IntroductionHyperinflammation drives mortality in severe or critical viral pneumonia. We evaluated the association of ulinastatin, an immunomodulatory agent, with 28 day mortality in patients with severe or critical pneumonia caused by COVID-19 or influenza.MethodsIn this multicenter, retrospective cohort study, we included adult patients admitted to the intensive care unit (ICU) with confirmed SARS-CoV-2 or influenza infection. To control for confounding, 1:1 propensity score matching (PSM) was performed.ResultsOf 330 eligible patients, 194 were included in the final matched cohort. In the overall matched cohort, ulinastatin treatment did not significantly reduce 28 day all-cause mortality compared with the control group (29.9% vs. 38.1%; HR 0.69, 95% CI 0.43 to 1.12, p = 0.128). However, exploratory subgroup analysis revealed that the survival benefit was driven predominantly by the critically ill subgroup (HR 0.51, 95% CI 0.30 to 0.87, p = 0.011), with no benefit observed in severe patients (HR 1.48, 95% CI 0.45 to 4.85, p = 0.513). This protective association in critical patients was consistent across COVID-19 and influenza etiologies (P for interaction = 0.313) and was not significantly modified by baseline metabolic comorbidities (all P for interaction > 0.05).ConclusionUlinastatin treatment did not significantly improve 28 day survival in the overall cohort of severe-to-critical viral pneumonia. However, exploratory subgroup analyses suggest a potential survival benefit specifically in critically ill patients, predominantly driven by the COVID-19 subset. Further studies are needed to confirm these findings across specific viral etiologies. These hypothesis-generating findings highlight the need for precision immunomodulation targeting the optimal therapeutic window.

Background Acute lung injury (ALI) is a severe, life-threatening inflammatory condition, characterized by uncontrolled neutrophilic inflammation and tissue damage. That emphasized the urgent need for innovative pharmacologic therapies. The aim of this study was to investigate the effects of Celastrol, a major bioactive compound extracted from the Thunder of God Vine, and the underlying mechanisms of its impact on ALI. Methods In this study, the effects of Celastrol on ALI were assessed using a lipopolysaccharide (LPS)-induced ALI model in C57BL/6 mice. Integrated network pharmacology and transcriptomics (RNA-seq) were utilized to screen for potential therapeutic targets. Furthermore, neutrophil functions, including respiratory burst, degranulation, chemotaxis, and neutrophil extracellular traps (NETs) formation, were assessed. The release of NETs was quantified by MPO-DNA complex ELISA. Crucially, experiments using the specific AKT activator SC79 were performed to validate the functional dependency on the AKT signaling pathway. Results Our results revealed that Celastrol exerted protective effects against LPS-induced ALI by reducing alveolar-capillary membrane dysfunction and suppressing neutrophil recruitment and activation. Multi-omics analysis indicated AKT as a pivotal target of Celastrol. Venn diagram analysis further identified 10 core consensus targets between network pharmacology and transcriptomics, including AKT1. Molecular docking revealed a high binding affinities between Celastrol and AKT1, AKT2 and AKT3, which was corroborated by kinase assays showing that Celastrol potently inhibited AKT kinase activity. Western blotting further confirmed this specific targeting, demonstrating that Celastrol decreased the phosphorylation of AKT (Ser473 and Thr308) without affecting the upstream PI3K. Furthermore, Celastrol suppressed LPS-induced neutrophil activation, evidenced by reduced ROS production, elastase release, chemotaxis, and NETs formation. Mechanistically, Celastrol inhibited NETs formation via the PAD4/citH3 axis and suppressed chemotaxis through the FAK/Rac1/Cdc42 pathway. Notably, the AKT activator SC79 significantly reversed these inhibitory effects, confirming that Celastrol mitigates neutrophil activation and NETs formation primarily by targeting AKT. Conclusion Celastrol has the potential to be developed as a therapeutic candidate for LPS-induced ALI by targeting AKT to inhibit neutrophil respiratory burst, degranulation, chemotaxis and NETs formation. These findings provide novel mechanistic insights into the immunomodulatory action of Celastrol, although its clinical application requires further validation.

Objective To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis. Design Multicentre, double blinded, placebo controlled phase 3 trial. Setting 22 centres in China, September 2016 to December 2020. Participants 1106 adults aged 18-85 years with a diagnosis of sepsis according to sepsis-3 criteria and randomly assigned in a 1:1 ratio to receive thymosin α1 (n=552) or placebo (n=554). A stratified block method was used for randomisation, and participants were stratified by age (<60 and ≥60 years) and centre. Interventions Subcutaneous injection of thymosin α1 or placebo every 12 hours for seven days unless discontinued owing to discharge from the intensive care unit, death, or withdrawal of consent. Main outcome measure The primary outcome was 28 day all cause mortality after randomisation. All analyses were based on a modified intention-to-treat set, including participants who received at least one dose of study drug. Results Of 1106 adults with sepsis enrolled in the study, 1089 were included in the modified intention-to-treat analyses (thymosin α1 group n=542, placebo group n=547). 28 day all cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) in the placebo group (hazard ratio 0.99, 95% confidence interval 0.77 to 1.27; P=0.93 with log-rank test). No secondary or safety outcome differed statistically significantly between the two groups. The prespecified subgroup analysis showed a potential differential effect of thymosin α1 on the primary outcome based on age (<60 years: hazard ratio 1.67, 1.04 to 2.67; ≥60 years: 0.81, 0.61 to 1.09; P for interaction=0.01) and diabetes (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; P for interaction=0.04). Conclusions This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis. Trial registration ClinicalTrials.gov NCT02867267 .

With the development of critical medical emergency technology, the success rate of sepsis treatment has been significantly improved, and the improvement of the long-term quality of life of sepsis survivors has also attracted more and more attention. ICU-acquired weakness (ICU-AW) refers to a group of syndromes with systemic and symmetrical muscle weakness during the intensive care unit (ICU) hospitalization and cannot be explained by the patient's own disease, which often involve diaphragm and skeletal muscle, resulting in difficulty in weaning and nosocomial infection. The incidence of ICU-AW in sepsis patients is over 50%, making it an important factor affecting the prognosis of these patients. The occurrence of sepsis ICU-AW is related to many factors, which can be summarized into two categories, including sepsis-related factors such as sepsis-associated inflammatory response, sepsis-associated encephalopathy (SAE), and treatment-related factors such as physical immobilization and insufficient nutritional support. The current ICU-AW risk assessment tools are mainly on subjective assessment scales, but there are some limitations in clinical application, and objective assessment tools including predictive model and imaging assessment, which are still in the research stage. "ABCDEF bundle strategy" is an important measure to prevent ICU-AW, in which early rehabilitation is the core element. This review of the literature from the risk factors, risk assessment and early rehabilitation of ICU-AW, and focuses on the timing, content, method and safety assessment of early rehabilitation, aims to improve the understanding of ICU-AW, strengthen the prevention of sepsis with ICU-AW, and improve the prognosis of sepsis patients, not only survive, but also live better.

OBJECTIVE:To investigate the potential mechanisms of sepsis pathogenesis in intensive care unit (ICU), with a specific focus on the role of skin microbiota, and to evaluate the causal relationships between skin microbiota and ICU sepsis using Mendelian randomization (MR). METHODS:A two-sample MR analysis was performed using skin microbiota genome-wide association study (GWAS) summary data from German population cohorts as exposures, combined with ICU sepsis susceptibility and 28-day mortality GWAS summary data from the IEU OpenGWAS database as outcomes. The primary causal effect estimates were generated using the inverse variance weighted (IVW) method, supplemented by validation through MR-Egger and weighted median approaches. Heterogeneity and pleiotropy tests, along with sensitivity analyses, were conducted to evaluate the robustness of the results. RESULTS:Regarding risk of ICU sepsis, IVW analysis showed that order Pseudomonadales [odds ratio (OR) = 0.93, 95% confidence interval (95%CI) was 0.88-0.98], family Flavobacteriaceae (OR = 0.93, 95%CI was 0.90-0.96), and genus Acinetobacter (OR = 0.96, 95%CI was 0.93-0.99) were significantly negatively correlated with the risk of ICU sepsis (all P < 0.05). There was a significant positive correlation between the risk of ICU sepsis and the presence of β-Proteobacteria (OR = 1.05, 95%CI was 1.00-1.11) and Actinobacteria (OR = 1.05, 95%CI was 1.00-1.11), both P < 0.05. Regarding 28-day mortality of ICU sepsis, IVW analysis showed that phylum Bacteroidetes (OR = 0.92, 95%CI was 0.86-0.99), family Streptococcaceae (OR = 0.92, 95%CI was 0.85-0.98), family Flavobacteriaceae (OR = 0.90, 95%CI was 0.83-0.97), genus Streptococcus (OR = 0.92, 95%CI was 0.86-0.99), ASV016 [Enhydrobacter] (OR = 0.92, 95%CI was 0.87-0.98), and ASV042 [Acinetobacter] (OR = 0.92, 95%CI was 0.88-0.97) were significantly negatively correlated with the 28-day mortality of ICU sepsis (all P < 0.05); family Moraxellaceae (OR = 1.09, 95%CI was 1.00-1.18) and ASV008 [Staphylococcus] (OR = 1.08, 95%CI was 1.03-1.14) was significantly positively correlated with the 28-day mortality of ICU sepsis (both P < 0.05). Sensitivity analysis and MR-PRESSO showed no heterogeneity, pleiotropy, or horizontal pleiotropy between skin microbiota and ICU sepsis risk and 28-day mortality rate. Analysis of confounding factors showed that single nucleotide polymorphisms (SNPs) associated with relevant skin bacteria could independently and causally affect the risk of ICU sepsis or ICU sepsis related mortality rate, independent of other confounding factors. The Steiger test results indicated that the established causal relationship was not due to reverse causality. CONCLUSIONS:Skin microbiota composition may influence both sepsis susceptibility and 28-day mortality in ICU settings. Family Flavobacteriaceae demonstrated protective effects against sepsis onset and mortality. These findings provide new perspectives for early detection and management strategies.

ImportancePrevious research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis.ObjectiveTo determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis.Design, Setting, and ParticipantsThe Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022.InterventionsThe patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days.Main Outcomes and MeasuresThe primary outcome was 28-day mortality.ResultsAmong the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group.Conclusions and RelevanceIn this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT03238742

早期恰当的有创机械通气是现行指南推荐的危重型新型冠状病毒感染(COVID-19)患者的重要救治手段之一,然而如何具体对有创机械通气危重型患者实施精准评估和有效治疗,对于实现整体救治成功率的提高,避免不同地区危重型患者有创机械通气临床救治质量的差异,减少治疗异质性,改善危重型新型冠状病毒感染患者预后,尤其是基层医院显得非常重要.为指导各地医院积极救治危重型新型冠状病毒感染患者,中国医药卫生事业发展基金会国家卫生健康技术推广应用服务粤港澳大湾区平台组织相关专家,根据国际、国内相关最新指南,编制进行有创机械通气的成人危重型新型冠状病毒感染患者救治流程.

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was allcause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference -0.40 [95% CI -0.71 to - 0.09]; P= 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P= 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P=0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.

Background Hand, foot, and mouth disease (HFMD) is an acute infectious disease caused by human enterovirus 71 (EV71), coxsackievirus, or echovirus, which is particularly common in preschool children. Severe HFMD is prone to cause pulmonary edema before progressing to respiratory and circulatory failure; thus hemodynamic monitoring and fluid management are important to the treatment process. Methods We did a review of young patients who had been successfully treated in our department for severe HFMD, which had been caused by EV71. A total of 20 patients met the inclusion criteria. Eight cases were monitored by the pulse indicator continuous cardiac output (PiCCO) technique, and fluid management was administered according to its parameters. With regard to the treatment with PiCCO monitoring, patients were divided into two groups: the PiCCO group (8 patients) and the control group (12 patients). The groups were then compared comprehensively to evaluate whether PiCCO monitoring could improve patients’ clinical outcomes. Results After analysis, the findings informed that although PiCCO failed to shorten the length of ICU stay, reduce the days of vasoactive drug usage, or lower the number of cases which required mechanical ventilation, PiCCO did reduce the incidence of fluid overload ( p = 0.085) and shorten the days of mechanical ventilation ( p = 0.028). After effective treatment, PiCCO monitoring indicated that the cardiac index (CI) increased gradually( p < 0.0001), in contrast to their pulse (P, p < 0.0001), the extra vascular lung water index (EVLWI, p < 0.0001), the global end diastolic volume index (GEDVI, p = 0.0043), and the systemic vascular resistance index (SVRI, p < 0.0001), all of which decreased gradually. Conclusion Our study discovered that PiCCO hemodynamic monitoring in young children with severe HFMD has some potential benefits, such as reducing fluid overload and the duration of mechanical ventilation. However, whether it can ameliorate the severity of the disease, reduce mortality, or prevent multiple organ dysfunction remain to be further investigated.

Sepsis is characterized by high mortality and poor prognosis and is one of the leading causes of death among patients in the intensive care unit (ICU). In the past, drugs that block early inflammatory responses have done little to reverse the progression of sepsis. Programmed cell death receptor 1 (PD-1) and its two ligands, programmed cell death receptor ligand 1(PD-L1) and programmed cell death receptor ligand 2 (PD-L2), are negative regulatory factors of the immune response of the body. Recently, the role of the PD-1 signaling pathway in sepsis has been widely studied. Studies showed that the PD-1 signaling pathways are closely related to the mortality and prognosis of sepsis patients. In the immunotherapy of sepsis, whether in animal experiments or clinical trials, anti-PD-1/PD-L1 antibodies have shown good promise. In this review, firstly, we focus on the immunosuppressive mechanism of sepsis and the structure and function of the PD-1 signaling pathway. The variety of the PD-1 signaling pathways in sepsis is introduced. Then, the relationship between the PD-1 signaling pathway and immune cells and organ dysfunction and the regulatory factors of the PD-1 signaling pathway in sepsis is discussed. Finally, the application of the PD-1 signaling pathway in sepsis is specifically emphasized.

There are few documents describing the characteristics of the lungs in the prolonged period of severe new coronavirus pneumonia. This case describes an 67-year-old man who has been tested positive for COVID-19, and who quickly progressed to severe illness. After mechanical ventilation, ECMO and antiviral treatments, his condition gradually improved. Through lung CT examination, we analyzed the changes in lung characteristics at different stages of the patient, especially the protracted period, which showed “watermelon lung” changes. These characteristics may help us adjust the treatment strategy.

Background: Equipoise exists regarding the implementation of evidence-based guidelines for nutritional therapy in critical illness because some previous cluster-randomised controlled trials (cRCTs) demonstrate patient benefits whilst others do not. We aimed to resolve this issue by initiating an appropriately powered cRCT to assess whether active implementation of an evidence-based guideline for nutrition therapy in critical illness could reduce mortality.Methods: We did a multicentre, cluster-randomised, parallel-controlled trial in 97 intensive care units (ICUs) throughout China. We developed an up-to-date, evidence-based nutrition guideline. ICUs randomly allocated to implement the guideline formed a local "intervention team", which actively implemented the guideline using standardized educational materials. ICUs assigned to the control group remained unaware of the guideline. All ICUs enroled critically ill patients who were expected to stay longer than seven days. The primary outcome was all-cause mortality within 28 days of enrolment .Findings Between March, 2018 and July, 2019, we enrolled 1,373 patients at 48 guideline ICUs and 1,399 patients at 49 control ICUs. Implementation of the nutrition guideline resulted in significantly earlier enteral nutrition (EN) initiation (1.20 vs. 1.55 mean days to initiation of EN; difference -0.40 [95% CI, -0.71 to -0.09]; P=0.01) and delayed parenteral nutrition (PN) initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI, 0.44 to 1.67]; P=0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference -1.6% [95% CI -4.3% to 1.2%]; p=0.42) between study groups.Interpretation: Active implementation of an evidence-based guideline can change practice. Our active implementation strategy improved the provision of nutrition therapy to critically ill patients. However, in our cRCT, this improvement in care did not translate to a reduction in mortality. We did not identify any safety concerns associated with the active implementation of our evidence-based guideline for nutrition therapy. Trial Registration: The study was registered in the ISRCTN registry before enrolment commenced (No. ISRCTN12233792). Funding Statement: The study was funded by the Key Research and Development Program Foundation of Jiangsu Province of China (no. BE2015685) and Nutricia, Wuxi, China.Declaration of Interests: Dr. GSD reported receiving academic research grants related to nutrition in critical illness from the Australian National Health and Medical Research Council, Fresenius Kabi Deutschland GmbH and Baxter Healthcare Pty Ltd and speakers honoraria from Fresenius Kabi Deutschland GmbH, Baxter Healthcare Australia, Pty Ltd, Nestle Healthcare, Vevy, Switzerland and Nutricia Pharmaceutical (Wuxi) Co., Ltd. China. Dr. AvZ reports personal fees from Baxter, personal fees from Nestle, personal fees from Fresenius Kabi, grants and personal fees from Nutricia, grants from Cardinal Health grants from Mermaid grants from Lyric, outside the submitted work. Dr. WqL reported receiving speakers honoraria from Nutricia Pharmaceutical (Wuxi) Co., Ltd. China. No other disclosures were reported.Ethics Approval Statement: The study was approved by the local hospital ethics committees of all the participating ICUs. At each site, informed consent was obtained from the patients or their next of kin before enrolment.

Most of the critically ill novel coronavirus 2019 pneumonia (NCP) patients progress promptly, and soon match the ARDS diagnostic criteria. When mechanical ventilation and prone position cannot reverse the fatal hypoxia—extra-corporeal-membrane-oxygenation (ECMO) will be applied as a salvage treatment if available. Here, we report a novel coronavirus 2019 pneumonia (NCP) patient, a male, 67 years old, who was treated with ECMO for 30 days. In the midst, bronchoscopy was utilized to comprehend the airway lesions and clear secretions. And computed tomography (CT) scans were performed before and after the treatment of ECMO. In the recovering phase of his disease, the patient experienced multiple times pneumothorax on both sides. Some newly developed lung bullae in the subpleural area and modest bronchiectasis were found by the CT scan. The newly developed lung bullae was the probable cause of pneumothorax. Notably, in the whole process of his illness, the serum IL-6 only had a slight elevation in the early period, there is no typical cytokine storm as that was seen in non-COVID-19 ARDS. After 3-months meticulous treatment, the patient made a full recovery and now is discharged from our hospital. Though COVID-19 may not cause typical cytokine storm, the inflammation in lung may inflict severe damage to lung. Severe NCP may cause lung bullae and bronchiectasis, making the patients hard to be weaned from mechanical ventilation or ECMO.

PURPOSE:Although immune dysfunction has been investigated in adult septic patients, early immune status remains unclear. In this study, our primary aim was to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality.PATIENTS AND METHODS:A post hoc analysis of a multicenter, randomized controlled trial was conducted; 273 patients whose immune status was evaluated within 48 hours after onset of sepsis were enrolled. Early immune status was evaluated by the percentage of monocyte human leukocyte antigen-DR (mHLA-DR) in total monocytes within 48 hours after onset of sepsis and it was classified as immunoparalysis (mHLA-DR ≤30%) or non-immunoparalysis (>30%). Three logistic regression models were conducted to explore the associations between early immunoparalysis and hospital mortality. We also developed two sensitivity analyses to find out whether the definition of early immune status (24 hours vs 48 hours after onset of sepsis) and immunotherapy affect the primary outcome.RESULTS:Of the 181 elderly (≥60yrs) and 92 non-elderly (<60yrs) septic patients, 71 (39.2%) and 25 (27.2%) died in hospital, respectively. The percentage of early immunoparalysis in the elderly was twice of that in the non-elderly patients (32% vs 16%, p=0.006). For the elderly, hospital mortality was higher in the immunoparalysis ones than the non-immunoparalysis ones (53.4% vs 32.5%, p=0.009). But there was no significant difference in hospital mortality between immunoparalysis non-elderly patients and non-immunoparalysis non-elderly ones (33.5% vs 26.0%, p=0.541). By means of logistic regression models, we found that early immunoparalysis was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status and immunotherapy did not affect the outcomes.CONCLUSION:The elderly were more susceptible to early immunoparalysis after onset of sepsis. Early immunoparalysis was independently associated with poor prognosis in elderly, but not in non-elderly patients.

目的 探讨Sectm1b在肺上皮细胞表达对急性肺损伤(ALI)的作用机制.方法 成年健康清洁级SD雄性大鼠36只随机平分为对照组和肺损伤组,肺损伤组建立ALI模型,对照组不进行处理.检测两组大鼠造模后6、24、72 h肺上皮细胞Sectm1b与血清炎症因子,并计算肺组织湿/干质量比.结果 肺损伤组大鼠造模后6 h便可以清楚看到腹水形成,行为状态明显异常,随着时间的延长,腹水颜色也发生改变,由淡红色浑浊液体逐渐变为深红色脓血性液体.肺损伤组病理表现为肺组织水肿,毛细血管内微血栓形成和白细胞附壁、聚集、炎性细胞浸润.肺损伤组大鼠造模后不同时间点血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)含量与肺组织湿/干质量比显著高于对照组(P<0.05).肺损伤组大鼠造模后6、24、72 h肺上皮细胞Sectm1b相对表达水平(12.12±1.24、14.42±1.49和18.28±1.44)显著高于对照组(1.27±0.24、1.11±0.14和1.32±0.25,P<0.05).在肺损伤组大鼠中,造模后不同时间点的肺上皮细胞Sectm1b相对表达水平与肺组织湿/干质量比及血清IL-6、TNF-α 含量都呈正相关性(P<0.05).结论 ALI模型大鼠肺上皮细胞Sectm1b呈现高表达状况,可能参与ALI的炎症损伤过程.

Objective:To summarize the effect of multiple hormone applications of adrenaline/noradrenaline, desmopressin, meprednisone and thyroxine for hemodynamics of brain-dead organ donors so as to provide rationales for maintaining brain-dead organ donors.Methods:A total of 45 brain-dead organ donors received regular therapy plus levothyroxine sodium tablets, meprednisone and desmopressin. Adrenaline and noradrenaline were tailored to the variations of blood pressure. The changes of hemodynamic parameters, such as mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), stroke volume (SV) and global ejection fraction (GEF) were recorded at Day 0 and Day 1.Results:The hemodynamic parameters of 45 brain-dead organ donors, including MAP(48.49±10.69) mmHg, CO(2.55±0.71) L/min, CI(1.57±0.43) L/min·m 2, SV(28.38±11.16) ml and GEF (32.56±12.43)% were lower than normal values before multiple hormone applications. As compared with the lower limits of normal values, the differences were statistically significant ( P<0.05). All hemodynamic parameters, including MAP(87.99±7.35) mmHg, CO(6.49±1.05) L/min, CI(4.01± 0.68) L/min·m 2, SV(60.21±8.75) ml and GEF (69.08±10.34)%, were within normal ranges at Day 1 after multiple hormone applications. As compared with those before hormone dosing, hemodynamic parameters improved significantly ( P<0.05). Conclusions:The hemodynamic parameters of brain-dead potential organ donors improve significantly after multiple hormone applications, ensuring blood perfusion of awaited donated organs. Therefore organ donors may be donated successfully. Thus our study provides clinical rationales for maintaining brain-dead organ donors.

Background: Although immunosuppression has been investigated in adult septic patients, early immune status remains unclear. In this study, we aimed to assess early immune status in adult patients with sepsis stratified by age and its relevance to hospital mortality. Methods: From post hoc analysis of a multicenter, randomized controlled trial, 273 patients whose levels of monocyte human leukocyte antigen-DR (mHLA-DR) were obtained within 48 hours after onset of sepsis were enrolled. All patients were divided into elderly (≥60yrs) group and non-elderly (<60yrs) group. Early immune status was evaluated by the percentage of mHLA-DR in total monocytes within 48 hours after onset of sepsis and it was classified as immunosuppression (mHLA-DR≤30%) or non-immunosuppression (>30%). Changes in immune status were assessed by the value change in mHLA-DR on day 3 compared with the first measurement. Three logistic regression models were conducted to test the associations between early immunosuppression and hospital mortality. We also did a sensitivity analysis to find out if the definition of early immune status (24 vs. 48 hours after onset of sepsis) affects the outcomes. Results: Of the 181 elderly and 92 non-elderly septic patients, 71 (39.2%) elderly and 25 (27.2%) non-elderly died in hospital. The percentage of early immunosuppression in the elderly was twice of that of the non-elderly patients (32% vs. 16%, p=0.006). Immunosuppressed elderly had higher hospital mortality than the non-immunosuppressed elderly (53.4% vs. 32.5%, p=0.009), but there was no significant difference in mortality between immunosuppresed non-elderly patients and non-immunosuppressed non-elderly patients (33.5% vs. 26.0%, p=0.541). In all of the three logistic regression models, we found that early immunosuppression was independently associated with increased hospital mortality in elderly, but not in non-elderly patients. Sensitivity analysis further confirmed the definition of early immune status did not affect the outcomes. In addition, immune status improvement on day 3 was associated with reduced hospital mortality in both elderly and non-elderly patients. Conclusion: In adult patients with sepsis, the elderly were more susceptible to early immunosuppression after onset of sepsis. Early immunosuppression was independently associated with poor prognosis in elderly patients. Trial registration: ClinicalTrials.gov NCT00711620 , 9 July 2008, https://clinicaltrials.gov/ct2/show/NCT00711620

Mesenchymal stromal cell (MSC) therapy is a potential therapy for treating acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), which was widely studied in the last decade. The purpose of our meta-analysis was to investigate the efficacy of MSCs for simulated infection-induced ALI/ARDS in animal trials. PubMed and EMBASE were searched to screen relevant preclinical trials with a prespecified search strategy. 57 studies met the inclusion criteria and were included in our study. Our meta-analysis showed that MSCs can reduce the lung injury score of ALI caused by lipopolysaccharide or bacteria (standardized mean difference (SMD) = −2.97, 95% CI [−3.64 to −2.30], P < 0.00001) and improve the animals’ survival (odds ratio = 3.64, 95% CI [2.55 to 5.19], P < 0.00001). Our study discovered that MSCs can reduce the wet weight to dry weight ratio of the lung (SMD = −2.58, 95% CI [−3.24 to −1.91], P < 0.00001). The proportion of the alveolar sac in the MSC group was higher than that in the control group (SMD = 1.68, 95% CI [1.22 to 2.13], P < 0.00001). Moreover, our study detected that MSCs can downregulate the levels of proinflammatory factors such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in the lung and it can upregulate the level of anti-inflammatory factor IL-10. MSCs were also found to reduce the level of neutrophils and total protein in bronchoalveolar lavage fluid, decrease myeloperoxidase (MPO) activity in the lung, and improve lung compliance. MSC therapy may be a promising treatment for ALI/ARDS since it may mitigate the severity of lung injury, modulate the immune balance, and ameliorate the permeability of lung vessels in ALI/ARDS, thus facilitating lung regeneration and repair.