Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.
Extracellular Traps/physiology* ; Humans ; Atherosclerosis/immunology* ; Neutrophils/physiology* ; Leukocyte Elastase/metabolism* ; Peroxidase/physiology* ; Matrix Metalloproteinases/physiology* ; Cathepsin G/metabolism* ; Cathelicidins ; HMGB1 Protein/physiology* ; Histones ; Animals ; Endothelium, Vascular

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

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 compare the safety of radial artery puncture in elderly patients aged 75 years and older who are undergoing neurointerventional procedures.Methods:A single-center retrospective study was conducted, involving 350 elderly patients aged 75 years and older who received neurointerventional treatment at Beijing Tiantan Hospital, Capital Medical University, from June to December 2022.The participants were divided into two groups based on the puncture site: femoral artery puncture and radial artery puncture.The safety indicators compared between the two groups included puncture failure, changes in puncture site, general puncture complications(such as subcutaneous bleeding, puncture site hematoma, and vasospasm), severe puncture complications(including distal limb ischemia and pseudoaneurysm), and lower limb venous thrombosis.Multivariate Logistic regression analysis was conducted to evaluate the impact of different puncture methods on the occurrence of complications.Results:Among the 350 patients, 280 underwent femoral artery puncture, while 70 underwent radial artery puncture.There were no statistically significant differences in baseline characteristics between the two groups(all P>0.05).The proportions of patients using antiplatelet drugs prior to surgery, puncture failure rates, rates of change in puncture sites, and the incidence of severe complications-including distal limb ischemia and pseudoaneurysm-were not significantly different between the two groups( χ2=2.051, 0.075, 0.588, 3.175; P=0.152, 0.784, 0.443, 0.075).In the femoral artery puncture group, 20.4%(57 cases)of patients experienced general puncture complications(including subcutaneous bleeding, puncture site hematoma, and vasospasm), whereas only 8.6%(6 cases)in the radial artery puncture group experienced such complications, revealing a statistically significant difference between the two groups( χ2=5.720, P=0.022).Multivariate Logistic regression analysis indicated that, compared to femoral artery puncture, radial artery puncture was associated with a reduced risk of all complications( OR=0.272, 95% CI: 0.139-0.532, P<0.001), general puncture complications( OR=0.375, 95% CI: 0.153-0.919, P=0.032)and lower limb venous thrombosis( OR=0.219, 95% CI: 0.050-0.954, P=0.043). Conclusions:In elderly patients aged 75 years and older who are undergoing neurointerventional procedures, radial artery puncture is associated with a reduced incidence of general puncture complications and lower limb venous thrombosis when compared to femoral artery puncture, indicating a superior safety profile.

Objective:To analyze differences in peripheral blood T-cell receptor(TCR)genes in patients with viral pneumo-nia by single cell sequencing,and to explore its possible pathogenesis.Methods:Data in NCBI database was obtained,and case and control groups were set up for experiments.Single cell sequencing data was analyzed of by R language in RStudio software,tables and images were plotted,and finally conclusions were drawn.Results:There was a significant difference in TCRs between case and healthy control groups.Frequency of use of V and J gene fragments of TCR α and β chains were analyzed,in which frequency of use of TRAV1-2,TRAV29/DV5,TRAJ33,TRAJ48,TRBV20-1,TRBV2,TRBJ2-3 and TRBJ1-1 genes were significantly higher in case group than in control group(P<0.05).Further V-J gene combination analysis showed that the most frequent use of α-chain V-J pairs in case group was TRAV1-2-J33,most frequent use of β-chain V-J pairs was TRBV20-1-J2-1,most frequent use of αβ double-chain V-J pairs was TRAV30-J24-TRBV3-1-J2-7.Conclusion:Peripheral blood TCR genes are significantly altered in patients with viral pneu-monia,which may be related to immunopathogenesis of virus.

Objective:Using single cell sequencing to analyze the characteristics of the immune repertoire of SARS-CoV-2 pa-tients at different infection stages,and to explore the possible pathogenesis.Methods:Obtaining data in the NCBI database,and healthy control,progression and convalescence groups were set up.Analysis of single cell sequencing data by RStudio,Origin,Hipliot and Excel software.Results:TCR plays an important role in antigen recognition and virus clearance.Characteristics of the three immune repertoires are very different.The number of clones exceeded 26.92%.The length distribution of α chain CDR3 was con-centrated on 14 amino acids,while β-chain was concentrated on 15 amino acids.The frequency of gene fragments in V and J regions were different,and the frequency of TRAV13-1,TRAJ20,TRBV20-1 and TRBJ2-1 were statistically significant(P<0.05).Further V-J gene combination analysis showed that there were significant differences in the frequency of single chain V-J between the control group and the progression group,the control group and the rehabilitation group(P<0.05).The highest frequency of αβ double chain V-J in the control group was TRAV19-J34-TRBV4-1-J2-1,the highest frequency of αβ double-stranded V-J in the progression group was TRAV12-1-J30-TRBV19-1-J2-1,and the highest frequency of αβ double chain V-J in the convalescence group was TRAV12-2-J52-TRBV7-9-J1-5.Conclusion:This study analyzes the global characteristics of T cells in the immune repertoire,which is helpful to understand the pathogenesis of SARS-CoV-2 patients,timely and effective treatment of patients in the early stages of infection.

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

In the surgical treatment of hemorrhoids, rectal prolapse, rectal cancer, anal fissures, or anal fistulas, inadvertent damage to the nerves or muscles responsible for bowel control may potentially lead to varying degrees of fecal incontinence (FI). Surgeons need to conduct preoperative assessments based on the patient's individual condition to select an appropriate surgical plan, aiming to minimize the incidence of postoperative FI and improve the patient's postoperative quality of life as much as possible while effectively treating the disease. Additionally, the proficiency of the surgeon's skills, appropriate preoperative dietary adjustments for the patient, regular bowel habits, and exercises targeting the pelvic floor muscles all contribute to reducing the incidence of postoperative FI in patients. For patients who have already developed FI after surgery, on the basis of suitable diet, regular bowel habits, and medication, clinical practitioners can adopt such methods as biofeedback, pelvic floor muscle exercise, sacral nerve stimulation, percutaneous tibial nerve stimulation, acupuncture, injectable bulking agents, anal or vaginal inserts, transanal irrigation, surgical interventions, psychological support, etc., to individualized treatment for patients' conditions. This article, combining the literature, summarizes the current status of common diseases that may lead to postoperative FI. It elaborates on strategies for the prevention and treatment of postoperative FI, aiming to serve as a reference for peers in the field.

In the surgical treatment of hemorrhoids, rectal prolapse, rectal cancer, anal fissures, or anal fistulas, inadvertent damage to the nerves or muscles responsible for bowel control may potentially lead to varying degrees of fecal incontinence (FI). Surgeons need to conduct preoperative assessments based on the patient's individual condition to select an appropriate surgical plan, aiming to minimize the incidence of postoperative FI and improve the patient's postoperative quality of life as much as possible while effectively treating the disease. Additionally, the proficiency of the surgeon's skills, appropriate preoperative dietary adjustments for the patient, regular bowel habits, and exercises targeting the pelvic floor muscles all contribute to reducing the incidence of postoperative FI in patients. For patients who have already developed FI after surgery, on the basis of suitable diet, regular bowel habits, and medication, clinical practitioners can adopt such methods as biofeedback, pelvic floor muscle exercise, sacral nerve stimulation, percutaneous tibial nerve stimulation, acupuncture, injectable bulking agents, anal or vaginal inserts, transanal irrigation, surgical interventions, psychological support, etc., to individualized treatment for patients' conditions. This article, combining the literature, summarizes the current status of common diseases that may lead to postoperative FI. It elaborates on strategies for the prevention and treatment of postoperative FI, aiming to serve as a reference for peers in the field.

ObjectiveTo study the effect of isoflavones from Sojae Semen Praeparatum （ISSP） on lipid metabolism in atherosclerotic mice， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor gamma/liver X receptor alpha/ATP-binding cassette transporter A1 （PPARγ/LXRα/ABCA1） signaling pathway. MethodFifty ApoE^-/- mice were randomly assigned into the model group， western medicine （atorvastatin calcium， 3.03 mg·kg^-1） group， and low-， medium-， and high-dose ISSP （2.5， 5， 10 mg·kg^-1， respectively） groups， with 10 rats in each group. Atherosclerosis model mice were established by bilateral ovariectomy and feeding high-fat diet. Another 10 ApoE^-/- mice receiving ovariectomy and high-fat diet were taken as the sham group. Some mice died of postoperative infection， and finally 6 mice were included in each group. One week after operation， each group was administrated with corresponding drugs or equivalent amount of normal saline. After 12 weeks， the levels of triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， and non-esterified fatty acids （NEFAs） in serum and liver tissue were measured. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining and oil red O staining were used for observation of aortic plaque formation and liver lipid deposition. The mRNA and protein levels of PPARγ， LXRα， ABCA1， and ATP-binding cassette transporter G1 （ABCG1） in liver were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the sham group， the modeling of atherosclerosis increased the aortic plaque area （P<0.01）， elevated the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the level of HDL-C （P<0.01）， increased the liver index （P<0.05） and the levels of TC， TG， and NEFAs in liver （P<0.01）， and caused obvious hepatic fat vacuoles and lipid deposition. In addition， the modeling down-regulated the mRNA levels of PPARγ， LXRα， ABCA1 in liver （P<0.05， P<0.01），and regulated the mRNA and protein levels of ABCG1（P<0.05， P<0.01）. Compared with the model group， atorvastatin calcium and middle-， high-dose ISSP reduced the serum TC， TG， LDL-C， TNF-α， and IL-6 levels （P<0.01）， decreased the liver index （P<0.01）， alleviated the liver fat vacuoles and lipid deposition， and increased the levels of TC， TG， and NEFAs in the liver （P<0.05， P<0.01）. Furthermore， they up-regulated the mRNA and protein levels of PPARγ， LXRα， ABCA1， and ABCG1 in the liver （P<0.05， P<0.01）. ConclusionISSP may regulate lipid metabolism through PPARγ/LXRα/ABCA1 signaling pathway to down-regulate the expression of inflammatory cytokines in serum and alleviate liver lipid deposition， thereby suppressing the formation of atherosclerotic plaque.