This editorial will focus on tumor immunity and the factors that alter the tumor immune micro-environment.The role of tumor infiltrating lymphocytes(TILs)will also be discussed in detail,including the types,mechanism ...This editorial will focus on tumor immunity and the factors that alter the tumor immune micro-environment.The role of tumor infiltrating lymphocytes(TILs)will also be discussed in detail,including the types,mechanism of action,and role.Gastric cancer(GC)often presents in the advanced stage and has various factors predicting the outcomes.The interplay of these factors and their correlation with the TILs is discussed.A literature review revealed high intratumoral TILs associated with higher grade,HER2-,and Helicobacter pylori negativity.Moreover,stromal(ST)TILs correlated with lower grade and lesser recurrence risk in GC.High TILs in ST and invasive border also correlated with mismatch repair deficiency status.Further characterization of the CD3+,CD8+,and other cells is also warranted.In the future,this complex correlation of cancer cells with the immune system can be explored for therapeutic avenues.展开更多
As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but t...As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.展开更多
Generally,a healthy immune system should be in dynamic balance,which can be maintained by both promoting and resisting inflammation.Lymphocyte apoptosis is indispensable for maintaining homeostasis[1]and participates ...Generally,a healthy immune system should be in dynamic balance,which can be maintained by both promoting and resisting inflammation.Lymphocyte apoptosis is indispensable for maintaining homeostasis[1]and participates in the entire process of lymphocyte differentiation,development,maturation,and immune effects.It has been reported that a large amount of lymphocyte apoptosis occurs in lymphoid organs during severe trauma[2].Lymphocytes consist of T and B lymphocytes,among which CD4^(+)T cells were the focus of this study.CD4^(+)T lymphocytes play an important role in the innate immunity.Apoptosis of CD4^(+)T lymphocytes is an important biological process that induces CD4^(+)T cell depletion[3].Numerous studies have shown that CD4^(+)T cell apoptosis participates in many pathological processes of diseases such as HIV infection,cancer,and systemic sclerosis[4].Classical apoptosis is induced by factors that can activate several pathways,including the mitochondrial,endoplasmic reticulum,and death receptor pathways[5].The mitochondrial pathway is mainly activated by the Bcl-2 family[6].The endoplasmic reticulum(ER)pathway is affected by endoplasmic reticulum disorders.Some external factors can trigger the death receptor pathway,such as the binding of TNF-TNFR and the combination of Fas-FasL[7].Considering these pathways,it is feasible to study the specific mechanisms of lymphocyte apoptosis,primarily in CD4^(+)T cells.展开更多
Background: In developed countries, colon cancer is the second most prevalent cancer, only exceeded by prostate cancer in men and breast cancer in women. After Hepatocellular carcinoma, breast cancer, bladder cancer, ...Background: In developed countries, colon cancer is the second most prevalent cancer, only exceeded by prostate cancer in men and breast cancer in women. After Hepatocellular carcinoma, breast cancer, bladder cancer, lung cancer, Non-Hodgkin Lymphoma and brain tumors, colon cancer is the 7<sup>th</sup> most common cancer in Egypt, in both sexes, representing 3.47% and 3%, in both male and female cancers, respectively. Aim of the Work: The aim of this study was to evaluate the prognostic and predictive significance of pretreatment Neutrophil/lymphocytes ratio (NLR), in terms of disease-free survival (DFS) and recurrence, in high-risk stage II and stage III Colorectal cancer patients who underwent curative resection. Patients and Methods: We retrospectively evaluated 103 patients, who were submitted to upfront surgery as first therapeutic option in curative intent, between January 2017 and December 2018. Pretreatment Neutrophil/lymphocytes ratio (NLR), as well as demographics, clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with disease free survival (DFS) and recurrence. Results: The cutoff point of Neutrophils/lymphocytes ratio (NLR) was calculated with Kaplan-Meier curves and log-rank test to 3. This study revealed that neutrophils/lymphocytes ratio (NLR) was significantly associated with disease free survival (p as no difference in efficacy between both chemotherapy regimens FOLFOX and XELOX in both high-risk stage II and stage III colon cancer regarding disease free survival & the toxicity profile associated with each regimen and its grades between patients. Conclusion: Our study suggests that preoperative Neutrophils/lymphocytes ratio (NLR) more than 3 may be an independent prognostic marker for TTR (time to recurrence) in high-risk stage II and stage III colon cancer patients.展开更多
T lymphocytes,the main participants of cellular immunity,can express a variety of surface molecules and form different lymphocyte subsets under the induction of different factors to play the functions of immune regula...T lymphocytes,the main participants of cellular immunity,can express a variety of surface molecules and form different lymphocyte subsets under the induction of different factors to play the functions of immune regulation and immune killing.Studies have shown that platelets play a crucial role in maintaining the stable differentiation of lymphocytes and the balance in immunomodulation.Therefore,it is necessary to study the effect of platelets on lymphocytes in vitro to better understand the role of platelets in the immune system and broaden the application of adoptive immunotherapy.Methods:Cell counting and microscopic observation were used to detect the effect of activated platelets on lymphocyte proliferation in vitro;Flow cytometry was used to detect whether changes in platelet activity affect the proportion of lymphocyte subpopulations in vitro,and to detect differences in the expression of granzyme B;lactate dehydrogenase assay(LDH)was used to determine the difference in lymphocyte killing activity caused by platelet activity in vitro.Results:This was the first to promote lymphocyte proliferation through the expression or release of certain molecules in vitro,demonstrating that platelet activation is one of the key factors.Secondly,activated platelets or inactivated platelets promoted lymphocyte subset differentiation by enhancing the proportion of CD3+CD8+T lymphocytes(CTL cells)but had a slight effect on the proportion of CD3+CD4+T(Th cells)and CD4+CD25+T lymphocytes(Treg cells).Then,it was found that either activated platelets or inactivated platelets down-regulated the proportion of natural killer(NK)T lymphocytes,while activated platelets significantly enhance the proportion of NK lymphocytes.Therefore,by further detecting the killing activity of PBMCs treated with platelets,it was found that activated platelets promoted the extensive anti-tumor activity of lymphocytes and significantly increased the expression of granzyme B.Conclusion:Our results suggest that activated platelets promote lymphocyte proliferation,optimize lymphocyte subpopulation ratio,and promote cytotoxic effect of lymphocytes in vitro,which may provide a new strategy for optimizing the adoptive immunotherapy culture system and improving its efficacy.展开更多
Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely un...Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely unknown,and the association between tumour infiltrating lymphocytes(TILs)and TLSs has been rarely explored in OSCC.In this study,associated markers of TLS,including peripheral node address(PNAd)in high endothelial venules,CD20 in B cells and CD3 in T cells,were examined in 168 OSCC patients,and survival analysis was performed between TLS-positive and TLS-negative cohorts.We detected the presence of TILs by staining CD8+cytotoxic T cells and CD57+NK cells as well.TLSs appeared as highly organized structures in 45(26.8%)cases.TLSpositive patients had a better 5-year overall survival(OS)rate(88.9%vs.56.1%,P<0.001)and relapse-free survival(RFS)rate(88.9%vs.63.4%,P=0.002).Moreover,the presence of TLS was an independent prognostic factor for both the 5-year OS rate(hazard ratio[HR]=3.784;95%confidence interval[CI],1.498–9.562)and RFS rate(HR=3.296;95%CI,1.279–8.490)in multivariate analysis.Furthermore,a higher density of CD8+T cells and CD57+NK cells was found in TLS-positive sections than in TLS-negative counterparts(P<0.001),and their combination provided a higher predictive accuracy(AUC=0.730;95%CI,0.654–0.805).In conclusion,our results suggest that TLS is an independent positive prognostic factor for OSCC patients.These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.展开更多
BACKGROUND Viral replication in blood cells with nucleuses may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions.AIM Of this investigation is to reveal the damage to...BACKGROUND Viral replication in blood cells with nucleuses may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions.AIM Of this investigation is to reveal the damage to peripheral blood lymphocytes (PBL)DNA in the patients with chronic liver diseases.MATERIALS AND METHODS Sixteen-ninepatients with chronic liver diseases (37 patients with chronic viral hepatitis, 2 patients with liver cirrhosis of mixed etiology (alcohol + virus G),30 women with primary biliary cirrhosis-PBC)were examined. The condition of DNA structure of PBL-was measured by the fluorescenceanalysis of DNA unwinding (FADU) technique with modification. Changes of fluorescence (in %) reflected the DNA distractions degree (thepresence of DNA single-stranded breaks and alkalinelabile sights).RESULTS AND CONCLUSION . The quantity of DNA single-stranded breaks and alkalinelabile sightsin DNA in all patients with chronic viral hepatitis .didnt differ from the control group,excluding the patients with chronic hepatitis (CH) C + G. Patients with HGV and TTV monoinfection had demonstrated the increase of the DNA single-stranded breaks PBL quantity.This fact may be connected with hypothesisabout the viruses replication in white blood cells discussed in the literature. Tendency to increase quantity of DNA PBL damages in the patients with primary biliary cirrhosis (PBC) accordingly to the alkaline phosphatase activity increase was revealed. Significant decrease of the DNA single-stranded breaks and alkalinelabile sights in the PBC patients that were treated with prednison was demonstrated. Probably, the tendency to increase the quantity of DNA singlestranded breaks and alkalinelabile sights in lymphocytes of the PBC patients was depended on the surplus of the blood bile acid content.展开更多
Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithel...Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens(HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive(specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiotahomeostasis, epithelial layer integrity, and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.展开更多
Objective This study was performed to investigate the effect of high mobility group box-1 protein (HMGB1) on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfu...Objective This study was performed to investigate the effect of high mobility group box-1 protein (HMGB1) on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfunction. Methods Fresh blood was obtained from healthy adult volunteers and peripheral blood mononuclear cells (PBMCs) were isolated, then rhHMGB1 was added to PBMCs. Four-color flow cytometric (FCM) analysis was used for the measurement of intracellular cytokine including interleukin IL-4 and interferon IFN- ? ELISA kits were employed for the determination of IL-2 and sIL-2R protein levels in cell culture supernatants. Results (1) Different stimulating time and dosage of rhHMGB1 did not alter the number of IFN- αpositive cells (Th1). rhHMGB1 stimulation provoked a dose-dependent and time-dependent increase in Th2 subset and decrease in ratio of Th1 to Th2. (2) Compared with the untreated cells, when the cells were coincubated with rhHMGB1 (10-100ng/ml) for 12 hrs, protein release of IL-2 and sIL-2R were significantly up-regulated. At 48 hrs, in contrast, protein production was relatively lower in cells after exposure to 100-1000 ng/ ml rhHMGB1. Conclusions These findings demonstrated that HMGB1 has a dual influence on immune functions of human T lymphocytes.展开更多
AIM To determine influence of neoadjuvant-chemotherapy(NAC) over tumor-infiltrating-lymphocytes(TIL) intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de...AIM To determine influence of neoadjuvant-chemotherapy(NAC) over tumor-infiltrating-lymphocytes(TIL) intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays(TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response(pCR)(P = 0.0251) and outcome(P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections(ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. PostNAC lesions with pC R had similar TIL levels than those without pCR(P = 0.6331). NAC produced a TIL decrease in full-face sections(P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival(DFS). Higher counts of CD3 in pre-NAC samples had longer overallsurvival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR.CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related.展开更多
In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically ...In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and highthroughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice.Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells.The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis.Induction of HSP70 expression by geranylgeranylacetone(GGA) administration alleviates ovariectomy-induced osteoporosis.Moreover, RANKL gene expression has a positive correlation with HIF1 A expression in human B cells. In conclusion, HIF-1αsignaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.展开更多
The main purpose of treatment of rheumatoid arthritis(RA) with disease modifying antirheumatic drugs(DMARDs) is to control activation of lymphocytes,although some patients do not respond adequately to such treatment. ...The main purpose of treatment of rheumatoid arthritis(RA) with disease modifying antirheumatic drugs(DMARDs) is to control activation of lymphocytes,although some patients do not respond adequately to such treatment. Among various mechanisms of multidrug resistance, P-glycoprotein(P-gp), a member of ATP-binding cassette transporters, causes drugresistance by efflux of intracellular drugs. Certain stimuli,such as tumor necrosis factor-α, activate lymphocytes and induce P-gp expression on lymphocytes, as evident in active RA. Studies from our laboratories showed spontaneous nuclear accumulation of human Y-boxbinding protein-1, a multidrug resistance 1 transcription factor, in unstimulated lymphocytes, and surface overexpression of P-gp on peripheral lymphocytes of RA patients with high disease activity. The significant correlation between P-gp expression level and RA disease activity is associated with active efflux of drugs from the lymphocyte cytoplasm and in drugresistance.However, the use of biological agents that reduce P-gp expression as well as P-gp antagonists(e.g., cyclosporine) can successfully reduce the efflux of corticosteroids from lymphocytes in vitro, suggesting that both types of drugs can be used to overcome drug-resistance and improve clinical outcome. We conclude that lymphocytes activated by various stimuli in RA patients with highly active disease acquire P-gpmediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. Expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable therapeutic target to prevent drug resistance in patients with active RA.展开更多
BACKGROUND In malignant tumors,inflammation plays a vital role in the development,invasion,and metastasis of cancer cells.Diffuse large B-cell lymphoma(DLBCL),the most common malignant proliferative disease of the lym...BACKGROUND In malignant tumors,inflammation plays a vital role in the development,invasion,and metastasis of cancer cells.Diffuse large B-cell lymphoma(DLBCL),the most common malignant proliferative disease of the lymphatic system,is commonly associated with inflammation.The international prognostic index(IPI),which includes age,lactate dehydrogenase(LDH),number of extranodal lesions,Ann Arbor score,and Eastern Cooperative Oncology Group(ECOG)score,can evaluate the prognosis of DLBCL.However,its use in accurately identifying highrisk patients and guiding treatment is poor.Therefore,it is important to find novel immune markers in predicting the prognosis of DLBCL patients.AIM To determine the association between the systemic immune inflammation index(SII),ratio of lymphocytes to monocytes(LMR),ratio of LMR to LDH(LMR/LDH),and prognosis of patients with DLBCL.METHODS A total of 68 patients diagnosed with DLBCL,treated in our hospital between January 2016 and January 2020,were included.χ2 test,Pearson’s R correlation,Kaplan Meier curves,and Cox proportional risk regression analysis were used.The differences in the SII,LMR,and LMR/LDH among patients with different clinicopathological features were analyzed.The differences in progression-free survival time among patients with different SII,LMR,and LMR/LDH expressions and influencing factors affecting the prognosis of DLBCL patients,were also analyzed.RESULTS The LMR and LMR/LDH in patients with Ann Arbor stage III–IV,ECOG score≥2,and SII,IPI score 2–5 were significantly higher than those of patients with Ann Arbor stage I-II and ECOG score<2(P<0.05).Patients with high SII,LMR,and LMR/LDH had progression-free survival times of 34 mo(95%CI:32.52–38.50),35 mo(95%CI:33.42–36.58)and 35 mo(95%CI:33.49–36.51),respectively,which were significantly lower than those with low SII,LMR,and LMR/LDH(P<0.05);the SII,LMR,and LMR/LDH were positively correlated(P<0.05).Cox proportional risk regression analysis showed that the SII,LMR,and LMR/LDH were influencing factors for the prognosis of DLBCL patients(hazard ratio=1.143,1.665,and 1.704,respectively;P<0.05).CONCLUSION The SII,LMR,and LMR/LDH are related to the clinicopathological features of DLCBL,and they also influence the prognosis of patients with the disease.展开更多
Immunotherapy has begun to revolutionize cancer treatment, by introducing therapies that target the host immune system instead of the tumor, therapies that possess unique adverse event profiles, and therapies that may...Immunotherapy has begun to revolutionize cancer treatment, by introducing therapies that target the host immune system instead of the tumor, therapies that possess unique adverse event profiles, and therapies that may cure certain types of cancer. The immune microenvironment of tumors is emerging as the most important means of understanding the relationship between a patient' immune system and their cancer, informing prognosis, and guiding immunotherapy, such as an antibody blockade of immune checkpoints. For some solid tumors, simple quantitation of lymphocyte infiltration would seem to have prognostic significance, suggesting that lymphocyte infiltration is not passive but may actively promote or inhibit tumor growth. For gastric cancers, several studies have provided strong evidence that immune cells contribute to determining prognosis. However, the exact role of immune cells in gastric cancer remains unclear. Therefore, this review focuses on the clinical significance of immune cells, especially tumor-infiltrating lymphocytes, in gastric cancer.展开更多
Background: Fibrosis results from inflammation and healing following injury. The imbalance between extracellular matrix(ECM) secretion and degradation leads to the ECM accumulation and liver fibrosis. This process is ...Background: Fibrosis results from inflammation and healing following injury. The imbalance between extracellular matrix(ECM) secretion and degradation leads to the ECM accumulation and liver fibrosis. This process is regulated by immune cells. T lymphocytes, including alpha beta( αβ) T cells, which have adaptive immune functions, and gamma delta( γδ) T cells, which have innate immune functions, are considered regulators of liver fibrosis. This review aimed to present the current understanding of the cross-talk between T lymphocytes and hepatic stellate cells(HSCs), which are the key cells in liver fibrosis. Data sources: The keywords "liver fibrosis", "immune", and "T cells" were used to retrieve articles published in Pub Med database before January 31, 2020. Results: The ratio of CD8 +(suppressor) T cells to CD4+(helper) T cells is significantly higher in the liver than in the peripheral blood. T cells secrete a series of cytokines and chemokines to regulate the inflammation in the liver and the activation of HSCs to influence the course of liver fibrosis. In addition, HSCs also regulate the differentiation and proliferation of T cells. Conclusions: The cross-talk between T cells and HSCs regulates liver fibrosis progression. The elucidation of this communication process will help us to understand the pathological process of liver fibrosis.展开更多
BACKGROUND Preoperative pulmonary function plays an important role in selecting surgical candidates and assessing postoperative complications.Reduced pulmonary function is associated with poor survival in several canc...BACKGROUND Preoperative pulmonary function plays an important role in selecting surgical candidates and assessing postoperative complications.Reduced pulmonary function is associated with poor survival in several cancers,but the prognostic value of preoperative pulmonary function in esophageal squamous cell carcinoma(ESCC)is unclear.Nutritional and systemic inflammation parameters are vital to cancer survival,and the combination of these parameters improves the prognostic value.The hemoglobin,albumin,lymphocytes and platelets(HALP)score is a novel prognostic indicator to reflect the nutritional and inflammation status,but the clinical effects of the HALP score combined with maximal voluntary ventilation(MVV),an important parameter of pulmonary function,have not been well studied in ESCC.AIM To investigate the prognostic value of MVV and HALP score for assessing postoperative survival of ESCC patients.METHODS Data form 834 ESCC patients who underwent radical esophagectomy with R0 resection were collected and retrospectively analyzed.Preoperative MVV and HALP data were retrieved from medical archives.The HALP score was calculated by the formula:Hemoglobin(g/L)×albumin(g/L)×lymphocytes(/L)/platelets(/L).The optimal cut-off values of MVV and HALP score were calculated by the receiver operating characteristic curve analysis.The Kaplan-Meier method with log-rank test was used to draw the survival curves for the variables tested.Multivariate Cox proportional hazard regression models were used to analyze the independent prognostic factors for overall survival.RESULTS MVV was significantly associated with gender(P<0.001),age at diagnosis(P<0.001),smoking history(P<0.001),drinking history(P<0.001),tumor length(P=0.013),tumor location(P=0.037)and treatment type(P=0.001).The HALP score was notably associated with gender(P<0.001),age at diagnosis(P=0.035),tumor length(P<0.001)and invasion depth(P=0.001).Univariate Cox regression analysis showed that low MVV and low HALP score were associated with worse overall survival(all P<0.001).Multivariate analysis showed that low MVV and the HALP score were both independent risk factors for overall survival(all P<0.001).The combination of MVV and HALP score improved the prediction performance for overall survival than tumor-node-metastasis.Also,low combination of MVV and HALP score was an independent risk factor for poor overall survival(P<0.001).CONCLUSION MVV,HALP score and their combination are simple and promising clinical markers to predict overall survival of ESCC patients.展开更多
The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bio...The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.展开更多
文摘This editorial will focus on tumor immunity and the factors that alter the tumor immune micro-environment.The role of tumor infiltrating lymphocytes(TILs)will also be discussed in detail,including the types,mechanism of action,and role.Gastric cancer(GC)often presents in the advanced stage and has various factors predicting the outcomes.The interplay of these factors and their correlation with the TILs is discussed.A literature review revealed high intratumoral TILs associated with higher grade,HER2-,and Helicobacter pylori negativity.Moreover,stromal(ST)TILs correlated with lower grade and lesser recurrence risk in GC.High TILs in ST and invasive border also correlated with mismatch repair deficiency status.Further characterization of the CD3+,CD8+,and other cells is also warranted.In the future,this complex correlation of cancer cells with the immune system can be explored for therapeutic avenues.
基金supported by 16POST27490032 American Heart Association post-doctoral fellowshipNational Institute of Neurological Disorders and Stroke Exploratory Neuroscience Research Grant R21 NS114836-01A1 (to AC)
文摘As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.
基金supported by the Beijing Hospital Authority’s Ascent Plan[grant no.DFL20221601]the Natural Science Foundation of Beijing[Grant No.7212053]Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine[Grant No.ZYYCXTD-C-202006]。
文摘Generally,a healthy immune system should be in dynamic balance,which can be maintained by both promoting and resisting inflammation.Lymphocyte apoptosis is indispensable for maintaining homeostasis[1]and participates in the entire process of lymphocyte differentiation,development,maturation,and immune effects.It has been reported that a large amount of lymphocyte apoptosis occurs in lymphoid organs during severe trauma[2].Lymphocytes consist of T and B lymphocytes,among which CD4^(+)T cells were the focus of this study.CD4^(+)T lymphocytes play an important role in the innate immunity.Apoptosis of CD4^(+)T lymphocytes is an important biological process that induces CD4^(+)T cell depletion[3].Numerous studies have shown that CD4^(+)T cell apoptosis participates in many pathological processes of diseases such as HIV infection,cancer,and systemic sclerosis[4].Classical apoptosis is induced by factors that can activate several pathways,including the mitochondrial,endoplasmic reticulum,and death receptor pathways[5].The mitochondrial pathway is mainly activated by the Bcl-2 family[6].The endoplasmic reticulum(ER)pathway is affected by endoplasmic reticulum disorders.Some external factors can trigger the death receptor pathway,such as the binding of TNF-TNFR and the combination of Fas-FasL[7].Considering these pathways,it is feasible to study the specific mechanisms of lymphocyte apoptosis,primarily in CD4^(+)T cells.
文摘Background: In developed countries, colon cancer is the second most prevalent cancer, only exceeded by prostate cancer in men and breast cancer in women. After Hepatocellular carcinoma, breast cancer, bladder cancer, lung cancer, Non-Hodgkin Lymphoma and brain tumors, colon cancer is the 7<sup>th</sup> most common cancer in Egypt, in both sexes, representing 3.47% and 3%, in both male and female cancers, respectively. Aim of the Work: The aim of this study was to evaluate the prognostic and predictive significance of pretreatment Neutrophil/lymphocytes ratio (NLR), in terms of disease-free survival (DFS) and recurrence, in high-risk stage II and stage III Colorectal cancer patients who underwent curative resection. Patients and Methods: We retrospectively evaluated 103 patients, who were submitted to upfront surgery as first therapeutic option in curative intent, between January 2017 and December 2018. Pretreatment Neutrophil/lymphocytes ratio (NLR), as well as demographics, clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were conducted to identify prognostic factors associated with disease free survival (DFS) and recurrence. Results: The cutoff point of Neutrophils/lymphocytes ratio (NLR) was calculated with Kaplan-Meier curves and log-rank test to 3. This study revealed that neutrophils/lymphocytes ratio (NLR) was significantly associated with disease free survival (p as no difference in efficacy between both chemotherapy regimens FOLFOX and XELOX in both high-risk stage II and stage III colon cancer regarding disease free survival & the toxicity profile associated with each regimen and its grades between patients. Conclusion: Our study suggests that preoperative Neutrophils/lymphocytes ratio (NLR) more than 3 may be an independent prognostic marker for TTR (time to recurrence) in high-risk stage II and stage III colon cancer patients.
文摘T lymphocytes,the main participants of cellular immunity,can express a variety of surface molecules and form different lymphocyte subsets under the induction of different factors to play the functions of immune regulation and immune killing.Studies have shown that platelets play a crucial role in maintaining the stable differentiation of lymphocytes and the balance in immunomodulation.Therefore,it is necessary to study the effect of platelets on lymphocytes in vitro to better understand the role of platelets in the immune system and broaden the application of adoptive immunotherapy.Methods:Cell counting and microscopic observation were used to detect the effect of activated platelets on lymphocyte proliferation in vitro;Flow cytometry was used to detect whether changes in platelet activity affect the proportion of lymphocyte subpopulations in vitro,and to detect differences in the expression of granzyme B;lactate dehydrogenase assay(LDH)was used to determine the difference in lymphocyte killing activity caused by platelet activity in vitro.Results:This was the first to promote lymphocyte proliferation through the expression or release of certain molecules in vitro,demonstrating that platelet activation is one of the key factors.Secondly,activated platelets or inactivated platelets promoted lymphocyte subset differentiation by enhancing the proportion of CD3+CD8+T lymphocytes(CTL cells)but had a slight effect on the proportion of CD3+CD4+T(Th cells)and CD4+CD25+T lymphocytes(Treg cells).Then,it was found that either activated platelets or inactivated platelets down-regulated the proportion of natural killer(NK)T lymphocytes,while activated platelets significantly enhance the proportion of NK lymphocytes.Therefore,by further detecting the killing activity of PBMCs treated with platelets,it was found that activated platelets promoted the extensive anti-tumor activity of lymphocytes and significantly increased the expression of granzyme B.Conclusion:Our results suggest that activated platelets promote lymphocyte proliferation,optimize lymphocyte subpopulation ratio,and promote cytotoxic effect of lymphocytes in vitro,which may provide a new strategy for optimizing the adoptive immunotherapy culture system and improving its efficacy.
基金This work was supported by the National Natural Science Foundations of China(Nos.81972532,81772896,81602383 and 81472524)the Science and Technology Planning Project of Guangzhou City of China(No.2017004020102).
文摘Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis.However,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely unknown,and the association between tumour infiltrating lymphocytes(TILs)and TLSs has been rarely explored in OSCC.In this study,associated markers of TLS,including peripheral node address(PNAd)in high endothelial venules,CD20 in B cells and CD3 in T cells,were examined in 168 OSCC patients,and survival analysis was performed between TLS-positive and TLS-negative cohorts.We detected the presence of TILs by staining CD8+cytotoxic T cells and CD57+NK cells as well.TLSs appeared as highly organized structures in 45(26.8%)cases.TLSpositive patients had a better 5-year overall survival(OS)rate(88.9%vs.56.1%,P<0.001)and relapse-free survival(RFS)rate(88.9%vs.63.4%,P=0.002).Moreover,the presence of TLS was an independent prognostic factor for both the 5-year OS rate(hazard ratio[HR]=3.784;95%confidence interval[CI],1.498–9.562)and RFS rate(HR=3.296;95%CI,1.279–8.490)in multivariate analysis.Furthermore,a higher density of CD8+T cells and CD57+NK cells was found in TLS-positive sections than in TLS-negative counterparts(P<0.001),and their combination provided a higher predictive accuracy(AUC=0.730;95%CI,0.654–0.805).In conclusion,our results suggest that TLS is an independent positive prognostic factor for OSCC patients.These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.
基金Grant source is the budget of the Central Research Institute of Gastroenterology that was supported by Department of Moscow Public Health.
文摘BACKGROUND Viral replication in blood cells with nucleuses may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions.AIM Of this investigation is to reveal the damage to peripheral blood lymphocytes (PBL)DNA in the patients with chronic liver diseases.MATERIALS AND METHODS Sixteen-ninepatients with chronic liver diseases (37 patients with chronic viral hepatitis, 2 patients with liver cirrhosis of mixed etiology (alcohol + virus G),30 women with primary biliary cirrhosis-PBC)were examined. The condition of DNA structure of PBL-was measured by the fluorescenceanalysis of DNA unwinding (FADU) technique with modification. Changes of fluorescence (in %) reflected the DNA distractions degree (thepresence of DNA single-stranded breaks and alkalinelabile sights).RESULTS AND CONCLUSION . The quantity of DNA single-stranded breaks and alkalinelabile sightsin DNA in all patients with chronic viral hepatitis .didnt differ from the control group,excluding the patients with chronic hepatitis (CH) C + G. Patients with HGV and TTV monoinfection had demonstrated the increase of the DNA single-stranded breaks PBL quantity.This fact may be connected with hypothesisabout the viruses replication in white blood cells discussed in the literature. Tendency to increase quantity of DNA PBL damages in the patients with primary biliary cirrhosis (PBC) accordingly to the alkaline phosphatase activity increase was revealed. Significant decrease of the DNA single-stranded breaks and alkalinelabile sights in the PBC patients that were treated with prednison was demonstrated. Probably, the tendency to increase the quantity of DNA singlestranded breaks and alkalinelabile sights in lymphocytes of the PBC patients was depended on the surplus of the blood bile acid content.
基金Supported by the Children’s Memorial Health Institute Grants,No.236/15,No.243/16 and No.S147/2016
文摘Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens(HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive(specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiotahomeostasis, epithelial layer integrity, and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.
基金the National NaturalScience Foundation of China (No. 30672178)NationalBasic Research Program of China (No. 2005CB522602)the National Natural Science Outstanding Youth Foun-dation of China (No. 30125020).
文摘Objective This study was performed to investigate the effect of high mobility group box-1 protein (HMGB1) on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfunction. Methods Fresh blood was obtained from healthy adult volunteers and peripheral blood mononuclear cells (PBMCs) were isolated, then rhHMGB1 was added to PBMCs. Four-color flow cytometric (FCM) analysis was used for the measurement of intracellular cytokine including interleukin IL-4 and interferon IFN- ? ELISA kits were employed for the determination of IL-2 and sIL-2R protein levels in cell culture supernatants. Results (1) Different stimulating time and dosage of rhHMGB1 did not alter the number of IFN- αpositive cells (Th1). rhHMGB1 stimulation provoked a dose-dependent and time-dependent increase in Th2 subset and decrease in ratio of Th1 to Th2. (2) Compared with the untreated cells, when the cells were coincubated with rhHMGB1 (10-100ng/ml) for 12 hrs, protein release of IL-2 and sIL-2R were significantly up-regulated. At 48 hrs, in contrast, protein production was relatively lower in cells after exposure to 100-1000 ng/ ml rhHMGB1. Conclusions These findings demonstrated that HMGB1 has a dual influence on immune functions of human T lymphocytes.
文摘AIM To determine influence of neoadjuvant-chemotherapy(NAC) over tumor-infiltrating-lymphocytes(TIL) intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays(TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response(pCR)(P = 0.0251) and outcome(P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections(ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. PostNAC lesions with pC R had similar TIL levels than those without pCR(P = 0.6331). NAC produced a TIL decrease in full-face sections(P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival(DFS). Higher counts of CD3 in pre-NAC samples had longer overallsurvival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR.CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related.
文摘In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and highthroughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice.Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells.The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis.Induction of HSP70 expression by geranylgeranylacetone(GGA) administration alleviates ovariectomy-induced osteoporosis.Moreover, RANKL gene expression has a positive correlation with HIF1 A expression in human B cells. In conclusion, HIF-1αsignaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.
基金Supported by In part by research Grants-In-Aid for Scientific Research by the Ministry of Health,Labor and Welfare of Japanthe Ministry of Education,Culture,Sports,Science and Technology of JapanUniversity of Occupational and Environmental Health,Japan
文摘The main purpose of treatment of rheumatoid arthritis(RA) with disease modifying antirheumatic drugs(DMARDs) is to control activation of lymphocytes,although some patients do not respond adequately to such treatment. Among various mechanisms of multidrug resistance, P-glycoprotein(P-gp), a member of ATP-binding cassette transporters, causes drugresistance by efflux of intracellular drugs. Certain stimuli,such as tumor necrosis factor-α, activate lymphocytes and induce P-gp expression on lymphocytes, as evident in active RA. Studies from our laboratories showed spontaneous nuclear accumulation of human Y-boxbinding protein-1, a multidrug resistance 1 transcription factor, in unstimulated lymphocytes, and surface overexpression of P-gp on peripheral lymphocytes of RA patients with high disease activity. The significant correlation between P-gp expression level and RA disease activity is associated with active efflux of drugs from the lymphocyte cytoplasm and in drugresistance.However, the use of biological agents that reduce P-gp expression as well as P-gp antagonists(e.g., cyclosporine) can successfully reduce the efflux of corticosteroids from lymphocytes in vitro, suggesting that both types of drugs can be used to overcome drug-resistance and improve clinical outcome. We conclude that lymphocytes activated by various stimuli in RA patients with highly active disease acquire P-gpmediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. Expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable therapeutic target to prevent drug resistance in patients with active RA.
文摘BACKGROUND In malignant tumors,inflammation plays a vital role in the development,invasion,and metastasis of cancer cells.Diffuse large B-cell lymphoma(DLBCL),the most common malignant proliferative disease of the lymphatic system,is commonly associated with inflammation.The international prognostic index(IPI),which includes age,lactate dehydrogenase(LDH),number of extranodal lesions,Ann Arbor score,and Eastern Cooperative Oncology Group(ECOG)score,can evaluate the prognosis of DLBCL.However,its use in accurately identifying highrisk patients and guiding treatment is poor.Therefore,it is important to find novel immune markers in predicting the prognosis of DLBCL patients.AIM To determine the association between the systemic immune inflammation index(SII),ratio of lymphocytes to monocytes(LMR),ratio of LMR to LDH(LMR/LDH),and prognosis of patients with DLBCL.METHODS A total of 68 patients diagnosed with DLBCL,treated in our hospital between January 2016 and January 2020,were included.χ2 test,Pearson’s R correlation,Kaplan Meier curves,and Cox proportional risk regression analysis were used.The differences in the SII,LMR,and LMR/LDH among patients with different clinicopathological features were analyzed.The differences in progression-free survival time among patients with different SII,LMR,and LMR/LDH expressions and influencing factors affecting the prognosis of DLBCL patients,were also analyzed.RESULTS The LMR and LMR/LDH in patients with Ann Arbor stage III–IV,ECOG score≥2,and SII,IPI score 2–5 were significantly higher than those of patients with Ann Arbor stage I-II and ECOG score<2(P<0.05).Patients with high SII,LMR,and LMR/LDH had progression-free survival times of 34 mo(95%CI:32.52–38.50),35 mo(95%CI:33.42–36.58)and 35 mo(95%CI:33.49–36.51),respectively,which were significantly lower than those with low SII,LMR,and LMR/LDH(P<0.05);the SII,LMR,and LMR/LDH were positively correlated(P<0.05).Cox proportional risk regression analysis showed that the SII,LMR,and LMR/LDH were influencing factors for the prognosis of DLBCL patients(hazard ratio=1.143,1.665,and 1.704,respectively;P<0.05).CONCLUSION The SII,LMR,and LMR/LDH are related to the clinicopathological features of DLCBL,and they also influence the prognosis of patients with the disease.
文摘Immunotherapy has begun to revolutionize cancer treatment, by introducing therapies that target the host immune system instead of the tumor, therapies that possess unique adverse event profiles, and therapies that may cure certain types of cancer. The immune microenvironment of tumors is emerging as the most important means of understanding the relationship between a patient' immune system and their cancer, informing prognosis, and guiding immunotherapy, such as an antibody blockade of immune checkpoints. For some solid tumors, simple quantitation of lymphocyte infiltration would seem to have prognostic significance, suggesting that lymphocyte infiltration is not passive but may actively promote or inhibit tumor growth. For gastric cancers, several studies have provided strong evidence that immune cells contribute to determining prognosis. However, the exact role of immune cells in gastric cancer remains unclear. Therefore, this review focuses on the clinical significance of immune cells, especially tumor-infiltrating lymphocytes, in gastric cancer.
基金supported by grants from the National Natural Science Foundation of China (81771722 and 81700658)。
文摘Background: Fibrosis results from inflammation and healing following injury. The imbalance between extracellular matrix(ECM) secretion and degradation leads to the ECM accumulation and liver fibrosis. This process is regulated by immune cells. T lymphocytes, including alpha beta( αβ) T cells, which have adaptive immune functions, and gamma delta( γδ) T cells, which have innate immune functions, are considered regulators of liver fibrosis. This review aimed to present the current understanding of the cross-talk between T lymphocytes and hepatic stellate cells(HSCs), which are the key cells in liver fibrosis. Data sources: The keywords "liver fibrosis", "immune", and "T cells" were used to retrieve articles published in Pub Med database before January 31, 2020. Results: The ratio of CD8 +(suppressor) T cells to CD4+(helper) T cells is significantly higher in the liver than in the peripheral blood. T cells secrete a series of cytokines and chemokines to regulate the inflammation in the liver and the activation of HSCs to influence the course of liver fibrosis. In addition, HSCs also regulate the differentiation and proliferation of T cells. Conclusions: The cross-talk between T cells and HSCs regulates liver fibrosis progression. The elucidation of this communication process will help us to understand the pathological process of liver fibrosis.
基金Supported by National Natural Science Foundation of China,No.U1301227,No.81872032 and No.U1804262Doctoral Team Foundation of the First Affiliated Hospital of Zhengzhou University,No.2016-BSTDJJ-03.
文摘BACKGROUND Preoperative pulmonary function plays an important role in selecting surgical candidates and assessing postoperative complications.Reduced pulmonary function is associated with poor survival in several cancers,but the prognostic value of preoperative pulmonary function in esophageal squamous cell carcinoma(ESCC)is unclear.Nutritional and systemic inflammation parameters are vital to cancer survival,and the combination of these parameters improves the prognostic value.The hemoglobin,albumin,lymphocytes and platelets(HALP)score is a novel prognostic indicator to reflect the nutritional and inflammation status,but the clinical effects of the HALP score combined with maximal voluntary ventilation(MVV),an important parameter of pulmonary function,have not been well studied in ESCC.AIM To investigate the prognostic value of MVV and HALP score for assessing postoperative survival of ESCC patients.METHODS Data form 834 ESCC patients who underwent radical esophagectomy with R0 resection were collected and retrospectively analyzed.Preoperative MVV and HALP data were retrieved from medical archives.The HALP score was calculated by the formula:Hemoglobin(g/L)×albumin(g/L)×lymphocytes(/L)/platelets(/L).The optimal cut-off values of MVV and HALP score were calculated by the receiver operating characteristic curve analysis.The Kaplan-Meier method with log-rank test was used to draw the survival curves for the variables tested.Multivariate Cox proportional hazard regression models were used to analyze the independent prognostic factors for overall survival.RESULTS MVV was significantly associated with gender(P<0.001),age at diagnosis(P<0.001),smoking history(P<0.001),drinking history(P<0.001),tumor length(P=0.013),tumor location(P=0.037)and treatment type(P=0.001).The HALP score was notably associated with gender(P<0.001),age at diagnosis(P=0.035),tumor length(P<0.001)and invasion depth(P=0.001).Univariate Cox regression analysis showed that low MVV and low HALP score were associated with worse overall survival(all P<0.001).Multivariate analysis showed that low MVV and the HALP score were both independent risk factors for overall survival(all P<0.001).The combination of MVV and HALP score improved the prediction performance for overall survival than tumor-node-metastasis.Also,low combination of MVV and HALP score was an independent risk factor for poor overall survival(P<0.001).CONCLUSION MVV,HALP score and their combination are simple and promising clinical markers to predict overall survival of ESCC patients.
文摘The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.
