Obesity has become a worldwide epidemic,and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes,cardiovascular disease and also for...Obesity has become a worldwide epidemic,and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes,cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis,and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease,advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.展开更多
Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 20...Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.展开更多
The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity...The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.展开更多
AIM: To compare anemia prevalence between matched chronic kidney disease(CKD) patients with and without diabetes mellitus(DM) and to assess factors associated with anemia development.METHODS: This is a nested case-con...AIM: To compare anemia prevalence between matched chronic kidney disease(CKD) patients with and without diabetes mellitus(DM) and to assess factors associated with anemia development.METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate(eG FR). Prevalence of anemia(hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia.RESULTS: The total prevalence of anemia was higher in diabetics(47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3(53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a(60.4% vs 26.4%, P < 0.001), whereas it was nonsignificantly higher in Stage 4(61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM(OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4(Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron(OR = 0.976, 95%CI: 0.968-0.985 per mg/d L increase) were independently associated with anemia.CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts.展开更多
BACKGROUND Few studies have examined intestinal motility disorders, which are disabling conditions associated with chronic functional constipation, whose pathogenesis is actually not well-defined.AIM To investigate th...BACKGROUND Few studies have examined intestinal motility disorders, which are disabling conditions associated with chronic functional constipation, whose pathogenesis is actually not well-defined.AIM To investigate the relationship between serum 25-hydroxyvitamin D levels and functional chronic constipation associated to intestinal motility disorders.METHODS We performed a prospective case-control study, from May-June to November2017. Glucose/lactulose breath tests, radiopaque markers(multiple capsule techniques) and wireless motility capsule analysis were used to assess colonicand oro-cecal transit time, after excluding small-intestinal bacterial overgrowth condition. Then, we measured 25-hydroxyvitamin D levels in patients with intestinal motility disorders and we further evaluated the influence of intestinal motility disorders on psychological symptoms/quality of life using validated questionnaires, the Irritable Bowel Syndrome Quality of life(IBS-QOL), the Short Form Health Survey 12, and the Hospital Anxiety and Depression Scale 14(HADS-14 A and HADS-14 D).RESULTS We enrolled 86 patients with chronic functional constipation associated to intestinal motility disorders and 86 matched healthy subjects. Patients with intestinal motility disorders had lower 25-hydroxyvitamin D levels(P < 0.001), and they showed a significant impairment of all health-related quality of life and psychological tests(IBS-QOL, Short Form Health Survey 12-Physical Component Summary, Short Form Health Survey 12-Mental Component Summary, HADS-14 A and HADS-14 D), as compared to the control group(P < 0.001), which significantly correlated with low vitamin D levels(r =-0.57, P < 0.001; r = 0.21, P = 0.01; r =-0.48, P < 0.001; r =-0.57, P < 0.001; r =-0.29, P < 0.001, respectively). At multivariate analysis vitamin D low levels remained a significant independent risk factor for the occurrence of intestinal motility disorder(odds ratio = 1.19; 95% confidence interval: 1.14-1.26, P < 0.001).CONCLUSION Vitamin D deficiency, anxiety and depress展开更多
Patients with kidney diseases continue to experience significant cardiovascular disease(CVD) morbidity and mortality. Although there are many important risk factors playing a role in the pathogenesis of CVD in chronic...Patients with kidney diseases continue to experience significant cardiovascular disease(CVD) morbidity and mortality. Although there are many important risk factors playing a role in the pathogenesis of CVD in chronic kidney disease(CKD) patients, dyslipidemia(elevated triglycerides, elevated oxidized low-densitylipoprotein and low/dysfunctional low high-density) represents one of the modifiable risk factors. Renal failure patients have unique lipid abnormalities which not only have complex role in pathogenesis of CVD but also cause relative resistance to usual interventions. Most of the randomized trials have been in hemodialysis population and data from CKD non-dialysis, peritoneal dialysis and renal transplant populations is extremely limited. Compared to general population, evidence of mortality benefit of lipid lowering medications in CKD population is scarce. Future research should be directed towards establishing long term benefits and side effects of lipid lowering medications, through randomized trials, in CKD population.展开更多
A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyper...A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyperosmolar state(HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 m Osm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with newonset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.展开更多
BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can signif...BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD.Currently,there is limited research on how social support mediates the relationship between dysphoria,despondency,and overall QOL in patients undergoing MHD.It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD,ultimately enhancing their overall QOL.AIM To investigate the mediating role of social support in relationships between dysphoria,despondency,and QOL among patients undergoing MHD.METHODS Participants comprised 289 patients undergoing MHD,who were selected using a random sampling approach.The Social Support Rating Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and QOL Scale were administered.Correlation analysis was performed to examine the associations between social support,dysphoria,despondency,and QOL in patients undergoing MHD.To assess the mediating impact of social support on dysphoria,despondency,and QOL in patients undergoing MHD,a bootstrap method was applied.RESULTS Significant correlations among social support,dysphoria,despondency,and quality in patients undergoing MHD were observed(all P<0.01).Dysphoria and despondency negatively correlated with social support and QOL(P<0.01).Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD(P<0.05).The direct effect of dysphoria on QOL was statistically significant(P<0.05).Social support mediated the relationship between dysphoria and QOL,and this mediating effect was significant(P<0.05).Similarly,the direct effect of despondency on QOL was significant(P<0.05).Moreover,social support played a mediating role between despondency and QOL,with a significant mediating effect(P<0.05).CONCLUSION These findings suggest that social support plays a signifi展开更多
Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperg...Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypo-volemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium defcit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the frst component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fuid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtainedby the corrected sodium concentration, which representsa calculated value of the serum sodium concentrationthat would result from reduction of the serum glucoseconcentration to a normal level.展开更多
Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK ne...Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy(BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.展开更多
AIM:To establish the frequency of hyperphosphate-mia following the administration of sodium phosphate laxatives in low-risk patients. METHODS:One hundred consecutive ASAⅠ-Ⅱindividuals aged 35-74 years,who were under...AIM:To establish the frequency of hyperphosphate-mia following the administration of sodium phosphate laxatives in low-risk patients. METHODS:One hundred consecutive ASAⅠ-Ⅱindividuals aged 35-74 years,who were undergoing colonic cleansing with oral sodium phosphate(OSP) before colonoscopy were recruited for this prospective study.Exclusion criteria:congestive heart failure, chronic kidney disease,diabetes,liver cirrhosis,intestinal obstruction,decreased bowel motility,increased bowel permeability,and hyperparathyroidism.The day before colonoscopy,all the participants entered a 24-h period of diet that consisted of 4 L of clear fluids with sugar or honey and 90 mL(60 g)of OSP in two 45-mL doses,5 h apart.Serum phosphate was measured before and after the administration of the laxative. RESULTS:The main demographic data(mean±SD) were:age,58.9±8.4 years;height,163.8±8.6 cm; weight,71±13 kg;body mass index,26±4;women, 66%.Serum phosphate increased from 3.74±0.56 to 5.58±1.1 mg/dL,which surpassed the normal value (2.5-4.5 mg/dL)in 87%of the patients.The highest serum phosphate was 9.6 mg/dL.Urea and creatinine remained within normal limits.Post-treatment OSP se-rum phosphate concentration correlated inversely with glomerular filtration rate(P<0.007,R 2=0.0755),total body water(P<0.001,R 2=0.156)and weight(P< 0.013,R 2=0.0635). CONCLUSION:In low-risk,well-hydrated patients, the standard dose of OSP-laxative-induced hyperphos-phatemia is related to body weight.展开更多
Respiratory failure complicating the course of diabetic ketoacidosis(DKA)is a source of increased morbidity and mortality.Detection of respiratory failure in DKA requires focused clinical monitoring,careful interpreta...Respiratory failure complicating the course of diabetic ketoacidosis(DKA)is a source of increased morbidity and mortality.Detection of respiratory failure in DKA requires focused clinical monitoring,careful interpretation of arterial blood gases,and investigation for conditions that can affect adversely the respiration.Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment.These conditions include deficits of potassium,magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema.Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system,pre-existing respiratory or neuromuscular disease and miscellaneous other conditions.Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA.展开更多
Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound ...Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound tubular damage and interstitial inflammation and fibrosis.Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to endstage renal disease(ESRD).This sequence of events,well recognized in the past in primary and enteric hyperoxalurias,has also been documented in a few cases of dietary hyperoxaluria.Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide,thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions.Studies addressing this question have the potential of improving population health and should be undertaken,alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate,and into the mechanisms of development of oxalate-induced renal parenchymal disease.Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.展开更多
While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs)...While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic regulation.lncRNAs are emerging as critical regulators of gene expression and genomic stability.However,it remains largely unknown about how lncRNAs are regulated.Here,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput fashion.Specifically,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP protein.We further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific siRNAs.Therefore,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders.展开更多
OBJECTIVE:To study the efficacy of Xiaoyao capsule(逍遥丸)in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019(COVID-19).METHODS:The study cohort comprised 200 p...OBJECTIVE:To study the efficacy of Xiaoyao capsule(逍遥丸)in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019(COVID-19).METHODS:The study cohort comprised 200 patients with sleep and mood disorders during recovery from COVID-19.Patients were randomized into the control group and the experimental group in a 1:1 ratio by blocked randomization.The patients received either Xiaoyao capsule(experimental group)or a placebo Xiaoyao capsule(control group)for 2 weeks.The improvements in the Traditional Chinese Medicine(TCM)syndrome scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep were compared between the two groups.RESULTS:The TCM syndrome pattern scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep did not significantly differ between the experimental group versus the control group in the full analysis set and the per protocol set after 1 and 2 weeks of treatment(P>0.05).CONCLUSIONS:Xiaoyao capsule do not significantly improve the clinical symptoms of sleep and mood disorders in patients in recovery from COVID-19.展开更多
The authors regret having an image assembly error in Figure 5Ca,in which the image for the "Oh dBiFP-AdRFp"group was erroneously duplicated with an overlapping image from the"36h BiFP dBIFP-AdR-simH19&q...The authors regret having an image assembly error in Figure 5Ca,in which the image for the "Oh dBiFP-AdRFp"group was erroneously duplicated with an overlapping image from the"36h BiFP dBIFP-AdR-simH19"group.We confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and unchanged.The authors would like to apologize for any inconvenience caused.展开更多
Background:We analysed data garnered during the ongoing Italian nationwide coronavirus disease 2019(COVID-19)vaccination campaign for comparing early COVID-19 monovalent vaccine efficacy in older persons who received ...Background:We analysed data garnered during the ongoing Italian nationwide coronavirus disease 2019(COVID-19)vaccination campaign for comparing early COVID-19 monovalent vaccine efficacy in older persons who received the primary vaccination cycle,the first vaccine booster,and the second vaccine booster.Methods:We conducted a retrospective analysis of early COVID-19 monovalent vaccine efficacy(i.e.,within 120 days)against COVID-19 related hospitalizations,intensive care unit(ICU)admissions and deaths in older persons(i.e.,aged≥80 years),by accessing official data of the COVID-19 national integrated surveillance program instituted by the Italian National Institute of Health.Vaccine efficacy was compared(odds ratio;OR)among cohorts receiving the primary vaccination cycle,the first vaccine booster,and the second vaccine booster.Results:A consistent decline could be seen in the rate of COVID-19 hospitalizations,ICU admissions and deaths with increasing number of monovalent immunizations.Within 120 days of administration,the first and second vaccine boosters had superior efficacy compared to the primary vaccination cycle,reducing the odds of all endpoints between 62%-71%and 69%-84%,respectively.A modestly superior early efficacy could also be noted for the second versus the first monovalent vaccine booster(ORs of all endpoints further reduced by 18%-48%).Conclusion:Since an increasing number of immunizations is associated with a lower risk of unfavourable COVID-19 outcomes,vaccine boosters may be useful for limiting the clinical burden of this infectious disease in elderly populations.展开更多
As multipotent progenitor cells,mesenchymal stem cells(MSCs)can renew themselves and give rise to multiple lineages including osteoblastic,chondrogenic and adipogenic lineages.It’s previously shown that BMP9 is the m...As multipotent progenitor cells,mesenchymal stem cells(MSCs)can renew themselves and give rise to multiple lineages including osteoblastic,chondrogenic and adipogenic lineages.It’s previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs.However,the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood.Emerging evidence indicates that noncoding RNAs,especially microRNAs,may play important roles in regulating MSC differentiation and bone formation.As highly conserved RNA binding proteins,Argonaute(AGO)proteins are essential components of the multi-protein RNA-induced silencing complexes(RISCs),which are critical for small RNA biogenesis.Here,we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs.We first found that BMP9 upregulated the expression of Ago1,Ago2 and Ago3 in MSCs.By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes,we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase(ALP)activity in MSCs.Furthermore,we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization,and ectopic bone formation.Collectively,our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.展开更多
BACKGROUND Acute kidney injury(AKI)is a common and severe complication after left ventricular assist device(LVAD)implantation with an incidence of 37%;13%of which require kidney replacement therapy(KRT).Severe AKI req...BACKGROUND Acute kidney injury(AKI)is a common and severe complication after left ventricular assist device(LVAD)implantation with an incidence of 37%;13%of which require kidney replacement therapy(KRT).Severe AKI requiring KRT(AKI-KRT)in LVAD patients is associated with high short and long-term mortality compared with AKI without KRT.While kidney function recovery is associated with better outcomes,its incidence is unclear among LVAD patients with severe AKI requiring KRT.AIM To identify studies evaluating the recovery rates from severe AKI-KRT after LVAD placement,which is defined by regained kidney function resulting in the discontinuation of KRT.Random-effects and generic inverse variance method of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies.METHODS A total of 268 patients from 14 cohort studies that reported severe AKI-KRT after LVAD were included.Follow-up time ranged anywhere from two weeks of LVAD implantation to 12 mo.Kidney recovery occurred in 78%of enrollees at the time of hospital discharge or within 30 d.Overall,the pooled estimated AKI recovery rate among patients with severe AKI-KRT was 50.5%(95%CI:34.0%-67.0%)at 12 mo follow up.Majority(85%)of patients used continuous-flow LVAD.While the data on pulsatile-flow LVAD was limited,subgroup analysis of continuous-flow LVAD demonstrated that pooled estimated AKI recovery rate among patients with severe AKI-KRT was 52.1%(95%CI:36.8%-67.0%).Metaregression analysis did not show a significant association between study year and AKI recovery rate(P=0.08).There was no publication bias as assessed by the funnel plot and Egger's regression asymmetry test in all analyses.RESULTS A total of 268 patients from 14 cohort studies that reported severe AKI-KRT after LVAD were included.Follow-up time ranged anywhere from two weeks of LVAD implantation to 12 mo.Kidney recovery occurred in 78%of enrollees at the time of hospital discharge or within 30 d.Overall,the pooled estimated AKI recovery rate among patients with seve展开更多
BACKGROUND Hepatorenal syndrome(HRS)is a life-threatening condition among patients with advanced liver disease.Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limi...BACKGROUND Hepatorenal syndrome(HRS)is a life-threatening condition among patients with advanced liver disease.Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited.AIM To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States.METHODS We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014(weighted sample of 23973 admissions).The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality.We estimated odds ratios from multilevel mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality.RESULTS Overall hospital mortality was 32%.Hospital mortality decreased from 44%in 2005 to 24%in 2014(P<0.001),while there was an increase in the rate of liver transplantation(P=0.02),renal replacement therapy(P<0.001),length of hospital stay(P<0.001),and hospitalization cost(P<0.001).On multivariable analysis,older age,alcohol use,coagulopathy,neurological disorder,and need for mechanical ventilation predicted higher hospital mortality,whereas liver transplantation,transjugular intrahepatic portosystemic shunt,and abdominal paracentesis were associated with lower hospital mortality.CONCLUSION Although there was an increase in resource utilizations,hospital mortality among patients admitted for HRS significantly improved.Several predictors for hospital mortality were identified.展开更多
文摘Obesity has become a worldwide epidemic,and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes,cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis,and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease,advocating healthy lifestyle and health policy measures that makes preventive behaviors an affordable option.
文摘Background:With the rising global prevalence of fatty liver disease related to metabolic dysfunction,the association of this common liver condition with chronic kidney disease(CKD)has become increasingly evident.In 2020,the more inclusive term metabolic dysfunction-associated fatty liver disease(MAFLD)was proposed to replace the term non-alcoholic fatty liver disease(NAFLD).The observed association between MAFLD and CKD and our understanding that CKD can be a consequence of underlying metabolic dysfunction support the notion that individuals with MAFLD are at higher risk of having and developing CKD compared with those without MAFLD.However,to date,there is no appropriate guidance on CKD in individuals with MAFLD.Furthermore,there has been little attention paid to the link between MAFLD and CKD in the Nephrology community.Methods and Results:Using a Delphi-based approach,a multidisciplinary panel of 50 international experts from 26 countries reached a consensus on some of the open research questions regarding the link between MAFLD and CKD.Conclusions:This Delphi-based consensus statement provided guidance on the epidemiology,mechanisms,management and treatment of MAFLD and CKD,as well as the relationship between the severity of MAFLD and risk of CKD,which establish a framework for the early prevention and management of these two common and interconnected diseases.
基金the Research Service of the Raymond G. Murphy VA Medical Center for its support of this work
文摘The development of formulas estimating glomerular filtration rate(eG FR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease(CKD),which is based on e GFR values and albuminuria.This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course. Disagreements between creatinine-based and cystatin-based e GFR values and between e GFR values and measured GFR have been reported in various cohorts. These disagreements are the consequence of variations in the rate of production and in factors, other than GFR, affecting the rate of removal of creatinine and cystatin C. The disagreements create limitations for all e GFR formulas developed so far. The main limitations are low sensitivity in detecting early CKD in several subjects, e.g., those with hyperfiltration, and poor prediction of the course of CKD. Research efforts in CKD are currently directed towards identification of biomarkers that are better indices of GFR than the current biomarkers and,particularly, biomarkers of early renal tissue injury.
文摘AIM: To compare anemia prevalence between matched chronic kidney disease(CKD) patients with and without diabetes mellitus(DM) and to assess factors associated with anemia development.METHODS: This is a nested case-control study of 184 type-2 diabetic and 184 non-diabetic CKD patients from a prospectively assembled database of a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate(eG FR). Prevalence of anemia(hemoglobin: Men: < 13 g/dL, women: < 12 g/dL and/or use of recombinant erythropoietin) was examined in comparison, in the total population and by CKD Stage. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with anemia.RESULTS: The total prevalence of anemia was higher in diabetics(47.8% vs 33.2%, P = 0.004). Accordingly, prevalence was higher in diabetics in CKD Stage 3(53.5% vs 33.1%, P < 0.001) and particularly in Stage 3a(60.4% vs 26.4%, P < 0.001), whereas it was nonsignificantly higher in Stage 4(61.3% vs 48.4%; P = 0.307). Serum ferritin was higher in diabetics in total and in CKD stages, while serum iron was similar between groups. In multivariate analyses, DM(OR = 2.206, 95%CI: 1.196-4.069), CKD Stages 3a, 3b, 4(Stage 4: OR = 12.169, 95%CI: 3.783-39.147) and serum iron(OR = 0.976, 95%CI: 0.968-0.985 per mg/d L increase) were independently associated with anemia.CONCLUSION: Prevalence of anemia progressively increases with advancing stages of CKD and is higher in diabetic than matched non-diabetic CKD patients and diabetes is independently associated with anemia occurrence. Detection and treatment of anemia in diabetic CKD patients should be performed earlier than non-diabetic counterparts.
文摘BACKGROUND Few studies have examined intestinal motility disorders, which are disabling conditions associated with chronic functional constipation, whose pathogenesis is actually not well-defined.AIM To investigate the relationship between serum 25-hydroxyvitamin D levels and functional chronic constipation associated to intestinal motility disorders.METHODS We performed a prospective case-control study, from May-June to November2017. Glucose/lactulose breath tests, radiopaque markers(multiple capsule techniques) and wireless motility capsule analysis were used to assess colonicand oro-cecal transit time, after excluding small-intestinal bacterial overgrowth condition. Then, we measured 25-hydroxyvitamin D levels in patients with intestinal motility disorders and we further evaluated the influence of intestinal motility disorders on psychological symptoms/quality of life using validated questionnaires, the Irritable Bowel Syndrome Quality of life(IBS-QOL), the Short Form Health Survey 12, and the Hospital Anxiety and Depression Scale 14(HADS-14 A and HADS-14 D).RESULTS We enrolled 86 patients with chronic functional constipation associated to intestinal motility disorders and 86 matched healthy subjects. Patients with intestinal motility disorders had lower 25-hydroxyvitamin D levels(P < 0.001), and they showed a significant impairment of all health-related quality of life and psychological tests(IBS-QOL, Short Form Health Survey 12-Physical Component Summary, Short Form Health Survey 12-Mental Component Summary, HADS-14 A and HADS-14 D), as compared to the control group(P < 0.001), which significantly correlated with low vitamin D levels(r =-0.57, P < 0.001; r = 0.21, P = 0.01; r =-0.48, P < 0.001; r =-0.57, P < 0.001; r =-0.29, P < 0.001, respectively). At multivariate analysis vitamin D low levels remained a significant independent risk factor for the occurrence of intestinal motility disorder(odds ratio = 1.19; 95% confidence interval: 1.14-1.26, P < 0.001).CONCLUSION Vitamin D deficiency, anxiety and depress
文摘Patients with kidney diseases continue to experience significant cardiovascular disease(CVD) morbidity and mortality. Although there are many important risk factors playing a role in the pathogenesis of CVD in chronic kidney disease(CKD) patients, dyslipidemia(elevated triglycerides, elevated oxidized low-densitylipoprotein and low/dysfunctional low high-density) represents one of the modifiable risk factors. Renal failure patients have unique lipid abnormalities which not only have complex role in pathogenesis of CVD but also cause relative resistance to usual interventions. Most of the randomized trials have been in hemodialysis population and data from CKD non-dialysis, peritoneal dialysis and renal transplant populations is extremely limited. Compared to general population, evidence of mortality benefit of lipid lowering medications in CKD population is scarce. Future research should be directed towards establishing long term benefits and side effects of lipid lowering medications, through randomized trials, in CKD population.
文摘A man with past lithium use for more than 15 years, but off lithium for two years and not carrying the diagnosis of diabetes mellitus or nephrogenic diabetes insipidus(NDI), presented with coma and hyperglycemic hyperosmolar state(HHS). Following correction of HHS, he developed persistent hypernatremia accompanied by large volumes of urine with low osmolality and no response to desmopressin injections. Urine osmolality remained < 300 m Osm/kg after injection of vasopressin. Improvement in serum sodium concentration followed the intake of large volumes of water plus administration of amiloride and hydrochlorothiazide. Severe hyperglycemia may trigger symptomatic lithium-induced NDI years after cessation of lithium therapy. Patients with newonset diabetes mellitus who had been on prolonged lithium therapy in the past require monitoring of their serum sodium concentration after hyperglycemic episodes regardless of whether they do or do not carry the diagnosis of NDI.
基金Supported by the Natural Science Foundation Project of Xinjiang Uygur Autonomous Region,No.2021D01C143.
文摘BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD.Currently,there is limited research on how social support mediates the relationship between dysphoria,despondency,and overall QOL in patients undergoing MHD.It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD,ultimately enhancing their overall QOL.AIM To investigate the mediating role of social support in relationships between dysphoria,despondency,and QOL among patients undergoing MHD.METHODS Participants comprised 289 patients undergoing MHD,who were selected using a random sampling approach.The Social Support Rating Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and QOL Scale were administered.Correlation analysis was performed to examine the associations between social support,dysphoria,despondency,and QOL in patients undergoing MHD.To assess the mediating impact of social support on dysphoria,despondency,and QOL in patients undergoing MHD,a bootstrap method was applied.RESULTS Significant correlations among social support,dysphoria,despondency,and quality in patients undergoing MHD were observed(all P<0.01).Dysphoria and despondency negatively correlated with social support and QOL(P<0.01).Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD(P<0.05).The direct effect of dysphoria on QOL was statistically significant(P<0.05).Social support mediated the relationship between dysphoria and QOL,and this mediating effect was significant(P<0.05).Similarly,the direct effect of despondency on QOL was significant(P<0.05).Moreover,social support played a mediating role between despondency and QOL,with a significant mediating effect(P<0.05).CONCLUSION These findings suggest that social support plays a signifi
文摘Hypertonicity causes severe clinical manifestations and is associated with mortality and severe short-term and long-term neurological sequelae. The main clinical syndromes of hypertonicity are hypernatremia and hyperglycemia. Hypernatremia results from relative excess of body sodium over body water. Loss of water in excess of intake, gain of sodium salts in excess of losses or a combination of the two are the main mechanisms of hypernatremia. Hypernatremia can be hypervolemic, euvolemic or hypo-volemic. The management of hypernatremia addresses both a quantitative replacement of water and, if present, sodium defcit, and correction of the underlying pathophysiologic process that led to hypernatremia. Hypertonicity in hyperglycemia has two components, solute gain secondary to glucose accumulation in the extracellular compartment and water loss through hyperglycemic osmotic diuresis in excess of the losses of sodium and potassium. Differentiating between these two components of hypertonicity has major therapeutic implications because the frst component will be reversed simply by normalization of serum glucose concentration while the second component will require hypotonic fuid replacement. An estimate of the magnitude of the relative water deficit secondary to osmotic diuresis is obtainedby the corrected sodium concentration, which representsa calculated value of the serum sodium concentrationthat would result from reduction of the serum glucoseconcentration to a normal level.
文摘Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy(BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.
文摘AIM:To establish the frequency of hyperphosphate-mia following the administration of sodium phosphate laxatives in low-risk patients. METHODS:One hundred consecutive ASAⅠ-Ⅱindividuals aged 35-74 years,who were undergoing colonic cleansing with oral sodium phosphate(OSP) before colonoscopy were recruited for this prospective study.Exclusion criteria:congestive heart failure, chronic kidney disease,diabetes,liver cirrhosis,intestinal obstruction,decreased bowel motility,increased bowel permeability,and hyperparathyroidism.The day before colonoscopy,all the participants entered a 24-h period of diet that consisted of 4 L of clear fluids with sugar or honey and 90 mL(60 g)of OSP in two 45-mL doses,5 h apart.Serum phosphate was measured before and after the administration of the laxative. RESULTS:The main demographic data(mean±SD) were:age,58.9±8.4 years;height,163.8±8.6 cm; weight,71±13 kg;body mass index,26±4;women, 66%.Serum phosphate increased from 3.74±0.56 to 5.58±1.1 mg/dL,which surpassed the normal value (2.5-4.5 mg/dL)in 87%of the patients.The highest serum phosphate was 9.6 mg/dL.Urea and creatinine remained within normal limits.Post-treatment OSP se-rum phosphate concentration correlated inversely with glomerular filtration rate(P<0.007,R 2=0.0755),total body water(P<0.001,R 2=0.156)and weight(P< 0.013,R 2=0.0635). CONCLUSION:In low-risk,well-hydrated patients, the standard dose of OSP-laxative-induced hyperphos-phatemia is related to body weight.
文摘Respiratory failure complicating the course of diabetic ketoacidosis(DKA)is a source of increased morbidity and mortality.Detection of respiratory failure in DKA requires focused clinical monitoring,careful interpretation of arterial blood gases,and investigation for conditions that can affect adversely the respiration.Conditions that compromise respiratory function caused by DKA can be detected at presentation but are usually more prevalent during treatment.These conditions include deficits of potassium,magnesium and phosphate and hydrostatic or non-hydrostatic pulmonary edema.Conditions not caused by DKA that can worsen respiratory function under the added stress of DKA include infections of the respiratory system,pre-existing respiratory or neuromuscular disease and miscellaneous other conditions.Prompt recognition and management of the conditions that can lead to respiratory failure in DKA may prevent respiratory failure and improve mortality from DKA.
文摘Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound tubular damage and interstitial inflammation and fibrosis.Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to endstage renal disease(ESRD).This sequence of events,well recognized in the past in primary and enteric hyperoxalurias,has also been documented in a few cases of dietary hyperoxaluria.Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide,thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions.Studies addressing this question have the potential of improving population health and should be undertaken,alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate,and into the mechanisms of development of oxalate-induced renal parenchymal disease.Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.
基金The reported work was supported in part by research grants from the National Institutes of Health(AT004418,DE020140 to TCH and RRR)the US Department of Defense(OR130096 to JMW)+5 种基金the Scoliosis Research Society(TCH and MJL)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906 to TCH)the National Natural Science Foundation of China(#81201916 to XW)ZZ was a recipient of protectorate fellowship from China Scholarship CouncilThis project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430.
文摘While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic regulation.lncRNAs are emerging as critical regulators of gene expression and genomic stability.However,it remains largely unknown about how lncRNAs are regulated.Here,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput fashion.Specifically,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP protein.We further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific siRNAs.Therefore,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders.
文摘OBJECTIVE:To study the efficacy of Xiaoyao capsule(逍遥丸)in improving the clinical symptoms of sleep and mood disorders during recovery from coronavirus disease 2019(COVID-19).METHODS:The study cohort comprised 200 patients with sleep and mood disorders during recovery from COVID-19.Patients were randomized into the control group and the experimental group in a 1:1 ratio by blocked randomization.The patients received either Xiaoyao capsule(experimental group)or a placebo Xiaoyao capsule(control group)for 2 weeks.The improvements in the Traditional Chinese Medicine(TCM)syndrome scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep were compared between the two groups.RESULTS:The TCM syndrome pattern scales,total effective rates,and disappearance rates of irritability,anxiety,and poor sleep did not significantly differ between the experimental group versus the control group in the full analysis set and the per protocol set after 1 and 2 weeks of treatment(P>0.05).CONCLUSIONS:Xiaoyao capsule do not significantly improve the clinical symptoms of sleep and mood disorders in patients in recovery from COVID-19.
文摘The authors regret having an image assembly error in Figure 5Ca,in which the image for the "Oh dBiFP-AdRFp"group was erroneously duplicated with an overlapping image from the"36h BiFP dBIFP-AdR-simH19"group.We confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and unchanged.The authors would like to apologize for any inconvenience caused.
文摘Background:We analysed data garnered during the ongoing Italian nationwide coronavirus disease 2019(COVID-19)vaccination campaign for comparing early COVID-19 monovalent vaccine efficacy in older persons who received the primary vaccination cycle,the first vaccine booster,and the second vaccine booster.Methods:We conducted a retrospective analysis of early COVID-19 monovalent vaccine efficacy(i.e.,within 120 days)against COVID-19 related hospitalizations,intensive care unit(ICU)admissions and deaths in older persons(i.e.,aged≥80 years),by accessing official data of the COVID-19 national integrated surveillance program instituted by the Italian National Institute of Health.Vaccine efficacy was compared(odds ratio;OR)among cohorts receiving the primary vaccination cycle,the first vaccine booster,and the second vaccine booster.Results:A consistent decline could be seen in the rate of COVID-19 hospitalizations,ICU admissions and deaths with increasing number of monovalent immunizations.Within 120 days of administration,the first and second vaccine boosters had superior efficacy compared to the primary vaccination cycle,reducing the odds of all endpoints between 62%-71%and 69%-84%,respectively.A modestly superior early efficacy could also be noted for the second versus the first monovalent vaccine booster(ORs of all endpoints further reduced by 18%-48%).Conclusion:Since an increasing number of immunizations is associated with a lower risk of unfavourable COVID-19 outcomes,vaccine boosters may be useful for limiting the clinical burden of this infectious disease in elderly populations.
基金The reported work was supported in part by research grants from the National Institutes of Health(CA226303 to TCH,and AR072731 to JY)the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(RRR),and the Scoliosis Research Society(TCH and MJL)+2 种基金WW was supported by the Medical Scientist Training Program of the National Institutes of Health(T32 GM007281)This project was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health(NIH)through Grant Number 5UL1TR002389-02 that funds the Institute for Translational Medicine(ITM).TCH was supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.
文摘As multipotent progenitor cells,mesenchymal stem cells(MSCs)can renew themselves and give rise to multiple lineages including osteoblastic,chondrogenic and adipogenic lineages.It’s previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs.However,the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood.Emerging evidence indicates that noncoding RNAs,especially microRNAs,may play important roles in regulating MSC differentiation and bone formation.As highly conserved RNA binding proteins,Argonaute(AGO)proteins are essential components of the multi-protein RNA-induced silencing complexes(RISCs),which are critical for small RNA biogenesis.Here,we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs.We first found that BMP9 upregulated the expression of Ago1,Ago2 and Ago3 in MSCs.By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes,we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase(ALP)activity in MSCs.Furthermore,we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization,and ectopic bone formation.Collectively,our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.
文摘BACKGROUND Acute kidney injury(AKI)is a common and severe complication after left ventricular assist device(LVAD)implantation with an incidence of 37%;13%of which require kidney replacement therapy(KRT).Severe AKI requiring KRT(AKI-KRT)in LVAD patients is associated with high short and long-term mortality compared with AKI without KRT.While kidney function recovery is associated with better outcomes,its incidence is unclear among LVAD patients with severe AKI requiring KRT.AIM To identify studies evaluating the recovery rates from severe AKI-KRT after LVAD placement,which is defined by regained kidney function resulting in the discontinuation of KRT.Random-effects and generic inverse variance method of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies.METHODS A total of 268 patients from 14 cohort studies that reported severe AKI-KRT after LVAD were included.Follow-up time ranged anywhere from two weeks of LVAD implantation to 12 mo.Kidney recovery occurred in 78%of enrollees at the time of hospital discharge or within 30 d.Overall,the pooled estimated AKI recovery rate among patients with severe AKI-KRT was 50.5%(95%CI:34.0%-67.0%)at 12 mo follow up.Majority(85%)of patients used continuous-flow LVAD.While the data on pulsatile-flow LVAD was limited,subgroup analysis of continuous-flow LVAD demonstrated that pooled estimated AKI recovery rate among patients with severe AKI-KRT was 52.1%(95%CI:36.8%-67.0%).Metaregression analysis did not show a significant association between study year and AKI recovery rate(P=0.08).There was no publication bias as assessed by the funnel plot and Egger's regression asymmetry test in all analyses.RESULTS A total of 268 patients from 14 cohort studies that reported severe AKI-KRT after LVAD were included.Follow-up time ranged anywhere from two weeks of LVAD implantation to 12 mo.Kidney recovery occurred in 78%of enrollees at the time of hospital discharge or within 30 d.Overall,the pooled estimated AKI recovery rate among patients with seve
文摘BACKGROUND Hepatorenal syndrome(HRS)is a life-threatening condition among patients with advanced liver disease.Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited.AIM To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States.METHODS We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014(weighted sample of 23973 admissions).The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality.We estimated odds ratios from multilevel mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality.RESULTS Overall hospital mortality was 32%.Hospital mortality decreased from 44%in 2005 to 24%in 2014(P<0.001),while there was an increase in the rate of liver transplantation(P=0.02),renal replacement therapy(P<0.001),length of hospital stay(P<0.001),and hospitalization cost(P<0.001).On multivariable analysis,older age,alcohol use,coagulopathy,neurological disorder,and need for mechanical ventilation predicted higher hospital mortality,whereas liver transplantation,transjugular intrahepatic portosystemic shunt,and abdominal paracentesis were associated with lower hospital mortality.CONCLUSION Although there was an increase in resource utilizations,hospital mortality among patients admitted for HRS significantly improved.Several predictors for hospital mortality were identified.
