Although the understanding of sepsis has evolved from "sepsis 1.0" to "sepsis 3.0", and the consensus on clinical management of sepsis has been continuously updated, the incidence rate and mortality of sepsis remain high. Therefore, in-depth investigation of the pathogenesis and related influencing factors of sepsis is of great significance for revealing the nature of sepsis and improving the clinical outcome of sepsis patients. This review will focus on the key issues in the basic research of sepsis, and summarize the recent advances and challenges in this field, mainly including genetic polymorphism, microorganisms, high-mobility group box 1 (HMGB1), endothelial dysfunction, immunotherapy, and biomarkers, aiming to provide new insights for the diagnosis and treatment of sepsis.

Sepsis-related organ dysfunction is associated with increased morbidity and mortality. Previous studies have found that the endothelium plays crucial roles in maintaining the vascular permeability during sepsis, as well as in regulating inflammation and thrombosis. During sepsis, endothelial cells may release cytokines, chemokines, and pro-coagulant factors, as well as express adhesion molecules. In general, endothelial responses during sepsis typically inhibit bacterial transmission and coordinate leukocyte recruitment to promote bacterial clearance. However, excessive or prolonged endothelial activation can lead to impaired microcirculation, tissue hypoperfusion, and organ dysfunction. Given the structural and functional heterogeneity of endothelial cells in different organs, there are potential differences in endothelial responses by organ type, and the risk of organ damage may vary accordingly. This article reviews the endothelial response observed in sepsis and its effects on organ function, summarizes current progress in the development of therapeutic interventions targeting the endothelial response, and discusses future research directions to serve as a reference for researchers in the field.
Sepsis/complications* ; Humans ; Multiple Organ Failure/etiology* ; Endothelium, Vascular/physiopathology* ; Endothelial Cells/metabolism* ; Cytokines/metabolism* ; Animals

BACKGROUND: D-dimer is the specific marker of cross-link fibers degraded by fibrinolysin. During cerebral hemorrhage, D-dimer is significantly increased; its decrease may reflect the absorption process of hematoma and be closely related with the substantial injuries of brain. Endothelin is remarkably increased during cerebral hemorrhage, which may result in ischemic necrosis of neural histiocytes. The endothelin volume in cerebral hemorrhagic patients can reflect the severity of illness and the function prognosis.OBJECTIVE: To observe the effect of xingnaojing he shengmai injection (compound injection) on D-dimer and endothelin in patients at acute stage of cerebral hemorrhage.DESIGN: A randomized and controlled trial.SETTING: Emergent Internal Department of the Affiliated Hospital of Medical College of Qingdao University and Department of Pathology of Jinan Military General Hospital.PARTICIPANTS: A total of 44 patients of inspected patients at acute stage of cerebral hemorrhage were collected in Emergent Internal Department of affiliated Hospital of Medical College of Qingdao University from September 1999 to May 2001, which were randomized into two groups, named as xingnaojing he shengmai injection(compound injection) group(23 patients) and xingnaojing group(21 patients).METHODS: ELISA method was applied to determine the level of D-dimer and endothelin of peripheral blood before and after treatment. SPSS 8.0 statistical software was applied to analyze the data.MAIN OUTCOME MEASURES: Effects of xingnaojing he shengmai injection(compound injection) on level of D-dimer and endothelin in patients at acute stage of cerebral hemorrhage, compare with xingnaojing group.RESULTS: Xingnaojing he shengmai injection(compound injection) significantly reduced the level of both D-dimer[ (0. 67 ± 0. 21), (0.34 ± 0.18) mg/L,P ＜ 0.01 ] and endothelin[ (94.52 ±30. 23), (51.30 ± 21.62) ng/L, P＜ 0.01 ] before and after treatment respectively. The improvement of which was obviously superior to those in xingnaojing group[ (0. 33 ±0. 11),(0.20±0.08)mg/L, P ＜0.01; (43.22±12.06), (26.52±8.13)ng/L respectively, concerning to the improvements in two groups, P ＜ 0. 01 ].CONCLUSION: To improve the fibrinolytic state in patients with cerebral hemorrhage may protect the substantial injuries of brain and prevent the secondary damage after cerebral hemorrhage. To inhibit cerebral vascular spasm after hemorrhage may improve ischemic oxygen deficiency in brain tissue and probably be taken as one of the ways for xingnaojing he shengmai injection giving play to its therapeutic effects.