BACKGROUND: Our previous study demonstrated that β2-microglobulin (β2M) promoted ER+/HER2- breast cancer survival via the SGK1/Bcl-2 signaling pathway. However, the role of β2M has not been investigated in ER-/HER2+ breast cancer. Here, we aimed to determine the role of β2M in ER-/HER2+ breast cancer.
METHODS: The interaction between β2M and HFE was confirmed by co-immunoprecipitation, mass spectrometry, yeast two-hybrid screening, and His pull-down. The knockdown and overexpression of β2M or HFE were performed in MDA-MB-453 cells, and ERK signaling pathway was subsequently analyzed via western blotting. Apoptotic cells were detected using flow cytometer. β2M, HFE, and p-ERK1/2 were examined in tumor and paired adjacent tissues via immunohistochemistry.
RESULTS: HFE was found to be an interacting protein of β2M in ER-/HER2+ breast cancer cells MDA-MB-453 by co-immunoprecipitation and mass spectrometry. A yeast two-hybrid system and His-pull down experiments verified that β2M directly interacted with HFE. β2M and HFE as a complex were mainly located in the cytoplasm, with some on the cytomembrane of MDA-MB-453 cells. In addition to breast cancer cells BT474, endogenous β2M directly interacted with HFE in breast cancer cells MDA-MB-453, MDA-MB-231, and MCF-7. β2M activated the ERK signaling pathway by interacting with HFE and induced apoptosis of MDA-MB-453 cells. The expression of HFE and p-ERK1/2 showed significantly high levels in HER2-overexpressing breast cancer tumor tissue compared with adjacent normal tissue, consistent with the results obtained from the cell experiments.
CONCLUSIONS: β2M induced apoptosis of tumor cells via activation of the ERK signal pathway by directly interacting with HFE in HER2-overexpressing breast cancer.

Derivation of hypoimmunogenic human cells from genetically manipulated pluripotent stem cells holds great promise for future transplantation medicine and adoptive immunotherapy. Disruption of beta-2-microglobulin (B2M) in pluripotent stem cells followed by differentiation into specialized cell types is a promising approach to derive hypoimmunogenic cells. Given the attractive features of CRISPR/Cas9-based gene editing tool and baculoviral delivery system, baculovirus can deliver CRISPR/Cas9 components for site-specific gene editing of B2M. Herein, we report the development of a baculoviral CRISPR/Cas9 vector system for the B2M locus disruption in human cells. When tested in human embryonic stem cells (hESCs), the B2M gene knockdown/out was successfully achieved, leading to the stable down-regulation of human leukocyte antigen class I expression on the cell surface. Fibroblasts derived from the B2M gene-disrupted hESCs were then used as stimulator cells in the co-cultures with human peripheral blood mononuclear cells. These fibroblasts triggered significantly reduced alloimmune responses as assessed by sensitive Elispot assays. The B2M-negative hESCs maintained the pluripotency and the ability to differentiate into three germ lineages in vitro and in vivo. These findings demonstrated the feasibility of using the baculoviral-CRISPR/Cas9 system to establish B2M-disrupted pluripotent stem cells. B2M knockdown/out sufficiently leads to hypoimmunogenic conditions, thereby supporting the potential use of B2M-negative cells as universal donor cells for allogeneic cell therapy.

UNASSIGNED: Numerous studies have linked the inflammatory pathway in psoriasis and metabolic disease, while no specific marker defined it. It is worth exploring the association of β2-microglobulin (β2M) in psoriasis severity and comorbidities.
UNASSIGNED: To investigate the correlation between blood β2M level and psoriasis severity, to explore the inflammatory factors influencing the occurrence of psoriasis comorbidities such as arthritis, diabetes, and hypertension.
UNASSIGNED: Ninety-seven psoriasis patients were analyzed in the cohort retrospective study during 12 weeks.
UNASSIGNED: Significantly higher levels of blood β2M and ESR were observed in the group that patients\' PASI ≥10 than in the group that PASI <10. Blood β2M level had strong significantly positive correlations with the PASI in Pearson\'s correlation analysis. In the model that systemic inflammatory factors to find psoriasis comorbidity risk factors, logistic regression analysis showed that blood β2M level was the significant risk factor associated with diabetes and hypertension. High-sensitivity C-reactive protein (hsCRP) was the significant risk factor associated with arthritis.
UNASSIGNED: Patients with a severer psoriasis tended to have higher blood β2M levels and severer inflammatory state. In the systemic inflammation indexes, the level of blood β2M affected the risk of hypertension and diabetes, and hsCRP affected the risk of arthritis in patients with psoriasis.

OBJECTIVE: The aim of this study is to identify risk factors contributing to central nervous system (CNS) invasion and to validate the suitability of the Central Nervous System International Prognostic Index (CNS-IPI) for individuals afflicted with diffuse large B-cell lymphoma (DLBCL).
METHODS: Based on the presence or absence of CNS invasion, 365 patients were stratified into two groups: the CNS group and the non-CNS group. The clinical data of the patients were retrospectively analyzed using univariate and multivariate analysis, and the differences in survival curves were compared. The dependent variable in this study was the presence or absence of CNS invasion, while the independent variables included age, stage, extranodal involvement, renal/adrenal involvement, and others. Statistical methods included the chi-squared test and Fisher\'s exact test for intergroup comparison and binary logistic regression for multi-factor analysis. The related risk factors were modeled using the Cox proportional hazards model. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used to compare the differences between survival curves. The optimal cutoff value of beta-2 (β2)-microglobulin was determined through the utilization of a receiver operating characteristic (ROC) curve. All P values were bidirectional, and P < 0.05 was considered statistically significant. Both SPSS 23.0 (IBM Inc., Armonk, NY, USA) and RStudio (R software version 4.0.2, R Project for Statistical Computing) software were used for data processing RESULTS: The five factors of the CNS-IPI were related to the prognosis of patients with CNS invasion. Bone involvement, albumin < 40 g/L, and P53 protein (+) were the risk factors for CNS invasion in patients with DLBCL. However, prognostic factors such as double strike, testicular involvement, breast involvement, uterine involvement, and bone marrow involvement did not apply to these patients. It was also discovered that elderly patients with DLBCL with reduced albumin levels were more susceptible to CNS invasion. Furthermore, extranodal involvement at multiple sites and elevated beta-2 (β2) microglobulin were independent prognostic factors CONCLUSION: Patients older than 60 years with DLBCL and decreased albumin are at increased risk for CNS invasion. In addition to the five factors in the CNS-IPI, bone involvement, albumin levels < 40 g/L, and P53 protein expression are risk factors affecting the prognosis of CNS invasion in patients with DLBCL.

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.

To investigate the distribution of nine (9) urine biomarkers in people living with type 2 diabetes mellitus (T2DM), with or without microvascular complications.
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.
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).
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.

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。.

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。.

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。.

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。.