A multifunctional ionic liquid coating on 3D-Printed prostheses: Combating infection, promoting osseointegration.

Periprosthetic infection and mechanical loosening are two leading causes of implant failure in orthopedic surgery that have devastating consequences for patients both physically and financially. Hence, advanced prostheses to simultaneously prevent periprosthetic infection and promote osseointegration are highly desired to achieve long-term success in orthopedics. In this study, we proposed a multifunctional three-dimensional printed porous titanium alloy prosthesis coated with imidazolium ionic liquid. The imidazolium ionic liquid coating exhibited excellent bacterial recruitment property and near-infrared (NIR) triggered photothermal bactericidal activity, enabling the prosthesis to effectively trap bacteria in its vicinity and kill them remotely via tissue-penetrating NIR irradiation. In vivo anti-infection and osseointegration investigations in infected animal models confirmed that our antibacterial prosthesis could provide long-term and sustainable prevention against periprosthetic infection, while promoting osseointegration simultaneously. It is expected to accelerate the development of next-generation prostheses and improve patient outcomes after prosthesis implantation.

A Contemporary Review of the Use of Extracorporeal CytoSorb® Hemoadsorption Therapy in Patients with Infective Endocarditis.

Infective endocarditis (IE) is a rare but severe disease with high morbidity and mortality. Cardiac surgery plays a major role in the contemporary clinical management of IE patients. During cardiac surgery, cardiopulmonary bypass significantly contributes to an increased risk of organ dysfunction and mortality by inducing an acute inflammatory response, vascular endothelial cell injury, impairment of the coagulation cascade, and ischemia-reperfusion injury. During the past decade, the use of extracorporeal hemoadsorption therapy with the CytoSorb® hemoadsorber (CytoSorbents Europe GmbH, Berlin, Germany) has been proposed as an adjuvant therapy to mediate inflammatory responses in IE patients undergoing cardiac surgery with cardiopulmonary bypass. However, there is currently no systematic evaluation of the effect of CytoSorb® hemoadsorption on clinical outcomes such as hemodynamics, organ dysfunction, and mortality in patients with IE. Therefore, in this review, we exclusively discuss contemporary findings concerning the rationale, clinical evidence, and future perspectives for CytoSorb® hemoadsorption therapy in IE patients.

Atorvastatin reduces contrast media-induced pyroptosis of renal tubular epithelial cells by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure. However, there is no effective treatment of CI-AKI, and its mechanism is unknown. Interestingly, atorvastatin has been reported to be effective in renal injury. Therefore, the aim of this study was to explore the effect and possible molecular mechanism of atorvastatin in CI-AKI. METHODS: On the CI-AKI in vitro model, rat tubular epithelial cells (NRK-52E) were treated with 18 mg I/ml meglumine diatrizoate (MEG) and then pretreated with atorvastatin. pcDNA3.1-TLR4 treatment was performed to overexpress toll-like receptor 4 (TLR4) in NRK-52E cells. Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) kits were used to detect NRK-52E cell viability as well as LDH release in each group, respectively; qRT-PCR to determine mRNA expression of TLR4 in cells; western blot to detect protein expression levels of pyroptosis-related proteins (NLRP3, caspase-1, ASC, and GSDMD) and TLR4/MyD88/NF-κB signaling pathway-related proteins (TLR4, MyD88, NF-κBp65, and p-NF-κB p65) in cells. RESULTS: MEG treatment significantly inhibited the viability of NRK-52E cells, increased pro-inflammatory factor levels and promoted pyroptosis, representing successful establishment of a rat tubular epithelial cell (NRK-52E) CI-AKI in vitro model. Notably, atorvastatin increased the activity of MEG-treated NRK-52E cells and alleviated cell injury in a concentration-dependent manner. In addition, atorvastatin significantly down-regulated the expression of TLR4 in MEG-treated NRK-52E cells. However, overexpression of TLR4 inhibited the effects of atorvastatin on increasing cell viability, alleviating cell injury, reducing pro-inflammatory factors (IL-1ß, IL-6, and TNF-α) levels, and inhibiting apoptosis (by down-regulating the expression of NLRP3, caspase-1, ASC, and GSDMD). Furthermore, atorvastatin also inhibited the expression of TLR4/MyD88/NF-κB pathway-related proteins (TLR4, MyD88, and p-NF-κB p65). CONCLUSION: Atorvastatin can attenuate CI-AKI through increasing the activity of MEG-treated renal tubular epithelial cells, relieving cell injury, as well as inhibiting pyroptosis and inflammation. More importantly, the mechanism was achieved by inhibiting the TLR4//MyD88/NF-κB signaling pathway.

Exosomal STAT1 derived from high phosphorus­stimulated vascular endothelial cells induces vascular smooth muscle cell calcification via the Wnt/ß­catenin signaling pathway.

Vascular calcification is commonly observed in chronic kidney disease. The mechanism of how the calcification signal from endothelial cells is transmitted to vascular smooth muscle cells (VSMCs) remains unknown. The aim of the present study was to investigate whether exosomes from HUVECs (HUVEC­Exos) could regulate VSMC calcification and its potential signaling pathway. HUVEC­Exos were isolated from HUVECs under no phosphorus (NP) and high phosphorus (HP) conditions. Alizarin Red S staining and calcium (Ca) content analysis were carried out to detect calcification in VSMCs. Proteomics analysis was carried out to detect the differential expression of exosomal proteins. Protein and mRNA levels were measured by western blot analysis and reverse transcription­quantitative PCR (RT­qPCR). Exosomes derived from HP­HUVECs promoted the calcification of VSMCs, as assessed by Alizarin Red S staining, alkaline phosphatase activity assays, Ca content measurements and the increased expression of runt­related transcription factor 2 and osteopontin. Proteomic analysis detected the upregulation of STAT1 in HP­exosomes from HUVECs (HUVEC­Exos) compared with NP­HUVEC­Exos, which was also confirmed by western blot analysis and RT­qPCR. Inhibition of STAT1 expression in VSMCs using fludarabine or knockdown of STAT1 expression using small interfering RNA alleviated the calcification of VSMCs. Furthermore, lithium chloride (Wnt activator) reversed the protective effect of STAT1 inhibition on VSMC calcification, while Dickkopf­1 (Wnt inhibitor) exerted the opposite effect, suggesting that activation of the Wnt/ß­catenin signaling pathway was involved in STAT1­mediated VSMC calcification. In conclusion, the present results indicated that exosomal STAT1 derived from HP­treated HUVECs could promote VSMC calcification, and activation of the Wnt/ß­catenin pathway may be a potential mechanism of the VSMC calcification promoted by exosomes.

Higher Blood Cadmium Concentration Is Associated With Increased Likelihood of Abdominal Aortic Calcification.

Aims: This study aimed to evaluate the association between blood cadmium concentration (BCC) and abdominal aortic calcification (AAC) in adults aged ≥40 years in the United States. Methods: Data were obtained from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). Participants without data about BCC and AAC scores were excluded. BCC was directly measured using inductively coupled plasma mass spectrometry (ICP-MS). AAC scores were quantified by the Kauppila scoring system, and severe AAC was defined as an AAC score >6. Weighted multivariable regression analysis and subgroup analysis were conducted to explore the independent relationship between cadmium exposure with AAC scores and severe AAC. Results: A total of 1,530 participants were included with an average BCC of 0.47 ± 0.02 µg/L and AAC score of 1.40 ± 0.10 [mean ± standard error (SE)]. The prevalence of severe AAC was 7.96% in the whole subjects and increased with the higher BCC tertiles (Tertile 1: 4.74%, Tertile 2: 9.83%, and Tertile 3: 10.17%; p = 0.0395). We observed a significant positive association between BCC and the AAC score (ß = 0.16, 95% CI: 0.01~0.30) and an increased risk of severe AAC [odds ratio (OR) = 1.45; 95% CI: 1.03~2.04]. Subgroup analysis and interaction tests revealed that there was no dependence for the association between BCC and AAC. Conclusion: Blood cadmium concentration was associated with a higher AAC score and an increased likelihood of severe AAC in adults in the United States. Cadmium exposure is a risk factor for AAC, and attention should be given to the management of blood cadmium.

Mussel-Inspired and In Situ Polymerization-Modified Commercial Sponge for Efficient Crude Oil and Organic Solvent Adsorption.

Oil spills and pollution of oily wastewater from the industrial field have not only caused serious economic losses but also imposed a huge threat to human beings. To solve these issues, the development of advanced materials and technologies for the purification of oily wastewater has garnered great concern and become a central topic. Hence, a superhydrophobic polyurethane (PU) sponge adsorbent is designed via mussel-inspired coatings by double bonds to PU sponge, followed by in situ polymerization with 1-hexadecene. The prepared PU sponge adsorbent (PU@DB@16ene sponge) showed outstanding mechanical properties including low density, high porosity, and compression recovery ability. Moreover, the prepared PU@DB@16ene sponge showed excellent adsorption of oils and organic solvents (up to 187 g g-1) and exhibited superior recyclability. Particularly, when the PU@DB@16ene sponge was applied in the continuous and rapid separation of oils and organic solvents, it still showed desired properties at a rapid velocity of 8.3 L m-3 s-1. Additionally, the PU@DB@16ene sponge could not only adsorb organic solvents in laboratories but also adsorb crude oil and industrial waxy oil in practice. Therefore, we proposed a simple and convenient method to construct PU sponge absorbents with great application prospects, which would be highly valuable for crude oil and organic solvents cleanup.

Higher visceral adiposity index is associated with increased likelihood of abdominal aortic calcification

Abstract Background: The negative effects of visceral adiposity accumulation on cardiovascular health have drawn much attention. However, the association between the Visceral Adiposity Index (VAI) and Abdominal Aortic Calcification (AAC) has never been reported before. The authors aimed to investigate the association between the VAI and AAC in US adults. Methods: Cross-sectional data were derived from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) of participants with complete data of VAI and AAC scores. Weighted multivariable regression and logistic regression analysis were conducted to explore the independent relationship between VAI and AAC. Subgroup analysis and interaction tests were also performed. Results: A total of 2958 participants were enrolled and participants in the higher VAI tertile tended to have a higher mean AAC score and prevalence of severe AAC. In the fully adjusted model, a positive association between VAI and AAC score and severe AAC was observed (β = 0.04, 95% CI 0.01‒0.08; OR = 1.04, 95% CI 1.01‒1.07). Participants in the highest VAI tertile had a 0.41-unit higher AAC score (β = 0.41, 95% CI 0.08‒0.73) and a significantly 68% higher risk of severe AAC than those in the lowest VAI tertile (OR = 1.68, 95% CI 1.04‒2.71). Subgroup analysis and interaction tests indicated that there was no dependence for the association of VAI and AAC. Conclusion: Visceral adiposity accumulation evaluated by the VAI was associated with a higher AAC score and an increased likelihood of severe AAC.

Low lean mass and cognitive performance: data from the National Health and Nutrition Examination Surveys.

BACKGROUND: Low lean mass and cognitive impairment are both age-related diseases. In addition, these conditions share many risk factors. However, the association between them has been controversial in recent years. OBJECTIVE: To investigate the association between low lean mass and cognitive performance in U.S. adults using NHANES data from 1999 to 2002. METHODS: A total of 2550 participants were identified in the National Health and Nutrition Examination Survey Database (1999-2002). The independent variable was low lean mass, and the dependent variable was cognitive performance. Men and women were classified as having low lean mass if appendicular lean mass (ALM) adjusted for BMI (ALMBMI) was < 0.789 and < 0.512, respectively. Cognitive performance was assessed using the Digit Symbol Substitution Test (DSST). Higher scores on the DSST indicated better cognitive performance. The covariates included sex, age, race, poverty income ratio, comorbidity index, educational level, physical activity and smoking status. RESULTS: For the primary outcome, our multivariate linear regression analysis indicated that participants without low lean mass were associated with better cognitive performance (ß = 1.50; 95% CI [0.12-2.89]). Subgroup analysis results indicated that the association was similar in sex, age, race, poverty income ratio, comorbidity index, educational level, physical activity and smoking status. CONCLUSIONS: Participants without low lean mass were associated with better cognitive performance. We might be able to improve cognitive performance by treating low lean mass, thus providing an opportunity for intervention at a younger age.

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04-2.60; score 2: HR 2.48, 95% CI 1.40-4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55-4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

Biomarkers upon discontinuation of renal replacement therapy predict 60-day survival and renal recovery in critically ill patients with acute kidney injury.

INTRODUCTION: There is no consensus on the specific indications for weaning critically ill patients with acute kidney injury (AKI) off renal replacement therapy (RRT). This study aimed to explore the prognostic value of several biomarkers measured upon discontinuation of RRT for their value in predicting 60-day survival and renal recovery in an effort to add knowledge to the decision-making process regarding RRT withdrawal. METHODS: We prospectively enrolled 102 patients with AKI who required RRT from the intensive care unit. Serum osteopontin (sOPN), serum interleukin 6 (sIL-6), serum cystatin C (sCysC), sIL-18, serum neutrophil gelatinase-associated lipocalin and urinary IL-18 and urinary neutrophil gelatinase-associated lipocalin were measured upon discontinuation of RRT. Patients were followed up at 60 days for survival and renal recovery. FINDINGS: Patients who survived showed lower levels of all serum and urinary biomarkers. Serum OPN (OR 1.029, 95% CI 1.013-1.047, P = 0.001), diabetes (OR 23.157, 95% CI 4.507-118.981, P < 0.001) and APACHE II score (OR 1.308, 95% CI 1.121-1.527, P = 0.001) were independent predictors of 60-day mortality. Patients whose sOPN values fell within the highest and middle tertiles showed 5.25- and 2.31-fold increased risks of mortality, respectively, compared with that of patients in the lowest tertile. The addition of sOPN to the clinical model resulted in significant net reclassification improvement of 0.453 (P = 0.026) and an integrated discriminative index of 0.155 (P = 0.032). Lower levels of sOPN and sIL-6 were associated with greater odds of 60-day survival (AUC 0.812 and 0.741). The AUC value for predicting survival reached its highest level when all biomarkers were combined with urine output (UO) and urinary and serum creatinine upon discontinuation of RRT (0.882). Lower sCysC performed as well as higher UO in predicting 60-day renal recovery with the greatest AUC of 0.743. DISCUSSION: Upon discontinuation of RRT, serum and urinary biomarkers, particularly sOPN, may predict 60-day survival and renal recovery in critically ill patients with AKI. The serum levels of OPN, IL-6 and CysC may be useful when considering withdrawal of RRT on the basis of conventional indicators.

Predictive Factors Upon Discontinuation of Renal Replacement Therapy for Long-Term Chronic Dialysis and Death in Acute Kidney Injury Patients.

The specific timing for discontinuing renal replacement therapy (RRT) in acute kidney injury (AKI) patients is debatable. The predictive abilities of variables at the time of discontinuation of RRT for the long-term prognoses of patients have not been explored. This study aimed to explore the prognostic factors upon discontinuation of RRT for long-term chronic dialysis and death of patients with acute RRT-requiring AKI, thus improving decision making regarding the discontinuation of RRT and the follow-up of patients thereafter. A cohort of 302 AKI patients who required acute RRT and remained alive and free of dialysis for at least 30 days after discharge from January 2009 to December 2012 were followed up. The predictive abilities of general characteristics, RRT details, and variables upon discontinuation of RRT for long-term chronic dialysis and all-cause death were evaluated using Cox proportional hazards models. Kaplan-Meier analysis with a log-rank test was used to compare the survival curves between the strata of levels of good predictors upon discontinuation of RRT. After a median follow-up time of 4.1 years, 20 (6.6%) patients initiated chronic dialysis and 56 (18.5%) patients died. A higher CysC level upon discontinuation of RRT (HR 1.520, 95% CI 1.082-2.135; P = 0.016), comorbid chronic kidney disease, and a higher non-renal Charlson comorbidity index (CCI) were independently predictive for chronic dialysis. The hemoglobin level upon discontinuation of RRT was inversely predictive of death (HR 0.986, 95% CI 0.973-0.999; P = 0.035), and comorbid malignancy, the presence of multiple organ dysfunction syndrome, and a higher non-renal CCI also predicted death. Urine output upon discontinuation of RRT was marginally inversely predictive of death (HR 0.997, 95% CI 0.994-1.000; P = 0.056). Patients who discontinued RRT with CysC levels <2.97 mg/L, hemoglobin levels >85 g/L, and urine output >1130 mL/24 h showed significantly higher non-chronic dialysis and survival rates according to a log-rank test. Our study suggested that upon discontinuation of RRT, higher serum CysC levels had the most promising predictive value for long-term chronic dialysis, and lower hemoglobin levels predicted long-term death; lower urine output also marginally predicted long-term death. Based on the remission of the comprehensive condition, lower CysC levels and higher hemoglobin levels and urine output should be considered in the decision to stop RRT. Patients showing worse levels of these indices upon discontinuation of RRT should undergo stricter follow-up and treatment to improve long-term outcomes.

Renal pathological implications in type 2 diabetes mellitus patients with renal involvement.

AIMS: To investigate the renal pathological implications in type 2 diabetes mellitus patients with renal involvement. METHODS: A total of 328 type 2 diabetes mellitus (T2DM) patients with renal involvement who underwent a renal biopsy and received follow-up for at least one year were recruited in our study. The patients were divided into the diabetic nephropathy (DN), non-diabetic renal disease (NDRD), and NDRD superimposed on DN groups based on the pathological diagnosis. Renal outcomes were defined by the initiation of renal replacement therapy or doubling of the serum creatinine. Kaplan-Meier analysis was used to compare renal survival, and Cox proportional hazard analysis was used to determine the predictors of renal outcomes in the DN group. RESULTS: Renal biopsy findings revealed that 188 patients (57.32%) had pure DN, 121 patients (36.89%) had NDRD alone, and 19 patients (5.79%) had NDRD superimposed on DN. The most frequent subclassification of NDRD was membranous nephropathy (MN). Compared with the NDRD and NDRD superimposed on DN groups, patients with pure DN had poorer renal function and lower renal survival rates. In the DN group, the five-year renal survival rates of glomerular classes of I, IIa, IIb, III and IV were 100%, 84.62%, 60%, 47.5% and 33.33%, respectively. Multivariate Cox proportional hazard analysis showed that the glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes, while interstitial fibrosis/inflammation and arteriolar hyalinosis were not independently associated with renal outcomes in the DN group. CONCLUSIONS: Making an accurate pathologic diagnosis by renal biopsy is crucial for diabetes mellitus (DM) patients with renal involvement. The findings of our present study indicated that patients with pure DN had poorer renal outcomes than patients with NDRD or NDRD superimposed on DN. The classification of glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes in the DN group. More studies with large samples and longer time follow-up are needed to evaluate the relationship between pathological changes and clinical characteristics in T2DM patients who have renal involvement.

Layer by layer assembly of sulfonic poly(ether sulfone) as heparin-mimicking coatings: scalable fabrication of super-hemocompatible and antibacterial membranes.

In this study, to approach the scalable fabrication of super-hemocompatible and antibacterial membranes, surface engineered 3D heparin-mimicking coatings were designed by layer by layer (LBL) assembly of water-soluble heparin-mimicking polymer (WHP) and quaternized chitosan (QC). The low cost and scalable WHP was synthesized by a combination of polycondensation and post-carboxylation method, and the antibacterial QC was prepared by a two-step quaternization reaction. Then, the as-prepared negatively charged WHP and positively charged QC were used to conduct the LBL assembly on the widely used poly(ether sulfone) (PES) membrane surface to prepare heparin-mimicking modified membrane. The results indicated that the assembled heparin-mimicking coating nanofilms exhibited 3D porous morphology. The systematic blood compatibility and antithrombotic evaluation revealed that the functionalized membrane owned prolonged clotting times and greatly suppressed platelet adhesion and activation; further contacting activation detection (TAT and PF-4) and complement activation (C3a and C5a) experiments indicated that the heparin-mimicking membranes had lower blood activation compared to the pristine membrane. The cell observations demonstrated that the surface assembled heparin-mimicking nanofilms showed superior performances in endothelial cells adhesion and growth than the pure PES membrane. The results of the antibacterial study indicated that the QC contained coating exhibited significant inhibition ability for both Escherichia coli and Staphlococcus aureus. In general, the LBL assembled heparin-mimicking coatings conferred the functionalized PES membranes with integrated blood compatibility, cytocompatibility and antibacterial property for multi-applications, which may forward the fabrication and application of heparin-mimicking biomedical devices.

Involvement of inflammation-related miR-155 and miR-146a in diabetic nephropathy: implications for glomerular endothelial injury.

BACKGROUND: MicroRNAs have been demonstrated to play an important role in the pathogenesis of diabetic nephropathy (DN). In this study, we investigated both the repertoire of miRNAs in the kidneys of patients with DN and their potential regulatory role in inflammation-mediated glomerular endothelial injury. METHODS: The miRNA expression profiling of the renal biopsy samples was performed by a microarray analysis; then, in situ hybridization and real-time polymerase chain reaction (PCR) were used to determine the localization and expression of two of the miRNAs significantly up-regulated in human DN kidney samples, miR-155 and miR-146a, in the kidney tissues from type 1 and type 2 DN rat models. Human renal glomerular endothelial cells (HRGECs) cultured under high-glucose conditions were transfected with miR-155 and miR-146a mimics, and the transforming growth factor (TGF)-ß1, tumor necrosis factor (TNF)-α, and nuclear factor (NF)-κB expressions were examined by western blot, real-time PCR, and an electrophoresis mobility shift assay. RESULTS: The expression of both miR-155 and miR-146a was increased more than fivefold in the kidney samples of the DN patients compared with the controls, and the miR-155 expression was closely correlated with the serum creatinine levels (R = 0.95, P = 0.004). During the induction and progression of the disease in type 1 and type 2 DN rat models, miR-155 and miR-146a were demonstrated to increase gradually. In vitro, high glucose induced the over-expression of miR-155 and miR-146a in the HRGECs, which, in turn, increased the TNF-α, TGF-ß1, and NF-κB expression. CONCLUSIONS: Taken together, these findings indicate that the increased expression of miR-155 and miR-146a in the DN patients and in the experimental DN animal models was found to contribute to inflammation-mediated glomerular endothelial injury.

[Contrast-enhanced ultrasound parameters for early chronic kidney diseases and their associations with laboratory results].

OBJECTIVE: To determine the value of contrast-enhanced ultrasound (CEUS) for assessing renal blood perfusion changes and severity of early chronic kidney diseases (CKD). METHODS: The study included 20 patients with clinical diagnosed CKD (grade 1-3) (case group) and fifteen normal adults (control group). They were given real time CEUS, assessing left renal cortex blood perfusion. We identified the time-intensity curve (TIC) parameters that could differentiate participants between the two groups, and tested their correlations with glomerular filtration rate (eGFR), quantity of urinary protein and cystatin C. RESULTS: Significant differences were found in rise time (RT), area under the curve (AUC), time from peak to one half, and time to peak (TTP) between the two groups (P< 0.05). eGFR was negatively correlated with all of the four TIC parameters (P<0. 05). The quantity of urinary protein was positively correlated with three of the four TIC parameters (except RT). Cystatin C was positively correlated with all of the four TIC parameters (P<0. 05). CONCLUSION: CEUS can detect changes of blood flow perfusion in patients with early chronic kidney disease. The perfusion parameters are associated with laboratory results reflecting renal damages.

Systemic sclerosis with thrombotic thrombocytopenia purpura and malignant hypertension.

Thrombotic thrombocytopenia purpura (TTP) is a rare clinical syndrome characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia, neurologic symptoms, acute renal impairment, and fever. It has been seldom reported in systemic sclerosis (SSc). Systemic renal crisis is an infrequent complication of SSc, and is characterized by new onset malignant hypertension, rapidly progressive oliguric renal failure, and MAHA. In this study, we present a case of SSc of 1 month duration, with TTP accompanied by new onset malignant hypertension. The patient responded to plasmapheresis but still died of septic shock.

Myoglobin clearance by continuous venous-venous haemofiltration in rhabdomyolysis with acute kidney injury: a case series.

BACKGROUND: Clearance of circulating myoglobin is a critical measure to prevent further damage in patients with rhabdomyolysis (RM) and acute kidney injury (AKI). Continuous venous-venous haemofiltration has emerged to be a novel approach for this purpose. The objective of present study is to evaluate the efficacy and safety of CVVH in myoglobin clearance for patients with RM complicated with AKI. METHOD: We prospectively analysed 15 patients with acute RM and AKI due to crush syndrome (n=7), bee stings (n=5), polymyositis (n=2) and heroin poisoning (n=1). All of them presented oliguria with high serum myoglobin and creatine kinase concentration. They were treated by CVVH for at least 48h until the conditions turned to be stable, then replaced by intermittent renal replacement therapy (intermittent haemofiltration or haemodialysis). Meanwhile intravascular volume expansion, urinary alkalinisation, and forced diuresis were administered. During the procedure, serum and effluent concentrations of myoglobin and creatinine were measured simultaneously at 2, 6, 12 and 24h. RESULT: The mean sieving coefficients for myoglobin were 0.28±0.06, 0.21±0.06, 0.15±0.02 and 0.11±0.02 during 2, 6, 12 and 24h of CVVH intervention, whilst mean clearance of myoglobin was 14.3±3.1ml/min during 2h and reduced to 11.5±3.2, 7.5±0.9, 5.6±1.0ml/min during 6, 12 and 24h. In contrast to myoglobin, the sieving coefficient for creatinine remained stable at 0.95±0.25, 1.02±0.12, 0.89±0.32, 0.98±0.27 during 24h of CVVH. In all of the 15 patients, serum myoglobin and creatine kinase were dramatically decreased in 24h (-56.2 and -32.1%), 3 days (-72.9 and -50.3%) and in 7 days (-97.6 and -96.7%). Seven patients (46.7%) complicated with hypophosphatemia during CVVH intervention improved in natural course after the cessation of CVVH. After 16±12 days, all of 15 patients came to polyuria stage and finally, discharged with normal renal function after 31±15 days. CONCLUSION: Our study showed CVVH can be employed to clear myoglobin effectively in patients with RM and AKI and presented oliguria. This indicate that CVVH would be better than other modes of renal replement treatment in acute RM with AKI because of the additional benefit of myoglobin removal, but large sample randomised controlled trials are still required to confirm it.

Evaluation of polyethersulfone highflux hemodialysis membrane in vitro and in vivo.

A new hemodialysis membrane manufactured by a blend of polyethersulfone (PES) and polyvinylpyrrolidone (PVP) was evaluated in vitro and in vivo. Goat was selected as the experimental animal. The clearance and the reduction ratio after the hemodialysis of small molecules (urea, creatinine, phosphate) for the PES membrane were higher in vitro than that in vivo. The reduction ratio of beta(2)-microglobulin was about 50% after the treatment for 4 h. The biocompatibility profiles of the membranes indicated slight neutropenia and platelet adhesion at the initial stage of the hemodialysis. Electrolyte, blood gas, and blood biochemistry were also analyzed before and after the treatment. The results indicated that PES hollow fiber membrane had a potential widely use for hemodialysis.

[Effects of interferon-gamma on tubular epithelial-myofibroblast transdifferentiation in vitro].

OBJECTIVE: To investigate the effects of interferon-gamma (IFN-gamma) on tubular epithelial-myofibroblast transdifferentiation (TEMT) induced by transforming growth factor (TGF-beta1). METHODS: The normal rat kidney tubular epithelial cells (NRK52E) were cultured and divided into blank (NRK52E cells only) control group, TGF-beta1 (3 ng/mL) treated group, IFN-gamma (1000 IU/mL) treated group, and IFN-gamma inhibition group (TGF-beta1 3 ng/mL + IFN-gamma 200, 400, 600, 1000, 2000, 3000 IU/mL). After 72 hours of treatment, the morphology of cells was observed under phase-contrast microscopy and scanning electron microscopy. The expressions of a-smooth muscle actin (alpha-SMA) and connective tissue growth factor (CTGF) were detected by immunocytochemistry. Flowcytometry was employed to measure the percentage of alpha-SMA+ cells and the mean channel fluorescence (MCF). The expressions of alpha-SMA mRNA and CTGF mRNA were examined by reverse transcription-polymerase chain reaction analyses (RT-PCR). The level of collagen in the culture supernatant was measured by Enzyme-linked immunoadsordent assay (ELISA). RESULTS: NRK52E cells cultured in the control group showed a classic cobblestone morphology. TGF-beta1 induced NRK52E cells to transdifferentiate into myofibroblast-like cells, which showed strong alpha-SMA immunostaining. The TGF-beta1 treated cells had higher percentage of a-SMA+ cells, MCF and alpha-SMA mRNA, increased CTGF mRNA expression, and ascended collagen III than the blank controls (P<0.05). IFN-gamma treated alone did not make any changes to the cell morphology, the expressions of alpha-SMA mRNA and CTGF mRNA and the level of collagen III (P>0.05). IFN-gamma exerted a strong inhibitory effect on the TEMT induced by TGF-beta1. With the increase of IFN-gamma, the percentage of alpha-SMA+ cells, the level of collagen III, and the expressions of alpha-SMA mRNA and CTGF mRNA decreased (P<0.05). CONCLUSION: IFN-gamma inhibits the TEMT induced by TGF-beta1 and reduces the level of collagen III.

[Effects of hepatocyte growth factor on IL-1alpha triggered tubular epithelial-myofibroblast transdifferentiation and fibronectin secretion in vitro].

OBJECTIVE: To observe the effects of hepatocyte growth factor (HGF) on tubular epithelial-myofibroblast transdifferentiation (TEMT) triggered by IL-1alpha and the fibronectin secretion of TEMT. METHODS: The normal rat kidney tubular epithelial cell line (NRK52E) was cultured for six days on plastic or collagen type I-coated plates in the presence or absence of HGF or IL-1alpha. The morphology of transdifferentiation tubular cells was observed by scanning electron microscopy (SEM) and phase-contrast microscopy. The number of alpha-SMA+ cells, the percentage of alpha-SMA+ cells and the mean channel fluorescence (MCF) were assessed by immunohistochemistry and flowcytometry. The level of fibronectin in supernatant was measured by ELISA. RESULTS: The NRK52E cells triggered by IL-1alpha became fibroblast-like morphologically, and strong alpha-SMA immunostaining of those cells was seen. The level of FN in the culture supernatant, the percentage of alpha-SMA+ cells and the MCF of cells triggered by IL-1alpha were obviously higher than those of blank control group (P<0.05). In the groups with IL-1alpha and different doses of HGF, the transdifferentiation of NRK52E cells was inhibited. With the increase of HGF dose, the percentage of alpha-SMA+ cells and the level of FN showed a tendency to decrease. There was no significant difference between the groups treated with only HGF at different dose levels and the blank control group (P>0.05). CONCLUSION: IL-1alpha can induce tubular epithelial cell to transdifferentiate to myofibroblast and increase the secretion of FN. These results suggest that TEMT may play an important role in the pathogenesis of renal fibrosis. HGF could block the transdifferentiation of tubular epithelial cell and inhibit the secretion of FN. These would provide a novel therapeutic strategy for the treatment of renal interstitial fibrosis and end stage renal disease.