[Effect of mild hypothermia on macrophage polarization in lipopolysaccharide-induced acute lung injury mice].

OBJECTIVE: To investigate the effect of mild hypothermia on macrophage polarization in lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice and to clarify its role in lung injury. METHODS: According to a random number table method, 18 male C57BL/6 mice were divided into sham operation group (Sham group), ALI normothermic model group (NT group) and ALI mild hypothermia treatment group (HT group), with 6 mice in each group. The ALI model in mice was established by the method of tracheal instillation of LPS, and temperature control was administered at 1 hour after surgery. The anus temperature in NT group was kept at 36-38?centigrade, while the anus temperature in HT group was kept at 32-34?centigrade. The target anus temperature in both groups were maintained for 6 hours and then slowly rewarmed to 36-38 centigrade. The Sham group was infused with an equal amount of physiological saline through the trachea without temperature control. After 24 hours of modeling, serum was collected and mice were sacrificed to obtain lung tissue. Pathological changes in lung tissue were observed under light microscopy and semi-quantitative lung injury score was performed. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum levels of interleukins (IL-1ß, IL-10). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to test the indicators of macrophage polarization, such as the mRNA expressions of CD86, IL-6, CD206 and arginase 1 (Arg1) in the lung tissue. The protein expression of M1 macrophage marker inducible nitric oxide synthase (iNOS) and M2 macrophage marker Arg1 were detected by Western blotting. RESULTS: Compared with the Sham group, the NT group appeared significant pulmonary hemorrhage and edema, thickened lung septum, inflammatory cell infiltration, and lung injury score was significantly increased; serum IL-1ß level was significantly elevated; IL-10 level was increased without statistical significance; the expressions of CD86 mRNA, IL-6 mRNA and iNOS protein were significantly elevated, and CD206 mRNA was significantly decreased; the mRNA and protein expressions of Arg1 decreased, but there were no significant differences. Compared with the NT group, the pathological injury of lung tissue in HT group was significantly reduced, and the lung injury score was significantly decreased (4.78±0.96 vs. 8.56±1.98, P < 0.01); serum IL-1ß level was decreased (ng/L: 13.52±1.95 vs. 27.18±3.87, P < 0.01), and IL-10 level was significantly increased (ng/L: 42.59±15.79 vs. 14.62±4.47, P < 0.01); IL-6 mRNA expression was decreased in lung tissue (2-ΔΔCt: 3.37±0.92 vs. 10.04±0.91, P < 0.05), the expression of M1 macrophage markers CD86 mRNA and iNOS protein were significantly decreased [CD86 mRNA (2-ΔΔCt): 0.52±0.16 vs. 1.95±0.33, iNOS protein (iNOS/ß-actin): 0.57±0.19 vs. 1.11±0.27, both P < 0.05], the expression of M2 macrophage markers CD206 mRNA, Arg1 mRNA and Arg1 protein were significantly increased [CD206 mRNA (2-ΔΔCt): 3.99±0.17 vs. 0.34±0.17, Arg1 mRNA (2-ΔΔCt): 2.33±0.73 vs. 0.94±0.23, Arg1 protein (Arg1/ß-actin): 0.96±0.09 vs. 0.31±0.11, all P < 0.05]. CONCLUSIONS: Mild hypothermia can alleviate the inflammatory response and protect lung tissue in ALI mice, which may be related to the inhibition of M1 macrophage polarization and promotion of M2 macrophage polarization.

Genetic Prediction of Causal Relationships between Osteoporosis and Sepsis: Evidence from Mendelian Randomization with two-sample Designs.

BACKGROUND: Recent observational studies have suggested that osteoporosis may be a risk factor for sepsis. To mitigate confounding factors and establish the causal relationship between sepsis and osteoporosis, we conducted a two-sample Mendelian randomization analysis using publicly available summary statistics. METHODS: Utilizing summary data from FinnGen Biobank, we employed a two-sample Mendelian randomization (MR) analysis to predict the causal relationship between osteoporosis and sepsis. The MR analysis primarily utilized the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode analyses, with Bayesian weighted MR (BWMR) analysis employed for result validation. Sensitivity analyses included MR-PRESSO, "leave-one-out" analysis, MR-Egger regression, and Cochran's Q test. RESULTS: In the European population, an increase of one standard deviation in osteoporosis was associated with an 11% increased risk of sepsis, with an odds ratio (OR) of 1.11 (95% CI, 1.06 - 1.16; p = 3.75E-06). BWMR yielded an OR of 1.11 (95% CI, 1.06 - 1.67; p = 1.21E-05), suggesting osteoporosis as a risk factor for sepsis. Conversely, an increase of one standard deviation in sepsis was associated with a 26% increased risk of osteoporosis, with an OR of 1.26 (95% CI, 1.11 - 1.16; p = 0.45E-03). BWMR yielded an OR of 1.26 (95% CI, 1.09 - 1.45; p = 1.45E-03), supporting sepsis as a risk factor for osteoporosis. CONCLUSION: There is a association between osteoporosis and sepsis, with osteoporosis may serving as a risk factor for the development of sepsis, while sepsis may also promote the progression of osteoporosis.

Novel application of nanomedicine for the treatment of acute lung injury: a literature review.

Nanoparticles have attracted extensive attention due to their high degree of cell targeting, biocompatibility, controllable biological activity, and outstanding pharmacokinetics. Changing the size, morphology, and surface chemical groups of nanoparticles can increase the biological distribution of agents to achieve precise tissue targeting and optimize therapeutic effects. Examples of their use include nanoparticles designed for increasing antigen-specific immune responses, developing vaccines, and treating inflammatory diseases. Nanoparticles show the potential to become a new generation of therapeutic agents for regulating inflammation. Recently, many nanomaterials with targeted properties have been developed to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS). In this review, we provide a brief explanation of the pathological mechanism underlying ALI/ARDS and a systematic overview of the latest technology and research progress in nanomedicine treatments of ALI, including improved nanocarriers, nanozymes, and nanovaccines for the targeted treatment of lung injury. Ultimately, these nanomedicines will be used for the clinical treatment of ALI/ARDS.

Causal relationships between peripheral immune cells and Alzheimer's disease: a two-sample Mendelian randomization study.

OBJECTIVE: Previous research suggests that peripheral immune cells may play a role in the development of Alzheimer's disease (AD). Our study aims to determine if the composition of peripheral immune cells directly contributes to the occurrence of AD. METHODS: We utilized a two-sample Mendelian randomization (MR) approach to examine the association between peripheral immune cells and AD.The primary analysis method used was the inverse variance weighted (IVW) method, and we also conducted analyses using MR Egger, weighted median, simple mode, and weighted mode methods to ensure the accuracy of the results.Heterogeneity and horizontal pleiotropy were evaluated using Cochran's Q statistics and the MR Egger intercept, respectively. RESULTS: The study found a significant correlation between increased IgD + CD24- AC cells (Odds Ratio [OR] = 1.03, 95% Confidence Interval [CI] = 1.01-1.06, P = 0.0172), increased CD4 + %leukocyte (OR = 1.08, 95% CI = 1.02-1.14, P = 0.0086), and increased CD4 + CD8dim AC cells (OR = 1.06, 95% CI = 1.01-1.11, P = 0.0218), with an increased susceptibility to AD. Conversely, an increase in EM DN (CD4-CD8-) %T cells (OR = 0.95, 95% CI = 0.92-0.99, P = 0.0164) and an increase in DN (CD4-CD8-) AC cells (OR = 0.93, 95% CI = 0.88-0.99, P = 0.0145) were associated with a protective effect against AD. CONCLUSION: Our findings establish a causal link between peripheral immune cells and AD. This study is the first to examine the relationship between peripheral immune cells and AD using MR, offering valuable insights for early diagnosis and treatment decisions.

[Evaluation of extravascular lung water index in critically ill patients based on lung ultrasound radiomics analysis combined with machine learning].

OBJECTIVE: To explore lung ultrasound radiomics features which related to extravascular lung water index (EVLWI), and to predict EVLWI in critically ill patients based on lung ultrasound radiomics combined with machine learning and validate its effectiveness. METHODS: A retrospective case-control study was conducted. The lung ultrasound videos and pulse indicated continuous cardiac output (PiCCO) monitoring results of critically ill patients admitted to the department of critical care medicine of the First Affiliated Hospital of Guangxi Medical University from November 2021 to October 2022 were collected, and randomly divided into training set and validation set at 8:2. The corresponding images from lung ultrasound videos were obtained to extract radiomics features. The EVLWI measured by PiCCO was regarded as the "gold standard", and the radiomics features of training set was filtered through statistical analysis and LASSO algorithm. Eight machine learning models were trained using filtered radiomics features including random forest (RF), extreme gradient boost (XGBoost), decision tree (DT), Naive Bayes (NB), multi-layer perceptron (MLP), K-nearest neighbor (KNN), support vector machine (SVM), and Logistic regression (LR). Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of models on EVLWI in the validation set. RESULTS: A total of 151 samples from 30 patients were enrolled (including 906 lung ultrasound videos and 151 PiCCO monitoring results), 120 in the training set, and 31 in the validation set. There were no statistically significant differences in main baseline data including gender, age, body mass index (BMI), mean arterial pressure (MAP), central venous pressure (CVP), heart rate (HR), cardiac index (CI), cardiac function index (CFI), stroke volume index (SVI), global end diastolic volume index (GEDVI), systemic vascular resistance index (SVRI), pulmonary vascular permeability index (PVPI) and EVLWI. The overall EVLWI range in 151 PiCCO monitoring results was 3.7-25.6 mL/kg. Layered analysis showed that both datasets had EVLWI in the 7-15 mL/kg interval, and there was no statistically significant difference in EVLWI distribution. Two radiomics features were selected by using LASSO algorithm, namely grayscale non-uniformity (weight was -0.006 464) and complexity (weight was -0.167 583), and they were used for modeling. ROC curve analysis showed that the MLP model had better predictive performance. The area under the ROC curve (AUC) of the prediction validation set EVLWI was higher than that of RF, XGBoost, DT, KNN, LR, SVM, NB models (0.682 vs. 0.658, 0.657, 0.614, 0.608, 0.596, 0.557, 0.472). CONCLUSIONS: The gray level non-uniformity and complexity of lung ultrasound were the most correlated radiomics features with EVLWI monitored by PiCCO. The MLP model based on gray level non-uniformity and complexity of lung ultrasound can be used for semi-quantitative prediction of EVLWI in critically ill patients.

Intravenous high-dose vitamin C monotherapy for sepsis and septic shock: A meta-analysis of randomized controlled trials.

BACKGROUND: Vitamin C has been used as an adjuvant in the treatment of sepsis and septic shock; however, its role remains controversial. This study aimed to assess the effectiveness of intravenous high-dose vitamin C in sepsis and septic shock patients by meta-analysis. METHODS: The PubMed, Embase, and Cochrane Library electronic databases were searched to identify relevant studies. The primary outcome was defined as the short-term all-cause mortality rate. Secondary outcomes included duration of vasoactive drug use, intensive care unit length of stay, sequential organ failure assessment scores up to 96 hours after treatment and 90-day mortality. Review Manager version 5.4 was used to perform the meta-analysis. Relative risk and mean differences (MD) with 95% confidence intervals were determined using fixed- or random-effects models. RESULTS: Eight randomized controlled trials (RCTs) comprising 1394 patients were eligible for assessment. Overall, the pooled results showed that high-dose vitamin C decreased short-term all-cause mortality in patients with sepsis, but no significant differences were observed in patients with septic shock. Additionally, high-dose vitamin C was associated with decreased duration of vasoactive drug use in patients with sepsis, but not in patients with septic shock. However, it did not significantly affect the duration of intensive care unit stay in RCTs of patients with sepsis and septic shock. Additionally, it did not significantly affect sequential organ failure assessment scores 96 hours post-treatment or 90-day mortality. CONCLUSION: These results suggest that intravenous high-dose vitamin C may improve outcomes in patients with sepsis, but do not benefit patients with septic shock. Further RCTs and other studies should be conducted to determine whether vitamin C should be recommended as an adjunctive sepsis treatment.

Mild Hypothermia Alleviates CLP-induced Multiple Organ Dysfunction by Mitigating Pyroptosis Through the TLR4/NF-κB/NLRP3 Signaling Pathway.

BACKGROUND: Multiple organ failure secondary to severe sepsis leads to increased morbidity and mortality and is often accompanied by inflammation and immune system dysfunction. Mild hypothermia has been shown to have anti-inflammatory properties, but whether it can exert a protective effect in cases of multiple organ failure remains unclear. Thus, in this study, we investigated the protective effect of mild hypothermia on septic multiple organ failure and the underlying mechanism for this effect. METHOD: Sepsis was induced through the cecal ligation and puncture (CLP) method. Rats were then housed at normal (36-38°C) or mild hypothermic (32-34°C) temperature for 10 h. RESULTS: CLP-induced effects on inflammatory cytokines and biochemical markers in serum were reversed by mild hypothermia. The pathological injury score and the expressions of pyroptosis markers, including TLR4, MyD88 and NF-κB signaling molecules, showed a similar trend. Moreover, 3 d survival of CLP rats was improved by mild hypothermia. CONCLUSIONS: Mild hypothermia alleviated CLP-induced organ failure and the downstream effects on pyroptosis, probably through the TLR4/NF-κB/NLRP3 signaling pathway.

Molecular mechanism analysis of m6A modification-related lncRNA-miRNA-mRNA network in regulating autophagy in acute pancreatitis.

This study aims to explore the molecular mechanism of N6-methyladenosine (m6A) modification-related long noncoding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA) network in regulating autophagy and affecting the occurrence and development of acute pancreatitis (AP). RNA-seq datasets related to AP were obtained from Gene Expression Omnibus (GEO) database and merged after batch effect removal. lncRNAs significantly related to m6A in AP, namely candidate lncRNA, were screened by correlation analysis and differential expression analysis. In addition, candidate autophagy genes were screened through the multiple databases. Furthermore, the key pathways for autophagy to play a role in AP were determined by functional enrichment analysis. Finally, we predicted the miRNAs binding to genes and lncRNAs through TargetScan, miRDB and DIANA TOOLS databases and constructed two types of lncRNA-miRNA-mRNA regulatory networks mediated by upregulated and downregulated lncRNAs in AP. Nine lncRNAs related to m6A were differentially expressed in AP, and 21 candidate autophagy genes were obtained. Phosphoinositide 3-kinase (PI3K)-Akt signaling pathway and Forkhead box O (FoxO) signaling pathway might be the key pathways for autophagy to play a role in AP. Finally, we constructed a lncRNA-miRNA-mRNA regulatory network. An upregulated lncRNA competitively binds to 13 miRNAs to regulate 6 autophagy genes, and a lncRNA-miRNA-mRNA regulatory network in which 2 downregulated lncRNAs competitively bind to 7 miRNAs to regulate 2 autophagy genes. m6A modification-related lncRNA Pvt1, lncRNA Meg3 and lncRNA AW112010 may mediate the lncRNA-miRNA-mRNA network, thereby regulating autophagy to affect the development of AP.

Dexmedetomidine Attenuates LPS-Stimulated Alveolar Type II Cells' Injury through Upregulation of miR-140-3p and Partial Suppression of PD-L1 Involving Inactivating JNK-Bnip3 Pathway.

Dexmedetomidine (DEX), which is reported to be a newly discovered, novel α-2 adrenoceptor agonist, is known to exhibit anti-inflammatory properties in several diseases. DEX regulates inflammation-related signaling pathways and genes through interactions with several miRNAs. This study verified that expression levels of miR-140-3p were diminished when alveolar type II cells were exposed to LPS. However, the levels of miR-140-3p were confirmed as showing an increase with DEX treatment. These observations revealed that the expression of miR-140-3p was related to the beneficial effects that accompanied the DEX treatment of LPS-induced ALI. In addition, PD-1/PD-L1 expression increased extensively when RLE-6TN cells were induced by LPS. The increased expression was reduced after treatment with DEX. Thus, it appears that the PD-L1 expression was targeted directly by miR-140-3p, resulting in the partial repression of PD-L1 levels, which involved the inhibition of p-JNK and Bnip3 expression. Therefore, DEX was shown to inhibit the PD-L1 expression by promoting partially increased miR-140-3p levels in RLE-6TN cells. DEX also inactivated the JNK-Bnip3 pathway, resulting in the inhibition of inflammation and alleviating alveolar type II cell injury.

Early initiation of norepinephrine in patients with septic shock: A propensity score-based analysis.

BACKGROUND: The use of vasopressors is vital in septic shock. However, the optimal timing of treatment remains unclear. Therefore, we aimed to explore the impact of early norepinephrine initiation on the survival of patients with septic shock. METHODS: We selected 4253 patients from the Medical Information Mart for Intensive Care IV database between 2008 and 2019. The primary outcome was 28-day mortality. Propensity score matching (PSM) was applied to minimize between-group imbalances, and a restricted mean survival time was used to quantify the beneficial impact of early norepinephrine treatment on survival. Sensitivity analyses were conducted to test the robustness of the study results in multiple cohorts. RESULTS: In the PSM cohort, 2862 patients were equally assigned to early (receiving norepinephrine within the first 3 h) and delayed (> 3 h) norepinephrine initiation groups. Patients in the early norepinephrine initiation group received significantly less fluid therapy (0 vs. 79 mL/kg), had lower 28-day mortality (30.0% vs. 37.8%), longer survival days (21.89 vs. 20.37 days), shorter duration of intensive care unit (4.9 vs. 7.2 days) and hospital stays (12.4 vs. 13.6 days), shorter duration of supportive norepinephrine and invasive mechanical ventilation, lower incidence of organ failure progression (64.4% vs. 79.2%) within 24 h after shock onset, and higher mean arterial pressure within 6 and 24 h after shock onset than patients in the delayed norepinephrine initiation group (p < 0.05). CONCLUSIONS: Norepinephrine initiation within the first 3 h, regardless of preload dependency, was associated with longer survival time and shorter duration of supportive norepinephrine and invasive mechanical ventilation and may delay or partially reverse rapid onset organ failure.

An Oxidative Stress-Related Genes Signature for Predicting Survival in Bladder Cancer: Based on TCGA Database and Bioinformatics.

Background: Oxidative stress (OS) responses have been linked to oncogenesis and tumor progression and have recently been regarded as a potential strategy for tumor therapy. However, OS-related therapeutic targets have not been identified to date in the bladder cancer (BC). Methods: The mRNA expression and clinical data of BC were downloaded from the public database. Prognostic risk score signature was constructed using LASSO Cox regression analysis. External validation was performed in GSE15307 cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithm were used to analyze immune cell infiltration and immune microenvironment. Next, functional enrichment analysis was performed to elucidate the mechanism underlying the signature. Additionally, we performed a nomogram to forecast the survival rate of individual BC patients. Results: An OS-related genes (OSRGs) signature was constructed. Overall survival was lower in the high-risk group than in the low-risk group, according to survival analyses. The area under the curve (AUC) of ROC curves further validated the prognostic signature's strong prediction performance in these two cohorts. The risk score was verified as an independent risk factor for BC by independent prognostic analysis. Moreover, as compared to TNM stage alone, a nomogram that integrated the risk score with TNM stage showed a much superior predictive value. Immune infiltration and tumor microenvironment studies indicated that immune cells and functions may play a significant role in carcinogenesis and development. The levels of expression of prognostic genes were shown to be substantially linked with drug sensitivity. Conclusion: We developed a novel OSRGs signature for predicting overall survival and impacting the immune status in patients with BC. New nomogram can help clinicians predict the survival rate of BC patients. These findings shed new light on the potential usage of OSRGs signature in BC patients.

Shenfu Injection Protects Brain Injury in Rats with Cardiac Arrest through Nogo/NgR Pathway.

The effect of Shenfu injection on brain injury after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) along with the underlying mechanism of axonal regeneration was explored. CA/CPR model in rats was established for subsequent experiments. A total of 160 rats were randomly divided into sham group, model group, conventional western medicine (CWM) group, Shenfu group, and antagonist group (n = 32 per group). After 3 hours, 24 hours, 3 days, and 7 days of drug administration, the modified Neurological Severity Score tests were performed. The ultrastructure of the brain and hippocampus was observed by electron microscopy. Real-time quantitative polymerase chain reaction (PCR), western blotting, and immunohistochemistry were used to detect Nogo receptor (NgR) expression in the hippocampus and cerebral cortex, and Nogo-NgR expression in CA/CPR model. Neurological deficits in the model group were severe at 3 hours, 24 hours, 3 days, and 7 days after the recovery of natural circulation, whereas the neurological deficits in CWM, antagonist, and Shenfu group were relatively mild. The ultrastructure of neuronal cells in Shenfu group had relatively complete cell membranes and more vesicles than those in the model group. The results of PCR and western blotting showed lower messenger ribonucleic acid and protein expression of NgR in Shenfu group than the model group and CWM group. Immunohistochemical examination indicated a reduction of Nogo-NgR expression in Shenfu group and antagonist group. Our results suggested that Shenfu injection reduced brain injury by attenuating Nogo-NgR signaling pathway and promoting axonal regeneration.

[Research progress on the mechanism of two-component systems in regulating carbapenem resistance of Klebsiella pneumoniae].

Carbapenem-resistant Klebsiella pneumoniae (CRKP) leads to high mortality of infected patients. How to deal with CRKP is an urgent problem in clinical practice, and it is imperative to carry out researchon carbapenem resistance mechanism of CRKP. The two-component systems (TCSs) areassociated with the development of drug resistance in a variety of bacteria, and TCSs were expected to be important therapeutic targets for CRKP. Therefore, this article reviewed the mechanisms of TCSs in the regulation of CRKP from the following several aspects: common mechanisms of carbapenem resistance of CRKP, research progress in drug resistance of TCSs, relationships between Klebsiella pneumoniae and TCSs, and so on. It may provide some research ideas for future research and the references for clinical diagnosis and treatment.

[Clinical characteristics and epidemiological analysis of pathogenic bacteria of severe abdominal infection in surgical intensive care unit].

OBJECTIVE: To study the clinical characteristics of patients with severe abdominal infection and the epidemiological characteristics of pathogenic bacteria in a hospital, to provide a basis for rational use of antibiotics and reduce the drug resistance rate of pathogens. METHODS: A retrospective analysis was performed on 237 patients with abdominal disease as the primary disease admitted to the surgical intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from January 1st, 2017 to December 31st, 2019. They were divided into two groups according to whether abdominal infection occurred or not. The clinical features of patients in both groups were analyzed, including gender, age, acute physiology and chronic health evaluation II (APACHE II) score, chronic underlying diseases, primary abdominal site, abdominal trauma or bleeding, multiple organ dysfunction syndrome (MODS) involving organs and surgical treatment. At the same time, the bacterial origin, bacterial distribution and antibiotics sensitivity test results of patients with abdominal infection were recorded. RESULTS: Abdominal infection occurred in 141 of the 237 patients and did not occur in the remaining 96 patients. There were no statistically significant differences between the abdominal infection group and the non-abdominal infection group in terms of gender, age, chronic underlying diseases, etiology and trauma. The APACHE II score in the abdominal infection group was obviously higher than that of the non-abdominal infection group (24.0±8.1 vs. 17.1±5.8, P < 0.01). Incidences of abdominal bleeding, MODS involving four or more organs, surgery and the times of surgery ≥ 3 in the abdominal infection group were significantly higher than those in the non-abdominal infection group (36.2% vs. 17.7%, 20.6% vs. 1.0%, 84.4% vs. 21.9%, 9.3% vs. 0%, all P < 0.05). Among the 141 patients with abdominal infection, 107 obtained positive microbial culture results, and a total of 133 pathogenic strains were detected, including 115 strains of bacteria (86.5%) and 18 strains of fungi (13.5%). The main source of bacteria was abdominal drainage (46.1% of non-bloody specimens and 13.9% of bloody specimens). Among the 115 bacteria, Gram-negative (G-) bacteria were the most common (72.2%) and Gram-positive (G+) bacteria accounted for 27.8%. Escherichia coli and Acinetobacter baumannii were the top two G- bacteria (40.9% and 13.9%, respectively), and enterococcus faecalis accounted for the largest proportion of G+ bacteria (7.8%). The pathogenic bacteria of abdominal infection were sensitive to tigacycline. CONCLUSIONS: The patients with abdominal infection in our hospital had high APACHE II score, more organs failure and were easily complicated with intraperitoneal hemorrhage and required surgical intervention and even repeated surgery. The pathogenic bacteria in patients with abdominal infection in ICU were mainly G- bacteria, and the rate of multi-drug resistance of Acinetobacter baumannii was high. Empirical anti-infective treatment should be started as soon as possible according to the microbial spectrum of the region until the pathogenic bacteria results are obtained. Broad-spectrum antimicrobial therapy and combined antimicrobial therapy are recommended for the healthcare acquired abdominal infection in hospital.

Novel noncoding RNAs biomarkers in acute respiratory distress syndrome.

Introduction: Acute respiratory distress syndrome (ARDS) is a very common condition associated with critically ill patients, which causes substantial morbidity and mortality. Currently, there is no effective clinical ARDS treatment strategy. Novel targets that effectively treat ARDS need to be found.Areas covered: Data sources were published articles through June 2019 in PubMed using the following keywords: 'acute respiratory distress syndrome,' 'miRNAs,' 'lncRNAs,' and 'biomarkers.' The selection of studies focused on in cellular model, animal model, and clinical studies of ARDS.Expert commentary: Accumulated evidence revealed that some specific miRNAs and lncRNAs could regulate the signaling pathways of the pathophysiology by targeting specific molecule in ARDS. The differentially expressed miRNAs exert a crucial role in apoptosis of neutrophil, antigen-presenting cells and lung epithelial cell, and the dysfunction of mitochondrial. Recently, the influence of lncRNAs upon miRNA function is also rapidly emerging. In some cases, lncRNA MALAT1 target TLR4 to mediate the p38 MAPK and NF-κB signaling pathway in ARDS rat model. In other cases, lncRNA CASC2 was found to act as a ceRNA of miR-144-3p which directly targeted AQP1 in LPS-induced A549 cell. In addition, other miRNA-lncRNA regulatory patterns in ARDS and novel biomarkers still require deeper research.

[The effect of mild hypothermia on interleukin-3 expression in septic mice].

OBJECTIVE: To investigate whether or not mild hypothermia can inhibit the expression and release of interleukin-3 (IL-3) in septic mice and whether it has a protective effect on septic mice. METHODS: According to random number table method, 120 male C57BL/6 mice were divided into sham operation group (Sham group), sepsis normal temperature group (NT group) and sepsis mild hypothermia group (HT group), with 40 mice in each group. The acute septic mice model was established by cecal ligation and puncture (CLP) method. In the HT group, body temperature decreased to 32-34 centigrade at 1 hour after CLP and was maintained for 8 hours, followed by rewarming slowly to 36-38 centigrade. In the NT group, mice were resuscitated after CLP and body temperature was maintained at 36-38 centigrade throughout the experimental periods, while in Sham group, the cecum was not ligated or punctured and resuscitated routinely. The average arterial pressure (MAP) of 20 mice in each group was monitored for 12 hours after CLP, and the survival time was observed for 4 days. The serum of remaining mice was collected at 12 hours after CLP, and the mice were killed for organ tissues. The serum levels of IL-3, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA). Western blotting was used to detect IL-3 protein expression in spleen and lung tissues. The pathological changes of lung and liver tissues were observed under microscope and the semi-quantitative scoring was performed. RESULTS: MAP of NT group and HT group decreased after CLP with the prolongation of time. MAP (mmHg, 1 mmHg = 0.133 kPa) of HT group at 10 hours and 12 hours after CLP were significantly higher than those of NT group (10 hours: 74.4±12.4 vs. 62.9±7.2, 12 hours: 68.4±3.7 vs. 57.5±9.6, both P < 0.01). Compared with Sham group, serum levels of IL-3, IL-6 and TNF-α in NT group and HT group were significantly increased at 12 hours after CLP [IL-3 (ng/L): 2.21±0.87, 0.18±0.04 vs. 0, IL-6 (ng/L): 51.22±18.65, 24.68±6.20 vs. 1.36±0.34, TNF-α (ng/L): 101.43±38.60, 72.15±25.12 vs. 14.49±5.17, all P < 0.01]. IL-3 protein expressions of spleen and lung tissues in NT group and HT group were significantly increased compared to those in Sham group (IL-3/ß-actin: spleen tissue 0.200±0.039, 0.135±0.023 vs. 0.090±0.023, lung tissue 0.085±0.009, 0.056±0.009 vs. 0.039±0.005, all P < 0.01). The serum levels of IL-3, IL-6 and TNF-α were significantly lower in HT group than those in the NT group [IL-3 (ng/L): 0.18±0.04 vs. 2.21±0.87, IL-6 (ng/L): 24.68±6.20 vs. 51.22±18.65, TNF-α (ng/L): 72.15±25.12 vs. 101.43±38.60, all P < 0.01]. The expressions of IL-3 protein in HT group were significantly lower than those in NT group (IL-3/ß-actin: spleen tissue 0.135±0.023 vs. 0.200±0.039, lung tissue 0.056±0.009 vs. 0.085±0.009, both P < 0.01). The lung tissue injury and liver tissue injury scores in HT group were significantly lower than those in NT group (lung tissue injury score: 4.00±1.41 vs. 6.67±2.16, P = 0.03, liver tissue injury score: 3.83±1.47 vs. 7.17±2.14, P = 0.01). Compared to NT group, the 4-day survival rate of HT group was significantly improved (50% vs. 30%, P < 0.01). CONCLUSIONS: Mild hypothermia can significantly inhibit the expression and release of IL-3 in septic mice, attenuate organ injury, and protecte septic mice.

[Investigation and analysis of questionnaire on clinical thinking in the diagnosis of severe infection in Guangxi].

OBJECTIVE: To understand the clinical thinking of clinical staff in the diagnosis of severe infection and evaluate their ability to recognize severe infection in the early stage. METHODS: A questionnaire survey was conducted to investigate the clinical thinking of clinical staff attending the academic annual meeting of critical care physicians of Guangxi Medical Doctors Association from September 26 to September 28, 2019. The objects of investigation included doctors, nurses, clinical pharmacists and medical graduate students, except for non-clinical personnel. The basis factors of clinical diagnosis of infection included clinical symptoms, specific biochemical examination, microorganism examination and Next-generation sequencing technology (NGS). The credibility level of each indicator was summarized as high (credibility of 51%-100%) and low (credibility of 0%-50%). RESULTS: Among the more than 600 participants, 540 people participated in the questionnaire survey (participation rate of about 90.0%), and 466 qualified questionnaires (effective rate of 86.3%) were collected, including 280 from doctors, 155 from clinical nurses, 10 from clinical pharmacists and 21 from clinical graduate students. The working years of doctors, nurses, clinical pharmacists and medical graduate students were (8.2±6.0), (6.4±6.3), (4.5±4.0) and (3.8±2.6) years, respectively. The intermediate title (43.2%) dominated in the doctors group, while junior title dominated in the nurses group, clinical pharmacists group and medical postgraduate group (53.5%, 80.0% and 81.0% respectively). Doctors and nurses were mainly from the general intensive care unit (ICU; 73.2% and 51.0% respectively). According to the results of investigation of clinical thinking on the diagnosis of severe infection, there was similar degree of recognition and credibility for infection-related symptoms in the four groups of doctors, nurses, clinical pharmacists and medical graduate students (the credibility of fever was 80.0%-91.1%, low blood pressure 76.2%-90.0%, disturbance of consciousness 80.0%-85.0%, breathing 81.0%-100.0%, reduced of urine 81.9%-90.0%). The interpretation for pathogen culture and NGS results was insufficient because 29.3%-42.6% of the medical staff did not understand NGS. There were differences in the interpretation of the results of pathogen culture (positive specimen culture could diagnose infection; medical vs. nursing vs. pharmacists vs. student: 93.6% vs. 85.2% vs. 90.0% vs. 85.7%, P = 0.021). There were significant differences among the four groups in some traditional infection-related laboratory indexes which included increased white blood cell count (WBC; χ2 = 8.542, P = 0.026), increased C-reactive protein (CRP; χ2 = 8.826, P = 0.024), increased interleukin-6 (IL-6; χ2 = 13.944, P = 0.002), positive 1, 3-ß-D glucan detection test (G test; χ2 = 10.988, P = 0.009) and positive galactomannan antigen detection test (GM test; χ2 = 12.306, P = 0.004). CONCLUSIONS: There is difference in clinical thinking of diagnosis of severe infection among clinical medical staff in different positions, and the comprehensive diagnostic ability needs to be improved.

The inhibitor of interleukin-3 receptor protects against sepsis in a rat model of cecal ligation and puncture.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. There are multiple cytokines involved in the process of sepsis. As an important upstream cytokine in inflammation, Interleukin-3 (IL-3) plays a crucial role during sepsis, however, its exact role is unclear. The purpose of this study is to discuss the role of IL-3 and its receptor in cecal ligation and puncture (CLP)-induced sepsis in a rat model. The Cluster of Differentiation 123 (CD123, IL-3 receptor alpha chain, IL-3Rac) antibody (anti-CD123) was used to directly target IL-3's receptor and alleviate the effect of IL-3 in the CLP + anti-CD123 group during the early stage of sepsis. CLP was performed in the CLP and CLP + anti-CD123 groups. The time points of observation included 12 h, 24 h, and 5d after the operation. The results showed that the rats in the CLP + anti-CD123 group had lower levels of lactate, serum tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), and Interleukin-6 (IL-6), and also exhibited a higher core temperature, mean arterial pressure (MAP), Oxygenation Index (PO2/FiO2), and end-tidal carbon dioxide (ETCO2) and serum Interleukin-10 (IL-10) levels after CLP than those in the CLP group. Additionally, administration of anti-CD123 led to a stable down-regulation of tyrosine phosphorylation of the IL-3 receptor, a decline in phosphorylation of the Janus kinase 2 (JAK2) protein, and the signal transduction and activation of transcription 5 (STAT5) proteins in lung tissues. Meanwhile, the study revealed that treatment of anti-CD123 can markedly attenuate histological damages in lung and kidney tissues, improve sublingual microcirculation, and prolong survival post sepsis. In conclusion, anti-CD123 reduces mortality and alleviates organ dysfunction by restraining the JAK2-STAT5 signaling pathway and reduces serum cytokines in the development of early sepsis in a rat model induced by CLP.

[Mild hypothermia can delay the occurrence of post-stroke infection: a propensity score matched-cohort study].

OBJECTIVE: To evaluate the effect of mild hypothermia on the incidence of post-stroke infection and explore the relationship between mild hypothermia and outcome of stroke patients by using propensity score matching. METHODS: Patients hospitalized in department of intensive care unit (ICU), neurology and neurosurgery in the First Affiliated Hospital of Guangxi Medical University due to stroke from March 2012 to April 2018 were retrospectively analyzed. According to whether or not mild hypothermia was provided, they were divided into the normal thermic group (NT group) and mild hypothermia treatment group (MHT group). The MHT group patients were matched with the NT group patients by the propensity score matching method at a ratio of 1:1. The observation period was within the first 7 days after admission. Baseline characteristics including age, gender, type of stroke, comorbidities, acute physiology and chronic health evaluation II (APACHE II) score and Glasgow coma score (GCS) on admission, surgical operation, dysphagia, invasive procedures and outcomes of these patients had been analyzed. The primary outcome was incidence of post-stroke infection, and the secondary outcomes included the time of initial infection (TII, the duration from stroke to initial infection), hospital mortality, sequential organ failure assessment (SOFA) at discharge, incidence of complications such as arrhythmia, coagulation dysfunction and multiple organ dysfunction syndrome (MODS). RESULTS: 201 stroke patients were enrolled, 41.8% (84/201) of whom underwent mild hypothermia. Comparison with NT group before matching, there were more males in MHT group (71.4% vs. 56.4%), the proportion of surgical operation, mechanical ventilation, deep vein catheterization and gastric catheterization were higher (78.6% vs. 54.7%, 84.5% vs. 39.3%, 90.5% vs. 37.6%, 98.8% vs. 70.9%), and so as incidence of infection (90.5% vs. 72.6%), in-hospital mortality (27.4% vs. 12.8%) and TII [hours: 62.00 (35.25, 93.00) vs. 42.00 (28.50, 69.50)]. All the differences were statistically significant (all P < 0.05). Fifty-three patients in the MHT group were matched with 53 patients in the NT group. After matching, there was no significant difference in 15 baseline characteristics between two groups. Significant differences in infection and hospital mortality between the MHT group and NT groups disappeared (92.5% vs. 88.7%, 22.6% vs. 26.4%, both P > 0.05), while TII of MHT group was longer than that of the NT group [hours: 62.00 (40.75, 92.25) vs. 40.00 (28.00, 63.00), P = 0.000]. There were no statistically significant differences in SOFA score or complications between the two groups either before or after matching. CONCLUSIONS: Mild hypothermia had no significant effect on the incidence of post-stroke infection and hospital mortality, it could delay the occurrence of infection and provide longer duration of treatment.