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Influenza virus is one of the common pathogens causing acute respiratory infectious diseases, and is easy to cause acute respiratory distress syndrome (ARDS) after infecting human body, which is an important cause of death of influenza patients. Influenza-induced ARDS results from a combination of overwhelming inflammation and immune response, causing tissue damage and apoptosis. Furthermore, virus-mediated oxidative stress is another important mechanism. Viral infection can produce excessive reactive oxygen species, which damage the epithelial-endothelial barrier with pulmonary edema. In this content, numerous studies have highlighted the importance of antioxidants as a new therapy aimed at blocking both viral replication and virus-induced inflammation. Therefore, this paper summarizes the epidemiology and mechanisms of influenza-induced ARDS, the role of oxidative stress in the occurrence and development of influenza-related ARDS and the role of antioxidants in anti influenza virus infection, in order to provide reference for effective treatment of influenza patients, reducing mortality, developing new anti influenza drugs and preventing and controlling influenza epidemic.
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As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.
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BackgroundIn December 2019, human infection with a novel coronavirus, known as SARS-CoV-2, was identified in Wuhan, China. The mortality of critical illness was high in Wuhan. Information about critically ill patients with SARS-CoV-2 infection outside of Wuhan is scarce. We aimed to provide the clinical features, treatment, and prognosis of the critically ill patients with SARS-CoV-2 infection in Guangdong Province. MethodsIn this multi-centered, retrospective, observational study, we enrolled critically ill patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) in Guangdong Province. Demographic data, symptoms, laboratory findings, comorbidities, treatments, and prognosis were collected. Data were compared between patients with and without intubation. ResultsForty-five critically ill patients with SARS-CoV-2 pneumonia were identified in 7 ICUs in Guangdong Province. The mean age was 56.7 years, and 29 patients (64.4%) were men. The most common symptoms at the onset of illness were high fever and cough. Majority of patients presented with lymphopenia and elevated lactate dehydrogenase. Treatment with antiviral drugs was initiated in all the patients. Thirty-seven patients (82.2%) had developed acute respiratory distress syndrome, and 13 (28.9%) septic shock. A total of 20 (44.4%) patients required intubation and 9 (20%) required extracorporeal membrane oxygenation. As of February 28th 2020, only one patient (2.2%) had died and half of them had discharged of ICU. ConclusionsInfection with SARS-CoV-2 in critical illness is characterized by fever, lymphopenia, acute respiratory failure and multiple organ dysfunction. Compared with critically ill patients infected with SARS-CoV-2 in Wuhan, the mortality of critically ill patients in Guangdong Province was relatively low. These data provide some general understandings and experience for the critical patients with SARS-CoV-2 outside of Wuhan.
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BackgroundAdministration of convalescent plasma may be of clinical benefit for treatment of severe acute viral respiratory infections. However, no clear evidence exists to support or oppose convalescent plasma use in clinical practice. We conducted a systematic review and meta-analysis to assess the evidence of randomized controlled trials (RCTs) in the convalescent plasma for the treatment of severe influenza. MethodsHealthcare databases were searched in February 2020. All records were screened against the eligibility criteria. Data extraction and risk of bias assessments were undertaken. The primary outcome was case-fatality rates by influenza. ResultsWe identified 5 RCTs of severe influenza. The pooled analyses showed no evidence for a reduction in mortality (Odds Ratio (OR) 1.06; 95% confidence interval (CI) 0.51-2.23; p = 0.87; I2 = 35%). We also found non-significant reductions in days in ICU and hospital, and days on mechanical ventilation. There seemed to have a biological benefit of increasing HAI titer levels and decreasing influenza B virus loads and cytokines after convalescent plasma treatment. No serious adverse events was reported between two groups. Studies were commonly of low risk of bias with high quality. ConclusionsConvalescent plasma appears safe but may not reduce mortality in severe influenza. This therapy should be studied within the context of a well-designed clinical trial for treatment of SARS-Cov-2 infection.
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Objective To investigate the effect of hydrochloric acid (HCl) stimulation and mechanical stretch on epithelial-mesenchymal transition (EMT) and hyaluronan (HA) production in human lung epithelial cells. Methods Human lung epithelial cell line BEAS-2B was cultured in vitro, which was divided into phosphate-buffer saline (PBS) + static group, HCl + static group, PBS + stretch group, and HCl + stretch group respectively in the logarithmic phase. The BEAS-2B cells in two stretching groups were challenged by cyclic stretch with 20% amplitude, frequency of 0.33 Hz, sine wave of the FX-5000T system for 48 hours. The morphology changes in cells before and after stretch were observed with inverted microscope. The protein expressions of epithelial markers E-cadherin and cytokeratin-8 (CK-8) as well as mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) were determined by Western Blot. The secretion of HA was determined by enzyme linked immunosorbent assay (ELISA). Results ① It was shown by microscopic observation that BEAS-2B cells displayed cobblestone morphology, linked closely and cell polarity in PBS + static group, which did not change obviously after HCl stimulation alone. Given purely mechanical stretch after 48 hours, the cells morphology changed from cobblestone shape into long spindle, and increased intercellular space obviously. Double hit of HCl and stretch changed the cells morphology more significantly. ② It was shown by Western Blot that compared with the PBS + static group, HCl alone or combined with purely mechanical stretch after 48 hours, the expressions of E-cadherin and CK-8 were decreased, while those of vimentin and α-SMA were increased, and it was more pronounced in HCl + stretch group [the expression quantity (gray value) as base 1 in PBS + static group, E-cadherin: 0.16±0.08 vs. 1, CK-8: 0.10±0.03 vs. 1, vimentin: 3.35±0.38 vs. 1, α-SMA: 3.10±0.45 vs. 1, all P < 0.01]. ③ It was shown by ELISA that both HCl stimulation and stretch could induce BEAS-2B cells secreting HA as compared with PBS + static group (μg/L: 55.763±0.687, 63.005±0.493 vs. 49.876±1.867), and the production of HA increased more remarkably after double hit (μg/L: 78.220±1.085 vs. 49.876±1.867, P < 0.01). Conclusions Both HCl and mechanical stretch could induce EMT and increase HA secretion in human lung epithelial cells in vitro. Double hit of HCl stimulation and mechanical stretch induced EMT apparently, and further increased the production of HA.
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Objective To analyze the potential factors affecting the prognosis of patients with sepsis and evaluate their values in predicting the disease outcome. Methods A clinical prospective study was conducted. Fifty-three septic patients admitted to intensive care unit (ICU) of the First Affiliated Hospital of Guangzhou Medical University from October 17th, 2012 to August 8th, 2013 were enrolled, and in the same term 35 volunteers having passedphysical check-up were assigned in the healthy control group. According to the severity of the patients, they were divided into sepsis, severe sepsis and septic shock groups. Furthermore, based on the difference in scores of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), the patients were divided into low-risk (APACHE Ⅱ scores 0.05). The IL-8 level of non-coagulation defect group was significantly lower than that of adjusted (ng/L:24.67 vs. 27.23, P0.05). Conclusions The grade of sepsis severity, APACHEⅡscore, whether existence of coagulation dysfunction being present or not and whether its presence being adjusted or not during the septic patients' stay in ICU, the levels of blood lactate, PCT, IL-6 and IL-8 on the first day in ICU are significantly correlated to the prognosis of septic patients. Whether the existence of coagulation dysfunction being present or not, whether coagulation dysfunction being adjusted or not and the blood lactate level are the independent prognostic factors of septic patients, and the plasma concentrations of IL-6 and IL-8 are the independent affecting factors of whether coagulation dysfunction occurring or not, therefore they have predicting value concerning the occurrence of coagulation dysfunction in septic patients.
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Objective To prospectively and directly compare the capability of whole-body DWI,MRI and/or CT (MRI-CT),and whole-body DWI with MRI-CT for assessment of lymphatic metastases in non-small cell lung cancer (NSCLC) patients.Methods The institutional review board approved this study; informed consent was obtained from patients.A total of 56 NSCLC patients underwent whole-body DWI and thoracic CT scan prospectively.Conventional MRI was performed in suspicious lymphatic metastases parts within one week after inspection.Final diagnosis of the lymphatic metastases in each patient was determined on the basis of results of all radiologic and follow-up examinations.Two chest radiologists independently assessed all examination results and used a five-point visual scoring system to evaluate the probability of metastases.Final diagnosis based on each of the methods was made by consensus of two readers.Receiver operating characteristic (ROC) analysis was used to compare the capability for lymphatic metastases assessment among whole-body DWI,MRI-CT and whole-body DWI with MRI-CT.The detection abilities of lymph nodes with different size were compared with x2 test.Value of apparent diffusion coefficient (ADC) in the differential diagnosis of benign and malignant lymph nodes was compared with the variance analysis.Results (1) Lymph nodes metastases were divided into 3 groups according to the length diameter (< 2,2-3,> 3 cm).A statistically significant difference (x2 =13.819,P < 0.01) was found in detection of lymph nodes (< 2 cm) among whole-body DWI,MRI-CT and whole-body DWI with MRI-CT(within the 123 lymph nodes,109,98 and 117 were detected respectively),whole-body DWI with MRI-CT was superior to conventional MRI-CT(x2 =13.324,P<0.01).There were no statistically significant difference between the other 2 groups (in the length diameter 2-3 cm group,43,40 and 45 of all 46 lymph nodes were detected respectively by whole-body DWI,MRI-CT and whole-body DWI with MRI-CT,x2 =3.816,P > 0.05,while in the length diameter > 3 cm group,all of the 27 lymph nodes were detected by each of them.(2) Conventional MRI-CT was superior to whole-body DWI in the diagnosis of lymph node metastasis in NSCLC.The area under ROC curve value of whole-body DWI with MRI-CT(Az =0.978),the sensitivity,specificity,accuracy (97.4% 、88.9% 、86.3% respectively) were significantly higher than conventional MRI-CT or whole-body DWI.(3)The ADC value of malignant lymph nodes were significantly lower than those of benign [(0.79 ± 0.15) × 10-3 mm2/s vs (1.59--0.15) × 10-3 mm2/s,F =332.813,P < 0.01].The sensitivity,specificity,accuracy were 100% with the cut-off value of 1.06 × 10-3mm2/s.Conclusions Whole-body DWI is the beneficial supplements of MRI-CT and can be used as a earlier clinical technique in patients with suspected NSCLC lymph node metastasis.Combined with ADC value,it can be used for assessment and differential diagnosis of lymphatic metastases in NSCLC patients.
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Objective To investigate the application of whole-body diffusion-weighted imaging (WB-DWI),and to detect bone metastasis in malignant tumor patients.Methods A total of 118 malignant tumor patients prospectively underwent WB-DWI,standard MRI/CT in suspicious bone metastases parts within one week after inspection.Final diagnosis of the bone metastases in each patient was determined on the basis of results of all radiologic and follow-up examinations.The differential diagnosis value of apparent diffusion coefficient (ADC) in benign and malignant bone metastases was compared with the variance analysis.Results Area under ROC curve value of WB-DWI with standard MRI/CT (0.999) was larger than that of WB-DWI (0.944) and standard MRI/CT (0.983),and the specificity,accuracy and positive predictive value were also the highest(100.0 %,97.4 %,100.0 %).The ADC values of malignant bone metastases were significantly lower than those of benign lesions[(0.71±0.15)×10-3 mmTs vs (1.50±0.23)×10-3 mm2/s] with a statistically significant difference(F =261.587,P < 0.001).Conclusion WB-DWI is the beneficial supplements of standard MRI/CT.Which can be used for assessment and differential diagnosis of bone metastases in malignant tumor patients combined with ADC value.
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Objective To study the safety, reasonableness and feasibility of D 3 lymphadenectomy(LC) for advanced right colon cancer(ARCC). Methods 97 cases of ARCC were divided randomly into two groups: D 2.LC group (55cases) and D 3 LC group (42cases). The climical data between D 3 LC and D 2LC were compared. Results Comparing to D 2 LC,D 3 had higher operative invasive degree, but the incidence of postoperative complications did not increase, the ratio of the curable resection and the three-year and five-year survival rate after operation were significantly higher (88.1% and 73.8% vs 72.8% and 52.7%) (all P
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Objective To assess the therapeutic effect and opportune time of surgical treatment of hepaticolithiasis . Methods The clinical data of 92 patients with hepaticolithiasis who underwent surgical treatment were analyzed retrospectively. Results (1) The incidence of postoperative complications was 14.1% (13/92 cases), in choledochoscopy group it was 9.3%(4/43 cases) and in the non choledochoscopy group 18.4%(9/49 cases) ; in the emergency operation group it was 36%(9/25 cases) and in selective operation group 5.97%(4/67 cases) . (2) The incidence of residual stones was 22.9%(21/92 cases); in choledochoscopy group it was 13.9%(6/43 cases) and the non choledochoscopy group 30.6%(15/49 cases); in emergency surgery group it was 36%(9/25 cases) and in selective operation group 17.9%(12/67 cases).(3)One pationt died from ACST two days after operation . All of the patients were followed up for 4-10 years; there were 80 cases (86.9%) who had a good therapeutic outcome. Conclusions Logical surgical procedure associated with choledochoscopy and appropriate timing of surgical intervention can markedly improve the effect of surgical treatment of hepaticolithiasis and reduce the incidence of postoperative complications.