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Background Acute type A aortic dissection (AAAD) is a devastating condition with the human aortic smooth muscle cells (HASMCs) reduced proliferation and increased apoptosis. Integrin α5β1 and FAK are the important proangiogenic factors involved in regulating angiogenesis. The aim of the study was to investigate the role of integrin α5β1 and FAK in AAAD patients and the potential mechanisms. Methods The aortic tissue samples were collected from 8 AAAD patients and 4 organ donors obtained from Zhongshan Hospital of Fudan University. The level of apoptosis in the aortic tissues were assessed by immunohistochemical staining (ICH) and Terminal-deoxynucleoitidyl transferase mediated nick end labeling assay (TUNEL). The expression of integrin α5β1 and FAK were detected. Furtherly, integrin α5β1 was dificiently expressed in HASMCs and the interaction with FAK was detected by co-immunoprecipitation analysis (Co-IP). The levels of proliferation and apoptosis were assessed by cell-counting Kit-8 analyses (CCK-8) and flow cytometry after integrin α5β1 dificiently. Results The levels of integrin α5β1 and FAK were both significantly decreased in AAAD patients. Down-regulating the expression of integrin α5β1-FAK compound could remarkablely induce the increased apoptosis and decreased proliferation in HASMC, which indicated integrin α5β1-FAK might play a important role in the development of AAAD. Conclusions The down-regulaiton of integrin α5β1-FAK associates with increased apoptosis and decreased proliferation in aortic smooth muscle cells, and might be a potential therapeutic target for AAAD.

Background: For thoracoscopic lung cancer surgery, the continuous relationship and the trigger point of operative duration with a risk of adverse perioperative outcomes (APOs) and early discharge remain unknown. Methods: This study enrolled 12,392 patients who underwent this surgical treatment. Five groups were stratified by operative duration

Postoperative pulmonary complications (PPCs) are the most common complications following minimally invasive esophagectomy (MIE) and can be associated with adverse outcomes. This study aims to construct a nomogram based on clinical factors to predict PPCs and investigate related early outcomes. Clinical data of 969 consecutive patients receiving MIE were retrospectively collected. Univariate and multivariate analysis were performed to select independent predictors. Using independent predictors to develop a nomogram and using a bootstrap-resampling approach to conduct internal verification. Early outcomes of PPCs were analyzed. The incidence of PPCs following MIE was 39.6% (384 out of 969). In multivariate analysis, older age (Odds ratio (OR) 1.034, P

BACKGROUND Endothelium injury and coagulation dysfunction play an important role in the pathogenesis of sepsis. Soluble thrombomodulin (sTM), tissue plasminogen activator-inhibitor complex (t-PAIC), thrombin-antithrombin complex (TAT) and α2-plasmin inhibitor-plasmin complex (PIC) are biomarkers of endothelium injury and coagulation dysfunction. This study aimed to explore the prognostic values and diagnostic performance for septic shock and sepsis-induced disseminated intravascular coagulation (DIC) of endothelial biomarkers. METHODS We conducted an observational study on patients with sepsis admitted to intensive care unit (ICU) at a teaching hospital from January 2016 to December 2018. Levels of sTM, t-PAIC, TAT and PIC were measured at admission day and day 5-7 after admission and detected by qualitative chemiluminescence enzyme immunoassay performed on HISCL automated analyzers. RESULTS A total of 179 septic patients and 125 non-septic ICU controls were enrolled. The level of sTM was higher in septic patients compared to ICU controls (OR =1.093, 95% CI: 1.045-1.151, P

Background: The lung microbiota and host immune response is thought to be a key player in the progression of pneumonia. However, the critical features of the microbiota have rarely been studied in severe community-acquired pneumonia (SCAP) patients. This study aimed to explore the correlations among the lung microbiota and the host immune defense, the disease severity, and the outcome in SCAP patients. Methods: A prospective and observational study in the intensive care unit (ICU) of four hospitals in China was performed. The lung microbiota was quantified and characterized using metagenomic next-generation sequencing (mNGS), collecting sputum and bronchoalveolar lavage fluid (BALF) in SCAP and CAP patients. Risk factors for disease progress and prognosis were investigated by logistic regression. In addition, transcriptomics was applied to explore host immune variation and the interaction between microbiota and host immune responses. Results: Our results showed that the microbiome α- and β-diversity in SCAP patients were significantly lower than those in CAP patients and lower in nonsurvivors than survivors. The Simpson index, the existence of Streptococcus pneumonia, the delta-SOFA score, the use of immunosuppressor, and activated partial thromboplastin time (APTT) were independently associated with the 28-day mortality of SCAP patients. Furthermore, the differentially expressed genes, including Opiorphin Prepropeptide (OPRPN), Histatin 1 (HTN1), Histatin 3 (HTN3), Lipocalin 1 (LCN1), Follicular Dendritic Cell Secreted Protein (FDCSP) and Statherin (STATH) in SCAP were correlated with immune response pathways. The neutrophil proportions and degranulation were suppressed in the nonsurvivors of SCAP. At the same time, interleukin-10 signaling was activated, while interferon-α, -β, and -γ responses were suppressed in the dismal outcome patients. Conclusions: Our findings confirmed that the lung microbiota played an essential role in association with the severity of pneumonia and represented a significant contributor to heterogeneity in SCAP by altering host immune responses.

Objective. This study sets out to explore if the relationship between the driving pressure and hospital mortality in ARDS patients is influenced by body mass index (BMI) level or the presence of abdominal obesity. Methods. Data were extracted from an online database named “Multiparameter Intelligent Monitoring in Intensive Care III.” A total of 1556 patients were included and divided into four subgroups based on both BMI level (BMI ≥30 kg/m2 or BMI ＜30 kg/m2) and abdominal assessment. Driving pressure [i.e., the difference between plateau pressure and positive end-expiratory pressure (PEEP)] within 24 h of invasive mechanical ventilation was compared between survivors and nonsurvivors during hospitalization in each group. A logistic regression model was used for hospital mortality. Results. There were 1556 patients with mild-to-severe ARDS, 666 (42.80%) nonobese patients with nonabdominal obesity, 259 (16.65%) nonobese patients with abdominal obesity, 97 (6.23%) obese patients with nonabdominal obesity, and 534 (34.32%) obese patients with abdominal obesity. Driving pressure in nonobese patients with nonabdominal obesity was significantly lower in survivors (12.77 ± 4.53 cm H2O) than in nonsurvivors (14.26 ± 5.52 cm H2O, p < 0.01 ). On the contrary, in the other three groups, driving pressure was not significantly different between survivors and nonsurvivors. After a logistic multivariable regression analysis, in nonobese (BMI p < 0.05 ) but not in the other three subgroups. Conclusion. Driving pressure is associated with increase in hospital mortality only in nonobese (BMI

Background Cardiac injury in patients with coronavirus disease 2019 (COVID-19) has been reported in recent studies. However, reports on the risk factors for cardiac injury and their prognostic value are limited. Results In total, 15.9% of all cases were defined as cardiac injury in our study. Patients with severe COVID-19 were significantly associated with older age and higher respiratory rates, Sequential Organ Failure Assessment (SOFA) scores, cardiac injury biomarkers and PaO2/FiO2 ratios. Male patients with chest distress and dyspnea were more likely to have severe disease. Patients with cardiac injury were significantly more likely to have a severe condition and have an outcome of death. However, no significant difference was found in respiratory rates, dyspnea or PaO2/FiO2 ratio between patients with or without cardiac injury. In the logistic regression model, pre-existing hypertension and higher SOFA score were independent risk factors for patients with COVID-19 developing cardiac injury. Conclusions Our study revealed that cardiac injury was an important predictor for patients having a severe or fatal outcome. Patients with pre-existing hypertension and higher SOFA scores upon admission were more likely to develop cardiac injury. Nevertheless, pulmonary ventilation dysfunction and oxygen inhalation insufficiency were not the main causes of cardiac injury in patients with COVID-19. Methods A total of 113 confirmed cases were included in our study. Severe patients were defined according to American Thoracic Society guidelines for community-acquired pneumonia. Cardiac injury was defined as a serum cTnI above the 99th-percentile of the upper reference limit. Patient characteristics, clinical laboratory data and treatment details were collected and analyzed. The risk factors for patients with and without cardiac injury were analyzed.

Background: The World Health Organization has declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the risk factors of illness severity. Results: The median age was 63 years, and 44.9% were severe cases. Severe patients had higher APACHE II (8.5 vs. 4.0) and SOFA (2 vs. 1) scores on admission. Among all univariable parameters, lymphocytes, CRP, and LDH were significantly independent risk factors of COVID-19 severity. LDH was positively related both with APACHE II and SOFA scores, as well as P/F ratio and CT scores. LDH (AUC = 0.878) also had a maximum specificity (96.9%), with the cutoff value of 344.5. In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocytes and its subsets. Conclusions: This study showed that LDH could be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases. Methods: We extracted data regarding 107 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society guidelines for community acquired pneumonia.

CD8A prospective observational study in an emergency department enrolled patients who were diagnosed with sepsis-associated ARDS according to the sepsis-3 criteria and Berlin definition. Peripheral blood samples were collected within 24 h post recruitment. CD8Sixty-two patients with ARDS met the inclusion criteria. CD8CD8

Background Diabetes mellitus (DM) has become a common risk factor for pyogenic liver abscess (PLA) patients, Klebsiella pneumoniae is a primary pathogen of PLA (KPLA). The purpose of this study was to evaluate the clinical and microbiological characteristics in PLA patients with or without DM induced by Klebsiella pneumoniae or not.Methods The clinical data of the total 557 PLA patients were collected in Zhongshan Hospital from January 2015 to December 2020. The liver abscess were confirmed using abdominal ultrasound (US)，computerized tomography (CT), and/or magnetic resonance imaging (MRI). The 557 patients were divided into two groups, PLA with DM and PLA without DM. In the group of PLA with DM, the patients were further separated into KPLA with DM and non-KPLA with DM.Results The total of 557 patients with PLA were analyzed, 225 (40.40%) patients comorbided DM. Among PLA patients with DM, there is a higher proportion of patients with hypertension (42.22%) and fatty liver diseases (38.67%), the most common clinical manifestation is frail and fatigue (18.22%), and more likely to progress to sepsis and metastatic infections such as periorbital infection. The PLA patients with DM have higher inflammatory markers (WBC, N%, CRP, ESR and PCT). There was significant difference between the group of PLA with DM and PLA without DM in the percentage of neutrophils, liver enzymes, albumin, glucose metabolism (blood glucose, glycated hemoglobin and glycated albumin), lipid metabolism (triglycerides, low density lipoprotein, high density lipoprotein), blood sodium and chlorine, blood urea nitrogen and higher heart markers ( proBNP and CK-MB). In KPLA patients with DM compared with non-KPLA with DM, inflammatory markers (WBC, N%, CRP, ESR and PCT), liver function index (TB, CB, ALT, AST, ALP and r-GT) and cardiac markers (cTnT and proBNP) are more higher. The level of albumin, serum sodium and ferritin are more lower between the KPLA patients with DM and non-KPLA with DM. Detection of liver abscess by high-throughput sequencing is more sensitive and accurate. There was no in-hospital mortality.Conclusions The study found that in the PLA patients with diabetic DM, Klebsiella pneumoniae infection is the most common, which is more prone to organ dysfunction and electrolyte disorder. High-throughput sequencing can help early diagnosis and accurate treatment of PLA patients.

Although combined thoracic paravertebral blockade (TPVB)-general anesthesia (GA) could improve pain control compared to GA alone after thoracoscopic lung cancer surgery, it has not been established whether this improvement in pain control could reduce associated adverse outcomes. Thus, this study aimed to explore the association between TPVB usage and adverse outcomes after thoracoscopic lung cancer surgery.Retrospective cohort study from a prospective database.A high-volume thoracic center in China.13966 consecutive patients who received thoracoscopic lung cancer surgery from January 2016 to December 2018 in Shanghai Chest Hospital were enrolled.With a 1:1 propensity score matching (PSM) analysis, adverse outcomes between GA alone and GA-TPVB were investigated. Multivariate and multiple linear regression analysis were used to identify factors and calculate odds radio (OR) for adverse outcomes.The rate of TPVB usage was 14.8% (2070 out of 13,966). TPVB combined with GA was associated with lower rates of postoperative pulmonary complications (PPCs) (30.4% vs 33.5%, P = 0.005) and postoperative atrial fibrillation (POAF) (2.1% vs 2.9%, P = 0.041), and shorter length of hospital stay (LOS) (Median [IQR]; 5[4-5] vs 5[4-6]) days, P 0.001) compared to GA alone. After a 1:1 PSM analysis, we investigated adverse outcomes in 2640 (1320 pairs) patients with or without TPVB usage, and this association remained existed, namely, the rates of PPCs (29.8% vs 34.2%, P = 0.014) and POAF (2.2% vs 3.6%, P = 0.028) were lower and LOS was shorter (5[4-5] vs 5[4-6] days, P 0.001) in the GA-TPVB group. In multivariate analysis, the combination of GA plus TPVB was independent predictor for PPCs (OR = 0.879, 95%CI, 0.793-0.974, P = 0.014) and POAF (OR = 0.714, 95%CI, 0.516-0.988, P = 0.042), respectively. However, in multiple linear analysis, lower rates of PPCs and POAF associated with TPVB usage, rather than TPVB usage, were responsible for the reduced LOS.The usage of TPVB may be a feasible and adjustable approach to reduce the rates of PPCs and POAF and associated LOS in thoracoscopic lung cancer surgery.

Sepsis is an inflammatory syndrome with life-threatening organ dysfunction resulting from a dysregulated host response to infection. Although the treatment for sepsis has improved a lot in the last 30 years, sepsis related mortality remains high. In the recent 10 years, high dose intravenous injection of vitamin C, the first line antioxidant of human, has received more and more attention in the field of critical care, its beneficial effect has been demonstrated by several small scale clinical trial and animal studies, but the effect of high dose vitamin C on sepsis in a larger trial seems warranted in further study. Here we will conduct a prospective, multi-center, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial named as HDVCIS. The trial protocol has been approved by Clinical Trail Ethics Committee of Ruijin Hospital of Shanghai JiaoTong University School of Medicine. This trial has been registered in Chinese Clinical Trial Registry (ChiCTR1800017633) in August 7, 2018. Patients will be recruited from 4 medical centers in China. Its object is to testify the efficacy and safety of high dose vitamin C in the treatment of sepsis.

Robot-assisted (RA) and thoracoscopic-assisted (TA) minimally invasive esophagectomy (MIE) are surgical techniques for the treatment of esophageal cancer. This study aims to compare short-term outcomes of RAMIE to TAMIE.We conducted a single-center retrospective analysis between January 2016 and December 2019, including 1012 consecutive patients who underwent MIE, 437 in the RAMIE group and 575 in the TAMIE group. A 1:1 propensity score matching (PSM) analysis was performed to compare short-term outcomes.The vast majority of patients had squamous cell carcinoma (972/1012, 96.0%). Radical resection (R0) was performed in 945 (93.4%) patients with a mean total number of dissected lymph nodes of 22.6±11.0. The incidence of postoperative pulmonary complications (PPCs) was 44.1% (446/1012). The median length of hospital stay was 9 days, and no 30-day mortality was observed. We evaluated short-term outcomes in 544 patients (272 pairs) treated with RAMIE or TAMIE after a 1:1 PSM. Compared with TAMIE group, patients received RAMIE had shorter operative time (291.6±60.5 vs 247.2±51.0min, P0.001), more left recurrent laryngeal lymph node dissected (2.0±1.9 vs 2.5±2.3, P=0.007), comparable total number of lymph node dissected (22.9±11.4 vs 22.8±9.8, P=0.913) and R0 resection rate (90.8% vs 93.4%, P=0.266) and similar short-term outcomes including PPCs, surgical complications, length of ICU and hospital stays, ICU readmission rate, 30-day readmission and mortality rates (P0.05).RAMIE is an alternative minimally invasive option to TAMIE, with promising oncological results especially in left RLN lymph node dissection and comparable short-term outcomes.

G protein-coupled receptor 174 (GPR174) is mainly expressed in thymus, spleen, lymph nodes, and leukocytes, and genetic variation in GPR174 is associated with susceptibility to autoimmune diseases, indicating that GPR174 is involved in the immune response. However, the function of GPR174 in regulating inflammatory responses against bacterial infection in sepsis remains unclear. In this study, we investigated the role of GPR174 in regulating suppressive function of regulatory T cells (Treg cells) and the underlying mechanism of Gpr174-deficient Treg cells in controlling cytokine storm of sepsis. We showed that Gpr174-dedicient mice were resistant to inflammatory shock induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP). Moreover, Gpr174 was highly expressed in Treg cells, and its deficiency in mice promoted the expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and interleukin (IL)−10 in Treg cells. By using the LPS-induced sepsis model, we demonstrated that anti-inflammatory macrophages (M2 macrophages) induction was Treg cell-dependent and Gpr174-deficient Treg cells protected mice against sepsis-induced lung damage through prompting M2 macrophages polarization. In vitro, Gpr174-deficient Treg cells also promoted the polarization of macrophages toward M2 cells and dampened the secretions of pro-inflammatory cytokines (IL-6 and tumor necrosis factor-α (TNF-α)) in macrophages. In conclusion, these findings suggested that GPR174 plays an important role in the initial period of sepsis through the regulation of macrophage polarization and pro- and anti-inflammatory cytokine secretions. Therefore, GPR174 may be a promising target for therapeutic agents to regulate inflammatory disorders.

The gut is hypothesized to be the "motor" of critical illness and plays an important role in the development of sepsis. Berberine (BBR) is an alkaloid compound extracted from herbs, which has anti-inflammatory, anti-oxidative effects and can be used in intestinal infectious diseases and inflammatory bowel disease (IBD). BBR could promote differentiation of Treg cells which play a key role in maintaining intestinal immune homeostasis. However, its effect on sepsis-induced intestinal injury remains poorly understood. This study investigated the effect of BBR on cecal ligation and puncture (CLP)-induced intestinal injury and explained the underlying mechanism. These results showed that BBR treatment decreased the mortality of septic mice, alleviated intestinal injury and reduced serum endotoxin level; at the same time, BBR had a protective effect on CLP-induced lung and liver apoptosis. Meanwhile, BBR treatment increased the proportion of Treg cells and CTLA-4 in Treg cells. Treg cells from BBR treatment mice could decrease the pro-inflammatory response by inhibiting the activation of macrophages, thus exerting a protective effect on CLP-induced intestinal injury, and CTLA-4 mediated cell-cell contact pathway is required for this protective effect.

Background Cavity effusion is common in patients with infectious diseases. However, the incidence rate and characteristics of serous cavity effusions (SCE) in septic patients are not clear to date. The objective of this study was to investigate the incidence and characteristics of SCE in septic patients and to explore the correlations between the bloody effusions and the illness severity/prognosis in septic patients. Methods From January 2010 to January 2015, a total of 214 patients with severe sepsis and septic shock were enrolled in this retrospective observational study. Thoracentesis or abdominal paracentesis was performed in 45 septic patients because of massive pleural effusions or ascites. The serum concentrations of VEGF, VEGFR, Ang, sICAM-1, sVCAM-1, E-selectin, Serpine1 and VE-cadherin in 45 septic patients underwent paracentesis were measured by enzyme-linked immunosorbent assay (ELISA). Results Of the 214 septic patients, 155 (72.4%) had SCE according to imaging or ultrasound manifestations. 45 subjects with SCE underwent therapeutic thoracentesis or abdominal paracentesis. Effusion laboratory analysis showed that exudates were predominant when compared with transudates (95.6% vs. 4.4%), and 16 (35.6%) patients suffered bloody effusions. Compared with patients with non-bloody effusions, those with bloody effusions showed higher critical illness scores (13 vs. 17 for APACHE II; 7 vs. 9 for SOFA), and higher mortality (6.9% vs. 62.5%). Moreover, patients with bloody effusions had delayed TT and APTT, increased D-dimer concentration, and higher serum levels of CRP and PCT (P

Readmission to intensive care unit (ICU) after esophageal cancer surgery is a major concern and can be associated with increased adverse outcomes. This study aims to explore causes, risk factors and early outcomes. We performed a monocentric retrospective analysis in 1140 patients who received esophageal cancer surgery in a higher volume surgeon group between January 2016 and December 2019, at Shanghai Chest Hospital. Univariate and multivariate analysis were performed to identify risk factors, and 1:4 propensity score matching (PSM) analysis was conducted to compare early outcomes. The incidence of ICU readmission was about 3.8% (43 of 1140). The most common cause was respiratory failure, found in 30 patients (70%). ICU readmission mainly occurred within 3 days after surgery, accounting for 46.5% (20 of 43), with the median length of stay was 3 days. Multivariate analysis identified heavy smoking (odds ratio[OR] = 2.445, 95% CI = 1.128 to 5.301, P = 0.024), intraoperative hypoxemia (OR = 2.461, 95% CI = 1.078 to 5.621, P = 0.033), mechanical ventilation during initial ICU stay (OR = 16.036, 95% CI = 7.332 to 35.074, P

BACKGROUND: Acute respiratory distress syndrome (ARDS) causes substantial mortalities. Alveolar epithelium is one of the main sites of cell injuries in ARDS. As an important kind of microRNAs (miRNAs), microRNA-145 (miR-145) has been studied in various diseases, while its role in ARDS has not been investigated. METHODS: Lipopolysaccharide (LPS) was intratracheally instilled to establish a rat ARDS model. Cytokines from bronchoalveolar lavage fluid (BALF) were measured using rat tumor necrosis factor-α and interleukin-6 enzyme-linked immunosorbent assay kits (R&D Systems), and the pathological structures were evaluated using hematoxylin and eosin (H&E) staining and transmission electron microscope; the lung miR-145 messenger RNA (mRNA) was detected using quantitative polymerase chain reaction. Bioinformatics focused on the target genes and possible pathways of gene regulation. RESULTS: A rat model of LPS-induced ARDS was successfully established. The miR-145 was down-regulated in the LPS-induced ARDS lung, and mitochondrial dysfunction was observed in alveolar epithelial cells, most obviously at 72 hours after LPS. TargetScan and miRDB databases were used to predict the target genes of miR-145. A total of 428 overlapping genes were identified, seven genes were associated with mitochondrial function, and Ogt, Camk2d, Slc8a3, and Slc25a25 were verified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the mitogen-activated protein kinase (MAPK) signaling pathway, and Gene Ontology (GO) biological process was mainly enriched in signal transduction and transcription regulation. CONCLUSIONS: The miR-145 is down-regulated in LPS-induced ARDS, and affects its downstream genes targeting mitochondrial functions.

BACKGROUNDThe World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the characteristic and risk factors of the illness severity.METHODSWe extracted data regarding 47 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University between February 1 and February 18, 2020. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP).RESULTSThe median age was 64.91 years, 26 cases (55.31%) were male of which, and 70.83% were severe cases. Severe patients had higher APACHE II (9.92 vs 4.74) and SOFA (3.0 vs 1.0) scores on admission, as well as the higher PSI (86.13 vs 61.39), Curb-65 (1.14 vs 0.48) and CT semiquantitative scores (5.0 vs 2.0) when compared with non-severe patients. Among all univariable parameters, APACHE II, SOFA, lymphocytes, CRP, LDH, AST, cTnI, BNP, et al were significantly independent risk factors of COVID-19 severity. Among which, LDH was most positively related both with APACHE II (R = 0.682) and SOFA (R = 0.790) scores, as well as PSI (R = 0.465) and CT (R = 0.837) scores. To assess the diagnostic value of these selected parameters, LDH (0.9727) had maximum sensitivity (100.00%) and specificity (86.67%), with the cutoff value of 283. As a protective factor, lymphocyte counts less than 1.045 ⨯ 109 /L showed a good accuracy for identification of severe patients with AUC = 0.9845 (95%CI 0.959-1.01), the maximum specificity (91.30%) and sensitivity (95.24%). In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocyte cells and its subsets, including CD3+, CD4+ and CD8+ T cells (P < 0.01).CONCLUSIONSThis study showed that LDH could be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases. And importantly, lymphocyte counts, especially CD3+, CD4+, and CD8+ T cells in the peripheral blood of COVID-19 patients, which was relevant with serum LDH, were also dynamically correlated with the severity of the disease.FUNDINGKey Project of Shanghai Municipal Health Bureau (2016ZB0202)

The objective of this study was to explore the prevalence of undiagnosed mild cognitive impairment (MCI) and its association with adverse outcomes in elderly patients undergoing thoracic surgery.A prospective cohort study.Large tertiary medical center.The authors enrolled 170 patients aged 65 years or older who were scheduled for thoracic surgery between November 7, 2018, and April 1, 2019, at the Shanghai Chest Hospital. Patients with a history of schizophrenia or dementia disease, uncorrected vision or hearing impairment, and refusal to participate were excluded.A total of 154 elderly patients completed the Chinese version of the Montreal Cognitive Assessment (MoCA) test preoperatively and were included in the final analysis. They were categorized into a normal group (MoCA ≥ 26 scores, group N) and an abnormal group (MoCA26 scores, group AN) based on test results. Delirium was assessed with the Confusion Assessment Method twice daily during the first 3 postoperative days.The primary outcome was the incidence of postoperative delirium (POD). Secondary outcomes included the incidence of postoperative pulmonary complications (PPCs), cardiovascular complications, other complications, intensive care unit (ICU) stay, and the hospital length of stay (LOS). The incidence of MCI before thoracic surgery in elderly patients was 49.4% (76 of 154). Compared with group N, MCI could increase the incidence of POD (14.1% v 30.3%, p = 0.016) and median LOS (4 d v 5 d, p = 0.016). However, the differences in pulmonary complications, cardiovascular and other complications, and ICU stay were not significant. Multivariable logistic regression analysis showed preoperative MCI (OR = 2.573, 95% CI =1.092 to 6.060, p = 0.031) as an independent risk factor of POD. Compared with the elderly patients without POD, POD could increase the risk of PPCs (17.5% v 35.3%, p = 0.026) and median LOS (4 d v 5 d, p0.001).The incidence of MCI before thoracic surgery in elderly patients was higher and associated with a higher rate of adverse postoperative outcomes. The findings may be important for preoperative patient counseling, operative planning, and eventually reducing potential risk exposure and related outcomes.

Background. Acute aortic dissection (AAD) is a devastating cardiovascular disease with a high rate of disability and mortality. This disease often rapidly progresses to fatal multiple organ hypoperfusion, and the incidence has been increasing in recent years. However, the molecular mechanisms have yet to be clarified. This study is aimed at identifying the differential abundance proteins (DAPs) of aortic arch tissues in patients with AAD by proteomics and select possible proteins involved in AAD pathogenesis. Methods. The fresh aortic arch tissues obtained from 5 AAD patients and 1 healthy donor were analyzed by amine-reactive tandem mass tag (TMT) labelling and mass spectrometry; then, the pathological sections of another 10 healthy donors and 20 AAD patients were chosen to verify the proteomic results by immunohistochemistry. Results. Of 809 proteins identified by proteomic analysis, 132 differential abundance proteins (DAPs) were screened, of which 100 proteins were significantly downregulated while 32 upregulated. Among 100 downregulated proteins, two proteins with known function, integrin alpha 3 (ITGA-3) and ITGA-5, were selected as target proteins involved in AAD pathogenesis. Two target DAPs were verified by immunohistochemisty, and the results showed that the integrated option density (IOD) of ITGA-3 and ITGA-5 in AAD patients was significantly lower than that in healthy donors, which were consistent with the proteomic results (P<0.001). Conclusion. ITGA-3 and ITGA-5 represent novel biomarkers for the pathogenesis of AAD and might be a therapeutic target in the future.

Background The dynamic monitoring of immune status is crucial to the precise and individualized treatment of sepsis. In this study, we introduced a model to describe and monitor the immune status of sepsis and explored 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 day 1 and 3. Serum cytokines levels (TNF-α, IL-2R, IL-6, IL-8 and IL-10) and CD14 + monocyte HLA-DR expression were measured to serve as immune markers. Cut-off values were acquired from ROC curves and serum cytokine level higher than or HLA-DR level lower than cut point was defined as “positive”, otherwise defined as “negative”. Classification of each immune status, namely SIRS, CARS and MARS, was defined by numbers of positive immune markers levels. Changes of immune status from day 1 to 3 were classified 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. In univariate analysis, serum levels of TNF-α, IL-2R, IL-6, IL-8 and IL-10 and HLA-DR expression at day 1 and 3 were associated with prognosis. Multivariate analysis discovered IL-10 and HLA-DR expression at day 3 were independent prognostic factors. Patients with MARS at day 1 had the highest mortality rate up to 58.7% among three immune status classifications, so did the patient with MARS at day 3 with mortality rate up to 69.2%. Immune status of 46.1% patients changed from day 1 to 3. Among four groups of immune status changes, DT had the highest mortality rate up to 77.8% followed by NR, RM and SB with mortality rate of 64.7%, 42.9% and 11.2% respectively. Conclusions Patients with severe immune disorder defined as MARS or deterioration of immune status defined as DT have the worst outcomes. The preliminary model of the classification and dynamic monitoring of immune status based on immune markers levels has prognostic values and worthy of further investigation. Trail Registration: ChiCTR-OCC-14005202 (Chinese Clinical Trial Registry), Registered 09 September 2014, http://www.chictr.org.cn/showproj.aspx?proj=4373

(5R)-5-hydroxytriptolide (LLDT-8) is a triptolide derivative with potent immunosuppressive property. This study aimed to investigate whether LLDT-8 manifests anti-inflammatory effects and influences dendritic cell function in early phase of lipopolysaccharide (LPS)-induced acute lung injury (ALI). C57BL/6 mice were administrated with LPS (6 mg/kg) to induce ALI and LLDT-8 were administrated at different doses (0.125 mg, 0.25 mg, 0.5 mg/kg). Histological changes were demonstrated by hematoxylin and eosin staining. Activation of dendritic cells were measured by flow cytometry. The concentrations of cytokines were measured by enzyme-linked immunosorbent assay. Bone marrow-derived dendritic cells (BMDCs) were acquired to explore immunosuppressive effects of LLDT-8 in vitro. Expression of Toll-like receptor 4 (TLR4), phosphorylation of inhibitor kappa B alpha (IκBα) and nuclear translocation of nuclear factor kappa B (NF-κB) were explored by immunoblot. Immunosuppressive property of LLDT-8-treated BMDCs were measured by adoptive transfer. The survival rate of ALI mice was significantly improved by LLDT-8 at the dose of 0.25 mg/kg. Moreover, systemic inflammatory response was suppressed and lung injury was relieved. LLDT-8 inhibited the activation of dendritic cells in vivo and influenced maturation, apoptosis and cytokine secretion capacity of BMDCs in vitro. Additionally, LLDT-8-treated BMDCs manifested reduced expression of TLR4, phosphorylation of IκBα and nuclear translocation of NF-κB. Adoptive transfer of LLDT-8-treated BMDCs alleviated LPS-induced lung injury. LLDT-8 also had protective effects on Pseudomonas aeruginosa-induced ALI. In conclusion, LLDT-8 played a protective role against ALI and suppressed dendritic cell activation potentially through affecting TLR4 expression and NF-κB signaling.

Ethnopharmacological relevance Xuanbai Chengqi decoction (XBCQ), a traditional Chinese medicine formulation, was reported to have a protective role in a variety of pulmonary infection diseases. However, its mechanism remains uncertain. In the current study, we investigated the potential mechanism of XBCQ, its therapeutic effects on organ injuries induced by sepsis and gut microbiota modulation. Material and methods 80 Male Sprague Dawley rats were performed cecal ligation and puncture (CLP) for sepsis model and 60 of them were treated with different doses of XBCQ (3.78, 7.56, 15.12 g/Kg, 20 rats per group) twice per day. After the most valid dose was determined, another 40 rats were divided randomly into four groups: sham group, sham + XBCQ group, sepsis group, sepsis + XBCQ group. The sepsis + XBCQ group was treated with XBCQ by intragastric administration and then twice per day. Feces of the rats were collected and the gut microbiota constituents were analyzed by 16S rDNA sequencing. Histological changes were observed by H&E staining. Occludin content in the colon was determined by immunohistochemical analysis. The concentrations of cytokines were determined by enzyme-linked immunosorbent assay (ELISA) kits. Results The survival rate of septic rats was increased significantly at the dose of 7.56 g/Kg from 50% to 80% at 72 h. The gut microbiota richness and composition were disturbed in septic rats. XBCQ altered the gut microbiota, involving alpha diversity changes, significantly reducing the relative abundance of Bacteroidaceae and ClostridiumXI and increasing that of Firmicutes and Actinobacteria. Furthermore, the relative abundances of Lactobacillus, Butyricicoccus and Bifidobacterium were increased by XBCQ. Moreover, the gut barrier dysfunction was improved by XBCQ through restoring the impaired tight conjunction protein Occludin. The concentration of diamine oxidase was decreased, while the D-lactate level was elevated. Meanwhile, the level of myeloperoxidase (MPO) in the lung tissue of the XBCQ-treated group was reduced. Lung injury was also alleviated by decreased levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and interleukin 10 (IL-10) in bronchoalveolar lavage fluids (BALFs). The relative abundance of potential microbial biomarkers in four groups significantly correlated with the concentration of inflammatory factors in BALFs. Conclusions Our results suggested that XBCQ had a protective role against sepsis by modulating the gut microbiota, restoring the intestinal epithelial barrier and decreasing inflammatory responses.

Background Secondary infection has a higher incidence in septic patients and affects clinical outcomes. This study aims to investigate the clinical characteristics, risk factors, immune status and prognosis of secondary infection of sepsis. Methods A four-year retrospective study was carried out in Zhongshan Hospital, Fudan University, enrolling septic patients admitted between January, 2014 and January, 2018. Clinical data were acquired from medical records. CD14+ monocyte human leukocyte antigen-D related (HLA-DR) expression and serum cytokines levels were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA) respectively. Results A total of 297 septic patients were enrolled, 92 of whom developed 150 cases of secondary infections. Respiratory tract was the most common site of secondary infection (n = 84, 56%) and Acinetobacter baumanii the most commonly isolated pathogen (n = 40, 31%). Urinary and deep venous catheterization increased the risk of secondary infection. Lower HLA-DR expression and elevated IL-10 level were found in secondary infection group. The expected prolonged in-hospital stay owing to secondary infection was 4.63 ± 1.87 days. Secondary infection was also associated with higher in-hospital, 30-day and 90-day mortality. Kaplan-Meier survival analysis and Log-rank test revealed that secondary infection group had worse survival between day 15 and day 90. Conclusions Urinary and deep venous catheterization increased the risk of secondary infection, in which underlying immunosuppression might also play a role. Secondary infection affected the prognosis of septic patients and prolonged in-hospital length of stay.

It remains unknown whether ambient air pollution could induce the onset of acute aortic dissection (AAD). This study aimed to investigate the potential association between fine particulate matter (PM2.5) and AAD onset. We collected new episodes of AAD between January 1, 2014 and December 31, 2018 from the emergency department of a major hospital in Shanghai, China. The overdispersed generalized additive model was used to estimate the association between PM2.5 and AAD emergency hospitalizations and was adjusted for time trends and weather conditions. During the study period, we identified a total of 1335 cases of AAD hospitalizations and recorded an average PM2.5 concentration of 45 ± 30 μg/m3. The association was statistically significant on the concurrent day of hospital admission, remained on the lag 1 day. For the average of the two lags, a 10 μg/m3 increase of PM2.5 was associated with 3.38% (95% confidence interval: 1.02%, 5.79%) increase of AAD hospitalizations. The association between PM2.5 and AAD remained when adjusting for the concomitant exposures to coarse particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone. The concentration-response curves increased apparently when daily PM2.5 concentration was beyond the China’s National Ambient Air Quality Standard (35 μg/m3). In stratified analyses, the significant association was only present among elders and males, and during cool season. This investigation demonstrated a significant and robust association between short-term PM2.5 exposure and increased AAD hospitalizations in Shanghai, China. Our findings have important implications for the prevention of AAD.