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Abstract The combination of micron zero-valent iron (mZVI) and microorganisms is an effective method for trichloroethylene (TCE) degradation, but electron transfer efficiency needs improvement. A new chem-bio hybrid process using a composite material (S-ZVI@biochar) was developed, consisting of sulfurized mZVI and biochar as a chemical remover, and Shewanella oneidensis MR-1 and dechlorinating bacteria (DB) as a biological agent for TCE degradation. S-ZVI@biochar showed improved stability, biocompatibility, and TCE removal compared to ZVI and S-ZVI. The hybrid system DB + MR-1 + S-ZVI@biochar exhibited the highest TCE removal efficiency at 96.5% after 30 days, which was 3.7 times higher than that of bare ZVI. The study revealed that the enhanced dechlorination performance was due to improved electron transfer efficiency, adjustment of microbial community structure, and iron recycling. S-ZVI@biochar constructed electron transport channels in the composite system, improving the overall dechlorination capacity. This system shows promise for long-term TCE removal in anaerobic environments.

Abstract Static magnetic field (SMF) promoting bone tissue remodeling is a potential non-invasive therapy technique to accelerate orthodontic tooth movement (OTM). The periodontal ligament stem cells (PDLSCs), which are mechanosensitive cells, are essential for force-induced bone remodeling and OTM. However, whether and how the PDLSCs influence the process of inflammatory bone remodeling under mechanical force stimuli in the presence of SMFs remains unclear. In this study, we found that local SMF stimulation significantly enhanced the OTM distance and induced osteoclastogenesis on the compression side of a rat model of OTM. Further experiments with macrophages cultured with supernatants from force-loaded PDLSCs exposed to an SMF showed enhanced osteoclast formation. RNA-seq analysis showed that interleukin-6 (IL-6) was elevated in force-loaded PDLSCs exposed to SMFs. IL-6 expression was also elevated on the pressure side of a rat OTM model with an SMF. The OTM distance induced by an SMF was significantly decreased after injection of the IL-6 inhibitor tocilizumab. These results imply that SMF promotes osteoclastogenesis by inducing force-loaded PDLSCs to secrete the inflammatory cytokine IL-6, which accelerates OTM. This will help to reveal the mechanism of SMF accelerates tooth movement and should be evaluated for application in periodontitis patients.

Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient’s urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.

Abstract Background Alzheimer’s disease (AD) is a common cause of dementia. Serum complement factor 5a (C5a) is exceedingly implicated in AD. We explored the role of C5a levels in AD patients of different severity. Methods Mild, moderate, and severe AD patients, and healthy controls were included. C5a and pro-inflammatory factor (TNF-α, IL-1β, IL-6, CRP) levels were assessed by ELISA, and cognitive function was evaluated by Mini-Mental state examination (MMSE) score. The correlations between C5a, inflammatory factor levels, MMSE score, and plasma Aβ42/Aβ40 ratio were analyzed by Pearson tests. Independent risk factors for AD aggravation were assessed by logistic multivariate regression analysis. According to the cut-off value of receiver operating characteristic (ROC) curve analysis of C5a level, AD patients were assigned into low/high expression groups, and severe AD incidence was compared. Severe AD cumulative incidence was analyzed by Kaplan-Meier curve. Results Serum C5a, TNF-α, IL-1β, IL-6 and CRP levels were raised, and MMSE score was lowered in AD. Serum C5a, TNF-α, IL-1β, IL-6 and CRP levels in severe AD patients were higher than those in mild/moderate AD patients, but there were no significant differences in these cytokines between moderate and mild AD groups. The MMSE score of severe AD patients was lower than that of mild/moderate AD patients. Serum C5a level was positively correlated with serum TNF-α, IL-1β, IL-6, and CRP levels, and negatively correlated with MMSE score, with no obvious correlation with plasma Aβ42/Aβ40 ratio. Serum C5a level was one of the independent risk factors for AD aggravation. The occurrence of severe AD might be related to an increase in serum C5a level. Conclusion Serum C5a level increased with AD severity, and its expression was positively correlated with serum pro-inflammatory factor levels, and negatively correlated with cognitive function.

Abstract Objective To evaluate the value of the ACEF II score in predicting postoperative hospital death and acute kidney injury requiring dialysis (AKI-D) in Chinese patients. Methods This retrospective study included adult patients who underwent cardiopulmonary bypass open heart surgery between January 2010 and December 2015 at Guangdong Provincial People’s Hospital. ACEF II was evaluated to predict in-hospital death and AKI-D using the Hosmer–Lemeshow goodness of fit test for calibration and area under the receiver operating characteristic (ROC) curve for discrimination in non-elective and elective cardiac surgery. Results A total of 9748 patients were included. Among them, 1080 underwent non-elective surgery, and 8615 underwent elective surgery. Mortality was 1.8% (177/9748). In elective surgery, the area under the ROC (AUC) of the ACEF II score was 0.704 (95% CI: 0.648–0.759), similar to the ACEF score of 0.709 (95% CI: 0.654–0.763). In non-elective surgery, the AUC of the ACEF II score was 0.725 (95% CI: 0.663–0.787), higher than the ACEF score (AUC = 0.625, 95% CI: 0.553–0.697). The incidence of AKI-D was 3.5% (345/9748). The AUC of the ACEF II score was 0.718 (95% CI: 0.687–0.749), higher than the ACEF score (AUC = 0.626, 95% CI: 0.594–0.658). Conclusion ACEF and ACEF II have poor discrimination ability in predicting AKI-D in non-elective surgery. The ACEF II and ACEF scores have the same ability to predict in-hospital death in elective cardiac surgery, and the ACEF II score is better in non-elective surgery. The ACEF II score can be used to assess the risk of AKI-D in elective surgery in Chinese adults.

Geologic interpretation results from conventional ground-penetrating radar (GPR) detection methods tend to have a certain degree of uncertainty. In order to improve the reliability of ground-penetrating radars in the detection of rock mass fissures in grottoes, this study proposes a ground-penetrating radar detection method with the logging data constraint, which is applied to detect the fractured rock mass in the Baodingshan Scenic Area of Dazu Rock Carvings, Chongqing, China. First, conventional logging and borehole televiewer data were compared and verified, yielding detailed lithological and wellbore fissure information. Next, electromagnetic wave velocity was calibrated using GPR profile and the depth of the stratigraphic interface determined by borehole data. Utilizing this calibrated velocity, we are able to accurately calculate the depth values of anomalies in GPR interpretation profiles. Subsequently, we compared the preliminary GPR interpretation profile with the borehole televiewer images. After eliminating false anomalies caused by interference, we obtained more reliable location information for detection targets such as fissures, fracture zones, and weak interlayers. The results of fissure detection in the Dazu Rock Carvings indicate that the detection results of ground-penetrating radar are verified and supplemented under the constraints of stratigraphic and well-wall fissure information obtained by logging. This effectively mitigates the influence of multiplicity and false anomalies of GPR detection on interpretation results. GPR with the logging data constraint enhances the accuracy of the fissure detection results, providing novel technical means for the protection and restoration of grotto relics.

Ground-penetrating radar (GPR) is an important tool for measuring soil water content (SWC) at the field scale. The amplitude analysis of the early time signal (ETS) of GPR may provide a rapid way to estimate SWC. By assuming a homogeneous medium, various studies have been conducted on the relationship between the amplitude of ETS and the topsoil layer’s electromagnetic parameters (dielectric permittivity and conductivity) through numerical simulations, laboratory experiments, and field experiments. Soil is a typical inhomogeneous medium, and soil cultivation is a factor affecting its heterogeneity. In this context, we discuss the ability of the amplitude of ETS to estimate the water content of heterogeneous soil. First, we establish a multi-scale stochastic medium model with the inhomogeneous distribution of dielectric permittivity and conductivity and simulate the GPR response by the finite-difference time-domain (FDTD) method to observe the influence of medium heterogeneity on the GPR response. The heterogeneity of the soil models is evaluated by a geostatistical analysis described by two parameters, correlation length and variability. Then, we analyze the relationship between variability and the average envelope amplitude (AEA) of ETS. A strong soil heterogeneity increases the error of the AEA method in estimating SWC. Finally, the AEA method is used to estimate the SWC of two adjacent fields with different heterogeneities, which were caused by different cultivation methods. The results of the numerical simulation and field experiment indicate that the soil heterogeneity can have an impact on the estimation of SWC using EST, with an error lower than 3% within a depth range of 1/2 λ to λ (wavelength). This suggests that the EST of GPR can be applied to soil layers with relatively large lateral changes in water content.

With continuous improvements in oil production, the environmental problems caused by oil exploitation are becoming increasingly serious. Rapid and accurate estimation of soil petroleum hydrocarbon content is of great significance to the investigation and restoration of environments in oil-producing areas. In this study, the content of petroleum hydrocarbon and the hyperspectral data of soil samples collected from an oil-producing area were measured. For the hyperspectral data, spectral transforms, including continuum removal (CR), first- and second-order differential (CR-FD, CR-SD), and Napierian logarithm (CR-LN), were applied to eliminate background noise. At present, there are some shortcomings in the method of feature band selection, such as large quantity, time of calculation, and unclear importance of each feature band obtained. Meanwhile, redundant bands easily exist in the feature set, which seriously affects the accuracy of the inversion algorithm. In order to solve the above problems, a new method (GARF) for hyperspectral characteristic band selection was proposed. It combined the advantage that the grouping search algorithm can effectively reduce the calculation time with the advantage that the point-by-point search algorithm can determine the importance of each band, which provided a clearer direction for further spectroscopic research. The 17 selected bands were used as the input data of partial least squares regression (PLSR) and K-nearest neighbor (KNN) algorithms to estimate soil petroleum hydrocarbon content, and the leave-one-out method was used for cross-validation. The root mean squared error (RMSE) and coefficient of determination (R2) of the estimation result were 3.52 and 0.90, which implemented a high accuracy with only 8.37% of the entire bands. The results showed that compared with the traditional characteristic band selection methods, GARF can effectively reduce the redundant bands and screen out the optimal characteristic bands in the hyperspectral data of soil petroleum hydrocarbon with the method of importance assessment, which retained the physical meaning. It provided a new idea for the research of other substances in soil.

Ground-penetrating radar (GPR) is an efficient and nondestructive geophysical method with great potential for detecting soil water content at the farmland scale. However, a key challenge in soil detection is obtaining soil water content rapidly and in real-time. In recent years, deep learning methods have become more widespread in the earth sciences, making it possible to use them for soil water content inversion from GPR data. In this paper, we propose a neural network framework GPRSW based on deep learning of GPR data. GPRSW is an end-to-end network that directly inverts volumetric soil water content (VSWC) through single-channel GPR data. Synthetic experiments show that GPRSW accurately identifies different VSWC boundaries in the model in time depth. The predicted VSWC and model fit well within 40 ns, with a maximum error after 40 ns of less than 0.10 cm3 × cm−3. To validate our method, we conducted GPR measurements at the experimental field of the Academy of Agricultural Sciences in Gongzhuling City, Jilin Province and applied GPRSW to VSWC measurements. The results show that predicted values of GPRSW match with field soil samples and are consistent with the overall trend of the TDR soil probe samples, with a maximum difference not exceeding 0.03 cm3 × cm−3. Therefore, our study shows that GPRSW has the potential to be applied to obtain soil water content from GPR data on farmland.

Abstract Autophagy is an important renal-protective mechanism in septic acute kidney injury (AKI). Receptor interacting protein kinase 3 (RIP3) has been implicated in the renal tubular injury and renal dysfunction during septic AKI. Here we investigated the role and mechanism of RIP3 on autophagy in septic AKI. We showed an activation of RIP3, accompanied by an accumulation of the autophagosome marker LC3II and the autophagic substrate p62, in the kidneys of lipopolysaccharide (LPS)-induced septic AKI mice and LPS-treated cultured renal proximal tubular epithelial cells (PTECs). The lysosome inhibitor did not further increase the levels of LCII or p62 in LPS-treated PTECs. Moreover, inhibition of RIP3 attenuated the aberrant accumulation of LC3II and p62 under LPS treatment in vivo and in vitro. By utilizing mCherry-GFP-LC3 autophagy reporter mice in vivo and PTECs overexpression mRFP-GFP-LC3 in vitro, we observed that inhibition of RIP3 restored the formation of autolysosomes and eliminated the accumulated autophagosomes under LPS treatment. These results indicated that RIP3 impaired autophagic degradation, contributing to the accumulation of autophagosomes. Mechanistically, the nuclear translocation of transcription factor EB (TFEB), a master regulator of the lysosome and autophagy pathway, was inhibited in LPS-induced mice and LPS-treated PTECs. Inhibition of RIP3 restored the nuclear translocation of TFEB in vivo and in vitro. Co-immunoprecipitation further showed an interaction of RIP3 and TFEB in LPS-treated PTECs. Also, the expression of LAMP1 and cathepsin B, two potential target genes of TFEB involved in lysosome function, were decreased under LPS treatment in vivo and in vitro, and this decrease was rescued by inhibiting RIP3. Finally, overexpression of TFEB restored the autophagic degradation in LPS-treated PTECs. Together, the present study has identified a pivotal role of RIP3 in suppressing autophagic degradation through impeding the TFEB-lysosome pathway in septic AKI, providing potential therapeutic targets for the prevention and treatment of septic AKI.

Abstract Background Although aging increases susceptibility to acute kidney injury (AKI), whether the AKI risk and the association between AKI and adverse outcomes are age-dependent remain unclear in older adults. The current study aimed to identify whether AKI risk was age-dependent in older adults and to investigate whether the association between AKI and mortality increased with increasing age. Methods Medical records from 47,012 adult hospital admissions, including 30,194 older adults aged 60 or older, in two tertiary general hospitals were studied retrospectively. AKI was identified based on changes in blood creatinine levels according to the Kidney Disease: Improving Global Outcomes criteria. Results Among the total population and 30,194 older adult patients, the raw incidences of AKI were 8.2 and 8.3%, respectively. The curve of the age-grouped AKI incidence was “U-shaped”, which revealed a positive relationship between the AKI incidence and age among the older adults aged 75 years or older. This trend of the age-AKI relationship was supported by further multivariable analysis. After adjusting for the Charlson Comorbidity Index score, the AKI was associated with in-hospital mortality; however, the associations did not increase with increasing age. Conclusion The AKI risk does not increase with age in older adults, except for those aged 75 and above. The association between AKI and in-hospital death did not increase in an age-dependent manner in older adults. Trial registration This study was retrospectively registered at clinicaltrials.gov ( NCT03054142 ) on February 13, 2017.

Background Diabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD. Methods We conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial. Results In this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group. Conclusion In summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR.

Background The study aimed to construct a clinical model based on preoperative data for predicting acute kidney injury (AKI) following cardiac surgery in patients with normal renal function. Methods A total of 22,348 consecutive patients with normal renal function undergoing cardiac surgery were enrolled. Among them, 15,701 were randomly selected for the training group and the remaining for the validation group. To develop a model visualized as a nomogram for predicting AKI, logistic regression was performed with variables selected using least absolute shrinkage and selection operator regression. The discrimination, calibration, and clinical value of the model were evaluated. Results The incidence of AKI was 25.2% in the training group. The new model consisted of nine preoperative variables, including age, male gender, left ventricular ejection fraction, hypertension, hemoglobin, uric acid, hypomagnesemia, and oral renin-angiotensin system inhibitor and non-steroidal anti-inflammatory drug within 1 week before surgery. The model had a good performance in the validation group. The discrimination was good with an area under the receiver operating characteristic curve of 0.740 (95% confidence interval, 0.726–0.753). The calibration plot indicated excellent agreement between the model prediction and actual observations. Decision curve analysis also showed that the model was clinically useful. Conclusions The new model was constructed based on nine easily available preoperative clinical data characteristics for predicting AKI following cardiac surgery in patients with normal kidney function, which may help treatment decision-making, and rational utilization of medical resources.

The evolution and current distribution of species on the Qinghai-Tibet Plateau have been significantly impacted by historical occurrences, including the uplift of the plateau and the Quaternary climate upheaval. As a remnant species, the plateau pika (Ochotona curzoniae) is a great model for researching historical events. In this study, 302 samples from 42 sample sites were utilized to analyze the impact of historical events on the evolution and distribution pattern of plateau pikas. The genetic diversity, patterns of differentiation, and historical dynamics of the plateau pika were investigated using molecular markers that included four mitochondrial genes (COI, D-loop, Cytb, and 12S rRNA) and three nuclear genes (GHR, IRBP, and RAG1). The results showed that: (1) The genetic diversity of the plateau pika was high in the Tibetan Plateau (Hd = 0.9997, π = 0.01205), and the plateau pika evolved into five lineages that occupied different geographical areas, with lineage 1 (Group 1) in the south of the Yarlung Zangbo River, lineage 2 (Group 2) in the hinterland of the plateau, lineage 3 (Group 3) in the northeastern part of the plateau, lineage 4 (Group 4) in the Hengduan Mountains, and lineage 5 (Group 5) in the eastern part of the plateau. (2) The gene flow among the five lineages was low, and the differentiation level was high (Nm < 0.25; Fst > 0.25), indicating that the geographical barriers between the five lineages, such as the Yarlung Zangbo River, the Qaidam-Ghuong-Guide Basin, and the Lancang River, effectively promoted the population differentiation of the plateau pika. (3) The plateau pika first spread from the Hengduan Mountains to the entire Qinghai-Tibet Plateau and then conducted small-scale migration and dispersal in several refuges across the plateau in response to climate changes during the glacial and interglacial periods. (4) Except for Group 1 and Group 4, all the other populations exhibited a rapid expansion between 0.06 and 0.01 Mya, but the expansion was considerably delayed or halted by the effects of climate change during the last glacial maximum (0.02 Mya). Overall, the plateau pika on the Qinghai-Tibet Plateau exhibits high genetic diversity, and topographic obstacles, including mountains, valleys, and basins, created by the uplift of the plateau and climatic changes since the Quaternary period have played an important role in the differentiation and historical dynamics of the plateau pika population.

Abstract We described protein A immunoadsorption combination with immunosuppressive treatment improved rapidly a patient with Neuropsychiatric systemic lupus erythematosus.

Abstract Background Idiopathic membranous nephropathy (IMN) is frequently coexisted with diabetes mellitus (DM). Few researches investigate clinical outcomes in IMN patients coexisting diabetes mellitus (DM), including remission rates, renal survival and complications. Concurrent DM also pose therapeutic challenges to IMN patients due to the influence of glucocorticoids and immunosuppressant on metabolic disorders. We performed this study to investigate the impact of DM on clinical outcomes in IMN and the influence of therapeutic regime on metabolic parameters in diabetic IMN patients. Methods Two hundred and six adult hospitalized patients diagnosed with biopsy-proven IMN were retrospectively studied, including 42 patients coexisted with DM. Clinical outcomes including remission rates, renal outcome and complications were compared between groups. Impact of cyclophosphamide and ciclosporin on metabolism and complications were analyzed in IMN patients coexisting DM. Results IMN patients coexisted with DM were presented with advanced age, lower level of eGFR and hemoglobin. Patients coexisted with DM experienced worse renal function deterioration and higher incidence of infection. COX regression analysis showed that DM was an independent risk factor for renal function deterioration in IMN patients. There was no significant difference in remission rates and incidence of venous thromboembolism between two groups. Further exploration on the impact of therapeutic regimens on complications and metabolism showed that cyclophosphamide and ciclosporin had no significant difference in incidence of complications including infection and venous thromboembolism, and posed comparable influences on blood glucose, uric acid and blood lipids in IMN patients coexisted with DM. Conclusion Coexisting DM was an independent risk factor for renal function deterioration in IMN patients but did not influence the remission of proteinuria. Glucocorticoids in combination with cyclophosphamide or ciclosporine had similar impact on complications and metabolic index including blood glucose, uric acid and blood lipids in IMN patients coexisted with DM.

Podocyte injury is sufficient to cause glomerulosclerosis and proteinuria, eventually leading to kidney failure. Previous studies found that podocytes and neurons had similar biological characteristics. Growth-associated protein-43 (GAP-43) is a growth cone protein in neurons, and a marker of axonal and synaptic growth. However, it is not known whether GAP-43 is expressed in podocytes. Compared with normal glomerular podocytes, GAP-43 was significantly reduced in patients with glomerular diseases. GAP-43 also significantly reduced in lipopolysaccharide (LPS)-treated podocytes. We found that the decreased expression of nephrin, the cell marker of the podocyte, was significantly recovered with GAP-43 overexpression. In contrast, the migration ability in LPS-treated podocyte was reduction after GAP-43 overexpressing. Moreover, overexpression of GAP-43 attenuated podocyte apoptosis by up-regulating the ratio of Bcl-2/Bax with LPS treatment. Finally, Plaue and Rcan1 which are downstream target gene of NFATc1 decreased with overexpression of GAP-43 podocytes. We concluded that GAP-43 attenuated podocyte injury by inhibiting calcineurin/NFATc1 signaling. The findings may provide a promising treatment for podocyte injury-related diseases.

Background/Aims: Acute kidney injury (AKI) is a serious complication of sepsis and has a high morbidity and mortality rate. Caspase-11 induces pyroptosis, a form of programmed cell death that plays a critical role in endotoxic shock, but its role in tubular epithelial cell death and whether it contributes to sepsis-associated AKI remains unknown. Methods: The caspase-11–/– mouse received an intraperitoneal injection of lipopolysaccharide (LPS, 40 mg/kg body weight). Caspase-11–/– renal tubular epithelial cells (RTECs) form C57BL caspase-11–/– mice were treated with LPS in vitro. The IL-1β ELISA kit and Scr assay kit were used to measure the level of interleukin-1β and serum creatinine. Annexin V-FITC assay and TUNEL staining assay were used to detect the cell death in different groups in vitro and in vivo. Western blot was performed to analyze the protein expression of caspase-11 and Gsdmdc1. Results: LPS-induced sepsis results in lytic death of RTECs, accompanied by increased expression of the pyroptosis-related proteins caspase-11 and Gsdmd. However, the increase in pyroptosis-related protein expression induced by LPS was attenuated with caspase-11 knockout, both in vitro and in vivo. Furthermore, when challenged with lethal doses of systemic LPS, pathologic abnormalities in renal structure, increased serum and kidney interleukin-1β, increased serum creatinine, and animal death were observed in wild-type mice but prevented in caspase-11–/– mice. Conclusions: Caspase-11-induced pyroptosis of RTECs is a key event during septic AKI, and targeting of caspase-11 in RTECs may serve as a novel therapeutic target in septic AKI.

Abstract Background Two-dimensional speckle-tracking echocardiography (2D-STE) enables objective assessment of left atrial (LA) deformation through the analysis of myocardial strain, which can be measured by different speckle-tracking software. The aim of this study was to compare the consistency of 3 different commercially available software, which include vendor-specific software for measuring left ventricle (VSSLV), vendor-independent software packages for measuring LV strain (VISLV) and vendor-independent software packages for measuring LA strain (VISLA). Methods Sixty-four subjects (mean age: 44 ± 16 years, 50% males) underwent conventional echocardiograms using a GE Vivid 9 (GE Ultrasound, Horten, Norway) cardiac ultrasound system. Standard apical 4 and 2 chamber views of the left atrium were obtained in each subject with a frame-rate range of 40–71 frames/s. LA strain during the contraction phase (Sct), conduit phase (Scd), reservoir phase (Sr = Sct + Scd) were analyzed by 2 independent observers and 3 different software. Results Sct, Scd, Sr were, respectively, − 11.26 ± 2.45%, − 16.77 ± 7.06%, and 28.03 ± 7.58% with VSSLV, − 14.77 ± 3.59%, − 23.17 ± 10.33%, and 38.23 ± 10.99% with VISLV, and − 14.80 ± 3.88%, − 23.94 ± 10.48%, and 38.73 ± 11.56% when VISLA was used. A comparison of strain measurements between VSSLV and VIS (VISLV and VISLA) showed VIS had significantly smaller mean differences and narrower limits of agreement. Similar results were observed in the coefficient of variation (CV) for measurements between VSSLV and VIS (VISLV and VISLA). Comparison of the intra-class correlation coefficients (ICCs) indicated that measurement reliability was weaker with VSSLV (ICC 0.9). For intra-observer ICCs, VISLA > VSSLV = VISLV. For inter-observer ICCs, VSSLV > VISLA > VISLV. Conclusions Software measurement results of LA strain vary considerably. We recommended not measuring LA strain across vendor platforms.

Diabetic kidney disease (DKD) is a serious and common complication of diabetes. Extracellular vesicles (EVs) have emerged as crucial vectors in cell-to-cell communication during the development of DKD. EVs may mediate intercellular communication between podocytes and proximal tubules. In this study, EVs were isolated from podocyte culture supernatants under high glucose (HG), normal glucose (NG), and iso-osmolality conditions, and then co-cultured with proximal tubular epithelial cells (PTECs). MicroRNAs (miRNA) sequencing was conducted to identify differentially expressed miRNAs of podocyte EVs and bioinformatics analysis was performed to explore their potential functions. The results showed that EVs secreted from HG-treated podocytes induced apoptosis of PTECs. Moreover, five differentially expressed miRNAs in response to HG condition were identified. Functional enrichment analysis revealed that these five miRNAs are likely involved in biological processes and pathways related to the pathogenesis of DKD. Overall, these findings demonstrate the pro-apoptotic effects of EVs from HG-treated podocytes on PTECs and provide new insights into the pathologic mechanisms underlying DKD.

Left atrial appendage (LAA) dysfunction identified by transesophageal echocardiography (TEE) is a powerful predictor of stroke in patients with atrial fibrillation (AF). The aim of our study is to assess if there is a correlation between the left atrial (LA) functional parameter and LAA dysfunction in the AF patients. This cross-sectional study included a total of 249 Chinese AF patients who did not have cardiac valvular diseases and were undergoing cardiac ablation. TEE was performed in all the patients who were categorized into two groups according to their left atrial appendage (LAA) function. A total of 120 of the 249 AF patients had LAA dysfunction. Univariate and multivariate logistic regression was conducted to assess the independent factors that correlated with the LAA dysfunction. Different predictive models for the LAA dysfunction were compared with the receiver operating characteristic (ROC) curve. The final ROC curve on the development and validation datasets was drawn based on the calculation of each area under the curves (AUC). Univariate and multivariate analysis showed that the peak left atrial strain (PLAS) was the most significant factor that correlated with the LAA dysfunction. PLAS did not show inferiority amongst all the models and revealed strong discrimination ability on both the development and validation datasets with AUC 0.818 and 0.817. Our study showed that a decrease in PLAS is independently associated with LAA dysfunction in the AF patients.

OBJECTIVE: Acute kidney injury (AKI) in patients hospitalized for acute heart failure (AHF) is usually type 1 of the cardiorenal syndrome (CRS) and has been associated with increased morbidity and mortality. Early recognition of AKI is critical. This study was to determine if the new KDIGO criteria (Kidney Disease: Improving Global Outcomes) for identification and short-term prognosis of early CRS type 1 was superior to the previous RIFLE and AKIN criteria. METHODS: The association between AKI diagnosed by KDIGO but not by RIFLE or AKIN and in-hospital mortality was retrospectively evaluated in 1005 Chinese adult patients with AHF between July 2008 and May 2012. AKI was defined as RIFLE, AKIN and KDIGO criteria, respectively. Cox regression was used for multivariate analysis of in-hospital mortality. RESULTS: Within 7 days on admission, the incidence of CRS type 1 was 38.9% by KDIGO criteria, 34.7% by AKIN, and 32.1% by RIFLE. A total of 110 (10.9%) cases were additional diagnosed by KDIGO criteria but not by RIFLE or AKIN. 89.1% of them were in Stage 1 (AKIN) or Stage Risk (RIFLE). They accounted for 18.4% (25 cases) of the overall death. After adjustment, this proportion remained an independent risk factor for in-hospital mortality [odds ratios (OR)3.24, 95% confidence interval(95%CI) 1.97-5.35]. Kaplan-Meier curve showed AKI patients by RIFLE, AKIN, KDIGO and [K(+)R(-)+K(+)A(-)] had lower hospital survival than non-AKI patients (Log Rank P

Pulmonary hypertension (PH) was recently recognized as a common complication of end-stage renal disease (ESRD) that causes an increased risk of mortality. Epidemiological data for this disorder in earlier stages of chronic kidney disease (CKD) and its association with cardiovascular (CV) morbidity are scarce.We retrospectively analyzed 2,351 Chinese CKD patients with complete clinical records and echocardiography data between Jan 2008 and May 2012. The patients were divided into the following 6 groups: CKD Stages 1-4; Stage 5 for those not on or initiated on hemodialysis for

BACKGROUND: Glomerulosclerosis correlates with reduction in podocyte number that occurs through mechanisms which include apoptosis. Podocyte injury or podocyte loss in the renal glomerulus has been proposed as the crucial mechanism in the development of glomerulosclerosis. However, the mechanism by which podocytes respond to injury is poorly understood. TNF and TNF receptor superfamilies are important in the pathogenesis of podocyte injury and apoptosis. The ligand of receptor activator of NF-kappaB (RANKL) and receptor activator of NF-kappaB (RANK) are members of the TNF and receptor superfamilies. We investigated whether RANK-RANKL is a receptor-ligand complex for podocytes responding to injury. METHODOLOGY/PRINCIPAL FINDINGS: In this study, RANKL and RANK were examined in human podocyte diseases and a rat model of puromycin aminonucleoside nephrosis (PAN). Compared with controls, RANK and RANKL were increased in both human podocyte diseases and the rat PAN model; double immunofluorescence staining revealed that RANK protein expression was mainly attributed to podocytes. Immunoelectron microscopy showed that RANK was localized predominantly at the top of the foot process membrane and the cytoplasm of rat podocyte. In addition, RANK was upregulated in mouse podocytes in vitro after injury induced by puromycin aminonucleoside (PA). Knockdown of RANK expression by small interference RNA (siRNA) exacerbated podocyte apoptosis induced by PA. However, RANKL inhibited significantly the apoptosis of podocytes induced by PA. CONCLUSIONS/SIGNIFICANCE: These findings suggest the increase in RANK-RANKL expression is a response to podocyte injury, and RANK-RANKL may be a novel receptor-ligand complex for the survival response during podocyte injury.