The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was pr...The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association betweenβ2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular(CV) and/or mortality risk have grown. In the current literature,clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the highrisk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.展开更多
Psychological depression is considered a major determinant of health status in patients with heart failure （HF）. The incidence of depression in HF is four to five times higher than that in the general population.
Objectives Increased lipoprotein （a） serum concentration seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper ins...Objectives Increased lipoprotein （a） serum concentration seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein （a） and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. Methods This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data （insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro and macrovascular complications were collected. Results Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein （a） was 22.2± 17.3 mg/dL （22.1± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females）. Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein （a）. Similarly, the patients with hyperlipoprotein （a） （≥30 mg/dL） presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein （a） is positively correlated with coronary heart disease and diabetic nephropathy （P 〈 0.01 and P 〈 0.005, respectively）. Conclusions The elevation of plasma levels of lipoprotein （a） are associ- ated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein （a） may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.展开更多
Objective:Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis.Based on its good clinical evidence and anti-hypertensive effectiveness,this st...Objective:Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis.Based on its good clinical evidence and anti-hypertensive effectiveness,this study aimed to investigate the potential mechanism of the hyperuricemic inhibitory effects of lotus leaf crude extract(LL)and lotus leaf total alkaloids fraction(LA).Methods:The xanthine oxidase(XOD)inhibitory effect of LL and LA was analyzed in vitro by determining mRNA expression and protein expression levels of hepatic XOD.The hyperuricemic inhibitory effect of the lotus leaf was analyzed in vivo in a potassium oxonate(PO)-induced rat model by determining mRNA expression for renal urate transporters.Results:At a concentration of 40mg/mL,LL and LA suppressed XOD enzymatic activity by 37.35%±9.50%and 47.73%±8.32%,respectively.Both LL and LA administration significantly reduced the concentration of uric acid in the serum and liver of PO-induced hyperuricemic rats.Both LL and LA administration could inhibit XOD mRNA and protein expression,activate renal organic anion transporter 1/3 mRNA expression,and inhibit renal urate reabsorption by decreasing renal GLUT9 and renal urate transporter 1.Conclusions:Insight was gained into the mechanism behind the hyperuricemic inhibitory effects of LL and LA.Our results suggest that they act on two targets:decreasing the production of uric acid by inhibiting mRNA and protein expression of XOD in the liver,and regulating the mRNA expression of renal urate transporters in the kidneys.展开更多
OBJECTIVE: To learn more about the clinical and laboratory features of patients with paroxysmal nocturnal hemoglobinuria (PNH) diagnosed in the past ten years. METHODS: Clinical and laboratory data for 78 cases of PNH...OBJECTIVE: To learn more about the clinical and laboratory features of patients with paroxysmal nocturnal hemoglobinuria (PNH) diagnosed in the past ten years. METHODS: Clinical and laboratory data for 78 cases of PNH diagnosed from January 1990 to November 1999 in our hospital were analyzed retrospectively. RESULTS: In comparison with PNH cases reported in the 1980s, the newly diagnosed PNH cases showed the following features: (1) older age of disease onset (from 27 to 34 years); more female cases (from 18.5% to 38.5%); more cases without hemoglobinuria (from 24.2% to 38.5%). (2) No positive family hereditary history. (3) Bone marrow dysplasia, abnormal karyotype and negative sister chromatid differentiation were found in 19.2%, 12.2% and 8.9% of the PNH patients, respectively. 12.3% of the patients had bone marrow hypoplasia, and most of them had no hemoglobinuria. Ham's tests were negative in about 34.2% of the cases. CD55 and CD59 on peripheral blood cells were deficient in 100.0% of the cases, suggesting that CD55 and CD59 tests can improve the diagnosis of PNH. (4) Adrenocortical hormone was effective in 83.8% of the patients, 54.2% of whom relapsed within one year. Eight refractory and relapsed patients were treated with low dose chemotherapy (MP therapy: Melphalan 2 - 6 mg x d(-1); Prednisone 0.5 mg x kg(-1) x d(-1)). Five (62.5%) of them showed positive responses. Bone marrow failure and other side effects were not serious in this group of patients. CONCLUSIONS: PNH, an acquired blood disease seen more often among adult males, can be diagnosed more sensitively by hemocyte member CD55 and CD59 tests and treated more effectively with adrenocortical hormone or low dose chemotherapy.展开更多
OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METH...OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.展开更多
OBJECTIVE: To determine whether affected reticulocytes could be a reliable marker for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), we analyzed CD59-antigen expression on the membranes of reticulocytes a...OBJECTIVE: To determine whether affected reticulocytes could be a reliable marker for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), we analyzed CD59-antigen expression on the membranes of reticulocytes and erythrocytes. METHODS: We studied 10 PNH patients and 5 healthy volunteers by two-color flow cytometry with a membrane permeable fluorescent dye, thiazole orange (TO), and anti-CD59 monoclonal antibodies (MoAb). TO was introduced to gate reticulocytes and anti-CD59 MoAb were used to identify glycosylphosphatidylinositol (GPI)-deficient cells. RESULTS: Cells from healthy individuals were only CD59 positive. However, in all PNH patients, CD59-antigen expression could be divided into 3 types: type I cells (CD59 normally positive), type II cells (CD59 partly positive) and type III cells (CD59 negative). The majority of reticulocytes belonged to type III cells, GPI-deficient cells (61.0%). In addition, the percentage of affected reticulocytes was higher than that of erythrocytes. CONCLUSIONS: Analyzing PNH reticulocytes was important, because most patients had elevated numbers of reticulocytes, which represent more closely the recent erythroid output of BM. However, circulating mature erythrocytes were subject to complement-mediated intravascular lysis. Therefore, the percentage of abnormal erythrocytes may not accurately reflect the proliferation rate of normal and abnormal erythroid progenitor cells. Thus, affected reticulocytes could be a more reliable indicator for the diagnosis of PNH than mature erythrocytes.展开更多
Objective To investigate the relationship between the expression and regulation of osteopontin (OPN) and urolithiasis.Methods Normal and stone model rats were treated with 1,25-dihydroxyvitamin D3 (D3), vitamin K, t...Objective To investigate the relationship between the expression and regulation of osteopontin (OPN) and urolithiasis.Methods Normal and stone model rats were treated with 1,25-dihydroxyvitamin D3 (D3), vitamin K, testosterone or estradiol for 7 days, and the expression of osteopontin and its mRNA were detected with immunohistochemistry and Northern blot, respectively. Crystals deposited in rat kidneys were observed with a polarization microscope. The concentrations of crystal components in rat urine were determined.Results The results showed that vitamin K, testosterone and estradiol up-regulated the expression of OPN mRNA and its protein, thus decreasing the precipitation of calcium oxalate in rat kidneys. D3 increased the concentration of calcium in urine, and accelerated the sedimentation of calcium oxalate in rat kidneys.Conclusions These findings indicate that OPN may be an important macromolecule in the normal endogenous inhibition of the formation of urolithiasis. Vitamin K, testosterone and estradiol inhibit the formation of stones via up-regulating the expression of OPN in kidneys, while D3 over dose may accelerate the process.展开更多
文摘The role of beta2-microglobulin(β2M) in dialysisrelated amyloidosis as a specific amyloid precursor was defined in the 1980 s. Studies in those years were largely related to β2M amyloidosis. In 2005, for what was probably the first time in the available literature, we provided data about the association betweenβ2M and early-onset atherosclerosis in hemodialysis patients without co-morbidities. In recent years, the role of uremic toxins in uremic atherosclerosis and the interest in β2M as a marker of cardiovascular(CV) and/or mortality risk have grown. In the current literature,clinical studies suggest that β2M is an independent, significant predictor of mortality, not only in dialysis patients, but also in predialysis patients and in the highrisk portion of the general population, and it seems to be a factor strongly linked to the presence and severity of CV disease. It is still unknown whether β2M is only a uremic toxin marker or if it also has an active role in vascular damage, but data support that it may reflect an increased burden of systemic atherosclerosis in a setting of underlying chronic kidney disease. Thus, although there have been some inconsistencies among the various analyses relating to β2M, it promises to be a novel risk marker of kidney function in the awareness and detection of high-risk patients. However, more research is required to establish the pathophysiological relationships between retained uremic toxins and further biochemical modifications in the uremic milieu to get answers to the questions of why and how. In this review, the recent literature about the changing role of β2M in uremic patients will be examined.
文摘Psychological depression is considered a major determinant of health status in patients with heart failure （HF）. The incidence of depression in HF is four to five times higher than that in the general population.
文摘Objectives Increased lipoprotein （a） serum concentration seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein （a） and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. Methods This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data （insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro and macrovascular complications were collected. Results Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein （a） was 22.2± 17.3 mg/dL （22.1± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females）. Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein （a）. Similarly, the patients with hyperlipoprotein （a） （≥30 mg/dL） presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein （a） is positively correlated with coronary heart disease and diabetic nephropathy （P 〈 0.01 and P 〈 0.005, respectively）. Conclusions The elevation of plasma levels of lipoprotein （a） are associ- ated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein （a） may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.
基金supported by the Program for New Century Excellent Talents in University(NCET-10-0958,NCET-12-1069)Important Drug Develop of MOST,China(2011ZX09307-002-01)National Natural Science Foundation of China(81173524).
文摘Objective:Lotus leaf is a traditional Chinese herb that has been used successfully for centuries for relieving edema by inducing diuresis.Based on its good clinical evidence and anti-hypertensive effectiveness,this study aimed to investigate the potential mechanism of the hyperuricemic inhibitory effects of lotus leaf crude extract(LL)and lotus leaf total alkaloids fraction(LA).Methods:The xanthine oxidase(XOD)inhibitory effect of LL and LA was analyzed in vitro by determining mRNA expression and protein expression levels of hepatic XOD.The hyperuricemic inhibitory effect of the lotus leaf was analyzed in vivo in a potassium oxonate(PO)-induced rat model by determining mRNA expression for renal urate transporters.Results:At a concentration of 40mg/mL,LL and LA suppressed XOD enzymatic activity by 37.35%±9.50%and 47.73%±8.32%,respectively.Both LL and LA administration significantly reduced the concentration of uric acid in the serum and liver of PO-induced hyperuricemic rats.Both LL and LA administration could inhibit XOD mRNA and protein expression,activate renal organic anion transporter 1/3 mRNA expression,and inhibit renal urate reabsorption by decreasing renal GLUT9 and renal urate transporter 1.Conclusions:Insight was gained into the mechanism behind the hyperuricemic inhibitory effects of LL and LA.Our results suggest that they act on two targets:decreasing the production of uric acid by inhibiting mRNA and protein expression of XOD in the liver,and regulating the mRNA expression of renal urate transporters in the kidneys.
文摘OBJECTIVE: To learn more about the clinical and laboratory features of patients with paroxysmal nocturnal hemoglobinuria (PNH) diagnosed in the past ten years. METHODS: Clinical and laboratory data for 78 cases of PNH diagnosed from January 1990 to November 1999 in our hospital were analyzed retrospectively. RESULTS: In comparison with PNH cases reported in the 1980s, the newly diagnosed PNH cases showed the following features: (1) older age of disease onset (from 27 to 34 years); more female cases (from 18.5% to 38.5%); more cases without hemoglobinuria (from 24.2% to 38.5%). (2) No positive family hereditary history. (3) Bone marrow dysplasia, abnormal karyotype and negative sister chromatid differentiation were found in 19.2%, 12.2% and 8.9% of the PNH patients, respectively. 12.3% of the patients had bone marrow hypoplasia, and most of them had no hemoglobinuria. Ham's tests were negative in about 34.2% of the cases. CD55 and CD59 on peripheral blood cells were deficient in 100.0% of the cases, suggesting that CD55 and CD59 tests can improve the diagnosis of PNH. (4) Adrenocortical hormone was effective in 83.8% of the patients, 54.2% of whom relapsed within one year. Eight refractory and relapsed patients were treated with low dose chemotherapy (MP therapy: Melphalan 2 - 6 mg x d(-1); Prednisone 0.5 mg x kg(-1) x d(-1)). Five (62.5%) of them showed positive responses. Bone marrow failure and other side effects were not serious in this group of patients. CONCLUSIONS: PNH, an acquired blood disease seen more often among adult males, can be diagnosed more sensitively by hemocyte member CD55 and CD59 tests and treated more effectively with adrenocortical hormone or low dose chemotherapy.
文摘OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.
文摘OBJECTIVE: To determine whether affected reticulocytes could be a reliable marker for the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), we analyzed CD59-antigen expression on the membranes of reticulocytes and erythrocytes. METHODS: We studied 10 PNH patients and 5 healthy volunteers by two-color flow cytometry with a membrane permeable fluorescent dye, thiazole orange (TO), and anti-CD59 monoclonal antibodies (MoAb). TO was introduced to gate reticulocytes and anti-CD59 MoAb were used to identify glycosylphosphatidylinositol (GPI)-deficient cells. RESULTS: Cells from healthy individuals were only CD59 positive. However, in all PNH patients, CD59-antigen expression could be divided into 3 types: type I cells (CD59 normally positive), type II cells (CD59 partly positive) and type III cells (CD59 negative). The majority of reticulocytes belonged to type III cells, GPI-deficient cells (61.0%). In addition, the percentage of affected reticulocytes was higher than that of erythrocytes. CONCLUSIONS: Analyzing PNH reticulocytes was important, because most patients had elevated numbers of reticulocytes, which represent more closely the recent erythroid output of BM. However, circulating mature erythrocytes were subject to complement-mediated intravascular lysis. Therefore, the percentage of abnormal erythrocytes may not accurately reflect the proliferation rate of normal and abnormal erythroid progenitor cells. Thus, affected reticulocytes could be a more reliable indicator for the diagnosis of PNH than mature erythrocytes.
基金ThisworkwassupportedbytheNationalNaturalScienceFoundationofChina (No 39670 72 2 )
文摘Objective To investigate the relationship between the expression and regulation of osteopontin (OPN) and urolithiasis.Methods Normal and stone model rats were treated with 1,25-dihydroxyvitamin D3 (D3), vitamin K, testosterone or estradiol for 7 days, and the expression of osteopontin and its mRNA were detected with immunohistochemistry and Northern blot, respectively. Crystals deposited in rat kidneys were observed with a polarization microscope. The concentrations of crystal components in rat urine were determined.Results The results showed that vitamin K, testosterone and estradiol up-regulated the expression of OPN mRNA and its protein, thus decreasing the precipitation of calcium oxalate in rat kidneys. D3 increased the concentration of calcium in urine, and accelerated the sedimentation of calcium oxalate in rat kidneys.Conclusions These findings indicate that OPN may be an important macromolecule in the normal endogenous inhibition of the formation of urolithiasis. Vitamin K, testosterone and estradiol inhibit the formation of stones via up-regulating the expression of OPN in kidneys, while D3 over dose may accelerate the process.
