Evaluation of droplet digital PCR rapid detection method and precise diagnosis and treatment for suspected sepsis (PROGRESS): a study protocol for a multi-center pragmatic randomized controlled trial.

BACKGROUND: Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice. METHODS: PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90. DISCUSSION: It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT's ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay's capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients. TRIAL REGISTRATION: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022-'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT05190861 .

CD47 blockade enhances therapeutic efficacy of cisplatin against lung carcinoma in a murine model.

Cisplatin (CDDP) is the first generation of platinum-based drug and is widely used to treat many cancers due to its potency. The present study aims to explore the effects of CDDP on lung carcinoma and its relationship with macrophage phagocytosis. In in vitro study, murine and human lung cancer cell lines were applied and treated with CDDP, CD47 antibody (aCD47), or CDDP plus aCD47. In in vivo study, a tumor xenograft animal model was treated with CDDP, aCD47, or CDDP plus aCD47. Real-time PCR was applied to determine the mRNA expressions. Enzyme-linked immunosorbent assay (ELISA), Western blotting, and Immunofluorescent staining were applied to determine the protein expressions. Flow cytometry was applied to analyze cell apoptosis, phagocytosis, and specific cell populations. CDDP enhanced the expressions of CD47 in lung cancer cells. Interestingly, the blockage of CD47 enhanced the macrophages' phagocytic activity on the CDDP-treated tumor cells. The treatment of CDDP and aCD47 exhibited anti-tumor effects and prolonged the LLC tumor-bearing mice survival time. Mechanistic studies revealed that the treatment of CDDP and aCD47 regulated the phagocytic activity of macrophage, percentage of CD8+ T cells, and cytokines (tumor growth factor (TGF)-ß, interleukin (IL)12p70, and interferon (IFN)-γ) in the tumor-bearing model. CD47 blockade enhanced therapeutic efficacy of cisplatin against lung carcinoma in vivo and in vitro.

miR-27a is up regulated and promotes inflammatory response in sepsis.

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of multiple target genes. Dysregulation of miRNAs is common in sepsis. Through microRNA microarray and qRT-PCR we found that the levels of miR-27a, miR-153 and miR-143 are up regulated, while let-7a, miR-218 and miR-129-5p are down regulated in lungs of septic mice. Knocking down of miR-27a down regulates expression levels of TNF-α and IL-6 significantly via reducing the phosphorylation level of NF-κB p65 and inhibiting its DNA binding activity. Furthermore, neutralisation of miR-27a up regulates PPARγ level, down regulates TNF-α expression, relieves pulmonary inflammation and promotes survival of septic mice, which demonstrates that miR-27a plays an important role in regulating inflammatory response in sepsis and provides a potential target for clinical sepsis research and treatment.

Comparison of outcomes between preoperative and postoperative systemic treatment in patients with hepatocellular carcinoma: a SEER database-based study.

Background: Significant advancements in systemic treatment for hepatocellular carcinoma have been made in recent years. However, the optimal timing of systemic treatment before or after surgery remains unknown. This study aims to evaluate the impact of sequencing systemic treatment and surgical intervention on the long-term prognosis of hepatocellular carcinoma patients. Methods: In our study, we analyzed data from patients diagnosed with primary liver cancer (2004-2015) extracted from the SEER database. Patients who underwent both systemic treatment and surgical intervention were selected, divided into preoperative and postoperative systemic therapy groups. The primary endpoint of the study is overall survival(OS), and the secondary endpoint is cancer-specific survival (CSS). Propensity score matching (PSM) reduced the influence of confounding factors, while Kaplan-Meier curves and a multivariable Cox proportional hazards model accounted for variables during survival analysis. Results: A total of 1918 eligible HCC patients were included, with 1406 cases in the preoperative systemic treatment group and 512 cases in the postoperative systemic treatment group. Survival analysis showed that both the preoperative group demonstrated longer median overall survival (OS) and median cancer-specific survival (CSS) before and after PSM. After conducting multivariate COX regression analysis with stepwise adjustment of input variables, the postoperative systemic treatment group continued to exhibit a higher risk of all-cause mortality (HR: 1.84, 95% CI: 1.55-2.1) and cancer-specific mortality (HR: 2.10, 95% CI: 1.73-2.54). Subgroup analysis indicated consistent results for overall survival (OS) across different subgroups. Conclusions: Hepatocellular carcinoma patients from the SEER database who received preoperative systemic therapy had superior OS and CSS compared to those who received postoperative systemic therapy.

Exposure of Danio rerio to environmental sulfamethoxazole may contribute to neurobehavioral abnormalities via gut microbiome disturbance.

The neurotoxic effects and mechanisms of low-dose and long-term sulfamethoxazole (SMZ) exposure remain unknown. This study exposed zebrafish to environmental SMZ concentrations and observed behavioral outcomes. SMZ exposure increased hyperactivity and altered the transcript levels of 17 genes associated with neurological function. It impaired intestinal function by reducing the number of intestinal goblet cells and lipid content. Metabolomic results indicated that the contents of several lipids and amino acids in the gut were altered, which might affect the expression levels of neurological function-related genes. Metagenomic results demonstrated that SMZ exposure substantially altered the composition of the gut microbiome. Zebrafish receiving a transplanted fecal microbiome from the SMZ group were also found to exhibit abnormal behavior, suggesting that the gut microbiome is an important target for SMZ exposure-induced neurobehavioral abnormalities. Multi-omics correlation analysis revealed that gut micrometabolic function was related to differential gut metabolite levels, which may affect neurological function through the gut-brain-axis. Reduced abundance of Lefsonia and Microbacterium was strongly correlated with intestinal metabolic function and may be the key bacterial genera in neurobehavioral changes. This study confirms for the first time that SMZ-induced neurotoxicity in zebrafish is closely mediated by alterations in the gut microbiome.

Prognostic value of poly-microorganisms detected by droplet digital PCR and pathogen load kinetics in sepsis patients: a multi-center prospective cohort study.

This study aimed to investigate the prognostic value of a novel droplet digital polymerase chain reaction (DDPCR) assay in sepsis patients. In this prospective cohort study, univariable and multivariable Cox regressions were used to assess risk factors for 28-day mortality. We also monitored pathogen load together with clinical indicators in a subgroup of the cohort. A total of 107 sepsis patients with positive baseline DDPCR results were included. Detection of poly-microorganisms [adjusted hazard ratio (HR) = 3.19; 95% confidence interval (CI) = 1.34-7.62; P = 0.009], high Charlson Comorbidity Index (CCI) score (adjusted HR = 1.14; 95% CI = 1.01-1.29; P = 0.041), and Sequential Organ Failure Assessment (SOFA) score (adjusted HR = 1.18; 95% CI = 1.05-1.32; P = 0.005) at baseline were independent risk factors for 28-day mortality while initial pathogen load was not associated (adjusted HR = 1.17; 95% CI = 0.82-1.66; P = 0.385). Among 63 patients with serial DDPCR results, an increase in pathogen load at days 6-8 compared to baseline was a risk factor for 28-day mortality (P = 0.008). Also, pathogen load kinetics were significantly different between day-28 survivors and nonsurvivors (P = 0.022), with a decline overtime only in survivors and an increase from days 3 and 4 to days 6-8 in nonsurvivors. Using DDPCR technique, we found that poly-microorganisms detected and increased pathogen load a week after sepsis diagnosis were associated with poor prognosis.IMPORTANCEThis prospective study was initiated to explore the prognostic implications of a novel multiplex PCR assay in sepsis. Notably, our study was the largest cohort of sepsis with droplet digital polymerase chain reaction pathogen monitoring to date, allowing for a comprehensive evaluation of the prognostic significance of both pathogen species and load. We found that detection of poly-microorganisms was an independent risk factors for 28-day mortality. Also, pathogen load increase 1 week after sepsis diagnosis was a risk factor for 28-day mortality, and differential pathogen load kinetics were identified between day-28 survivors and nonsurvivors. Overall, this study demonstrated that pathogen species and load were highly correlated with sepsis prognosis. Patients exhibiting conditions mentioned above face a more adverse prognosis, suggesting the potential need for an escalation of antimicrobial therapy.Registered at ClinicalTrials.gov (NCT05190861).

Intermittent hypoxia inhibits anti-tumor immune response via regulating PD-L1 expression in lung cancer cells and tumor-associated macrophages.

Accumulating evidence has shown an increased tumor incidence and reduced survival rate in cancer patients with obstructive sleep apnea (OSA). Although intermittent hypoxia is known to play a crucial role, the molecular mechanism by which intermittent hypoxia accelerates lung cancer progression remains to be elucidated.A lung cancer xenograft mouse model was established by subcutaneously injecting LLC cells into C57BL/6 mice. The tumor-bearing mice were exposed to either normoxia or intermittent hypoxia and received either IgG2a, anti-programmed death ligand-1 (PD-L1), PX-478, or anti-PD-L1 + PX-478 treatment.A significant upregulation of tumor associated macrophages (TAMs) papulation and PD-L1 levels was observed in lung adenocarcinoma patients with OSA. We further confirmed that hypoxia-inducible factor-1 alpha (HIF-1α) regulates PD-L1 at transcriptional levels, mainly through binding to the hypoxia response element 4. Using a lung cancer xenograft mouse model, we observed that intermittent hypoxia exposed tumors grew faster and bigger with upregulated HIF-1α and PD-L1 expression, enhanced TAMs and Treg populations, and reduced cytotoxic T cells and cytokine secretion. Finally, we found a combination of PX-478 and anti-PD-L1 exerted an encouraging tumor inhibition effect compared to single treatment. Combination therapies based on HIF-1α and PD-L1 blockade might serve as a promising strategy to treat lung cancer patients with OSA.

Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFß signaling.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear. METHODS: Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFß expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo. RESULTS: OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFß signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression. CONCLUSIONS: IH promotes lung cancer progression by upregulating TGFß signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.

Laser speckle contrast imaging to monitor microcirculation: An effective method to predict outcome in patients with sepsis and septic shock.

Background: This study examines the microcirculation of patients with sepsis and septic shock using Laser Speckle Contrast Imaging (LSCI) technology, to enhance monitoring and predict outcomes of sepsis and septic shock. Methods: From 01 July 2021, to 31 January 2022, 44 patients diagnosed with septic shock and sepsis were included in the study, their clinical data were collected, and LSCI was used to monitor the mean peripheral blood flow perfusion index (PI). Results: The average peripheral blood flow PI of septic shock patients was significantly lower than that of septic patients, with a cutoff value of 26.25. The average peripheral blood flow PI negatively correlated with acute physiology and chronic health evaluation (APACHE) Ⅱ score (p = .01 < .05), sequential organ failure assessment (SOFA) score (p < .01), and lactic acid levels (p = .01 < .05). We report average peripheral blood flow no correlation with age, mean arterial pressure, body temperature, oxygen saturation, heart rate, and body mass index. There was no correlation with procalcitonin, C-reactive protein (CRP), red blood cell distribution width, or platelet distribution width (p > .05). PI significantly correlated with the group sepsis and septic shock (p < .001, r = -.865). And PI significantly correlated with the outcome or mortality (p = .007 < .05, r = -.398). The ROC curve was calculated for PI and the sensitivity was 81.3%, and the specificity was 75% when PI cutoff value chooses 20.88. Conclusion: LSCI technology successfully detected the fingertip microcirculation of patients with septic shock. LSCI can reliably differentiate patients with sepsis vs patients with septic shock. Additionally, the average peripheral blood PI negatively correlated with APACHE Ⅱ, SOFA score, and lactate acid levels, providing useful and supplementary information for the diagnosis and monitoring of septic shock. Trial registration: Chictr2100046761. Registered on May 28, 2021. Clinical Trial Registration: clinicaltrials.gov, identifier Chictr2100046761.

Lung-specific exosomes for co-delivery of CD47 blockade and cisplatin for the treatment of non-small cell lung cancer.

A cluster of differentiation 47 (CD47) and immune-modulatory protein for myeloid cells has been implicated in cisplatin (CDDP) resistance. Exosome delivery of drugs has shown great potential for targeted drug delivery in the treatment of various diseases. In the current study, we explored the approach of co-delivering CDDP and CD47 antibody with MDA-MB-231 cell-derived exosome 231-exo (CaCE) and assessed the phagocytosis activity of bone marrow flow cytometry derived macrophages (BMDM) against co-cultured A549 cells. CD8+ T-cell proliferation was examined with flow cytometry analysis. In vivo, we used the Lewis lung carcinoma (LLC) tumor-bearing mouse model and assessed survival rate, tumor weight, phagocytosis, and T-cell proliferation, as well as cytokine levels in tumors analyzed by enzyme-linked immunoassay (ELISA). Although co-administration of CDDP with anti-CD47 (CDDP and aCD47) showed a significant antitumor effect, CaCE had an even more dramatic anticancer effect in survival rate and tumor weight. We observed increased phagocytosis activity selectively against lung tumor cells in vivo and in vitro with exosome CaCE treatment. CaCE treatment also increased T-cell proliferation compared to the vehicle treatment and co-administration groups. Furthermore, immunostimulatory interleukin (IL)-12p and interferon (IFN)-γ were increased, whereas transforming growth factor ß (TGF-ß) were decreased, indicating the improved CDDP anticancer effect is related to a tumor microenvironmental change. Our study demonstrates a dramatically improved anticancer effect of CDDP when administered by exosome co-delivery with anti-CD47.

Development of a model for early differentiation of adenovirus pneumonia from Mycoplasma pneumoniae pneumonia.

Background: Adenovirus pneumonia (AVP) and Mycoplasma pneumoniae pneumonia (MPP) have similar clinical manifestations such as a high prevalence of lung consolidation, making the differential diagnosis difficult before the etiology is reported. This study aimed to compare AVP and MPP, and to build a predictive model to differentiate them early. Methods: We selected 198 cases of AVP and 876 cases of MPP. Clinical manifestations, computed tomography (CT) features, and biomarkers were compared. A logistic regression model was built to predict AVP. The area under the curve (AUC) of the receiver-operating characteristic was calculated to evaluate the discriminant ability of the prediction model. Results: Patients in the AVP group were mainly infants and toddlers, while the MPP group had more pre-school age children. The rate of hypoxemia and severe pneumonia was 3- and 11-times higher, respectively, in the AVP group than in the MPP group (5.6% vs. 1.8%, 27.8% vs. 2.5%, P<0.01). The proportion of patients with a Pediatric Logistic Organ Dysfunction-2 score ≥2 was 10 times higher in the AVP group than in the MPP group (17.4% vs. 1.7%, P<0.01). Bilateral pneumonia was present in 90.2% of the AVP group. Biomarkers, such as interleukin (IL)-2 receptor, IL-10 and lactic dehydrogenase (LDH), were considerably higher in the AVP group than in the MPP group (P<0.01). The predictive model included eight variables, namely: age, severe pneumonia, bilateral pneumonia, ground-glass attenuation, consolidation, atelectasis, C-reactive protein, and LDH. The AUC was 86.6%. Conclusions: Compared with MPP, AVP affects younger children, presents a more severe respiratory tract involvement, results in a larger range of lung lesions, and is associated with higher inflammatory biomarkers. Our predictive model includes a combination of clinical features, imaging findings, and biomarkers. It may help pediatricians in the early differentiation of AVP from MPP.

Phosphoproteome profiling provides insight into the mechanisms of ventilator-induced lung injury.

The incidence of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common health problem in the clinic and is projected to increase in prevalence in the future. Mechanical ventilation is commonly used to provide respiratory support and has become indispensable in emergency and critical medicine. However, ventilator use can result in lung tissue damage, collectively termed ventilator-induced lung injury (VILI). In the present study, phosphoprotein profiling of blood and tissue samples from ventilated and non-ventilated mice was performed and key changes in protein levels and cell signaling during VILI were identified. Activation of the PI3K/AKT and mitogen activated protein kinase signaling pathways, in addition to changes in expression of cancer, inflammatory and cell-death related proteins were detected in response to mechanical ventilation. Focal adhesion-related protein levels and signaling pathways were also significantly altered in an injury model compared with control. VILI can affect patient mortality in ALI and ARDS cases, and no targeted treatment options currently exist. Identifying biomarkers and understanding the signaling pathways associated with VILI is critical for the development of future therapies.

Potential mechanism and key genes involved in mechanical ventilation and lipopolysaccharide­induced acute lung injury.

Mechanical ventilation (MV) and lipopolysaccharide (LPS) infection are common causes of acute lung injury. The aim of the present study was to identify the key genes and potential mechanisms involved in mechanical ventilation (MV) and lipopolysaccharide (LPS)­induced acute lung injury (ALI). Gene expression data of adult C57BL/6 mice with ALI induced by inhaling LPS, MV and LPS + MV were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) associated with MV, LPS and LPS + MV were screened, followed by functional enrichment analysis, protein­protein interaction network construction, and prediction of transcription factors and small molecule drugs. Finally, the expression of key genes was verified in vivo using reverse transcription­quantitative PCR. A total of 63, 538 and 1,635 DEGs were associated with MV, LPS and LPS + MV, respectively. MV­associated genes were significantly enriched in the 'purine ribonucleotide metabolic process'. LPS and LPS + MV­associated genes were significantly enriched in 'cellular response to cytokine stimulus' and 'cell chemotaxis'. All three conditions were enriched in 'TNF signaling pathway' and 'IL­17 signaling pathway'. Expression levels of C­X­C motif chemokine ligand (CXCL)2, CXCL3 and CXCL10 were upregulated in the LPS and LPS + MV groups. Adenosine A2b receptor, zinc finger and BTB domain­containing 16 and hydroxycarboxylic acid receptor 2 were identified as DEGs in the MV group. Compared with the control group, Early growth response 1 and activating TF 3 was upregulated in all three groups. Similarities and differences were observed among the MV­ and LPS­induced ALI, and MV may enhance the effects of LPS on gene expression. MV may affect urine ribonucleotide metabolic­related processes, whereas LPS may cause cell chemotaxis and cytokine stimulus responses in ALI progression. The inflammatory response was shared by MV and LPS. The results of the present study may provide insight into a theoretical basis for the study and treatment of ALI.

In silico comparative molecular docking analysis and analysis of the anti-inflammatory mechanisms of action of tanshinone from Salvia miltiorrhiza.

Tanshinones are a class of abietane diterpene compounds extracted from Salvia miltiorrhiza, and have been used for medical purposes in traditional Chinese medicinal practices. This herb has been used in the treatment of chronic obstructive pulmonary disease (COPD), breast cancer and inflammatory disorders. This study examined the anti-inflammatory properties of tanshinones. In addition, lipid-soluble compounds which were specific to Tanshinone class were also highlighted, out of which two compounds, dihydrotanshinone I and cryptotanshinone were selected with the aim of creating a new research perspective in order to further elucidate the mechanisms of the pathogenesis of inflammatory diseases. Moreover, interaction analyses were carried out successfully to determine the interactions formed between both dihdrotanshinone I and cryptotanshinone, and target proteins. The bioactivity properties and various other pharmacokinetic and pharmacodynamic analyses discerned that crytptotanshinone was more effective dihydrotanshinone and more 'drug-like' than its counterpart. It was found to have a better solubility and permeability, and thus has potential for use as an anti-inflammatory agent.

Assessment of vocal cord movement by ultrasound in the ICU.

PURPOSE: Ultrasound can be used to non-invasively and rapidly examine airway conditions, but vocal cord visualization with the traditional approaches is poor. Our aim was to compare the accuracies of front-side transverse-axis ultrasound (FTU), lateral-side longitudinal-axis ultrasound (LLU), and the combination of both approaches for vocal cord movement disorder diagnoses (e.g., vocal cord paralysis or arytenoid cartilage dislocation). METHODS: We compared FTU, LLU, and the combination of both methods for patients in the intensive care unit (ICU). We used nasal fiber-optic endoscopy to confirm vocal cord injury. RESULTS: Among the 120 patients examined, 24 (20%) had vocal cord paralysis. The visualization rate of vocal cords for FTU was 71.7% (assessable, 86; non-assessable, 34), that for LLU was 88.3% (assessable, 106; non-assessable, 14), and that for the combined approach was 96.7% (assessable, 116; non-assessable, 4). The sensitivities and specificities were 58.3% (14/24) and 75% (72/96) for FTU, 91.7% (22/24) and 87.5% (84/96) for LLU, and 100% (24/24) and 95.8% (92/96) for the combined approach. Visualization rates for LLU were significantly higher than for FTU (P = 0.002); FTU + LLU rates were higher than those for FTU (P = 0.001). The difference between LLU and FTU + LLU was not statistically significant (P = 0.025). CONCLUSION: LLU can be used to evaluate arytenoid cartilage activity in ICUs, and the results are highly correlated with the diagnosis of nasal fiber-optic endoscopy. The combination of FTU and LLU shows promise as a rapid primary screening method for vocal cord injury.

Celastrol attenuates ventilator induced lung injury in mouse through inhibition of MAPK pathway.

PURPOSE: Previous studies have shown that celastrol has anti-inflammatory, anti-oxidative and anti-tumor activities, but little is known about its protective effects on ventilator induced lung injury (VILI). This study is aimed to investigate the effects of celastrol on VILI and explore its potential mechanism. METHODS: A total of 40 ICR male mice aged 7-9 weeks were randomly divided into 4 groups (n=10 per group): control group (Con), control + celastrol group (Con+Ce), mechanical ventilation group (Ven) and mechanical ventilation + celastrol group (Ven+Ce). The lungs were collected for histological examination, detection of W/D, and MPO, MDA, SOD, inflammatory cytokines (IL-1ß, IL-6, IL-10 and TNF-α) by ELISA, p-P38 and p-JNK 1/2 protein by Western blotting, and collagen-1 and TGF-ß mRNA expression by RT-PCR. RESULTS: The W/D in the Ven group was significantly higher than the W/D in the Con group and the Ven+Ce group (both P<0.01). Mechanical ventilation for 4 h markedly increased lung MPO and MDA activity, TNF-α, IL-1ß and IL-6, but dramatically reduced SOD and IL-10 (all P<0.01). However, celastrol pre-treatment compromised the increased MPO, MDA, TNF-α, IL-1ß, IL-6 (all P<0.01) and significantly increased SOD (P=0.035<0.05) and IL-10 (P<0.01). In addition, mRNA level of collagen-1 and TGF-ß as well as p-P38 and p-JNK 1/2 protein expression increased significantly (P<0.01) after mechanical ventilation, which however were markedly reduced in the presence of celastrol pre-treatment. CONCLUSION: Celastrol pre-treatment may exert anti-oxidative and anti-inflammatory effects and related lung fibrosis to attenuate VILI in mice, which may be related to the inhibition of p-P38 and p-JNK 1/2 by MAPK pathway.

Bedside monitoring of patients with shock using a portable spatially-resolved near-infrared spectroscopy.

Clinical monitoring of shock mainly depends on blood-oxygen-indices obtained from invasive blood sample tests. The central internal jugular central vein oxygenation level (ScvO2) has been considered as a gold standard indicator for shock prediction. We developed a noninvasive spatially-resolved near-infrared spectroscopy (SR-NIRS) to measure tissue blood oxygen saturation (StO2) surrounding the region of taking blood sample for the ScvO2 test in 25 patients with shock. StO2 values were found to be highly correlated (r = 0.84, p < 0.001) with ScvO2 levels and the concordance coefficient of 0.80 is high. The results suggest the potential of noninvasive SR-NIRS for bedside shock monitoring.