Objective: The purpose was to confirm the significance of Anti-endothelial cell antibodies(AECA) in chronic obstructive pulmonary disease (COPD) and validate the effect of methylprednisolone intervention.
Since December 2019, the outbreak of pneumonia infected by the novel coronavirus (SARS-CoV-2) emerged in China, it caused serious public health event and thus caused worldwide attention. Recent researches revealed that the blockage of small airways by mucus plug is considered to be an important pathophysiological change in COVID-19 patients. So far, there is no definite and effective treatments have been presented for COVID-19. Vitamin C is widely available and has shown the potential inhibiting the airway mucus secretion, but its effect on improving the outcome of COVID-19 patient is unclear.
With the expansion of 2019 novel coronavirus disease(COVID-19), large of suspected cases were reported. This essay compares the clinical features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and other viral infections among the suspected COVID-19 patients, and attempts to explore an ideal diagnostic model of COVID-19. 60 viral pneumonia patients from 86 suspected patients were enrolled and grouped into two: the COVID-19 group (19 cases) and other viral infections group (41 cases). Compare and analyze the blood test results, biochemical indicators and chest CT scan changes of patients. 60 patients were mainly young and middle-aged men, of which 60%were infected with influenza virus, and 31.6%were infected with SARS-COV-2 according to pathogenic distribution. And we found statistic differences among blood cell counts and blood biochemistry between the two groups. The COVID-19 patients' chest CT showed that the lung lesions were mainly bilateral nodule or appeared to be patchy and ground glass shadowed. While most of the lung lesions caused by other virus were mainly unilateral patchy shadow (P＜0.05). We found a new multi-marker PTG, which composed of platelet-to-neutrophil ratio(PNR), total bilirubin(TBIL) and ground-grass density, The area sunder curves(AUC)of PTG was 0.908, the sensitivity was 73.17%and the specificity was 94.44%. The ratio of blood RT to its sub-group and chest CT were considered as important reference in differential diagnosis. The PTG, with extremely high specificity and sensitivity in early differential diagnosis of COVID-19 and other viral pneumonia, had a significant clinical value.
The purpose of our study was to screen the plasma cytokines to find possible indicators of disease progression and prognosis of patients with infection. With a prospective cohort study, selected patients were divided into sepsis group and non-sepsis group. Demographic and clinical information were collected. Blood samples were tested for the levels of plasma cytokines and metagenomic next-generation sequencing (mNGS). 30-day follow-up information was recorded, and data was analyzed by SPSS22.0 (SPSS Inc, Chicago, IL). A total of 95 patients were selected. After propensity score matching of age and gender, 36 patients with sepsis and 36 with non-sepsis were enrolled. 30-day follow-up data exhibited that 41 patients died and 31 survived. Patients with sepsis and 30-day death had higher plasma levels of cytokines, including macrophage-stimulating factor (M-CSF), monocyte chemoattractant protein-3 (MCP-3), etc., than patients with non-sepsis and 30-day survival, respectively. M-CSF > 8.21pg/ml was an independent risk factor for 30-day death, and the reads of pathogens in mNGS reports was positively correlated with the plasma concentrations of various cytokines, including M-CSF.
A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. The major presentations of patients are fever, fatigue, and dry cough. No cases have been reported with night sweats as the first symptom. This article present a case which diagnosed with COVID-19 pneumonia with night sweats as the first symptom. Chest CT showed patches of ground-glass opacity, qRT-PCR of SARS-CoV-2 were positive. After treatment, the patient did not present with night sweats again. A recheck of the chest CT showed that the ground-glass opacity was completely absorbed and the SARS-CoV-2 nucleic acid test was negative. This case suggests that night sweats might be the first and major symptom of COVID-19 pneumonia.
The coronavirus disease 2019 (COVID-19) has swept across all countries in the world within half a year, which is taking the world by surprise. We reported an elderly, severe, complicated COVID-19 case, describing the clinical manifestations, laboratory examinations, CT findings, diagnosis, treatment and dynamic disease course. 3D post-processing technique was used to reconstruct different pulmonary lesions, and it was found to be useful for highlighting and observing them, thereby helping diagnose and distinguish different diseases.
The detection of viral nucleic acid by real time RT-PCR is the main confirmative diagnostic method for COVID-19 in clinical practice in China and worldwide. However, its sensitivity is unclear. Here we report two cases in a family in Guizhou, southwestern China. The father had a history of long stay in Wuhan, the center of the first recorded COVID-19 outbreak. Surprisingly, although the son was diagnosed positive using the nasopharyngeal swab specimen and the rRT-PCR method, the father was diagnosed negative continuously for multiple times. Only after the alveolar lavage fluid sample was used, the father's rRT-PCR diagnosis turned positive. Their CT diagnosis and clinical symptoms did not completely align with their rRT-PCR diagnostic results. The underlying mechanisms and their implications to clinical practice are discussed.
Coronavirus disease 2019 (COVID-19) is a novel infectious disease that spreads rapidly around the world and endangers global public health. Because of the lack of specificity of previously identified CT images, such as peripheral and subpleural ground glass opacities, early diagnosis is still a big challenge for radiologists. How to improve the accuracy of diagnosis and make diagnosis as early as possible is a problem concerned by the medical field. This article reports two important CT manifestations in COVID-19 patients
Most of the clinical research on coronavirus disease 2019 (COVID-2019) has focused on patients in Wuhan, Hubei, China. This study describes the clinical characteristics of COVID-19 patients outside of Hubei. Eighteen confirmed COVID-19 patients at Guizhou Provincial People's Hospital were included. They were divided into nonsevere and severe groups, and their epidemiological characteristics, demographics, clinical manifestations, and laboratory results were reviewed and compared. All patients were infected through human-to-human transmission, and 9 were imported cases. The clinical features were mainly cough (16 [89%]), fever (11 [61%]), and sputum production (9 [50%]). Most patients had bilateral pneumonia. There were significant differences in the level of lactate dehydrogenase (LDH) (179 [142-193] vs 289 [260.25-368.75]), level of serum ferritin (267.2 [100.5-675.2] vs 614.85 [528.5-870.78]), lymphocyte count (1.52 [1.40-1.60] vs 0.59 [0.47- 1.05]), and CD cell count (1576 [1040-1696] vs 444 [312-592] CD3+ T cells, 692 [420-708] vs 144 [128-320] CD4+ T cells, 796 [632- 892] vs 228 [152-284] CD8+ T cells) between the nonsevere group and the severe group (P <0.05). As of Feb. 11th, 9 people had been discharged after treatment. This study suggests that COVID-19 cases often occur in clusters. Patients with severe COVID-19 had abnormalities in inflammation and immune indicators. Most patients outside Hubei had a good prognosis.
Psoriasis is immune-mediated chronic inflammatory disorder related to Th1 pattern, in which, 2 to 3% of white population worldwide have been affected. It is demonstrated that excessive secretion of pro-inflammatory cytokines such as IL-17A, TNF-α, IL-6, IFN-γ, IL-2 and IL-12 are involved in the immunopathogenesis and clinical manifestations of the disease. Common and previous therapeutics strategies have not been beneficial for all patients, yet. So, there is increasing considerations, leading basic medical scientists toward new directions. During last decade, exponential growth of immune based methods with easy accessibility, less morbidity and operatively yields in clinical trials, has opened a new window to novel clinical applications. Recently, approaches with immunological perspectives such as special immunobiomarkers recruitment, stem cells and vectors have been appropriated to psoriasis immunotherapy purposes. Various evidences suggest that interleukin-35 (IL-35) has important roles in immune system regulation as a promising anti-inflammatory agent. Also, it is demonstrated that Mesenchymal Stem Cells (MSCs) are able to hold anti-inflammatory and immunosuppressive properties, too. Here, we suggest a hypothetical cell and gene-based immunotherapy method that it could be advantageous for pro-inflammatory agents diminution in psoriatic patients. We hope that anti-inflammatory effects of IL-35 gene transfer via Adenoassociated virus as a vector by Bone Marrow derived-MSCs (BM-MSCs) in an Imiquimod-induced psoriasis-like mouse model, will probably be efficient in psoriasis global dilemma domination. Keywords: Psoriasis, IL-35, Mesenchymal stem cell, Regenerative medicine, Clinical applications.
Asthma is a chronic inflammatory airway disease, with an array of cells involved in the pathogenesis of the disease. The role of neutrophils in asthma pathogenesis is controversial. This review highlights the mechanisms of neutrophils about their aberrant functionality involved in asthma and factors contributed to impaired response to corticosteroids, which may contribute to a better understanding of asthma pathogenesis and consequently, facilitate the development of novel strategies for managing and treating neutrophilia in asthma.
Alzheimer’s Disease (AD) is characterized by a slowly progressive decline of cognition and memory and is the most frequent cause of dementia. HM contribute to the regulation of multiple neuro-chemical and neuro-metabolic pathways. The pathological features of AD include amyloid beta peptide (Aβ) deposition, neuronal tangle formation and granulovacuolar degeneration. Aβ protein is a normal part of the innate immune system, the bodyu0027s first-line defense against infection. However recent report shows that Ab expression protects against fungal and bacterial infections in mouse, nematode, and cell culture models of AD. However, recent research has shown that these proteins are also expressed on bacterial and fungal cell surfaces and might contribute to immune response. In addition to commensal microbes there are other pathogens like Chlamydophila pneumoniae, Toxoplasma gondii, HIV- associated neurocognitive disorders (HAND, Viroids, Hepatitis, Cytomegalovirus have been suspected to be involved in AD. Microbes are proposed to be involved in pathophysiology of neurodegenerative disease through their ability to produce relevant neurotransmitter level, immune modulation due to excess inflammation and translocation to brain from the site of infection trough blood or lymphatic system. Here we elaborated on the emerging ideas showing the contribution of the gut microbiome to human neurological diseases with special emphasis on AD. The evidences outlined in this review may prove useful in designing further studies for taxonomic and functional profiling of microbiota in patients with AD leading to new advanced therapeutic inventions.
The innate immune sensing of pathogens is important for host to mount defensive responses. STING has emerged in recent years as a critical signaling adaptor in the immune response to cytosolic DNA and RNA derived from pathogens. Liu et al. (2016) demonstrate that the RIG-I-dependent RNA sensing signaling induces STING expression via a TNF-α and IFN-α synergy. The up-regulation of STING is vital for 5'pppRNA restriction of HSV, a DNA virus that infects humans and causes herpes, in vitro and in vivo. This study provides new insights into the cross talk between DNA and RNA pathogen-sensing systems via the control of STING.
The mechanism of bile acid induced cholestatic liver injury remains controversial, thus hindering the development of new therapies for these diseases. In this research highlight, we briefly review the evolution of our understanding of the pathogenesis of bile acid induced liver injury, and summarize our recent findings on this topic. Our data suggests that under pathophysiological conditions bile acid induced liver injury is mediated by inflammatory responses that are initiated from stressed hepatocytes. We conclude by mentioning potential new therapeutic approaches for treating cholestatic liver injury based on these pathophysiologic concepts.
Uveitis, the pathological condition of inflammation of the uvea, commonly causes severe visual impairment and blindness. Possible causes of uveitis include infection, injury, or an autoimmune or inflammatory disease. However, the pathogenesis of uveitis is not fully understood. Glucocorticoids are widely used for the treatment of uveitis, but long-term steroid use carries a risk of potential complications. Early diagnosis and proper treatment are important to prevent the complications of uveitis. Thus far, researchers have not identified an effective biological marker for auxiliary diagnosis or an appropriate method for monitoring the inflammatory activity of uveitis. S100A8/A9, also known as calprotectin, belongs to the Ca 2+ -binding S100 protein family; is mainly expressed in myeloid leukocytes; and plays a prominent role in a variety of pathological process, such as inflammation, infection and autoimmune diseases. Extracellular S100A8/A9 released from granulocytes and monocytes has recently gained a great deal of attention as a critical alarmin for the modulation of the inflammatory response. This review will summarize recent insights into the biological function of S100A8/A9 in uveitis and provide an outlook on diagnostic, inflammation monitoring and therapeutic applications targeting S100A8/A9 for the treatment of uveitis.
Latency is a hallmark of all herpesviruses, during which the viral genomes are silenced through DNA methylation and suppressive histone modifications. When latent herpesviruses reactivate to undergo productive lytic replication, the suppressive epigenetic marks are replaced with active ones to allow for transcription of viral genes. Interestingly, by using Kaposi's sarcoma-associated herpesvirus (KSHV) as a model, we recently demonstrated that the newly transcribed viral RNAs are also subjected to post-transcriptional N6-adenosine methylation (m6A). Blockade of this post-transcriptional event abolishes viral protein expression and halts virion production. We found that m6A modification controls RNA splicing, stability, and protein translation to regulate viral lytic gene expression and replication. Thus, our finding for the first time reveals a critical role of this epitranscriptomic mechanism in the control of herpesviral replication, which shall shed lights on development of novel strategies for the control of herpesviral infection.
There is a growing body of evidence that bilirubin, which is generated during the physiological breakdown of heme, exerts potent anti-inflammatory effects. Previous work by our group suggests that bilirubin is able to suppress inflammatory responses by preventing the migration of leukocytes into target tissues through disruption of vascular cell adhesion molecule-1 (VCAM-1)-dependent cell signaling. As VCAM-1 is an important mediator of tissue injury in the dextran sodium sulfate (DSS) murine model of inflammatory colitis, we examined whether bilirubin prevents colonic injury in DSS-treated mice. As anticipated, bilirubin-treated animals manifested significantly less colonic injury and reduced infiltration of inflammatory cells into colon tissues. We further observed that bilirubin administration was associated with a reduced number of eosinophils and monocytes in the small intestine, with a corresponding increase in peripheral blood eosinophilia, regardless of whether mice received DSS. These findings suggest that bilirubin impairs the normal migration of eosinophils into intestinal tissues, as supported by in vitro experiments showing that bilirubin blocks the VCAM-1-dependent movement of Jurkat cells across human endothelial cell monolayers. Taken together, our findings support that bilirubin ameliorates DSS-induced colitis and disrupts the physiological trafficking of leukocytes to the intestine by preventing transmigration across the vascular endothelium, potentially through the inhibition VCAM-1-mediated signaling. Our findings raise the possibility that bilirubin functions as an endogenous regulator of inflammatory responses.
The recent discovery of the role played by gut microbiota on the control of metabolic disease opens novel routes for the identification of the causes of type 2 diabetes and obesity. This paradigm could explain the infiltration, by innate and adaptive immune cells, of the adipose tissue, liver, and islets of Langerhans which is responsible for the metabolic inflammation state that leads to impaired insulin action and secretion, and therefore, type 2 diabetes. The identification of the causal role of circulating lipopolysaccharides LPS and peptidoglycans in the development of metabolic inflammation, due to an increased intestinal permeability, led to the leaky gut hypothesis. In addition, whole live bacteria were found in metabolic tissues establishing a tissue microbiota which upon a fat-enriched diet becomes dysbiotic. The process of intestinal bacterial translocation was responsible for the onset of a leaky gut causal to the disease. The translocation of selective sets of intestinal bacteria to the blood could be identified. These blood bacterial 16SrRNA-DNA sequences are considered as biomarkers of the bacterial translocation process. An increased of the corresponding bacterial DNA concentration was predicting the occurrence of type 2 diabetes. Associated to the dysbiotic microbiota translocation, an impaired intestinal immune defense was identified as a cause of the selective leaky gut. The change in small intestine mucosal microbiota induced by a fat-enriched diet reduces the number of IL17-secreting CD4 T cells within the lamina propria of the intestine. This loss of IL17-secreting CD4 T cells is the consequence of an impaired capacity of intestinal antigen presenting cells to activate and trigger the expression of RORgt and the production of IL17 by CD4 T cells. Altogether, an impaired intestinal immune defense, notably the reduced differentiation of RORgt expressing IL17-producing CD4 T cells, favors the onset of a leaky gut leading to the translocation of bacterial factors and live bacteria towards tissues triggering metabolic inflammation; insulin resistance and type 2 diabetes. Hence, the triggering of intestinal defense surrounding RORgt pathway now appears as a potential target mechanism for the control of type 2 diabetes.
Glioblastoma Multiforme (GBM, Astrocytoma grade-IV) is the most common primary malignant brain tumour in adults and unfortunately the most deadly. Patients with GBM exhibit a deficient anti-tumor immune response. Immunotherapy is rapidly becoming one of the pillars of anti-cancer therapy. GBM has not received similar clinical successes as of yet, a fact which may be attributed to its relative inaccessibility,its poor immunogenicity, or any of the many other immune mechanisms known to be inactivated in these tumor cells. Focused Ultrasound (FUS) is emerging as a promising treatment approach. The effects of FUS on the tissue are not merely thermal. Reported FUS-induced acoustic cavitation which carries both mechanical and molecular implications as well as FUS induced immunomodulation play important roles. This is a concise research highlights on a comprehensive report by the same group. We separately discuss the different pertinent immunosuppressive mechanisms harnessed by GBM and the immunomodulatory effects of FUS. The three modes of FUS action can all be assigned a molecular final common pathway of immunomodulation. Thermal ablation induced immune effects, microbubbles effects in disrupting the BBB and introducing antigens and drugs to the tumor milieu as well as FUS induced molecular effects are discussed. The effect of FUS on the pro-inflammatory cytokines secretion profile, the stress response, the intra-tumoral immune-cellspopulations, dendritic cells activitymoderation and FUS induced increased cytotoxic cells potency are all discussed. A conceptual synopsis of the synergistic treatment of GBM utilizing FUS and immunotherapy is presented. The interaction of multiple approaches harnessing immune-components and circumventing immunosuppressing mechanisms may herald a new era in the fight against GBM.
