Aeroacoustic performance of a seal vibrissa shaped cylinder.

Bio-inspired geometries have many applications in engineering, including in the field of noise control. In this work, the aeroacoustic performance of a seal vibrissa shaped cylinder (SVSC) is investigated and compared to that of a circular cylinder at Re = 37 000. Experiments conducted in an anechoic wind tunnel are compared to results from a hybrid aeroacoustic simulation with excellent agreement observed between the two. The overall sound pressure level is found to be 24.3 dB lower for the SVSC, and no prominent narrowband component is observed in the acoustic spectrum. Analysis of the flow field and surface pressure fluctuations reveals that this is because the usual large-scale alternating vortex shedding realized for bluff body flows is absent for the SVSC. Instead, smaller uncorrelated vortices are shed from the upper and lower sides of the geometry, which, when combined with a lower spanwise correlation, results in a much lower acoustic intensity spread over a broader frequency range.

Pain management of nalbuphine and sufentanil in patients admitted intensive care unit of different ages.

BACKGROUND: Pain relief for patients in the intensive care unit (ICU) can improve treatment outcomes and reduce the burden on doctors and nurses. This study aims to report the clinical analgesic and sedative effects of nalbuphine and sufentanil on ICU patients. METHODS: This study retrospectively analyzed the medical records of 87 critically ill patients who received nalbuphine or sufentanil infusion in the ICU, including demographic data, diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II, Critical Care Pain Observation Tool (CPOT), Richmond Agitation-Sedation Scale (RASS), systolic and diastolic blood pressure, heart rate and blood oxygen saturation (SpO2). The primary outcomes of this study were CPOT and RASS scores. The secondary outcomes were hemodynamic changes, including systolic blood pressure, diastolic blood pressure, heart rate, and SpO2. The adverse events recorded during pain management, such as hypoxemia, respiration depression and bradycardia, were also collected and analyzed. RESULTS: None of the patients in both groups experienced episode of hypoxemia, respiration depression and bradycardia. However, age-stratified analyses showed that nalbuphine has a better analgesic effect than sufentanil for patients aged ≤ 60 (P < 0.05). In contrast, sufentanil showed a better analgesic effect than nalbuphine for patients aged > 60 ( P < 0.05). Furthermore, nalbuphine has a significantly better sedative effect than sufentanil for patients aged ≤ 60 (P < 0.05). CONCLUSION: ICU patients of different age groups may be suitable for different analgesics. For patients under the age of 60, nalbuphine has better analgesia and sedation than sufentanil, and does not cause respiratory depression and drastic hemodynamic changes.

Optimization of Micafungin Dosage for Chinese Patients with Sepsis in the Intensive Care Unit Based on a Population Pharmacokinetic-Pharmacodynamic Analysis.

PURPOSE: This study aimed to identify parameters that influence micafungin pharmacokinetics in Chinese patients with sepsis in the intensive care unit and optimize micafungin dosage by determining the probability of reaching pharmacodynamic targets. METHODS: Blood samples were collected from 32 Chinese patients with sepsis who were treated with micafungin. The samples were analyzed and used to build a population pharmacokinetic model. Monte Carlo simulations were performed to estimate the probability of achieving adequate plasma levels of micafungin against Candida species. RESULTS: Alanine aminotransferase and sequential organ failure assessment score were found to significantly influence the clearance and peripheral distribution volume of micafungin, respectively. Monte Carlo simulations based on area under the plasma concentration-time curve over 24 h showed that patients must be administered at least 200 and 250 mg micafungin daily to reach minimum inhibitory concentration breakpoints of 0.032 and 0.064 mg/L for Candida glabrata and Candida tropicalis, respectively. Additionally, a probability of target attainment of ≥ 90% could not be achieved for Candida krusei or Candida parapsilosis with a 300 mg daily dose. CONCLUSIONS: The recommended daily dose of micafungin (100 mg) may produce low clinical success ratios in non-Candida albicans infections; therefore, higher doses should be administered to improve clinical outcomes.

MIP-1α induces inflammatory responses by upregulating chemokine receptor 1/chemokine receptor 5 and activating c-Jun N-terminal kinase and mitogen-activated protein kinase signaling pathways in acute pancreatitis.

OBJECTIVE: We aimed to investigate the association of macrophage inflammatory protein (MIP)-1α (CCL3) expression with the severity of acute pancreatitis (AP). METHODS: The patients with AP were selected and divided into mild AP (MAP), moderately severe AP (MSAP), and severe AP (SAP) groups according to the severity of AP. The pancreatic acinar cell line Ar42 j was treated with cerulein to induce in vitro cell AP model. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and the activation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) signaling pathway in stimulated or transfected Ar42 j cells were detected. RESULTS: We detected that the upregulation of MIP-1α was associated with the severity of AP. Patients with SAP showed the highest MIP-1α contents, followed by MSAP, and, lastly, MAP. In cerulein-stimulated Ar42 j cells, the upregulation of MIP-1α, CCR5, TNF-α, and IL-6 was time dependent. In addition, in human recombinant MIP-1α treated Ar42 j cells, the upregulation of TNF-α and IL-6 was MIP-1α-dose-dependent. In contrast, we detected the inhibition of TNF-α and IL-6 in MIP-1α small interfering RNA (siRNA)-treated cells. Also, the activation of the JNK/p38 MAPK signaling pathway was induced and inhibited by human recombinant MIP-1α and MIP-1α siRNA, respectively. CONCLUSION: These results suggested that MIP-1α might be used as a biomarker for the prognosis of AP severity. The MIP-1α-induced inflammatory responses in AP were mediated by TNF-α and IL-6, which were associated with the activation of the JNK/p38 MAPK signaling pathway.

microRNA-542-5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen-activated protein kinase signaling pathway through the negative regulation of P21-activated kinase 1.

Severe acute pancreatitis (SAP) is a condition associated with high rates of mortality and lengthy hospital stays. In the current study, SAP mouse models were established in BALB/c wild-type and P21-activated kinase 1 (PAK1) knockdown mice with the objective of determining the expression of microRNA-542-5p (miR-542-5p) and the subsequent elucidation of the mechanism by which it influences acute lung injury (ALI) by mediating mitogen-activated protein kinase (MAPK) signaling and binding to PAK1. The targeting relationship between miR-542-5p and PAK1 was verified using the bioinformatics prediction website and by the means of a dual-luciferase reporter assay. Following the SAP model establishment, the mice were assigned into various groups with the introduction of different mimic and inhibitors in an attempt to investigate the effects involved with miR-542-5p on inflammatory reactions among mice with SAP-associated ALI. Our results indicated that PAK1 was targeted and negatively mediated by miR-542-5p. Mice with SAP-associated ALI exhibited an increased wet-to-dry weight ratio, myeloperoxidase activity, serum amylase activity, TNF-α, interleukin-1 beta (IL-1ß), and intercellular adhesion molecule-1 (ICAM-1) contents, p-p38MAPK, p-ERK1/2, and p-JNK protein levels as well as PAK1 positive expression, while decreased miR-542-5p levels were observed. Functionally, overexpression of miR-542-5p improves ALI in mice with SAP via inhibition of the MAPK signaling pathway by binding to PAK1.Based on the evidence from experimental models, miR-542-5p was shown to improve ALI among mice with SAP, while suggesting that the effect may be related to the inactivation of the MAPK signaling pathway and downregulation of PAK1 gene. Thus, miR-542-5p could serve as a promising target for ALI treatment.

MicroRNA-339-3p alleviates inflammation and edema and suppresses pulmonary microvascular endothelial cell apoptosis in mice with severe acute pancreatitis-associated acute lung injury by regulating Anxa3 via the Akt/mTOR signaling pathway.

Severe acute pancreatitis (SAP) is a disease with a high mortality. Patients with SAP may also be complicated with acute lung injury (ALI). So far the therapy for SAP-ALI is still limited. Emerging evidences demonstrate that microRNAs (miRs) could play a role in SAP-ALI. This study aims to define the role of miR-339-3p in SAP-ALI via Anxa3 through the Akt/mTOR signaling pathway. Ten mice were selected as sham group and 36 mice as model group which further assigned into different groups. Relationship between miR-339-3p and Anxa3 was detected by dual luciferase reporter gene assay. Levels of TNF-α, IL-6, and serum amylase (AMS) and myeloperoxidase (MPO) in lung tissues were determined by ELISA. Expression of related genes in pulmonary vascular endothelial cells (PMVECs) and lungs tissues was determined by Western blot analysis and RT-qPCR. Cell apoptosis was detected by flow cytometry and TUNEL. SAP-ALI mice had decreased survival rate, increased levels of TNF-α, IL-6, AMS, MPO, and Schmidt scores. miR-339-3p was poorly expressed in lung tissue of SAP-ALI mice while Anxa3 was reciprocal. Anxa3 was targeted by miR-339-3p. miR-339-3p inhibited the relative expression of the Akt/mTOR signaling pathway-related proteins, alleviated inflammation and edema of SAP-ALI mice, and suppressed apoptosis of PMVECs; Anxa3 exhibited opposite trends. In conclusion, overexpressed miR-339-3p could suppress Anxa3 to inhibit the Akt/mTOR signaling pathway, so as to decrease tissue edema, inflammation, and PMVEC apoptosis in SAP-ALI mice.

Soluble dietary fiber improves energy homeostasis in obese mice by remodeling the gut microbiota.

Intervention with dietary fibers is an important strategy to combat the global epidemic of obesity which is a consequence of energy imbalance. However, a possible role of the gut microbiota in effects of dietary fibers on energy homeostasis remains unclear. Here, we treated a high fat diet-induced obese (DIO) mouse model with soluble dietary fiber. Our results showed that soluble dietary fiber reduced body weight gain and the excessive accumulation of white fat tissue in DIO mice. Notably, soluble dietary fiber increased energy expenditure, but not change energy intake in DIO mice. In accordance, 16S rRNA sequencing revealed that the diversity of the gut microbiota was restored by soluble dietary fiber. Moreover, compared with controls, soluble dietary fiber resulted in a decreased ratio of Firmicutes/Bacteroidetes at the phylum level, and an increased relative abundance of the genera Roseburia at the genus level. Taken together, these findings indicate that soluble dietary fiber improves energy homeostasis and prevents obesity by increasing the diversity of the gut microbiota and the colonization of beneficial bacteria.

Enteral nutrition feeding in Chinese intensive care units: a cross-sectional study involving 116 hospitals.

BACKGROUND: There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. METHODS: This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. RESULTS: A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2-19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2-3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353-0.599; p < 0.001). AGI 4 was significantly associated with lower hazard of EN administration (HR 0.056; 95% CI 0.008-0.398; p = 0.004). In a linear regression model, greater Sequential Organ Failure Assessment scores (coefficient - 0.002, 95% CI - 0.008 to - 0.001; p = 0.024) and male gender (coefficient - 0.144, 95% CI - 0.203 to - 0.085; p < 0.001) were found to be associated with lower EN proportion. As compared with AGI 1, AGI 2-3 was associated with lower EN proportion (coefficient - 0.206, 95% CI - 0.273 to - 0.139; p < 0.001). CONCLUSIONS: The study showed that EN delivery was suboptimal in Chinese ICUs. More attention should be paid to EN use in the early days after ICU admission.

Invasive candidiasis in intensive care units in China: in vitro antifungal susceptibility in the China-SCAN study.

OBJECTIVES: The objectives of this study were to determine species distribution and in vitro antifungal susceptibility of Candida isolates identified in the multicentre China-SCAN study of invasive Candida infection (ICI) in intensive care units (ICUs) across China. METHODS: Candida isolates from patients in the China-SCAN study with documented ICI were evaluated by a central laboratory. Species were identified using chromogenic culture media or the API 20C AUX kit. Susceptibility to fluconazole, voriconazole, itraconazole, caspofungin and amphotericin B was determined using the CLSI broth microdilution method (M27-A3) and updated clinical breakpoints or epidemiological cut-off values. RESULTS: A total of 389 isolates from 244 patients were analysed. Species identified most frequently were Candida albicans (40.1%), Candida parapsilosis (21.3%), Candida tropicalis (17.2%) and Candida glabrata (12.9%). Rarer species such as Lodderomyces elongisporus and Candida ernobii were also identified. Fluconazole susceptibility was evident in 85.9% (134/156) of C. albicans, 62.7% (42/67) of C. tropicalis and 48.2% (40/83) of C. parapsilosis isolates. Susceptibility to voriconazole was ≥ 90% among all species. All isolates were susceptible to amphotericin B and caspofungin except C. glabrata [86.0% (43/50) susceptible to caspofungin]. Cross-resistance between fluconazole and voriconazole was observed for C. parapsilosis and C. glabrata. CONCLUSIONS: Although C. albicans was the predominant single species, non-albicans species constituted >50% of isolates. Fluconazole susceptibility was lower in most non-albicans species, indicating that fluconazole resistance should be closely monitored. Susceptibility to voriconazole, amphotericin B and caspofungin is encouraging. Differences between these data and those from other regions emphasize the importance of assessing regional variations.

Catheter-related Candida bloodstream infection in intensive care unit patients: a subgroup analysis of the China-SCAN study.

BACKGROUND: In patients hospitalized in intensive care units (ICU), Candida infections are associated with increased morbidity, mortality and costs. However, previous studies reported confused risk factors for catheter-related Candida bloodstream infection (CRCBSI). The objective was to describe the risk factors, microbiology, management and outcomes of CRCBSI in the China-SCAN population. METHODS: Patients with ≥1 Candida-positive peripheral blood culture were selected from the China-SCAN study. Peripheral and catheter blood samples were collected for Candida isolation. Patients with the same strain of Candida in peripheral and catheter blood samples were considered as being with CRCBSI, while patients with Candida-positive peripheral blood cultures only or different strains were considered as non-CRCBSI. Data were collected from the China-SCAN study. RESULTS: CRCBSI incidence in ICU was 0.03% (29/96,060), accounting for 9.86% of all candidemia observed in ICU (29/294). The proportion of CRCBSI due to Candida parapsilosis reached 33.3%, more than that of Candida albicans (28.6%). In univariate analyses, older age (P=0.028) and lower body weight (P=0.037) were associated with CRCBSI. Multivariate analysis showed that the sequential organ failure assessment (SOFA) score was independently associated with CRCBSI (odds ratio (OR)=1.142, 95% confidence interval = 1.049-1.244, P=0.002). Catheter removal and immune enhancement therapy were often used for CRCBSI treatment. CONCLUSIONS: In China, CRCBSI was more likely to occur in old patients with low body weight. SOFA score was independently associated with CRCBSI. Candida parapsilosis accounted for a high proportion of CRCBSI, but the difference from non-CRCBSI was not significant.

α-Lipoic acid prolongs survival and attenuates acute kidney injury in a rat model of sepsis.

Acute kidney injury is a frequent and serious complication in patients with severe sepsis. α-Lipoic acid (ALA), a naturally occurring dithiol compound, has been shown to possess anti-inflammatory and anti-oxidative properties. In the present study we investigated whether ALA could attenuate acute kidney injury and improve survival in a rat model of sepsis. Rats were subjected to caecal ligation and puncture (CLP) to induce sepsis. α-Lipoic acid (200 mg/kg) was administered by oral gavage either immediately (early treatment) or 12 h after the surgical procedure (delayed treatment). Both early and delayed ALA treatment effectively prolonged survival, improved pathological damage in kidney tissues and reduced serum blood urea nitrogen and creatinine levels in CLP-induced septic rats. Furthermore, early treatment with ALA markedly inhibited the release of tumour necrosis factor-α, interleukin (IL)-6 and IL-1ß into the serum and reduced mRNA and protein expression of inducible nitric oxide synthase and high mobility group box 1 in kidney tissues from CLP-induced rats. Finally, CLP-induced nuclear factor-κB activation in kidney tissues was significantly suppressed by early ALA treatment. Together, the results indicate that ALA is able to reduce mortality and attenuate acute kidney injury associated with sepsis, possibly by anti-inflammatory actions. α-Lipoic acid may be a promising novel agent for the treatment of conditions associated with septic shock.

SOLUBLE GUANYLATE CYCLASE STIMULATORS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: A SYSTEMATIC REVIEW AND META-ANALYSIS.

ABSTRACT: Aims: We conducted a systemic review and meta-analysis to evaluate the therapeutic efficacy and safety of soluble guanylate cyclase (sGC) stimulators in patients with heart failure with preserved ejection fraction (HFpEF). Methods : We systematically searched PubMed, Embase, and Cochrane Library databases for original randomized controlled trials comparing sGC stimulators with placebo in HFpEF patients. A random-effects model was applied to evaluate the mortality, quality of life, and drug-related adverse events. This meta-analysis is registered in PROSPERO under the number CRD42023457382. Results : We included five studies involving 1,600 HFpEF patients. Comprehensively, the combined risk ratio (RR) for mortality was not significant (RR [95% CI] = 1.44 [0.71 to 2.91], P = 0.31). Furthermore, there were no statistically significant differences in the Kansas City Cardiomyopathy Questionnaire results, including the clinical summary score (weighted mean difference [WMD] [95% CI] =0.32 [-7.38 to 8.02], P = 0.94) and the overall summary score (WMD [95% CI] = -0.87 [-8.87 to 7.14], P = 0.83). Similarly, there was no significant improvement in the 6-minute walk distance (WMD [95% CI] = -6.22 [-18.56 to 6.12], P = 0.32). In addition, drug-related adverse events were more common in patients treated with sGC stimulators (RR [95% CI] = 1.63 [1.25-2.14], P < 0.05). Conclusion : Oral sGC stimulators do not significantly improve mortality outcomes, functional capacity, and quality of life in HFpEF patients but are associated with increased drug-related adverse events. Therefore, we should consider using sGC stimulators in HFpEF patients carefully.

Prolonged versus intermittent ß-lactam infusion in sepsis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The two latest studies on prolonged versus intermittent use of ß-lactam antibiotics in patients with sepsis did not reach consistent conclusions, further contributing to the controversy surrounding the effectiveness of the prolonged ß-lactam antibiotics infusion strategy. We conducted a systemic review and meta-analysis to evaluate the efficacy and safety of prolonged and intermittent ß-lactam infusion in adult patients with sepsis. METHODS: We systematically searched PubMed, EMBASE, and Cochrane Library databases for original randomized controlled trials comparing prolonged and intermittent ß-lactam infusion in sepsis patients. A random-effects model was used to evaluate mortality, clinical success, microbiological success, and adverse events. We also conducted subgroup analyses to explore the impact of various factors on the mortality rates. Relative risk (RR) and corresponding 95% confidence intervals (CIs) were used to calculate the overall effect sizes for dichotomous outcomes. This meta-analysis was registered in PROSPERO (CRD42023463905). RESULTS: We assessed 15 studies involving 2130 patients. In our comprehensive assessment, we found a significant reduction in all-cause mortality (RR, 0.83; 95% CI 0.72-0.97; P = 0.02) and a notable improvement in clinical success (RR, 1.16; 95% CI 1.03-1.31; P = 0.02) in the prolonged infusion group compared to the intermittent infusion group, whereas microbiological success did not yield statistically significant results (RR, 1.10; 95% CI 0.98-1.23; P = 0.11). No significant differences in adverse events were observed between the two groups (RR, 0.91; 95% CI 0.64-1.29; P = 0.60). Additionally, remarkable conclusions were drawn from subgroup analyses including studies with sample sizes exceeding 20 individuals per group (RR, 0.84; 95%CI 0.72-0.98; P = 0.03), research conducted post-2010 (RR, 0.84; 95%CI 0.72-0.98; P = 0.03), cases involving infections predominantly caused by Gram-negative bacteria (RR, 0.81; 95%CI 0.68-0.96; P = 0.02), as well as the administration of a loading dose (RR, 0.84; 95% CI 0.72-0.97; P = 0.02) and the use of penicillin (RR, 0.61; 95% CI 0.38-0.98; P = 0.04). CONCLUSIONS: Compared to intermittent infusion, prolonged infusion of ß-lactam antibiotics significantly decreases all-cause mortality among patients with sepsis and enhances clinical success without increasing adverse events.

Invasive candidiasis in intensive care units in China: a multicentre prospective observational study.

OBJECTIVES: To describe the epidemiology, microbiology and management of invasive Candida infection (ICI) in intensive care units (ICUs) in China. METHODS: A multicentre, prospective, observational study in 67 hospital ICUs across China. Patients were ≥18 years old with clinical signs of infection and at least one of the following diagnostic criteria: (i) histopathological, cytopathological or microscopic confirmation of yeast cells from a normally sterile site; (ii) at least one peripheral blood culture positive for Candida; and (iii) positive Candida culture from a normally sterile site. The China-SCAN study is registered with ClinicalTrials.gov (NCT T01253954). RESULTS: ICI incidence was 0.32% (306 patients/96,060 ICU admissions) and median time between ICU admission and diagnosis was 10.0 days. Candida albicans was the most prevalent single isolate (41.8% of patients), although non-albicans species accounted for the majority of infections. Diagnostic confirmation was based solely on at least one positive blood culture in 290 (94.8%) cases. Treatment was initiated after diagnostic confirmation in 166/268 (61.9%) patients. Triazoles (62.7%) and echinocandins (34.2%) were the most commonly used antifungal agents; first-line therapy was typically fluconazole (37.7%). The median duration of antifungal therapy was 14 days. The mortality rate was 36.6% (112/306); the median time between diagnosis and death was 14.5 days. Mortality was higher in older individuals, those with solid tumours, those with recent invasive mechanical ventilation and those with a higher sequential organ failure assessment score at diagnostic confirmation. Susceptibility to first-line antifungals was associated with lower mortality than dose-dependent susceptibility or complete resistance (P=0.008). CONCLUSIONS: More infections were caused by non-albicans than Candida albicans strains. The majority of patients were treated only after diagnostic confirmation, rather than empirically. First-line antifungal susceptibility was associated with lower mortality.

Safety, tolerability, pharmacokinetics, and efficacy of kukoamine B in patients with sepsis: A randomized phase IIa trial.

PURPOSE: To evaluate the safety, tolerability, pharmacokinetics, and efficacy of kukoamine B (KB), an alkaloid compound with high affinity for both lipopolysaccharide (LPS) and oligodeoxynucle-otides containing CpG motifs (CpG DNA), in patients with sepsis-induced organ failure. MATERIALS AND METHODS: This was a multicenter, randomized, double-blind, placebo-controlled phase IIa trial. Patients with sepsis-induced organ failure were randomized to receive either KB (0.06, 0.12, or 0.24 mg/kg) or placebo, every 8 h for 7 days. Primary endpoint was safety, and secondary endpoints included pharmacokinetic (PK) parameters, changes in inflammatory mediators' level, and prognostic parameters. RESULTS: Of 44 patients enrolled, adverse events occurred in 28 patients [n = 20, 66.7% (KB pooled); n = 8, 57.1% (placebo)], while treatment emergent adverse events were reported in 14 patients [n = 10, 33.3% (KB pooled); n = 4, 28.6% (placebo)]. Seven patients died at 28-day follow-up [n = 4, 13.3% (KB pooled); n = 3, 21.4% (placebo)], none was related to study drug. PK parameters suggested dose-dependent drug exposure and no drug accumulation. KB did not affect clinical outcomes such as ΔSOFA score, vasopressor-free days or ventilator-free days. CONCLUSIONS: In patients with sepsis-induced organ failure, KB was safe and well tolerated. Further investigation is warranted. TRIAL REGISTRATION: http://ClinicalTrials.gov, NCT03237728.

Integrin alphavbeta6 is involved in measles protein-induced airway immune suppression.

BACKGROUND AND AIMS: Measles infection causes immune suppression that contributes to morbidity and mortality of the patients; the mechanism is poorly understood. Regulatory T cells (Treg) play a critical role in immune suppression. Integrin alphavbeta6 (avb6) is associated with Treg's function. This study aims to investigate into the mechanism by which measles C protein (MVP)-induced avb6 contributes the generation of Tregs in the lung. METHOD: MVP was introduced to mouse lung by nasal drops. The expression of avb6 by lung tissue was examined by reverse transcription polymerase chain reaction and Western blotting. The development of tolerogenic dendritic cells (DC) and Tregs in the lung and their functions was examined by flow cytometry. The suppressor function of MVP-induced Tregs was examined by cell culture models. RESULTS: The exposure to MVP markedly increased the expression of avb6 in the lung epithelial cells. Administration of MVP significantly suppressed the levels of IL-4 and IFNγ as well as increases in Tregs in lung tissue. DCs captured the MVP in the lung and differentiate into tolerogenic DCs; the latter has the ability to induce Treg development in the lung. Activation of MVP-induced Tregs powerfully suppressed polarized CD4(+) T cells. CONCLUSIONS: Exposure to MVP can induce Treg development in the lung that plays an important role in the suppression of CD4(+) T cell function.