BACKGROUND: Immunosuppression is closely related to the pathogenesis of sepsis, but the underlying mechanisms have not yet been fully elucidated. In this study, we aimed to examine the role of the Sterile Alpha Motif, Src Homology 3 domain and nuclear localization signal 1 (SAMSN1) in sepsis and elucidate its potential molecular mechanism in sepsis induced immunosuppression. METHODS: RNA sequencing databases were used to validate SAMSN1 expression in sepsis. The impact of SAMSN1 on sepsis was verified using gene knockout mice. Flow cytometry was employed to delineate how SAMSN1 affects immunity in sepsis, focusing on immune cell types and T cell functions. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-mediated gene editing in RAW264.7 macrophages enabled interrogation of SAMSN1 's regulatory effects on essential macrophage functions, including cell proliferation and phagocytic capacity. The mechanism of SAMSN1 in the interaction between macrophages and T cells was investigated using the RAW264.7 cell line and primary cell lines. RESULTS: SAMSN1 expression was significantly increased in patients with sepsis and was positively correlated with sepsis mortality. Genetic deletion of Samsn1 in murine sepsis model improved T cell survival, elevated T cell cytolytic activity, and activated T cell signaling transduction. Concurrently, Samsn1 knockout augmented macrophage proliferation capacity and phagocytic efficiency. In macrophage, SAMSN1 binds to Kelch-like epichlorohydrin-associated protein 1 (KEAP1), causing nuclear factor erythroid 2-related factor 2 (NRF2) to dissociate from the KEAP1-NRF2 complex and translocate into the nucleus. This promotes the transcription of the coinhibitory molecules CD48/CD86/carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), which bind to their corresponding receptors natural killer cell receptor 2B4/CD152/T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) on the surface of T cells, inducing T-cell exhaustion. CONCLUSIONS SAMSN1 deletion augmented adaptive T cell immunity and macrophage phagocytic-proliferative dual function. Furthermore, it mediates the KEAP1-NRF2 axis, which affects the expression of coinhibitory molecules on macrophages, leading to T-cell exhaustion. This novel immunosuppression mechanism potentially provides a candidate molecular target for sepsis immunotherapy.
Animals ; NF-E2-Related Factor 2/metabolism* ; Mice ; Macrophages/immunology* ; Sepsis/metabolism* ; Kelch-Like ECH-Associated Protein 1/genetics* ; T-Lymphocytes/immunology* ; Humans ; Signal Transduction/physiology* ; RAW 264.7 Cells ; Mice, Knockout ; Mice, Inbred C57BL ; Male ; Flow Cytometry ; T-Cell Exhaustion

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the short-term efficacy of the intelligent robot-assisted fracture reduction system (RAFR) in the treatment of Tile-type C1-2 pelvic fractures.Methods:A retrospective study was conducted to analyze the clinical data of the 15 patients who had been treated for Tile-type C pelvic fractures at Department of Orthopedic Trauma, Foshan Hospital of Traditional Chinese Medicine between June 2022 and November 2023. The cohort were 7 males and 8 females, with an age of (51.6±22.1) years and a body mass index of (22.35±2.14) kg/m 2. According to the Tile classification, there were 9 cases of type C1 and 6 cases of type C2. The interval from injury to surgery was (11.3±3.9) days. Minimally invasive closed reduction and internal fixation of pelvic fractures were performed with the assistance of RAFR system. The anterior pelvic ring was fixed with percutaneous hollow screws from the pubic branch, and the posterior pelvic ring fixed with percutaneous hollow screws from the sacroiliac joint. If necessary, external fixation brackets and internal stent fixation technique for the anterior pelvic ring were used to enhance the stability of the pelvic ring. The frequency and time of intraoperative fluoroscopy, reduction time, surgical time, intraoperative bleeding volume, fracture reduction quality, follow-up time, fracture healing time, pelvic function recovery at the last follow-up, and incidence of complications were recorded. Results:With the assistance of RAFR system, 15 patients were all successfully treated with minimally invasive closed reduction and internal fixation for pelvic fractures. For this cohort, intraoperative fluoroscopy frequency was 31 (20, 55) times, fluoroscopy time 25.8 (18.0, 33.0) seconds, reduction time (57.7±3.5) minutes, surgical time 205 (200, 210) minutes, intraoperative bleeding volume 100 (100, 200) mL, and residual displacement (7.55±3.51) mm. According to the Matta scoring, the postoperative quality of fracture reduction was evaluated as excellent in 4 cases, as good in 8 cases, and as fair in 3 cases. Fourteen patients were followed up for 15.0 (10.8, 18.0) months after surgery, and 1 patient was lost to the follow-up. The fracture healing time for the 14 patients was 3.6 (3.2, 4.7) months. The Majeed functional score at the last follow-up was (83.4±6.4) points, giving 4 excellent and 10 good cases.Conclusion:The RAFR system can facilitate precise and minimally invasive closed reduction for the majority of patients with Tile-type C1-2 pelvic fracture, achieving satisfactory fracture reduction quality and short-term efficacy.

Astrocytes (ASTs) and oligodendroglial lineage cells (OLGs) are major macroglial cells in the central nervous system. ASTs communicate with each other through connexin (Cx) and Cx-based network structures, both of which allow for quick transport of nutrients and signals. Moreover, ASTs interact with OLGs through connexin (Cx)-mediated networks to modulate various physiological processes in the brain. In this article, following a brief description of the infrastructural basis of the glial networks and exocrine factors by which ASTs and OLGs may crosstalk, we focus on recapitulating how the interactions between these two types of glial cells modulate myelination, and how the AST-OLG interactions are involved in protecting the integrity of the blood-brain barrier (BBB) and regulating synaptogenesis and neural activity. Recent studies further suggest that AST-OLG interactions are associated with myelin-related diseases, such as multiple sclerosis. A better understanding of the regulatory mechanisms underlying AST-OLG interactions may inspire the development of novel therapeutic strategies for related brain diseases.
Humans ; Myelin Sheath ; Astrocytes ; Oligodendroglia ; Brain ; Brain Diseases

Objective:To investigate the efficacy and safety of targeted therapy with Crizotinib for children with ALK gene mutation positive inflammatory myofibroblastic tumor (IMT). Methods:A retrospective analysis was performed on 4 children with ALK gene mutation positive IMT admitted to Shanghai Children′s Hospital from January 2019 to June 2021.Among them, 3 cases were given the targeted drug Crizotinib[280 mg/(m 2· time), q12h] orally, and 1 case was observed after complete tumor resection to analyze the efficacy and adverse drug reactions. Results:All 4 cases were male, aged from 2 years and 3 months to 11 years and 3 months.The tumors originated from the abdominal cavity in 2 cases, the right orbit in 1 case, and the right lung in 1 case.Pathological immunohistochemistry and fluorescence in situ hybridization were both positive for ALK gene mutation, and complete remission was achieved after comprehensive treatment.Among them, 3 patients were treated with oral Crizotinib, and 2 patients were tried to stop taking the drug for 1 year, relapsed 1 month later, and still achieved complete remission after the second treatment.The 4 cases were followed up for 8-30 months, and all survived.All the cases showed no abnormalities in blood image, liver and kidney function, myocardial enzyme profile, cardiac function, hearing and vision, and 2 cases showed prolonged Q-T interval in the course of Crizotinib treatment, which could be recovered by temporary withdrawal of drug, and no abnormality in electrocardiogram was found in continued drug use. Conclusions:Crizotinib was used to treat ALK mutation positive IMT, shrink tumor and consolidate postoperative treatment, which is a good choice for IMT in children with difficult surgical resection and refractory recurrence.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

The epidemic of coronavirus disease 2019 (COVID-19) puts higher demands on critical care medicine. Lots of studies have been conducted to solve COVID-19-related problems. Therefore, we reviewed the annual progress for COVID-19-related issues including antivirals threapies, respiratory support and immunomodulatory therapies and other critical issues, including the effect of antibiotic on mitochondrial damage and its relationship with sepsis, the goal and direction of antimicrobial de-escalation, drug prophylaxis of constipation, bleeding in gastrointestinal disorders and management of critical illness in the informalization era and so on. We hope to provide reference for clinical and scientific research work of the intensivists.

The study was to investigate whether the application of checklist during ward rounds could improve the prognosis of critical ill patients.The results suggested that the checklist used during ward rounds could not improve the inhospital mortality of critically ill patients, but it increased the proportion of deep vein thrombosis prophylaxis, and shortened prophylaxis treatment of gastric stress ulcer.

Autophagy is a dynamic process that allows recycling of long-lived proteins and damaged organelles into biosynthetic materials for maintaining the normal cellular homeostasis. Recently, accumulating evidence has indicated that autophagy played important roles in the pathogenesis of neuronal diseases. In this article, the research progress of autophagy in the pathogenesis and regulation mechanism of common nervous system diseases were reviewed to deepen the understanding of autophagy, and arouse researchers' attention on dynamic regulation of autophagy and alleviating autophagic flow injury.