The Relationship Between Acute Kidney Injury in Sepsis Patients and Coagulation Dysfunction and Prognosis.

Purpose: The aim of this study was to investigate the relationship between ARF and coagulopathy in patients with sepsis and to explore the prognostic value of these conditions. Patients and Methods: The data of 271 patients with sepsis-associated coagulopathy admitted from June 2021 to June 2022 were reviewed. The patients were divided into a survival group and a nonsurviving group according to patient prognosis. Independent sample t tests were utilized to compare laboratory parameters within 24 hours of admission, as well as the APACHE II and SOFA scores, between the two patient groups. According to the sepsis-associated coagulation dysfunction (SAC) grading criteria for grading, Spearman correlation analysis was used to study the relationship between blood creatinine and SAC grading and assignment scores, and receiver operating characteristic (ROC) curves and Cox's proportional risk regression model were used to explore the factors affecting the prognosis of SAC patients. Results: Spearman correlation analysis revealed strong associations between serum creatinine (Scr) concentration, SAC classification, and SAC score, with coefficients above 0.7. SAC classification outcomes varied significantly with severity: mild severity had a 77.6% survival rate versus 22.4% mortality; moderate severity had 21.5% survival versus 78.5% mortality; and severe cases had a 0.7% survival rate versus 99.3% mortality (P<0.01 for all). Multivariate analysis revealed significant predictors of outcome, including multiple organ dysfunction syndrome (MODS), with an OR of 2.070 (P=0.019); the SOFA score (OR=1.200, P<0.01); the international normalized ratio (INR) (OR=0.72, P=0.013); and the Scr level (OR=0.995, P<0.01). The areas under the ROC curves for the SOFA score, APACHE II score, and SAC classification were >0.8, all P < 0.05. Conclusion: In patients with sepsis, SAC grade 3 or a SAC score of 4 or higher is associated with poorer prognosis, and the interaction of acute kidney injury exacerbates the degree of SAC, consequently affecting prognosis.

To investigate the relationship between acute renal dysfunction and coagulation dysfunction in patients with sepsis and to explore the prognostic value of these conditions. We collected information and laboratory indicators from 271 patients, classified these two groups of patients according to the grading criteria for sepsis-associated coagulation dysfunction (SAC), and compared the differences between them. We utilized Spearman correlation analysis to investigate the relationship between blood creatinine and the severity of sepsis-associated coagulation dysfunction (SAC). Additionally, we employed a Cox proportional hazards regression model to study the factors influencing the prognosis of SAC patients. This study revealed a significant positive correlation between blood creatinine levels and SAC grade. Furthermore, the presence of MODS, INR, blood creatinine, and SOFA score can serve as independent predictive factors for mortality. We can infer that there is a significant correlation between coagulation function parameters and blood creatinine levels, which play a crucial role in the diagnosis and prognostic analysis of sepsis. In patients with sepsis, a higher grade of SAC or an SAC score of 4 or higher indicates a poorer prognosis. Additionally, the interaction with acute kidney injury exacerbates the severity of SAC, thereby impacting patient prognosis.

Predictive value of miR-7110-5p and miR-223-3p as biomarkers for sepsis secondary to pneumonia.

BACKGROUND: Investigating the secondary sepsis of pneumonia is of great significance for rapid diagnosis and early treatment of sepsis. OBJECTIVE: This study aimed to investigate the predictive value of micro ribonucleic acids (miRNA) 7110-5p and miR-223-3p in sepsis secondary to pneumonia. A miRNA microarray was used to analyze the differences in miRNA expression between patients with pneumonia and those with sepsis secondary to pneumonia. METHODS: The study included a total of 50 patients with pneumonia and 42 patients with sepsis secondary to pneumonia. Quantitative polymerase chain reaction analysis was conducted to measure the circulating miRNA expression levels in patients and assess their correlations with clinical characteristics and prognosis. In this study, nine miRNAs - hsa-miR-4689-5p, hsa-miR-4621-5p, hsa-miR-6740-5p, hsa-miR-7110-5p, hsa-miR-765, hsa-miR-940, hsa-miR-213-5p, hsa-miR-223-3p, and hsa-miR-122 - met the screening criteria of having a fold change ⩾ 2 or < 0.5; p< 0.01 indicated significant differences in the results. RESULTS: The expression levels of miR-7110-5p and miR-223-3p differed between the two patient groups, being up-regulated in the plasma of patients with sepsis secondary to pneumonia. miR-7110-5p and miR-223-3p showed higher expression levels in both patients with pneumonia and sepsis compared to healthy controls. Moreover, the receiver operating characteristic curve revealed that the areas under the curve for predicting pneumonia using miR-7110-5p were 0.781 while those for predicting sepsis secondary to pneumonia were 0.862. For miR-223-3p, the corresponding values for predicting pneumonia and sepsis secondary to pneumonia were 0.879 and 0.924, respectively. However, there were no significant differences in the levels of miR-7110-5p and miR-223-3p between the plasma of survived and deceased patients with sepsis. CONCLUSIONS: MiR-7110-5p and miR-223-3p have the potential to serve as biological indicators for predicting sepsis secondary to pneumonia.

Analysis of the fatigue status of medical security personnel during the closed-loop period using multiple machine learning methods: a case study of the Beijing 2022 Olympic Winter Games.

Using machine learning methods to analyze the fatigue status of medical security personnel and the factors influencing fatigue (such as BMI, gender, and wearing protective clothing working hours), with the goal of identifying the key factors contributing to fatigue. By validating the predicted outcomes, actionable and practical recommendations can be offered to enhance fatigue status, such as reducing wearing protective clothing working hours. A questionnaire was designed to assess the fatigue status of medical security personnel during the closed-loop period, aiming to capture information on fatigue experienced during work and disease recovery. The collected data was then preprocessed and used to determine the structural parameters for each machine learning algorithm. To evaluate the prediction performance of different models, the mean relative error (MRE) and goodness of fit (R2) between the true and predicted values were calculated. Furthermore, the importance rankings of various parameters in relation to fatigue status were determined using the RF feature importance analysis method. The fatigue status of medical security personnel during the closed-loop period was analyzed using multiple machine learning methods. The prediction performance of these methods was ranked from highest to lowest as follows: Gradient Boosting Regression (GBM) > Random Forest (RF) > Adaptive Boosting (AdaBoost) > K-Nearest Neighbors (KNN) > Support Vector Regression (SVR). Among these algorithms, four out of the five achieved good prediction results, with the GBM method performing the best. The five most critical parameters influencing fatigue status were identified as working hours in protective clothing, a customized symptom and disease score (CSDS), physical exercise, body mass index (BMI), and age, all of which had importance scores exceeding 0.06. Notably, working hours in protective clothing obtained the highest importance score of 0.54, making it the most critical factor impacting fatigue status. Fatigue is a prevalent and pressing issue among medical security personnel operating in closed-loop environments. In our investigation, we observed that the GBM method exhibited superior predictive performance in determining the fatigue status of medical security personnel during the closed-loop period, surpassing other machine learning techniques. Notably, our analysis identified several critical factors influencing the fatigue status of medical security personnel, including the duration of working hours in protective clothing, CSDS, and engagement in physical exercise. These findings shed light on the multifaceted nature of fatigue among healthcare workers and emphasize the importance of considering various contributing factors. To effectively alleviate fatigue, prudent management of working hours for security personnel, along with minimizing the duration of wearing protective clothing, proves to be promising strategies. Furthermore, promoting regular physical exercise among medical security personnel can significantly impact fatigue reduction. Additionally, the exploration of medication interventions and the adoption of innovative protective clothing options present potential avenues for mitigating fatigue. The insights derived from this study offer valuable guidance to management personnel involved in organizing large-scale events, enabling them to make informed decisions and implement targeted interventions to address fatigue among medical security personnel. In our upcoming research, we will further expand the fatigue dataset while considering higher precisionprediction algorithms, such as XGBoost model, ensemble model, etc., and explore their potential contributions to our research.

Sivelestat ameliorates sepsis-induced myocardial dysfunction by activating the PI3K/AKT/mTOR signaling pathway.

The cardioprotective role of sivelestat, a neutrophil elastase inhibitor, has already been demonstrated, but the underlying molecular mechanism remains unclear. This study aimed to explore the mechanism underlying the role of sivelestat in sepsis-induced myocardial dysfunction (SIMD). We found that sivelestat treatment remarkably improved the viability and suppressed the apoptosis of lipopolysaccharide (LPS)-stimulated H9c2 cells. In vivo, sivelestat treatment was associated with an improved survival rate; reduced serum cTnT, TNF-α, IL-1ß levels and myocardial TNF-α and IL-1ß levels; ameliorated cardiac function and structure; and reduced cardiomyocyte apoptosis. Moreover, sivelestat treatment substantially increased Bcl-2 expression and suppressed caspase-3 and Bax expression in LPS-induced H9c2 cells and in the heart tissues of septic rats. Furthermore, the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway was activated both in vitro and in vivo. The protective effect of sivelestat against SIMD was reversed by the PI3K inhibitor LY294002. In summary, sivelestat can protect against SIMD by activating the PI3K/AKT/mTOR signaling pathway.

Developing an early warning system for detecting sepsis in patients with trauma.

The purpose of this study was to analyse the risk factors for sepsis in patients with trauma and develop a new scoring system for predicting sepsis in patients with trauma based on these risk factors. This will provide a simple and effective early warning method for the rapid and accurate detection and evaluation of the probability of sepsis in patients with trauma to assist in planning timely clinical interventions. We undertook a retrospective analysis of the clinical data of 216 patients with trauma who were admitted to the emergency intensive care unit of the emergency medicine department of the Hebei Medical University Third Hospital, China, between November 2017 and October 2022. We conducted a preliminary screening of the relevant factors using univariate logistic regression analysis and included those factors with a p value of <0.075 in the multivariate logistic regression analysis, from which the risk factors were screened and assigned, and obtained a total score, which was the sepsis early warning score. The incidence of sepsis in patients in the intensive care unit with trauma was 36.9%, and the mortality rate due to sepsis was 19.4%. We found statistically significant differences in several factors for patients with sepsis. The risk factors for sepsis in patients with trauma were the activated partial thromboplastin time, the New Injury Severity Score, growth differentiation factor-15 levels, shock, mechanical ventilation and the Acute Physiology and Chronic Health Evaluation II score. The area under the receiver operating characteristic curve of the sepsis early warning score for predicting sepsis in patients with trauma was 0.725. When the cutoff value of the early warning score was set at 5.0 points, the sensitivity was 69.9% and the specificity was 60.3%. The incidence of sepsis in patients with trauma can be reduced by closely monitoring patients' hemodynamics, implementing adequate fluid resuscitation promptly and by early removal of the catheter to minimize the duration of unnecessary invasive mechanical ventilation. In this study, we found that the use of the sepsis early warning score helped in a more accurate and effective evaluation of the prognosis of patients with trauma.

A biomarker panel of C-reactive protein, procalcitonin and serum amyloid A is a predictor of sepsis in severe trauma patients.

Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients.

Knockdown of histone deacetylase 9 attenuates sepsis-induced myocardial injury and inflammatory response.

Myocardial cell damage is associated with apoptosis and excessive inflammatory response in sepsis. Histone deacetylases (HDACs) are implicated in the progression of heart diseases. This study aims to explore the role of histone deacetylase 9 (HDAC9) in sepsis-induced myocardial injury. Lipopolysaccharide (LPS)-induced Sprague Dawley rats and cardiomyocyte line H9C2 were used as models in vivo and in vitro. The results showed that HDAC9 was significantly upregulated after LPS stimulation, and HDAC9 knockdown remarkably improved cardiac function, as evidenced by decreased left ventricular internal diameter end diastole (LVEDD) and left ventricular internal diameter end systole (LVESD), and increased fractional shortening (FS)% and ejection fraction (EF)%. In addition, HDAC9 silencing alleviated release of inflammatory cytokines (tumor necrosis factor-α (TNF-α), IL-6 and IL-1ß) and cardiomyocyte apoptosis in vivo and in vitro. Furthermore, HDAC9 inhibition was proved to suppress nuclear factor-kappa B (NF-κB) activation with reducing the levels of p-IκBα and p-p65, and p65 nuclear translocation. Additionally, interaction between miR-214-3p and HDAC9 was determined through bioinformatics analysis, RT-qPCR, western blot and dual luciferase reporter assay. Our data revealed that miR-214-3p directly targeted the 3'UTR of HDAC9. Our findings demonstrate that HDAC9 suppression ameliorates LPS-induced cardiac dysfunction by inhibiting the NF-κB signaling pathway and presents a promising therapeutic agent for the treatment of LPS-stimulated myocardial injury.

Vitamin C alleviates LPS-induced myocardial injury by inhibiting pyroptosis via the ROS-AKT/mTOR signalling pathway.

BACKGROUND: The efficacy of vitamin C in sepsis remains controversial. Whether vitamin C can alleviate lipopolysaccharide (LPS)-induced myocardial injury by inhibiting pyroptosis has not been studied. This study aimed to evaluate the effects of vitamin C on LPS-induced myocardial injury in vitro. METHODS: H9C2 cells were treated with indicated concentrations of LPS, and the cell viability was then assessed by CCK-8 assay. The levels of lactate dehydrogenase (LDH), CK-MB, IL-18 and IL-1ß were examined by enzyme-linked immunosorbent assay (ELISA). The levels of intracellular reactive oxygen species (ROS) were measured using the fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA). Western blot assays were conducted to determine the levels of the ROS-associated protein nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) and pyroptosis-associated proteins, such as NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3), caspase-1 and gasdermin D (GSDMD). The AKT inhibitor MK-2206 was then applied to explore the signalling pathway. Finally, H9C2 cells were divided into the control group, LPS group, vitamin C + LPS group, and N-acetyl-L-cysteine (NAC) + LPS group. The intracellular ROS, levels of associated proteins, cell viability, and release of LDH, CK-MB, IL-18 and IL-1ß were examined. RESULTS: LPS decreased cell viability and induced ROS and pyroptosis in H9C2 cells in a dose-dependent manner. Moreover, LPS activated the AKT/mTOR pathway in H9C2 cells. The AKT inhibitor MK-2206 protected H9C2 cells from LPS-induced death by suppressing pyroptosis, without changing intracellular ROS level. Vitamin C significantly inhibited intracellular ROS and cell pyroptosis in LPS-treated H9C2 cells. Moreover, vitamin C suppressed the activation of the AKT/mTOR pathway. CONCLUSIONS: Our data suggest that vitamin C alleviates LPS-induced myocardial injury by inhibiting pyroptosis via the ROS-AKT/mTOR signalling pathway and thus provide novel insights into the prevention of sepsis-induced myocardial dysfunction.

Protective effect of growth differentiation factor 15 in sepsis by regulating macrophage polarization and its mechanism.

This study aims to investigate the protective effect of growth differentiation factor 15 (GDF15) in sepsis by regulating macrophage polarization and its mechanism. The mouse macrophages were cultured and treated with lipopolysaccharide (LPS), and some cells were intervened with GDF15 and LY294002. The proinflammatory activated (M1) macrophages and the anti-inflammatory activated (M2) macrophages were measured and observed, and the messenger RNA expression levels of their biomarkers, phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) were detected. The survival rate, cardiac function, and histopathological sections were observed. In the LPS group, after GDF15 intervention, the percentage of M1 macrophages decreased and M2 macrophages increased, the infiltration of monocytes/macrophages into the heart was inhibited, systemic and cardiac inflammation was reduced, and the survival time of the mice was prolonged. GDF15 regulated macrophage polarization and played an anti-inflammatory role by activating the phosphorylation of the PI3K/Akt signaling pathway. In patients with sepsis, the serum GDF15 level increased and was closely related to the severity of the sepsis and the 28-day mortality rate and could be used as a prognostic marker of sepsis. GDF15 regulates macrophage polarization through activating the PI3K/Akt signaling pathway and has a protective effect on survival and the cardiac function of patients with sepsis and sepsis mouse models. The increase in serum GDF15 level is closely related to severity and mortality in patients with sepsis and is therefore a prognostic marker of sepsis.

An analysis of the treatment effect of two modes of oxygenation on patients with radiation pneumonia complicated by respiratory failure.

BACKGROUND: Stereotactic radiotherapy (SBRT) is widely used in the treatment of thoracic cancer. OBJECTIVE: To evaluate the efficacy of a non-rebreather mask (NRBM) and high-flow nasal cannula (HFNC) in patients with radiation pneumonia complicated with respiratory failure. METHODS: This was a single-center randomized controlled study. Patients admitted to the EICU of the Fourth Hospital of Hebei Medical University were selected and divided into NRBM and HFNC group. Arterial blood gas analysis, tidal volume, respiratory rates and the cases of patients receiving invasive assisted ventilation were collected at 0, 4, 8, 12, 24, 48, and 72 h after admission. RESULTS: (1) The PaO2/FiO2, respiratory rates, and tidal volume between the two groups at 0, 4, 8, 12, 24, 48, and 72 h were different, with F values of 258.177, 294.121, and 134.372, all P< 0.01. These indicators were different under two modes of oxygenation, with F values of 40.671, 168.742, and 55.353, all P< 0.01, also varied with time, with an F value of 7.480, 9.115, and 12.165, all P< 0.01. (2) The incidence of trachea intubation within 72 h between HFNC and NRBM groups (23 [37.1%] vs. 34 [54.0%], P< 0.05). The transition time to mechanical ventilation in the HFNC and NRBM groups (55.3 ± 3.2 h vs. 45.9 ± 3.6 h, P< 0.05). (3) The risk of intubation in patients with an APACHE-II score > 23 was 2.557 times than score ⩽ 23, and the risk of intubation in the NRBM group was 1.948 times more than the HFNC group (P< 0.05). CONCLUSION: Compared with the NRBM, HFNC can improve the oxygenation state of patients with radiation pneumonia complicated with respiratory failure in a short time, and reduce the incidence of trachea intubation within 72 h.

Retrospective Analysis of the Clinical Efficacy of Early Goal-Directed Therapy Combined with Meticulous Nursing Intervention in Patients with Posttraumatic Sepsis.

Objective: To explore the intervention effect of early goal-directed therapy (EGDT) combined with meticulous nursing on patients with posttraumatic sepsis. Methods: The data of 50 patients with posttraumatic sepsis undergoing EGDT in the emergency department of our hospital from January 2020 to December 2020 were retrospectively analyzed. According to different nursing methods, they were divided into control group (n = 25) with routine nursing measures and observation group (n = 25) with meticulous nursing measures. The application effect of the two nursing modes was scientifically evaluated. Results: No statistical differences in general data were found between the two groups (P > 0.05). After 6 h of intervention, the circulatory function, oxygenation function, and renal function of both groups were better than those before intervention, and central venous pressure (CVP), mean arterial pressure (MAP), blood oxygen (PaO2), oxygenation index (PaO2/FiO2), central venous oxygen saturation (ScvO2), and urine volume in the observation group were notably higher than those in the control group (P < 0.05). The heart rate (HR), serum creatinine (SCr), and blood lactic acid in the observation group were notably lower than those in the control group (P < 0.05). The 28-day survival rate and quality of life after intervention in the observation group were notably higher than those in the control group, with obvious differences between the two groups (P < 0.05). Conclusion: Meticulous nursing intervention for patients with posttraumatic sepsis undergoing EGDT can effectively improve the body's functional indexes, which is superior to the routine nursing in controlling the patients' condition, improving the survival rate and quality of life after intervention, and ensuring the clinical treatment effect. Therefore, it is worthy of promotion.

Application Evaluation of High-Flow Humidified Oxygen in Patients with Respiratory Failure after General Anesthesia Extubation for Multiple Injuries.

Objective: To explore the effect of high-flow humidified oxygen therapy (HFNC) on patients with respiratory failure after general anesthesia extubation for multiple injuries. Methods: 214 patients with multiple injuries in our hospital who underwent general anesthesia and suffered respiratory failure after weaning extubation and received sequential treatment were included. And, they were divided into control group (HFNC group) and observation group (NIMV group) according to the random number table method. Patients in the control group (125 cases) used high-flow nasal cannula (HFNC) after general anesthesia extubation, while patients in the observation group (89 cases) used NIMV. The respiratory rate, heart rate, finger pulse oxygen, oxygenation index (PaO2/FiO2), and re-tracheal intubation rate in the two groups were compared at 2, 8, and 24 hours after sequential treatment, and the mortality rate and hospital stay of ICU time were whole-course observation. And, the effect of conventional oxygen inhalation or HFNC on oxygenation and prognosis was analyzed. Then, SPSS21.0 software was applied for statistical analysis. To analyze the effect of conventional oxygen inhalation or HFNC on the improvement of oxygenation and prognosis, the receiver operating characteristic (ROC) curve can be used to evaluate the feasibility and treatment effect of high-flow nasal oxygen therapy (HFNC) for patients with respiratory failure after general anesthesia extubation for multiple injuries. Results: Compared with the NIMV group, the respiratory frequency and heart rate of the HFNC group were significantly improved after 2 h, 8 h, and 24 h. At the same time, the finger pulse oxygen and oxygenation index increased significantly and returned to normal levels. HFNC can significantly reduce the reintubation rate, ICU hospital stay, and mortality rate. The area under the ROC curve was 0.9102, with 95% CI (0.8256, 0.9949) and P < 0.0001. Conclusion: For patients with multiple injuries undergoing general anesthesia and respiratory failure after weaning and extubation, the application of HFNC can moderate patients' heart rate and respiratory rate faster, increase oxygenation index and finger pulse oxygen, and reduce the reintubation rate, mortality rate, and ICU stay. At the same time, it can effectively improve the respiratory failure of patients after extubation and reduce the occurrence of complications.

miR­214 ameliorates sepsis­induced acute kidney injury via PTEN/AKT/mTOR­regulated autophagy.

Previous studies have suggested that oxidative stress and autophagy results in acute kidney injury (AKI) during sepsis and microRNA (miR)­214 serves a vital role in the protection of kidneys subjected to oxidative stress. The present study aimed to test whether the renoprotection of miR­214 is related to autophagy in sepsis. The role of autophagy was investigated in a mouse model of cecal ligation and puncture (CLP). Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) was used to analyze the expression of miR­214. The structure and function of kidneys harvested from the mice were evaluated. Kidney autophagy levels were detected with immunohistochemical, immunofluorescent and western blotting. It was found that miR­214 could alleviate AKI in septic mice by inhibiting the level of kidney autophagy. Furthermore, miR­214 inhibited autophagy by silencing PTEN expression in the kidney tissues of septic mice. These findings indicated that miR­214 ameliorated CLP­induced AKI by reducing oxidative stress and inhibiting autophagy through the regulation of the PTEN/AKT/mTOR pathway.

Circ_0091702 relieves lipopolysaccharide (LPS)-induced cell injury by regulating the miR-182/PDE7A axis in sepsis.

Circular RNA plays an important role in the progression of sepsis. Circ_0091702 has been found to be an important regulator of sepsis progression, so its role and mechanism in sepsis progression deserve to be further explored. Lipopolysaccharide (LPS) could suppress cell viability, while enhance cell apoptosis and inflammation to induce cell injury. Circ_0091702 was downregulated in LPS-induced HK2 cells, and its overexpression alleviated LPS-induced cell injury. MiR-182 could be sponged by circ_0091702. Moreover, miR-182 inhibitor could relieve LPS-induced cell injury, and its overexpression also reversed the inhibition of circ_0091702 on LPS-induced cell injury. PDE7A was a target of miR-182, and its expression was reduced in LPS-induced HK2 cells. Additionally, silencing of PDE7A reversed the suppressive effect of circ_0091702 on LPS-induced cell injury. Our data suggested that circ_0091702 sponged miR-182 to regulate PDE7A, thereby alleviating LPS-induced cell injury in sepsis.

A competing endogenous RNA network reveals key lncRNAs associated with sepsis.

BACKGROUND: This study set out to determine key lncRNAs correlated with sepsis via constructing competing endogenous RNA (ceRNA) network. METHODS: Three septic patients and three healthy controls were recruited to obtain lncRNA profiles in this current study. Combined with the mRNA profiles by RNA-sequencing, an integrated analysis of mRNA expression profiles downloaded from GEO was performed to obtain the differentially expressed mRNAs (DEmRNAs). Based on differentially expressed lncRNAs (DElncRNAs) and DEmRNAs acquired in this present study and differentially expressed miRNAs (DEmiRNAs) acquired in previous study, a ceRNA network was constructed. Furthermore, LINC00963 was validated in THP-1 cells by performing loss of function assays. RESULTS: In this analysis, a total of 290 DEmRNAs and 46 DElncRNAs were detected in sepsis. Parkinson's disease, Oxidative phosphorylation and Cardiac muscle contraction were significantly enriched KEGG pathways in sepsis. XPO1, CUL4A, and NEDD8 were three hub proteins of sepsis-specific PPI network. A ceRNA network, which contained 16 DElncRNA-DEmiRNA pairs and 82 DEmiRNA-DEmRNA pairs, involving 5 lncRNAs, 10 miRNAs, and 60 mRNAs, was obtained. The function experiments indicated that knockdown of LINC00963 could promote cell proliferation, reduce cytokine expression, and suppress inflammasome activation and phagocytosis in LPS-induced THP-1 cells. CONCLUSION: This study determined key lncRNAs involved in sepsis, which may contribute to the development for novel treatment strategy of sepsis.

Autophagy participates in the protection role of 1,25-dihydroxyvitamin D3 in acute myocardial infarction via PI3K/AKT/mTOR pathway.

Vitamin D deficiency is associated with acute myocardial infarction (AMI); thus we aimed to explore improvement effects of 1,25-dihydroxyvitamin D3 (VD3) on the AMI and its potential mechanism. AMI models were constructed using male C57/BL6J mice and randomly treated with normal saline or VD3, using sham rats as control. Heart functions, myocardial damage, apoptosis, and inflammation were evaluated. Cardiomyocytes isolated from 3-day-old suckling mice were used for in vitro verification. After VD3 treatment, AMI-induced cardiac dysfunction was reversed with better cardiac function parameters. VD3 treatment reduced inflammatory cell infiltration and myocardial infarction area accompanied by the reduction of inflammatory factors and myocardial infarction markers compared with the AMI group. VD3 treatment obviously alleviated AMI-induced myocardial apoptosis, along with Bcl-2 upregulation and downregulation of caspase-3, caspase-9, and Bax. Both in vivo and in vitro experiments revealed that VD3 enhanced the expression of LC3II and Beclin-1 and decreased soluble p62. Furthermore, VD3 enhanced the AMI-caused inhibition of PI3K, p-AKT, and p-mTOR expression, which was conversely reversed by the addition of 3-methyladenine in vitro. The study highlights the improvement effects of VD3 on cardiac functions. We proposed a potential mechanism that VD3 protects against myocardial damage, inflammation, and apoptosis by promoting autophagy through PI3K/AKT/mTOR pathway.

miR-214-3p Attenuates Sepsis-Induced Myocardial Dysfunction in Mice by Inhibiting Autophagy through PTEN/AKT/mTOR Pathway.

Aims. More than half of the patients with sepsis would develop cardiac dysfunction, which is termed as sepsis-induced myocardial dysfunction (SIMD). Previous studies suggest that autophagy may play an important role in SIMD. The present study investigated whether miR-214-3p could attenuate SIMD by inhibiting autophagy. Main Methods. In this article, we investigated the role of autophagy in a mouse model of cecal ligation and puncture (CLP). The structure and function of hearts harvested from the mice were evaluated. Myocardial autophagy levels were detected with immunohistochemical, immunofluorescent, and Western blot. Key Findings. miR-214-3p can alleviate SIMD in septic mice by inhibiting the level of cardiac autophagy to attenuate myocardial dysfunction. Moreover, this study showed that miR-214-3p inhibited autophagy by silencing PTEN expression in the myocardial tissues of septic mice. Significance. This study showed that miR-214-3p attenuated SIMD through myocardial autophagy inhibition by silencing PTEN expression and activating the AKT/mTOR pathway. The present findings supported that miR-214-3p may be a potential therapeutic target for SIMD.

Screening key genes and microRNAs in sepsis by RNA-sequencing.

BACKGROUND: Sepsis is a life-threatening organ dysfunction, initiated by a dysregulated host response to infection. This study aimed to determine key genes and microRNAs (miRNAs) correlated with sepsis. METHODS: Three patients with sepsis and three healthy individuals treated as controls were recruited in the current study. To identify differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) between patients with sepsis and controls, RNA-sequencing and bioinformatics analysis were conducted. DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. Dataset GSE46955, used to validate the expression of selected DEmRNAs, was downloaded from the Gene Expression Omnibus database. RESULTS: Compared with septic patients, a total of 1199 DEmRNAs and 23 DEmiRNAs were identified. Based on DEmiRNA-target DEmRNAs analysis, hsa-miR-106b-5p (degree = 155), hsa-miR-128-3p (degree = 128), and hsa-miR-144-3p (degree = 79) were the top 3 DEmiRNAs that covered most DEmRNAs. The T cell receptor signaling pathway, pathways in cancer, FoxO signaling pathway, and influenza A were the significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways of DEmiRNA-target DEmRNAs in sepsis. CONCLUSION: We identified key genes and miRNAs related to sepsis. Our findings will provide new insights into understanding sepsis pathogenesis.

Protective Effects of Erythropoietin towards Acute Lung Injuries in Rats with Sepsis and Its Related Mechanisms.

The aim of this study was to explore the effects of erythropoietin (EPO) in acute lung injuries in rats with sepsis. 127 male SD rats were divided into 3 groups (n=8): group Sham, group ALI (sepsis-caused lung injury), group EPO (EPO intervention). The blood gas analysis, C-reactive protein level (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10 were detected and compared. The water content fraction and myeloperoxidase (MPO) activities, apoptosis, and expression level of nuclear factor -κB (NF-κB p65) in lung tissues were also detected. Compared to group Sham, the oxygenation index of group ALI was decreased (140.66±12.82 vs. 194.7±16.36), CRP (peak value: 2.31±0.33 mg/L vs. 1.00±0.16 mg/L), IL-10 (peak value: 711.26±84.97 ng/L vs. 51.21±11.45 ng/L), TNF-a (63.69±6.85 ng/L vs. 12.92±0.91 ng/L), and IL-6 (peak value: 1768.93±195.11 ng/L vs. 68.71±11.48 ng/L) increased (P<0.01), and the lung cell apoptosis and expression of NF-κB p65 (302.75±51.38 vs. 121.46±11.79) were also increased (P<0.01), and there was a recovery of EPO group (P<0.01). Group ALI exhibited pulmonary interstitial and alveolar edema, hemorrhage, and lung collapse, but the EPO intervention significantly reduced the above lung pathological changes (the water content was 70.36±1.24% in Sham group, 84.26±3.07% in ALI group and 75.72±1.96% in EPO group, P<0.01; MPO: 2.23±0.67, 7.56±1.02, 5.73±0.86, P<0.01; apoptotic index: 3.73±0.39, 25.69±4.54, 9.59±2.59, P<0.01). EPO could inhibit the expression of NF-κB in lung tissues, inhibit the levels of proinflammatory cytokines TNF-a and IL-6, but improve the level of anti-inflammatory cytokine IL-10, thus reducing the pathological changes of lung tissues and producing protective effects towards lung tissues.