AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure.METHODS This cohort study evaluated...AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure.METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics(etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory(calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ~2 test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables.RESULTS Fifty-three patients(66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product(P = 0.03 and P = 0.006, respectively). They also had lower mortality(32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events(27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg^2/dL^2 [RR 1.48(1.06, 2.08), P = 0.03], presence of vascular calcification [1.33(1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25(1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality.CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure.展开更多
Currently,the growing number of end-stage renal disease patients in developing countries consumes a greater proportion of healthcare budget,and increasing attention is being focused on the cost-effectiveness of the pr...Currently,the growing number of end-stage renal disease patients in developing countries consumes a greater proportion of healthcare budget,and increasing attention is being focused on the cost-effectiveness of the procedure.We aimed to assess the cost-effectiveness of living-related renal transplantation (RTx) as compared with that for hemodialysis (HD) and identify medical factors associated with charges for RTx in northwestern China.This study was a retrospective analysis of 372 patients on regular HD and 122 living-related kidney transplant recipients on regular follow-up for at least 3 years in northwestern China.All data on charges included HD procedure,RTx procedure,the cost for donor operation,immunosuppression,and follow-up medicare.The average annual cost to all patients on HD and kidney recipients during the first 3 years after RTx was $14482/$31027,$13502/$11038,and $13382/$10243,respectively.The three variables were found to be significant in predicting increased costs for RTx:diltiazem administration,acute rejection and infection complications.We concluded that from the second year on,RTx in China was more effective and less costly than dialysis treatment,although recipients without diltiazem administration and with acute rejection or infection proved costlier during the first year after transplantation.展开更多
Objective:To investigate the association between serum HIF-1α,β-catenin levels and the vascular calcification in the rat model of chronic kidney disease(CKD)vascular calcification.Methods:30 SD male rats were random...Objective:To investigate the association between serum HIF-1α,β-catenin levels and the vascular calcification in the rat model of chronic kidney disease(CKD)vascular calcification.Methods:30 SD male rats were randomly divided into normal control group(CON group,n=10)and CKD vascular calcification group(CKD group,n=20).Rats in calcification group were fed with adenine combined with high phosphorus diet.At the end of the 6th week,the blood and urine of the two groups were collected to detect renal function,calcium,phosphorus and 24-hour urinary protein,the renal tissue was stained with HE,the aorta of rats was stained with Von Kossa and calcium content was determined,and the levels of HIF-1α and β-catenin in serum were detected by ElISA method.Results:compared with CON group,24-hour urinary protein,blood BUN,Scr,P,Ca×P,aortic calcium content,serum HIF-1α and β-catenin levels were significantly increased and serum calcium decreased in CKD group(P<0.05);Glomerular atrophy,renal tubule dilatation and interstitial fibrosis were seen in CKD group,Von Kossa staining of calcified nodules in aorta showed more black substance deposition.The levels of serum HIF-1α,β-catenin and serum P,Ca×P were positively correlated with the content of calcium in rat aorta.Conclusion:the levels of serum HIF-1α and β-catenin are significantly increased in patients with vascular calcification in CKD,and they are significantly related to the degree of aortic calcification.展开更多
AIM To investigate the prevalence of nutritional parameters of risk for cardiovascular disease(CVD) and kidney diseases in healthy preschool children.METHODS This is an observational cross-sectional study with 60 heal...AIM To investigate the prevalence of nutritional parameters of risk for cardiovascular disease(CVD) and kidney diseases in healthy preschool children.METHODS This is an observational cross-sectional study with 60 healthy children, of both genders, aged two to six years old and 56 mothers, in Belo Horizonte, Minas Gerais, Brazil. Preschool children and their families with regular activities at public schools were invited to paticipate in the study. The following characteristics were assessed: Socio-demographic condictions, clinical health, anthropometric, biochemical, lifestyle and data on food consumption. The 56 healthy children were divided into two groups, overweight(C1) and non-overweight(C2), as well as their mothers, respectively, in overweight(M1) and non-overweight(M2). Nutritional status was defined according to results obtained through the Anthro? Software for nutritional analysis. RESULTS Thirty-five children were male, with mean age of 4.44 ± 1.0 years old. Eighty-nine percent of them were eutrophic, 86.7% were sedentary and they had five meals a day. Body mass index(BMI) for age and total cholesterol(TC) was higher on C1(P = 0.0001) and high density lipoprotein cholesterol(HDL-c) was higher on C2. Mothers were 32.5 ± 7.1 years old, mostly married and employed. Eighty-six percent of them were sedentary and 62.5% were overweight with BMI = 26.38 ± 5.07 kg/m2. Eighteen percent of the overweight mothers had isolated total hypercholesterolemia(TC levels elevated) and 12.5% had low HDL-c levels. The present study showed an association between overweight and obesity during the preschool years and the correspondent mothers' nutritional status of overweight and obesity(OR = 4.96; 95%CI: 0.558-44.17). There was a positive correlation between the food risk associated with CVD by children and mothers when their consumption was 4 times/wk(P = 0.049; r = 0.516) or daily(P = 0.000008; r = 0.892).CONCLUSION Analyzed children showed high rates of physical inactivity, high serum cholesterol levels and high consumption of food associated with risk for CVD and renal disease. Changes in habits should be encouraged early in kindergarten.展开更多
In the past few decades pediatric urolithiasis has become more frequent. The reason for this increase is not completely clear but has been attributed to changes in climate, nutritional habits and possibly other enviro...In the past few decades pediatric urolithiasis has become more frequent. The reason for this increase is not completely clear but has been attributed to changes in climate, nutritional habits and possibly other environ-mental factors. Although less frequent than adult stone disease, urolithiasis in the pediatric age group is also related to significant morbidity, particularly since stones tend to recur, and, thus, should not be underestimated. Most children with idiopathic stone disease have an underlying metabolic abnormality substantiating the importance of metabolic evaluation already following initial diagnosis of urolithiasis. Identification of the metabolic abnormality allows for more specifc prescription of non pharmacological and pharmacological interventions aimed at preventing recurrent stone formation. A better understanding of the causes of kidney stone disease will provide better strategies for stone prevention in children.展开更多
Background：Improving islet graft revascularization has become a crucial task for prolonging islet graft survival.Endothelial cells （ECs） are the basis of new microvessels in an isolated islet,and EC coating has bee...Background：Improving islet graft revascularization has become a crucial task for prolonging islet graft survival.Endothelial cells （ECs） are the basis of new microvessels in an isolated islet,and EC coating has been demonstrated to improve the vascularization and survival of an islet.However,the traditional method of EC coating of islets has low efficiency in vitro.This study was conducted to evaluate the effect of a polyglycolic acid （PGA） scaffold on the efficiency of islet coating by ECs and the angiogenesis in the coated islet graft.Methods：A PGA fibrous scaffold was used for EC coating of islet culture and was evaluated for its efficiency of EC coating on islets and islet graft angiogenesis.Results：In in vitro experiments,we found that apoptosis index of ECs-coating islet in PGA group （27% ± 8%） was significantly lower than that in control group （83% ± 20%,P 〈 0.05） after 7 days culture.Stimulation index was significantly greater in the PGA group than in the control group at day 7 after ECs-coating （2.07 ± 0.31 vs.1.80 ± 0.23,P 〈 0.05）.vascular endothelial growth factor （VEGF） level in the PGA group was significantly higher than the coating in the control group after 7 days culture （52.10 ± 13.50 ng/ml vs.16.30 ± 8.10 ng/ml,P 〈 0.05）.Because of a tight,circumvallated,adhesive and three-dimensional growth microenvironment,islet cultured in a PGA scaffold had higher coating efficiency showing stronger staining intensity of enzyme than those in the control group after 14 days of culture following ECs-coating.For in vivo study,PGA scaffold significantly prolonged the average survival time of EC-coated islet graft after transplantation compared with control group （15.30 ± 5.60 days vs.8.30 ± 2.45 days,P 〈 0.05）.The angiogenesis and area of survived grafts were more in the PGA group compared with the control group by measuring the mean microvessel density （8.60 ± 1.21/mm2 vs.5.20 ± 0.87/mm2,P 〈 0.05）.In addition,expression of VEGF and tyrosin-protein kinase receptor （Tie-2） gene increased in PGA scaffold group than that in control group by real-time reverse transcription-polymerase chain reaction analysis.Conclusions：These results demonstrate that the efficiency of EC coating of islets was successfully increased by culturing ECs on a PGA scaffold.This method enhances the function,survival,and vascularization of isolated islets in vitro and in vivo.展开更多
Coronavirus disease 2019(COVID-19)is an infectious disease caused by a newly discovered coronavirus and has rapidly spread to most of the world and resulted in a global pandemic.However,there is a paucity of informati...Coronavirus disease 2019(COVID-19)is an infectious disease caused by a newly discovered coronavirus and has rapidly spread to most of the world and resulted in a global pandemic.However,there is a paucity of information available to characterize the immunodeficient population in the COVID-19 pandemic,especially information that focuses on patients after renal transplantation as the typical representative of this population.展开更多
Dear Editor, As a mitochondrial deacetylase, SIRT3 deacetylates many enzymes involved in central metabolism and maintains mitochondrial proteostasis （Verdin et al., 2010; Papa and Germain, 2014）. Substrates of SIRT3...Dear Editor, As a mitochondrial deacetylase, SIRT3 deacetylates many enzymes involved in central metabolism and maintains mitochondrial proteostasis （Verdin et al., 2010; Papa and Germain, 2014）. Substrates of SIRT3 include components of the respiratory complexes, proteins involved in fatty acid oxidation and TCA cycle （Yu et al., 2012）. SIRT3 activates MnSOD to maintain reactive oxygen species （ROS） home- ostasis and a loss of SIRT3 contributes to the age-associ- ated diseases （McDonnell et al., 2015; Qiu et al., 2010）. SIRT3 plays dual roles functioning as a tumor suppressor or a promoter in tumorigenesis and progression （Alhazzazi et al., 2011 ）. On one hand, SIRT3 regulates the cellular ROS level and maintains genomic stability, and mediates meta- bolic reprogramming to prevent tumorigenesis （Finley and Haigis, 2012）. As a result, the low expression of SIRT3 has been found in breast cancer, glioblastoma, colon cancer, osteosarcoma, prostate, and ovarian cancers （Kim et al., 2010; Finley and Haigis, 2012）. On the other hand, SIRT3 is a prosurvival factor that modulates p53 activities and is upregulated in oral cancer, the node-positive breast cancer, and bladder cancer （Ashraf et al., 2006; Alhazzazi et al., 2011）. These results suggest that SIRT3 possesses the tumor-type dependent function and its precise role needs to be elucidated in the context of a specific cancer. Clear cell renal cell carcinoma （ccRCC） is the most common histo- logical subtype of renal cancer （Cohen and McGovern, 2005）. The aims of the present study were to examine the expression of SIRT3 in ccRCC and to characterize effects of SIRT3 on tumorigenesis and progression using 293T human embryonic kidney cells as the model system that has cancer stem cell-like features （Debeb et al., 2010）.展开更多
Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system.In contrast,interferons are a crucial component of host antiviral immunity and can be ...Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system.In contrast,interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids.To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity,we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids.Among patients receiving glucocorticoids,early interferon therapy was associated with earlier hospital discharge(adjusted HR 1.68,95%Cl 1.19-2.37)and symptom relief(adjusted HR 1.48;95%Cl 1.06-2.08),while these associations were insignificant among glucocorticoids nonusers.Early interferon therapy was also associated with lower prevalence of prolonged viral shedding(adjusted OR 0.24,95%Cl 0.10-0.57)only among glucocorticoids users.Additionally,these associations were glucocorticoid cumulative dose-and timing-dependent.These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.展开更多
The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients f...The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang,China at 1-year after diagnosis.Among them,chemiluminescence immunoassay-based screening showed 99%(95%CI,98–100%)seroprevalence 10–12 months after infection,comparing to 0.8%(95%CI,0.7–0.9%)in the general population.Total anti-receptor-binding domain(RBD)antibodies remained stable since discharge,while anti-RBD IgG and neutralization levels decreased over time.A predictive model estimates 17%(95%CI,11–24%)and 87%(95%CI,80–92%)participants were still 50%protected against detectable and severe re-infection of WT SARS-CoV-2,respectively,while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced.All non-severe patients showed normal chest CT and 21%reported COVID-19-related symptoms.In contrast,53%severe patients had abnormal chest CT,decreased pulmonary function or cardiac involvement and 79%were still symptomatic.Our findings suggest long-lasting immune protection after SARS-CoV-2 infection,while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.展开更多
To the Editor:To reduce the risk of acute rejection(AR)after renal transplantation,immunosuppressive induction therapy has been commonly used in the perioperative period.At present,rabbit anti-thymocyte globulin(rATG)...To the Editor:To reduce the risk of acute rejection(AR)after renal transplantation,immunosuppressive induction therapy has been commonly used in the perioperative period.At present,rabbit anti-thymocyte globulin(rATG)and basiliximab are the two main induction agents used for kidney transplantation.In adult kidney transplantation,the incidence of AR with rATG induction is generally lower than that with basiliximab.[1]Children have different immune systems than adults do.In pediatric kidney transplantation,which induction therapy is more effective in preventing early AR is an important clinical question worth answering.Because there are few reports in this field and differences in the immune systems of children at different ages,we have now conducted a total and age-stratified analysis of Chinese multicenter cohort data to compare the AR rates and other outcomes between rATG and basiliximab induction therapy groups in pediatric deceased-donor kidney transplantation.展开更多
Background：Core fucosylation （CF）,catalyzed by α-1,6 fucosyltransferase （Fut8） in mammals,plays an important role in pathological processes through posttranslational modification of key signaling receptor protei...Background：Core fucosylation （CF）,catalyzed by α-1,6 fucosyltransferase （Fut8） in mammals,plays an important role in pathological processes through posttranslational modification of key signaling receptor proteins,including transforming growth factor （TGF）-β receptors and platelet-derived growth factor （PDGF） receptors.However,its effect on peritoneal fibrosis is unknown.Here,we investigated its influence on epithelial-mesenchymal transition （EMT） of rat peritoneal mesothelial cells （PMCs） in vitro induced by a high-glucose （HG） culture solution.Methods：Rat PMCs were first cultured in a HG （2.5%） culture solution to observe the CF expression level （fluorescein isothiocyanate-lens culinaris agglutinin）,we next established a knockdown model of rat PMCs in vitro with Fut8 small interfering RNA （siRNA） to observe whether inhibiting CF decreases the messenger RNA （mRNA） expression and protein expression of Fut8 and reverses EMT status.Rat PMCs were randomly divided into control group,mock group （transfected with scrambled siRNA）,Fut8 siRNA group,HG group,HG ＋ mock group,and HG ＋ Fut8 siRNA group.Finally,we examined the activation of TGF-β/Smad2/3 signaling and PDGF/extracellular signal-regulated kinase （ERK） signaling to observe the influence of CF on them.Results：CF,Fut8 mRNA,and protein expression were all significantly upregulated in HG-induced EMT model than those in the control rat PMCs （P 〈 0.05）.Fut8 siRNA successfully blocked CF of TGF-β receptors and PDGF receptors and attenuated the EMT status （E-cadherin and α-SMA and phenotypic changes） in HG-induced rat PMCs.In TGF-β/Smad2/3 signaling,Fut8 siRNA did not suppress the protein expression of TGF-3 receptors and Smad2/3;however,it significantly suppressed the phosphowlation of Smad2/3 （relative expression folds of HG ＋ Fut8 group vs.HG group：7.6 ± 0.4 vs.15.1 ± 0.6,respectively,P 〈 0.05）.In PDGF/ERK signaling,Fut8 siRNA did not suppress the protein expression of PDGF receptors and ERK,but it significantly suppressed the phosphorylation of ERK （relative expression folds of HG ＋ Fut8 group vs.HG group：8.7 ± 0.9 vs.15.6 ± 1.2,respectively,P 〈 0.05）.Blocking CF inactivated the activities of TGF-β and PDGF signaling pathways,and subsequently blocked EMT.Conclusions：These results demonstrate that CF contributes to rat PMC EMT.and that blocking it attenuates EMT.CF regulation is a potential therapeutic target of peritoneal fibrosis.展开更多
文摘AIM To evaluate the parathyroid ultrasonography and define parameters that can predict poor response to treatment in patients with secondary hyperparathyroidism due to renal failure.METHODS This cohort study evaluated 85 patients with chronic kidney disease stage V with parathyroid hormone levels above 800 pg/mL. All patients underwent ultrasonography of the parathyroids and the following parameters were analyzed: Demographic characteristics(etiology of chronic kidney disease, gender, age, dialysis vintage, vascular access, use of vitamin D), laboratory(calcium, phosphorus, parathyroid hormone, alkaline phosphatase, bone alkaline phosphatase), and the occurrence of bone changes, cardiovascular events and death. The χ~2 test were used to compare proportions or the Fisher exact test for small sample frequencies. Student t-test was used to detect differences between the two groups regarding continuous variables.RESULTS Fifty-three patients(66.4%) had parathyroid nodules with higher levels of parathyroid hormone, calcium and phosphorus. Sixteen patients underwent parathyroidectomy and had higher levels of phosphorus and calcium × phosphorus product(P = 0.03 and P = 0.006, respectively). They also had lower mortality(32% vs 68%, P = 0.01) and lower incidence of cardiovascular or cerebrovascular events(27% vs 73%, P = 0.02). Calcium × phosphorus product above 55 mg^2/dL^2 [RR 1.48(1.06, 2.08), P = 0.03], presence of vascular calcification [1.33(1.01, 1.76), P = 0.015] and previous occurrence of vascular events [RR 2.25(1.27, 3.98), P < 0.001] were risk factors for mortality in this population. There was no association between the occurrence of nodules and mortality.CONCLUSION The identification of nodules at ultrasonography strengthens the indication for parathyroidectomy in patients with secondary hyperparathyroidism due to renal failure.
基金Supported by the Science Foundation of Shaanxi Province (No. SJ08C201)
文摘Currently,the growing number of end-stage renal disease patients in developing countries consumes a greater proportion of healthcare budget,and increasing attention is being focused on the cost-effectiveness of the procedure.We aimed to assess the cost-effectiveness of living-related renal transplantation (RTx) as compared with that for hemodialysis (HD) and identify medical factors associated with charges for RTx in northwestern China.This study was a retrospective analysis of 372 patients on regular HD and 122 living-related kidney transplant recipients on regular follow-up for at least 3 years in northwestern China.All data on charges included HD procedure,RTx procedure,the cost for donor operation,immunosuppression,and follow-up medicare.The average annual cost to all patients on HD and kidney recipients during the first 3 years after RTx was $14482/$31027,$13502/$11038,and $13382/$10243,respectively.The three variables were found to be significant in predicting increased costs for RTx:diltiazem administration,acute rejection and infection complications.We concluded that from the second year on,RTx in China was more effective and less costly than dialysis treatment,although recipients without diltiazem administration and with acute rejection or infection proved costlier during the first year after transplantation.
基金Research project of Sichuan medical association(No.2018SHD2-6)。
文摘Objective:To investigate the association between serum HIF-1α,β-catenin levels and the vascular calcification in the rat model of chronic kidney disease(CKD)vascular calcification.Methods:30 SD male rats were randomly divided into normal control group(CON group,n=10)and CKD vascular calcification group(CKD group,n=20).Rats in calcification group were fed with adenine combined with high phosphorus diet.At the end of the 6th week,the blood and urine of the two groups were collected to detect renal function,calcium,phosphorus and 24-hour urinary protein,the renal tissue was stained with HE,the aorta of rats was stained with Von Kossa and calcium content was determined,and the levels of HIF-1α and β-catenin in serum were detected by ElISA method.Results:compared with CON group,24-hour urinary protein,blood BUN,Scr,P,Ca×P,aortic calcium content,serum HIF-1α and β-catenin levels were significantly increased and serum calcium decreased in CKD group(P<0.05);Glomerular atrophy,renal tubule dilatation and interstitial fibrosis were seen in CKD group,Von Kossa staining of calcified nodules in aorta showed more black substance deposition.The levels of serum HIF-1α,β-catenin and serum P,Ca×P were positively correlated with the content of calcium in rat aorta.Conclusion:the levels of serum HIF-1α and β-catenin are significantly increased in patients with vascular calcification in CKD,and they are significantly related to the degree of aortic calcification.
文摘AIM To investigate the prevalence of nutritional parameters of risk for cardiovascular disease(CVD) and kidney diseases in healthy preschool children.METHODS This is an observational cross-sectional study with 60 healthy children, of both genders, aged two to six years old and 56 mothers, in Belo Horizonte, Minas Gerais, Brazil. Preschool children and their families with regular activities at public schools were invited to paticipate in the study. The following characteristics were assessed: Socio-demographic condictions, clinical health, anthropometric, biochemical, lifestyle and data on food consumption. The 56 healthy children were divided into two groups, overweight(C1) and non-overweight(C2), as well as their mothers, respectively, in overweight(M1) and non-overweight(M2). Nutritional status was defined according to results obtained through the Anthro? Software for nutritional analysis. RESULTS Thirty-five children were male, with mean age of 4.44 ± 1.0 years old. Eighty-nine percent of them were eutrophic, 86.7% were sedentary and they had five meals a day. Body mass index(BMI) for age and total cholesterol(TC) was higher on C1(P = 0.0001) and high density lipoprotein cholesterol(HDL-c) was higher on C2. Mothers were 32.5 ± 7.1 years old, mostly married and employed. Eighty-six percent of them were sedentary and 62.5% were overweight with BMI = 26.38 ± 5.07 kg/m2. Eighteen percent of the overweight mothers had isolated total hypercholesterolemia(TC levels elevated) and 12.5% had low HDL-c levels. The present study showed an association between overweight and obesity during the preschool years and the correspondent mothers' nutritional status of overweight and obesity(OR = 4.96; 95%CI: 0.558-44.17). There was a positive correlation between the food risk associated with CVD by children and mothers when their consumption was 4 times/wk(P = 0.049; r = 0.516) or daily(P = 0.000008; r = 0.892).CONCLUSION Analyzed children showed high rates of physical inactivity, high serum cholesterol levels and high consumption of food associated with risk for CVD and renal disease. Changes in habits should be encouraged early in kindergarten.
文摘In the past few decades pediatric urolithiasis has become more frequent. The reason for this increase is not completely clear but has been attributed to changes in climate, nutritional habits and possibly other environ-mental factors. Although less frequent than adult stone disease, urolithiasis in the pediatric age group is also related to significant morbidity, particularly since stones tend to recur, and, thus, should not be underestimated. Most children with idiopathic stone disease have an underlying metabolic abnormality substantiating the importance of metabolic evaluation already following initial diagnosis of urolithiasis. Identification of the metabolic abnormality allows for more specifc prescription of non pharmacological and pharmacological interventions aimed at preventing recurrent stone formation. A better understanding of the causes of kidney stone disease will provide better strategies for stone prevention in children.
文摘Background：Improving islet graft revascularization has become a crucial task for prolonging islet graft survival.Endothelial cells （ECs） are the basis of new microvessels in an isolated islet,and EC coating has been demonstrated to improve the vascularization and survival of an islet.However,the traditional method of EC coating of islets has low efficiency in vitro.This study was conducted to evaluate the effect of a polyglycolic acid （PGA） scaffold on the efficiency of islet coating by ECs and the angiogenesis in the coated islet graft.Methods：A PGA fibrous scaffold was used for EC coating of islet culture and was evaluated for its efficiency of EC coating on islets and islet graft angiogenesis.Results：In in vitro experiments,we found that apoptosis index of ECs-coating islet in PGA group （27% ± 8%） was significantly lower than that in control group （83% ± 20%,P 〈 0.05） after 7 days culture.Stimulation index was significantly greater in the PGA group than in the control group at day 7 after ECs-coating （2.07 ± 0.31 vs.1.80 ± 0.23,P 〈 0.05）.vascular endothelial growth factor （VEGF） level in the PGA group was significantly higher than the coating in the control group after 7 days culture （52.10 ± 13.50 ng/ml vs.16.30 ± 8.10 ng/ml,P 〈 0.05）.Because of a tight,circumvallated,adhesive and three-dimensional growth microenvironment,islet cultured in a PGA scaffold had higher coating efficiency showing stronger staining intensity of enzyme than those in the control group after 14 days of culture following ECs-coating.For in vivo study,PGA scaffold significantly prolonged the average survival time of EC-coated islet graft after transplantation compared with control group （15.30 ± 5.60 days vs.8.30 ± 2.45 days,P 〈 0.05）.The angiogenesis and area of survived grafts were more in the PGA group compared with the control group by measuring the mean microvessel density （8.60 ± 1.21/mm2 vs.5.20 ± 0.87/mm2,P 〈 0.05）.In addition,expression of VEGF and tyrosin-protein kinase receptor （Tie-2） gene increased in PGA scaffold group than that in control group by real-time reverse transcription-polymerase chain reaction analysis.Conclusions：These results demonstrate that the efficiency of EC coating of islets was successfully increased by culturing ECs on a PGA scaffold.This method enhances the function,survival,and vascularization of isolated islets in vitro and in vivo.
基金This work is funded by a Key Project of Health and Family Planning Commission of Hubei Province of China(No.WJ2019Z007)the National Key Research&Development Program of China(2018YFA0108804)+3 种基金the National Natural Science Foundation of China(Nos.81970650 and 81770753)the Youth Program of National Natural Science Foundation of China(No.81800661)the Fundamental Research Funds for the Central Universities(No.20ykpy34)the China Postdoctoral Science Foundation Funded Project(No.2020M683083).
文摘Coronavirus disease 2019(COVID-19)is an infectious disease caused by a newly discovered coronavirus and has rapidly spread to most of the world and resulted in a global pandemic.However,there is a paucity of information available to characterize the immunodeficient population in the COVID-19 pandemic,especially information that focuses on patients after renal transplantation as the typical representative of this population.
文摘Dear Editor, As a mitochondrial deacetylase, SIRT3 deacetylates many enzymes involved in central metabolism and maintains mitochondrial proteostasis （Verdin et al., 2010; Papa and Germain, 2014）. Substrates of SIRT3 include components of the respiratory complexes, proteins involved in fatty acid oxidation and TCA cycle （Yu et al., 2012）. SIRT3 activates MnSOD to maintain reactive oxygen species （ROS） home- ostasis and a loss of SIRT3 contributes to the age-associ- ated diseases （McDonnell et al., 2015; Qiu et al., 2010）. SIRT3 plays dual roles functioning as a tumor suppressor or a promoter in tumorigenesis and progression （Alhazzazi et al., 2011 ）. On one hand, SIRT3 regulates the cellular ROS level and maintains genomic stability, and mediates meta- bolic reprogramming to prevent tumorigenesis （Finley and Haigis, 2012）. As a result, the low expression of SIRT3 has been found in breast cancer, glioblastoma, colon cancer, osteosarcoma, prostate, and ovarian cancers （Kim et al., 2010; Finley and Haigis, 2012）. On the other hand, SIRT3 is a prosurvival factor that modulates p53 activities and is upregulated in oral cancer, the node-positive breast cancer, and bladder cancer （Ashraf et al., 2006; Alhazzazi et al., 2011）. These results suggest that SIRT3 possesses the tumor-type dependent function and its precise role needs to be elucidated in the context of a specific cancer. Clear cell renal cell carcinoma （ccRCC） is the most common histo- logical subtype of renal cancer （Cohen and McGovern, 2005）. The aims of the present study were to examine the expression of SIRT3 in ccRCC and to characterize effects of SIRT3 on tumorigenesis and progression using 293T human embryonic kidney cells as the model system that has cancer stem cell-like features （Debeb et al., 2010）.
基金This study was supported by US Department of Veterans Affairs(5101BX001353)National Natural Science Foundation of China(31501116)+1 种基金Shenzhen Sanming Project of Medicine(SZSM201911013)Shenzhen Science and Technology Innovation Commission(JCYJ20190809100005672).
文摘Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system.In contrast,interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids.To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity,we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids.Among patients receiving glucocorticoids,early interferon therapy was associated with earlier hospital discharge(adjusted HR 1.68,95%Cl 1.19-2.37)and symptom relief(adjusted HR 1.48;95%Cl 1.06-2.08),while these associations were insignificant among glucocorticoids nonusers.Early interferon therapy was also associated with lower prevalence of prolonged viral shedding(adjusted OR 0.24,95%Cl 0.10-0.57)only among glucocorticoids users.Additionally,these associations were glucocorticoid cumulative dose-and timing-dependent.These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.
基金This work was supported by Xiangyang Science and Technology Bureau(2020YL10,2020YL14,2020YL17,and 2020YL39)National Natural Science Foundation of China(31501116)+2 种基金Shenzhen Science and Technology Innovation Commission(JCYJ20190809100005672)Shenzhen Sanming Project of Medicine(SZSM201911013)US Department of Veterans Affairs(5I01BX001353).
文摘The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life.Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang,China at 1-year after diagnosis.Among them,chemiluminescence immunoassay-based screening showed 99%(95%CI,98–100%)seroprevalence 10–12 months after infection,comparing to 0.8%(95%CI,0.7–0.9%)in the general population.Total anti-receptor-binding domain(RBD)antibodies remained stable since discharge,while anti-RBD IgG and neutralization levels decreased over time.A predictive model estimates 17%(95%CI,11–24%)and 87%(95%CI,80–92%)participants were still 50%protected against detectable and severe re-infection of WT SARS-CoV-2,respectively,while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced.All non-severe patients showed normal chest CT and 21%reported COVID-19-related symptoms.In contrast,53%severe patients had abnormal chest CT,decreased pulmonary function or cardiac involvement and 79%were still symptomatic.Our findings suggest long-lasting immune protection after SARS-CoV-2 infection,while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.
基金supported by the Clinical Research Flagship Project of Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology(No.2019CR108).
文摘To the Editor:To reduce the risk of acute rejection(AR)after renal transplantation,immunosuppressive induction therapy has been commonly used in the perioperative period.At present,rabbit anti-thymocyte globulin(rATG)and basiliximab are the two main induction agents used for kidney transplantation.In adult kidney transplantation,the incidence of AR with rATG induction is generally lower than that with basiliximab.[1]Children have different immune systems than adults do.In pediatric kidney transplantation,which induction therapy is more effective in preventing early AR is an important clinical question worth answering.Because there are few reports in this field and differences in the immune systems of children at different ages,we have now conducted a total and age-stratified analysis of Chinese multicenter cohort data to compare the AR rates and other outcomes between rATG and basiliximab induction therapy groups in pediatric deceased-donor kidney transplantation.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81530021）.
文摘Background：Core fucosylation （CF）,catalyzed by α-1,6 fucosyltransferase （Fut8） in mammals,plays an important role in pathological processes through posttranslational modification of key signaling receptor proteins,including transforming growth factor （TGF）-β receptors and platelet-derived growth factor （PDGF） receptors.However,its effect on peritoneal fibrosis is unknown.Here,we investigated its influence on epithelial-mesenchymal transition （EMT） of rat peritoneal mesothelial cells （PMCs） in vitro induced by a high-glucose （HG） culture solution.Methods：Rat PMCs were first cultured in a HG （2.5%） culture solution to observe the CF expression level （fluorescein isothiocyanate-lens culinaris agglutinin）,we next established a knockdown model of rat PMCs in vitro with Fut8 small interfering RNA （siRNA） to observe whether inhibiting CF decreases the messenger RNA （mRNA） expression and protein expression of Fut8 and reverses EMT status.Rat PMCs were randomly divided into control group,mock group （transfected with scrambled siRNA）,Fut8 siRNA group,HG group,HG ＋ mock group,and HG ＋ Fut8 siRNA group.Finally,we examined the activation of TGF-β/Smad2/3 signaling and PDGF/extracellular signal-regulated kinase （ERK） signaling to observe the influence of CF on them.Results：CF,Fut8 mRNA,and protein expression were all significantly upregulated in HG-induced EMT model than those in the control rat PMCs （P 〈 0.05）.Fut8 siRNA successfully blocked CF of TGF-β receptors and PDGF receptors and attenuated the EMT status （E-cadherin and α-SMA and phenotypic changes） in HG-induced rat PMCs.In TGF-β/Smad2/3 signaling,Fut8 siRNA did not suppress the protein expression of TGF-3 receptors and Smad2/3;however,it significantly suppressed the phosphowlation of Smad2/3 （relative expression folds of HG ＋ Fut8 group vs.HG group：7.6 ± 0.4 vs.15.1 ± 0.6,respectively,P 〈 0.05）.In PDGF/ERK signaling,Fut8 siRNA did not suppress the protein expression of PDGF receptors and ERK,but it significantly suppressed the phosphorylation of ERK （relative expression folds of HG ＋ Fut8 group vs.HG group：8.7 ± 0.9 vs.15.6 ± 1.2,respectively,P 〈 0.05）.Blocking CF inactivated the activities of TGF-β and PDGF signaling pathways,and subsequently blocked EMT.Conclusions：These results demonstrate that CF contributes to rat PMC EMT.and that blocking it attenuates EMT.CF regulation is a potential therapeutic target of peritoneal fibrosis.
