Features of gene mutations and its correlation with the therapeutic efficacy by using whole exome sequencing in acute myeloid leukemia / 白血病·淋巴瘤

Objective:To investigate the characteristics of gene mutation by using whole exome sequencing (WES) and its relationship with therapeutic efficacy in patients with acute myeloid leukemia (AML).Methods:The data of 30 patients with AML from the Second Hospital of Anhui Medical University between December 2014 and September 2019 were retrospectively analyzed; the result of WES, disease type and classification, genetic prognostic stratification and therapeutic efficacy were summarized. The mutation types and mutation frequency of AML patients stratified by the different clinical characteristics and genetic prognosis were compared.Results:Among 30 AML patients, 26 cases (86.7%) had 1 gene mutation at least. The genes with a mutation frequency more than 10.0% were NRAS, RUNX1, TET2, CEBPA, IDH2 and ASXL1. The function of the mutated genes was involved in signaling pathways, transcription factors, epigenetics, and RNA splicing and other biological functions; in terms of mutation pattern, 19 cases (63.3%) of all AML patients mainly presented combined mutations of many combinations. There were no significant differences in mutation rates among age, gender, disease type, disease classification and genetic prognosis stratification groups (all P > 0.05). Of the 8 fusion gene positive cases, 7 were mutated, the average mutation frequency was 175.0% (14/8). There were 19 mutations in 22 patients with negative fusion gene, the average mutation frequency was 213.6% (47/22), and the difference in mutation frequency between the two groups was statistically significant ( P = 0.001). Of the 14 cases of continuous remission, 11 had mutations, with average mutation frequency of 157.1% (22/14); there were 9 cases of mutations in 10 relapsed patients, and the average mutation frequency was 200.0% (20/10); mutations occurred in 5 patients with primary drug resistance, and the average mutation frequency was 300.0% (15/5); and the difference of mutation frequency among the three groups was statistically significant ( P = 0.009). Conclusions:Through WES analysis, it is found that most AML patients have complex and variable gene mutations; and the higher the gene mutation frequency is, the worse the prognosis of the disease is.

Acute promyelocytic leukemia combined with hereditary fibrinogen deficiency: report of one case and review of literature / 白血病·淋巴瘤

Objective:To improve the clinical recognition of hereditary fibrinogen deficiency.Methods:The diagnosis and treatment process of a patient with acute promyelocytic leukemia (APL) complicated with hereditary fibrinogen deficiency who was admitted to the second Affiliated Hospital of Anhui Medical University in December 2018 was retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was initially diagnosed as APL, and the complete remission was obtained after dual-induction therapy of all-trans retinoid acid and arsenous acid. During the first consolidation treatment, repeated reviews of fibrinogen fluctuated between 1.0-1.5g/L, and further improving the fibrinogen gene sequencing to diagnose APL combined with hereditary fibrinogen deficiency.Conclusion:For APL patients in remission who have decreased fibrinogen for many times and patients with hereditary fibrinogen deficiency who have significantly decreased fibrinogen in a short period, bone marrow biopsy and genetic testing should be further conducted to determine the pathogenesis.

Skin recurrence after remission of primary nasopharyngeal myeloid sarcoma: report of one case and review of literature / 白血病·淋巴瘤

Objective:To improve the awareness of primary myeloid sarcoma.Methods:The clinical data of one primary myeloid sarcoma patient with first symptom involving nasopharynx who was admitted to the Second Affiliated Hospital of Anhui Medical University in June 2017 were retrospectively analyzed, and the related literature was reviewed.Results:The patient presented with nasal congestion with tinnitus; it took half a year for the myeloid sarcoma diagnosis to be clear with biopsy and immunohistochemical examinations for many times. The patient was treated with chemotherapy regimens for acute myeloid leukemia (AML). Isolated myeloid sarcoma relapsed with skin masses after remission for more than 2 years. Further improvement of the bone marrow-related examinations showed that the bone marrow was not involved, and it was still isolated myeloid sarcoma. The skin mass disappeared completely after the induction chemotherapy of AML. Six months after the recurrence, the patient was in stable condition and was still under follow-up treatment.Conclusions:The primary nasopharyngeal myeloid sarcoma lacks specificity and is easy to be misdiagnosed. The prognosis of isolated myeloid sarcoma is better than that of AML. Isolated recurrence after chemotherapy remission is rare, and usually progresses to the leukemia stage quickly. Early and correct diagnosis is very important for the prognosis, and clinicians should improve the awareness of primary myeloid sarcoma.

Chimeric antigen receptor T-cell therapy for relapsed/refractory acute B-cell lymphoblastic leukemia with T315I mutation: report of one case and review of literature / 白血病·淋巴瘤

Objective:To explore the safety and efficacy of chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory acute B-cell lymphoblastic leukemia (B-ALL) with T315I mutation.Methods:The clinical data of a patient with relapsed/refractory B-ALL with T315I mutation who underwent CAR-T therapy in the Second Affiliated Hospital of Anhui Medical University was analyzed, and the related literature was reviewed.Results:The patient was a 34-year-old man. He was diagnosed with chronic myelogenous leukemia (CML) in January 2017 and started to take imatinib orally. However, the primary affection transformed to B-ALL 4 months later. Because of the E355G gene mutation, the treatment drug was adjusted to dasatinib, and induction chemotherapy was given at the same time. The sequential consolidation chemotherapy was given for 3 times after complete remission (CR). After half a year of remission, T315I mutation was detected and re-induced chemotherapy was given, but ineffective. The patient was treated with CAR-T 3 days after FC regimen (fludarabine 30 mg/m 2 per day, day 1 to day 3; cyclophosphamide 200 mg/m 2, day 1 to day 3). The number of CD19 CAR-T was 1.0×10 9, 98% activity degree. Grade 1 cytokine-releasing syndrome appeared after infusion, and was resolved after symptomatic treatment. No serious adverse reactions were observed. CR was achieved half-month after CAR-T treatment, and umbilical cord blood transplantation was successfully performed 1 month later. At the last follow-up, the relapse-free survival time of the patient was 396 days. Conclusion:CAR-T therapy may be a new, safe and effective therapy for patients with relapsed/refractory B-ALL with T315I mutation.

High calcium risk in patients with diffuse large B-cell lymphoma during the chemotherapy: report of one case and review of literature / 白血病·淋巴瘤

Objective@#To improve the understanding of high calcium risk in patients with diffuse large B-cell lymphoma (DLBCL) during the chemotherapy.@*Methods@#The diagnosis and treatment of high calcium risk in one patient with DLBCL during the chemotherapy in the Second Affiliated Hospital of Anhui Medical University was retrospectively analyzed, and the relevant literatures were reviewed.@*Results@#A 52-year-old man who was diagnosed with DLBCL (non-specific, non-germinal center source; stage Ⅳ group A; International prognosis index score 4 points, high-risk group) in June 2017. Two times R-CHOP chemotherapy was performed before diagnosis. This patient was admitted to the hospital for the third chemotherapy, and the disease assessment showed that the enlarged lymph nodes were not significantly smaller than before, and the tumor burden was still high. Therefore, the chemotherapy regimen was adjusted to R-GDP regimen. However, on the 8th day after the end of rituximab treatment, the patient had head pain, which might be related to the patient's poor sleep and primary invasion of the primary disease (blood calcium: 2.94 mmol/L). And then the ibuprofen and diuresis treatments were given, but the symptoms were still gradually worsening, and vomiting appeared on the 9th day, systemic fatigue with drowsiness and irritability appeared on the 12th day. Review blood calcium: 5.02 mmol/L. Adequate fluid hydration, diuretic, renal replacement treatments were given, and the level of blood calcium gradually returned to normal. Finally, the patient's symptoms were improved significantly, and he successfully completed R-GDP chemotherapy.@*Conclusion@#If a DLBCL patient has symptoms such as headache, lethargy, irritability or even coma during the chemotherapy, it is necessary to alert the possibility of hypercalcemia and to timely improve the relevant examination and make symptomatic treatment.

Value of Red Cell Distribution Width in the Prognosis of Patients with Multiple Myeloma / 现代检验医学杂志

Objective To investigate the relationship between red blood cell distribution width (RDW) and prognosis in patients with multiple myeloma (MM).Methods The population that studied consisted of 27 patients with multiple myeloma and 30 healthy controls.The RDW was calculated according to the results of blood routine examination and compared between patients and healthy controls.Then,compared the difference between the two groups of RDW.MM patients were treated with international standard staging (ISS),and the differences of RDW in different stages were analyzed.ISS staging was used to draw the receiver operating curve (receiver operating characteristic curve,ROC curve),then take RDW14.65 ％ as the best cut-off point,the MM patients were divided into low RDW group (RDW=14.65 ％) and high RDW group (RDW ＞14.65％).Overall survival (OS) condition were compared between the above two groups.The impacts of RDW on OS were analyzed by Kaplan-Meier and Log-rank test.Results The average RDW value in experimental and controlled were 15.60 ％ ± 2.35 ％ vs 12.72 ％ ±0.61 ％ separately (t=6.201,P＜0.001),with statistical differences.The average RDW value in low ISS(Ⅰ + Ⅱ stage) and high ISS (Ⅲ stage) were 13.99 ％ ± 1.08％ vs 16.55 ％±2.39％ separately (t=3.800,P=0.001).The median survival time of low RDW and high RDW group was 13 months and 8 months respectively,and the difference was statistically significant (x2=6.481,P =0.011).Conclusion RDW increased in patients with MM,the risk stratification higher prognosis is worse.

Research progress of T cells expressing CD123 chimeric antigen receptor for treatment of AML / 中国药理学通报

Acute myeloid leukemia ( AML) is the most common acute leukemia in adults and has the highest death rate of all leukemias. Compared with other hematologic malignancies , there was only a small increment in the 5-year relative overall survival for patients with AML in the last 40 years, despite the advancement in our understanding of AML .CD123 is an AML-associated antigen that expresses at a high level in leukemic stem cells and leukemic blasts and a low level in normal hematopoiet-ic stem cells.As an attractive surface target for AML therapies , immune-based therapies targeting CD 123 are being developed re-cently, especially chimeric antigen receptor ( CAR) T-cell-based immunotherapy .Preclinical data have demonstrated that CD 123 CAR-T cells exhibit potent antileukemic activity and various im-pacts on normal hematopoiesis .This will probably be a promis-ing treatment for patients with relapsed/refractory AML.

Neutrophil to lymphocyte ratio and its relationship with the chemotherapy effect and the prognosis in patients with diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective To explore the neutrophil to lymphocyte ratio (NLR) and its relationship with the effect of chemotherapy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL).Methods The clinicopathological characteristics and outcome of 51 patients with DLBCL diagnosed by pathological biopsy and immunohistochemistry who received CHOP or R-CHOP regimen were collected and reviewed.According to the median of NLR,the patients were divided into low NLR group (NLR≤2.32) and high NLR group (NLR＞2.32).The prognostic influence of the NLR on overall survival (OS) was studied by Kaplan-Meier method and Log-rank test.To evaluate the independent prognostic relevance of NLR,univariate and multivariate Cox regression models were applied.Results The complete response (CR) rates of the low and high NLR groups were 71.4 ％ (20/28) and 39.1％ (9/23),respectively (P =0.02).The OS in the low NLR group was significantly better than that in the high NLR group (1,2 and 3-year OSs were 96.4 ％,90.4 ％ and 72.3 ％ vs 63.9 ％,52.7 ％ and 42.2 ％,respectively,P =0.009).Univariate and multivariate Cox regression models analysis showed that NLR ＞ 2.32 was an independent prognostic factor (P =0.016).Conclusion An elevated NLR before treatment indicates the poor effect of chemotherapy and prognosis of patients.NLR is an independent prognostic factor for DLBCL.

Diagnostic value of flow cytometry in aggressive natural killer-cell leukemia: a case report and review of literatures / 白血病·淋巴瘤

Objective To explore clinical characteristics and diagnosis of aggressive natural killercell leukemia (ANKL),and evaluate the value of flow cytometry (FCM) in diagnosing it.Methods A case of ANKL was reported and literatures were reviewed.Results The patient presented with persistent high fever,progressive pancytopenia and hepatosplenomegaly.The untypical cells could be seen by morphology.By FCM,NK cells consisted 83.3 ％ of total lymphocytes in bone marrow and immunophenotypes were CD34-,CD2+,CD7+,CD3-,CyCD3+,CD5-,CD16+,CD56+,CD30-,CD4-,CD8-,CD117-,CD11c,CD19-,CD45++,SSC+-++.T-cell receptor (TCR) and IgH gene rearrangement were negative and chromosome was normal.The patient was diagonised ANKL eventually.Conclusions ANKL is a quite rare disease with highly aggressive,poor prognosis and could be misdiagnosed easily.FCM combined with morphology is a convenient,handy,practicable and less invasive device for the diagnosis,and can be a preferred detection technique in some cases.

The expression features and clinical significance of CD4+ CD25+ regulatory T cells in elderly patients with acute myelocytic leukemia / 中华老年医学杂志

Objective To investigate the expression features and clinical significance of CD4+ CD25+ regulatory T cells in elderly patients with newly diagnosed acute myelocytic leukemia.Methods Totally 65 patients newly diagnosed as acute myeloid leukemia (AML group) and 72 healthy volunteers (control group) were divided into the elderly group (aged over 60 years) and the young group aged (44.6±2.9) years.The expression of CD4+ CD25+ regulatory T cells was detected by CD4,CD25 and CD127 three-color fluorescein-labeled and multiparameter flow cytometry.The expression features and clinical significance of CD4+ CD25+ regulatory T cells in each group were analyzed.Results After being gated on CD4+ lymphocytes,the expression level of CD4+ CD25+regulatory T cells was significantly increased in AML group as compared to control group [(7.06±2.60) ％ vs.(5.61 ± 1.06) ％,t =4.19,P=0.000].The expression level of CD4 + CD25 + regulatory T cells was higher in elderly AML patients than in elderly controls [(7.55 ± 2.78)％ vs.(5.98 ±1.08) ％,t=3.42,P=0.001].The expression of CD4+ CD25+ regulatory T cells was higher in young AML patients than in young controls [(6.09±1.91)％ vs.(5.14±0.82)％,t=2.21,P=0.036].The expression level of CD4+ CD25+ regulatory T cells was higher in elderly AML patients than in young AML patients [(7.55±2.78)％ vs.(6.09±1.91)％,t=2.19,P=0.032].Conclusions The dual roles of immunosenescence and tumor may cause the excessive accumulation of CD4+ CD25+regulatory T cells in elderly patients with newly diagnosed acute myeloid leukemia.

Clinical significance of detecting Cyclin D1 and bcl-2 using flow cytometry in the diagnosis of B-cell lymphoma / 白血病·淋巴瘤

Objective To explore the feasibility and significance of detecting Cyclin D1 and bcl-2 with flow cytometry in the diagnosis of B-cell lymphoma.Methods 45 patients patients with confirmed hematologic diseases in final diagnosis were collected and recorded 45 cases in detail included in the study.25 healthy persons showing normal results in routine physical examinations and laboratory tests were also selected and matched according to the age and gender.In addition,according to the age and gender matching principle,selected routine physical examination and all tests were within the normal range in 25 healthy persons as a healthy control group.Select the pathologically confirmed Cyclin D1 or bcl-2 positive cases were selected as the positive control group,select and the negative cases as the negative control group.Four-color monoclonal antibodies directly immunofluorescence monoclonal antibody labelinged with immunofluorescence were used to analyze the surface and cytoplasmic antigens,and multi-parameter flow cytometry was used to investigate the peripheral blood Cyclin D1 and bcl-2 subsets in lymphoma patients.Results The normal values of Cyclin D1 MFI and bcl-2 were obtained from the 25 normal volunteers by analyzing the (x)±s values and 95 ％ confidence interval,thus establishing the diagnostic criteria.Compared to the healthy control (0.356±0.159,1.938±0.324),all B-cell lymphoma patients had increased expression in Cyclin D1 (1.824±0.312)and bcl-2 MFI (4.259±0.541) in their peripheral blood,results showing statistical significance (P ＜ 0.01).Patients with different subtypes of lymphoma expressed differing Cyclin D1 MFI.In patients with Hodgkin' s lymphoma,Cyclin D1 MFI (0.386±0.112) was significantly lower than that in the non-Hodgkin' s lymphoma patients (1.623±1.987) (P ＜ 0.01).Further,in non-Hodgkin' s lymphoma patients,mantle cell lymphoma was 100 ％ positive for Cyclin D1,while the remaining subtypes were negative.Patients with different subtypes of lymphoma also showed differences in bcl-2 expression.In the Hodgkin' s lymphoma,bcl-2 (2.045±0.877) was significantly lower than the non-Hodgkin' s lymphoma (4.045±0.499) (P ＜ 0.01).In non-Hodgkin' s lymphoma,T cell lymphoma expressed the lowest,while MCL and FL showed 100 ％ positivity.In patients with positive Cyclin D1 or bcl-2,the mean fluorescence intensity level of Cyclin D1 (before treatment 3.099±0.349; after treatment 1.008±0.279) or bcl-2 (before treatment 7.814± 1.030,after treatment 3.131±0.522) was significantly lowered after treatment (P ＜ 0.01).Conclusion Using the method of flow cytometry for detecting Cyclin D1 and bcl-2 in lymphoma cells is feasible,and it can be applied clinically to evaluate the treatment.

Relapse presenting as granulocytic sarcoma without bone marrow involvement in acute myeloid leukemia with complete remission: a case report and review of literature / 白血病·淋巴瘤

ObjectiveTo explore clinical characteristics and diagnosis of patients with granulocytic sarcoma (GS),and to evaluate the value of FCM in diagnosing it.MethodsClinical data of one patient with GS was reviewed and related literature was reviewed. ResultsThe patient was diagnosed as AML-M2,chromosomal karyotype was 46.XY, t (8;21)(q22;q22)and the AML/ETO gene was positive. Systemic chemotherapy with daunorubicin plus cytarabine was given and complete remission was received. Then a nodular in medial angle of right eye was found. Result of CT indicated the possibility of leukemia infiltration.Needle aspiration cytology was conducted and many blast cells were found by microscope.CD34+ CD117+ CD13+ CD33+CD45dim SSC+ can be found by FCM. The cytology was complete remission and minimal residual disease was negative. Finally diagnosis was GS, relapse of AML. After a systemic chemotherapy with large dose of cytarabine plus teniposide (cytarabine 6.0 g/d, d1-3;teniposide 50 mg/d, d1-3), the mass could not be touched and the follow-up was continued.Conclusion Although relapse of AML often occurs in the testicle or the central nervous system,it pay attention to the possibility of relapse of AML presenting as GS.Fine needle aspiration cytology(FNAC)combined with FCM can provide an convenient, handy, practicable and less invasive way of the diagnosis and can be a preferred detection technique.

Retrospective analysis of t (8;21) acute myeloid leukemia patients with MICM classification / 白血病·淋巴瘤

Objective To study the significance of morphologic, immunophenotype, cytogenetic features, molecular biology (MICM) and prognosis of t (8;21) acute myeloid leukemia (AML) patients.Methods Morphological, FAB subtypes, flow cytometric immunophenotyping, G-binding technique and RTPCR were performed in 70 AML patients with t (8;21) and AML1-ETO fusion transcripts as compared with normal karyotype 70 AML patients. Results In 70 AML patients with t(8;21), 1 case of M1, 64 cases of M2, 3cases of M4 and 2 cases of ambiguity AL according to FAB classification. The CD13, CD33, CD34 and CD117expression were higher, meanwhile CD19 was positive in 40 %, CD15 was 11%, CD11b was 10 % and CD7 was 7 %. Cytogenetically, 50 % cases had additional chromosomal abnormalities, and main associated recurrent additional abnormalities were loss of a sex chromosome, 9q- and hyperdiploid. AML1/ETO fusion gene transcripts were detected in all 70 AML patients with t(8;21) by RT-PCR. CR rate of t(8;21) AML with CD19were 72 %, t(8;21) AML with CD19 and CD7 were 0; in normal karyotype AML were 31%. Conclusion The t(8;21) is the characteristic chromosome abnormality of M2. In the t(8;21), CD19, CD34 and CD117 expression are high, while CD7 are low. These antigen expression in t(8;21) AML closely correlated with karyotype. CD19 is a marker of good prognosis, but CD7 is a marker of low CR.

DNT cells isolated and identified in the peripheral blood and its content detection / 国际外科学杂志

Objective The immune magnetic separation(MACS)method of DNT cells was set up and their content Was detected in peripheral blood of healthy man.Methods DNT cells were separated from the peripheral blood.Trypan blue staining and flow cytometry were used to detect their activity and purity,and flow cytometry Was used to detect their content in normal human peripheral blood.Results DNT cell activi ty using MACS sorting was＞97%,the purity Was 82.77%;DNT cells accounted for(6.25±2.61)% (n=45)in the TCRαβ+T cells.Conclusion MACS Can quickly sort out high purity DNT cells,and do not affect the vitality of cells.DNT cells accounted for(6.25±2.61)%in the TCRCD3+T cells.

Relationship of CD_4~+ CD_(25)~+ regulatory T cells and acute myeloid leukemia / 白血病·淋巴瘤

Objective To investigate the proportion of CD_4~+ CD_(25)~+ Tregs in the peripheral blood of the patients suffering from acute myeloid leukemia (AML) with or without chemotherapy and clinical significance.Methods The flow cytometry was used to evaluate the proportion of CD_4~+ CD_(25)~+ CD_(127)~(low) T cells in the peripheral blood of the patients with primary AML group (group A), AML who achieved complete remission over 3 years (group C) or less than 3 years(group B) and the healthy donors. Results The percentages of CD_4~+ CD_(25)~+ Tregs of group A and B was significantly higher than that of control group (P 0.05). The percentages of CD_4~+ CD_(25)~+ Tregs of group A was significantly higher than that of group B and C. Conclusion These results suggested that CD_4~+ CD_(25)~+ Tregs played an important role in acute myeloid leukemia.

Clinical analysis of mixed acute leukemia / 白血病·淋巴瘤

Objective To analyze the clinical and biological features of mixed acute leukemia(MAL).Methods Bone marrow specimens of 38 MAL patients were evaluated to prove the diagnosis and the classification by morphoiogic,immunologic examinations.These patients were treated with protocols suitable for both acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL).Results All MAL patients had a leukemia syndrome.Morphologically,the subtypes of M1,M2 and M5 were predominant in AML,as L2 Was in ALL.Immunologically,coexpression of myeloid and B lineage associated antigens was predominant,about 68.4%;cytogenetically,Ph chromosome was observed in 33.3%(5/15)of MAL patients,and immunophenotype was B-M;1 Ph chromosome(+)MAL patient,fusion gene bcr-abl 190(+)and immunophenotype was B-M.In 38 cases,32 patients received chemotherapy.The complete remission rate was 28.1%(9/32).CR of.normal karyotype was significantly higher than that of abnormal ones.Conclusion Patients with MAL have unique biological features and the complete remission rate was low and the prognosis was poor.

Clinical significance of CD4+CDHi25 regulatory T cells in childhood acute leukemia / 白血病·淋巴瘤

Objective To evaluate the proportion and clinical significance of CD4+CD25+ regulatory T cells in childhood acute lymphocyte leukemia(AEL)during different therapeutic stages.Methods 55 peripheral blood samples from 40 children patients with ALL were detected by muhiparameter flow cytometry with fluoresce-hbeled monoclonal antibody.Results Treg cells phenotypically express not only CD62L but also FoxP3 protein.In patients with ALL standard-risk the proportion of CD4+CD25Hi was(1.04±0.33)% in the first course of induction treatment, (1.60±0.44)% in maintenance treatment groups, and(1.29±0.30)% in complete remission groups respectively,while in patients with ALL the intermediate and high risk during maintenance therapy was(2.24±0.75)%.Conclusion Compared with healthy children,the proportion of Treg ceHs in ALL is significantly higher,and may be related to the effect of chemical treatment and severity of ALL.The elevated proportion of Treg may contribute to disease relapse.

The frequency and clinical significance of CD4+CD25+ regulatory T cells in peripheral blood from elderly tumor patients / 中华老年医学杂志

Objective To investigate the relationship between CD4+CD25+ regulatory T(T-Reg)ceils and the higher prevalence of tumor in elderly people. Methods The frequencies of T-Reg in peripheral blood from 64 health adults.52 healthy elderly people and 64 elderly cancer patients were determined by multi-color detection and multi-parameter flow cytometry.and the relationships among the 3 groups were analyzed and the correlation among CD4+CD25high,CD4+CD25+FoxP3+and CD4+CD25+CD127low were studied. Results Be gated on CD4+ lymphocytes,the reference ranges of CD4+CD25high T cells in the groups of health adults.healthy elderly people and elderly cancer patients were(1.390±0.412)%,(1.729±0.247)%and(2.150±O.769)%respectively,while CD4+CD25+FoxP3+ T cells were(1.1 80±0.343)%,(2.477±0.400)%and (4.980±2.177)%respectively,and CD4+CD25+CD127low T cells were(5.213±0.942)%,(6.186±1.196)%and(7.194±1.538)%respectively.There was the same change rule in CD4+CD25high,CD4+CD25+FoxP3+and CD4+CD25+CD127low T cells of the 3 groups.elderly cancer patients was at the highest.then was healthy elderly people,and the last was health adults.The 3 markers were positively correlated among 3 groups(all P＜0.05).There were gender difference in 3 groups of CD4+CD25high,CD4+CD25+FoxP3+ and CD4+CD25+CD127low T cells. Conclusions The percentages of CD4+CD25high are increased with age and its excessive accumulation is possibly correlated with immunosenescence and the tumor development.

Novel link between E2F1 and Smac/DIABLO: proapoptotic Smac/DIABLO is transcriptionally upregulated by E2F1.

Deregulated expression of E2F1 not only promotes S-phase entry but also induces apoptosis. Although it has been well documented that E2F1 is able to induce p53-dependent apoptosis via raising ARF activity, the mechanism by which E2F induces p53-independent apoptosis remains unclear. Here we report that E2F1 can directly bind to and activate the promoter of Smac/DIABLO, a mitochondrial proapoptotic gene, through the E2F1-binding sites BS2 (-542 approximately -535 bp) and BS3 (-200 approximately -193 bp). BS2 and BS3 appear to be utilized in combination rather than singly by E2F1 in activation of Smac/DIABLO. Activation of BS2 and BS3 are E2F1-specific, since neither E2F2 nor E2F3 is able to activate BS2 or BS3. Using the H1299 ER-E2F1 cell line where E2F1 activity can be conditionally induced, E2F1 has been shown to upregulate the Smac/DIABLO expression at both mRNA and protein levels upon 4-hydroxytamoxifen treatment, resulting in an enhanced mitochondria-mediated apoptosis. Reversely, reducing the Smac/DIABLO expression by RNA interference significantly diminishes apoptosis induced by E2F1. These results may suggest a novel mechanism by which E2F1 promotes p53-independent apoptosis through directly regulating its downstream mitochondrial apoptosis-inducing factors, such as Smac/DIABLO.

Pathogens Caused Acute Respiratory Tract Infection in Hefei Area:Epidemiological Studies / 中华医院感染学杂志

OBJECTIVE To investigate the etiology of acute respiratory tract infection(ARI)in Hefei area and risk factors that may influence the distribution of common pathogens.METHODS Direct immunofluorescence assay was applied to detect the respiratory syncytial virus(RSV),adenovirus(ADV),influenza virus A(FluA),influenza virus B(FluB),parainfluenza virus PIV(1,2,3)and real time fluorescent quantitation polymerase chain reaction (FQ-PCR)was applied to measuring Mycoplasma pneumoniae(MP)and Chlamydia pneumoniae(CP)in nasopharyngeal secretions and sputum specimens.RESULTS Among 530 cases included in this study,421 cases (79.43%)showed positive viral etiology.ADV accounted for 73(13.77%),FluA-68(12.83%),FluB-56 (10.56%),RSV-48(9.05%),PIVl-47(8.86%),PIV3-42(7.92%),PIV2-33(6.22%),MP-32(6.03%)and CP-22(4.15%).The detected positive rate of pathogens isolated in winter was the highest(85.07%).CONCLUSIONS Acute upper respiratory tract infection(AURTI)is common and more than 75%pathogens in Hefei area are virus in which the most commonly virus is ADV.Meanwhile atypical pathogens of infection should not be ignored.