Focus on the role of calcium signaling in ferroptosis: a potential therapeutic strategy for sepsis-induced acute lung injury.

By engaging in redox processes, ferroptosis plays a crucial role in sepsis-induced acute lung injury (ALI). Although iron stimulates calcium signaling through the stimulation of redox-sensitive calcium pathways, the function of calcium signals in the physiological process of ferroptosis in septic ALI remains unidentified. Iron homeostasis disequilibrium in ferroptosis is frequently accompanied by aberrant calcium signaling. Intracellular calcium overflow can be a symptom of dysregulation of the cellular redox state, which is characterized by iron overload during the early phase of ferroptosis. This can lead to disruptions in calcium homeostasis and calcium signaling. The mechanisms controlling iron homeostasis and ferroptosis are reviewed here, along with their significance in sepsis-induced acute lung injury, and the potential role of calcium signaling in these processes is clarified. We propose that the development of septic acute lung injury is a combined process involving the bidirectional interaction between iron homeostasis and calcium signaling. Our goal is to raise awareness about the pathophysiology of sepsis-induced acute lung injury and investigate the relationship between these mechanisms and ferroptosis. We also aimed to develop calcium-antagonistic therapies that target ferroptosis in septic ALI and improve the quality of survival for patients suffering from acute lung injury.

The U-shaped association between serum osmolality and 28-day mortality in patients with sepsis: a retrospective cohort study.

BACKGROUND: Sepsis is a recognized global health challenge that places a considerable disease burden on countries. Although there has been some progress in the study of sepsis, the mortality rate of sepsis remains high. The relationship between serum osmolality and the prognosis of patients with sepsis is unclear. METHOD: Patients with sepsis who met the criteria in the Medical Information Mart for Intensive Care IV database were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined using multivariable Cox regression. The relationship between serum osmolality and the 28-day mortality risk in patients with sepsis was investigated using curve fitting, and inflection points were calculated. RESULTS: A total of 13,219 patients with sepsis were enrolled in the study; the mean age was 65.1 years, 56.9 % were male, and the 28-day mortality rate was 18.8 %. After adjusting for covariates, the risk of 28-day mortality was elevated by 99% (HR 1.99, 95%CI 1.74-2.28) in the highest quintile of serum osmolality (Q5 >303.21) and by 59% (HR 1.59, 95%CI 1.39-1.83) in the lowest quintile (Q1 ≤285.80), as compared to the reference quintile (Q3 291.38-296.29). The results of the curve fitting showed a U-shaped relationship between serum osmolality and the risk of 28-day mortality, with an inflection point of 286.9 mmol/L. CONCLUSION: There is a U-shaped relationship between serum osmolality and the 28-day mortality risk in patients with sepsis. Higher or lower serum osmolality is associated with an increased risk of mortality in patients with sepsis. Patients with sepsis have a lower risk of mortality when their osmolality is 285.80-296.29 mmol/L.

Relationship between an ageing measure and chronic obstructive pulmonary disease, lung function: a cross-sectional study of NHANES, 2007-2010.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a disease associated with ageing. However, actual age does not accurately reflect the degree of biological ageing. Phenotypic age (PhenoAge) is a new indicator of biological ageing, and phenotypic age minus actual age is known as phenotypic age acceleration (PhenoAgeAccel). This research aimed to analyse the relationship between PhenoAgeAccel and lung function and COPD. DESIGN: A cross-sectional study. PARTICIPANTS: Data for the study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. We defined people with forced expiratory volume in 1 s/forced vital capacity <0.70 after inhaled bronchodilators as COPD and the rest of the population as non-COPD. Adults aged 40 years or older were enrolled in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Linear and logistic regression were used to investigate the relationship between PhenoAgeAccel, lung function and COPD. Subgroup analysis was performed by gender, age, ethnicity and smoking index COPD. In addition, we analysed the relationship between the smoking index, respiratory symptoms and PhenoAgeAccel. Multiple models were used to reduce confounding bias. RESULTS: 5397 participants were included in our study, of which 1042 had COPD. Compared with PhenoAgeAccel Quartile1, Quartile 4 had a 52% higher probability of COPD; elevated PhenoAgeAccel was also significantly associated with reduced lung function. Further subgroup analysis showed that high levels of PhenoAgeAccel had a more significant effect on lung function in COPD, older adults and whites (P for interaction <0.05). Respiratory symptoms and a high smoking index were related to higher indicators of ageing. CONCLUSIONS: Our study found that accelerated ageing is associated with the development of COPD and impaired lung function. Smoking cessation and anti-ageing therapy have potential significance in COPD.

The association between sleep duration, respiratory symptoms, asthma, and COPD in adults.

Introduction: The association between sleep duration and cough, wheezing, and dyspnea was unclear. This research aimed to test this relationship. Methods: Research data were obtained from people who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. We used weighted logistic regression analysis and fitted curves to explore the association between sleep and respiratory symptoms. In addition, we investigated the association between sleep duration, chronic obstructive pulmonary disease (COPD), and asthma. The stratified analysis is used to analyze inflection points and specific populations. Results: The 14,742 subjects are weighted to reflect the 45,678,491 population across the United States. Weighted logistic regression and fitted curves show a U-shaped relationship between sleep duration and cough and dyspnea. This U-shaped relationship remained in people without COPD and asthma. The stratified analysis confirmed that sleep duration before 7.5 h was negatively associated with cough (HR 0.80, 95% CI 0.73-0.87) and dyspnea (HR 0.82, 95% CI 0.77-0.88). In contrast, it was positively associated with cough and (HR 1.30, 95% CI 1.14-1.48) dyspnea (HR 1.12, 95% CI 1.00-1.26) when sleep duration was >7.5 h. In addition, short sleep duration is associated with wheezing, asthma, and COPD. Conclusion: Both long and short sleep duration are associated with cough and dyspnea. And short sleep duration is also an independent risk factor for wheezing, asthma, and COPD. This finding provides new insights into the management of respiratory symptoms and diseases.

The association between lactate dehydrogenase to serum albumin ratio and the 28-day mortality in patients with sepsis-associated acute kidney injury in intensive care: a retrospective cohort study.

BACKGROUND: The mortality rate of patients with sepsis-associated acute kidney injury (SA-AKI) in the intensive care unit (ICU) is high, and there is a need for early identification of SA-AKI patients with poor prognoses. This study investigated the relationship between the lactate dehydrogenase to serum albumin ratio (LAR) and prognosis in patients with SA-AKI. METHODS: We performed a retrospective cohort study of patients with SA-AKI who are represented in the Medical Information Mart for Intensive Care IV (MIMIC-IV). We used multivariable Cox regression analysis to determine adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analysis, survival curves, and curve fitting were used to evaluate a connection between the LAR and prognosis in patients with SA-AKI. RESULTS: There were a total of 6453 participants in this research. The average age of the participants was 63.9 ± 16.1 years, and the average LAR was 11.0 (7.6, 17.7)/IU/g. After controlling for variables, the HRs for 28-day mortality were 1.20 (HR: 1.20, 95% CI: 1.05-1.38, p = 0.008) and 1.61 (HR: 1.61, 95% CI: 1.41-1.84, p < 0.001) for Tertile 2 (T2, 8.59≤ LAR< 14.66) and Tertile 3 (T3, LAR ≥ 14.66), respectively, compared to Tertile 1 (T1, LAR < 8.59). The outcomes for 90-day mortality and in-hospital death rate were comparable. The Kaplan-Meier (KM) analysis revealed that the group with greater LAR had higher 28-day and 90-day death rates. CONCLUSION: Our study shows that LAR is associated with poor prognosis in patients with SA-AKI. Higher LAR is associated with higher 28-day, 90-day, and in-hospital mortality.

Association between B-vitamins intake and frailty among patients with chronic obstructive pulmonary disease.

PURPOSE: Gain insight into the impact of B vitamins, including vitamin B1, vitamin B2, niacin, vitamin B6, total folate, and vitamin B12 on the risk of frailty in patients with chronic obstructive pulmonary disease (COPD). METHODS: This study was an American population-based cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). A total of 1201 COPD patients were included in the analysis. Of these, the intake of B vitamins was determined by the two 24-h recall interviews. We followed the method constructed by Hakeem et al. to calculate the frailty index (FI), which is used as a reliable tool to assess the debilitating status of patients with COPD. Missing data were imputed by the MissForest method based on random forests. Multivariate logistic regression model and inverse probability weighted based on propensity scores were used to correct for confoundings. RESULTS: Logistic regression models showed that vitamin B6 intake was negatively correlated with frailty risk in COPD patients, while other B vitamins including B1, B2, niacin (vitamin B3), total folic acid and vitamin B12 were not. After adjusting for covariates, the association between vitamin B6 and frailty risk (adjusted OR = 0.80, 95%CI = 0.66-0.95, P = 0.013) remained significant. At the same time, sensitivity analysis proves the robustness of the results. CONCLUSION: COPD patients with lower vitamin B6 intake have a higher risk of frailty. However, intake of vitamin B1, B2, niacin, total folic acid, and vitamin B12 was not associated with frailty risk in COPD patients.

Association of serum total bilirubin and potential predictors with mortality in acute respiratory failure: A retrospective cohort study.

BACKGROUND: Total serum bilirubin (TBIL) levels are a risk factor in critically ill patients. However, the relationship between the dynamics of TBIL and the prognosis of acute respiratory failure (ARF) patients is unclear. OBJECTIVES: This study aimed to investigate the impact of different levels of TBIL during hospitalization on mortality in ARF patients. METHODS: This study used a retrospective cohort study. We extracted information on ARF patients from the Medical Information Bank for Intensive Care (MIMIC)-III (version 1.4). We used propensity score matching (PSM) to adjust for the level of potential baseline-level differences between groups. Cox regression was used to analyze mortality risk factors in patients with ARF. Subgroup analysis was used to explore special populations. RESULTS: 2673 patients were included in the study, and 19.7% developed hyperbilirubinemia (TBIL ≥ 2 mg/dL) during their hospitalization. After PSM, multivariate Cox regression showed a 50% and 135% increased risk of death for a maximum value of TBIL ≥ 5 mg/dL and minimum value of TBIL ≥ 2 mg/dL during hospitalization, respectively, compared to the control population. In addition, age ≥ 65 years, previous comorbid malignancies, respiratory rate ≥ 22 beats/min, SpO2 ≥ 95, BUN ≥ 20 mg/dL, lactate ≥ 5 mmol/L, platelet < 100 * 10 ^ 9/L were independent risk factors for 1-year mortality in ARF patients. Subgroup analysis showed that high bilirubin had a greater effect on patients aged less than 65 years (P for interaction < 0.05). CONCLUSIONS: Hyper TBIL (TBIL max ≥ 5 mg/dL or TBIL min ≥ 2 mg/dL) was an independent risk factor for 1-year mortality in patients with ARF. This study suggests that clinicians should be aware of TBIL levels and intervene early in these patients.

Cr3X4 (X = Se, Te) monolayers as a new platform to realize robust spin filters, spin diodes and spin valves.

Two-dimensional ferromagnetic (FM) half-metals are promising candidates for advanced spintronic devices with small size and high capacity. Motivated by a recent report on controlling the synthesis of FM Cr3Te4 nanosheets, herein, to explore their potential application in spintronics, we designed spintronic devices based on Cr3X4 (X = Se, Te) monolayers and investigated their spin transport properties. We found that the Cr3Te4 monolayer based device shows spin filtering and a dual-spin diode effect when applying a bias voltage, while the Cr3Se4 monolayer is an excellent platform to realize a spin valve. These different transport properties are primarily ascribed to the semiconducting spin channel, which is close to and away from the Fermi level in Cr3Te4 and Cr3Se4 monolayers, respectively. Interestingly, the current in the Cr3Se4 monolayer based device also displays a negative differential resistance effect (NDRE) and a high magnetoresistance ratio (up to 2 × 103). Moreover, we found a thermally induced spin filtering effect and a NDRE at the Cr3Se4 junction under a temperature gradient instead of a bias voltage. These theoretical findings highlight the potential of Cr3X4 (X = Se, Te) monolayers in spintronic applications and put forward realistic materials to realize nanoscale spintronic devices.

The Association of Renin-Angiotensin System Blockades and Mortality in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Acute Respiratory Failure: A Retrospective Cohort Study.

Background: Acute respiratory failure (ARF) is a common cause of admission to the intensive care unit (ICU) for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There is still a lack of effective interventions and treatments. ACE inhibitors (ACEI)/ angiotensin II receptor blockers (ARB) were effective in COPD patients. We aimed to study the effect of ACEI/ARB use on AECOPD combined with ARF and evaluate the effect of in-hospital continuation of medication. Methods: We included patients with AECOPD and ARF from the Medical Information Bank for Intensive Care (MIMIC-III) database. MIMIC III is a large cohort database from Boston, USA. Patients were divided into two groups according to the use of ACEI/ARB before admission. Propensity score matching (PSM) was used to reduce potential bias between the two groups. Cox regression and Kaplan-Meier curves compared 30-day mortality in ACEI/ARB users and non-users. We also defined and analyzed the use of in-hospital ACEI/ARB. Multiple models were used to ensure the robustness of the findings. Subgroup analysis was used to analyze the variability between groups. Results: A total of 544 patients were included in the original study. After PSM, 256 patients were included in the matched cohort. Multivariate Cox regression showed 30-day mortality was significantly lower in ACEI/ARB users compared with controls (HR = 0.50, 95% CI: 0.29-0.86, p= 0.013). In PSM and inverse probability-weighted models, the results are stable Continued in-hospital use of ACEI/ARB remains effective (HR 0.40, 95% CI 0.22-0.74, p = 0.003). Kaplan-Meier showed a significant difference in survival between the two groups. Conclusion: This study found that pre-hospital ACEI/ARB use was associated with reduced mortality in patients with AECOPD and ARF.

The Association Between Mean Corpuscular Hemoglobin Concentration and Prognosis in Patients with Acute Pulmonary Embolism: A Retrospective Cohort Study.

INTRODUCTION: Acute pulmonary embolism (APE) is a typical cardiovascular emergency worldwide. Mean hemoglobin concentration (MCHC) is a standard indicator of anemia. Studies on the association between MCHC and APE are scarce. We aimed to investigate the relationship between MCHC and APE. METHODS: Clinical data were extracted from the Medical Information Bank for Intensive Care (MIMIC)-III. Adult (≥18 years) patients with APE admitted for the first time were included in this study. An analysis was conducted to evaluate the association between MCHC and the prognosis of patients by the Cox regression analysis, generalized additives models and Kaplan-Meier survival curves. The primary outcome was 30-day mortality, and the secondary outcomes were 1-year and 3-year mortality. RESULTS: A total of 813 patients who met the selection criteria were enrolled, of whom 130 (16.0%) died within 30 days of admission. Univariate Cox regression indicated that MCHC was significantly associated with mortality (30-day: HR = 0.74, 95% CI = 0.66-0.82, P < 0.001; 1-year: HR = 0.80, 95% CI = 0.74-0.86, P < 0.001; 3-year: HR = 0.82, 95% CI = 0.77-0.88, P < 0.001). MCHC remains stable after adjusting multiple models. Kaplan-Meier survival curves showed that patients with lower MCHC had a poorer 30-day prognosis. CONCLUSIONS: Lower MCHC is an independent risk factor for increased mortality in patients with APE. As an inexpensive biomarker, MCHC should receive more attention.

A novel prognostic signature for lung adenocarcinoma based on cuproptosis-related lncRNAs: A Review.

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease with complex pathogenesis, high mortality, and poor prognosis. Cuproptosis is a new type of programmed cell death triggered by copper accumulation that may play an important role in cancer. LncRNAs are becoming valuable prognostic factors in cancer patients. The effect of cuproptosis-related lncRNAs (CRlncRNAs) on LUAD has not been clarified. Based on the Cancer Genome Atlas database, CRlncRNAs were screened by co-expression analysis of cuproptosis- related genes and lncRNAs. Using CRlncRNAs, Cox and LASSO regression analyses constructed a risk prognostic model. The predictive efficacy of the model was assessed and validated using survival analysis, receiver operating characteristic curve, univariate and multifactor Cox regression analysis, and principal component analysis. A nomogram was constructed and calibration curves were applied to enhance the predictive efficacy of the model. Tumor Mutational Burden analysis and chemotherapeutic drug sensitivity prediction were performed to assess the clinical feasibility of the risk model. The novel prognostic signature consisted of 5 potentially high-risk CRlncRNAs, MAP3K20-AS1, CRIM1-DT, AC006213.3, AC008035.1, and NR2F2-AS1, and 5 potentially protective CRlncRNAs, AC090948.1, AL356481.1, AC011477.2, AL031600.2, and AC026355.2, which had accurate and robust predictive power for LUAD patients. Collectively, the novel prognostic signature constructed based on CRlncRNAs can effectively assess and predict the prognosis of patients and provide a new perspective for the diagnosis and treatment of LUAD.

Causal Effects of Genetically Predicted Iron Status on Sepsis: A Two-Sample Bidirectional Mendelian Randomization Study.

Background/Aim: Several observational studies showed a significant association between elevated iron status biomarkers levels and sepsis with the unclear direction of causality. A two-sample bidirectional mendelian randomization (MR) study was designed to identify the causal direction between seven iron status traits and sepsis. Methods: Seven iron status traits were studied, including serum iron, ferritin, transferrin saturation, transferrin, hemoglobin, erythrocyte count, and reticulocyte count. MR analysis was first performed to estimate the causal effect of iron status on the risk of sepsis and then performed in the opposite direction. The multiplicative random-effects and fixed-effects inverse-variance weighted, weighted median-based method and MR-Egger were applied. MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran's Q statistic methods were used to assess heterogeneity and pleiotropy. Results: Genetically predicted high levels of serum iron (OR = 1.21, 95%CI = 1.13-1.29, p = 3.16 × 10-4), ferritin (OR = 1.32, 95%CI = 1.07-1.62, p =0.009) and transferrin saturation (OR = 1.14, 95%CI = 1.06-1.23, p = 5.43 × 10-4) were associated with an increased risk of sepsis. No significant causal relationships between sepsis and other four iron status biomarkers were observed. Conclusions: This present bidirectional MR analysis suggested the causal association of the high iron status with sepsis susceptibility, while the reverse causality hypothesis did not hold. The levels of transferrin, hemoglobin, erythrocytes, and reticulocytes were not significantly associated with sepsis. Further studies will be required to confirm the potential clinical value of such a prevention and treatment strategy.

Identification of Mucus-Associated Molecular Subtypes of Chronic Obstructive Pulmonary Disease: A Latent Profile Analysis Based on MUC5B-Associated Genes.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a disease with high heterogeneity, which is a major challenge in clinical individualized treatment. A mucus phenotype is one of the main characteristics of COPD. MATERIAL AND METHODS Gene expression profiles of lung tissue samples were from the Lung Genomics Research Consortium. MUC5B-associated gene signatures were obtained based on a nonlinear feature screening algorithm. These signatures were used to fit a latent profile analysis (LPA) model to identify COPD molecular subtypes and build a subtype classifier to verify the subtypes. Then, we explored the characteristics of cilium assembly and beating signatures, transcriptome features, immune infiltration among the 3 subtypes by xCell, single-sample gene set enrichment analysis, network perturbation amplitude, and weighted gene co-expression network analysis algorithms. An external dataset was used to verify the above COPD subtypes. RESULTS Three subtypes associated with mucus were identified by LPA and verified in an external dataset. Subtype 1 displayed higher T helper type 1 (Th1) and basophil infiltration, higher Th17/regulatory T cells (Tregs) ratio, a higher level of cilium assembly and beating, and lower mast cell and Treg infiltration. The subtypes 2 and 3 demonstrated higher macrophage M2 infiltration in lung tissue, while subtype 3 had higher neutrophil and eosinophil infiltration than subtype 2. CONCLUSIONS Overall, this work identified 3 mucus-associated molecular subtypes related to MUC5B expression, which deepens the understanding of airway mucus secretion in COPD and potentially provides valuable information for precision therapy.

Identification of Metabolism-Associated Molecular Subtypes of Chronic Obstructive Pulmonary Disease.

Purpose: This study aimed to identify the COPD molecular subtypes reflecting pulmonary function damage on the basis of metabolism-related gene expression, which provided the opportunity to study the metabolic heterogeneity and the association of metabolic pathways with pulmonary function damage. Methods: Univariate linear regression and the Boruta algorithm were used to select metabolism-related genes associated with forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) in the Evaluation of COPD to Longitudinally Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. COPD subtypes were further identified by consensus clustering with best-fit. Then, we analyzed the differences in the clinical characteristics, metabolic pathways, immune cell characteristics, and transcription features among the subtypes. Results: This study identified two subtypes (C1 and C2). C1 exhibited higher levels of lower pulmonary function and innate immunity than C2. Ten metabolic pathways were confirmed as key metabolic pathways. The pathways related to N-glycan, hexosamine, purine, alanine, aspartate and glutamate tended to be positively associated with the abundance of adaptive immune cells and negatively associated with the abundance of innate immune cells. In addition, other pathways had opposite trends. All results were verified in Genetic Epidemiology of COPD (COPDGene) datasets. Conclusion: The two subtypes reflect the pulmonary function damage and help to further understand the metabolic mechanism of pulmonary function in COPD. Further studies are needed to prove the prognostic and therapeutic value of the subtypes.

International Expert Consensus and Recommendations for Neonatal Pneumothorax Ultrasound Diagnosis and Ultrasound-guided Thoracentesis Procedure.

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

LncRNA H19/microRNA-675/PPARα axis regulates liver cell injury and energy metabolism remodelling induced by hepatitis B X protein via Akt/mTOR signalling.

Emerging evidence indicates that the lncRNAs/microRNA/mRNA axis plays important roles in a variety of diseases. This study was aimed to investigate the potential roles and underlying molecular mechanisms of lncRNA H19 and H19-derived miR-675 in regulating hepatitis B virus (HBV)-associated liver injury. mRNA and miR-675 levels were determined by quantitative real-time PCR (qRT-PCR), protein levels were determined by western blot, cell viability was measured by the MTT assay, cell apoptosis was measured by flow cytometry, inflammatory cytokine production was determined by ELISA, oxidative stress and energy metabolism were assessed by commercial kits, and the target relationship between PPARα and miR-675 was confirmed by the dual-luciferase reporter assay. The results showed that the expression of lncRNA H19 and miR-675 was up-regulated in patients with chronic hepatitis B (n = 20). Inhibition of lncRNA H19 or miR-675 in L02 cells increased cell viability, suppressed hepatitis B X protein (HBx)-induced cell apoptosis, inflammatory cytokine production, and oxidative stress, and remodelled energy metabolism. Furthermore, PPARα was found to be a target gene of miR-675. The expression of PPARα was down-regulated in patients with chronic hepatitis B, and there was a negative correlation between the expression of lncRNA H19 and PPARα, or between miR-675 and PPARα. Moreover, by knocking down the expression of PPARα, the actions (apoptosis, inflammatory factors, oxidative stress, and energy metabolism) of lncRNA H19 or miR-675 inhibition in HBx-induced L02 cells were at least partially reversed. In addition, HBx-induced elevated levels of p-AktSer473, p-AktThr308 and p-mTORSer2448 were down-regulated by lncRNA H19 or miR-675 inhibition. Furthermore, PPARα knockdown partly reversed the down-regulated effects of H19 or miR-675 inhibition. Taken together, these data indicate that the lncRNA H19/miR-675/PPARα axis regulates liver cell injury and energy metabolism remodelling induced by HBx, which may be related to the modulation of Akt/mTOR signalling.

miR-370 inhibits the oxidative stress and apoptosis of cardiac myocytes induced by hydrogen peroxide by targeting FOXO1.

Myocardial infarction, one of the main factors that threatens human health, leads to cardiac cell death. Myocardial cells suffer ischemia and hypoxia for a long period of time, which can lead to irreversible cell death or apoptosis and cardiac dysfunction. MicroRNAs (miRs) have been reported to play an important role in a wide range of biological processes in cardiac myocytes, which respond to inflammation and oxidative stress. The aim of the present study was to investigate the effect of miR-370 on oxidative stress and apoptosis of cardiac myocytes in ischemic H9C2 cells induced by hydrogen peroxide (H2O2). H9C2 cells were cultured and treated with different concentrations of H2O2 solution. Then, cells were transfected with miR-370 mimic or negative control (NC) mimic, small interfering (si)-RNA-Forkhead box O1 (FOXO1) and NC siRNA. A Cell Counting Kit-8 and flow cytometry assay were conducted to detect cell viability and cell apoptosis. The expression of oxidative stress associated factors were detected by ELISA. The levels of miR-370 and FOXO1 were examined using western blotting and reverse transcription-quantitative PCR. A luciferase reporter gene assay was performed to verify whether FOXO1 was a target gene of miR-370. The results revealed that miR-370 expression was downregulated and FOXO1 expression was increased in H9C2 cells induced by H2O2. Additionally, FOXO1 was proven to be a target of miR-370. The ELISA and flow cytometry assay revealed that miR-370 overexpression and FOXO1 silencing reversed H2O2-induced oxidative stress and apoptosis. The results indicated that miR-370 could inhibit the oxidative stress and apoptosis of H9C2 cells induced by H2O2 by targeting FOXO1. Therefore, miR-370 may be a new therapeutic target for ischemic heart disease.

[Value of power Doppler ultrasound to evaluate acute kidney injury].

OBJECTIVE: To explore the value of power Doppler ultrasound (PDU) in the evaluation of acute kidney injury(AKI). METHODS: Renal blood flow of 40 AKI cases was monitored by power Doppler ultrasound and 4-level semiquantitative PDU score method employed. All cases were divided into 3 groups by PDU score. AKI stage and duration were compared. And the co-variables of death and (continuous renal replacement therapy) CRRT days (> 3) were also analyzed by Logistic regression analysis. RESULTS: A total of 40 AKI case were recruited. The 3-score group (n = 13)has lower mortality in intensive care unit and at 28 days than the 2-score group (n = 15) and the 1-score group (n = 12). The number of stage-3 AKI in the 3-score group was less than that in the 2-score and 1-score groups (n = 1, 4, 9 correspondingly, χ(2) = 16.103, degree of freedom = 4, P = 0.003). The number of persistent AKI in the 3-score group was less than that in the 2-score and 1-score groups (n = 3, 9, 10 correspondingly, P < 0.05). Age, APACHEII score and PDU score (< 3) were closely correlated with death while age, APACHEII score, level of serum creatinine and PDU score (< 3) with CRRT days (> 3) (P < 0.05). CONCLUSION: PDU may be used to monitor renal hemodynamics in AKI patients and its score helps clinicians to evaluate the severity and prognosis of AKI.

Bone biomechanical and histomorphometrical investment in type 2 diabetic Goto-Kakizaki rats.

This study was performed to characterize the bone metabolism in ten 6-month-old male Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic model, with ten age- and sex-matched non-diabetic Wistar rats as controls. The femora and the fifth lumbar vertebrae were analyzed by a dual energy X-ray absorptiometry for bone mineral density. Histomorphometrical analyses were performed on the sections from the tibia embedded in methylmethacrylate. Biomechanical characterizations were made by a three-point bending test and a compressive test on the femur and the fifth vertebral body respectively. Compared to the control rats, the bone mineral density was significantly deceased and the histomorphometrical studies showed significantly decreased trabecular bone volume, trabecular thickness and number, osteoid surface and thickness, mineralizing surface, mineral apposition rate and bone formation rate, and also a significant increase in mineralization lag time in the diabetic rats. Strength in both bones and elastic modulus of vertebral body significantly decreased in the diabetic rats as well. In addition, the serum osteocalcin levels were significantly decreased and the serum tartrate-resistant acid phosphatase activity was significantly increased. In conclusion, the 6-month-old GK diabetic rats developed osteopenia with an increased risk of fracture owing to the decreased bone formation, and might be a useful model for unraveling the effects of diabetes on bones independent of obesity frequently seen in the type 2 diabetic patients.