Machine Learning for Predicting Risk and Prognosis of Acute Kidney Disease in Critically Ill Elderly Patients During Hospitalization: Internet-Based and Interpretable Model Study.

BACKGROUND: Acute kidney disease (AKD) affects more than half of critically ill elderly patients with acute kidney injury (AKI), which leads to worse short-term outcomes. OBJECTIVE: We aimed to establish 2 machine learning models to predict the risk and prognosis of AKD in the elderly and to deploy the models as online apps. METHODS: Data on elderly patients with AKI (n=3542) and AKD (n=2661) from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were used to develop 2 models for predicting the AKD risk and in-hospital mortality, respectively. Data collected from Xiangya Hospital of Central South University were for external validation. A bootstrap method was used for internal validation to obtain relatively stable results. We extracted the indicators within 24 hours of the first diagnosis of AKI and the fluctuation range of some indicators, namely delta (day 3 after AKI minus day 1), as features. Six machine learning algorithms were used for modeling; the area under the receiver operating characteristic curve (AUROC), decision curve analysis, and calibration curve for evaluating; Shapley additive explanation (SHAP) analysis for visually interpreting; and the Heroku platform for deploying the best-performing models as web-based apps. RESULTS: For the model of predicting the risk of AKD in elderly patients with AKI during hospitalization, the Light Gradient Boosting Machine (LightGBM) showed the best overall performance in the training (AUROC=0.844, 95% CI 0.831-0.857), internal validation (AUROC=0.853, 95% CI 0.841-0.865), and external (AUROC=0.755, 95% CI 0.699-0.811) cohorts. In addition, LightGBM performed well for the AKD prognostic prediction in the training (AUROC=0.861, 95% CI 0.843-0.878), internal validation (AUROC=0.868, 95% CI 0.851-0.885), and external (AUROC=0.746, 95% CI 0.673-0.820) cohorts. The models deployed as online prediction apps allowed users to predict and provide feedback to submit new data for model iteration. In the importance ranking and correlation visualization of the model's top 10 influencing factors conducted based on the SHAP value, partial dependence plots revealed the optimal cutoff of some interventionable indicators. The top 5 factors predicting the risk of AKD were creatinine on day 3, sepsis, delta blood urea nitrogen (BUN), diastolic blood pressure (DBP), and heart rate, while the top 5 factors determining in-hospital mortality were age, BUN on day 1, vasopressor use, BUN on day 3, and partial pressure of carbon dioxide (PaCO2). CONCLUSIONS: We developed and validated 2 online apps for predicting the risk of AKD and its prognostic mortality in elderly patients, respectively. The top 10 factors that influenced the AKD risk and mortality during hospitalization were identified and explained visually, which might provide useful applications for intelligent management and suggestions for future prospective research.

Upper gastrointestinal haemorrhage patients' survival: A causal inference and prediction study.

BACKGROUND: Upper gastrointestinal (GI) bleeding is a common medical emergency. This study aimed to develop models to predict critically ill patients with upper GI bleeding in-hospital and 30-day survival, identify the correlation factor and infer the causality. METHODS: A total of 2898 patients with upper GI bleeding were included from the Medical Information Mart for Intensive Care-IV and eICU-Collaborative Research Database, respectively. To identify the most critical factors contributing to the prognostic model, we used SHAP (SHapley Additive exPlanations) for machine learning interpretability. We performed causal inference using inverse probability weighting for survival-associated prognostic factors. RESULTS: The optimal model using the light GBM (gradient boosting algorithm) algorithm achieved an AUC of .93 for in-hospital survival, .81 for 30-day survival in internal testing and .87 for in-hospital survival in external testing. Important factors for in-hospital survival, according to SHAP, were SOFA (Sequential organ failure assessment score), GCS (Glasgow coma scale) motor score and length of stay in ICU (Intensive critical care). In contrast, essential factors for 30-day survival were SOFA, length of stay in ICU, total bilirubin and GCS verbal score. Our model showed improved performance compared to SOFA alone. CONCLUSIONS: Our interpretable machine learning model for predicting in-hospital and 30-day mortality in critically ill patients with upper gastrointestinal bleeding showed excellent accuracy and high generalizability. This model can assist clinicians in managing these patients to improve the discrimination of high-risk patients.

METTL3-mediated N6-methyladenosine modification stimulates mitochondrial damage and ferroptosis of kidney tubular epithelial cells following acute kidney injury by modulating the stabilization of MDM2-p53-LMNB1 axis.

N6-methyladenosine (m6A) and MELLT3 assume a role in the development of acute kidney injury (AKI). However, their mechanism in AKI remains under-explored. On this basis, this study explored the mechanism of MELLT3 in mitochondrial damage and ferroptosis of kidney tubular epithelial cells after AKI. HK-2 cells were induced by lipopolysaccharide (LPS) to simulate AKI, followed by gain and loss of function of genes, detection of mitochondrial damage and ferroptosis indicators, and analysis of gene interactions. An AKI mouse model was developed using the cecal ligation and puncture (CLP) method to investigate the effect of METTL3 knockdown on kidney injury. MDM2 and LMNB1 were upregulated and p53 was downregulated in LPS-treated HK-2 cells. Mechanistically, the E3 ubiquitin ligase MDM2 increased p53 ubiquitination to activate LMNB1. METTL3 knockdown decreased m6A methylation of MDM2, thus diminishing YTHDF1-mediated MDM2 mRNA stability and translation in LPS-treated HK-2 cells. Knockdown of LMNB1, MDM2, or METTL3 reduced NO, MDA, iron ion, and ROS levels as well as mitochondrial damage and raised SOD, GSH, XCT, GPX4, FPN1, and TFR1 levels in LPS-treated HK-2 cells. The in vivo results showed that METTL3 knockdown reduced renal injury and ferroptosis in CLP mice. METTL3 knockdown prevents mitochondrial damage and ferroptosis of kidney tubular epithelial cells after AKI via the MDM2-p53-LMNB1 axis.

Targeting EB3-IP3R3 Interface with Cognate Peptide Protects from Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is a lung disease characterized by acute onset of noncardiogenic pulmonary edema, hypoxemia, and respiratory insufficiency. The current treatment for ARDS is mainly supportive in nature, providing a critical need for targeted pharmacological management. We addressed this medical problem by developing a pharmacological treatment for pulmonary vascular leakage, a culprit of alveolar damage and lung inflammation. Our novel therapeutic target is the microtubule accessory factor EB3 (end binding protein 3), which contributes to pulmonary vascular leakage by amplifying pathological calcium signaling in endothelial cells in response to inflammatory stimuli. EB3 interacts with IP3R3 (inositol 1,4,5-trisphosphate receptor 3) and orchestrates calcium release from endoplasmic reticulum stores. Here, we designed and tested the therapeutic benefits of a 14-aa peptide named CIPRI (cognate IP3 receptor inhibitor), which disrupted EB3-IP3R3 interaction in vitro and in lungs of mice challenged with endotoxin. Treatment with CIPRI or depletion of IP3R3 in lung microvascular endothelial monolayers mitigated calcium release from endoplasmic reticulum stores and prevented a disassembly of vascular endothelial cadherin junctions in response to the proinflammatory mediator α-thrombin. Furthermore, intravenous administration of CIPRI in mice mitigated inflammation-induced lung injury, blocked pulmonary microvascular leakage, prevented activation of NFAT (nuclear factor of activated T cells) signaling, and reduced production of proinflammatory cytokines in the lung tissue. CIPRI also improved survival of mice from endotoxemia and polymicrobial sepsis. Together, these data demonstrate that targeting EB3-IP3R3 interaction with a cognate peptide is a promising strategy to address hyperpermeability of microvessels in inflammatory lung diseases.

Exosomal microRNA-342-5p secreted from adipose-derived mesenchymal stem cells mitigates acute kidney injury in sepsis mice by inhibiting TLR9.

BACKGROUND: Sepsis-related acute kidney injury (AKI) is an inflammatory disease associated with extremely high mortality and health burden. This study explored the possibility of exosomes secreted by adipose-derived mesenchymal stem cells (AMSCs) serving as a carrier for microRNA (miR)-342-5p to alleviate sepsis-related AKI and investigated the possible mechanism. METHODS: Serum was obtained from 30 patients with sepsis-associated AKI and 30 healthy volunteers for the measurement of miR-342-5p, blood urea nitrogen (BUN), and serum creatinine (SCr) levels. For in vitro experiments, AMSCs were transfected with LV-miR-342-5p or LV-miR-67 to acquire miR-342-5p-modified AMSCs and miR-67-modified AMSCs, from which the exosomes (AMSC-Exo-342 and AMSC-Exo-67) were isolated. The human renal proximal tubular epithelial cell line HK-2 was induced by lipopolysaccharide (LPS) to construct a cellular model of sepsis. The expression of Toll-like receptor 9 (TLR9) was also detected in AKI cells and mouse models. The interaction between miR-342-5p and TLR9 was predicted by dual luciferase reporter gene assay. RESULTS: Detection on clinical serum samples showed that BUN, SCr, and TLR9 were elevated and miR-342-5p level was suppressed in the serum of patients with sepsis-associated AKI. Transfection with LV-miR-342-5p reinforced miR-342-5p expression in AMSCs and AMSC-secreted exosomes. miR-342-5p negatively targeted TLR9. LPS treatment enhanced TLR9 expression, reduced miR-342-5p levels, suppressed autophagy, and increased inflammation in HK-2 cells, while the opposite trends were observed in LPS-induced HK-2 cells exposed to AMSC-Exo-342, Rapa, miR-342-5p mimic, or si-TLR9. Additionally, the effects of AMSC-Exo-342 on autophagy and inflammation in LPS-induced cells could be weakened by 3-MA or pcDNA3.1-TLR9 treatment. Injection of AMSC-Exo-342 enhanced autophagy, mitigated kidney injury, suppressed inflammation, and reduced BUN and SCr levels in sepsis-related AKI mouse models. CONCLUSION: miR-342-5p transferred by exosomes from miR-342-5p-modified AMSCs ameliorated AKI by inhibiting TLR9 to accelerate autophagy.

Sphingosine Kinase 1 Deficiency in Smooth Muscle Cells Protects against Hypoxia-Mediated Pulmonary Hypertension via YAP1 Signaling.

Sphingosine kinase 1 (SPHK1) and the sphingosine-1-phosphate (S1P) signaling pathway have been shown to play a role in pulmonary arterial hypertension (PAH). S1P is an important stimulus for pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling. We aimed to examine the specific roles of SPHK1 in PASMCs during pulmonary hypertension (PH) progression. We generated smooth muscle cell-specific, Sphk1-deficient (Sphk1f/f TaglnCre+) mice and isolated Sphk1-deficient PASMCs from SPHK1 knockout mice. We demonstrated that Sphk1f/f TaglnCre+ mice are protected from hypoxia or hypoxia/Sugen-mediated PH, and pulmonary vascular remodeling and that Sphk1-deficient PASMCs are less proliferative compared with ones isolated from wild-type (WT) siblings. S1P or hypoxia activated yes-associated protein 1 (YAP1) signaling by enhancing its translocation to the nucleus, which was dependent on SPHK1 enzymatic activity. Further, verteporfin, a pharmacologic YAP1 inhibitor, attenuated the S1P-mediated proliferation of hPASMCs, hypoxia-mediated PH, and pulmonary vascular remodeling in mice and hypoxia/Sugen-mediated severe PH in rats. Smooth muscle cell-specific SPHK1 plays an essential role in PH via YAP1 signaling, and YAP1 inhibition may have therapeutic potential in treating PH.

Development and deployment of interpretable machine-learning model for predicting in-hospital mortality in elderly patients with acute kidney disease.

BACKGROUND: Acute kidney injury (AKI) is more likely to develop in the elderly admitted to the intensive care unit (ICU). Acute kidney disease (AKD) affects ∼45% of patients with AKI and increases short-term mortality. However, there are no studies on the prognosis of AKD in the elderly. METHODS: Data from 2666 elderly patients with AKD in the Medical Information Mart for Intensive Care IV were used for model development and 535 in the eICU Collaborative Research Database for external validation. Based on 5 machine learning algorithms, 33 noninvasive parameters were extracted as features for modeling. RESULTS: In-hospital mortality of AKD in the elderly was 29.6% and 31.8% in development and validation cohorts, respectively. The comprehensive best-performing algorithm was the support vector machine (SVM), and a simplified online application included only 10 features employing SVM (AUC: 0.810 and 0.776 in the training and external validation cohorts, respectively) was deployed. Model interpretation by SHapley Additive exPlanation (SHAP) values revealed that the difference (AKD day - ICU day) in sequential organ failure assessment (delta SOFA), Glasgow coma scale (GCS), delta GCS, delta peripheral oxygen saturation (SpO2), and SOFA were the top five features associated with prognosis. The optimal target was determined by SHAP values from partial dependence plots. CONCLUSIONS: A web-based tool was externally validated and deployed to predict the early prognosis of AKD in the elderly based on readily available noninvasive parameters, assisting clinicians in intervening with precision and purpose to save lives to the greatest extent.

Visual performance of painting colors based on psychological factors.

Humans have been exploring colors since ancient times, but relatively complete color systems appeared one after another in the twentieth century. Even without language and other information exchanges, colors can still convey information and stimulate emotions. Therefore, color can have both physical and psychological effects on people. In this context, this paper studies the visual representation of painting colors based on psychological factors. The article studies the theory of personality traits and introduces the related content of visual psychology. To explore the relationship between each variable and color psychology and the visual representation of painting colors, a binary logistic regression analysis is performed. The colors in the post-impressionist paintings of Van Gogh and Gauguin is contrasted, and experiments on psychological factors and color research is conducted. The factors that affect the color tone of the picture and the influence of psychological factors on the judgment of color brightness are investigated. Finally, the correlation analysis of personality trait dimension and irrational behavior is carried out. The experimental results of the article show that after the analysis of variance, the significance levels of regression model 1 and model 2 both reach 0.000, and the adjusted R squares are 0.319 and 0.356, respectively. In this study, regression model 2 was selected as the final model. According to Model 2, the standardized regression coefficients of agreeableness and neuroticism are 0.438 and -0.251, respectively, and the significance of the regression coefficients are 0.000 and 0.021, respectively. The research on the visual performance of painting colors based on psychological factors has been well completed.

CircHIPK2 promotes proliferation of nasopharyngeal carcinoma by down-regulating HIPK2.

Background: Circular RNAs (circRNAs) are a new family of endogenous non-coding RNAs generated by a covalently closed loop, and a mounting body of data suggests they control gene expression. While the circRNA-homeodomain-interacting protein kinase-2 (circHIPK2) is generated from the homeodomain-interacting protein kinase 2 (HIPK2) gene, the function of circHIPK2 in nasopharyngeal cancer (NPC) along with the responsible mechanisms are still unclear. Methods: RNA-sequencing data was utilized to determine the differentially expressed circRNAs, and circHIPK2 was established as a novel prospective circRNA. The expressions of circRNAs along with messenger RNAs (mRNAs) in NPC tissues and cells was assessed via quantitative real-time polymerase chain reaction (qRT-PCR), and the transfection of NPC cells with plasmids in vitro and in vivo was adopted to explore the effects of circHIPK2 in NPC. Western blotting was adopted to assess the expressions of HIPK2 and ß-catenin, while Cell Counting Kit (CCK)-8 assay coupled with colony-forming assay were utilized to assess the biological functions. The expression of nuclear and cytoplasmic HIPK2 was detected via nucleocytoplasmic separation assay. Results: Herein, we established that circHIPK2 was upregulated in NPC tissues. Over-expression of circHIPK2 promoted cell proliferation in vitro and in vivo, and further studies revealed it inhibited the protein level of HIPK2 in a post-transcriptional pattern, decreasing ß-catenin expression and suppressing the proliferation of NPC. Conclusions: Our findings demonstrated elevated circHIPK2 facilitated the cell proliferation of NPC cells via the circHIPK2/HIPK2 axis, suggesting circHIPK2 might be an oncogene to promote the process of NPC and could be a novel treatment target for its management.

Establishment and external validation of an online dynamic nomogram for predicting in-hospital death risk in sepsis-associated acute kidney disease.

OBJECTIVES: Approximately one-third of patients with sepsis-associated acute kidney injury (AKI) progress to acute kidney disease (AKD) with higher short-term mortality. We aimed to identify the clinical characteristics that influence in-hospital death in sepsis-associated AKD and develop a nomogram to facilitate early warning. METHODS: Logical regression was applied to screen variables based on clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A nomogram was established to predict in-hospital death risk in patients with sepsis-associated AKD. The eICU Collaborative Research Database (eICU-CRD) was used for external validation. The receiver operating characteristic and calibration curves were used to determine the model's performance. RESULTS: A total of 1,779 patients with sepsis-associated AKD were included from the MIMIC-IV and 344 from the eICU-CRD. Age, Glasgow coma scale score, systolic blood pressure, peripheral oxygen saturation, platelet count, white blood cell count, and bicarbonate levels were significantly correlated with death. The nomogram demonstrated high discrimination in the training (C-index, 0.829; 95% confidence interval [CI] [0.807-0.852]) and testing sets (C-index: 0.760; 95% CI [0.706-0.814]). At the optimal cut-off value of 0.270, the model's sensitivity in the training and validation datasets was 72.8% (95% CI [68.3-76.9%]) and 64.5% (95% CI [54.9-73.4%]), while the specificity was 79.2% (95% CI [76.9-81.4%]) and 74.8% (95% CI [68.7-80.2%]), respectively. CONCLUSION: We identified seven predictors of in-hospital death in patients with sepsis-associated AKD. In addition, we developed an online dynamic nomogram to accurately and conveniently predict short-term outcomes, which performed well in the external dataset.

Sarcopenia and Mortality Risk of Patients with Sepsis: A Meta-Analysis.

Background: The association between sarcopenia at admission and mortality in patients with sepsis has not been comprehensively evaluated. We performed a meta-analysis to systematically evaluate the above association. Methods: This meta-analysis included relevant observational studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intrastudy heterogeneity was selected to pool the results. Subgroup analyses were applied to evaluate the influences of study characteristics on relationship. Results: Ten cohort studies including 2396 patients with sepsis were included, and 1496 (62.4%) of them had sarcopenia at presentation. Pooled results showed that compared to those without sarcopenia, septic patients with sarcopenia had a significantly increased early (in-hospital or 1-month) mortality risk (risk ration (RR): 2.14, 95% confidence interval (CI): 1.60-2.87, P < 0.001; I 2 = 46%). Subgroup analyses showed consistent association between sarcopenia and increased acute mortality risk in septic patients which were not affected by study characteristics such as study design, country of the study, clinical settings, diagnostic criteria for sepsis, age, gender of the patients, and methods for diagnosis of sarcopenia (P for all subgroup analyses >0.05). Further meta-analyses showed that sarcopenia was also associated with increased mortality risk in septic patients at 3-6 months (RR: 2.13, 95% CI: 1.58-2.89, P < 0.001; I 2 = 0%) and at 1 year (RR: 1.57, 95% CI: 1.09-2.24, P = 0.01; I 2 = 29%). Conclusions: Current evidence suggests that sarcopenia may be a predictor of mortality in patients with sepsis.

The Role of Three-Dimensional Reconstruction of Medical Images and Virtual Reality in Nursing Experimental Teaching.

With the continuous advancement of medicine and computer science, medical image processing technology is also constantly advancing, and at the same time, it puts forward the needs of its own development. The purpose of this article is to combine the three-dimensional reconstruction of medical images and virtual reality (VR) technology in nursing experiment teaching to help students understand more easily and to simplify the teachers' teaching process and make the VR application technology. It is the most popular and effective in medical teaching. This article proposes the C-V model and the geometric active contour model to help us more clearly understand the pathology in this environment, where the specific symptoms appear, and bring a more easy-to-understand model for teaching and improving teaching quality. This article also designs nursing experiment teaching. The experimental results of this paper show that, after using VR courseware for teaching, the optimal test rate of the experimental class is 15% higher than that of the control class, and the transition rate is 8%. The actual test excellent rate and success rate of the experimental class are much higher than those of the control class. Therefore, it can be concluded that the application of VR technology in nursing teaching helps teachers improve their practical ability. The excellent teaching feedback rate is 95%, which is higher than 80.5% in the control group, indicating that the patient teaching simulation is approved by the observation group. The program can effectively improve the feedback rate of excellent teaching and provide students with better teaching services.

Enhanced effect of recombinant adenoviruses co-expression of ING4 and OSM on anti-tumour activity of laryngeal cancer.

The inhibitor of growth family member 4 (ING4) is one of the ING family genes, serves as a repressor of angiogenesis or tumour growth and suppresses loss of contact inhibition. Oncostatin M (OSM) is a multifunctional cytokine that belongs to the interleukin (IL)-6 subfamily with several biological activities. However, the role of recombinant adenoviruses co-expressing ING4 and OSM (Ad-ING4-OSM) in anti-tumour activity of laryngeal cancer has not yet been identified. Recombinant Ad-ING4-OSM was used to evaluate their combined effect on enhanced anti-tumour activity in Hep-2 cells of laryngeal cancer in vivo. Moreover, in vitro function assays of co-expression of Ad-ING4-OSM were performed to explore impact of co-expression of Ad-ING4-OSM on biological phenotype of laryngeal cancer cell line, that is Hep-2 cells. In vitro, Ad-ING4-OSM significantly inhibited the growth, enhanced apoptosis, altered cell cycle with G1 and G2/M phase arrest, and upregulated the expression of P21, P27, P53 and downregulated survivin in laryngeal cancer Hep-2 cells. Furthermore, in vivo functional experiments of co-expressing of Ad-ING4-OSM demonstrated that solid tumours in the nude mouse model were significantly suppressed, and the co-expressing Ad-ING4-OSM showed a significant upregulation expression of P21, P53, Bax and Caspase-3 and a downregulation of Cox-2, Bcl-2 and CD34. This study for the first time demonstrated the clinical value and the role of co-expressing Ad-ING4-OSM in biological function of laryngeal cancer. This work suggested that co-expressing Ad-ING4-OSM might serve as a potential therapeutic target for laryngeal cancer patients.

The Lactate/Albumin Ratio Predicts Mortality in Critically Ill Patients with Acute Kidney Injury: An Observational Multicenter Study on the eICU Database.

OBJECTIVE: The serum lactate/albumin ratio (LAR) can be used to independently predict mortality due to sepsis. However, whether the LAR predicts the outcomes of critically ill patients with acute kidney injury (AKI) remains unclear. This study was performed to assess the prognostic value of the LAR in critically ill AKI patients. METHODS: This retrospective observational study enrolled AKI patients, and all data were collected through the eICU Collaborative Research Database. Outcomes included in-hospital and intensive care unit (ICU) death. Multivariate Cox regression analysis was used to determine independent risk factors. Forest plots and smoothing curves were generated. A series of subgroup analyses were performed to further validate the robustness of the findings. RESULTS: A total of 4666 eligible patients were enrolled. We divided the participants into four groups according to the LAR: quartile (Q)1 (LAR < 0.46, n = 1167), Q2 (0.46 ≤ LAR < 0.79, n = 1162), Q3 (0.79 ≤ LAR < 1.49, n = 1170), and Q4 (LAR ≥ 1.49, n = 1167). The LAR, when analyzed as a continuous variable, was associated with hospital and ICU mortality (adjusted hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.18-1.26, P < 0.0001 for both). The risk of in-hospital and ICU mortality increased with increasing LAR Q relative to Q1. The smoothing curves revealed a continuous linear association after adjusting for all covariates. By the Kaplan-Meier analysis, patients in the higher LAR group showed significantly shorter survival time. By the receiver operating characteristic analysis, LAR was efficient in predicting in-hospital mortality (area under the curve [AUC]: 0.717) and ICU mortality (AUC: 0.733). A positive and consistent effect of the LAR was seen in all subgroups analyses after adjusting for all covariates. CONCLUSION: A high LAR is an independent risk factor for in-hospital and ICU mortality in critically ill patients with AKI. Further prospective studies are needed to validate these result.

Nomogram to predict the risk of septic acute kidney injury in the first 24 h of admission: an analysis of intensive care unit data.

Background: Acute kidney injury (AKI) is a significant cause of morbidity and mortality, especially in sepsis patients. Early prediction of AKI can help physicians determine the appropriate intervention, and thus, improve the outcome. This study aimed to develop a nomogram to predict the risk of AKI in sepsis patients (S-AKI) in the initial 24 h following admission.Methods: Sepsis patients with AKI who met the Sepsis 3.0 criteria and Kidney Disease: Improving Global Outcomes criteria in the Massachusetts Institute of Technology critical care database, Medical Information Mart for Intensive Care (MIMIC-III), were identified for analysis. Data were analyzed using multiple logistic regression, and the performance of the proposed nomogram was evaluated based on Harrell's concordance index (C-index) and the area under the receiver operating characteristic curve.Results: We included 2917 patients in the analysis; 1167 of 2042 patients (57.14%) and 469 of 875 patients (53.6%) had AKI in the training and validation cohorts, respectively. The predictive factors identified by multivariate logistic regression were blood urea nitrogen level, infusion volume, lactate level, weight, blood chloride level, body temperature, and age. With the incorporation of these factors, our model had well-fitted calibration curves and achieved good C-indexes of 0.80 [95% confidence interval (CI): 0.78-0.82] and 0.79 (95% CI: 0.76-0.82) in predicting S-AKI in the training and validation cohorts, respectively.Conclusion: The proposed nomogram effectively predicted AKI risk in sepsis patients admitted to the intensive care unit in the first 24 h.

[Clinical analysis of sepsis with extensively drug resistant Gram-negative bacteria in intensive care unit treated with polymyxin B-based combination therapy].

OBJECTIVE: To investigate the clinical efficacy and safety of polymyxin B in the treatment of sepsis caused by extensively-drug resistant (XDR) Gram-negative bacteria. METHODS: A retrospective analysis of 39 septic patients with XDR Gram-negative bacterial infection treated with polymyxin B in the department of critical care medicine of Xiangya Hospital of Central South University from June 2018 to September 2019 were enrolled. The clinical characteristics, bacterial culture, the sensitivity antibacterial drugs, types and courses of antibiotics, biochemical indexes, and acute physiology and chronic health evaluation II (APACHE II) before and after polymyxin B treatment were collected, to assess microbial clearance and efficacy, drug related adverse effects, and 28-day mortality in septic patients with XDR. RESULTS: Of the 39 septic patients with XDR, 32 (82.1%) were male, with the mean age of (53.6±12.6) years old. The main infection site was pulmonary infection (51.2%), and the treatment courses of polymyxin B were ≥ 5 days. A total of 66 pathogenic bacteria were detected from 39 patients. Among them, with the high estrate of detecting Acinetobacter baumannii of 51.5% (34/66). After treatment with polymyxin B, the results showed that the clearance rate of microorganisms was 65.2% (43/66), the overall effective rate was 59.0% (23/39), and the 28-day all-cause mortality was 41.0% (16/39). There were no significant differences in clinical efficacy and microbial clearance among patients with different treatment groups of polymyxin B [< 10 days, 10-15 days, and > 15 days groups: effective rates were 56.5% (13/23), 54.5% (6/11), 80.0% (4/5), χ 2 = 0.999, P = 0.728; the microbial clearance rates were 43.5% (10/23), 54.5% (6/11), and 80.0% (4/5), χ 2 = 2.141, P = 0.393]. The effective and microbial clearance rates of the polymyxin B daily doses of 150 mg and 200 mg groups were significantly higher than those of the daily dose of 100 mg [effectiveness: 85.7% (6/7), 87.5% (7/8) vs. 41.7% (10/24); microbial clearance rate: 71.4% (5/7), 87.5% (7/8) vs. 33.3% (8/24), all P < 0.05], however, there were no significant differences in the length of intensive care unit (ICU) stay and mechanical ventilation time among different daily dose groups. The APACHE II score after polymyxin B administration was significantly lower than before administration (all patients: 16.20±9.24 vs. 24.40±4.73, effective patients: 11.30±4.08 vs. 23.00±4.56, both P < 0.05). Four patients with renal injury had an increase in serum creatinine during the administration of polymyxin B, and recovered after discontinuation of the drug without other adverse reactions. CONCLUSIONS: Polymyxin B can be used as an effective treatment option for patients with severe infection of XDR Gram-negative bacteria.

Anticoagulation Effect and Safety Observation of Regional Citrate Anticoagulation for Double-Filtration Plasmapheresis in Critical Patients.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) is a semi-selective blood purification method based on dual filtration system. Regional citrate anticoagulation (RCA) is an appealing anticoagulation alternative in DFPP. However, there are still few reports on the safety of RCA in DFPP treatment. OBJECTIVE: To investigate the anticoagulation effect and safety of RCA for DFPP in critical patients. METHODS: A total of 34 critical patients treated with DFPP were retrospectively studied. The incidence of coagulation during extracorporeal circulation after single treatment was compared before and after treatment. Heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, blood routine indexes, blood gas analysis, peripheral ionic calcium (iCa), total peripheral calcium (TCa), TCa/iCa, and complications before and after single treatment were compared. The changes of transmembrane pressure, pressure drop were measured, and the indexes of coagulation before and after treatment were compared. RESULTS: The blood coagulation 0.05). Level of TCa was significantly decreased at 5 min after treatment (p < 0.05), but there was no statistically significant difference at 6 and 24 h (p > 0.05). No treatment-related serious complications were observed in any of the patients. CONCLUSIONS: For critical patients who underwent DFPP procedure, RCA is safety and had significant anticoagulation effects, which is worthy of clinical application.

MicroRNA410 Inhibits Pulmonary Vascular Remodeling via Regulation of Nicotinamide Phosphoribosyltransferase.

Nicotinamide phosphoribosyltransferase (NAMPT) upregulation in human pulmonary artery endothelial cells (hPAECs) is associated with pulmonary arterial hypertension (PAH) progression and pulmonary vascular remodeling. The underlying mechanisms regulating NAMPT expression are still not clear. In this study, we aimed to study the regulation of NAMPT expression by microRNA410 (miR410) in hPAECs and explore the role of miR410 in the pathogenesis of experimental pulmonary hypertension. We show that miR410 targets the 3' UTR of NAMPT and that, concomitant with NAMPT upregulation, miR410 is downregulated in lungs of mice exposed to hypoxia-induced pulmonary hypertension (HPH). Our results also demonstrate that miR410 directly inhibits NAMPT expression. Overexpression of miR410 in hPAECs inhibits basal and VEGF-induced proliferation, migration and promotes apoptosis of hPAECs, while miR410 inhibition via antagomirs has the opposite effect. Finally, administration of miR410 mimics in vivo attenuated induction of NAMPT in PAECs and prevented the development of HPH in mice. Our results highlight the role of miR410 in the regulation of NAMPT expression in hPAECs and show that miR410 plays a potential role in PAH pathobiology by targeting a modulator of pulmonary vascular remodeling.

Protective effect and mechanisms of exogenous neutrophil gelatinase-associated lipocalin on lipopolysaccharide-induced injury of renal tubular epithelial cell.

PURPOSES: To investigate the protective effect of exogenous neutrophil gelatinase-associated lipocalin (NGAL) on the lipopolysaccharide-induced injury of renal tubular epithelial cells and its regulation of autophagy. METHODS: Renal tubular epithelial cells were treated with lipopolysaccharide (LPS) at different concentrations (0-100 µg/mL) and at different times (0-24 h), the expression of NGAL was detected to determine the optimal time and concentration of LPS treatment. The NGAL gene knockdown lentivirus (NGAL-RNAi) was constructed and verified its knockdown rate and inhibition effect. Renal tubular epithelial cells were randomly divided into Control group, LPS group, LPS + NGAL group, NGAL-RNAi + LPS group, and NGAL-RNAi + LPS + NGAL group. Western blot and immunofluorescence tested the expression of autophagy-associated proteins, the changes in the number of autophagosomes were observed by electron microscopy, analyzed the role of exogenous NGAL. RESULTS: The study showed the expression of autophagy-associated proteins (LC3-II and Beclin-1) in NGAL-RNAi + LPS group was significantly lower than the LPS group (P < 0.0100). The expression of LC3-II and Beclin-1 in the NGAL-RNAi + LPS + NGAL group was significantly higher than the NGAL-RNAi + LPS group (P < 0.0100). After the addition of exogenous NGAL, the autophagosomes in the LPS + NGAL group and the NGAL-RNAi + LPS + NGAL group were significantly increased under the electron microscope compared with the LPS group and the NGAL-RNAi + LPS group, and the cell proliferation rate and cell viability was significantly higher than unjoined groups (P < 0.0500). CONCLUSION: NGAL knockdown can significantly reduce the level of autophagy and decrease the proliferation rate and viability of cells.The addition of exogenous NGAL can increase the level of autophagy. This suggests that NGAL may play a protective role in the LPS-induced injury of renal tubular epithelial cells by promoting autophagy.

N-cadherin signaling via Trio assembles adherens junctions to restrict endothelial permeability.

Vascular endothelial (VE)-cadherin forms homotypic adherens junctions (AJs) in the endothelium, whereas N-cadherin forms heterotypic adhesion between endothelial cells and surrounding vascular smooth muscle cells and pericytes. Here we addressed the question whether both cadherin adhesion complexes communicate through intracellular signaling and contribute to the integrity of the endothelial barrier. We demonstrated that deletion of N-cadherin (Cdh2) in either endothelial cells or pericytes increases junctional endothelial permeability in lung and brain secondary to reduced accumulation of VE-cadherin at AJs. N-cadherin functions by increasing the rate of VE-cadherin recruitment to AJs and induces the assembly of VE-cadherin junctions. We identified the dual Rac1/RhoA Rho guanine nucleotide exchange factor (GEF) Trio as a critical component of the N-cadherin adhesion complex, which activates both Rac1 and RhoA signaling pathways at AJs. Trio GEF1-mediated Rac1 activation induces the recruitment of VE-cadherin to AJs, whereas Trio GEF2-mediated RhoA activation increases intracellular tension and reinforces Rac1 activation to promote assembly of VE-cadherin junctions and thereby establish the characteristic restrictive endothelial barrier.