Objective·To investigate the role of interleukin-1β(IL-1β)in predicting the severity of oral and maxillofacial space infection(OMSI),and to explore the key mechanisms regulating IL-1β release,the critical immune cell subpopulations involved,and the intercellular communication networks among immune cells in OMSI patients.Methods·A total of 62 OMSI patients admitted to the Department of Oral Surgery,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,from January to November 2023 were enrolled,including 20 patients with moderate infection,21 with severe infection,and 21 with extremely severe infection.Logistic regression analysis was performed to identify risk factors for extremely severe infection,and receiver operating characteristic(ROC)curves were constructed to evaluate the ability of the above indicators to predict extremely severe infection.Peripheral blood mononuclear cells(PBMCs)from 2 patients in each group(moderate,severe and extremely severe)and 2 healthy controls(GSE224198)were analyzed using single-cell RNA sequencing(scRNA-seq)to identify key pro-inflammatory cell subtypes and genes,and to examine their changing trends with increasing infection severity.Cell-cell communication was assessed using CellChat.Quantitative real-time polymerase chain reaction(qPCR)and Western blotting were used to validate inflammasome activation levels in PBMCs.Results·Compared with patients with moderate and severe infections,levels of procalcitonin(PCT)(P<0.05)and IL-1β(P<0.05)were significantly elevated in patients with extremely severe infection.Logistic regression identified IL-1β as an independent risk factor for extremely severe infection(OR=1.814,95%CI 1.256?2.621,P=0.002).The area under the ROC curve(AUC)for the combined prediction of extremely severe infection using IL-1β and PCT was 0.943.scRNA-seq revealed continuous upregulation of NLRP3(NOD-like receptor family pyrin domain-containing 3)and IL1B gene expression in monocytes as infection severity increased,with intermediate monocytes being the main IL1B-expressing cell subtype.IL-1Β-IL-1R signaling,C-C motif chemokine ligand(CCL)and intercellular adhesion molecule(ICAM)signaling were significantly enhanced in monocytes.Macrophage migration inhibitory factor(MIF)signaling between T cells and monocytes also increased notably.With infection progression,the mRNA levels of NLRP3 and IL1B in peripheral blood rose steadily,and the protein levels of NLRP3,caspase-1 p20,apoptosis-associated speck-like protein containing a CARD(ASC)and IL-1β were persistently elevated.Conclusion·The combined levels of IL-1β and PCT at admission can effectively predict extremely severe OMSI.NLRP3 inflammasome activation is observed in PBMCs of OMSI patients.The elevation of IL-1β is closely associated with intermediate monocytes.Monocyte-mediated IL-1Β-IL-1R,CCL and ICAM signaling pathways,along with T cell-mediated MIF signaling pathways,collectively promote the inflammatory response.

Objective·To investigate the role of interleukin-1β(IL-1β)in predicting the severity of oral and maxillofacial space infection(OMSI),and to explore the key mechanisms regulating IL-1β release,the critical immune cell subpopulations involved,and the intercellular communication networks among immune cells in OMSI patients.Methods·A total of 62 OMSI patients admitted to the Department of Oral Surgery,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,from January to November 2023 were enrolled,including 20 patients with moderate infection,21 with severe infection,and 21 with extremely severe infection.Logistic regression analysis was performed to identify risk factors for extremely severe infection,and receiver operating characteristic(ROC)curves were constructed to evaluate the ability of the above indicators to predict extremely severe infection.Peripheral blood mononuclear cells(PBMCs)from 2 patients in each group(moderate,severe and extremely severe)and 2 healthy controls(GSE224198)were analyzed using single-cell RNA sequencing(scRNA-seq)to identify key pro-inflammatory cell subtypes and genes,and to examine their changing trends with increasing infection severity.Cell-cell communication was assessed using CellChat.Quantitative real-time polymerase chain reaction(qPCR)and Western blotting were used to validate inflammasome activation levels in PBMCs.Results·Compared with patients with moderate and severe infections,levels of procalcitonin(PCT)(P<0.05)and IL-1β(P<0.05)were significantly elevated in patients with extremely severe infection.Logistic regression identified IL-1β as an independent risk factor for extremely severe infection(OR=1.814,95%CI 1.256?2.621,P=0.002).The area under the ROC curve(AUC)for the combined prediction of extremely severe infection using IL-1β and PCT was 0.943.scRNA-seq revealed continuous upregulation of NLRP3(NOD-like receptor family pyrin domain-containing 3)and IL1B gene expression in monocytes as infection severity increased,with intermediate monocytes being the main IL1B-expressing cell subtype.IL-1Β-IL-1R signaling,C-C motif chemokine ligand(CCL)and intercellular adhesion molecule(ICAM)signaling were significantly enhanced in monocytes.Macrophage migration inhibitory factor(MIF)signaling between T cells and monocytes also increased notably.With infection progression,the mRNA levels of NLRP3 and IL1B in peripheral blood rose steadily,and the protein levels of NLRP3,caspase-1 p20,apoptosis-associated speck-like protein containing a CARD(ASC)and IL-1β were persistently elevated.Conclusion·The combined levels of IL-1β and PCT at admission can effectively predict extremely severe OMSI.NLRP3 inflammasome activation is observed in PBMCs of OMSI patients.The elevation of IL-1β is closely associated with intermediate monocytes.Monocyte-mediated IL-1Β-IL-1R,CCL and ICAM signaling pathways,along with T cell-mediated MIF signaling pathways,collectively promote the inflammatory response.

Aim To investigate the effect of icariin(ICA)on chronic ulcerative colitis(UC)in mice.Methods Male SPF-grade C57BL/6J mice were ran-domly divided into the control group,model group,low-dose ICA group,and high-dose ICA group.Except for the control group,the rest of the mice were established as chronic UC models.Expressions of tight junction proteins,inflammatory factors,fibrosis markers,macro-phage markers,and MAPK signaling pathways in the colonic epithelium of each group were determined by Western blot,qPCR,immunohistochemistry;the degree of intestinal damage and fibrosis was detected by HE and Masson staining;the co-localization of different macrophage markers with related factors was examined by immunofluorescence.Results Treatment of ICA significantly improved the general condition of chronic UC mice,decreased the infiltration of M1-type macro-phages and the secretion of pro-inflammatory factors,inhibited the MAPK signaling pathway,reduced the co-localization expression of M1-type macrophages with the MAPK signaling pathway,and downregulated the infiltration of M2-type macrophages and the secretion of pro-fibrotic factors in the colon.Conclusion ICA mitigates the inflammatory damage and fibrosis of colon in chronic UC mice.

Aim To investigate the effect of icariin(ICA)on chronic ulcerative colitis(UC)in mice.Methods Male SPF-grade C57BL/6J mice were ran-domly divided into the control group,model group,low-dose ICA group,and high-dose ICA group.Except for the control group,the rest of the mice were established as chronic UC models.Expressions of tight junction proteins,inflammatory factors,fibrosis markers,macro-phage markers,and MAPK signaling pathways in the colonic epithelium of each group were determined by Western blot,qPCR,immunohistochemistry;the degree of intestinal damage and fibrosis was detected by HE and Masson staining;the co-localization of different macrophage markers with related factors was examined by immunofluorescence.Results Treatment of ICA significantly improved the general condition of chronic UC mice,decreased the infiltration of M1-type macro-phages and the secretion of pro-inflammatory factors,inhibited the MAPK signaling pathway,reduced the co-localization expression of M1-type macrophages with the MAPK signaling pathway,and downregulated the infiltration of M2-type macrophages and the secretion of pro-fibrotic factors in the colon.Conclusion ICA mitigates the inflammatory damage and fibrosis of colon in chronic UC mice.

Multiple myeloma(MM),a common malignancy of plasma cells,remains an incurable disease de-spite significant therapeutic advancements.A defining characteristic of MM is the recurrent occurrence of cytogenetic ab-normalities,particularly the gains of chromosome 1q21(1q21+),which are among the most frequently observed anoma-lies in this condition,affecting approximately 40%of patients with newly diagnosed MM.While numerous studies have identified 1q21+as an independent prognostic marker linked to poor outcomes in MM,its prognostic significance continues to be debated.An increasing number of national and international prognostic stratification systems classify 1q21+as a high-risk factor;however,its predictive value remains contentious.Variations in 1q21 copy numbers significantly impact genomic instability,drug resistance,and the likelihood of early disease progression,highlighting its growing importance in clinical management strategies.Despite the availability of various therapeutic approaches,such as autologous hemato-poietic stem cell transplantation,immunomodulatory drugs,and proteasome inhibitors,the adverse prognostic implica-tions of 1q21+persist unresolved.This review will explore the latest advancements in understanding the 1q21+in MM,fo-cusing on its pathogenesis,prognostic relevance,and implications for clinical management.

Objective This study explores the clinical correlation between different low-density lipoprotein cholesterol(LDL-C)levels and prognosis,providing evidence-based guidance for the development of personalized lipid-lowering goals.Methods Patients who underwent elective percutaneous coronary intervention(PCI)treatment at Beijing Anzhen Hospital from January 2020 to June 2023 and received lipid-lowering therapy with the addition of Evolocumab were selected.Based on the results of blood lipid rechecks 3 to 6 months after surgery,the patients were divided into five groups:low-density lipoprotein＜0.5 mmol/L,0.5 to＜1.0 mmol/L,1.0 to＜1.4 mmol/L,1.4 to＜1.8 mmol/L,and above 1.8 mmol/L.All patients were followed up for more than one year,and clinical conditions and major adverse cardiovascular events(MACE)were recorded.Results A total of 1 106 patients undergoing PCI were enrolled;after propensity score matching and exclusion of patients lost to follow up,550 remained(110 per group).During 12 months of follow-up,58 patients(10.5％)experienced a MACE,with incidence rising step-wise across LDL-C categories.In multivariable Cox models adjusted for age,sex,diabetes,hypertension,baseline LDL-C,follow-up LDL-C,estimated glomerular filtration rate(eGFR),and left ventricular ejection fraction,the hazard ratios[HR(95％CI)]for MACE,relative to the＜0.5 mmol/L group,were 1.810(0.507-6.454,P=0.361),3.036(0.945-9.749,P=0.062),5.228(1.737-15.735,P=0.003),7.708(2.633-22.565,P＜0.001)for LDL-C levels of 0.5 to＜1.0,1.0 to＜1.4,1.4 to＜1.8 and≥ 1.8 mmol/L,respectively.A restricted cubic spline model demonstrated a significant non-linear positive association between LDL-C and MACE(P-overall≤0.001;P-non-linear=0.008).Stratified analyses by age,sex,hypertension and diabetes showed consistent HR with no significant interactions(all P＞0.05).There were no statistically significant differences among the groups in the incidence of bleeding events,elevated creatinine levels,or abnormal liver function(all P＞0.05).Conclusions In patients using PCSK9 after PCI,there is a significant positive correlation between LDL-C levels and the risk of MACE,and no correlation was observed between different LDL-C levels and the risk of adverse events such as bleeding.

Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Blonanserin,a second-generation atypical antipsychotic agent,acts as an antagonist for dopamine D2,D3,and serotonin 5-HT2A receptors.Clinical studies have demonstrated that blonanserin is non-inferior to other antipsychotics,such as haloperidol and risperidone,in alleviating the symptoms of schizophrenia.Moreover,it exhib-its beneficial effects on cognitive symptoms and social functioning,with a favorable safety profile,making it one of the key treatment options for schizophrenia.With extensive clinical experience accumulated in China,this expert consensus aims to provide psychiatrists with updated and localized guidance on the optimal use of blonan-serin.Based on a systematic review of the latest evidence-particularly studies in Chinese population,this paper pres-ents the updated Chinese expert recommendations for the clinical use of blonanserin in 2024.

Objective This study explores the clinical correlation between different low-density lipoprotein cholesterol(LDL-C)levels and prognosis,providing evidence-based guidance for the development of personalized lipid-lowering goals.Methods Patients who underwent elective percutaneous coronary intervention(PCI)treatment at Beijing Anzhen Hospital from January 2020 to June 2023 and received lipid-lowering therapy with the addition of Evolocumab were selected.Based on the results of blood lipid rechecks 3 to 6 months after surgery,the patients were divided into five groups:low-density lipoprotein＜0.5 mmol/L,0.5 to＜1.0 mmol/L,1.0 to＜1.4 mmol/L,1.4 to＜1.8 mmol/L,and above 1.8 mmol/L.All patients were followed up for more than one year,and clinical conditions and major adverse cardiovascular events(MACE)were recorded.Results A total of 1 106 patients undergoing PCI were enrolled;after propensity score matching and exclusion of patients lost to follow up,550 remained(110 per group).During 12 months of follow-up,58 patients(10.5％)experienced a MACE,with incidence rising step-wise across LDL-C categories.In multivariable Cox models adjusted for age,sex,diabetes,hypertension,baseline LDL-C,follow-up LDL-C,estimated glomerular filtration rate(eGFR),and left ventricular ejection fraction,the hazard ratios[HR(95％CI)]for MACE,relative to the＜0.5 mmol/L group,were 1.810(0.507-6.454,P=0.361),3.036(0.945-9.749,P=0.062),5.228(1.737-15.735,P=0.003),7.708(2.633-22.565,P＜0.001)for LDL-C levels of 0.5 to＜1.0,1.0 to＜1.4,1.4 to＜1.8 and≥ 1.8 mmol/L,respectively.A restricted cubic spline model demonstrated a significant non-linear positive association between LDL-C and MACE(P-overall≤0.001;P-non-linear=0.008).Stratified analyses by age,sex,hypertension and diabetes showed consistent HR with no significant interactions(all P＞0.05).There were no statistically significant differences among the groups in the incidence of bleeding events,elevated creatinine levels,or abnormal liver function(all P＞0.05).Conclusions In patients using PCSK9 after PCI,there is a significant positive correlation between LDL-C levels and the risk of MACE,and no correlation was observed between different LDL-C levels and the risk of adverse events such as bleeding.