Reactive oxygen species- (ROS-) induced lipid peroxidation plays a critical role in cell death including apoptosis, autophagy, and ferroptosis. This fundamental and conserved mechanism is based on an ...excess of ROS which attacks biomembranes, propagates lipid peroxidation chain reactions, and subsequently induces different types of cell death. A highly evolved sophisticated antioxidant system exists that acts to protect the cells from oxidative damage. In this review, we discussed how ROS propagate lipid peroxidation chain reactions and how the products of lipid peroxidation initiate apoptosis and autophagy in current models. We also discussed the mechanism of lipid peroxidation during ferroptosis, and we summarized lipid peroxidation in pathological conditions of critical illness. We aim to bring a more global and integrative sight to know how different ROS-induced lipid peroxidation occurs among apoptosis, autophagy, and ferroptosis.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The role of circulating exosomal microRNAs (miRNAs) in colorectal cancer (CRC) has drawn more and more attention during the past few years. Previously, we have identified several specific miRNAs in ...serum exosomes as potential CRC biomarkers. However, little is known about the association between exosome‐encapsulated miR‐548c‐5p and outcomes of patients with CRC. In the current study, the expression of serum exosomal miR‐548c‐5p was investigated by quantitative real‐time polymerase chain reaction. Its correlation with CRC prognosis was estimated by Kaplan‐Meier survival and log‐rank tests. Cox regression analysis based on uni‐ and multivariate analyses was performed to estimate the relationship of exosome‐encapsulated miR‐548c‐5p with the clinicopathological factors of patients with CRC. Reduced levels of serum exosomal miR‐548c‐5p were more significant in CRC patients with liver metastasis and at later TNM stage (III/IV tumor stages). Serum exosomal miR‐548c‐5p could inhibit the proliferation of CRC cells, while the precise molecular mechanisms warranted further elucidation. In addition, decreased levels of serum exosomal miR‐548c‐5p were independently associated with shorter overall survival in CRC adjusted by age, sex, tumor grade vascular infiltration, TNM stage (III/IV tumor stages) and metastasis (hazard ratio = 3.40, 95% confidence interval 1.02‐11.27; P = 0.046). The downregulation of exosomal miR‐548c‐5p in serum predicts poor prognosis in patients with CRC. Exosomal miR‐548c‐5p may be a critical biomarker for CRC diagnosis and prognosis.
Our study first suggests that the downregulation of exosome‐delivered miR‐548c‐5p in serum predicts poor prognosis in patients with CRC. In addition to a candidate as the prognostic factor, serum exosomal miR‐548c‐5p may also be an important biomarker for CRC diagnosis. This study highlights the role of serum exosome‐encapsulated miR‐548c‐5p as a novel predictive biomarker and a promising drug target in CRC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Mesenchymal stem cell (MSC) therapy is a promising approach against myocardial infarction (MI). Studies have demonstrated that MSCs can communicate with other cells by secreting exosomes. In the ...present study, we aimed to identify exosomal microRNAs that might contribute to MSC-mediated cardioprotective effects. Primary cardiomyocytes were deprived of oxygen and glucose to mimic MI in vitro. For the animal model of MI, the left anterior descending artery was ligated for 1 h, followed by reperfusion for 12 h. MSC-derived exosomes were used to treat primary cardiomyocytes or mice. Cardioprotection-related microRNAs were determined, followed by target gene identification and functional studies with quantitative PCR, western blotting, MTT assay, flow cytometry assay, chromatin immunoprecipitation and dual-luciferase assay. We found that MSC co-culture reduced OGD-induced cardiomyocyte apoptosis and inflammatory responses. Cardioprotection was also observed upon treatment with MSC-derived exosomes in vitro and in vivo. In line with this, exosome uptake led to a significant increase in miR-25-3p in cardiomyocytes. Depletion of miR-25-3p in MSCs abolished the protective effects of exosomes. Mechanistically, miR-25-3p directly targeted the pro-apoptotic genes FASL and PTEN and reduced their protein levels. Moreover, miR-25-3p decreased the levels of EZH2 and H3K27me3, leading to derepression of the cardioprotective gene eNOS as well as the anti-inflammatory gene SOCS3. Inhibition of EZH2 or overexpression of miR-25-3p in cardiomyocytes was sufficient to confer cardioprotective effects in vitro and in vivo. We concluded that exosomal miR-25-3p from MSCs alleviated MI by targeting pro-apoptotic proteins and EZH2.
Acute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID‐19) and is associated with in‐hospital death. We investigated the incidence of AKI in 223 hospitalized COVID‐19 ...patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID‐19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID‐19 and 99 with severe COVID‐19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID‐19 and 4.0% for moderate COVID‐19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio OR: 3.132, 95% confidence interval CI: 1.150–8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361–13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622–22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 10⁹/L, interquartile range IQR 11.3 vs. 8.3 × 10⁹/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID‐19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID‐19 patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Behcet's disease (BD) is a systemic vasculitis characterized by oral and genital aphthosis, and ocular and skin lesions. The disease is involved in vascular, gastrointestinal, and central nervous ...systems. Vasculitis may exacerbate fatal problems, such as anastomotic pseudoaneurysms. If the mesenteric vessels are involved, severe abdominal symptoms such as intestinal obstruction may occur.
This case report describes a young female patient who suffered from BD with recurrent abdominal aortic pseudoaneurysms, as well as deep venous thrombosis and subsequent complications of incomplete intestinal obstruction. This patient first underwent stent grafting, which was followed by rupture of two newly formed anastomotic pseudoaneurysms within six months. Emergency open surgical repair (OSR) was then performed on the ruptured pseudoaneurysms. Thrombosis and incomplete ileus occurred five months after surgery. This case was unique due to the presence of incomplete intestinal obstruction being the possible main complaint for a patient with Behcet's disease, and it is the first ever case to be reported.
Intestinal obstruction may present as the possible main complaint in BD. Careful and attentive strategy should be carried out to prevent fatal outcomes.
Purpose
To investigate the effect of transcutaneous cervical vagus nerve stimulation (tcVNS) on motor cortex excitability in healthy adults.
Method
Twenty eight healthy subjects were assigned to ...receive real and sham tcVNS for 30 min. The interval between the real and sham conditions was more than 24 h, and the sequence was random. The central and peripheral motor-evoked potential (MEP) of the right first dorsal interosseous (FDI) muscle was measured by transcranial magnetic stimulation (TMS) before and after stimulation. MEP latency, MEP amplitude and rest motor threshold (rMT) were analyzed before and after stimulation.
Results
MEP amplitude, MEP latency and rMT had significant interaction effect between time points and conditions (
p
< 0.05). After real stimulation, the MEP amplitude was significantly increased (
p
< 0.001). MEP latency (
p
< 0.001) and rMT (
p
= 0.006) was decreased than that of baseline. The MEP amplitude on real condition was higher than that of sham stimulation after stimulation (
p
= 0.027). The latency after the real stimulation was significantly shorter than that after sham stimulation (
p
= 0.005). No significantly difference was found in rMT after stimulation between real and sham conditions (
p
> 0.05).
Conclusion
tcVNS could improve motor cortex excitability in healthy adults.
Background： The management of pain, agitation, and deliriunl （PAD） in Intensive Care Unit （ICU） is beneficial for patients and makes it widely applied in clinical practice. Previous studies showed ...that the clinical practice of PAD in ICU was improving： yet relatively little intbrmation is available in China. This study aimed to investigate the practice of PAD in ICUs in China. Methods： A multicenter, nationwide survey was conducted using a clinician-directed questionnaire from September 19 to December 18, 2016. The questionnaire focused on the assessment and naanagement of PAD by the clinicians in ICUs. The practice of PAD was compared among the lbur regions of China （North, Southeast, Northwest, and Southwest）. The data were expressed as percentage and fi＇equency. The Chi-square test, Fisher＇s exact test, and line-row Chi-square test were used. Results： Of the 1011 valid questionnaire lbrms, the response rtite was 80.37%. The clinicians came from 704 hospitals across 158 cities of China. The rate of PAD assessment was 75.77%, 90.21%, and 66.77%, respectively. The rates of PAD scores were 45.8%, 68.94%, and 34.03%, respectively. The visual analog scale, Richmond agitation-sedation scale, and conlktsion assessment method lbr the ICU were the first choices of scales for PAl） assessment. Fentanyl, midazolam, and dexmedetomidine were the first choices of agents for analgesic, sedation, and delirium treatment. While choosing analgesics and sedatives, the clinicians put the pharmacological characteristics of drugs in the first place （66.07% and 76.36%）. Daily interruption for sedation was carried out by 67.26% clinicians. Most of the clinicians （87.24%） used analgesics while using sedatives. Of the 738 （73%） clinicians titrating the sedatives oil the basis of the proposed target sedation level, 268 （26.61%） clinicians just depended on their clinical experience. Totally, 519 （51.34%） clinicians never used other nondrug strategies tbr PAD. The working time of clinicians was an important thctor in the management of analgesia and sedation rather than their titles and educational background. The ratios of pain score and sedation score in the Southwest China were the highest and the North China were the lowest. The ratios of delirium assessment and score were the same in the four regions of China. Moreover, the first choices of scales for PAD in the four regions were the same. However, the top three choices of agents in PAD treatment in the four regions were not the same. Conclusions： The practice of PAD in China lbllows the international guidelines; however, the pain assessment should be improved. The PAD practice is a little different across the four regions of China： however, the trend is consistent. Trial Registration： The study is registered at http：//www.clinicaltrials.gov （No. ChiCTR-OOC-16000014, www.chictr, org.cn/index.aspx.）.
The cytokine, macrophage migration inhibitory factor (MIF), is encoded in a functionally polymorphic locus and subjects with high-expression MIF alleles are at an increased risk of inflammatory ...disease. Severe sepsis is the leading cause of death in intensive care units, and the prevailing hypothesis is that an excessive innate response contributes to its pathogenesis. To assess if MIF alleles influence the clinical course of infection, we conducted a case-control study to assess susceptibility and a parallel inception cohort study of community-acquired pneumonia (CAP) to assess risk of severe sepsis and 90-d mortality. Two distinct polymorphisms in the MIF promoter were analyzed: a G/C transition at -173 and a CATT repeat at -794. The frequency of both polymorphisms was similar in the CAP cohort (n=1739) and controls (n=639); however, the 90-d mortality was lower for the high-expression C allele (P=0.003). This association remained significant after adjusting for demographics, comorbid conditions, and disease severity score hazard ratio=0.64 (0.44-0.91), P=0.01. The hazard ratio was similar in different geographic subcohorts, and the association remained significant after adjusting for false discovery. These data indicate that polymorphisms associated with higher MIF expression may have a beneficial effect in community-acquired pneumonia.--Yende, S., Angus, D. C., Kong, L., Kellum, J. A., Weissfeld, L., Ferrell, R., Finegold, D., Carter, M., Leng, L., Peng, Z.-Y., Bucala, R. The influence of macrophage migration inhibitory factor gene polymorphisms on outcome from community-acquired pneumonia.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Acute kidney injury (AKI) is an independent risk factor for the increased risk of death in patients with sepsis. In the current study, we first investigated the expression of circMTO1 in ...sepsis-induced AKI, and the underlying mechanism was further elucidated. The results showed that circMTO1 expression level was significantly decreased in serums and kidney tissues of US rats and RMCs treated with LPS. Besides, circMTO1 overexpression promoted cell viability, suppressed cell apoptosis and cytokines production of LPS-treated RMCs. Bioinformatics analysis showed that circMTO1 served as a sponge for miR-337. Furthermore, circMTO1 could inhibit the expression of KLF6. Altogether, our study first reported that circMTO1 expression was decreased in sepsis-induced AKI rat models and RMCs treated with LPS. CircMTO1 overexpression could attenuate AKI development by sponging miR-337 and regulating KLF6 expression, which may provide new ideas for evaluation the pathogenesis and the treatment of sepsis-induced AKI.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people ...around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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