OBJECTIVE: To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients. METHODS: Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM. RESULTS: 36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients. CONCLUSION Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.
Humans ; Multiple Myeloma ; Ferroptosis ; Prognosis ; Hematopoietic System ; Blood Coagulation

OBJECTIVE: To screen better promoters and provide more powerful tools for basic research and gene therapy of hemophilia. METHODS: Bioinformatics methods were used to analyze the promoters expressing housekeeping genes with high abundance, so as to select potential candidate promoters. The GFP reporter gene vector was constructed, and the packaging efficiency of the novel promoter was investigated with EF1 α promoter as control, and the transcription and activities of the reporter gene were investigated too. The activity of the candidate promoter was investigated by loading F9 gene. RESULTS: The most potential RPS6 promoter was obtained by screening. There was no difference in lentiviral packaging between EF1 α-LV and RPS6-LV, and their virus titer were consistent. In 293T cells, the transduction efficiency and mean fluorescence intensity of RPS6pro-LV and EF1 αpro-LV were proportional to the lentiviral dose. The transfection efficiency of both promoters in different types of cells was in the following order: 293T>HEL>MSC; Compared with EF1 αpro-LV, RPS6pro-LV could obtain a higher fluorescence intensity in MSC cells, and RPS6pro-LV was more stable in long-term cultured HEL cells infected with two lentiviruses respectively. The results of RT-qPCR, Western blot and FIX activity (FIX∶C) detection of K562 cell culture supernatant showed that FIX expression in the EF1 α-F9 and RPS6-F9 groups was higher than that in the unloaded control group, and there was no significant difference in FIX expression between the EF1 α-F9 and RPS6-F9 groups. CONCLUSION After screening and optimization, a promoter was obtained, which can be widely used for exogenous gene expression. The high stability and viability of the promoter were confirmed by long-term culture and active gene expression, which providing a powerful tool for basic research and clinical gene therapy of hemophilia.
Humans ; Transduction, Genetic ; Genetic Vectors ; Hemophilia A/genetics* ; Transfection ; Blood Coagulation Factors/genetics* ; Lentivirus/genetics*

Effective haemostatic materials can quickly control bleeding and achieve the purpose of saving patients' lives. In recent years, chitosan-based haemostatic materials have shown good haemostatic effects, but their application is limited because chitosan is almost insoluble in water. Carboxymethyl chitosan-based haemostatic materials can promote hemostasis by activating red blood cells and aggregating platelets. In addition, carboxymethyl chitosan can bind with Ca²⁺ to activate platelets and coagulation factors, and start endogenous coagulation pathways, which can adsorb fibrinogen in plasma to promote haemostasis. In this paper, the latest research progress of carboxymethyl chitosan-based haemostatic materials and their haemostatic mechanism were reviewed, in order to further strengthen the understanding of the haemostatic mechanism of carboxymethyl chitosan-based haemostatic materials, and provide new idea for the research and clinical application of carboxymethyl chitosan-based haemostatic materials.
Humans ; Hemostatics ; Chitosan/pharmacology* ; Hemostasis ; Blood Coagulation/physiology* ; Hemorrhage

Sepsis-associated coagulopathy refers to extensive coagulation activation accompanied by a high risk of bleeding and organ failure. In severe cases, it is manifested as disseminated intravascular coagulation (DIC) and leads to multiple organ dysfunction syndrome (MODS). Complement is an important component of the innate immune system and plays an important role in defending against invasion of pathogenic microorganisms. The early pathological process of sepsis involves excessive activation of the complement system, which forms an extremely complex network through interactions with the coagulation, kinin and fibrinolytic system, amplifying and exacerbating the systemic inflammatory response. In recent years, it has been suggested that uncontrolled complement activation system can exacerbate sepsis-associated coagulation dysfunction or even DIC, indicating the potential value of intervening in the complement system in the treatment of septic DIC, and related research progress is reviewed in this article in order to provide new ideas for the discovery of sepsis-associated coagulopathy therapy drugs.
Humans ; Blood Coagulation Disorders ; Complement Activation ; Blood Coagulation ; Multiple Organ Failure ; Sepsis

BACKGROUND: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. METHODS: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. RESULTS: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. CONCLUSIONS One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
Young Adult ; Humans ; Male ; Proteome ; Cardiovascular Diseases ; Proteomics ; Ischemia ; Blood Coagulation

Circadian rhythm is an internal regulatory mechanism formed in organisms in response to the circadian periodicity in the environment, which modulates the pathophysiological events, occurrence and development of diseases, and the response to treatment in mammals. It significantly influences the susceptibility, injury, and recovery of ischemic stroke, and the response to therapy. Accumulating evidence indicates that circadian rhythms not only regulate the important physiological factors of ischemic stroke events, such as blood pressure and coagulation-fibrinolysis system, but also participate in the immuno-inflammatory reaction mediated by glial cells and peripheral immune cells after ischemic injury and the regulation of neurovascular unit(NVU). This article aims to link molecular, cellular, and physiological pathways in circadian biology to the clinical consequences of ischemic stroke and to illustrate the impact of circadian rhythms on ischemic stroke pathogenesis, the regulation of NVU, and the immuno-inflammatory responses. The regulation of circadian rhythm by traditional Chinese medicine is reviewed, and the research progress of traditional Chinese medicine intervention in circadian rhythm is summarized to provide a reasonable and valuable reference for the follow-up traditional Chinese medicine research and molecular mechanism research of circadian rhythm.
Animals ; Ischemic Stroke ; Medicine, Chinese Traditional ; Circadian Rhythm ; Blood Coagulation ; Blood Pressure ; Mammals

The Sepsis Coagulopathy Asahi Recombinant LE Thrombomodulin (SCARLET) trial has many defects, and thus cannot be the terminator of recombinant thrombomodulin (rTM). On the contrary, it provides sufficient evidence for further research. Based on analysis focusing on the failure of SCARLET and several previous anticoagulant studies, it is most important for new studies to grasp the following two points: (1) The enrolled cases should have sufficient disease severity and a clear standard for disseminated intravascular coagulation; (2) Heparin should not be used in combination with the investigated drugs. Multiple post-hoc analyses show that no combination of heparin will not increase the risk of thromboembolism. In fact, the combination of heparin can mask the true efficacy of the investigated drug. Due to the complexity of sepsis treatment and the limitations of clinical studies, the results of all treatment studies should be repeatedly verified, rather than be determined at one stroke. Some research conclusions contrary to disease physiology, pharmacology and clinical practice may be deceptive, and should be cautious rather than be simply accepted. On the other hand, the dissenting voices in the "consensus" scene are often well discussed by the authors and should be highly valued.
Humans ; Anticoagulants/therapeutic use* ; Thrombomodulin/therapeutic use* ; Blood Coagulation Disorders ; Disseminated Intravascular Coagulation/drug therapy* ; Sepsis/drug therapy* ; Heparin/therapeutic use* ; Recombinant Proteins

OBJECTIVES: To study the clinical characteristics and prognosis of SARS-CoV-2 Omicron variant infection-associated acute necrotizing encephalopathy (ANE) in children . METHODS: A retrospective analysis was conducted on the medical data of 12 children with SARS-CoV-2 Omicron variant infection-associated ANE who were admitted to the Pediatric Intensive Care Unit, Qingdao Women and Children's Hospital from December 18 to 29, 2022. The children were divided into two groups based on outcomes: death group (7 cases) and survival group (5 cases). The clinical manifestations and auxiliary examination results were compared between the two groups. RESULTS: The median age of the 12 patients was 30 months, with a male-to-female ratio of 1:1. All patients presented with persistent high fever, with a median highest body temperature of 41℃. The median time from fever onset to seizure or consciousness disturbance was 18 hours. The death group had a higher proportion of neurogenic shock, coagulation dysfunction, as well as elevated lactate, D-dimer, interleukin-6, interleukin--8, and interleukin-10 levels compared to the survival group (P<0.05). CONCLUSIONS Children with SARS-CoV-2 Omicron variant infection-associated with ANE commonly present with persistent high fever, rapidly progressing disease, and have a high likelihood of developing consciousness disorders and multiorgan dysfunction within a short period. The occurrence of neurogenic shock, coagulation dysfunction, and significantly elevated cytokine levels suggests an increased risk of mortality.
Humans ; Female ; Child ; Male ; Infant ; SARS-CoV-2 ; Retrospective Studies ; COVID-19/complications* ; Brain Diseases/etiology* ; Prognosis ; Fever ; Blood Coagulation Disorders

OBJECTIVES: To investigate the clinical value of complement-3a receptor 1 (C3aR1) and neutrophil extracellular traps (NETs) in predicting sepsis-induced coagulopathy (SIC). METHODS: A prospective study was conducted among 78 children with sepsis who attended Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from June 2022 to June 2023. According to the presence or absence of SIC, they were divided into two groups: SIC (n=36) and non-SIC (n=42) . The two groups were compared in terms of clinical data and the levels of C3aR1 and NETs. The factors associated with the occurrence of SIC were analyzed. The receiver operating characteristic (ROC) curve was used to evaluate the performance of C3aR1 and NETs in predicting SIC. RESULTS: Compared with the non-SIC group, the SIC group had significantly higher levels of C-reactive protein, interleukin-6 (IL-6), interleukin-10, C3aR1, and NETs (P<0.05). The multivaiate logistic regression analysis showed that the increases in C3aR1, NETs, and IL-6 were closely associated with the occurrence of SIC (P<0.05). The ROC curve analysis showed that C3aR1 combined with NETs had an area under the curve (AUC) of 0.913 in predicting SIC (P<0.05), which was significantly higher than the AUC of C3aR1 or IL-6 (P<0.05), while there was no significant difference in AUC between C3aR1 combined with NETs and NETs alone (P>0.05). CONCLUSIONS There are significant increases in the expression levels of C3aR1 and NETs in the peripheral blood of children with SIC, and the expression levels of C3aR1 and NETs have a high clinical value in predicting SIC.
Child ; Humans ; Extracellular Traps ; Interleukin-6 ; Prospective Studies ; Sepsis/complications* ; C-Reactive Protein ; Blood Coagulation Disorders ; ROC Curve ; Prognosis

OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.
Humans ; Leukemia, Promyelocytic, Acute/diagnosis* ; Cytokines/metabolism* ; Interleukin-10 ; Interleukin-17/metabolism* ; Interleukin-6/metabolism* ; Interleukin-5/metabolism* ; Blood Coagulation Disorders ; Ferritins ; Tretinoin