Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.

Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

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.

Predictive Value of the Neutrophil to Lymphocyte Ratio (NLR) to Predict the Development of Preeclampsia and Pregnancy Induced Hypertension at 1st Trimester

Introduction: Hypertensive disorder in pregnancy affects 4 to 6 percent of all pregnancies and carries risks for the both baby and the mother. Only a few groups of women who are at high-risk pregnancies are received prophylaxis Aspirin, more than 15 percent of women develop pre-eclampsia with a single minor risk factor. Methods: This descriptive cross-sectional study was conducted to compare the 1st trimester NLR value of normotensive, pregnancy induced hypertensive and pre-eclamptic pregnant women. The study was conducted with a sample of 416, antenatal patients who were admitted to ward 25, at Colombo North Teaching Hospital Ragama. Data was collected as separated three groups. NLR value was calculated separately and ANOVA test was used to analyze the 3 categorical data. Post HOC test was done to assess the multiple comparison. Results: The prevalence rates of pregnancy induced hypertension and pre-eclampsia among the pregnant women were 8.6% and 5.7%. The mean NLR values of normotensive group was 2.708, pregnancy induced hypertensive group was 2.650 and pre eclamptic group was 3.789. There was a significant difference in NLR value between pre eclamptic group and other two groups with P value of Conclusion: The 1st trimester NLR value of pre eclamptic patients significantly increased compared to normotensive women.

Donor-derived CD 19 CAR-T Cells versus Chemotherapy Plus Donor Lymphocyte Infusion for Treatment of Recurrent CD 19-positive B-ALL after Allogeneic Hematopoietic Stem Cell Transplantation

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.

Hemoglobin, albumin, lymphocyte, and platelet score as a predictor of prognosis in metastatic gastric cancer

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.

免疫检查点抑制剂相关肺炎的危险因素及机制

免疫检查点抑制剂(Immune Checkpoint Inhibitors, ICI)是恶性肿瘤治疗的突破性进展。常见ICI包括细胞程序性死亡蛋白1(Programmed Cell Death Protein 1,PD-1)抑制剂、细胞程序性死亡配体1(Programmed Death-Ligand 1, PD-L1)抑制剂、细胞毒性T淋巴细胞相关蛋白4(Cytotoxic T-Lymphocyte-Associated Protein 4, CTLA-4)抑制剂。

Expression characteristics of peripheral lymphocyte programmed death 1 and FoxP3+ Tregs in gastric cancer during surgery and chemotherapy

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.

Effects of platelets on characteristics of lymphocytes cultured in vitro and optimization of adoptive immunotherapy

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.

Immune microenvironment of medulloblastoma:The association between its molecular subgroups and potential targeted immunotherapeutic receptors

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.

Tuberculosis-induced aplastic crisis and atypical lymphocyte expansion in advanced myelodysplastic syndrome:A case report and review of literature

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.

A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma:A retrospective study

Intravesical Bacillus Calmette Guerin(BCG)is the gold standard therapy for intermediate/high-risk nonmuscle invasive bladder cancer(NMIBC).However,the response rate is~60%,and 50%of non-responders will progress to muscle-invasive disease.BCG induces massive local infiltration of inflammatory cells(Th1)and ultimately cytotoxic tumor elimination.We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte(TIL)polarization in the tumor microenvironment(TME)in pre-treatment biopsies.Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG(n=32)were evaluated retrospectively by immunohistochemistry.TME polarization was assessed by quantifying the T-Bet+(Th1)and GATA-3+(Th2)lymphocyte ratio(G/T),and the density and degranulation of EPX+eosinophils.In addition,PD-1/PD-L1 staining was quantified.The results correlated with BCG response.In most non-responders,Th1/Th2 markers were compared in pre-and post-BCG biopsies.ORR was 65.6%in the study population.BCG responders had a higher G/T ratio and a greater number of degranulated EPX+cells.Variables combined into a Th2-score showed a significant association with higher scores in responders(p=0.027).A Th2-score cut-off value>48.1 allowed discrimination of responders with 91%sensitivity but lower specificity.Relapse-free survival was significantly associated with the Th2-score(p=0.007).In post-BCG biopsies from recurring patients,TILs increased Th2-polarization,probably reflecting BCG failure to induce a pro-inflammatory status and,thus,a lack of response.PD-L1/PD-1 expression was not associated with the response to BCG.Our results support the hypothesis that a preexisting Th2-polarized TME predicts a better response to BCG,assuming a reversion to Th1 polarization and antitumor activity.

Coexistence of diffuse large B-cell lymphoma,acute myeloid leukemia,and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient:A case report

BACKGROUND The Coexistence of myeloid and lymphoid malignancies is rare.Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies.Synchronous diagnoses of diffuse large B-cell lymphoma(DLBCL),acute myeloid leukemia(AML),and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia(LPL/WM)in the same patient have not been reported.Here we report one such case.CASE SUMMARY An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL.The bone marrow and peripheral blood contained two groups of cells.One group of cells fulfilled the criteria of AML,and the other revealed the features of small B lymphocytic proliferative disorder,which we considered LPL/WM.Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells,including ATM deletion,CCND1 amplification,mutations of MYD88(L265P)and TP53,WT1 overexpression,and fusion gene of BIRC2-ARAP1,as well as complex chromosomal abnormalities.The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis.CONCLUSION The coexistence of DLBCL,AML,and untreated LPL/WM in the same patient is extremely rare,which probably results from multiple steps of genetic abnormalities.Asymptomatic LPL/WM might have occurred first,then myelodysplastic syndromerelated AML developed,and finally aggressive DLBCL arose.Therefore,medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.

The immunomodulatory effects of bone marrow-derived mesenchymal stem cells on lymphocyte in spleens of aging rats

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.

Therapeutic Effect of Daphnetin on Mastitis Induced by Staphylococcus aureus in Mice

[Objectives]To observe the effects of daphnetin on mastitis induced by Staphylococcus aureus in mice.[Methods]18 postpartum ICR female mice were used to establish mastitis animal model,and were randomly divided into three groups(A,B,and C)with 6 mice in each group.Group A:blank control group;group B:S.Aureus model group;group C:S.Aureus model+daphnetin group.The experimental groups were injected 1 mL of 1.0×104 CFU/100μL of S.aureus of along the nipple catheter.The suspension was placed in the 3 rd and 4 th pairs of mammary glands,and the control group was injected with the same dose of normal saline.On the second day after infection,the rats in group A,B and C were given drugs by gavage,while the rats in group A and B were given normal saline and the rats in group C were given daphnetin once a day for 6 consecutive days.Blood samples were collected from living eyeballs,and blood cells were analyzed by automatic flow cytometer after anticoagulation.[Results]The NLR and Systemie Immune Inflammati-on Index(SII)in the blood of mastitis mice induced by S.aureus were significantly higher than those in the control group(P<0.01),suggesting that neutrophil to lymphocyte ratio(NLR)and SII can be used as diagnostic indicators of mastitis,and the levels of NLR and SII decreased significantly after daphnetin intervention.[Conclusions]NLR and SII showed high levels in mastitis mice,which are valuable for the diagnosis of mastitis and the evaluation of its prognosis.After the intervention of daphnetin,both of them decreased significantly,indicating that daphnetin has a good prognosis trend in mastitis mice induced by S.aureus.

Association of T lymphocyte subset counts with the clinical features of colorectal cancer

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.

Prognostic Value of Neutrophil to Lymphocyte Ratio in Acute Myeloid Leukemia

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.

Haematology Parameters of Apparently Healthy Prospective Whole Blood Donors in a Nigerian Hospital Setting

Background: Adequate selection of a prospective whole blood donor protects his health and safety of the recipient. Objectives: The main objective of this study was to determine the haematology parameters of apparently healthy prospective whole blood donors. Participants and Methods: This was a hospital based prospective study carried out from August to October 2020 at the blood transfusion unit of the Lagos State University Teaching Hospital (LASUTH), Ikeja, Nigeria. A structured pretested questionnaire was used for data collection. The socio demographic status and the haematology parameters of apparently healthy prospective whole blood donors who tested negative for HIV, hepatitis B and C markers were captured. Obtained data were analysed with the statistical package for the social scientist software version 20. Results: One hundred male (97.1%) and three female (2.9%) apparently healthy prospective whole blood donors were studied. The median age of study subjects was 30 years. Obtained median haematology parameter values were 13 g/dl, 40%, 4.9/nl and 203.9/nl for haemoglobin concentration, haematocrit, total white cell and platelet counts respectively. The median values for the mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) of participants were 32.6 g/dl, 27.7 pg and 85.7 fl respectively. Observed prevalence of subnormal haematology parameters for haemoglobin concentration, total white cells, platelets were 12.6%, 25.2%, and 13.6% respectively. Also subnormal values for MCHC, MCH, MCV were 11.7%, 26.2%, and 16.5% respectively among prospective whole blood donors in this study. No higher than normal haematology parameter values were observed. Median values for erythrocyte sedimentation rate was 8.4 mm/hr. Conclusion: A significant percentage of apparently healthy prospective whole blood donors had subnormal haematology parameters values. Obtained normal values in our study are comparable with local reference range reports from previous studies in Nigeria and other parts of Africa. 124947 .

尾静脉注射和鼻腔接种禽流感H5N1亚型病毒对血细胞的影响

[目的]Balb/c小鼠通过尾静脉注射和鼻腔接种禽流感H5N1亚型病毒造疾病模型,观察其血细胞变化。[方法]以禽流感H5N1亚型病毒通过静脉和鼻腔接种Balb/c小鼠,分别在0~7天和0~11天取血进行血细胞计数和分类,同时对于静脉接种方法进行了0~8小时的短时间监控。[结果]静脉接种途径在接种病毒后2小时就能显著的降低小鼠的白细胞总数、粒细胞及淋巴细胞数,白细胞总数及淋巴细胞数在第3天、粒细胞数在第2天就恢复正常而后均显著升高;而鼻腔接种仅在1~3天淋巴细胞有所降低,而后恢复正常;1~6天白细胞总数及粒细胞数显著升高,而后恢复正常。[结论]从血细胞变化而言,静脉接种相比鼻腔接种方法要好。

免疫检验点:肿瘤免疫治疗的新视点

随着免疫生物学的不断发展，免疫检验点将逐渐成为新的视点，在促进肿瘤逃逸中有着非常重要的作用，促使了新型免疫治疗的发展，主要包括CTLA?4（cytotoxicT?lymphocyte?associatedprotein4，CD152）和PD-1/PD-L1（programmedcelldeathprotein1，CD279；programmeddeath?ligand1，CD274/B7?H1）的免疫检验点的研究［1-2］。传统的抗肿瘤治疗，如化疗、放疗及靶向治疗的目的都是杀死癌细胞，然而，抗肿瘤治疗的疗效不仅取决于它们对于肿瘤细胞的直接效应，还取决于宿主细胞免疫系统的脱靶效应。

阿特珠单抗联合白蛋白结合型紫杉醇治疗晚期三阴性乳腺癌的Ⅲ期临床试验——IMpassion130研究解读

【简评】乳腺癌一直被认为是低免疫原性的“冷肿瘤”,因此免疫疗法在乳腺癌中乏善可陈。三阴性乳腺癌(triple-negative breastcancer,TNBC)是一种特殊亚型,治疗方案有限却又极具侵袭性。越来越多的研究发现,TNBC肿瘤突变负荷较大,肿瘤细胞免疫检查点程序性死亡[蛋白]-1(programmeddeath-1,PD-1)表达量较高,肿瘤微环境中富含肿瘤浸润淋巴细胞(tumor-infiltrating lymphocyte,TIL),故推测其可能是一种对免疫积极应答的“热肿瘤”。IMpassion130是全球首个在晚期TNBC患者中获得阳性结果的Ⅲ期免疫治疗临床试验,结果令人鼓舞。