BACKGROUND Malignancy prediction remains important to preoperative diagnosis and postoperative follow-up in laryngeal neoplasm.AIM To evaluate the circulating immune population and develop a nomogram for prediction of...BACKGROUND Malignancy prediction remains important to preoperative diagnosis and postoperative follow-up in laryngeal neoplasm.AIM To evaluate the circulating immune population and develop a nomogram for prediction of malignancy in patients with laryngeal neoplasm.METHODS A primary cohort of 156 patients was divided into laryngeal benign lesion,premalignant lesion and malignant lesion groups.Peripheral blood from patients was measured by blood routine test and flow cytometry.A nomogram was developed and applied to a validation cohort containing 55 consecutive patients.RESULTS Age,gender and seven circulating immune parameters exhibited significant differences between laryngeal benign lesion and premalignant lesion.The nomogram incorporated predictors,including gender,age,smoke index,proportions of monocytes,CD8+T cells,CD4+T cells,B cells and CD4/CD8+T cell ratio.It showed good discrimination between laryngeal premalignant lesion and malignant lesion,with a C-index of 0.844 for the primary cohort.Application of this nomogram in the validation cohort(C-index,0.804)still had good discrimination and good calibration.Decision curve analysis revealed that the nomogram was clinically useful.CONCLUSION This novel nomogram,incorporating both clinical risk factors and circulating immune parameters,could be appropriately applied in preoperative individualized prediction of malignancy in patients with laryngeal neoplasm.展开更多
The etiology of Meniere disease (MD) is unknown. Among the several factors which can provoke the disease is a pathological immune response. Objective: To investigate whether MD is due to a pathological immune reaction...The etiology of Meniere disease (MD) is unknown. Among the several factors which can provoke the disease is a pathological immune response. Objective: To investigate whether MD is due to a pathological immune reaction. Materials and methods: Immunological assay (IA) was evaluated in a consecutive study on 159 patients with MD (mean age 47.8. years) and the results compared with those from 26 patients operated on because of vestibular schwannoma (VS, mean age 54.1 years), who served as a control group. In cases of MD, transtympanic electrocochleography (ECoG) and hearing threshold were measured. Results: The average hearing level (HL) in the affected ears of patients with MD was 30 dB. Evidence of abnormal plasma protein pattern was found in 127 MD patients (80%). Elevations were found in β1-globulin (54.5%), β2-globulin (26.5%), a2-globulin (34.3%), g-globulin (17.3%), complement (CH100, 36.4%) and antinuclear antibodies (ANA, 43.4%). The onset of the disease did not correlate with the level of the plasma protein neither with the level of IgG titers. Conclusion: Elevated certain plasma proteins in patients with Meniere’s disease could be a sign that Meniere’s disease is a consequence of pathological immune reaction.展开更多
Chronic hepatitis B(CHB)infection is characterized by ongoing viral replication in infected hepatocytes,leading to persistent production of viral nucleic acids and expression of viral antigens.Hepatitis B surface anti...Chronic hepatitis B(CHB)infection is characterized by ongoing viral replication in infected hepatocytes,leading to persistent production of viral nucleic acids and expression of viral antigens.Hepatitis B surface antigen(HBsAg)is one of the most important viral antigens,secreted at levels at least 1,000-fold higher than infectious virions in the bloodstream.1 HBsAg consists of three isoforms:large(LHBs),middle(MHBs),and small(SHBs)surface proteins,transcribed and translated from the open reading frame S of the HBV genome.展开更多
While immune checkpoint inhibitors(ICIs)are adopted as standard therapy for advanced non-small cell lung cancer(NSCLC),genetic determinants of response heterogeneity remain elusive[1].As most hematopoietic lineages un...While immune checkpoint inhibitors(ICIs)are adopted as standard therapy for advanced non-small cell lung cancer(NSCLC),genetic determinants of response heterogeneity remain elusive[1].As most hematopoietic lineages undergo dynamic changes during tumor pathogenesis and immunotherapy[2],elucidating how germline variants modulate their transcriptomes is critical.Expression quantitative trait loci(eQTL)analysis,especially integrated with single-cell RNA sequencing(scRNA-seq),enables gene regulation mapping at single-cell resolution[3,4].Detailed methodologies are described in the Supplementary Materials.展开更多
Conglutinin was extracted and purified from bovine’s sera and was used in ELISA for the detection of circulating immune complexes in the sera of patients suffering from epidemic hemorrhagic fever (EHF). The detected ...Conglutinin was extracted and purified from bovine’s sera and was used in ELISA for the detection of circulating immune complexes in the sera of patients suffering from epidemic hemorrhagic fever (EHF). The detected rates of circu-展开更多
Primary open-angle glaucoma(POAG),a leading cause of irreversible blindness,involves complex neurodegeneration in which the contribution of systemic immunity remains enigmatic.Here,we dissect the circulating immune la...Primary open-angle glaucoma(POAG),a leading cause of irreversible blindness,involves complex neurodegeneration in which the contribution of systemic immunity remains enigmatic.Here,we dissect the circulating immune landscape in POAG patients via high-resolution single-cell RNA sequencing of~1.4 million peripheral blood mononuclear cells(PBMCs)from 110 patients and 110 controls of Chinese ancestry.We revealed significant immune remodeling in POAG,characterized by increased CD4+T lymphocytes and myeloid cells and impaired cytolytic potential,as evidenced by reduced cell proportions of terminally differentiated CD8+GZMK+T cells and NK cells.Transcriptomic analysis revealed a sophisticated dual transcriptional landscape in which both proinflammatory and neuroprotective signaling pathways coexist across multiple immune cell lineages.While TNF and IFNG pathway genes were broadly downregulated,specific inflammatory activation components and neuroprotective genes were upregulated in distinct cell populations,suggesting that POAG represents a complex immunometabolic syndrome characterized by a dysregulated balance between inflammatory and neuroprotective signaling.Cell type-specific eQTL mapping and SMR analysis revealed that POAG genetic risk loci exert their effects through immune gene regulation in specific PBMC subsets.Functional validation using Ifng-/-and Tnf+/-mice in an LPS/NMDA-induced retinal injury model,which mirrored the immune alterations observed in human POAG,demonstrated that genetic deficiency in these pathways markedly exacerbated retinal ganglion cell loss and visual pathway deficits.Our study establishes a crucial link between systemic immune dysregulation-specifically the disrupted balance between inflammatory and neuroprotective signaling-and retinal health,highlighting the importance of restoring this balance for future POAG therapeutic strategies.展开更多
Alcohol-related liver disease(ALD),which is caused by excessive alcohol consumption,is one of the most common types of liver disease and a primary cause of hepatic injury,with a disease spectrum that in-cludes steatos...Alcohol-related liver disease(ALD),which is caused by excessive alcohol consumption,is one of the most common types of liver disease and a primary cause of hepatic injury,with a disease spectrum that in-cludes steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.Various lines of evi-dence have indicated that immune cells play a significant role in the inflammatory processes of ALD.On the one hand,the liver contains various resident immune cells that have been proven to perform different functions in ALD.For example,in the progression of the disease,Kupffer cells(KCs)are activated by lipopolysaccharide-Toll-like receptor 4 signaling and release various proinflammatory cytokines.Moreover,alcohol intake has been shown to depress the function of natural killer cells.Additionally,two types of unconventional T cells(natural killer T cells and mucosal-associated invariant T cells)are involved in the development of ALD.On the other hand,alcohol and many different cytokines stimulate the recruitment and infiltration of circulating immune cells(neutrophils,T cells,macrophages,and mast cells)into the liver.The neutrophils can produce proinflammatory mediators and cause the dysfunction of anti-infection processes.Additionally,alcohol intake can change the phenotype of T cells,resulting in their increased production of interleukin-17.Aside from KCs,infiltrating macrophages have also been observed in patients with ALD,but the roles of all of these cells in the progression of the disease have shown both similarities and differences.Additionally,the activated mast cells are also associated with the development of ALD.Herein,we review the diverse roles of the various immune cells in the progression of ALD.展开更多
The structural and cellular organisation of the liver has unique features that define it as both a metabolic and an immunological organ.Noteworthy,liver resident macrophages,named Kupffer cells,represent the most freq...The structural and cellular organisation of the liver has unique features that define it as both a metabolic and an immunological organ.Noteworthy,liver resident macrophages,named Kupffer cells,represent the most frequent tissue resident macrophage population in the human body.Nonetheless,on acute or chronic tissue injury,Kupffer cells seem rather static and may undergo cell death,while the liver is massively infiltrated by circulating immune cells such as bone marrow-derived macrophages,also termed monocyte-derived macrophages,which drastically alter the hepatic immune landscape.Over the last decade,our knowledge on liver macrophage populations during homeostasis and liver diseases has greatly expanded.This particularly holds true in light of the recent fast-paced technological advances that brought novel dimensions to our knowledge,either in single-cell suspensions,in a two-dimensional plane or a three-dimensional space,or even in time-lapse(intravital)microscopy.This novel understanding goes from unravelling a previously underestimated macrophage diversity(eg,in terms of activation phenotype or cellular origins)to identifying spatially or temporally restricted responses that drive liver disease outcome.This review aims at providing insights into the most recent breakthroughs in our understanding of liver macrophage biology and its roles in liver(patho)physiology,in a four-dimensional perspective.展开更多
基金Health and Family Planning Commission of Shanghai Municipality of China,No.2019SY059.
文摘BACKGROUND Malignancy prediction remains important to preoperative diagnosis and postoperative follow-up in laryngeal neoplasm.AIM To evaluate the circulating immune population and develop a nomogram for prediction of malignancy in patients with laryngeal neoplasm.METHODS A primary cohort of 156 patients was divided into laryngeal benign lesion,premalignant lesion and malignant lesion groups.Peripheral blood from patients was measured by blood routine test and flow cytometry.A nomogram was developed and applied to a validation cohort containing 55 consecutive patients.RESULTS Age,gender and seven circulating immune parameters exhibited significant differences between laryngeal benign lesion and premalignant lesion.The nomogram incorporated predictors,including gender,age,smoke index,proportions of monocytes,CD8+T cells,CD4+T cells,B cells and CD4/CD8+T cell ratio.It showed good discrimination between laryngeal premalignant lesion and malignant lesion,with a C-index of 0.844 for the primary cohort.Application of this nomogram in the validation cohort(C-index,0.804)still had good discrimination and good calibration.Decision curve analysis revealed that the nomogram was clinically useful.CONCLUSION This novel nomogram,incorporating both clinical risk factors and circulating immune parameters,could be appropriately applied in preoperative individualized prediction of malignancy in patients with laryngeal neoplasm.
文摘The etiology of Meniere disease (MD) is unknown. Among the several factors which can provoke the disease is a pathological immune response. Objective: To investigate whether MD is due to a pathological immune reaction. Materials and methods: Immunological assay (IA) was evaluated in a consecutive study on 159 patients with MD (mean age 47.8. years) and the results compared with those from 26 patients operated on because of vestibular schwannoma (VS, mean age 54.1 years), who served as a control group. In cases of MD, transtympanic electrocochleography (ECoG) and hearing threshold were measured. Results: The average hearing level (HL) in the affected ears of patients with MD was 30 dB. Evidence of abnormal plasma protein pattern was found in 127 MD patients (80%). Elevations were found in β1-globulin (54.5%), β2-globulin (26.5%), a2-globulin (34.3%), g-globulin (17.3%), complement (CH100, 36.4%) and antinuclear antibodies (ANA, 43.4%). The onset of the disease did not correlate with the level of the plasma protein neither with the level of IgG titers. Conclusion: Elevated certain plasma proteins in patients with Meniere’s disease could be a sign that Meniere’s disease is a consequence of pathological immune reaction.
文摘Chronic hepatitis B(CHB)infection is characterized by ongoing viral replication in infected hepatocytes,leading to persistent production of viral nucleic acids and expression of viral antigens.Hepatitis B surface antigen(HBsAg)is one of the most important viral antigens,secreted at levels at least 1,000-fold higher than infectious virions in the bloodstream.1 HBsAg consists of three isoforms:large(LHBs),middle(MHBs),and small(SHBs)surface proteins,transcribed and translated from the open reading frame S of the HBV genome.
基金the Korean Research Foundation(NRF-2021R1A2C3014067,NRF-RS-2023-00207857 to Murim Choi,NRF-2020R1A2C3006535,NRF-RS-2025-00519956 to Se-Hoon Lee)the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(HR20C0025 to Se-Hoon Lee)Future Medicine 20*30 Project of the Samsung Medical Center(SMX1230041 to Se-Hoon Lee).
文摘While immune checkpoint inhibitors(ICIs)are adopted as standard therapy for advanced non-small cell lung cancer(NSCLC),genetic determinants of response heterogeneity remain elusive[1].As most hematopoietic lineages undergo dynamic changes during tumor pathogenesis and immunotherapy[2],elucidating how germline variants modulate their transcriptomes is critical.Expression quantitative trait loci(eQTL)analysis,especially integrated with single-cell RNA sequencing(scRNA-seq),enables gene regulation mapping at single-cell resolution[3,4].Detailed methodologies are described in the Supplementary Materials.
文摘Conglutinin was extracted and purified from bovine’s sera and was used in ELISA for the detection of circulating immune complexes in the sera of patients suffering from epidemic hemorrhagic fever (EHF). The detected rates of circu-
基金supported by the National Natural Science Foundation of China(82271105,82571240,81970839)the Sichuan Science and Technology Program(2023ZYD0059 and 2021YFS0033).
文摘Primary open-angle glaucoma(POAG),a leading cause of irreversible blindness,involves complex neurodegeneration in which the contribution of systemic immunity remains enigmatic.Here,we dissect the circulating immune landscape in POAG patients via high-resolution single-cell RNA sequencing of~1.4 million peripheral blood mononuclear cells(PBMCs)from 110 patients and 110 controls of Chinese ancestry.We revealed significant immune remodeling in POAG,characterized by increased CD4+T lymphocytes and myeloid cells and impaired cytolytic potential,as evidenced by reduced cell proportions of terminally differentiated CD8+GZMK+T cells and NK cells.Transcriptomic analysis revealed a sophisticated dual transcriptional landscape in which both proinflammatory and neuroprotective signaling pathways coexist across multiple immune cell lineages.While TNF and IFNG pathway genes were broadly downregulated,specific inflammatory activation components and neuroprotective genes were upregulated in distinct cell populations,suggesting that POAG represents a complex immunometabolic syndrome characterized by a dysregulated balance between inflammatory and neuroprotective signaling.Cell type-specific eQTL mapping and SMR analysis revealed that POAG genetic risk loci exert their effects through immune gene regulation in specific PBMC subsets.Functional validation using Ifng-/-and Tnf+/-mice in an LPS/NMDA-induced retinal injury model,which mirrored the immune alterations observed in human POAG,demonstrated that genetic deficiency in these pathways markedly exacerbated retinal ganglion cell loss and visual pathway deficits.Our study establishes a crucial link between systemic immune dysregulation-specifically the disrupted balance between inflammatory and neuroprotective signaling-and retinal health,highlighting the importance of restoring this balance for future POAG therapeutic strategies.
基金This work was supported by the National Natural Science Foundation of China(81900554)the Major Program for Sup-porting Outstanding Talents in Colleges of Ministry of Human Re-sources and Social Security of the People's Republic of Anhui(gxyqZD2020013).
文摘Alcohol-related liver disease(ALD),which is caused by excessive alcohol consumption,is one of the most common types of liver disease and a primary cause of hepatic injury,with a disease spectrum that in-cludes steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.Various lines of evi-dence have indicated that immune cells play a significant role in the inflammatory processes of ALD.On the one hand,the liver contains various resident immune cells that have been proven to perform different functions in ALD.For example,in the progression of the disease,Kupffer cells(KCs)are activated by lipopolysaccharide-Toll-like receptor 4 signaling and release various proinflammatory cytokines.Moreover,alcohol intake has been shown to depress the function of natural killer cells.Additionally,two types of unconventional T cells(natural killer T cells and mucosal-associated invariant T cells)are involved in the development of ALD.On the other hand,alcohol and many different cytokines stimulate the recruitment and infiltration of circulating immune cells(neutrophils,T cells,macrophages,and mast cells)into the liver.The neutrophils can produce proinflammatory mediators and cause the dysfunction of anti-infection processes.Additionally,alcohol intake can change the phenotype of T cells,resulting in their increased production of interleukin-17.Aside from KCs,infiltrating macrophages have also been observed in patients with ALD,but the roles of all of these cells in the progression of the disease have shown both similarities and differences.Additionally,the activated mast cells are also associated with the development of ALD.Herein,we review the diverse roles of the various immune cells in the progression of ALD.
基金supported by the German Research Foundation(DFG SFB/TRR 296 and CRC1382Project ID 403224013)and the German Ministry of Education and Research(BMBF DEEP-HCC consortium)FT’s lab has received research funding from Allergan,Bristol Myers Squibb,Gilead and Inventiva.
文摘The structural and cellular organisation of the liver has unique features that define it as both a metabolic and an immunological organ.Noteworthy,liver resident macrophages,named Kupffer cells,represent the most frequent tissue resident macrophage population in the human body.Nonetheless,on acute or chronic tissue injury,Kupffer cells seem rather static and may undergo cell death,while the liver is massively infiltrated by circulating immune cells such as bone marrow-derived macrophages,also termed monocyte-derived macrophages,which drastically alter the hepatic immune landscape.Over the last decade,our knowledge on liver macrophage populations during homeostasis and liver diseases has greatly expanded.This particularly holds true in light of the recent fast-paced technological advances that brought novel dimensions to our knowledge,either in single-cell suspensions,in a two-dimensional plane or a three-dimensional space,or even in time-lapse(intravital)microscopy.This novel understanding goes from unravelling a previously underestimated macrophage diversity(eg,in terms of activation phenotype or cellular origins)to identifying spatially or temporally restricted responses that drive liver disease outcome.This review aims at providing insights into the most recent breakthroughs in our understanding of liver macrophage biology and its roles in liver(patho)physiology,in a four-dimensional perspective.
