Background Long‐term efficacy and safety of mavacamten in Chinese patients with obstructive hypertrophic cardiomyopathy are unknown. Methods Patients who completed the 30‐week, double‐blind, placebo‐controlled treatment period in EXPLORER‐CN (A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM), with no active safety concerns, were eligible to enter the long‐term extension period to receive 48‐week mavacamten treatment. Patients previously on mavacamten continued mavacamten (dose at week 30; mavacamten–mavacamten group); patients previously on placebo received mavacamten (starting dose, 2.5 mg once daily; placebo–mavacamten group). Key efficacy end points included change from baseline in echocardiographic measures, New York Heart Association functional class, 23‐item Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and cardiac biomarkers through week 78. Analyses were descriptive; no between‐group hypothesis testing was performed. Results Seventy‐nine patients (mean age, 51.6 years; 27.8% women) entered the long‐term extension period (mavacamten–mavacamten, n=54; placebo–mavacamten, n=25). In the mavacamten–mavacamten group, numerical improvements in Valsalva and resting left ventricular outflow tract peak gradients were maintained through week 78 (mean change from baseline, −73.0 mm Hg [95% CI, −86.4 to −59.5]; and −56.3 mm Hg [95% CI, −67.1 to −45.5], respectively). Numerical improvements were also observed for other echocardiographic parameters, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, and cardiac biomarkers through week 78. In the placebo–mavacamten group, numerical improvements with mavacamten in these parameters were noted from week 30 to week 78. Long‐term mavacamten treatment appeared well tolerated; left ventricular ejection fraction <50% was rare. Conclusions In this exploratory long‐term extension study, 78‐week mavacamten treatment appeared well‐tolerated and was associated with numerical improvements from baseline in echocardiographic parameters, New York Heart Association class, patient‐reported health status, and cardiac biomarkers in Chinese patients with obstructive hypertrophic cardiomyopathy. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05174416.

Improvement of symptoms, physical function, and quality of life is one treatment goal for patients with obstructive hypertrophic cardiomyopathy (HCM). Mavacamten improved left-ventricular outflow tract gradients in Chinese patients with obstructive HCM in the EXPLORER-CN trial. We report here a detailed analysis of patient-reported health status per the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) in Chinese patients after 78 weeks of mavacamten. Patients who completed the double-blind, placebo-controlled (DBPC) period of EXPLORER-CN with no active safety concerns could enter a long-term extension (LTE) period to receive mavacamten for 48 weeks at either the 30-week dose (mavacamten-mavacamten group) or a once-daily starting dose of 2.5 mg (subsequently adjusted via pharmacodynamics-based dose titration: placebo-mavacamten group). Health status endpoints included KCCQ-23 clinical summary score (CSS), overall symptom score (OSS), total symptom score (TSS), physical limitations score, and quality-of-life scores through week 78. Week 78 endpoint analyses were descriptive. In the DBPC period, 54 patients received mavacamten and 27 received placebo; of these, 54 and 25, respectively, entered the LTE period. KCCQ-23 CSS, OSS, and TSS improved with mavacamten and worsened with placebo during the DBPC period (mean change baseline to week 30: 5.7, 6.4, and 8.1, respectively [mavacamten-mavacamten group] and – 5.4, – 4.3, and – 4.8, respectively [placebo-mavacamten group]). CSS, OSS, and TSS continued to improve in the mavacamten-mavacamten group during the LTE period (mean change baseline to week 78: 7.1, 8.2, and 10.0, respectively). Scores improved in the placebo-mavacamten group after switching to mavacamten (mean change week 30 to week 78: 7.3, 9.5, and 5.7, respectively). Similar improvements in KCCQ-23 physical limitations and quality-of-life scores with mavacamten were observed throughout both study periods. Long-term mavacamten treatment for up to 78 weeks led to sustained improvements in patient-reported health status, supporting long-term treatment with mavacamten for Chinese patients with symptomatic obstructive HCM. ClinicalTrials.gov identifier NCT05174416.

Mavacamten, a cardiac myosin inhibitor, has demonstrated positive outcomes in left ventricular outflow tract (LVOT) gradient reduction and improvements of symptoms and function in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-CN. This exploratory analysis aimed to evaluate the effect of mavacamten on echocardiographic measures of cardiac structure and function and its relationship with other clinical biomarkers. Key echocardiographic parameters acquired over 30 weeks from 81 patients (n = 54 on mavacamten and n = 27 on placebo) were assessed in a central laboratory. At 30 weeks, greater improvements in measures of diastolic function were observed with mavacamten versus placebo, including lateral E/e′ (least-squares mean [LSM] change from baseline [CFB] − 5.1 vs. 0.6; between-group LSM difference − 5.7; 95

Pulmonary fibrosis involves destruction of the lung parenchyma and extracellular matrix deposition. Effective treatments for pulmonary fibrosis are lacking and its pathogenesis is still unclear. Studies have found that epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AECs) plays an important role in progression of pulmonary fibrosis. Thus, an in-depth exploration of its mechanism might identify new therapeutic targets. In this study, we revealed that a novel circular RNA, MKLN1 (circMKLN1), was significantly elevated in two pulmonary fibrosis models (intraperitoneally with PQ, 50 mg/kg for 7 days, and intratracheally with BLM, 5 mg/kg for 28 days). Additionally, circMKLN1 was positively correlated with the severity of pulmonary fibrosis. Inhibition of circMKLN1 expression significantly reduced collagen deposition and inhibited EMT in AECs. EMT was aggravated after circMKLN1 overexpression in AECs. MiR-26a-5p/miR-26b-5p (miR-26a/b), the targets of circMKLN1, were confirmed by luciferase reporter assays. CircMKLN1 inhibition elevated miR-26a/b expression. Significantly decreased expression of CDK8 (one of the miR-26a/b targets) was observed after inhibition of circMKLN1. EMT was exacerbated again, and CDK8 expression was significantly increased after circMKLN1 inhibition and cotransfection of miR-26a/b inhibitors in AECs. Our research indicated that circMKLN1 promoted CDK8 expression through sponge adsorption of miR-26a/b, which regulates EMT and pulmonary fibrosis. This study provides a theoretical basis for finding new targets or biomarkers in pulmonary fibrosis.

Purpose:Septic cardiomyopathy (SCM) is a significant global public health concern characterized by substantial morbidity and mortality, which has not been improved for decades due to lack of early diagnosis and effective therapies. This study aimed to identify hub biomarkers in SCM and explore their potential mechanisms. Methods:We utilized the GSE53007 and GSE207363 datasets for transcriptome analysis of normal and SCM mice. Hub biomarkers were identified through a protein-protein interaction (PPI) network and validated using LPS-treated C57/BL6 mice. Functional enrichment analysis was performed to uncover relevant signaling pathways, while single-cell RNA sequencing was used to examine key genes and regulatory mechanisms associated with SCM. Results:A total of 374 differentially expressed genes (DEGs) were identified, with 268 genes up-regulated and 106 genes down-regulated. Functional enrichment highlighted chemokine activity and receptor binding, with KEGG pathways revealing significant involvement of the TNF and IL-7 signaling pathways. Deterioration of cardiac function, elevated inflammatory markers such as IL-1β, IL-6, and increased cardiac injury biomarkers such as cTnI indicated the successful establishment of our SCM model. Subsequently, qPCR was conducted to validate the expression of the top 10 genes, through which we identified Cd40, Tlr2, Cxcl10, Ccl5, Cxcl1, Cd14, Gbp2, Ifit2, and Vegfa as key biomarkers. Single-cell sequencing indicated increased neutrophil and macrophage populations, with decreased B cells and cardiomyocytes. Additionally, transcription regulators Irf1 and Stat1 were found to potentially regulate the expression of Gbp2, Cxcl10, Ccl5, and Cd40, linking SCM to immune response, ferroptosis, pyroptosis, cuproptosis, and m6A RNA methylation modification. Conclusion:This study identified nine hub biomarkers and two transcription regulators associated with SCM. Exploring the connections between SCM and immunity, ferroptosis, pyroptosis, cuproptosis, and m6A RNA methylation might provide insights into the underlying mechanisms. These findings enhanced our understanding of SCM's underlying mechanisms and might pave the way for novel therapeutic strategies to improve clinical outcomes.

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm. However, the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated. Here, we identified hypoxia inducible factor-1α (HIF-1α) as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells. Specifically, HIF-1α protein expression is upregulated after H1N1 infection. Deficiency of HIF-1α attenuates pulmonary injury, viral replication and cytokine storm in vivo. In addition, viral replication and cytokine storm were inhibited after HIF-1α knockdown in vitro. Mechanistically, the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis, with rapid production of ATP and lactate. Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses. Further analysis revealed that H1N1-induced HIF-1α can promote the expression of hexokinase 2 (HK2), the key enzyme of glycolysis, and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate, which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/β production. In conclusion, this study demonstrated that the upregulation of HIF-1α by H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2, providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

As global aging accelerates, the super-elderly population is at higher risk of infectious diseases, especially sepsis, a condition that may be associated with declining immune system function and abnormal inflammatory responses. The aim of this study was to investigate the role of CARD16 protein in sepsis susceptibility in the elderly population and its potential mechanism, and to reveal the expression characteristics of CARD16-related genes through blood transcriptomic analysis. Transcriptome sequencing was conducted on peripheral blood samples obtained from patients suffering from senile sepsis, along with samples from a healthy elderly control group. To examine the differences in gene expression, bioinformatics techniques were employed to compare the expression levels of CARD16-related genes between the two groups. Additionally, a comprehensive analysis was performed on the downstream inflammatory pathways and cytokines that are regulated by CARD16.The findings from the transcriptome analysis indicated that the expression of CARD16 was markedly upregulated in the cohort of patients experiencing hypersenile sepsis. This upregulation was associated with an increase in a variety of pro-inflammatory factors. Further network analysis suggested that CARD16 may potentiate the inflammatory response by modulating the NF-κB signaling pathway, which could consequently heighten the patients' vulnerability to sepsis.In comparison to the healthy elderly control group, the levels of anti-inflammatory genes in the super-elderly cohort were found to be significantly diminished. This observation points to a notable imbalance in immune regulation, further emphasizing the altered immune response in individuals with senile sepsis.

BackgroundLight chain cardiac amyloidosis (AL-CA) is associated with a high incidence of mortality. Big endothelin-1 (ET-1), the precursor of endothelial-vasoconstrictive ET-1, is closely related to the concentration of bioactive ET-1. Association between big ET-1 and prognosis of AL-CA has not yet been documented. The purpose of this study was to evaluate the prognostic value of big ET-1 for poor outcomes in moderate to severe AL-CA.MethodsBig ET-1 levels were determined on admission in patients with newly diagnosed AL-CA with modified Mayo 2004 stage II or III. Primary outcome was all-cause mortality. The secondary outcomes included death from cardiac cause and the composite of the primary outcome or hospitalisations due to worsening heart failure.ResultsOverall, 141 patients were retrospectively included (57 stage II, 34 stage IIIa, 50 stage IIIb). During a median follow-up time of 25.7 months, 84 (59.6%) patients died. Patients with big ET-1 levels of ≤0.88 pmol/L had longer survival than those with >0.88 pmol/L (median survival time: 34.1 months vs 15.3 months, log-rank p<0.001), which was also observed in the validation cohort (log-rank p=0.026). Higher big ET-1 levels were predictive for all-cause mortality after multivariable adjustment (HR 1.91, 95% CI 1.05 to 3.49, p=0.035). Big ET-1 levels added an incremental prognostic value over modified Mayo 2004 stage (C-index: from 0.671 to 0.696, p=0.025; integrated discrimination improvement 0.168, p=0.047).ConclusionsBig ET-1 is a strong and independent predictor of mortality in patients with moderate to severe AL-CA, which may indicate a possible role for risk stratification in patients with this disease.

Paraquat (PQ) is a bipyridine herbicide and oral exposure is the main way of PQ exposure with a very high mortality. At present, it is believed that large number of oxygen free radicals are generated and cause lipid peroxidation of tissue and organ cell membranes after PQ is absorbed. PQ exposure could cause multiple organ dysfunction, among which acute lung injury is the most common and most serious. However, its specific mechanism is still unclear. In this study, the C57BL/6J mouse (alveolar epithelial cell-specific knockout HIF-1α) model of acute lung injury (40 mg/kg PQ) at several time pointes and a model of acute type II alveolar epithelial cell (A549, 800 μM PQ) injury constructed. The oxidative stress (ROS, MDA) and inflammatory response (IL-1β, IL-6, TNF-α) were significantly inhibited in the alveolar epithelial cell-specific knockout of HIF-1α mice and siRNA technology to inhibit HIF-1α in alveolar epithelial cells. Further proteomic analysis showed that the expression of Rac2 protein, which is closely related to oxidative stress, was significantly increased after PQ exposure. And the inhibition of Rac2 expression in vitro significantly alleviated PQ-induced oxidative stress and inflammatory response. The expression of Rac2 protein was regulated by HIF-1α. The above suggests that HIF-1α may promote oxidative stress and inflammatory response in alveolar epithelial cells by regulating the expression of Rac2, and then participate in the promotion of PQ exposure-induced acute lung injury.

Introduction Lung cancer is a major global health problem because of its high incidence and mortality. Targeted therapies have transformed treatment of driver-mutated metastatic non-small cell lung cancer (NSCLC). Nevertheless, recent studies demonstrated that cardiovascular disease (CVD) was the second leading cause of mortality in cancer survivors now, management of patients’ cardiovascular health during the course of anticancer therapy has become a great challenge faced by the oncologists. Anticancer related cardiovascular (CV) complications are not limited to traditional chemotherapy, but are also increasingly recognized in targeted therapy. Case Report We present a case of pulmonary embolism (PE) and bradycardia in a 91-year-old NSCLC patient treated with crizotinib for a rare MET Y1003S mutation. To our knowledge, this is the second report to show antitumor response of crizotinib in lung cancer patients with such a rare mutation. However, the patient complained chest tightness and shortness of breath after a month of standard dose crizotinib therapy. Non-invasive examination revealed new onset bradycardia and PE. Management & Outcome Such clinical manifestations were associated with targeted therapy-related CV toxicity, on which the emerging discipline cardio-oncology focused, and a multidisciplinary investigation and treatment was conducted. Discussion This case highlights the CV adverse events of novel therapies and the current challenges to be tackled in cardio-oncology.

We aimed to explore factors associated with mortality of diabetic kidney disease (DKD), and to establish a prediction model for predicting the mortality of DKD. This was a cohort study. In total, 1,357 DKD patients were identified from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, with 505 DKD patients being identified from the MIMIC-III as the testing set. The outcome of the study was 1-year mortality. COX proportional hazard models were applied to screen the predictive factors. The prediction model was conducted based on the predictive factors. A receiver operating characteristic (ROC) curve with the area under the curve (AUC) was calculated to evaluate the performance of the prediction model. The median follow-up time was 365.00 (54.50,365.00) days, and 586 patients (43.18%) died within 1 year. The predictive factors for 1-year mortality in DKD included age, weight, sepsis, heart rate, temperature, Charlson Comorbidity Index (CCI), Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA), lymphocytes, red cell distribution width (RDW), serum albumin, and metformin. The AUC of the prediction model for predicting 1-year mortality in the training set was 0.771 [95% confidence interval (CI): 0.746-0.795] and the AUC of the prediction model in the testing set was 0.795 (95% CI: 0.756-0.834). This study establishes a prediction model for predicting mortality of DKD, providing a basis for clinical intervention and decision-making in time.

Background: With the development of new techniques, blood and other humoral biomarkers have become increasingly important in the diagnosis of sepsis-associated acute kidney injury (AKI).We aimed to review and summarize the biomarkers associated with the diagnosis of sepsis-associated AKI. Methods: We performed a systematic review in PubMed, Embase, Web of Science, Cochrane and CNKI literature databases.Chinese and English articles published before January 30, 2021.We extracted information on the sensitivity and specificity of biomarkers to diagnose sepsis-associated AKI, the sample size of individuals with sepsis-associated AKI, the demographic variables, the diagnostic criteria and the sample acquisition protocol.Revman 5.3 software was used to analyze data.The sources of heterogeneity of included studies main were different diagnostic criteria for sepsis and AKI, time of sample collection and Patients came from different departments.We defined the inclusion of related studies by using PICOs (Patient, Intervention, Comparison and Outcome) criteria, in particular the design of studies to be included.P: Patients of sepsis.I: Patients of sepsis-associated AKI.C: Patients without sepsis-associated AKI.O: Diagnosis of sepsis associated kidney injury.Results: A total of 1,227 articles, including 42 studies, were identified.Increases in urine and serum neutrophil gelatinase-related lipid carrier protein (NGAL), urinary interleukin-18, urinary Kim-1, urinary Netrin-1, urinary sCD163, serum estradiol levels, and serum soluble thrombolytic regulatory protein were most strongly correlated with the diagnosis of sepsis-associated AKI.The SROC of urinary KIM-1 ranked first, followed by the other biomarkers: urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18.According to the sample size, the SROC values of urinary NGAL, blood NGAL, urinary IL-18 and urinary KIM-1 were 0.907, 0.857, 0.861 and 0.931, respectively.The sequence was still urinary KIM-1 > urinary NGAL > blood NGAL > urinary IL-18.Conclusions: According to the SROC curve area, the diagnostic sequence of sepsis-associated AKI biomarkers was urinary Kim-1 > urinary NGAL > blood NGAL > urinary IL-18.This meta-analysis provided diagnostic features of blood and urine biomarkers based on their association with the diagnosis of sepsis-associated AKI.

Subsequently to the publication of this paper, the authors' noticed that the same β‑actin control bands were inadvertently used in the western blots shown in Figs. 1A and 2A. After having examined their original data, the authors realized the control bands were chosen incorrectly for Fig. 1, but were able to identify the data that should have been used for this figure. The revised version of Fig. 1, showing the correct western blotting data for Fig. 1A, is shown opposite. Note that this error did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to the corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused.[Molecular Medicine Reports 24: 869, 2021; DOI: 10.3892/mmr.2021.12509].

Abstract Objective: Sepsis often causes myocardial injury with a high mortality. We wanted to investigate the effects of thrombospondin-1 (THBS1) expression on myocardial cell injury, oxidative stress and apoptosis in sepsis.Methods: The expression of THBS1 mRNA in LPS-induced mouse primary cardiomyocytes was detected by real-time fluorescence quantitative PCR. We constructed a eukaryotic siRNA expression vector and used liposome transfection to knockdown THBS1 mRNA expression in myocardial cells. We detected the THBS1 mRNA expression level using real-time fluorescent quantitative PCR. Four groups were used: control, LPS, THBS1 siRNA, and LPS + THBS1 siRNA. ELISA was used to detect cTnI, proBNP, ROS, caspase3 and other indicators of cell damage. At the same time, sepsis mouse models were prepared for H&E, TUNEL and caspase-3 staining to evaluate myocardial cell injury and apoptosis. Clinical samples were collected to analyze the serum THBS1 level and correlate it with the prognosis of patients with myocardial injury of sepsis.Results: The expression level of THBS1 mRNA in myocardial cells induced by LPS was increased, and the serum THBS1 level in patients with myocardial injury in sepsis was also significantly increased. In the THBS1 siRNA group with myocardial injury, the levels of cTnI and proBNP were significantly decreased, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly decreased, ROS were significantly decreased, and caspase3 was significantly decreased, and myocardial cell apoptosis was also reduced in the sepsis mouse model. Conclusion: THBS1 is closely related to the biological behavior of myocardial cells and may be a therapeutic target for myocardial injury in sepsis.

The incidence of sepsis-associated acute kidney injury (AKI) is on the rise. Recent studies have found a correlation between antithrombin III and AKI. We established a predictive model for sepsis-associated AKI based on plasma ATIII levels. A prospective study (March 2018–January 2020) was conducted in sepsis patients admitted to the Critical Care Medicine Department at Shanghai General Hospital. ATIII levels were obtained within 48 h after admission to the ICU and before the diagnosis of sepsis-associated AKI was recorded. Renal function was assessed by measuring serum creatinine levels and urine volume. Male sex, other cardiovascular disease, and low ATIII levels were identified as independent risk factors for AKI. Age, immune disease, and low ATIII levels were identified as independent risk factors for death. Plasma ATIII levels in the non-AKI group were higher than those in the AKI group, plasma ATIII levels were higher in the survival group than in the non-survival group, plasma ATIII levels in the non-CRRT group were higher than those in the CRRT group, and plasma ATIII levels in the non-CKD group were higher than those in the CKD group. ATIII was significantly higher in the group with pulmonary infection than in the group without pulmonary infection. ATIII was significantly lower in the celiac infection group than in the nonceliac infection group. There was no statistically significant difference between the ATIII in the gram-positive group and the gram-negative group. ATIII was significantly higher in medical patients than in surgical patients. The predictive model of sepsis-associated AKI established based on ATIII was ln[P/(1 − p)] = −1.211 × sex − 0.017 × ATIII + 0.022 × Cr + 0.004 × BUN − 2.8192. The model goodness-of-fit test (p = 0.000) and the area under the ROC curve of the model (0.9862) suggested that the model has a high degree of discrimination and calibration. ATIII reduction was closely related to the prognosis of patients with sepsis. ATIII reduction was an independent risk factor for sepsis-associated AKI and an independent risk factor for mortality in patients with sepsis. ATIII reduction could predict sepsis-associated AKI. Low ATIII predicted a poor prognosis.

OBJECTIVE:To explore clinical predictive value of short-term dynamic changes in platelet counts (PLT) for prognosis of sepsis patients in intensive care unit (ICU).METHODS:A retrospective cohort study was conducted. The patients aging 18 to 80 years old who were diagnosed by Sepsis-3 admitted to ICU of South Branch of Shanghai General Hospital from November 2015 to October 2018 were enrolled. According to whether the patients died within 28 days, they were divided into death and survival groups. General information and clinical baseline data [including disease severity score, infection biomarkers, PLT and organ function parameters (cardiac, liver, kidney, coagulation) and inflammatory cytokines] between the two groups were compared. Based on clinical indicators which had statistically significance, receiver operating characteristic (ROC) curve was drawn to predict the prognosis of the patients within 28 days. Then, risk factors of 28-day mortality of sepsis patients in ICU were screened by univariate and multivariate Logistic regression analysis. On the basis of multivariate Logistic regression analysis results, a multiparameter model was built, and the ROC curve was drawn to predict its prognosis within 28 days.RESULTS:A total of 220 sepsis patients were enrolled. Among them, 61 patients died and 159 patients survived within 28 days with a 28-day mortality of 27.7%. Compared with the survival group, the patients in the death group were senior in age, more likely to suffer from chronic cardiovascular, chronic kidney and immune system disease, had higher scores in acute physiologic and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, disseminated intravascular coagulation (DIC) score and less PLT on the 1st and 7th day, sustained a higher incidence of persistent thrombocytopenia (PLT were all < 100×109/L in the first week after ICU admission) or acquired thrombocytopenia (PLT ≥ 100×109/L on the day of ICU admission, but dropped over 50% during the first week after ICU admission), were subjected to higher procalcitonin (PCT) and interleukin-6 (IL-6) levels and endured worse organ function (cardiac, kidney, coagulation) with statistically significant differences. However, there was no significant difference in gender, disease type, infection sites, pathogens or liver function. The ROC curve analysis for the 28-day prognosis of sepsis illustrated that the three disease severity scores could predict the 28-day prognosis of sepsis in ICU, and the area under ROC curve (AUC) of SOFA score was the highest (AUC = 0.878). The AUC of PLT on the 7th day was higher than that on the 1st day (AUC: 0.862 vs. 0.674), and the AUC of other clinical indicators were all < 0.8. Univariate and multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.423, 95% confidence interval (95%CI) was 1.089-1.859, P = 0.010], troponin I (TnI; OR = 2.056, 95%CI was 1.057-3.999, P = 0.034), and persistent or acquired thrombocytopenia (OR = 13.028, 95%CI was 4.033-42.090, P < 0.001) were three independent risk factors for 28-day mortality of the sepsis patients in ICU. Based on the multivariate Logistic regression analysis results, a multiparameter model was built with SOFA score, TnI and persistent or acquired thrombocytopenia, which showed a AUC of 0.926 to predict the 28-day mortality of sepsis patients in ICU. When the optimum cut-off value was 0.398 in the model, the sensitivity was 76.8%, and the specificity was 92.8%.CONCLUSIONS:Persistent or acquired thrombocytopenia within the first week of hospitalization proves to have a relatively momentous clinical predictive value for prognosis of sepsis patients in ICU. Clinical intervention focusing on thrombocytopenia may become a new potential therapy for these sepsis patients.

BACKGROUNDSevere diarrhea is a common complication of enteral nutrition in intensive care unit (ICU) patients. CD55 not only plays a vital role in immune but also plays a crucial role in intestinal function. We intended to build a prediction model of enteral nutrition complicated with severe diarrhea in ICU patients based on CD55.METHODSThis was a prospective, single-center, observational study. We collected 116 patients with enteral nutrition in the ICU. We collected blood samples from patients at the time of admission, tested blood biomarkers [CD55, interleukin-10 (IL-10), diamine oxidase, D-lactic acid and endotoxin], and recorded daily defecation and enteral nutrition. Finally, through multi-factor logistic regression model, a prediction model based on multiple prediction indicators was formed, and new joint predictive factors were calculated. The prediction model of enteral nutrition complicated with severe diarrhea in ICU patients was constructed through data processing analysis.RESULTSA total of 116 adult patients with enteral nutrition were divided into two groups: 77 patients without severe diarrhea and 39 with severe diarrhea. Compared with patients without severe diarrhea, CD55 on granulocyte membrane surface(gCD55) of patients with severe diarrhea was significantly reduced (P<0.0001), and CD55 on erythrocyte membrane surface(eCD55) of patients with diarrhea was significantly reduced (P<0.0001), serum IL-10 in patients with diarrhea significantly decreased compared with those without diarrhea, P<0.0001.The area under the curve of receiver operating characteristic (AUCROC) was 0.919 in gCD55 predicting severe diarrhea, when cutoff value =99.95%, the optimal sensitivity was 96.2%, and specificity was 100%. The AUROC of eCD55 and IL-10 in predicting severe diarrhea was 0.658 and 0.558 respectively. Based on this, a prediction model was established. The prediction model was: In[P/(1- P)] =-24.68 gCD55 -2.26 eCD55 +0.0041 IL-10 +2,691, the goodness of fit test of the model was P=0.44, and the AUCROC of the model was 0.92.CONCLUSIONSgCD55 and eCD55 had certain predictive value in enteral nutrition complicated with severe diarrhea.

Elderly people represent the age group most frequently affected by acute kidney injury (AKI). The potential of Antithrombin III (ATIII) level for predicting AKI among elderly patients with sepsis is yet to be elucidated. Therefore, the purpose of the present study was to evaluate the ability of ATIII to predict AKI nondevelopment and prognosis in elderly patients with sepsis, in an intensive care unit (ICU). The present study was retrospective and included 107 elderly patients with sepsis who had been admitted to ICUs between October 2015 and March 2018. An assessment of renal function was performed daily by measuring serum creatinine (Cr) level and urine output, and ATIII level was obtained within 48 h of sepsis diagnosis. Among all enrolled patients, 29 (27.1%) developed AKI. ATIII expression was a predictor of AKI nondevelopment [Area under the curve (AUC)-Receiving operator characteristic (ROC)=0.729; sensitivity, 0.700; specificity, 0.714], and the ATIII/Creatine ratio was also a predictor of AKI nondevelopment (AUC-ROC=0.971; sensitivity, 0.900; specificity, 1). The accuracy of ATIII (AUC-ROC=0.681; sensitivity, 0.802; specificity, 0.542) and ATIII/Cr (AUC-ROC=0.804; sensitivity, 0.596; specificity, 0.875) in predicting survival was intermediate. However, the ATIII serum level was able to accurately predict AKI nondevelopment in elderly patients with sepsis, who were admitted to ICUs. Patients were divided into low- and high-ATIII groups using either 66.95% or 55.7% as cut-off values, both of which were used for further analysis. By comparison, the ICU stay was significantly lower in the high-ATIII group [P=0.020 (69.95%) and 0.049 (55.7%)] and off mechanical ventilation time, off continuous renal replacement therapy time and survival time were significantly higher in the high ATIII group [P=0.049, 0.048, and 0.014, respectively (66.95%); and P=0.041, 0.036, and 0.021, respectively (55.7%)]. The current study indicated that ATIII serum level predicts AKI in elderly patients with sepsis, and that low ATIII levels predicted a poorer prognosis.

Objective: Massive obstetric hemorrhage (MOH) is one of the major causes of maternal morbidity and mortality. The purpose of our study was to investigate the risk factors of MOH and further explore the effect of MOH on prognosis. Study design: Retrospective study of maternal near miss (MNM) with MOH was managed in a maternity center during a 10-year study period. Risk factors including maternal age, gestational age, weekend delivery, polyembryony, and comorbidities were analyzed. Maternal outcomes including disseminated intravascular coagulopathy (DIC), acute renal failure, abdominal hematoma, need for transfusion of blood products, shock, MODS, stroke, cardiac arrest, maternal mortality, neonatal mortality, hysterectomy, and abortion were also analyzed. Other clinical outcomes included ICU stay and hospital stay. Results: A total of 283 women with MNM were included in this study. MOH was present in 15.5%, shock was present in 7.07%, and DIC was present in 2.47%. The rate of transfusion of blood products was 30.03%. The rate of MOH declined significantly when gestational age increased (OR = 0.940, 95% CI = 0.908 0.974), and was higher in parous women than in nulliparous women (OR = 3.789, 95% CI = 1.769 8.116). Our results showed there was a remarkable connection between gestational age and childbearing history (P = 0.001). The rate of adverse maternal outcomes was higher in women with MOH than those without this history (P < .05). DIC was significantly correlated with MOH (P < .0001) and abdominal hematoma (P < .0001). AUROC of SOFA was significantly higher than that of other scores (P = 0.002) on reoperation. The AUROC of DIC was significantly higher than that of other scores (P = 0.001) on abdominal hematoma. Conclusion: Among women with MNM, gestational age and childbearing history were risk factors for MOH. SOFA scores had relatively good predictive abilities on reoperation, and the DIC scores had relatively good predictive abilities on abdominal hematoma.

Pulmonary fibrosis (PF) is one of the most prevalent causes of death following paraquat (PQ) poisoning. As demonstrated in previous studies by the present authors, epithelial-to-mesenchymal transition (EMT) is associated with PQ-induced PF. In addition, hypoxia-inducible factor-1α (HIF-1α) and lysyl oxidase (LOX) promote EMT following PQ poisoning. However, the association between HIF-1α- and LOX-mediated regulation of EMT remains unclear. The present study investigated the association between HIF-1α and LOX with regard to PQ-induced EMT. A549 and RLE-6TN cells were treated with PQ, and HIF-1α and LOX expression was silenced with short interfering RNAs. Changes in the expression of HIF-1α, LOX, β-catenin and EMT-related makers were detected using real-time quantitative polymerase chain reaction, immunofluorescence, and western blotting. HIF-1α and LOX were associated with PQ-induced EMT, and their expression levels were significantly increased (P<0.05). LOX expression was significantly decreased following PQ poisoning when HIF-1α expression was inhibited (P<0.05). However, the level of HIF-1α did not change significantly when LOX was silenced. The expression level of β-catenin and the degree of EMT were significantly decreased following HIF-1α and LOX silencing in both cell lines (P<0.05). The association between HIF-1α and LOX in regulating EMT during PQ-induced PF may be unidirectional. HIF-1α may regulate PQ-induced EMT through the LOX/β-catenin pathway.