Search

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: 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.

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.

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.

To analyze the prognostic risk factors of patients with sepsis and the clinical characteristics of patients with septic myocardial injury.A retrospective study was conducted. The clinical data of 300 patients with sepsis admitted to emergency department of Zhongshan Hospital of Fudan University from September 2017 to June 2020 were enrolled, including basic information, blood test indicators and auxiliary inspection indicators. The patients were grouped according to myocardial injury and the clinical characteristics of patients with septic myocardial injury were analyzed. According to 28-day prognosis, they were divided into survival group and non-survival group. The differences in various indicators between the two groups were compared, and binary Logistic regression was used to explore independent risk factors for death in patients with sepsis.In 300 patients, 47 patients were excluded for previous heart disease or lack of the main inspections, and 253 patients were enrolled finally. (1) Myocardial injury occurred in 136 out of 253 patients (53.8%), and 117 without myocardial injury. Compared with the non-myocardial injury group, the myocardial injury group had higher blood white blood cell count [WBC (×10Myocardial injury is an independent risk factor for death in patients with sepsis. PCT elevation, LVEF decreased and sinus tachycardia are main characteristics of patients with septic myocardial injury, which should attract clinical attention.

Raw data

Background. The prognostic nutritional index (PNI) has been reported to significantly correlate with poor survival and postoperative complications in patients with various diseases, but its relationship with mortality in COVID-19 patients has not been addressed. Method. A multicenter retrospective study involving patients with severe COVID-19 was conducted to investigate whether malnutrition and other clinical characteristics could be used to stratify the patients based on risk. Results. A total of 395 patients were included in our study, with 236 patients in the training cohort, 59 patients in the internal validation cohort, and 100 patients in the external validation cohort. During hospitalization, 63/236 (26.69%) and 14/59 (23.73%) patients died in the training and validation cohorts, respectively. PNI had the strongest relationships with the neutrophil-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level but was less strongly correlated with the CURB65, APACHE II, and SOFA scores. The baseline PNI score, platelet (PLT) count, LDH level, and PaO2/FiO2 (P/F) ratio were independent predictors of mortality in COVID-19 patients. A nomogram incorporating these four predictors showed good calibration and discrimination in the derivation and validation cohorts. A PNI score less than 33.405 was associated with a higher risk of mortality in severe COVID-19 patients in the Cox regression analysis. Conclusion. These findings have implications for predicting the risk of mortality in COVID-19 patients at the time of admission and provide the first direct evidence that a lower PNI is related to a worse prognosis in severe COVID-19 patients.

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)

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.

Objectives Acute aortic dissection (AAD) is a severe clinical emergency with a high mortality, and is easily misdiagnosed in its early stage. This study aimed at discovering serum metabolomic markers with the potential to diagnose AAD and distinguish between two subtypes of AAD. Methods Thirty-five patients with AAD, including 20 with Stanford type A and 15 with Stanford type B were enrolled in this study, together with 20 healthy controls. All patients with AAD were admitted within 72 h of onset. Serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and the data were analysed by principal component analysis and partial least squares discriminant analysis. Results A total of 17 metabolites differing between the control and AAD groups were finally screened and identified as lysophosphatidylcholines (LPC) and sphingolipids including sphinganine, phytosphingosine, sphingomyelin, and ceramide. Compared with those in the healthy control group, LPC levels were significantly lower in both the Stanford type A and type B AAD groups. Interestingly, sphingolipids, including sphinganine, phytosphingosine, and ceramide, were remarkably reduced in the Stanford type A AAD group, but not in the Stanford type B AAD group. Subgroup analysis showed that the changes in LPC and sphingolipid levels were unrelated to hypertension or gender. Conclusions The present results indicate that LPCs and sphingolipids are significantly altered in patients with AAD, and several sphingolipids, such as sphinganine, phytosphingosine, and ceramide, were dramatically decreased in patients with Stanford type A AAD. A combination of these two families of metabolites could serve as a potential biomarker for the diagnosis of AAD and distinguishing between Stanford type A and Stanford type B.

The aim of the present study was to investigate the association between serum lumican levels and acute aortic dissection (AAD) severity. A total of 82 patients with chest or back pain and 30 healthy volunteers were recruited. Among the patients, there were 70 cases of AAD and 12 cases of intramural hematoma (IMH). AAD severity was determined using multi-slice computed tomography angiography (MSCTA). Serum was collected from the patients upon admission, and lumican levels were detected using an enzyme-linked immunosorbent assay. In addition, correlation analyses were conducted between lumican levels and AAD severity by designing a 'SCORE X, RANGE Y' system to measure the number of affected vital arteries and vertical range of false lumen, based on the MSCTA. Lumican levels differed significantly among the AAD patients (2.32±4.29 ng/ml), IMH patients (0.72±0.32 ng/ml) and healthy volunteers (0.85±0.53 ng/ml; P=0.003). In the AAD patients presenting within 12-72 h of symptom onset, the Spearman's rho correlation coefficient between lumican and SCORE or RANGE was 0.373 (P=0.046) and 0.468 (P=0.010), respectively. The present results suggest that lumican may be a potential marker for aiding the diagnosis and screening for AAD, and may be used to predict the severity of AAD.

The purpose of this study was to evaluate the utility of potential serum biomarkers for acute aortic dissection (AAD) that were identified by isobaric Tags for Relative and Absolute Quantitation (iTRAQ) approaches. Serum samples from 20 AAD patients and 20 healthy volunteers were analyzed using iTRAQ technology. Protein validation was performed using samples from 120 patients with chest pain. A total of 355 proteins were identified with the iTRAQ approach; 164 proteins reached the strict quantitative standard, and 125 proteins were increased or decreased more than 1.2-fold (64 and 61 proteins were up- and downregulated, resp.). Lumican, C-reactive protein (CRP), thrombospondin-1 (TSP-1), and D-dimer were selected as candidate biomarkers for the validation tests. Receiver operating characteristic (ROC) curves show that Lumican and D-dimer have diagnostic value (area under the curves [AUCs] 0.895 and 0.891,P<0.05). For Lumican, the diagnostic sensitivity and specificity were 73.33% and 98.33%, while the corresponding values for D-dimer were 93.33% and 68.33%. For Lumican and D-dimer AAD combined diagnosis, the sensitivity and specificity were 88.33% and 95%, respectively. In conclusion, Lumican has good specificity and D-dimer has good sensitivity for the diagnosis of AAD, while the combined detection of D-dimer and Lumican has better diagnostic value.

The endotoxin tolerance phenotype is characterized with decreased inflammation and increased phagocytosis. We hypothesized that endotoxin tolerance would provide protective effects on experimental sepsis with multiple organ injuries induced by cecal ligation and puncture (CLP). Endotoxin tolerance was induced in male Sprague–Dawley rats with daily intraperitoneal injection of either 0.6 mg/kg of lipopolysaccharide (LPS) or vehicle for four consecutive days before subsequent CLP. Biochemical parameters, histological changes, inflammatory cytokine production, and lung tissue nuclear factor-κB (NF-κB) activation were assessed post-CLP. In a separate experiment, survival rate was monitored for 7 days after CLP. In vehicle-treated animals, CLP caused multiple organ injuries confirmed by the biochemical variables and histological examination. This was accompanied by an early activation of NF-κB in the lung and a substantial increase in plasma levels of tumor necrosis factor-α, interleukin-6, and interleukin-10. In contrast, pretreatment with LPS not only alleviated the development of multiple organ injuries after CLP, but also decreased sepsis-induced activation of pulmonary NF-κB and reduced plasma cytokines production. In addition, LPS pretreatment improved the survival in rats subjected to CLP. The beneficial effects of endotoxin tolerance indicate the potential of immunomodulatory strategies in the management of severe sepsis.

Acute aortic dissection (AAD) is a serious vascular disease. Currently the diagnosis relies on clinical and radiological means whereas serum biomarkers are lacking. The purpose of this study was to identify potential serum biomarkers for AAD using isobaric tags for relative and absolute quantitation (iTRAQ) approach. A total of 120 serum samples were collected from three groups: AAD patients (n=60), patients with acute myocardial infarction (AMI,n=30), and healthy volunteers (n=30), whereas the first 10 samples from each group were used for iTRAQ analysis. Using iTRAQ approach, a total of 174 proteins were identified as significantly different between AAD patients and healthy subjects. Among them, forty-six proteins increased more than twofold, full-scale analysis using serum sample for the entire 120 subjects demonstrated that Lumican level was significantly increased relative to control and AMI samples. Further, Lumican level correlated with time from onset to admission in AAD but not AMI samples. Using iTRAQ approach, our study showed that Lumican may be a potential AAD-related serum marker that may assist the diagnosis of AAD.