BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining t...BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.展开更多
Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospec...Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospective and observational study,we recruited 500 patients with ACS.For all the eligible patients,demographic details were collected,and laboratory parameters were evaluated.The CAD severity was evaluated in terms of the number of involved vessels.The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed.Results:77.2%of Patients was male,and 52%of the patients aged between 55-70 years.Based on the type of ACS,396 out of 500 patients had ST-elevation myocardial infarction.An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among classⅣpatients.The mean NLR value among the non-survivors were higher compared to the survivors(9.52±5.72 vs.4.76±2.36;P<0.01).Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0%and a specificity of 77.3%.Conclusions:The NLR can be used as an independent prognostic marker in ACS.An elevated NLR value serves as a reliable predictor for short-term complications,notably in-hospital mortality.展开更多
Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy people...Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.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
Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac...Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.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
Recently,fuzzy multi-sets have come to the forefront of scientists’interest and have been used in algebraic structures such asmulti-groups,multirings,anti-fuzzy multigroup and(α,γ)-anti-fuzzy subgroups.In this pape...Recently,fuzzy multi-sets have come to the forefront of scientists’interest and have been used in algebraic structures such asmulti-groups,multirings,anti-fuzzy multigroup and(α,γ)-anti-fuzzy subgroups.In this paper,we first summarize the knowledge about the algebraic structure of fuzzy multi-sets such as(α,γ)-anti-multi-fuzzy subgroups.In a way,the notion of anti-fuzzy multigroup is an application of anti-fuzzy multi sets to the theory of group.The concept of anti-fuzzy multigroup is a complement of an algebraic structure of a fuzzy multi set that generalizes both the theories of classical group and fuzzy group.The aim of this paper is to highlight the connection between fuzzy multi-sets and algebraic structures from an anti-fuzzification point of view.Therefore,in this paper,we define(α,γ)-antimulti-fuzzy subgroups,(α,γ)-anti-multi-fuzzy normal subgroups,(α,γ)-antimulti-fuzzy homomorphism on(α,γ)-anti-multi-fuzzy subgroups and these been explicated some algebraic structures.Then,we introduce the concept(α,γ)-anti-multi-fuzzy subgroups and(α,γ)-anti-multi-fuzzy normal subgroups and of their properties.This new concept of homomorphism as a bridge among set theory,fuzzy set theory,anti-fuzzy multi sets theory and group theory and also shows the effect of anti-fuzzy multi sets on a group structure.Certain results that discuss the(α,γ)cuts of anti-fuzzy multigroup are explored.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
To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type 3(MHV-3) induced chronic viral hepatitis in C3H/Hej mice,ninety C3H/Hej mice were chosen to individually receive 10 plaque...To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type 3(MHV-3) induced chronic viral hepatitis in C3H/Hej mice,ninety C3H/Hej mice were chosen to individually receive 10 plaque forming units(PFU)of MHV-3 intraperitoneally.The changes of virus titer and pathology in liver tissue were examined by standard plaque assay and by the hematoxylin/eosin(HE) staining method from 2 days post MHV-3 infection.The ratios of T cell subsets including CD3+CD4+CD8-,CD3+CD4-CD8+,CD3+CD4-CD8-,CD3+CD4+CD25+,CD3+CD4+CD25-and CD3+ CD4-CD25+ T lymphocyte of total T lymphocytes in blood,spleen and liver were examined at 0,2,4,6,8,10,12,15,20,25,30,40 days post MHV-3 infection by flow cytosorting.We observed that the virus titer raised and showed persistent virus duplications and inflammatory changes in the livers of C3H/Hej mice from 2 days post MHV-3 infection.The double negative T cell(DN Treg cell) and CD4+CD25+ T cell ratios increased significantly from 2 days post MHV-3 infection in C3H/Hej mice,and CD3+CD4+CD8-,CD3+CD4-CD8+,CD3+CD4+CD25-and CD3+CD4-CD25+ T cell ratios decreased accordingly.In conclusion,the changes of virus titer and pathology in the livers of C3H/Hej mice post MHV-3 suggest their contribution to viral persistence.Further characterizations of DN Treg cells are that infection indicates that MHV-3 could induce the chronic inflammation in livers of C3H/Hej mice.The increase of the DN Treg cell and CD4+CD25+ T cell ratios in C3H/Hej mice post MHV-3 infection suggests that DN Treg cells and CD4+CD25+ T cells may both have important suppressive immunomodulation functions in the development of chronic viral hepatitis and have important roles in the virus persistent infection.Further characterizations of DNT cell and CD4+CD25+ T cell are under investigation.展开更多
BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of ear...BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.展开更多
BACKGROUND Programmed death 1(PD-1)and CD4^(+)CD25^(+)FoxP3^(+)expression in peripheral blood T-cells has been previously reported in various types of cancer.However,the specific variation tendency during surgery and ...BACKGROUND Programmed death 1(PD-1)and CD4^(+)CD25^(+)FoxP3^(+)expression in peripheral blood T-cells has been previously reported in various types of cancer.However,the specific variation tendency during surgery and chemotherapy,as well as their relationship in gastric cancer patients,still remain unclear.Understanding this aspect may provide some novel insights for future studies on tumor recurrence and tumor immune escape,and also serve as a reference for determining the optimal timing and dose of clinical anti-PD-1 antibodies.AIM To observe and analyze the expression characteristics of peripheral lymphocyte PD-1 and FoxP3^(+)regulatory T cells(FoxP3^(+)Tregs)before and after surgery or chemotherapy in gastric cancer patients.METHODS Twenty-nine stomach cancer patients undergoing chemotherapy after a D2 gastrectomy provided 10 mL peripheral blood samples at each phase of the perioperative period and during chemotherapy.This study also included 29 agematched healthy donors as a control group.PD-1 expression was detected on lymphocytes,including CD4^(+)CD8^(+)CD45RO^(+),CD4^(+)CD45RO^(+),and CD8^(+)CD45RO^(+)lymphocytes as well as regulatory T cells.RESULTS We observed a significant increase of PD-1 expression on immune subsets and a larger number of FoxP3^(+)Tregs in gastric cancer patients(P<0.05).Following D2 gastrectomy,peripheral lymphocytes PD-1 expression and the number of FoxP3^(+)Tregs notably decrease(P<0.05).However,during postoperative chemotherapy,we only observed a decrease in PD-1 expression on lymphocytes in the CD8^(+)CD45RO^(+)and CD8^(+)CD45RO^(+)populations.Additionally,linear correlation analysis indicated a positive correlation between PD-1 expression and the number of CD4^(+)CD45RO^(+)FoxP3high activated Tregs(aTregs)on the total peripheral lymphocytes(r=0.5622,P<0.0001).CONCLUSION The observed alterations in PD-1 expression and the activation of regulatory T cells during gastric cancer treatment may offer novel insights for future investigations into tumor immune evasion and the clinical application of anti-PD-1 antibodies in gastric cancer.展开更多
Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occu...Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occurs in 30%of cases.The persistent mortality rates,the failure of current therapies to extend life expectancy,and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches.Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.Recently,MBs have been segregated into four molecular subgroups:Wingless-activated(WNT-MB)(Group 1);Sonichedgehog-activated(SHH-MB)(Group 2);Group 3 and 4 MBs.These molecular alterations follow specific gene mutations and disease-risk stratifications.The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.However,the need to explore new therapies targeting specific receptors in MB microenvironment became essential.The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment,and their role are still under investigation.In this review,we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment,with an overview of the recent investigations and clinical trials.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
BACKGROUND The hemoglobin,albumin,lymphocyte,and platelet(HALP)score,derived from a composite evaluation of markers reflecting the tumor-inflammation relationship and nutritional status,has been substantiated as a not...BACKGROUND The hemoglobin,albumin,lymphocyte,and platelet(HALP)score,derived from a composite evaluation of markers reflecting the tumor-inflammation relationship and nutritional status,has been substantiated as a noteworthy prognostic determinant for diverse malignancies.AIM To investigate how the HALP score relates to prognosis in patients with metastatic gastric cancer.METHODS The cutoff values for the HALP score,neutrophil/lymphocyte ratio,and platelet/lymphocyte ratio were determined using receiver operating characteristic analysis.Low HALP scores were defined as those less than 24.79 and high HALP scores as those greater than 24.79.RESULTS The study cohort comprised 147 patients and 110 of them(74.8%)were male.The patients'median age was 63(22-89)years.The median overall survival was significantly superior in the patients with high HALP scores than in those with low HALP scores(10.4 mo vs 7.5 mo,respectively;P<0.001)CONCLUSION The HALP score was found to be a prognostic factor in patients with metastatic gastric cancer.展开更多
Objective:To investigate the effects of bone marrow-derived mesenchymal stem cells(BMSCs)on the proliferation and secretion of IgM,IgG and IL-2 in spleen lymphocytes(L)of aging rats.Methods:BMSCs were isolated by the ...Objective:To investigate the effects of bone marrow-derived mesenchymal stem cells(BMSCs)on the proliferation and secretion of IgM,IgG and IL-2 in spleen lymphocytes(L)of aging rats.Methods:BMSCs were isolated by the whole bone marrow adherence method and characterized.A rat model of aging was produced by daily subcutaneous injection of D-galactose into the back of the neck.Rat spleen lymphocyte isolate kit to isolate spleen lymphocytes from aging rats and young rats.In vitro,the co-culture system of BMSCs and aging rats lymphocytes was established,and under the induction of mitogen LPS and ConA,the proliferative activity of lymphocytes in each group was detected by CCK-8 assay,the levels of IgM and IgG in the culture supernatant of each group was detected by ELISA,and the IL-2 radioimmunoassay kits were used to detect the content of IL-2 in the supernatant of each group.Results:(1)The isolated adherent cells showed the characteristics of BMSCs,including spindle-shaped morphology,high expression of CD29,CD44,low expression of CD34 and CD45,and osteogenic/adipogenic ability.(2)Under LPS induction,lymphocyte proliferative activity and secretion of immunoglobulin IgG were reduced in the aging group compared with the young group,and co-culture with BMSCs reversed this trend.(3)Under ConA induction,the IL-2 content of BMSCs co-cultured with aging lymphocytes was higher than that of aging lymphocytes alone(P<0.0001);the IL-2 content of CsA co-cultured with aging lymphocytes was lower than that of aging lymphocytes alone(P<0.0001).Conclusion:BMSCs have immunomodulatory effects on the spleen lymphocytes of aging rats in vitro.展开更多
Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course o...Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course of the disease, response to therapy, and overall survival (OS). Materials and Methods: A total of 124 patients followed-up with the diagnosis of AML from 2016 to 2019 were retrospectively examined. Results: 69 of the cases (55.6%) were men and 55 (44.3%) were women. The average age at the time of diagnosis was 53.44 ± 30.3 years old. We determined the NLR as median 0.46 (0.16 - 1.1). In AML, 69 patients were responsive to the induction regimen (57.9%) while 46 patients were unresponsive (37.8%). 5 patients died before completing the regimen. D-dimer was found to be higher and fibrinogen was found to be lower in the responsive group. Lower OS was observed in cases of >60 years of age, male gender, non-APL AML, high NLR, and recurrence at diagnosis. Recurrences were detected in 23 patients (18.5%) and the median time to the recurrence was 416 (236 - 639) days. Fibrinogen level and the bone marrow blast ratio at the time of application were determined to be associated with recurrence. The median follow-up time was 856 (143 - 1276) days. Final condition analysis reveals that 74 patients (59.6%) are alive. Conclusion: We determined in our study that the NLR is effective on survival. Medical literature on this subject is scanty and prospective studies with large patient groups are needed.展开更多
Background:Colorectal cancer(CRC)is a common gastrointestinal malignancy.The T lymphocyte subsets are important in the develop-ment,invasion and metastasis of tumors,including CRC.Nevertheless,limited research has exp...Background:Colorectal cancer(CRC)is a common gastrointestinal malignancy.The T lymphocyte subsets are important in the develop-ment,invasion and metastasis of tumors,including CRC.Nevertheless,limited research has explored the relationship between T cell subpopu-lations and the clinical characteristics of CRC.This study compared the T lymphocyte subsets in patients with CRC and healthy individuals,and assessed the relationship between these values and clinical characteristics.Methods:Peripheral blood was collected from 100 patients with CRC and 54 healthy individuals.The numbers of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes,NK cells,and the CD4^(+)T/CD8^(+)T ratio in peripheral blood were measured using flow cytometry,and were compared between CRC patients and healthy individuals.Spearman's correlation analysis was performed to investigate the relationship between the T lymphocyte subsets in patients diagnosed with CRC and the levels of carcinoembryonic antigen(CEA)and thymidine kinase 1(TK1).Receiver operating characteristic(ROC)curves were utilized to evaluate the potential utility of the T lymphocyte counts in predicting lymph node metastasis,vas-cular infiltration,and high Ki-67 expression.Results:The CRC patients had lower counts of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes compared to the healthy population(P<0.05).However,no significant differences were observed in the CD4^(+)/CD8^(+)ratio or NK cells(P>0.05).Notably,the CD3^(+)T,CD4^(+)T,and CD8^(+)T lym-phocyte counts were higher in patients with stageⅠ-Ⅱdisease,no lymph node metastasis,no vascular invasion,and low Ki-67 expression than in those with stageⅢ,lymph node metastasis,vascular invasion,and high Ki-67 expression(P<0.05).There was a negative association be-tween the CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts and CEA and TK1 levels in patients with CRC.The ROC curves demonstrated that CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts had significant predictive value for lymph node metastasis,vascular infiltration,and high Ki-67 expression.Conclusions:The peripheral blood CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts are related to the clinical traits of patients with CRC and can predict the prognosis of the disease.展开更多
基金The research protocol was approved by the Clinical Trial Ethics Committee of the Affiliated Hospital of Southwest Medical University(approval number:KY2021063)registered in the Chinese Clinical Trial Registry(registration number:ChiCTR2100044198).
文摘BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.
文摘Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospective and observational study,we recruited 500 patients with ACS.For all the eligible patients,demographic details were collected,and laboratory parameters were evaluated.The CAD severity was evaluated in terms of the number of involved vessels.The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed.Results:77.2%of Patients was male,and 52%of the patients aged between 55-70 years.Based on the type of ACS,396 out of 500 patients had ST-elevation myocardial infarction.An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among classⅣpatients.The mean NLR value among the non-survivors were higher compared to the survivors(9.52±5.72 vs.4.76±2.36;P<0.01).Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0%and a specificity of 77.3%.Conclusions:The NLR can be used as an independent prognostic marker in ACS.An elevated NLR value serves as a reliable predictor for short-term complications,notably in-hospital mortality.
基金supported by the National Natural Science Foundation of China(No.81602020).
文摘Background:CD8 positive T lymphocytes and natural killer(NK)cells in the peripheral blood of cervical cancer patients exhibit varying sensitivities to radiotherapy and chemotherapy.Methods:A total of 50 healthy peoples and 60 cervical cancer patients were recruited.The patients with cervical cancer were separated into two groups:radiation and chemotherapy,and blood sample were collected before and after treatment.Data on the proportion of CD8 positive T lymphocytes and NK cells were gathered for analytical evaluation.Results:Compared to healthy individuals,patients with cervical cancer exhibit a reduced proportion of CD8 positive T cells within their peripheral blood.And for patients with cervical cancer,radiation therapy has been found to be more effective than chemotherapy in increasing the proportion of CD8 positive T lymphocytes and NK cells.Conclusions:These results suggest that radiation therapy increases the levels of CD8 positive T lymphocytes and NK cells within the peripheral blood of patients with cervical cancer.The study hypothesis that the changes in the percentage of CD8 positive T lymphocytes may serve as a potential indicator for predicting treatment efficacy.
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 grants from the National Natural Science Foundation of China(No.82020108004)the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University(No.2018JSLC0020)+1 种基金Chongqing Science and Technology Innovation Leading Talent(No.CSTCCXLJRC201718)Natural Science Foundation of Chongqing Innovation Group Science Program(No.cstc2021jcyj-cxttX0001).
文摘Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
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.
基金Yibin University Pre-research Project,Research on the coupling and coordinated development ofmanufacturing and logistics industry under the background of intelligentmanufacturing,(2022YY001)Sichuan ProvincialDepartment of EducationWater Transport EconomicResearch Center,Research on the Development Path and Countermeasures of the Advanced Manufacturing Industry in the Sanjiang New District of Yibin under a“dual circulation”development pattern(SYJJ2020A06).
文摘Recently,fuzzy multi-sets have come to the forefront of scientists’interest and have been used in algebraic structures such asmulti-groups,multirings,anti-fuzzy multigroup and(α,γ)-anti-fuzzy subgroups.In this paper,we first summarize the knowledge about the algebraic structure of fuzzy multi-sets such as(α,γ)-anti-multi-fuzzy subgroups.In a way,the notion of anti-fuzzy multigroup is an application of anti-fuzzy multi sets to the theory of group.The concept of anti-fuzzy multigroup is a complement of an algebraic structure of a fuzzy multi set that generalizes both the theories of classical group and fuzzy group.The aim of this paper is to highlight the connection between fuzzy multi-sets and algebraic structures from an anti-fuzzification point of view.Therefore,in this paper,we define(α,γ)-antimulti-fuzzy subgroups,(α,γ)-anti-multi-fuzzy normal subgroups,(α,γ)-antimulti-fuzzy homomorphism on(α,γ)-anti-multi-fuzzy subgroups and these been explicated some algebraic structures.Then,we introduce the concept(α,γ)-anti-multi-fuzzy subgroups and(α,γ)-anti-multi-fuzzy normal subgroups and of their properties.This new concept of homomorphism as a bridge among set theory,fuzzy set theory,anti-fuzzy multi sets theory and group theory and also shows the effect of anti-fuzzy multi sets on a group structure.Certain results that discuss the(α,γ)cuts of anti-fuzzy multigroup are explored.
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National Nature Science Foundation (30571643, 30672380)Major State Basic Research Development Program of China (2005CB522901,2007CB512904)
文摘To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type 3(MHV-3) induced chronic viral hepatitis in C3H/Hej mice,ninety C3H/Hej mice were chosen to individually receive 10 plaque forming units(PFU)of MHV-3 intraperitoneally.The changes of virus titer and pathology in liver tissue were examined by standard plaque assay and by the hematoxylin/eosin(HE) staining method from 2 days post MHV-3 infection.The ratios of T cell subsets including CD3+CD4+CD8-,CD3+CD4-CD8+,CD3+CD4-CD8-,CD3+CD4+CD25+,CD3+CD4+CD25-and CD3+ CD4-CD25+ T lymphocyte of total T lymphocytes in blood,spleen and liver were examined at 0,2,4,6,8,10,12,15,20,25,30,40 days post MHV-3 infection by flow cytosorting.We observed that the virus titer raised and showed persistent virus duplications and inflammatory changes in the livers of C3H/Hej mice from 2 days post MHV-3 infection.The double negative T cell(DN Treg cell) and CD4+CD25+ T cell ratios increased significantly from 2 days post MHV-3 infection in C3H/Hej mice,and CD3+CD4+CD8-,CD3+CD4-CD8+,CD3+CD4+CD25-and CD3+CD4-CD25+ T cell ratios decreased accordingly.In conclusion,the changes of virus titer and pathology in the livers of C3H/Hej mice post MHV-3 suggest their contribution to viral persistence.Further characterizations of DN Treg cells are that infection indicates that MHV-3 could induce the chronic inflammation in livers of C3H/Hej mice.The increase of the DN Treg cell and CD4+CD25+ T cell ratios in C3H/Hej mice post MHV-3 infection suggests that DN Treg cells and CD4+CD25+ T cells may both have important suppressive immunomodulation functions in the development of chronic viral hepatitis and have important roles in the virus persistent infection.Further characterizations of DNT cell and CD4+CD25+ T cell are under investigation.
基金Supported by The Specialized Scientific Research Fund Projects of The Medical Group of Qingdao University,No.YLJT20201002.
文摘BACKGROUND Myelodysplastic syndrome(MDS)is caused by malignant proliferation and ineffective hematopoiesis.Oncogenic somatic mutations and increased apoptosis,necroptosis and pyroptosis lead to the accumulation of earlier hematopoietic progenitors and impaired productivity of mature blood cells.An increased percentage of myeloblasts and the presence of unfavorable somatic mutations are signs of leukemic hematopoiesis and indicators of entrance into an advanced stage.Bone marrow cellularity and myeloblasts usually increase with disease progression.However,aplastic crisis occasionally occurs in advanced MDS.CASE SUMMARY A 72-year-old male patient was definitively diagnosed with MDS with excess blasts-1(MDS-EB-1)based on an increase in the percentages of myeloblasts and cluster of differentiation(CD)34+hematopoietic progenitors and the identification of myeloid neoplasm-associated somatic mutations in bone marrow samples.The patient was treated with hypomethylation therapy and was able to maintain a steady disease state for 2 years.In the treatment process,the advanced MDS patient experienced an episode of progressive pancytopenia and bone marrow aplasia.During the aplastic crisis,the bone marrow was infiltrated with sparsely distributed atypical lymphocytes.Surprisingly,the leukemic cells disappeared.Immunological analysis revealed that the atypical lymphocytes expressed a high frequency of CD3,CD5,CD8,CD16,CD56 and CD57,suggesting the activation of autoimmune cytotoxic T-lymphocytes and natural killer(NK)/NKT cells that suppressed both normal and leukemic hematopoiesis.Elevated serum levels of inflammatory cytokines,including interleukin(IL)-6,interferon-gamma(IFN-γ)and tumor necrosis factor-alpha(TNF-α),confirmed the deranged type I immune responses.This morphological and immunological signature led to the diagnosis of severe aplastic anemia secondary to large granule lymphocyte leukemia.Disseminated tuberculosis was suspected upon radiological examinations in the search for an inflammatory niche.Antituberculosis treatment led to reversion of the aplastic crisis,disappearance of the atypical lymphocytes,increased marrow cellularity and 2 mo of hematological remission,providing strong evidence that disseminated tuberculosis was responsible for the development of the aplastic crisis,the regression of leukemic cells and the activation of CD56+atypical lymphocytes.Reinstitution of hypomethylation therapy in the following 19 mo allowed the patient to maintain a steady disease state.However,the patient transformed the disease phenotype into acute myeloid leukemia and eventually died of disease progression and an overwhelming infectious episode.CONCLUSION Disseminated tuberculosis can induce CD56+lymphocyte infiltration in the bone marrow and in turn suppress both normal and leukemic hematopoiesis,resulting in the development of aplastic crisis and leukemic cell regression.
基金the National Natural Science Foundation of China,No.81871317and Military Medical Innovation Project,No.18CXZ025.
文摘BACKGROUND Programmed death 1(PD-1)and CD4^(+)CD25^(+)FoxP3^(+)expression in peripheral blood T-cells has been previously reported in various types of cancer.However,the specific variation tendency during surgery and chemotherapy,as well as their relationship in gastric cancer patients,still remain unclear.Understanding this aspect may provide some novel insights for future studies on tumor recurrence and tumor immune escape,and also serve as a reference for determining the optimal timing and dose of clinical anti-PD-1 antibodies.AIM To observe and analyze the expression characteristics of peripheral lymphocyte PD-1 and FoxP3^(+)regulatory T cells(FoxP3^(+)Tregs)before and after surgery or chemotherapy in gastric cancer patients.METHODS Twenty-nine stomach cancer patients undergoing chemotherapy after a D2 gastrectomy provided 10 mL peripheral blood samples at each phase of the perioperative period and during chemotherapy.This study also included 29 agematched healthy donors as a control group.PD-1 expression was detected on lymphocytes,including CD4^(+)CD8^(+)CD45RO^(+),CD4^(+)CD45RO^(+),and CD8^(+)CD45RO^(+)lymphocytes as well as regulatory T cells.RESULTS We observed a significant increase of PD-1 expression on immune subsets and a larger number of FoxP3^(+)Tregs in gastric cancer patients(P<0.05).Following D2 gastrectomy,peripheral lymphocytes PD-1 expression and the number of FoxP3^(+)Tregs notably decrease(P<0.05).However,during postoperative chemotherapy,we only observed a decrease in PD-1 expression on lymphocytes in the CD8^(+)CD45RO^(+)and CD8^(+)CD45RO^(+)populations.Additionally,linear correlation analysis indicated a positive correlation between PD-1 expression and the number of CD4^(+)CD45RO^(+)FoxP3high activated Tregs(aTregs)on the total peripheral lymphocytes(r=0.5622,P<0.0001).CONCLUSION The observed alterations in PD-1 expression and the activation of regulatory T cells during gastric cancer treatment may offer novel insights for future investigations into tumor immune evasion and the clinical application of anti-PD-1 antibodies in gastric cancer.
文摘Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occurs in 30%of cases.The persistent mortality rates,the failure of current therapies to extend life expectancy,and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches.Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.Recently,MBs have been segregated into four molecular subgroups:Wingless-activated(WNT-MB)(Group 1);Sonichedgehog-activated(SHH-MB)(Group 2);Group 3 and 4 MBs.These molecular alterations follow specific gene mutations and disease-risk stratifications.The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.However,the need to explore new therapies targeting specific receptors in MB microenvironment became essential.The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment,and their role are still under investigation.In this review,we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment,with an overview of the recent investigations and clinical trials.
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BACKGROUND The hemoglobin,albumin,lymphocyte,and platelet(HALP)score,derived from a composite evaluation of markers reflecting the tumor-inflammation relationship and nutritional status,has been substantiated as a noteworthy prognostic determinant for diverse malignancies.AIM To investigate how the HALP score relates to prognosis in patients with metastatic gastric cancer.METHODS The cutoff values for the HALP score,neutrophil/lymphocyte ratio,and platelet/lymphocyte ratio were determined using receiver operating characteristic analysis.Low HALP scores were defined as those less than 24.79 and high HALP scores as those greater than 24.79.RESULTS The study cohort comprised 147 patients and 110 of them(74.8%)were male.The patients'median age was 63(22-89)years.The median overall survival was significantly superior in the patients with high HALP scores than in those with low HALP scores(10.4 mo vs 7.5 mo,respectively;P<0.001)CONCLUSION The HALP score was found to be a prognostic factor in patients with metastatic gastric cancer.
基金supported by joint funds for the innovation of science and technology,Fujian province(2020Y9027)Fujian Natural Science Foundation(2020J011062)Medical Innovation Project of Fujian Provincial Health Commission(2021CXA004).
文摘Objective:To investigate the effects of bone marrow-derived mesenchymal stem cells(BMSCs)on the proliferation and secretion of IgM,IgG and IL-2 in spleen lymphocytes(L)of aging rats.Methods:BMSCs were isolated by the whole bone marrow adherence method and characterized.A rat model of aging was produced by daily subcutaneous injection of D-galactose into the back of the neck.Rat spleen lymphocyte isolate kit to isolate spleen lymphocytes from aging rats and young rats.In vitro,the co-culture system of BMSCs and aging rats lymphocytes was established,and under the induction of mitogen LPS and ConA,the proliferative activity of lymphocytes in each group was detected by CCK-8 assay,the levels of IgM and IgG in the culture supernatant of each group was detected by ELISA,and the IL-2 radioimmunoassay kits were used to detect the content of IL-2 in the supernatant of each group.Results:(1)The isolated adherent cells showed the characteristics of BMSCs,including spindle-shaped morphology,high expression of CD29,CD44,low expression of CD34 and CD45,and osteogenic/adipogenic ability.(2)Under LPS induction,lymphocyte proliferative activity and secretion of immunoglobulin IgG were reduced in the aging group compared with the young group,and co-culture with BMSCs reversed this trend.(3)Under ConA induction,the IL-2 content of BMSCs co-cultured with aging lymphocytes was higher than that of aging lymphocytes alone(P<0.0001);the IL-2 content of CsA co-cultured with aging lymphocytes was lower than that of aging lymphocytes alone(P<0.0001).Conclusion:BMSCs have immunomodulatory effects on the spleen lymphocytes of aging rats in vitro.
文摘Objective: Acute myeloid leukemia (AML) is a heterogeneous, hematologic malignancy at which short survival may be seen. Our study aims to evaluate the effect of the neutrophil-to-lymphocyte ratio (NLR) on the course of the disease, response to therapy, and overall survival (OS). Materials and Methods: A total of 124 patients followed-up with the diagnosis of AML from 2016 to 2019 were retrospectively examined. Results: 69 of the cases (55.6%) were men and 55 (44.3%) were women. The average age at the time of diagnosis was 53.44 ± 30.3 years old. We determined the NLR as median 0.46 (0.16 - 1.1). In AML, 69 patients were responsive to the induction regimen (57.9%) while 46 patients were unresponsive (37.8%). 5 patients died before completing the regimen. D-dimer was found to be higher and fibrinogen was found to be lower in the responsive group. Lower OS was observed in cases of >60 years of age, male gender, non-APL AML, high NLR, and recurrence at diagnosis. Recurrences were detected in 23 patients (18.5%) and the median time to the recurrence was 416 (236 - 639) days. Fibrinogen level and the bone marrow blast ratio at the time of application were determined to be associated with recurrence. The median follow-up time was 856 (143 - 1276) days. Final condition analysis reveals that 74 patients (59.6%) are alive. Conclusion: We determined in our study that the NLR is effective on survival. Medical literature on this subject is scanty and prospective studies with large patient groups are needed.
基金supported by the New Technology and New Project of Jinxiang Hospital Affiliated to Jining Medical University(No.JY2023026).
文摘Background:Colorectal cancer(CRC)is a common gastrointestinal malignancy.The T lymphocyte subsets are important in the develop-ment,invasion and metastasis of tumors,including CRC.Nevertheless,limited research has explored the relationship between T cell subpopu-lations and the clinical characteristics of CRC.This study compared the T lymphocyte subsets in patients with CRC and healthy individuals,and assessed the relationship between these values and clinical characteristics.Methods:Peripheral blood was collected from 100 patients with CRC and 54 healthy individuals.The numbers of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes,NK cells,and the CD4^(+)T/CD8^(+)T ratio in peripheral blood were measured using flow cytometry,and were compared between CRC patients and healthy individuals.Spearman's correlation analysis was performed to investigate the relationship between the T lymphocyte subsets in patients diagnosed with CRC and the levels of carcinoembryonic antigen(CEA)and thymidine kinase 1(TK1).Receiver operating characteristic(ROC)curves were utilized to evaluate the potential utility of the T lymphocyte counts in predicting lymph node metastasis,vas-cular infiltration,and high Ki-67 expression.Results:The CRC patients had lower counts of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes compared to the healthy population(P<0.05).However,no significant differences were observed in the CD4^(+)/CD8^(+)ratio or NK cells(P>0.05).Notably,the CD3^(+)T,CD4^(+)T,and CD8^(+)T lym-phocyte counts were higher in patients with stageⅠ-Ⅱdisease,no lymph node metastasis,no vascular invasion,and low Ki-67 expression than in those with stageⅢ,lymph node metastasis,vascular invasion,and high Ki-67 expression(P<0.05).There was a negative association be-tween the CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts and CEA and TK1 levels in patients with CRC.The ROC curves demonstrated that CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts had significant predictive value for lymph node metastasis,vascular infiltration,and high Ki-67 expression.Conclusions:The peripheral blood CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts are related to the clinical traits of patients with CRC and can predict the prognosis of the disease.
