View clinical trials related to Pathogenesis.
Filter by:This study aims to collect serum samples from healthy non-pregnant women, pregnant women with and without Gestational Diabetes Mellitus (GDM). We will analyze the metabolite changes among the three groups using clinical metabolomics and identify potential biomarkers and metabolic pathways. This study will provide scientific evidence for early clinical diagnosis, prevention, control, and treatment research of GDM.
Biomarkers and mechanisms in the progression of aortic valve stenosis are sometimes not sufficiently understood. The current project will take into account image morphological and immunological aspects that predict the development of hemodynamically relevant aortic valve stenosis in order to identify high-risk patients and to develop further therapeutic options.
To study the molecular pathogenesis of cataract and explore possible treatments，anterior lens capsules were collected from cataract patients
Literature basis Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by respiratory distress and progressive hypoxemia, which is caused by diffuse alveolar and pulmonary interstitial edema caused by various pulmonary and extrapulmonary factors other than cardiogenic factors. ARDS incidence rate is as high as 75 /10 000 per year, and sepsis and pulmonary infection are the most common causes. In the past, it was generally believed that excessive immune activation is the core of the pathophysiology of ARDS, and neutrophils are recognized as the core driver of inflammatory hyperactivity and lung injury in ARDS. Although some progress has been made in the epidemiology, pathogenesis and pathophysiology of ARDS in the past 50 years, and the clinical outcomes of some patients with ARDS have been improved by optimizing the mode of mechanical ventilation and fluid treatment, as well as prone ventilation and the use of muscle relaxants, ARDS is still one of the most common causes of death and disability in intensive care units, The mortality rate of the disease is currently as high as 30-40%. There is still a lack of effective drugs for the treatment of ARDS in clinic, and even glucocorticoids applied for immune overactivation have not achieved good results. This is related to the unclear pathogenesis of ARDS. Therefore, it is still a hot and difficult point to further explore the pathogenesis and progression of ARDS and find new therapeutic targets. In the past, mature PMN in peripheral blood was generally considered as a functional cell in the end stage, but it is widely involved in different innate immune responses (including inflammation, infection, tumor, autoimmunity, etc.) and can adopt very different effector mechanisms. Therefore, with the deepening of research, neutrophil subtypes with different functions (such as immune regulation and repair) have been identified in recent years: cd16dimcd62lbrightpmn and cd16brightcd62ldimmpmn. In the steady state of healthy people, the classic mature neutrophils (cd16brightcd62lbright) in peripheral blood account for more than 98% of the total PMN, and the proportion of the two neutrophil subtypes is relatively low. In the inflammatory state, the proportion of cd16dimcd62lbright and cd16brightcd62ldim neutrophils increased significantly. Proteomic analysis showed that there were significant differences between the two subtypes of neutrophils. The nucleus of cd16dimcd62lbright neutrophil subgroup is banded, which is released from bone marrow after being stimulated by lipopolysaccharide (LPS). It accounts for 20% - 25% of PMN in whole blood in LPS infection model. The apoptosis rate is significantly reduced, and the bacteriostatic effects such as oxidative burst and phagocytosis are significantly enhanced; On the contrary, cd16brightcd62ldim neutrophil subgroup has reduced antibacterial ability and shows immunosuppressive phenotype. It is a newly discovered neutrophil subtype with immunosuppressive function in recent years, which can inhibit T cell proliferation, which is related to immunosuppression in the experimental human endotoxemia model. In our previous studies, we have successfully obtained a new amino acid derivative of ocotillol ginsenoside, which may have the pharmacological activities of ocotillol ginsenoside and glycine, and has a potential role in improving the delay of apoptosis and immunosuppression of ARDS neutrophil subtypes, and has the potential of new drug development for the treatment of ARDS. The experimental steps are as follows: Firstly, the peripheral blood of ARDS patients in ICU was collected, and neutrophils were isolated from the peripheral blood. The proportion of neutrophil subtypes and the degree of apoptosis were detected by flow cytometry. Co culture with human T lymphocytes in vitro to observe its ability to inhibit T cell proliferation. Then, the neutrophils of ARDS patients were cultured with different doses of ginsenoside glycine derivatives, and the detection of the above indexes was repeated again. Finally, the mechanism of neutrophils in the pathogenesis and progression of ARDS was discussed.
Background: Survival in Granzyme A gene (gzmA) knocked-out mice was significantly longer than in wild-type mice in a murine peritonitis model (cecal ligation puncture). Hypothesis: GZM A has a pathogenic role in sepsis in humans and gzmA polymorphisms can help to predict the risk of sepsis among patients with systemic infections (E. coli bacteremic urinary tract infections). Objectives: 1. To assess the correlation between GZM A serum levels and systemic inflammatory response in a human model of infection/sepsis (E. coli bacteremic UTI) 2. To characterize gzmA polymorphisms among patients with E. coli bacteremic UTI 3. To determine GZM A serum kinetics among patients with E. coli bacteremic UTI 4. To characterize E. coli strains causing bacteremic UTI: antimicrobial phenotype and virulence factors ("virulome"). Methods: - Design and setting: Prospective nested case-control study - Study population: consecutive adult patients with bacteremic urinary tract infections (UTIs) caused by E. coli - Exclusion criteria: Patients with conditions that significantly compromise immune status or patients exposed to urologic procedures - Estimated sample size: 50 patients with a sepsis/ non sepsis 1:1 ratio. Septic and non septic patients will be matched on gender, age (+/- 10 years), comorbidity (Charlson score +/-1), time symptom onset to blood culture (+/- 24h) - Measurements: GZM A serum levels will be determined on day 0, day 2-3, day 30. GZM A kinetics, gzmA polymorphisms (whole exome sequencing).Whole genome sequencing of E. coli isolates retrieved from blood cultures will be performed. - Analysis: Association between GZM A levels and gzmA polymorphisms and sepsis will be analyzed adjusting for patient, infection and microorganism-related factors (multivariate analysis).
Continuous observation of acute renal injury after cardiac surgery, at the same time retention of blood samples, to test indicators，and to select the research route from the clinical actual test results .
Subjects with cardiovascular diseases (CVD) have higher incidence of cancers compared to general population. The investigators hypothesized that shared molecular mechanism play a pivotal role in the pathogenesis of CVD including heart failure (HF) and cancers. To address this hypothesis, the investigators are going to explore the expression pattern of micro RNA (miRNA) and cell free DNA (cfDNA) derived from host, gut microbiota and gut microbiota composition extensively in patients with or without CVD, non-ischemic HF (NIHF), and cancers. The participants will be recruited from the outpatient clinic in Sakakibara Heart Institute or Japanese Foundation for Cancer Research. By comparing the expression pattern of miRNA, cfDNA, or gut microbiota composition, the investigators are seeking to find the pathogenic mechanisms shared by those diseases.
Background: -Sjogren s Disease is a disease that affects about 1-4 million Americans. It is more common in women. It mainly affects the glands that produce saliva and tears, leading to dry eyes and dry mouth. The cause of Sjogren s Disease is unknown, but inflammation plays an important role. The purpose of this study is to learn more about Sjogren s Disease. Objectives: -To better understand how Sjogren s Disease begins and how it affects patients so that we can develop better ways to treat them. Eligibility: - Participants must be 16 years of age or older. - They must have a diagnosis of Sjogren s Disease or have at least two symptoms of Sjogren s Disease. Design: - People taking part in the study will come to the NIH Clinical Center for at least three visits. - During these visits, participants will have a medical history and physical exam. They will have oral and dental assessments, and saliva collection. Lab tests (blood and urine) and dry eye exams will be done. Participants will answer questionnaires and have salivary scintigraphy (adults only unless required for diagnosis). - Other optional tests may also be done. Participants may have to come in for additional visits if they have these optional tests or if their disease changes. - The only treatment provided as part of this study is for medical emergencies or complications that occur while you are at NIH for evaluation.