Prognosis-related classifi cation and dynamic monitoring of immune status in patients with sepsis:A prospective observational study

BACKGROUND:The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis.In this study,we aim to introduce a model to describe and monitor the immune status of sepsis and to explore its prognostic value.METHODS:A prospective observational study was carried out in Zhongshan Hospital,Fudan University,enrolling septic patients admitted between July 2016 and December 2018.Blood samples were collected at days 1 and 3.Serum cytokine levels(e.g.,tumor necrosis factor-α[TNF-α],interleukin-10[IL-10])and CD14+monocyte human leukocyte antigen-D-related(HLA-DR)expression were measured to serve as immune markers.Classifi cation of each immune status,namely systemic inflammatory response syndrome(SIRS),compensatory anti-inflammatory response syndrome(CARS),and mixed antagonistic response syndrome(MARS),was defined based on levels of immune markers.Changes of immune status were classifi ed into four groups which were stabilization(SB),deterioration(DT),remission(RM),and non-remission(NR).RESULTS:A total of 174 septic patients were enrolled including 50 non-survivors.Multivariate analysis discovered that IL-10 and HLA-DR expression levels at day 3 were independent prognostic factors.Patients with MARS had the highest mortality rate.Immune status of 46.1%patients changed from day 1 to day 3.Among four groups of immune status changes,DT had the highest mortality rate,followed by NR,RM,and SB with mortality rates of 64.7%,42.9%,and 11.2%,respectively.CONCLUSIONS:Severe immune disorder defi ned as MARS or deterioration of immune status defi ned as DT lead to the worst outcomes.The preliminary model of the classifi cation and dynamic monitoring of immune status based on immune markers has prognostic values and is worthy of further investigation.

Bone marrow-derived mesenchymal stem cells modulate autophagy in RAW264.7 macrophages via the phosphoinositide 3-kinase/protein kinase B/heme oxygenase-1 signaling pathway under oxygen-glucose deprivation/restoration conditions

Background: Autophagy of alveolar macrophages is a crucial process in ischemia/reperfusion injury-induced acute lung injury (ALI). Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent cells with the potential for repairing injured sites and regulating autophagy. This study was to investigate the influence of BM-MSCs on autophagy of macrophages in the oxygen-glucose deprivation/restoration (OGD/R) microenvironment and to explore the potential mechanism.Methods: We established a co-culture system of macrophages (RAW264.7) with BM-MSCs under OGD/R conditionsin vitro. RAW264.7 cells were transfected with recombinant adenovirus (Ad-mCherry-GFP-LC3B) and autophagic status of RAW264.7 cells was observed under a fluorescence microscope. Autophagy-related proteins light chain 3 (LC3)-I, LC3-II, and p62 in RAW264.7 cells were detected by Western blotting. We used microarray expression analysis to identify the differently expressed genes between OGD/R treated macrophages and macrophages co-culture with BM-MSCs. We investigated the gene heme oxygenase-1 (HO-1), which is downstream of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway.Results: The ratio of LC3-II/LC3-I of OGD/R treated RAW264.7 cells was increased (1.27 ± 0.20vs. 0.44 ± 0.08,t = 6.67,P < 0.05), while the expression of p62 was decreased (0.77 ± 0.04vs. 0.95 ± 0.10,t = 2.90,P < 0.05), and PI3K (0.40 ± 0.06vs. 0.63 ± 0.10,t = 3.42,P < 0.05) and p-Akt/Akt ratio was also decreased (0.39 ± 0.02vs. 0.58 ± 0.03,t = 9.13,P < 0.05). BM-MSCs reduced the LC3-II/LC3-I ratio of OGD/R treated RAW264.7 cells (0.68 ± 0.14vs. 1.27 ± 0.20,t = 4.12,P < 0.05), up-regulated p62 expression (1.10 ± 0.20vs. 0.77 ± 0.04,t = 2.80,P < 0.05), and up-regulated PI3K (0.54 ± 0.05vs. 0.40 ± 0.06,t = 3.11,P < 0.05) and p-Akt/Akt ratios (0.52 ± 0.05vs. 0.39 ± 0.02,t = 9.13,P < 0.05). A whole-genome microarray assay screened the differentially expressed geneHO-1, which is downstream of the PI3K/Akt signaling pathway, and the alteration ofHO-1 mRNA and protein expression was consistent with the data on PI3K/Akt pathway.Conclusions: Our results suggest the existence of the PI3K/Akt/HO-1 signaling pathway in RAW264.7 cells under OGD/R circumstancesin vitro, revealing the mechanism underlying BM-MSC-mediated regulation of autophagy and enriching the understanding of potential therapeutic targets for the treatment of ALI.

Long-term Follow-up of 5 Survivors after the First Outbreak of Human Infections with Avian Influenza A（H7N9） Virus in Shanghai, China

At the end of March 2013, the first case of human infection with avian influenza A（H7N9） virus was confirmed in Shanghai. From April to May 2013, 18 patients with avian influenza A（H7N9） virus infection were hospitalized in Shanghai Public Health Clinical Center, and finally, 12 of them survived. The short-term prognosis of these patients had been described previously, but the long-term prognosis remained unclear.

Pharmacotherapy for Adult Patients with Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome （ARDS） is one of the leading death reasons in Intensive Care Unit （ICU）. It is frustrating that there is no pharmacotherapy effective enough to reduce the mortality of ARDS. The most important treatment of ARDS nowadays is supportive treatment, including mechanical ventilation （MV）, fluid management, and sedation. Successful trials of ARDS treatments usually aim to avoid further lung injury of ARDS patients, such as low tidal volume of MV and conservative fluid strategy. These strategies can only maintain the mortality around 40%.

Diagnostic value of artificial intelligence in early-stage lung cancer

To the Editor:Lung cancer has the highest morbidity and mortality rate among malignancies in the world.The key to improve the 5-year survival rate is early diagnosis and treatment.Artificial intelligence(AI)based on deep learning has the ability of efficient self-optimization,which improves not only the recognition ability of pulmonary nodules,but also help improving the diagnostic efficiency of early-stage lung cancer.