To detect interleukin-33(IL-33)level and investigate the effect of IL-33 signaling pathway on monocytes in patients with hepatitis B virus(HBV)-associated hepatocellular carcinoma(HCC),total of 31 HBV-HCC patients,33 chronic hepatitis B(CHB)patients and 21 normal controls were enrolled in the study.Peripheral blood was collected to isolate plasma and peripheral blood mononuclear cells(PBMC),then CD14+monocytes were purified by magnetic-activated cell sorting.Intrahepatic lymphocytes(IHL)were isolated from para-tumor tissues and tumor tissues of 11 HBV-HCC patients.IL-33 and soluble suppressor of tumorigenicity 2(sST2)levels in plasma were measured by enzyme-linked immunosorbent assay;ST2 expression in CD14+monocytes was investigated by flow cytometry.Recombinant human IL-33 was used to stimulate CD14+monocytes,then the cytokine secretion and HLA-DR proportion in CD14+monocytes were assessed.Furthermore,cytotoxicity of monocytes was also investigated.Data showed that plasma IL-33 level in CHB patients and HBV-HCC patients were lower than that in controls(P<0.01).Plasma sST2 level of HBV-HCC patients was higher than those of CHB patients and controls(P<0.01).ST2+CD14+proportion in PBMC from HBV-HCC patients was lower than those of from CHB patients and controls(P<0.000 1).ST2 mean fluorescence intensity(MFI)in PBC from HBV-HCC patients was lower than those from CHB patients and controls(P<0.0001).ST2+CD14+proportion in IHL was also lower in tumor tissues than that in para-tumor tissues(P<0.05);ST2 MFI in IHL was lower in tumor tissues than that in para-tumor tissues(P<0.05).As compared with controls,monocytes activity of HBV-HCC and CHB patients were lower,especially in tumor tissues,which was presented as downregulation of HLA-DR proportion,TNF-α,IL-6,IL-1β and granzyme B secretion(P<0.05).IL-33 stimulation did not affect ST2 level in CD14+monocytes(P>0.05).Both 0.1 ng/ml and 1 ng/ml of IL-33 stimulation elevated cytokine production and HLA-DR+CD14+monocytes percentage in CD14+monocytes from HBV-HCC patients(P<0.05).However,only 1 ng/ml of IL-33 stimulation promoted monocytes-induced target cell death(P<0.000 1).Taken together,monocytes activity is down-regulated in HBV-HCC patients,and IL-33 signaling pathway could enhance monocytes function in HBV-HCC patients.

The study was designed to investigate the value of PD-1 expression on T cells in early diagnosis and prognosis of sepsis.From January 2019 to December 2022,135 patients with sepsis admitted in intensive care unit of Fengxian Central hospital were enrolled.According to the severity of sepsis,the patients were divided into sepsis group(n=89),severe sepsis group(n=22)and septic shock group(n=24).The general clinical data,laboratory indexes,constituent ratio of T cell subsets and the expression of PD-1 on the cell surface were recorded within 24 hours after the admission.Data showed that after considering sex,age and other factors,the expression of CD4+PD-1 and CD8+PD-1 were positively correlated with the severity of sepsis(P<0.05).The mortality of sepsis group,severe sepsis group and septic shock group increased successively(P=0.002).C-reactive protein(CRP),septic shock,CD4+T cells,CD4/CD8,CD4+PD-1 and CD8+PD-1 were independent risk factors for death in patients with sepsis(P<0.05).Restricted cubic spline(RCS)model was used to analyze the positive correlation of CD4+PD-1 and CD8+PD-1 with the risk of death in patients with sepsis.It can be concluded that CD4+PD-1 and CD8+PD-1 positively correlate with sepsis severity.CD4/CD8,CD4+T cells,CD8+PD-1,and CD4+PD-1 are independent risk factors for mortality in sepsis patients.

To investigate the clinical significance of platelet-neutrophil ratio in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis(AAV),a total of 128 patients were recruited and retrospectively analyzed in our department from March 2015 to July 2023.Spearman correlation analysis indicated that there was negative correlation between the level of PNR and Birmingham vasculitis activity score(BVAS)in AAV patients(r=-0.268,P=0.002).According to the PNR optimal cutoff value(26.4)determinated by X-tile bioinformatics software version 3.6.1 for predicting the survival rate,AAV patients were divided into high level PNR(HPNR)group(≥26.4)(n=105)and low level PNR(LPNR)group(<26.4)(n=23).Kaplan-Meier survival analysis showed that the survival rate of HPNR group was significantly higher than that of LPNR group(P<0.001).The level of PNR was correlated with poor prognosis of kidney(OR=2.54,95%CI:1.1-5.88,P=0.029).In conclusion,the level of PNR is closely related to disease activity and prognosis of AAV,and it might be a potential biomarker for predicting the disease activity and predicting the prognosis.

This study performed to investigate the differences of plasma gene expression profiles between primary biliary cirrhosis(PBC)patients and healthy controls,and the effect of tryptase Alpha/Beta 1(TPSAB1)on the proliferation of naive CD4+T cells derived from peripheral blood mononuclear cell(PBMC)in patients with PBC.The plasma samples of three PBC patients and three healthy controls were analyzed by microarray;Immune cell isolation kits were used to isolate natural killer(NK)cells,B cells,naive CD4+T and naive CD8+T cells from PBMC;The expression level of TPSAB1 in NK cells,B cells,naive CD4+T cells and naive CD8+T cells were analyzed by qRT-PCR;The expression of TPSAB1 in CD4+T cells was analyzed by Western blotting after interference by short hairpin RNA(shRNA)targeting TPSAB1.WST-1 proliferation kit and 5-Ethynyl-2'-deoxyuridine(EdU)staining assay were used to detect the proliferation of naive CD4+T cells after CD3/CD28 stimulation in vitro.The apoptosis of CD4+T cells was measured by flow cytometry.Enzyme linked immunosorbent assay(ELISA)was used to determine interferon-γ(IFN-γ),interleukin-4(IL-22),and IL-17 secretion in TPSAB1 knock-down CD4+T cells.Data showed that the expression level of TPSAB1 in NK cells and naive CD4+T cells from PBC patients were significantly higher than those of healthy control group.Naive CD4+T cells from PBC patients showed enhanced proliferative capacity after CD3/CD28 stimulation compared with controls.However,there was no difference in apoptosis between the two groups.The levels of IL-22,IL-17 and IFN-γ were significantly increased in PBC patients.Compared with the control group,knockdown of TPSAB1 inhibited the proliferation ability of naive CD4+T cells under CD3/CD28 stimulation.At the same time,the levels of IL-22,IL-17 and IFN-γ were decreased.In conclusion,inhibition of TPSAB1 protein expression can block the proliferation of naive CD4+T cells,suggesting that TPSAB1 may be a new target for the treatment of PBC.

This study was designed to explore the transcription level,genome alteration,potential abnormal expression mechanism,prognostic value and the association with immune cells of the tetraspan MS4A6A(membrane-spanning 4A(MS4A)subfamily protein 6A)in pan-cancer.Public databases,such as UCSC Xena,cBioPortal and Timer2,were used to collect relative data,and thenbioinformatic approaches were used to analyze the correlation of MS4A6A genome and MS4A6A expression with immune infiltration,tumor mutation burden(TMB),microsatellite instability(MSI)etc.TMB and MSI were further calculated by R package maftools.Immune score,stromal score and ESTIMATE score were calculated by R package ESTIMATE.The correlation between immune score and MS4A6A expression was conducted based on Spearman correlation coefficient.Data showed that DNA methylation of MS4A6A in most cancer tissues was negatively correlated with its expression level,suggesting the possible relation of differential MS4A6A expression to the methylation level of its promoter region.Univariate Cox analysis revealed that high expression of MS4A6A was the risk factor for LGG,TGCT,UVM and THYM;MS4A6A expression was positively correlated with the immune score in 32 types of cancer;MS4A6A expression was positively correlated with the infiltration levels of various immune cells,such as tumor associated fibroblasts(CAF),regulatory T cells(Treg),B cells,neutrophils,macrophages,monocytes,and CD8+T cells.In conclusion,MS4A6A may participate in the development of cancer,suggesting it is a potential new biomarker for cancer treatment and prevention.

The study aimed to investigate the expression of ITGB1 in gastric cancer tissues and its impact on the efficacy of immunotherapy,and to find a new biomarker for prognosis assessment and prediction of immunotherapy response in gastric cancer.By utilizing bioinformatics methods to analyze the transcriptomic data,clinical pathological characteristics,and survival information of gastric cancer patients in the Cancer Genome Atlas(TCGA)database,this study evaluates the expression of ITGB1 in gastric cancer and its correlation with clinical features.Furthermore,an in-depth analysis was conducted for evaluating the relationship of ITGB1 expression with immune infiltration,immune checkpoint-related genes,immune subtypes and immunotherapy response.Data showed that high ITGB1 expression in gastric cancer tissues is associated with later T stage,lower survival rates,and lower overall survival.Analysis of immune infiltration scores showed the score for CD4+T cells,CD8+T cells,neutrophils,macrophages and dendritic cells were higher in the high ITGB1 expression group.Additionally,the levels of immune checkpoint-related genes such as SIGLEC15,TIGIT,CD274,HAVCR2,CTLA4 and PDCD1LG2 were elevated in the high ITGB1 expression group,and the expression of ITGB1 was positively correlated with the expression of immune checkpoint-related genes including SIGLEC15,TIGIT,CD274,HAVCR2,CTLA4,LAG3 and PDCD1LG2.Analysis based on the data from the TISIDB database revealed differential expression of ITGB1 in various immune subtypes of gastric cancer,with significantly higher expression levels in the C6 subtype(TGF-β dominant type).The TIDE algorithm indicated a high score for the group with high ITGB1 expression,suggesting poor efficacy of immune checkpoint blockade therapy.To sum up,we find that high expression of ITGB1 in gastric cancer tissues is a poor prognostic indicator for gastric cancer patients,thus ITGB1 may serve as a potential biomarker for assessing prognosis and predicting the efficacy of immunotherapy in gastric cancer.

Personalized neoantigen vaccines,a cutting-edge technology in cancer immunotherapy,have garnered significant attention in recent years.Neoantigens are unique antigens produced by tumor-specific mutations,capable of being recognized by the immune system and eliciting a specific anti-tumor immune response.This review summarizes the current state of research on neoantigen vaccines,including the mechanisms of neoantigen generation and relatively screening methods,vaccine design and production,preclinical and clinical research progress,as well as the current challenges and future development trends.We present the potential of neoantigen vaccines in personalized treatment and their significant role in improving the survival rates and quality of life of cancer patients.Additionally,this review highlights the key issues in current research and proposes potential solutions,providing a reference for future studies.

As the main product of anaerobic or aerobic glycolysis,lactic acid has long been considered to be only the metabolic waste of this process,but now researches have are gradually revealing that lactic acid,as an important signaling molecule,plays a key immune regulatory role by acting on lactic acid transporters,lactate receptors and intracellular direct sensors in immune cells.In chronic inflammatory diseases,lactic acid helps maintain a pro-inflammatory environment that encourages immune cells to remain at the site of inflammation.In the event of infection,lactic acid impairs host immunity.In the tumor microenvironment(TME),the increase in lactic acid production and the resulting TME acidification promote tumor growth and invasion,and inhibit the body's immune response to tumor antigens.This review focuses on the recent research progress on the role of lactic acid in immune regulation.

This study was designed to explore the role of F.nucleatum in macrophage polarization and colorectal cancer metastasis.F.nucleatum and RAW264.7 cells were cocultured at the MOI of 100∶1,and then glucose uptake was measured by 2-NBDG,expression levels of M1 and M2 macrophage markers were determined by qPCR,glycosylation modification level and polarization marker expression of macrophages were tested by Western blotting,and STAT6 glycosylation modification was verified by Co-IP experiment.Meanwhile,F.nucleatum was co-cultured with RAW264.7(MOI=100∶1),and the supernatant was removed to treat RKO cells.The migration ability of colorectal cancer was detected by transwell experiment and scratch experiment.Data showed that F.nucleatum promoted M2 macrophage polarization and enhance the metastasis of colorectal cancer cells RKO;F.nucleatum also promoted the glucose intake of macrophages and enhanced the expression of M2-related markers.Taken together,F.nucleatum promotes the level of glycosylation in macrophages,which induces its polarization to M2 by modifying O-GlcNAc of STAT6,to regulate colorectal cancer metastasis.

This study was designed to investigate the potential protective effect of isopimpinelline against para-chlorophenylalanine(PCPA)-induced pineal gland damage in rats.Forty male Sprague-Dawley(SD)rats were divided into four groups(n=10 each):a normal group,a model group,a melatonin-treated group(10 mg/kg),and an isopimpinelline-treated group(1.5 mg/kg).All groups,except for the normal,received intraperitoneal injection of PCPA(450 mg/kg)to induce pineal gland damage.Subsequent treatments were administered orally for 7 days.Sleep latency and duration were evaluated on the sixth day using the pentobarbital sodium sleep synergy test.After the treatment period,serum melatonin levels and pineal gland inflammation markers were assessed alongside oxidative and antioxidative parameters.Histological examinations of the pineal gland were conducted,and the expression of proteins related to the Nrf2 and NF-κB signaling pathways were quantified.Data showed that isopimpinelline alleviates the structural damage in the pineal gland of model rats,significantly elevated serum melatonin levels,and markedly improved sleep latency and duration(P＜0.05).Isopimpinelline activated the Nrf2 signaling pathway by inhibiting Keap1 expression,which facilitated the nuclear translocation of Nrf2 and upregulated the antioxidant proteins NQO1 and HO-1,thereby mitigating oxidative stress in the pineal gland(P＜0.05).Furthermore,isopimpinelline significantly reduced the levels of pro-inflammatory cytokines IL-2,TNF-α and IL-6.Isopimpinelline also suppressed the NF-κB signaling pathway,reducing the expression of NF-κB p65,IKKβ,and p-IKKβ proteins,as well as the nuclear translocation of NF-κB p65(P＜0.05),thereby providing anti-inflammatory benefits.In conclusion,isopimpinelline could protect pineal gland from damage by activating the Nrf2 signaling pathway and inhibiting the NF-κB pathway.