OBJECTIVE: To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics. METHODS: A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment. RESULTS: A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β ₂-microglobulin (β ₂M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β ₂M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β ₂M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84. CONCLUSIONS Based on proteomic analysis, CST3, β ₂M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans ; Sepsis/complications* ; Acute Kidney Injury/blood* ; Proteomics ; Prospective Studies ; Biomarkers/blood* ; Male ; Female ; beta 2-Microglobulin/blood* ; Middle Aged ; Cystatin C/blood* ; Aged

OBJECTIVE: To investigate the significance of HALP score as a prognostic indicator for newly diagnosed multiple myeloma (MM). METHODS: Clinical data of 62 newly diagnosed MM patients in our hospital from January 2020 to December 2022 were collected and retrospectively analyzed. The difference in age, sex, DS stage, R-ISS stage, M protein type, serum creatinine (Scr), β₂-microglobulin (β₂-MG), blood calcium, lactate dehydrogenase (LDH), hemoglobin (Hb), albumin (ALB), platelet count (PLT), and absolute lymphocyte count (ALC) between patients with low and high HALP scores were analyzed. The prognostic value of the above indexes in newly diagnosed MM patients was analyzed by univariate and multivariate analysis. RESULTS: The optimal cut-off value of HALP score was 41 determined by X-tile software. Based on this, 62 patients were divided into a high HALP group (HALP>41, n=25) and a low HALP group (HALP≤41, n=37). The proportion of patients with Hb≥100 g/L in the high HALP group was significantly higher than that in the low HALP group (P <0.05). The median overall survival (OS) time of patients in the high HALP group and low HALP group were 29 (9-39) months and 20 (4-29) months, respectively, with statistically significant difference between the two groups (P <0.01). Univariate analysis showed that R-ISS stage, ALB, Hb, ALC and HALP were closely related to the prognosis of patients (P <0.05). COX regression multivariate analysis showed that R-ISS stage Ⅲ (HR=4.443, 95%CI : 1.480-13.343，P =0.008) and HALP≤41(HR=8.823, 95%CI : 1.858-41.910，P =0.006) were independent risk factors for shortened OS in newly diagnosed MM patients. The median OS of patients with high HALP at R-ISS stage Ⅲ was significantly higher than that of patients with low HALP at the same stage, and the difference was statistically significant (P <0.05). CONCLUSION HALP score can be used as a prognostic indicator for newly diagnosed MM patients.
Humans ; Multiple Myeloma/diagnosis* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; beta 2-Microglobulin ; Lymphocyte Count

OBJECTIVE: To investigate the prognostic value of serum and cerebrospinal fluid β2-microglobulin (β2-MG) in acute lymphoblastic leukemia (ALL) with central nervous system invasion after chemotherapy. METHODS: 40 patients with leukemia who had been confirmed to have central nervous system infiltration were selected for treatment at the Second Affiliated Hospital of Chongqing Medical University from January 2015 to May 2017, and the serum levels of β2-MG and CSF-β2MG were dynamically monitored and performed statistical analysis. RESULTS: After chemotherapy, the changes in serum β2-MG were not statistically significant (P>0.05); the absolute level of CSF-β2MG and the percentage of relative baseline changes were statistically different in different clinical outcome groups(P<0.05), and the decreasing CSF-β2MG levels suggest a better prognosis, with cut-off values of 1.505 and -25%, respectively. CONCLUSION The best cut-off point may be a predictor of complete remission; the reduction of the absolute and relative levels of CSF-β2MG can suggest a good prognosis for patients.
Central Nervous System ; Cerebrospinal Fluid ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Remission Induction ; beta 2-Microglobulin

OBJECTIVE: To investigate the expression of HSP90 in bone marrow samples of multiple myeloma (MM) patients and explore its clinical significance. METHODS: Maxvision immunohistochemistry technique was used to detect the protein expression level of HSP90 76 MM patients and 29 normal healthy donors. The clinical characteristics of the patients were collected, and the correlation between the HSP90 expression and the clinical characteristics was analyzed. RESULTS: The count of MM patients with positive HSP90 protein was significantly higher than that of normal healthy donor, and there were no significant correlation between HSP90 expression and age, sex, hemoglobin (Hb), creatinine (CREA), blood calcium, lactate dehydrogenase (LDH), bone marrow plasma cell proportion and MM subtypes (P>0.05), but HSP90 expression was correlated with β CONCLUSION HSP90 protein was over-expressed in MM patients, and was correlated with β
Bone Marrow ; HSP90 Heat-Shock Proteins ; Humans ; Multiple Myeloma ; Prognosis ; beta 2-Microglobulin

The β2m (Beta-2-microglobin) gene encodes a non-glycosylated protein that functions as an important component of major histocompatibility complexⅠ(MHCⅠ) for antigen presentation. To evade immune mediated clearance, human tumors and pathogens have adopted different strategies, including loss of MHCⅠexpression. Appropriate animal models are essential for understanding the mechanisms underpinning the clinical treatment of tumor and other human diseases. We constructed β2m knockout mice using CRISPR/Cas9 gene editing tool through embryo microinjection. Subsequently, genotyping and phenotyping of knockout mice were performed by PCR, qPCR, and flow cytometry. Mice genotyping showed that the coding region of the target gene was absent in the knockout mice. Real time PCR showed that mRNA level of β2m was significantly downregulated. Flow cytometry showed that the proportions of CD8+ killer T cells was significantly reduced in a variety of tissues and organs of the immune system. Taken together, we have successfully constructed a strain of β2m knockout mice, which will facilitate subsequent in vivo study on the function and mechanism of the β2m gene.
Animals ; Histocompatibility Antigens Class I ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; T-Lymphocytes, Cytotoxic ; beta 2-Microglobulin/genetics*

BackgroundAs a major complication after orthotopic liver transplantation (OLT), the occurrence of acute kidney injury (AKI) is frequently defined by serum creatinine (Cr); however, the accuracy of commonly used blood urea nitrogen (BUN), uric acid (UA), and &beta;-microglobulin (&beta;-MG) remains to be explored. This retrospective study compared the accuracy of these parameters for post-OLT AKI evaluation.

MethodsPatients who underwent OLT in three centers between July 2003 and December 2013 were enrolled. The postoperative AKI group was diagnosed by the Kidney Disease Improving Global Outcomes (KDIGO) criteria and classified by stage. Measurement data were analyzed using the t-test or Wilcoxon rank-sum test; enumerated data were analyzed using the Chi-square test or Fisher's exact test. Diagnostic reliability and predictive accuracy were evaluated using receiver operating characteristic (ROC) curve analysis.

ResultsThis study excluded 976 cases and analyzed 697 patients (578 men and 119 women); the post-OLT AKI incidence was 0.409. Compared with the no-AKI group, the AKI group showed very significant differences in Model for End-stage Liver Disease score (14.74 ± 9.91 vs. 11.07 ± 9.54, Z = 5.404; P < 0.001), hepatic encephalopathy (45 [15.8%] vs. 30 [7.3%], χ = 12.699; P < 0.001), hemofiltration (28 [9.8%] vs. 0 [0.0%], χ = 42.171; P < 0.001), and 28-day mortality (23 [8.1%] vs. 9 [2.2%], χ = 13.323; P <0.001). Moreover, mean values of Cr, BUN, UA, and &beta;-MG in the AKI group differed significantly at postoperative days 1, 3, and 7 (all P < 0.001). ROC curve area was 0.847 of Cr for the detection of AKI Stage 1 (sensitivity 80.1%, specificity 75.7%, cutoff value 88.23 μmol/L), 0.916 for Stage 2 (sensitivity 87.6%, specificity 82.6%, cutoff value 99.9 μmol/L), and 0.972 for Stage 3 (sensitivity 94.1%, specificity 88.2%, cutoff value 122.90 μmol/L).

ConclusionThe sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.

Acute Kidney Injury ; blood ; Adult ; Blood Urea Nitrogen ; Creatinine ; blood ; Female ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Retrospective Studies ; Uric Acid ; blood ; beta 2-Microglobulin ; blood

In multiple myeloma (MM), hyperdiploidy (HD) is known to impart longer overall survival. However, it is unclear whether coexistent HD ameliorates the adverse effects of known high-risk cytogenetics in MM patients. To address this issue, we investigated the clinicopathological characteristics of HD with high-risk cytogenetics in MM. Ninety-seven patients with MM were included in the study. For metaphase cytogenetics (MC), unstimulated cells from bone marrow aspirates were cultured for either 24 or 48 hours. To detect HD by interphase fluorescence in situ hybridization (iFISH), we assessed trisomies of chromosomes 5, 7, 9, 11, 15, and 17. Of the 97 MM patients, 40 showed HD. The frequency of co-occurrence of HD and high-risk cytogenetics was 14% (14/97). When the clinicopathological characteristics were compared between the two groups of HD with high-risk cytogenetics vs. non-HD (NHD) with high-risk cytogenetics, the level of beta 2 microglobulin and stage distribution significantly differed (P=0.020, P=0.032, respectively). This study shows that some of the clinicopathological characteristics of MM patients with high-risk cytogenetics differ according to HD or NHD status.
beta 2-Microglobulin ; Bone Marrow ; Cytogenetics* ; Fluorescence ; Humans ; In Situ Hybridization ; Interphase ; Metaphase ; Multiple Myeloma* ; Trisomy

OBJECTIVEThis review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (&beta;2M), a conservative immune molecule in vertebrate.

DATA SOURCESThe data used in this review were obtained from PubMed up to October 2015. Terms of &beta;2M, immune response, and infection were used in the search.

STUDY SELECTIONSArticles related to &beta;2M were retrieved and reviewed. Articles focusing on the characteristic and function of &beta;2M were selected. The exclusion criteria of articles were that the studies on &beta;2M-related molecules.

RESULTS&beta;2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of &beta;2M is associated with multiple diseases, including endogenous and infectious diseases. &beta;2M could directly participate in the development of cancer cells, and the level of &beta;2M is deemed as a prognostic marker for several malignancies. It also involves in forming major histocompatibility complex (MHC class I or MHC I) or like heterodimers, covering from antigen presentation to immune homeostasis.

CONCLUSIONSBased on the characteristic of &beta;2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, &beta;2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of &beta;2M on applications.

Antigens, CD1 ; physiology ; Hemochromatosis Protein ; analysis ; Histocompatibility Antigens Class I ; physiology ; Humans ; Receptors, Fc ; physiology ; beta 2-Microglobulin ; blood ; chemistry ; deficiency ; physiology

OBJECTIVES: To investigate the clinical findings upon initial diagnosis and extraglandular manifestations in Korean patients with primary Sjogren's syndrome (pSS). METHODS: We collected clinical and laboratory data from 238 pSS patients enrolled at Seoul National University Hospital, Seoul National University Bundang Hospital and Seoul Medical Center from March 2011 to December 2014. All patients met the American-European Consensus Group criteria for pSS. RESULTS: Upon initial diagnosis, sicca symptoms (xerophthalmia or xerostomia) as the chief complaint were only observed in 129 (54.2%) pSS patients, while extraglandular manifestation was more common as the chief complaint in male patients or those with younger age (<40 years) than female or older patients (both p<0.05). Extraglandular manifestations were found in 178 (74.8%) patients, with musculoskeletal manifestations being most common (53.8%). Peripheral neuropathy in pSS patients was associated with Raynaud phenomenon and elevated serum total immunoglobulin G (IgG) levels (both p<0.05). Serum beta2-microglobulin (beta2-M) levels were significantly correlated with European League against Rheumatism (EULAR) Sjogren's syndrome disease activity index, erythrocyte sedimentation rate and serum total IgG (all p<0.001), and were higher in patients with extraglandular manifestations than those without (p<0.05). Serum C3 levels were decreased in patients with extraglandular manifestation, compared to those without (p<0.05). Malignant lymphoma was found in Korean pSS patients (1.7%) and associated with elevated serum beta2-M levels (p<0.0001). CONCLUSION: Extraglandular manifestations were common in pSS patients and may be a diagnostic tool for male or younger pSS patients. Serum beta2-M levels can be useful markers for monitoring pSS patients.
beta 2-Microglobulin ; Consensus ; Diagnosis ; Erythrocyte Indices ; Female ; Humans ; Immunoglobulin G ; Lymphoma ; Male ; Peripheral Nervous System Diseases ; Raynaud Disease ; Rheumatic Diseases ; Seoul ; Sjogren's Syndrome*

OBJECTIVEThe aim of this study was to investigate the effectiveness of treatment, survival and prognostic factors in Chinese patients with Hodgkin lymphoma.

METHODSA total of previously untreated 415 patients with histologically confirmed Hodgkin lymphoma admitted in the Cancer Hospital, Chinese Academy of Medical Sciences from February 1999 to February 2011 were included in this study. Their short-term and long-term survivals, as well as prognostic factors were analyzed.

RESULTSFor the whole group, 371 cases (89.4%) had complete remission (CR), 33 cases (8.0%) had partial remission (PR) and 11 cases (2.7%) experienced disease progression. The CR rates for stage I, II, III and IV patients were 96.6% (56/58), 92.0% (219/238), 83.6% (51/61) and 77.6% (45/58), respectively (P < 0.001). The 5-year disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) were 90.6%, 84.1% and 92.5%. The stage I-II patients were significantly better than stage III-IV patients in terms of 5-year DFS rate (94.5% vs. 79.2%, P < 0.001), 5-year PFS rate (91.2% vs. 66.4%, P < 0.001) and 5-year OS rate (97.0% vs. 81.5%, P < 0.001). For stage I-II patients, combined modality therapy was related to better DFS, PFS and OS as compared with radiotherapy alone, and was associated with a better PFS compared with chemotherapy alone. There was a trend that consolidative radiotherapy could improve the long-term survival for stage III-IV patients who achieved disease remission after chemotherapy. What's more, consolidative radiotherapy could significantly improve PFS for those stage II-IV patients who achieved PR after chemotherapy. Multivariate analysis showed that clinical stage and pathological type were independent prognostic factors for the 5-year DFS rate (both P < 0.05), and the stage, elevated serum &beta;2-microglobulin and none-ABVD/BEACOP chemotherapy regimen were independent prognostic factors for 5-year PFS rate and 5-year overall survival rate (P < 0.05 for all).

CONCLUSIONSPatients with HL treated in China have a good prognosis. Combined modality therapy is the preferred treatment for stage I-II patients. Consolidative radiotherapy is recommended to those of stage III-IV patients who experienced PR after chemotherapy. Stage, serum &beta;2-microglobulin and first-line chemotherapy regimen significantly affect the prognosis for patients with Hodgkin lymphoma.

Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Bleomycin ; China ; Combined Modality Therapy ; mortality ; Dacarbazine ; Disease Progression ; Disease-Free Survival ; Doxorubicin ; Hodgkin Disease ; mortality ; pathology ; therapy ; Humans ; Multivariate Analysis ; Prognosis ; Radiotherapy, Adjuvant ; mortality ; Remission Induction ; Survival Rate ; Treatment Outcome ; Vinblastine ; beta 2-Microglobulin ; blood