β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to...β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.展开更多
BACKGROUND Retinopathy is the most common microvascular disease of type 2 diabetes,and seriously threatens the life,health and quality of life of patients.It is worth noting that the development of diabetic retinopath...BACKGROUND Retinopathy is the most common microvascular disease of type 2 diabetes,and seriously threatens the life,health and quality of life of patients.It is worth noting that the development of diabetic retinopathy(DR)can be hidden,with few symptoms.Therefore,the preliminary screening of diabetic patients should identify DR as soon as possible,delay disease progression,and play a vital role in its diagnosis and treatment.AIM To investigate the correlation between glycated hemoglobin A1c(HbA1c),urinary microalbumin(U-mALB),urinary creatinine(U-CR),mALB/U-CR ratio,β2 microglobulin(β2MG),retinol binding protein(RBP)and DR.METHODS A total of 180 patients with type 2 diabetes mellitus attending the Second People’s Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists.Based on whether they had combined retinopathy and its degree,68 patients with diabetes mellitus without retinopathy(NDR)were assigned to the NDR group,54 patients with non-proliferative DR(NPDR)to the NPDR group,and 58 patients with proliferative DR to the PDR group.General data,and HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR results were collected from the patients and compared among the groups.Pearson's correlation method was used to analyze the correlation between HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR indices,and multiple linear regression was applied to identify the risk factors for DR.Receiver operator characteristic(ROC)curves were also drawn.RESULTS The differences in age,gender,systolic and diastolic blood pressure between the groups were not statistically significantly(P>0.05),but the difference in disease duration was statistically significant(P<0.05).The differences in fasting blood glucose,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,total cholesterol,and triglyceride between the groups were not statistically significant(P>0.05).HbA1c in the PDR group was higher than that in the NPDR and NDR groups(P<0.05).The levels of mALB,β2MG,RBP,mALB/U-CR and UCR in the PDR group were higher than those in the NPDR and NDR groups(P<0.05).Multiple linear regression analysis showed that disease duration,HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR were risk factors for the development of DR.The ROC curve showed that the area under the curve(AUC)for the combination of indices(HbA1c+mALB+mALB/U-CR+U-CR+β2MG+RBP)was 0.958,with a sensitivity of 94.83%and specificity of 96.72%,which was higher than the AUC for single index prediction(P<0.05).CONCLUSION HbA1c,mALB,mALB/U-CR,U-CR,β2MG and RBP can reflect the development of DR and are risk factors affecting PDR,and the combination of these six indices has predictive value for PDR.展开更多
AIM: To investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of inflammatory bowel disease (IBD).
Objective To evaluate the effect of revascularization of the renal artery on urinary microglobulin in patients with coronaryartery disease and significant renal artery stenosis(RAS).Methods Forty-four patients with co...Objective To evaluate the effect of revascularization of the renal artery on urinary microglobulin in patients with coronaryartery disease and significant renal artery stenosis(RAS).Methods Forty-four patients with coronary artery disease and severe RAS(luminal narrowing>70%)underwent percutaneous transluminal renal artery angioplasty(PTRA)and stenting,as well as percutaneous coronary intervention.The urine-microglobulin(α_(1)-MG)andβ_(2)-Cmicroglobulin(β_(2)-MG)at baseline and at 3 months after the procedures were measured.Procedural success rate,procedural complications,serum creatinine concentration at baseline and at 3-months were also recorded.Results At 3-months after the renal revascularization therapy,there was no significant change of urineα_(1)-MG ompared with that of the baseline,however,the urineβ_(2)-MG decreased significantly 3-months after the treatment(237±187μg/L vs 377±173μg/L,P<0.01).Multivariate analysis revealed that persistent elevation of urine was an independent predictor of severe events(including re-admission and renal failure)after renal revascularization therapy in patients with severe RAS(OR=3.01,95%CI 1.01-8.95,P=0.036).Conclusions In patients with coronary artery disease and severe RAS,revascularization with PTRA and stenting may improve renal tubular function,but a continuous high level of urinary microglobulins after intervention is associated with more frequent re-hospitalization and renal failure.展开更多
Urineβ_2-microglobulin (β_2-m) was measured in 433 persons with low-level, long-term environmental exposure to Cd, and in 124 control persons from unpolluted area. In 152 of the exposed persons, and some of the cont...Urineβ_2-microglobulin (β_2-m) was measured in 433 persons with low-level, long-term environmental exposure to Cd, and in 124 control persons from unpolluted area. In 152 of the exposed persons, and some of the controls, the urine β-m exceeded the limit. Of the 433 exposed persons, 74 cases with both urine Cd and β_2-m exceeding the limit were matched by the control. This study suggests that after the stratification of the degrees of renal tubular injury according to the fractional β_2-m excretion (FE β_2-m) and coordination of clinical examination, FE β_2-m could contribute to identifying renal tubular dysfunction due to Cd exposure and kidney lesion when both Cd exposure and original nephropathy exist.展开更多
Objectives: Evaluation of diagnostic performance of rapid testing of cervico-vaginal fluid (CVF) for fetal fibronectin (FFN) and placental α-microglobulin 1 (PAMG-1) as screening of women presented by threatened pret...Objectives: Evaluation of diagnostic performance of rapid testing of cervico-vaginal fluid (CVF) for fetal fibronectin (FFN) and placental α-microglobulin 1 (PAMG-1) as screening of women presented by threatened preterm labor (TPTL) with intact membranes for duration till getting spontaneous labor (SL). Patients & Methods: 37 women presenting with TPTL underwent CVF samplings before digital examination and then underwent transvaginal ultrasonography for estimation of cervical length (CL). All women received fluid and anxiolytic therapy and if uterine contractions persisted, all had received tocolytic therapy with oral nifedipine or intravenous magnesium sulphate according to requirements. Incidence of SL within Results: Incidence of SL was 13.5%, 35.2% and 51.3% within 48-hr, 2 - 7 and 7 - 14 days, respectively. Duration till labor after sampling was positively correlated with CL, while was negatively correlated with positive FFN and PAMG-1 tests. Positive FFN test had high specificity, while positive PAMG-1 test had high sensitivity for labor within 7 days. Regression analysis defined short CL and positive PAMG-1 test as significant predictors for short duration till SL. ROC curve analysis defined short cervix and positive PAMG-1 test as significant predictors for labor within 48-hr and within 2 - 7 days respectively and combined negative PAMG-1 test and CL of 20 - 25 mm were significant predictors for labor within 7 - 14 days. Conclusion: PAMG-1 test had high specificity, if positive, for predicting SL and high NPP, if negative, for excluding labor within 7 days, so it can be used as rapid adjuvant to clinical evaluation to help management decision-making. Moreover, PAMG-1 test is recommended screening test for being easy-to-use bedside test, provides rapid results, can be used after vaginal exam and coitus and does not require a speculum examination or specialized equipment to analyze results.展开更多
Recent research by Gao et al.published in Cell proposes that circulatingβ2-microglobulin impairs synaptic function through antagonizing NMDA receptors in two mouse models of Down syndrome(DS),providing a potentially ...Recent research by Gao et al.published in Cell proposes that circulatingβ2-microglobulin impairs synaptic function through antagonizing NMDA receptors in two mouse models of Down syndrome(DS),providing a potentially novel therapeutic target to combat cognitive deficits in the early stage of DS.^(1)展开更多
基金supported by the National Natural Science Foundation of China,No.81771337(to RQY).
文摘β2-Microglobulin(β2M),a component of the major histocompatibility complex class I molecule,is associated with aging-related cognitive impairment and Alzheimer’s disease.Although upregulation ofβ2M is considered to be highly related to ischemic stroke,the specific role and underlying mechanistic action ofβ2M are poorly understood.In this study,we established a rat model of focal cerebral ischemia by occlusion of the middle cerebral artery.We found thatβ2M levels in the cerebral spinal fluid,serum,and brain tissue were significantly increased in the acute period but gradually decreased during the recovery period.RNA interference was used to inhibitβ2M expression in the acute period of cerebral stroke.Tissue staining with 2,3,5-triphenyltetrazolium chloride and evaluation of cognitive function using the Morris water maze test demonstrated that decreasedβ2M expression in the ischemic penumbra reduced infarct volume and alleviated cognitive deficits,respectively.Notably,glial cell,caspase-1(p20),and Nod-like receptor pyrin domain containing 3(NLRP3)inflammasome activation as well as production of the inflammatory cytokines interleukin-1β,interleukin-6,and tumor necrosis factor-αwere also effectively inhibited byβ2M silencing.These findings suggest thatβ2M participates in brain injury and cognitive impairment in a rat model of ischemic stroke through activation of neuroinflammation associated with the NLRP3 inflammasome.
文摘BACKGROUND Retinopathy is the most common microvascular disease of type 2 diabetes,and seriously threatens the life,health and quality of life of patients.It is worth noting that the development of diabetic retinopathy(DR)can be hidden,with few symptoms.Therefore,the preliminary screening of diabetic patients should identify DR as soon as possible,delay disease progression,and play a vital role in its diagnosis and treatment.AIM To investigate the correlation between glycated hemoglobin A1c(HbA1c),urinary microalbumin(U-mALB),urinary creatinine(U-CR),mALB/U-CR ratio,β2 microglobulin(β2MG),retinol binding protein(RBP)and DR.METHODS A total of 180 patients with type 2 diabetes mellitus attending the Second People’s Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists.Based on whether they had combined retinopathy and its degree,68 patients with diabetes mellitus without retinopathy(NDR)were assigned to the NDR group,54 patients with non-proliferative DR(NPDR)to the NPDR group,and 58 patients with proliferative DR to the PDR group.General data,and HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR results were collected from the patients and compared among the groups.Pearson's correlation method was used to analyze the correlation between HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR indices,and multiple linear regression was applied to identify the risk factors for DR.Receiver operator characteristic(ROC)curves were also drawn.RESULTS The differences in age,gender,systolic and diastolic blood pressure between the groups were not statistically significantly(P>0.05),but the difference in disease duration was statistically significant(P<0.05).The differences in fasting blood glucose,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,total cholesterol,and triglyceride between the groups were not statistically significant(P>0.05).HbA1c in the PDR group was higher than that in the NPDR and NDR groups(P<0.05).The levels of mALB,β2MG,RBP,mALB/U-CR and UCR in the PDR group were higher than those in the NPDR and NDR groups(P<0.05).Multiple linear regression analysis showed that disease duration,HbA1c,mALB,β2MG,RBP,mALB/U-CR and U-CR were risk factors for the development of DR.The ROC curve showed that the area under the curve(AUC)for the combination of indices(HbA1c+mALB+mALB/U-CR+U-CR+β2MG+RBP)was 0.958,with a sensitivity of 94.83%and specificity of 96.72%,which was higher than the AUC for single index prediction(P<0.05).CONCLUSION HbA1c,mALB,mALB/U-CR,U-CR,β2MG and RBP can reflect the development of DR and are risk factors affecting PDR,and the combination of these six indices has predictive value for PDR.
文摘AIM: To investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of inflammatory bowel disease (IBD).
文摘Objective To evaluate the effect of revascularization of the renal artery on urinary microglobulin in patients with coronaryartery disease and significant renal artery stenosis(RAS).Methods Forty-four patients with coronary artery disease and severe RAS(luminal narrowing>70%)underwent percutaneous transluminal renal artery angioplasty(PTRA)and stenting,as well as percutaneous coronary intervention.The urine-microglobulin(α_(1)-MG)andβ_(2)-Cmicroglobulin(β_(2)-MG)at baseline and at 3 months after the procedures were measured.Procedural success rate,procedural complications,serum creatinine concentration at baseline and at 3-months were also recorded.Results At 3-months after the renal revascularization therapy,there was no significant change of urineα_(1)-MG ompared with that of the baseline,however,the urineβ_(2)-MG decreased significantly 3-months after the treatment(237±187μg/L vs 377±173μg/L,P<0.01).Multivariate analysis revealed that persistent elevation of urine was an independent predictor of severe events(including re-admission and renal failure)after renal revascularization therapy in patients with severe RAS(OR=3.01,95%CI 1.01-8.95,P=0.036).Conclusions In patients with coronary artery disease and severe RAS,revascularization with PTRA and stenting may improve renal tubular function,but a continuous high level of urinary microglobulins after intervention is associated with more frequent re-hospitalization and renal failure.
文摘Urineβ_2-microglobulin (β_2-m) was measured in 433 persons with low-level, long-term environmental exposure to Cd, and in 124 control persons from unpolluted area. In 152 of the exposed persons, and some of the controls, the urine β-m exceeded the limit. Of the 433 exposed persons, 74 cases with both urine Cd and β_2-m exceeding the limit were matched by the control. This study suggests that after the stratification of the degrees of renal tubular injury according to the fractional β_2-m excretion (FE β_2-m) and coordination of clinical examination, FE β_2-m could contribute to identifying renal tubular dysfunction due to Cd exposure and kidney lesion when both Cd exposure and original nephropathy exist.
文摘Objectives: Evaluation of diagnostic performance of rapid testing of cervico-vaginal fluid (CVF) for fetal fibronectin (FFN) and placental α-microglobulin 1 (PAMG-1) as screening of women presented by threatened preterm labor (TPTL) with intact membranes for duration till getting spontaneous labor (SL). Patients & Methods: 37 women presenting with TPTL underwent CVF samplings before digital examination and then underwent transvaginal ultrasonography for estimation of cervical length (CL). All women received fluid and anxiolytic therapy and if uterine contractions persisted, all had received tocolytic therapy with oral nifedipine or intravenous magnesium sulphate according to requirements. Incidence of SL within Results: Incidence of SL was 13.5%, 35.2% and 51.3% within 48-hr, 2 - 7 and 7 - 14 days, respectively. Duration till labor after sampling was positively correlated with CL, while was negatively correlated with positive FFN and PAMG-1 tests. Positive FFN test had high specificity, while positive PAMG-1 test had high sensitivity for labor within 7 days. Regression analysis defined short CL and positive PAMG-1 test as significant predictors for short duration till SL. ROC curve analysis defined short cervix and positive PAMG-1 test as significant predictors for labor within 48-hr and within 2 - 7 days respectively and combined negative PAMG-1 test and CL of 20 - 25 mm were significant predictors for labor within 7 - 14 days. Conclusion: PAMG-1 test had high specificity, if positive, for predicting SL and high NPP, if negative, for excluding labor within 7 days, so it can be used as rapid adjuvant to clinical evaluation to help management decision-making. Moreover, PAMG-1 test is recommended screening test for being easy-to-use bedside test, provides rapid results, can be used after vaginal exam and coitus and does not require a speculum examination or specialized equipment to analyze results.
文摘Recent research by Gao et al.published in Cell proposes that circulatingβ2-microglobulin impairs synaptic function through antagonizing NMDA receptors in two mouse models of Down syndrome(DS),providing a potentially novel therapeutic target to combat cognitive deficits in the early stage of DS.^(1)
文摘目的探讨肾小管及肾小球相关标志物在2型糖尿病(type 2 diabetes mellitus,T2DM)患者不同肾损伤阶段的诊断价值。方法选取于2018年4月1日至2019年10月31日入住首都医科大学附属北京同仁医院内分泌科的T2DM患者272例,完善临床生化指标及尿蛋白四项:尿微量白蛋白/肌酐(urinary albumin to creatinine ratio,ACR)、α1-微球蛋白/肌酐(urinary α1-microglobulin to creatinine ratio,UA1CR)、免疫球蛋白G/肌酐(urinary immunoglobulin G to creatinine ratio,UIGG)、转铁蛋白/肌酐(urinary transferrin to creatinine ratio,UTRF);进行眼底照相、核医学99mTc-EC检测肾有效血浆流量(effective renal plasma flow,ERPF)和99mTc-DTPA检测肾小球滤过率(glomerular filtration rate,GFR)。根据ACR和眼底检查结果分为4组:正常蛋白尿无糖尿病视网膜病变(diabetic retinopathy,DR)132例,即对照组(ACR≤30 mg/g);正常蛋白尿合并DR 32例,为糖尿病肾病(diabetic kidney disease,DKD)前期组;微量蛋白尿组78例(30<ACR≤300 mg/g)和大量蛋白尿组30例(ACR>300 mg/g)。比较四组间尿蛋白四项和ERPF、GFR的水平,通过受试者工作特征(receiver operating characteristic,ROC)曲线评价上述各指标在不同肾损伤阶段的诊断价值。结果尿蛋白四项和ERPF、GFR的水平在不同组间差异有统计学意义(P<0.05)。在尿蛋白正常组中,DR组中肾小管功能标志物UA1CR较对照组明显升高(P<0.01);肾小球功能标志物ACR、UTRF和GFR在两组间差异无统计学意义(P>0.05),DR组UIGG较对照组升高(P<0.01)。在微量蛋白尿组和大量蛋白尿组,尿蛋白四项随肾损伤程度增加而增加,而ERPF和GFR随肾损伤程度增加而降低。ROC曲线分析显示,在尿蛋白排出正常的T2DM患者中合并DR组中肾小管功能标志物UA1CR和ERPF的曲线下面积(area under the curve,AUC)分别为68.2%(P<0.01)和60.5%(P<0.05),而肾小球功能标志物ACR和GFR的AUC均小于60%,差异无统计学意义(P>0.05)。尿蛋白四项及GFR在微量和大量蛋白尿组的AUC均大于60%(P<0.05),ERPF在大量蛋白尿组AUC为67.2%(P<0.05)。结论T2DM极早期微血管改变即ACR正常仅有DR时,肾小管标志物UA1CR先于肾小球标志物ACR和GFR发生变化。肾损伤早期,肾小管标志物诊断效能优于肾小球;肾损伤后期,肾小球标志物诊断效能优于肾小管。提示DKD肾小管功能的改变可能早于肾小球。
