of T2DM were almost close to those of the DR(-)UACR(-) group (21.37%, and 12.10%, respectively).
    CONCLUSIONS: Renal tubule biomarkers may be used as an indicator in the early detection and monitoring of renal injury in diabetes mellitus. The u-NAG biomarker should be measured for the people with T2DM of the first-time diagnosis.
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  • 文章类型: Journal Article
    背景:尽管免疫组织化学技术和蛋白质组学分析被广泛用于淀粉样变性的分型诊断,免疫组织化学评估的诊断效用尚不清楚.
    方法:我们使用免疫组织化学技术来表征内部兔多克隆抗κ,反λ,抗甲状腺素运载蛋白抗体,40例尸检病例中的商业抗淀粉样蛋白A和抗β2-微球蛋白抗体。
    结果:在30例(75%)中,该亚型是通过使用淀粉样蛋白对一种抗体强烈呈弥漫性阳性而对其他抗体呈阴性的标准来确定的。然后,我们对所有40例病例进行了蛋白质组学分析。在39个案例中,我们仅鉴定了一种淀粉样蛋白,并证实了上述30例患者的免疫组织化学确定的亚型。在其他七种情况下,我们可以通过使用蛋白质组学分析的信息,用免疫组织化学方法回顾性地确定亚型,免疫组化诊断率提高到92.5%(37/40)。在一个案例中,我们确定了双亚型,免疫组织化学和蛋白质组学分析。在其余三个案例中,蛋白质组分析对于分型诊断是必不可少的。
    结论:目前的研究结果表明,联合的免疫组织化学和蛋白质组学分析比单独的免疫组织化学更有用。我们的发现强调了仔细解释抗TTR和轻链的免疫组织化学的重要性,并提供了可以通过免疫组织化学指导淀粉样蛋白分型的见解。
    BACKGROUND: Although immunohistochemical techniques and proteomic analysis are widely used for typing diagnosis of amyloidosis, the diagnostic utility of immunohistochemical evaluation is not well understood.
    METHODS: We used immunohistochemical techniques to characterize staining patterns of in-house rabbit polyclonal anti-κ, anti-λ, anti-transthyretin antibodies, and commercial anti-amyloid A and anti-β2-microglobulin antibodies in 40 autopsy cases.
    RESULTS: In thirty cases (75%), the subtype was determined by using the criterion that amyloid is strongly and diffusely positive for one antibody while negative for other antibodies. We then performed proteomic analysis of all 40 cases. In 39 cases, we identified only one amyloid protein and confirmed the immunohistochemically determined subtypes of the abovementioned 30 cases. In seven other cases, we could retrospectively determine subtypes with immunohistochemistry by using information from proteomic analysis, which increased the immunohistochemistry diagnosis rate to 92.5% (37/40). In one case, we identified double subtypes, both immunohistochemically and with proteomic analysis. In the remaining three cases, proteomic analysis was essential for typing diagnosis.
    CONCLUSIONS: The present findings suggest that combined immunohistochemistry and proteomic analysis is more useful than immunohistochemistry alone. Our findings highlight the importance of carefully interpreting immunohistochemistry for anti-TTR and light chain and offer insights that can guide amyloid typing through immunohistochemistry.
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  • 文章类型: Journal Article
    背景:干燥综合征(SS)是一种慢性自身免疫性疾病,其特征是外分泌腺中的淋巴细胞浸润。建议SS患者的腕管综合征(CTS)比普通人群更常见。这项研究的目的是寻求CTS与SS患者的实验室和临床表现之间的关联。
    方法:对50例原发性SS(pSS)患者进行检查。由风湿病学家进行临床评估和电生理研究。收集实验室测试结果的数据。对照组由50名性别和年龄相匹配的骨关节炎(OA)患者组成。
    结果:研究组50例患者中有27例(54%)被诊断为CTS。对照组50人的CTS患病率为8%。在患有CTS的pSS患者中,关节受累并不比非CTS组患者更常见[15vs.13(p=0.945)]。睡眠障碍存在预期差异[18vs.9(p=0.012)]和感觉异常[23vs.13(p=0.024)]。主要发现是β2-微球蛋白(B2MG)升高的显着差异[23vs.13(p=0.024)]。其他研究因素,在文献中建议在pSS相关的神经病中具有重要意义,组间没有统计学差异。
    结论:我们的研究证实,CTS在pSS患者中比在一般人群中更普遍,并提示需要一种新的方法来治疗这种现象的发病机制。我们假设CTS比关节受累更与整体疾病活动相关。
    BACKGROUND: Sjögren\'s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the exocrine glands. Carpal tunnel syndrome (CTS) is suggested to be more frequent among SS patients than in the general population. The aim of this study was to seek associations between the CTS and the laboratory and clinical findings of SS patients.
    METHODS: Fifty patients diagnosed with primary SS (pSS) were examined. Clinical evaluation by a rheumatologist and electrophysiological studies were conducted. Data on laboratory tests results was collected. Control group consisted of 50 sex and age-matched individuals with osteoarthritis (OA).
    RESULTS: Out of 50 patients in the study group 27 (54%) were diagnosed with CTS. The prevalence of CTS among 50 individuals in the control group was 8%. Among pSS patients with CTS the joint involvement was not more common than in those from the non-CTS group [15 vs. 13 (p = 0.945)]. There was an expected difference in sleep disorders [18 vs. 9 (p = 0.012)] and paresthesia [23 vs. 13 (p = 0.024)]. The major finding was a significant difference in elevated beta2-microglobulin (B2MG) [23 vs. 13 (p = 0.024)]. Other studied factors, suggested in the literature as significant in the pSS-related neuropathy, were not statistically different between the groups.
    CONCLUSIONS: Our study confirms that CTS is more prevalent among pSS patients than in the general population and suggests that a new approach is required towards the pathogenesis of this phenomenon. We hypothesize that CTS is more associated with an overall disease activity than joint involvement as such.
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  • 文章类型: English Abstract
    Objective: To explore the correlation of bone marrow polychonal plasma cell proportion (pPC% ) and clinical features in newly diagnosed multiple myeloma (NDMM) patients. Methods: A retrospective analysis of 317 patients with NDMM admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to January 2023 was performed. The results of the pPC% in all patients were clear. The relationship between the pPC% and clinical characteristics was analyzed. Results: A total of 317 patients were included, comprising 180 males and 137 females. The median age at diagnosis was 61 (26-91) years, and 55.8% were 60 years or older. The pPC% in the bone marrow of patients with NDMM was different in the DS, International Staging System (ISS), and revised ISS (R-ISS) stages (P=0.002, 0.010, and 0.049, respectively), whereas no statistical difference in pPC% was observed among patients with different FISH risk stratigrams (P=0.971). The correlation coefficient between pPC% and hemoglobin (HGB) at the first diagnosis in patients was 0.211 (P<0.01). The correlation coefficients with serum calcium, serum creatinine, M protein level, and β(2)-microglobulin were -0.141, -0.120, -0.181, and -0.207, respectively, and the results of the significance test were P=0.012, 0.033, 0.004, and 0.002, respectively, indicating a negative correlation. Compared with the patients with a pPC% of ≥2.5%, the group of patients with a pPC% of <2.5% had significantly higher levels of light chain, serum calcium, serum creatinine, M protein, and β(2)-microglobulin at the initial diagnosis (P<0.05) ; lower HGB level (P<0.001) ; and a higher proportion of patients in ISS stage Ⅲ (P=0.034) . Conclusion: In this study, the pPC% in patients with NDMM was associated with clinical features of good prognosis, including higher HGB, lower serum calcium, serum creatinine, M protein quantity, β(2)-microglobulin, light chain involvement, lower proportion of advanced disease (DS stage and ISS stage Ⅲ), and clinical features showing lower tumor burden.
    目的: 探究初诊多发性骨髓瘤(NDMM)患者骨髓多克隆浆细胞占比(pPC%)与临床特征的相关性。 方法: 回顾性分析2018年1月至2023年1月在华中科技大学同济医学院附属同济医院收治的317例NDMM患者,纳入患者均有明确的pPC%结果。分析pPC%与临床特征的关系。 结果: 共纳入317例患者,其中男180例,女137例,中位确诊年龄61(26~91)岁,≥60岁患者占55.8%。NDMM患者骨髓pPC%在各DS分期、ISS分期、R-ISS分期组差异均有统计学意义(P值分别为0.002、0.010、0.049),而不同的FISH危险分层患者pPC%差异无统计学意义(P=0.971)。NDMM患者pPC%与患者初诊时HGB呈正相关(r=0.211,P<0.01);与血钙、血肌酐、单克隆免疫球蛋白(M蛋白)定量、β(2)微球蛋白水平呈负相关(r分别为-0.141、-0.120、-0.181、-0.207,P值为0.012、0.033、0.004、0.002)。与pPC%≥2.5%患者相比,pPC%<2.5%组患者初诊时受累轻链、血钙、血肌酐、M蛋白和β(2)微球蛋白水平明显升高(P值均<0.05),HGB降低(P<0.001),ISS分期Ⅲ期比例更高(P=0.034)。 结论: NDMM患者pPC%与良好预后的临床特征相关,包括更高的HGB,更低的血钙、血肌酐、M蛋白定量、β(2)微球蛋白,受累轻链,更低的晚期疾病占比(DS分期、ISS分期Ⅲ期),在临床特点上表现为肿瘤负荷较小。.
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  • 文章类型: English Abstract
    OBJECTIVE: To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma (MM) bone disease (MBD) patients with different blood separation results.
    METHODS: A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group [119 cases, serum, colloid and red blood cell (RBC) from top to bottom of sample] and abnormal group (15 cases, serum, mixed layer of RBC and serum, colloid and RBC from top to bottom of sample) according to the results of blood separation. According to the imaging findings, MBD was classified into grade 0-4, grade 0-2 was mild, and grade 3-4 was severe. The MBD grade of patients in the two groups was analyzed. The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated. The correlation between β2-microglobulin (MG) and bone metabolic indexes was analyzed by Pearson correlation analysis.
    RESULTS: In the control group, there were 69 cases of grade 0-2 and 50 cases of grade 3-4, while in the abnormal group, there were 5 cases of grade 0-2 and 10 cases of grade 3-4, the difference was statistically significant (P < 0.05). The serum β2-MG, β-CTX levels in abnormal group were both significantly higher than those in control group, while the levels of P1NP and osteocalcin (OC) were significantly lower (all P < 0.001). In the control group, there were 95 patients with ≥ partial response (PR) and the blood separation results were not changed, while 24 patients with 0.05). Compared with before treatment, the levels of β-CTX and β2-MG in the control group with unchanged blood separation results were significantly decreased (both P < 0.001), while the levels of P1NP and OC were significantly increased (P < 0.01, P < 0.001), and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change (P >0.05); the levels of β-CTX and β2-MG in the abnormal group transformed to normal blood separation result were significantly decreased (both P < 0.01), while the levels of P1NP and OC were significantly increased (P < 0.001, P < 0.01), and the level of each index in patients with unchanged blood separation results did not significantly change (P>0.05). Pearson correlation analysis showed that serum β2-MG was positively correlated with β-CTX (r =0.709, P < 0.001), and negatively correlated with P1NP and OC (r =-0.410,r =-0.412, both P < 0.001).
    CONCLUSIONS: MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis, which is closely related to the significant increase of bone resorption index β-CTX level and decrease of bone formation index P1NP and OC levels, leading to more serious bone metabolic homeostasis disorder. The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition, efficacy monitoring and prognosis evaluation of MBD patients.
    UNASSIGNED: 不同血液分离结果的多发性骨髓瘤骨病患者骨代谢水平研究.
    UNASSIGNED: 探讨不同血液分离结果的骨髓瘤骨病(MBD)患者骨代谢指标对病情评估及疗效监测的临床意义。.
    UNASSIGNED: 纳入2016年3月至2020年3月河北省沧州中西医结合医院收治的134例初诊MM患者,根据血液离心结果,分为对照组119例(样本自上而下依次为血清、胶体、红细胞),异常组15例(样本自上而下依次为血清、红细胞、胶体、红细胞),根据影像学表现将MBD分为0-4级,0-2级为骨病较轻者,3-4级为骨病较重者,分析两组患者MBD的分级情况,并对不同血液分离结果的MBD患者进行疗效评价,分析治疗前后血液分离结果及骨代谢指标水平的变化,采用Pearson相关分析法分析β2-微球蛋白(MG)与骨代谢指标水平的相关性。.
    UNASSIGNED: 对照组0-2级69例,3-4级50例;异常组0-2级5例,3-4级10例,比较差异具有统计学意义(P < 0.05)。异常组血清β2-MG、Ⅰ型胶原羧基端肽β特殊序列(β-CTX)水平显著高于对照组,而Ⅰ型前胶原氨基端前肽(P1NP)、骨钙素(OC)水平显著低于对照组(均P < 0.001)。对照组95例疗效≥部分缓解(PR),其血液分离结果未改变;24例疗效< PR,其中5例血液分离结果转为异常。异常组9例疗效≥PR,血液分离结果均转为正常;6例疗效< PR,其中5例血液分离结果仍为异常。与治疗前相比,对照组疗效≥PR的患者β-CTX、β2-MG水平显著降低,而P1NP、OC水平显著升高(均P < 0.001);异常组疗效≥PR的患者β-CTX、β2-MG水平亦显著降低(P < 0.001,P < 0.01),而P1NP、OC水平显著升高(P < 0.001,P < 0.01)。两组疗效 < PR的患者各指标水平与治疗前相比无明显变化(P >0.05)。与疗前相比,对照组治疗后血液分离结果未改变的患者β-CTX、β2-MG水平显著降低(均P < 0.001),P1NP、OC水平显著升高(P < 0.01,P < 0.001),而血液分离结果转为异常的患者各指标水平无明显变化(P >0.05);异常组治疗后血液分离结果转为正常的患者β-CTX、β2-MG水平显著降低(均P < 0.01),P1NP、OC水平显著升高(P < 0.001,P < 0.01),而血液分离结果未改变的患者各指标水平无明显变化。Pearson相关分析显示,患者血清β2-MG与β-CTX水平呈正相关(r =0.709,P < 0.001),与P1NP、OC水平呈负相关(r =-0.410、-0.412,均P < 0.001)。.
    UNASSIGNED: 存在血液异常分离结果的MBD患者骨病分级较高、预后较差,与骨吸收指标β-CTX水平显著升高,骨形成指标P1NP、OC水平显著降低,引起更严重的骨代谢动态平衡紊乱密切相关。血液分离结果联合骨代谢指标水平的变化可作为MBD患者病情、疗效监测及预后评估的综合预测指标之一。.
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  • 文章类型: English Abstract
    OBJECTIVE: To investigate the relative expression level and clinical significance of LINC00475 in serum of patients with multiple myeloma (MM).
    METHODS: The expression of LINC00475 in serum of 108 MM patients and five MM cell lines including RPMI 8226, NCI-H929, U266, OPM2 and CAG were detected by real-time fluorescence quantitative PCR. The diagnostic value of LINC00475 in MM was evaluated by receiver operating characteristic (ROC) curve analysis. The correlation of LINC00475 with patients\' characteristics was analyzed.
    RESULTS: Compared with control groups, the expression of LINC00475 was up-regulated in serum of MM patients and MM cell lines (all P < 0.05). ROC curve analysis showed that the optimal cut-off value of LINC00475 was 262.4, the area under curve (AUC) was 0.924(95%CI : 0.884-0.964), and sensitivity and specificity was 83.3% and 91.7%, respectively, which indicated that LINC00475 had good evaluation value in MM patients. Compared with low-LINC00475 expression group, patients in high-LINC00475 expression group had higher levels of β2microglobulin (β2-MG) and Cystatin C (Cys-C) but lower albumin (ALB) (all P < 0.05). Compared with MM patients with International Staging System (ISS) stage I, the expression level of LINC00475 was significantly higher in patients with stage II and III (both P < 0.05).
    CONCLUSIONS: LINC00475 is helpful to distinguish MM patients from healthy adults, which is correlated with the prognostic indicators such as β2-MG, ALB, and ISS stage.
    UNASSIGNED: LINC00475在多发性骨髓瘤中的表达与临床意义.
    UNASSIGNED: 探讨LINC00475在多发性骨髓瘤(MM)患者血清中的相对表达水平及临床意义。.
    UNASSIGNED: 用实时荧光定量PCR技术检测108例MM患者血清及RPMI 8226、NCI-H929、U266、OPM2、CAG这5个MM细胞系中LINC00475的表达情况,受试者工作特征曲线评估其对MM的诊断价值,并结合患者的临床资料分析LINC00475与患者临床特征的关系。.
    UNASSIGNED: 与健康对照组相比,MM患者血清及MM细胞系中LINC00475的表达明显上调(均P < 0.05)。受试者工作特征曲线分析显示,LINC00475的最佳截断值为262.4,曲线下面积为0.924(95%CI :0.884-0.964),灵敏度83.3%,特异度91.7%,表明LINC00475在MM患者中具有良好的评估价值。与LINC00475低表达组的MM患者相比,高表达组的患者具有较高水平的β2微球蛋白和胱抑素C(均P < 0.05),但白蛋白水平较低(P < 0.05)。与ISS分期Ⅰ期的MM患者相比,Ⅱ期和Ⅲ期患者LINC00475的表达水平均明显增高(均P < 0.05)。.
    UNASSIGNED: 检测LINC00475的相对表达水平有助于区分MM患者和正常人群,其相对表达水平与MM患者的β2-微球蛋白、白蛋白、ISS分期等预后指标相关。.
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  • 文章类型: English Abstract
    OBJECTIVE: To investigate the role of serum adenosine deaminase (ADA) combined with globulin (GLB), creatinine (CREA), β2-microglobulin (β2-MG) and hemoglobin (HGB) in the initial screening of multiple myeloma (MM), in order to reduce missed diagnosis and misdiagnosis of MM.
    METHODS: A retrospective analysis was performed on 62 newly diagnosed multiple myeloma (NDMM) patients who were admitted to the Department of Hematology of the First Affiliated Hospital of Chengdu Medical College from April 2018 to December 2021, and 33 patients with benign hematologic diseases and 30 healthy subjects were selected as the control group. The expression of ADA in pan-cancer was analyzed using TCGA and GTEx databases. The general data and laboratory indicators of the subjects were collected, and the differences of ADA activity and other laboratory indicators in each group were compared. The relationship between serum ADA activity and clinical data of NDMM patients was analyzed. The changes of ADA activity before and after chemotherapy in NDMM patients and the differences of ADA activity in NDMM patients with different DS and ISS stages were compared. Multivariate logistic regression was used to analyze the risk factors of NDMM. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of ADA and other laboratory indicators in MM. Bioinformatics method was used to analyze the co-expression networks and enrichment pathways of ADA.
    RESULTS: ADA level was significantly upregulated in tissues of 14 types of cancer in TCGA database, and ADA was highly expressed in 11 types of cancer in TCGA combined with GTEx databases. The serum levels of ADA, GLB, uric acid (UA), cystatin C (CysC) and β2-MG in the NDMM group were significantly higher than those in benign hematologic disease group and healthy control group ( P < 0.05), while the levels of ALB and the value of albumin to globulin ratio (A∶G) in the NDMM group were significantly lower than those in the other two groups ( P < 0.001). There were significant differences in DS stage (P =0.036), ISS stage (P =0.019) and the levels of CREA (P =0.036), UA (P =0.034), β2-MG (P =0.019) in NDMM patients with different ADA activity levels. After primary chemotherapy, ADA activity and β2-MG concentration were decreased in NDMM patients ( P < 0.01). The comparison results of patients in different stages showed that ADA activity of patients in DS stage I+II was significantly lower than that of patients in DS stage III (P <0.05), and ADA activity of patiens in ISS stage I+II was significantly lower than that of patients in ISS stage III ( P < 0.01). Multivariate logistic regression analysis showed that increased GLB, increased ADA activity, increased CREA, increased β2-MG and decreased HGB were independent risk factors for NDMM. The area under the curve (AUC) of ADA in the diagnosis of MM was 0.847, and the AUC of ADA combined with GLB, CREA, β2-MG and HGB in the diagnosis of MM was 0.940. The results of co-expression network and enrichment pathway analysis showed that ADA bounded to 20 proteins and it was significantly associated with the metabolic pathways of purine, pyrimidine, nicotinate and nicotinamide.
    CONCLUSIONS: The detection of ADA activity in serum is of positive significance for the auxiliary diagnosis, therapeutic evaluation and monitoring the progress of NDMM patients. ADA combined with GLB, CREA, β2-MG and HGB can improve the detection rate of MM, and reduce missed diagnosis and misdiagnosis to a certain extent.
    UNASSIGNED: 血清ADA联合GLB、CREA、β2-MG、HGB在初诊多发性骨髓瘤中的临床意义.
    UNASSIGNED: 研究血清腺苷脱氨酶(ADA)联合球蛋白(GLB)、肌酐(CREA)、β2-微球蛋白(β2-MG)、血红蛋白(HGB)对多发性骨髓瘤(MM)的初筛作用,减少MM的漏诊及误诊。.
    UNASSIGNED: 回顾性分析2018年4月至2021年12月成都医学院第一附属医院血液科收治的62例初诊多发性骨髓瘤(NDMM)患者的资料,并以33例良性血液病患者和30例健康体检者作为对照组。用TCGA和GTEx数据库分析ADA在泛癌中的表达。收集受试者的一般资料及实验室检测指标,比较各组ADA活性及其他实验室指标水平的差异。分析血清ADA活性与NDMM患者临床资料的关系。比较NDMM患者化疗前后ADA活性的变化以及不同DS、ISS分期NDMM患者中ADA活性的差异。多因素Logistic回归分析NDMM发生的危险因素。采用ROC曲线评价ADA及其联合其他实验室指标对MM的诊断效能。生物信息学分析ADA的共表达网络和富集途径。.
    UNASSIGNED: TCGA 数据库中有14种癌组织中ADA水平显著上调,TCGA联合GTEx 数据库中ADA 在11种癌症中高表达。NDMM组外周血清ADA、GLB、UA、CysC、β2-MG水平明显高于良性血液病组及健康对照组( P < 0.05),ALB、A∶G明显低于良性血液病组及健康对照组( P < 0.001)。不同ADA活性水平的NDMM患者的DS分期(P =0.036)、ISS分期(P =0.019)、CREA(P =0.036)、UA(P =0.034)、β2-MG(P =0.019)水平具有统计学差异。NDMM患者初次化疗后ADA活性及β2MG浓度有所下降( P < 0.01)。不同DS分期和ISS分期患者比较结果显示,DS I+II期患者ADA活性明显低于Ⅲ期患者( P < 0.05),ISS I+II期患者ADA活性也明显低于Ⅲ期患者( P < 0.01)。多因素Logistic回归分析结果显示,GLB增高、ADA活性增加、CREA增高、β2-MG增高、HGB降低是NDMM的独立危险因素。ADA诊断MM的曲线下面积为0.847,其联合GLB、CREA、β2-MG、HGB诊断MM的曲线下面积为0.940。共表达网络和富集途径分析结果显示,ADA与20种蛋白质结合,并与嘌呤代谢、嘧啶代谢、烟酸和烟酰胺代谢通路显著相关。.
    UNASSIGNED: 检测血清中的ADA活性,对MM患者的辅助诊断、疗效评估以及监测疾病的发展有着积极的意义。ADA联合GLB、CREA、β2-MG、HGB可提高MM的初筛检出率,可在一定程度上减少漏诊及误诊。.
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  • 文章类型: Journal Article
    心脏移植与主要障碍有关,包括可供移植的器官数量有限,由于遗传差异而导致排斥的风险,和免疫抑制的负担。在这项研究中,我们证明了在离体灌注期间对心脏进行永久性基因工程的可行性。在常温EVHP的两个小时内,将编码靶向β2-微球蛋白(shβ2m)和II类反式激活因子(shCIITA)的短发夹RNA的慢病毒载体输送到移植物。在内皮细胞和心肌细胞中稳定表达的报告基因表明了高效的基因工程。值得注意的是,猪白细胞抗原(SLA)Ⅰ类和SLAⅡ类的表达水平分别下降了66%和76%,分别,在血管内皮。乳酸的评价,肌钙蛋白T,灌注液中的LDH水平和组织学分析显示,没有由慢病毒载体引起的其他细胞损伤或组织损伤。此外,未转导和慢病毒载体转导的心脏的细胞因子分泌谱(IL-6,IL-8和TNF-α)相当。这项研究证明了在不损害组织完整性的情况下离体产生基因工程心脏。SLA表达的下调可能有助于降低心脏的免疫原性并支持同种异体或异种移植后的移植物存活。
    Heart transplantation is associated with major hurdles, including the limited number of available organs for transplantation, the risk of rejection due to genetic discrepancies, and the burden of immunosuppression. In this study, we demonstrated the feasibility of permanent genetic engineering of the heart during ex vivo perfusion. Lentiviral vectors encoding for short hairpin RNAs targeting beta2-microglobulin (shβ2m) and class II transactivator (shCIITA) were delivered to the graft during two hours of normothermic EVHP. Highly efficient genetic engineering was indicated by stable reporter gene expression in endothelial cells and cardiomyocytes. Remarkably, swine leucocyte antigen (SLA) class I and SLA class II expression levels were decreased by 66% and 76%, respectively, in the vascular endothelium. Evaluation of lactate, troponin T, and LDH levels in the perfusate and histological analysis showed no additional cell injury or tissue damage caused by lentiviral vectors. Moreover, cytokine secretion profiles (IL-6, IL-8, and TNF-α) of non-transduced and lentiviral vector-transduced hearts were comparable. This study demonstrated the ex vivo generation of genetically engineered hearts without compromising tissue integrity. Downregulation of SLA expression may contribute to reduce the immunogenicity of the heart and support graft survival after allogeneic or xenogeneic transplantation.
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