Cerebrospinal Fluid β2-Microglobulin for Prognostic Evaluation of Patients with Central Nervous System Infiltration in Acute Lymphoblastic Leukemia / 中国实验血液学杂志

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.

Construction of β2m knockout mice / 生物工程学报

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.

Expression and Clinical Significance of Heat Shock Protein 90 in Multiple Myeloma Patients / 中国实验血液学杂志

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

Síndrome de hiperviscosidade em paciente com mieloma múltiplo / Hyperviscosity syndrome in multiple myeloma patients

O mieloma múltiplo é uma neoplasia progressiva e incurável de células B, caracterizado pela proliferação desregulada e clonal de plasmócitos na medula óssea. A síndrome de hiperviscosidade é uma das complicações relacionadas às gamopatias monoclonais, sendo considerada emergência oncológica. O objetivo deste estudo foi descrever o quadro clínico de um paciente diagnosticado com mieloma múltiplo que apresentou síndrome de hiperviscosidade, avaliando a prevalência de sinais e sintomas, bem como características fisiopatológicas dessa entidade clínica. Foi revisado o prontuário de um paciente internado na enfermaria da Clínica Médica do Hospital Regional do Cariri (CE) no período de junho a julho de 2018. Além disso, foi realizada revisão de literatura em base de dados (PubMed®) direcionada ao tema proposto. O diagnóstico de mieloma múltiplo foi comprovado por mielograma, sendo prontamente iniciada a corticoterapia e avaliada a resposta clínica após essa terapêutica. Apesar de incomum e menos frequentemente relacionada ao mieloma múltiplo, a síndrome de hiperviscosidade está relacionada a uma grande taxa de mortalidade quando apresenta diagnóstico tardio. A terapia de primeira linha indicada para a síndrome de hiperviscosidade foi a plasmaferese, no entanto, as condições clínicas (instabilidade hemodinâmica) impossibilitaram sua realização. O desfecho deste caso foi o óbito do paciente. Concluiu-se que o diagnóstico precoce e a intervenção terapêutica estão diretamente relacionados à ocorrência de menor incidência de complicações relacionadas ao mieloma múltiplo e à síndrome de hiperviscosidade.

Multiple myeloma is a progressive and incurable B-cell neoplasm characterized by unregulated and clonal proliferation of plasmocytes in the bone marrow. Hyperviscosity syndrome is one of the complications related to monoclonal gammopathies and is considered an oncological emergency. The aim of this study was to describe the clinical condition of a patient diagnosed with multiple myeloma who presented hyperviscosity syndrome, evaluating the prevalence of symptoms and signs, as well as the pathophysiological characteristics of this clinical entity. The medical records of a patient admitted to the Internal Medicine ward of the Hospital Regional do Cariri (CE) from June to July of 2018 were reviewed. In addition, we conducted a literature review in a database (PubMed®) directed to the theme proposed. The diagnosis of multiple myeloma was confirmed by myelogram, and corticosteroid therapy was promptly initiated and the clinical response was evaluated after this therapy. Although uncommon and less frequently related to multiple myeoloma, hyperviscosity syndrome is related to a high mortality rate when diagnosed late. The first line therapy indicated to hyperviscosity syndrome was plasmapheresis; however, the clinical conditions (hemodynamic instability) precluded its performance. The outcome of this case was the patient's death. Thus, it was concluded that early diagnosis and therapeutic intervention are directly related to the occurrence of lower incidence of complications related to multiple myeloma and hyperviscosity syndrome.

ß2-Microglobulina un biomarcador de actividad en pacientes con lupus eritematoso sistémico / ß2-Microglobulin a biomarker of disease activity in systemic lupus erythematosus patients

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune, caracterizada por daño crónico a órganos o sistemas, caracterizada por la activación anormal de linfocitos T y/o B debido a una presentación y reconocimiento antigénico anormal que favorece la producción de citoquinas pro inflamatorias y auto-anticuerpos fijadores de complemento que promueven la formación y depósito de complejos inmunes con el consecuente daño celular. También se caracteriza por periodos cíclicos de brote y remisión de la enfermedad. La búsqueda de biomarcadores clínicamente útiles para conocer de manera anticipada un brote de la enfermedad aún está en curso, entre los biomarcadores se sugiere que la ß2-microglobulina (ß2M) puede ser útil para evaluar la actividad del LES. El objetivo del estudio fue correlacionar la concentración de ß2M sérica con los marcadores comúnmente evaluados para establecer la actividad del LES. MATERIAL Y MÉTODO La población de estudio consistió en 119 pacientes con LES activo y no activo (57 pacientes control, 42 pacientes con LES activo y 20 pacientes con LES inactivo) los cuales firmaron su consentimiento para participar en el estudio. El grupo control correspondía a pacientes sin antecedentes clínicos y familiares de enfermedad autoinmune. El grupo de pacientes con LES cumplía al menos 4 criterios de clasificación de LES del Colegio Americano de Reumatología. La concentración de ß2M se midió por ELISA. La actividad del LES fue evaluada mediante parámetros clínicos, niveles séricos de anti-ds-DNA, fracción del complemento C3 y C4. Los niveles de ß2M fueron asociados con marcadores serológicos de anti-nucleosoma, anti-C1q y creatinina. RESULTADOS El estudio reveló diferencia significativa en los niveles séricos de ß2M (p<0.001) entre los tres grupos de estudio, en los pacientes con LES activo se observó una mediana 5,4 ug/mL, P25 3,17 ug/mL P75 6,72 ug/mL; el grupo control presentó una mediana menor al grupo LES activo de 1,8 ug/mL P25 1,6 ug/mL P75 1,9 ug/mL y al grupo de LES inactivo con mediana de 3,25 ug/mL P25 2,63 ug/mL P75 3,55 ug/mL. Además, se observó correlación de resultados entre la concentración de ß2M y niveles de anti-ds-DNA (p<0,01; r=0,595) y niveles séricos del complemento C3 (p<0,01; r=−0,519) y C4 (p=0,019; r=−0,345). CONCLUSIONES La medición de la ß2M sérica puede ser un biomarcador útil para evaluar la actividad de la enfermedad del LES siempre y cuando sea empleado con otros test de laboratorio que se utilizan de manera rutinaria para evaluar la actividad de LES.

Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by chronic damage to organs or systems, due to abnormal activation of T and/or B-lymphocytes, caused by abnormal antigenic presentation and recognition that gives the production of pro- inflammatory cytokines and complement-fixing autoantibodies that promote formation of immune complexes and cellular damage. It is also characterized by cyclic periods of activation and remission. The search for clinically useful biomarkers for early knowledge of disease outbreak is going; biomarkers suggest that ß2-microglobulin (ß2M) is useful for evaluating the activity of the SLE. The objective of this study was to analyze the relationship between serum ß2M concentrations with markers of SLE activity. MATERIAL AND METHODS One hundred nineteen patients were included (control 57, active SLE 42 and inactive SLE 20) who signed their consent to participate in the study. The control group corresponded to patients without clinical and family history of autoimmune disease. The patients group with SLE met at least four criteria of the American Society of Rheumatology for lupus diagnostic. ß2M concentration was measured using an ELISA test. SLE activity was evaluated by clinical parameters, serum levels of anti-ds-DNA, complement levels C3 and C4. ß2M levels were associated with anti-nucleosome, anti-C1q and creatinine. RESULTS The study revealed a significant difference between the three study groups (p<0,01), in active SLE group a median 5,4 ug/mL, P25 3,17 ug/mL P75 6,72 ug/mL was observed. The control group presented a lower median to the active SLE group of 1,8 ug/mL P25 1,6 ug/mL P75 1,9 ug/mL and to the inactive SLE group with a median 3,25 ug/mL P25 2,63 ug/mL P75 3,55 ug/mL. In addition, correlation of results was observed between ß2M concentration and anti-ds-DNA levels (p<0,01, r=0,595) and complement serum level C3 (p<0,01, r=-0,519) and C4 (p=0,019; r=-0,345). CONCLUSION ß2M serum measurement can be a useful biomarker to assess the SLE activity as long as it is used with other laboratory tests that are routinely used to evaluate the activity of SLE.

Predictive Value of Serum Creatinine, Blood Urea Nitrogen, Uric Acid, and β-Microglobulin in the Evaluation of Acute Kidney Injury after Orthotopic Liver Transplantation / 中华医学杂志(英文版)

<p><b>Background</b>As 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 β-microglobulin (β-MG) remains to be explored. This retrospective study compared the accuracy of these parameters for post-OLT AKI evaluation.</p><p><b>Methods</b>Patients 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.</p><p><b>Results</b>This 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 β-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).</p><p><b>Conclusion</b>The sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.</p>

Clinicopathological Characteristics of Hyperdiploidy with High-Risk Cytogenetics in Multiple Myeloma

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.

The Implication and Significance of Beta 2 Microglobulin: A Conservative Multifunctional Regulator / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>This review focuses on the current knowledge on the implication and significance of beta 2 microglobulin (β2M), a conservative immune molecule in vertebrate.</p><p><b>DATA SOURCES</b>The data used in this review were obtained from PubMed up to October 2015. Terms of β2M, immune response, and infection were used in the search.</p><p><b>STUDY SELECTIONS</b>Articles related to β2M were retrieved and reviewed. Articles focusing on the characteristic and function of β2M were selected. The exclusion criteria of articles were that the studies on β2M-related molecules.</p><p><b>RESULTS</b>β2M is critical for the immune surveillance and modulation in vertebrate animals. The dysregulation of β2M is associated with multiple diseases, including endogenous and infectious diseases. β2M could directly participate in the development of cancer cells, and the level of β2M 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.</p><p><b>CONCLUSIONS</b>Based on the characteristic of β2M, it or its signaling pathway has been targeted as biomedical or therapeutic tools. Moreover, β2M is highly conserved among different species, and overall structures are virtually identical, implying the versatility of β2M on applications.</p>

Urinary markers for early detection of Diabetic Nephropathy in type 1 Diabetes Mellitus

Background: diabetic nephropathy [DN] is a serious complication of diabetic mellitus associated with increased risk of morbidity and mortality. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney functions and improve patient outcomes. N-acetyl Beta d-glucosaminidase [NAG] is a lysosomal enzyme, present in high concentrations in renal proximal tubular cells, Gamma-glutamyltransferase [GGT] is an enzyme which located along the proximal tubular brush border, Malondialdehyde [MDA] is a highly toxic product, formed in part by lipid oxidation derived free radicals, Reactive carbonyl derivatives [RCD[S]] is an oxidative stress marker in urine, as a measure of the oxidative modification of proteins and beta-2-microglobulin is filtered by the glomerulus, absorbed and catabolized by the proximal tubules. The aim of this study is to investigate the urinary outcome of these markers as early detectors of diabetic nephropathy in type 1 diabetic children

Subjects and methods: This case-control study included 67 children with type 1 diabetes mellitus [33 male; 34 female], age [11.03 +/- 1.05 years] and thirty one age [10.58 +/- 1.11 years] and sex [13 male; 18 female] matched healthy children [13 male; 18 female]. Type 1 diabetic children were further subdivided into microalbuminuric and normoalbuminuric subgroups according to microalbuminuria concentration [30 mg/ g creatinine]. Age, sex, diabetic duration and the current daily insulin dose, and family history of diabetes, weight, height, body mass index, systolic and diastolic blood pressure were recorded. Fasting plasma glucose, glycated hemoglobin, blood urea nitrogen, plasma creatinine, urinary creatinine, micoalbumin, N-acetyl-B-D glucosaminidase [NAG], Gama glutamyl transferase [GGT], Beta-2-microglobulin, Malondialdehyde [MDA] and Reactive carbonyl groups [RCDS[S]] were measured in all subjects

Results: a significant increase in tubular injury markers of diabetes [NAG, GGT, beta-2-microglobulin] and oxidative stress parameters [MDA, RCDS[S]] as compared to control subjects was found. Microalbuminuric subjects showed a significant elevatation in the urinary markers including NAG, GGT, beta-2-microglobulin, MDA, RCDS[S] as compared to normoalbuminuric subjects. The studied urinary tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta-2- microglobulin showed positive correlations with one another

Conclusion: The results of this study introduced the possibility of depending on tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta2 microglobulin as early, reliable, and sensitive predictors for diabetic nephropathy. The NAG activity index proved to be the most sensitive biomarker, then beta-2- microglobulin for early discovering the tubule cells damage

A analysis of the outcome and prognostic factors in 415 patients with Hodgkin lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the effectiveness of treatment, survival and prognostic factors in Chinese patients with Hodgkin lymphoma.</p><p><b>METHODS</b>A 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.</p><p><b>RESULTS</b>For 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 β2-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).</p><p><b>CONCLUSIONS</b>Patients 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 β2-microglobulin and first-line chemotherapy regimen significantly affect the prognosis for patients with Hodgkin lymphoma.</p>

The impact of renal function on prognostic value of β₂-microglobulin of ISS stage system in multiple myeloma patients--Clinical data analysis of 666 patients in a single center / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the influence of renal function on the level of β₂-microglobulin (β₂-MG) as prognostic factor in newly diagnosed multiple myeloma (MM) patients, and to analyze the overall survival (OS) in different level of β₂-MG with relatively normal or abnormal renal function in MM patients.</p><p><b>METHODS</b>According to the level of β₂-MG, 666 newly diagnosed MM patients were divided into three groups as β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L. According to the level of serum creatinine, these patients were divided into two groups:serum creatinine <177 μmol/L as relatively normal group, serum creatinine ≥177 μmol/L as abnormal group.</p><p><b>RESULTS</b>Among 666 patients, there were 416 male and 250 female, the median age was 58 (25-86) years old. Comparison of OS among β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L groups indicated that the median OS of the three groups were 85.75 (95% CI 70.99-100.50), 47.25 (95% CI 40.98-53.53) and 35.05 (95% CI 30.75-39.35) months, respectively (P<0.01). Comparison of OS between serum creatinine <177 and ≥177 mmol/L groups, the median OS of the two groups were 64.67 (95% CI 56.57-72.77) and 32.74 (95% CI 27.74-37.73) months, respectively (P<0.01). In β₂-MG≥5.5 mg/L, the median OS of relatively normal and abnormal groups were 37.25 (95% CI 31.45-43.06) and 32.55 (95% CI 26.26-38.83) months, respectively (P=0.142).</p><p><b>CONCLUSION</b>High level of β₂-MG and renal function correlated with shorter survival of MM patients. Higher level of β₂-MG with abnormal renal function can't change the prognostic value of β₂-microglobulin on MM.</p>

Optimization of Prokaryotic Expression Conditions of Human β2-microglobulin in E. Coli and Its Purification / 生物医学工程学杂志

To obtain recombinant human β2-microglobulin (rhβ2M) with properties of good solubility and high purity from E. coli, prokaryotic expression conditions were optimized and protein purification was performed in this study. After testing the effect of different IPTG concentrations, temperatures and induction times on the production of rhβ2M, the optimum expression conditions were determined, i. e. joining IPTG to final concentration being 0.8 mmol/L and inducing time 6 h and at temperature of 25 degrees C. Under the optimum induction conditions, the ratio of soluble rhβ2M to soluble bacterial protein was 63.7%. After purified by Ni Sepharose 6 Fast Flow, the purity of rhβ2M achieved a greater value of 95%. Western blot analysis revealed that rhβ2M possessed the antigen property that specifically interacted with anti-β2M antibody.

Extraglandular Manifestations in Korean Patients with Primary Sjogren's Syndrome

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.

Values of Detecting the Levels of β2-MG, TNF-α, CRP, IL-6 in the Patients with Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the values of detecting the serum levels of β2-MG, TNF-α, CRP, IL-6 in the patients with multiple myeloma.</p><p><b>METHODS</b>A total of 40 patents with multiple myeloma were included in the experiment group, and 40 healthy volunteers were selected as the control group. The levels of β2-MG, TNF-α, CRP and IL-6 were detected and compared in 2 groups, the different durie-salmon (DS) stages of β2-MG, TNF-α, CRP and IL-6 in the experiment group were analyzed.</p><p><b>RESULTS</b>The levels of β2-MG, CRP, IL-6 in the experiment group were higher than those in control group (P < 0.05); the level of TNF-α in the experiment group was lower than that in control group (P < 0.05); the levels of β2-MG, CRP, IL-6 at stage I, II, III in the experiment group was higher than those in control group (P < 0.05); the level of TNF-α at stage I, II, III in the experiment group was lower than that in the control group (P < 0.05); the levels of β2-MG, CRP, IL-6 at stage I, II, III in the experiment group displayed an increasing tendency, the levels of TNF-α at stage I, II, III in the experiment group displayed a declining trend (P < 0.05); the levels of β2-MG, CRP, IL-6 in the experiment group after treatment for 8, 16 weeks were higher than those in control group (P < 0.05); the level of TNF-α in the experiment group after treatment for 8, 16 weeks was lower than that in control group (P < 0.05); the levels of β2-MG, CRP and IL-6 in the experiment group after treatment for 16 weeks were lower than those for 8 weeks (P < 0.05); the levels of TNF-α in the experiment group after treatment for 16 weeks were higher than those for 8 weeks (P < 0.05). The levels of APE1 after treatment in the experiment group were lower than that before treatment.</p><p><b>CONCLUSION</b>The serum levels of β2-MG, TNF-α, CRP and IL-6 can be as index for diagnosis of multiple myeloma, can effectively evaluate the disease severity; their combination with APE1 expression level can evaluate the therapeutic efficacy; thus the detection of above-mentioned indexes is possessed of higher value for clinical applications.</p>

Caracterización de factores pronósticos en pacientes con linfoma B difuso de células grandes / Characterization of prognostic factors to diagnosis of patients with diffuse large B cell lymphoma

Objetivo: describir los factores pronósticos demográficos, clínicos, hematológicos, inmunohistoquímicos y bioquímicos al diagnóstico de pacientes con linfoma B difuso de células grandes y su asociacióncon la severidad según el Índice Pronóstico Internacional en un Hospital Universitario, 2009-2012. Métodos: se realizó un estudio descriptivo en 40 pacientes con dicho linfoma. Se comparó laconcentración de β2 microglobulina con los factores pronósticos que componen el IPI y otros que nohacen parte; se determinó la asociación entre el IPI e IPI revisado y la concentración de β2 microglobulina,infiltración medular, masa voluminosa y expresión de BCL-2 y Ki-67. La información se analizó en SPSS. Resultados: 40% de los pacientes pertenecían al grupo de riesgo alto según el IPI y 55% al grupocon pronóstico pobre según el IPI revisado; 82.5% expresaron BCL-2 y 61.5% tenían un Ki-67>70%.Se observó asociación entre la β2 microglobulina y el Ann Arbor (p=0.036), la β2 microglobulina y lainfiltración medular (p=0.003), y la β2 microglobulina y el IPI revisado (p=0.037). Conclusiones: es probable que el tiempo transcurrido entre la aparición de los síntomas y eldiagnóstico haya favorecido que los pacientes se presentaran en estados avanzados de la enfermedady como consecuencia, con un pronóstico pobre. Así mismo, el estudio de la infiltración medular, elporcentaje de expresión de Ki-67 y la concentración de β2 microglobulina favorece a la identificaciónde pacientes con un pronóstico adverso. (Acta Med Colomb 2014: 39: 137-147).

Objective: to describe demographic, clinical, hematological, and immunohistochemical and biochemical prognostic factors to the diagnosis of patients with diffuse large B cell lymphoma and itsassociation with the severity according to the International Prognostic Index in a University Hospital,2009-2012. Methods: a descriptive study was conducted in 40 patients with this lymphoma. β2 microglobulinconcentration was compared with prognostic factors that compose the IPI and others which are not part of it; the association between IPI and revised IPI and β2 microglobulin concentration, bone marrow infiltration, bulky mass and expression of BCL -2 and Ki p-67 was determined. Data was analyzed in SPSS. Results: 40% of the patients were in the high risk group according to IPI and 55% to the group with poor prognosis according to the revised IPI; 82.5% expressed BCL-2 and 61.5% had a Ki-67 > 70%. Association between β2 microglobulin and Ann Arbor (p = 0.036), the β2 microglobulin and bone marrow infiltration (p = 0.003), and β2 microglobulin and revised IPI (p = 0.037) was observed. Conclusions: it is likely that the time between onset of symptoms and diagnosis has favored tha patients presented in advanced stages of the disease and as a result, with a poor prognosis. Likewise, the study of bone marrow infiltration, the percentage of Ki-67 expression and the concentration of β2 microglobulin favors the identification of patients with an adverse prognosis. (Acta Med Colomb 2014: 39: 137-147).

Expression of serum GDF15 and its clinical significance in multiple myeloma patients / 中南大学学报(医学版)

OBJECTIVE@#To determine the serum level of the growth differentiation factor 15 (GDF15) in multiple myeloma (MM) patients and analyze its level with other clinical parameters, and to investigate its significance in the formation, development and prognosis assessment of MM.@*METHODS@#We used enzyme-linked immunosorbent assay (ELISA) to measure the serum level of GDF15 in an MM group (24 pre-treatment patients) and in 20 healthy controls. All patients' clinical data were collected.@*RESULTS@#The serum GDF15 level was significantly higher in the MM group [(1.37±0.64) ng/mL] than in the normal control group [(0.14±0.06) ng/mL, P0.05). After 3 cycles of chemotherapy, patients with a>50% reduction of M protein had a significant reduction of GDF15, while for the patients whose M protein did not decrease obviously, their corresponding serum GDF15 level increased.@*CONCLUSION@#The serum GDF15 level may reflect the tumor burden in the MM patients, which increases obviously, is related with ISS, positively correlated with serum M protein level, β2- microglobulin level, serum creatinine and negatively with hemoglobin concentration and platelet count. The change of serum GDF15 level has some relation with the extent of M protein reduction, suggesting it may be used as a marker for therapy response.

Effects of tank operation on renal function of crews / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of harmful factors in tank cabins on renal function of tank crews.</p><p><b>METHODS</b>One hundred and fifty two tank crews as the observation group and 37 soldiers without tank environment exposure as control group were selected in the study. α1-microglobulin(α1-MG), β2-microglobulin(β2-MG), IgG, N-acetyl-β-glucosidase (NAG) and urinary albumin excretion rate (UAER) in morning and 24 h urine were measured.</p><p><b>RESULTS</b>Compared to the control group, the levels of α1-MG, β2-MG, NAG, UAER in observation group were increased significantly (P < 0.05). β2-MG, NAG, UAER of Soldiers with more than 50 motorized hours in observation group were significantly higher than those of control group (P < 0.05). β2-MG, NAG and UAER of soldiers divorced from tank occupation more than 3 years decreased to the normal levels. β2-MG of soldiers divorced from tank occupation more than 10 years was significantly higher than that of 6-10 years group.</p><p><b>CONCLUSION</b>Tank occupational exposure influences the renal function of tank crews but not to a degree of clinical kidney disease. The renal function of crews divorced from tank occupation may recover but dysfunction of renal tubular reabsorption still exists.</p>

Endocrine disruption of cadmium in rats using the OECD enhanced TG 407 test system / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To evaluate the endocrine disrupting effects of cadmium (Cd) using OECD enhanced TG407 test guideline.</p><p><b>METHODS</b>Sprague-Dawley (SD) rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg•BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary β2-microglobulin, organ weights and histopathology and estrous cycle were detected.</p><p><b>RESULTS</b>Cd could significantly decrease animals' body weight (P<0.05). Serum luteinizing hormone (LH) at 10-20 mg/kg•BW groups and testosterone (T) at 2.5 and 10 mg/kg•BW groups decreased significantly (P<0.05). However, no statistically significant change was found in urinary β2-microglobulin among Cd-treatment groups (P>0.05). Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg•BW groups showed significant increase (P<0.05). While among male rats in 2.5, 10, 20 mg/kg•BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased (P<0.05). Moreover, no histopathological change was observed in kidney.</p><p><b>CONCLUSION</b>Results suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.</p>

Urinary excretion of beta2-microglobulin as a prognostic marker in immunoglobulin A nephropathy

BACKGROUND/AIMS: beta2-microglobulin (beta2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary beta2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear. METHODS: We included urinary beta2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between beta2-MG levels and clinical parameters as a prognostic biomarker of IgAN. RESULTS: A total of 51 patients (30 males, 21 females; mean age, 33.01 +/- 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 +/- 34.78 mL/min/1.73 m2 and 1.28 +/- 1.75 g/day, respectively. The mean level of urinary beta2-MG was 1.92 +/- 7.38 microg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of beta2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary beta2-MG (p < 0.01). Cox regression analysis showed that albumin, beta2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN. CONCLUSIONS: Urinary beta2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary beta2-MG may be an additional prognostic factor in patients with IgAN.

relationship between salivary beta-2 microglobulin and uremia intensity in men with chronic renal failure

This study defines the relationship between salivary beta-2 microglobulin [beta 2-M] and intensity of uremia in male patients diagnosed with chronic renal failure [CRF]. In total of 42 males were enrolled in a case-control study. There were 21 cases of CRF and 21 control cases. We collected 10cc of saliva plus 5 cc of blood from all patients to determine beta 2-M, blood urea nitrogen [BUN] and creatinine [Cr] levels. There was a correlation between the level of serum BUN and salivary urea in controls and patients, which was statistically significant for controls [p=0.028].The correlation between serum and salivary Cr was 0.195 in controls [p=0.398] and 0.598 in patients [p=0.006], which was statistically significant in patients. The correlation between serum and saliva was 0.133 [p=0.566] in controls and 0.078 [p=0.737] in patients, which was not statistically significant. The correlation between serum BUN and beta 2-M was 0.168 [p=0.469] in the control group and 0.629 [p=0.002] in patients, which was statistically significant in patients. The correlation between serum Cr and beta 2-M was 0.110 [p=0.635] in the control group and 0.678 [p=0.001] in patients, which was statistically significant in patients. The correlation between serum BUN and salivary beta 2-M was 0.093 [p=0.0690] in controls and 0.152 [p=0.152] in patients, which was not statistically significant. The correlation between serum Cr and salivary beta 2-M was 0.072 [p=0.070] in the control group and 0.286 [p=0.209] in patients, which was not statistically significant in either group. The results of the study indicated that salivary beta 2-M cannot be used as a non-invasive indicator to detect the severity of renal failure