Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

3,4,5-Trimethoxycinnamic acid, one of the constituents of Polygalae Radix exerts anti-seizure effects by modulating GABAAergic systems in mice.

Polygalae Radix is an important medicinal plant that is widely used in most of Africa. 3,4,5-Trimethoxycinnamic acid (TMCA) is one of the constituents of Polygalae Radix. Until now, the mechanisms involved in the anti-seizure property of TMCA are still unclear. We examined the anti-seizure effect of TMCA. TMCA administered at doses of 5, 10 and 20 mg/kg and evaluated anti-seizure effects by maximal electroshock (MES) and pentylenetetrazol (PTZ) models in mice. TMCA administered at doses of 10 and 20 mg/kg significantly reduced the incidence of MES-induced tonic hindlimb extension (THE). TMCA significantly delayed the onset of myoclonic jerks (MJ), and decreased the seizure severity and mortality compared with the vehicle-treated animals in PTZ seizure model. TMCA 10 and 20 mg/kg treated groups also did not determined generalized clonic seizures (GCS). Pretreatment with a GABAA/benzodiazepine (BZ) receptor antagonist flumazenil blocked the anti-seizure effects of TMCA. These data support the further investigation of TMCA as a GABAA/BZ receptor agonist for anti-seizure therapy.

Efficacy and Safety of Danshen Compound Tablets in Preventing Thalidomide-Associated Thromboembolism in Patients with Multiple Myeloma: A Multicenter Retrospective Study.

BACKGROUND Currently available antithrombotic prophylaxis is not perfectly reliable in elderly patients. The aim of this retrospective study was to evaluate the efficacy and safety of Compound Danshen Tablet (CDT) in preventing thromboembolism in multiple myeloma (MM) patients treated with thalidomide-based regimens. MATERIAL AND METHODS MM patients treated with thalidomide-based regimens were retrospectively reviewed between January 2008 and March 2015. Patients were categorized into 3 cohorts based on thromboembolic prophylaxis used: CDT, Warfarin Tablet, and no prophylaxis. Venous thromboembolism (VTE), other adverse effects (AEs), and the changes of D-dimer and fibrinogen levels were monitored. RESULTS Seven out of 313 MM patients (2.24%) developed venous thrombosis events (VTE) in this retrospective study, all clustering in the no prophylaxis cohort. Three patients of the Warfarin cohort (3.19%) experienced hemorrhage. Neither VTE events nor serious AEs were observed in the CDT cohort. Following Compound Danshen or Warfarin treatment for 3 months, the D-dimer and fibrinogen levels (in particular the D-dimer level) (all P<0.05), were obviously decreased relative to their respective baselines and the no prophylaxis cohort. In contrast, the 2 blotting parameters were significantly increased in the no prophylaxis cohort relative to the baseline level (All P<0.05), and were even higher in the patients experiencing VTE compared to the no VTE patients (P<0.0001 and P=0.016, respectively). CONCLUSIONS Our findings indicate CDT is an effective therapy for preventing VTE in MM patients treated with thalidomide-based regimens, and is well tolerated in long-term use.

Association between the neutrophil-to-lymphocyte ratio and cancer in adults from NHANES 2005-2018: a cross-sectional study.

Inflammation plays a crucial role in cancer development. The neutrophil-to-lymphocyte ratio (NLR), a measure of inflammation, is obtained from a complete blood count. However, little is known about the association between NLR and cancer in the general adult population in the United States. This study aimed to evaluate whether NLR is associated with cancer in American adults. This retrospective cross-sectional study included 28,016 adult participants from the National Health and Nutrition Examination Survey (NHANES) dataset spanning 2005 to 2018. Data on demographics (age, sex, race, marital status, Poverty-Income Ratio, education level), lifestyle factors (smoking, alcohol consumption, body mass index), medical conditions (hypertension, diabetes, cardiovascular disease), and laboratory parameters (hemoglobin, platelet count, alanine aminotransferase, creatinine, albumin, and lactate dehydrogenase), were collected. Logistic regression analysis was used to investigate the research objectives. Of the total 28,016 participants, 2639 had cancer. The mean age was 49.6 ± 17.6 years, and 50% were male. A positive association between NLR and cancer risk was observed after multivariate adjustment (OR = 1.20, 95% confidence interval (CI) = 1.05-1.36, p = 0.006). Similar patterns were observed in subgroup analyses (all p-values for interaction > 0.05). A higher NLR was directly correlated with an increased risk of developing cancer in adults.

Low incidence of hepatitis B virus reactivation in patients with hematological malignancies receiving novel anticancer drugs: A report from a high epidemic area and literature review.

BACKGROUND: More and more novel anticancer drugs have been approved for patients with hematological malignancies in recent years, but HBV reactivation (HBV-R) data in this population is very scarce. This study aimed to evaluated HBV-R risk in patients with hematological malignancies receiving novel anticancer drugs. METHODS: HBV markers and serum HBV DNA levels of patients with hematological malignancies receiving novel anticancer drugs in a tertiary cancer hospital were retrospectively collected. HBV-R risk in the whole cohort and subgroups was described. The relevant literature was reviewed to make a pooled analysis. RESULTS: Of 845 patients receiving novel anticancer drugs, 258 (30.5%) were considered at risk for HBV-R. The median duration of exposure to novel drugs was 5.6 (0.1-67.6) months. The incidence of HBV-R was 2.1% in patients with past HBV infection without prophylactic antiviral treatment (PAT) and 1.2% in all patients at risk of HBV-R. In a pooled analysis of 11 studies with 464 patients, the incidence of HBV-R was 2.4% (95% CI: 1.3-4.2) in all at-risk patients receiving novel anticancer drugs and 0.6% (95% CI: 0.03-3.5) in patients with anticancer drugs plus PAT. The incidence of death due to HBV-R was 0.4% (95% CI: 0.1-1.6) in all at-risk patients and 18.2% (95% CI: 3.2-47.7) in patients with HBV-R. CONCLUSION: Most episodes of HBV-R are preventable, and most cases with HBV-R are manageable. We recommend that novel anticancer drugs should not be intentionally avoided when treating cancer patients with HBV infection.

[Effect of Age on the Time of Neutropenia after Initial Induction Therapy for Patients with Newly Diagnosed Acute Myeloid Leukemia].

OBJECTIVE: To explore the effect of age on the time of neutropenia after initial induction therapy for newly diagnosed acute myeloid leukemia (AML) patients. METHODS: Data of 18-65 years old AML patients treated in our hospital from Junuary 2015 to July 2020 were retrospectively analyzed. The clinical characteristics, time of neutropenia after initial induction treatment, early responses, and related influencing factors for the time of neutropenia were analyzed and compared between 18-40 years old group and 41-65 years old group. RESULTS: There were 112 patients enrolled in this study, including 66 (58.9%) males, and their median age was 46 years old. Compared with 18-40 years old group, the incidence of FLT3-ITD gene mutation increased (P=0.039) but core binding factor (CBF) decreased (P=0.003) significantly in 41-65 years old group. The incidence of neutropenia was 97.3%, and the average time was (18.70±1.192) days. The time of neutropenia was (21.43±1.736) days in 41-65 years old group, which was longer than (14.91±1.356) days in 18-40 years old group (P=0.006). The time of neutropenia in CBF positive group was shorter than that in negative group (P=0.012), as well as in patients with remission (CR+CRi) (≤ 2 courses) than those with non-remission (NR) (P=0.024), while in high-risk group was longer than that in low-risk group (P=0.040). Multivariate analysis showed that age, FLT3-ITD gene mutation positive, and non-remission (NR) after two courses of treatment were independent risk factors for the time of neutropenia. CONCLUSION: In non-elderly patients with newly diagnosed AML, age is an influencing factor for the time of neutropenia. Key words　　;

Middle thyroid vein tumor thrombus in metastatic papillary thyroid microcarcinoma: A case report and review of literature.

BACKGROUND: Although papillary thyroid microcarcinoma (PTMC) is not considered a threatening tumor, in some cases, it can be aggressive. Metastatic thrombosis of papillary thyroid carcinoma, follicular thyroid carcinoma, Hürthle cell carcinoma, poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma have been reported in the literature, but there have been no reports about PTMC. CASE SUMMARY: A 45-year-old woman presented with a thyroid mass and thrombosis in a middle thyroid vein during a physical examination. She had no symptoms, and the physical examination showed no positive signs. Subsequent ultrasonography-guided fine-needle aspiration biopsy results indicated an atypical lesion of ambiguous significance, with some actively growing cells (TBSRTC III) and the BRAFV600E mutation not present. This patient underwent left thyroidectomy, isthmus lobectomy, prophylactic central lymph node dissection and thromboembolectomy. Postoperative pathology showed papillary microcarcinoma of the left thyroid, and the thrombus in the middle thyroid vein was a tumor thrombus. CONCLUSION: Middle thyroid vein tumor thrombus is an extremely rare condition in PTMC, but it does exist. Lobectomy and thromboembolectomy may be an option for patients with thrombi in the middle vein of the thyroid, and we strongly suggest close follow-up of these patients.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

[CLAG Regimen Composed of Continuous Intravenous Infusion of Cladribine in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To study the efficacy and safety of continuous intravenous infusion of 2-Chlorodeoxyadenosine (2-CdA) combined with high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) (CLAG regiem) in the treatment of relapsed/refractory acute myeloid leukemia (AML). METHODS: Fifteen patients with refractory/relapsed AML hospitalized in 5 medical units such as Department of Hematology, the Affiliated Tumor Hospital of Zhengzhou University and received one course of CLAG regimen from June 2014 to August 2019 were analyzed retrospectively (specifically: cladribine 5 mg/M2, day 1 to day 5, continuous 24-hour intravenous infusion; Ara-C 2 g/M2, 1 time/day, day 1 to day 5, intravenous infusion; G-CSF 300 mg, 1 time/day, day 0 to day 5, subcutaneous injection). RESULTS: Among the 15 patients with refractory/relapsed AML, 9 males and 6 females, the median age was 35 (13-63) years old. FAB classification: 1 case of M1, 3 cases of M2a, 4 cases of M2b (including 1 case with extramedullary invasion), 1 case of M4 with extramedullary invasion, 5 cases of M5, 1 case of HAL; NCCN classification: 6 cases in intermediate risk group, 9 cases in high risk group; 8 cases refractory, 7 cases relapsed. The median time of pre-chemotherapy was 4 (2-8) (of which NO.15 had received 8 cycles of chemotherapy and received CLL1-CAR-T), and the median white blood cell count before chemotherapy was 12.27 (from 0.78 to 5.29)×109/L. After 1 course of treatment with CLAG regimen, 12 patients achieved complete remission (12/15, 80%), and the median duration of CR was 65 days (0-528) days. IV grade leukopenia and thrombocytopenia was found in all the patients after chemotherapy. The median duration of granulocytosis was 20 (14 to 33) days, and 1 patient died. Seven patients received allogeneic hematopoietic stem cell transplantation. The median EFS and OS time of 15 patients was 85 (19-558) days and 117 (19-558) days, respectively. CONCLUSION: The CLAG regimen consisting of continuous intravenous infusion of cladribine shows high CR in the treatment of AML patients, but the duration of CR is short, myelosuppression is sever, so that infection control is the key. Allogeneic hematopoietic stem cells transplantation should be performed as soon as possible after CR.

[PX-12 Promoting Apoptosis of Multiple Myeloma Cell Line H929 Induced by Bortezomib].

OBJECTIVE: To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib. METHODS: MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 µmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H2DCFDA probe labeling. RESULTS: MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G2/M phase was increased to 28% and 40%, respectively. The cells in bortezomib group also showed a similar distribution after being treated. After treated with PX-12 and bortezomib, the cells in G1 phase were decreased significantly to 19% and 12% in S phase, but increased significantly to 68% in G2/M phase, which was significantly different from PX-12 group and bortezomib group (P<0.01). After culture for 72 hours, the apoptosis rate was 71.3% in the combination group, which was significantly higher than that in PX-12 group, bortezomib group, and control group (20.6%, 33.3%, 10.6%)(P<0.01). After culture for 24 hours, the intracellular ROS level in the combination group was 12015±430.2, which was higher than that in the PX-12 group, bortezomib group, and control group (6729±352.8, 2651±228.3, 1098±164.6, respectively) (P<0.01). CONCLUSION: PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.

[Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). METHODS: Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. RESULTS: The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of perforin and Granzyme B of NK cells in the peripheral blood of patients with hematological malignancies were lower than those of healthy controls. The level of VEGF, IL-6 and TNF-α in the peripheral plasma were higher than those of the healthy control group, and the difference was statistically significant. The level of IFN-γ was lower, and the difference was not statistically significant. The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of Granzyme B and Perforin of NK cells in peripheral blood were higher after the therapy of thalidomide combined with rhIFNα-1b for 3 months as compared with those before treatment of ITI, the level of the IFN-γ in peripheral plasma was higher while that of VEGF was lower, the difference was statistically significant; after treatment, the ratio of CD3+ CD4+ and CD3+ CD8+ lymphocytes and the level of TNF-α in peripheral blood were higher those that before treatment, IL-6 was lower, while the difference was not statistically significant. CONCLUSION: The ITI regimen can raise the ratio of CD4+/CD8+ T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.

[Clinical Analysis of Gene Mutation in Adult Patients with B-ALL and Its Influence on Clinical Prognosis].

OBJECTIVE: To investigate the gene mutation in adult patients with B-ALL and its influence on clinical prognosis. METHODS: Clinical data of 226 adult patients with B-ALL were retrospectively analyzed in the period from August 2011 to February 2018. The incidence of gene mutation in all patients were detected, and the influence of mutation gene on clinical prognosis were estimated. Cox regression model were used to evaluate the independent prognostic factors. RESULTS: 208 (92.04%) of 226 patients showed gene mutations, and the median mutation number was 2 (0-8). Among them, 54 cases (23.89%) showed 14 or more mutations. The top five mutation types of all patients were SF1, FAT1, MPL, PTPNII and N-RAS respectively. The median OS and median RFS times of 226 patients were 27.0 (5.5-84.0) months and 22.5 (0-81.0) months respectively. The OS and RFS times of Ph- B-ALL patients with JAK1 and JAK2 mutations were significantly shorter than those of patients without JAK2 mutations (P＜0.05). The OS and RFS times of Ph- B-ALL patients with abnormal JAK-STAT signaling pathway were significantly shorter than those of patients without abnormal JAK-STAT signaling pathway (P＜0.05). The OS and RFS times of Ph+ B-ALL patients with epigenetic related signaling pathway mutations were significantly shorter than those of patients without epigenetic related signaling pathway mutations (P＜0.05). Cox regression model multivariate analysis showed that WBC level was the independent influencing factor for total survival time and relapse-free survival time in adult B-ALL patients (P＜0.05). With or without JAK2 mutation and WBC level were the independent influencing factor for overall survival time and relapse-free survival time of adult Ph- B-ALL patients (P＜0.05). CONCLUSION: Gene mutations are common in all adult B-ALL patients, and the clinical prognosis of patients with JAK and epigenetics-related signaling pathway mutations is worsen, while the WBC level closely relates to the clinical prognosis of the patients.

[ABVD chemotherapy scheme at day 1 and 8 for treatment of primary Hodgkin's lymphomas].

OBJECTIVE: To explore the effect of adriamycin, bleomycin, vincristine and dacarbazinum (ABVD) chemotherapy scheme executed at day 1 and day 8 for primary Hodgkin's lymphomas (HL). METHODS: 62 patients with primary HL in stages II - IV treated in our department from October 2005 to October 2006 were divided into group A and B at random with 31 patients in each group. The patients in group A received ABVD chemotherapy scheme executed at day 1 and day 8 for 6 - 8 cycles. The patients in group B received ABVD chemotherapy scheme executed at day 1 and day 15 for 6 - 8 cycles. The patients of the groups received radiotherapy by the same doctor after chemotherapy according to the patients condition and the radiotherapy regimens were not affected by the grouping. RESULTS: The complete remission rate (CR) in group A after chemotherapy was 90.3% (28/31); the one-year and two-year disease free survival (DFS) rates were 87.1% (27/31) and 80.0% (20/25) respectively. The CR rate in group B after chemotherapy was 83.9% (26/31); the one-year and two-year DFS rates were 80.6% (25/31) and 72.0% (18/25) respectively. The discrepancy of CR rates and the one-year and two-year DFS rates between the two groups was not significant (P > 0.05). The incidences of therapeutic side effects such as myocardial ischemia grade III - IV liver function impairment, pulmonary fibrosis and serious marrow inhibition between the two groups were not significant too (P > 0.05). Average chemotherapy period for the patients in group A was 159 days; it was 69 days shorter than that in group B. CONCLUSION: The CR rate, 1-year DFS rate and 2-year DFS rate of ABVD chemotherapy scheme executed at day 1 and 8 are similar to those of ABVD chemotherapy scheme executed at day 1 and 15 for primary HL in stages II - IV. The side-effects of chemotherapy between group A and B are similar too. The chemotherapy period in group A is shortened significantly.

[Expression of Ki-67 in Adult and Children Acute Lymphoblastic Leukemia and Its Clinical Significance].

OBJECTIVE: To investigate the relationship of Ki-67 level with clinical features, immunophenotype, gene mutation, curative efficacy and prognosis in patients with acute lymphoblastic leukemia(ALL). METHODS: Flow cytometry gated at CD45/SSC was used to detect the expression of Ki-67, and the correlation of Ki-67 expression with clinical manifestation, laboratorial indexes, curative efficacy and prognosis was analysed. RESULTS: Ki-67 expression level increased in ALL patients, the median expression rate was 29.22%, there was significant difference as compared with the healthy control (P<0.01). In adult ALL, the median expression rate of Ki-67 in the high-risk group was 31.49%, and the difference was statistically significant as compared with the low-risk group (P<0.05). In children ALL, the median expression rate of Ki-67 in high-risk group was 42.28%, and the difference was statistically significant (P<0.05). The results of unvariate analysis showed that the age, WBC count at newly diagnosed and extramedullary invasion were adverse factors affecting OS and DFS; the results of multivariate analysis showed that age and extramedullary invasion were independent risk factors for OS and DFS in patients. CONCLUSION: Age≥14 years old, intramedullary invasion are the poor factors for prognosis; the Ki-67 level is not an independent factor for the prognosis of patients.

[Effect of RNA Interference-silenced TAK1 on Kasumi-1 cell Proliferation Inhibition Induced by As2O3 and Its Mechanism].

OBJECTIVE: To explore the effect of transforming growth factor-ß activated kinase-1(TAK1) gene silenced by RNA interference on proliferation inhibition of Kasumi-1 cells induced by As2O3 and its mechanism. METHODS: The experiments were divided into 4 groups, including control group(Kasumi-1 cells treated with non-specific siRNA), TAK1 specific siRNA treated group (Kasumi 1 treated with TAK specific siRNA), As2O3 treated group (Kasumi 1 cells treated with As2O3) and combined treated group (Kasumi 1 cells treated with TAK1 specific siRNA plus As2O3). The proliferation inhibition rate of Kasami 1 cells was detected by CCK-8 method, the apoptotic rate of cells was detected by flow eytometry, the expressions of TAK1, phosphorylated c-Jun N-terminal kinase(p-JNK) and apoptosis-related proteins were detected by Western blot. RESULTS: As2O3 could inhibit Kasumi-1 cell proliferation in a dose-dependent manner between 0.5 to 20 µmol/L with IC50 of (3.79±0.36) µmol/L at 24 h, and also inhibit Kasumi-1 cell proliferation in a dose-dependent manner between 0.5 to 10 µmol/L with IC50 of (2.38±0.17) µmol/L at 48 h, but then the inhibitory effect reached plateau. After treating Kasumi-1 cells with TAK1 siRNA and 3.5 µmol/L As2O3 for 24 h, the proliferation inhibition rate was (10.86±1.64)% and (49.80±2.19)%, meanwhile the apoptosis rate was (8.47±0.75)% and (24.78±2.14)%, all significantly higher than those in control group (P<0.05, P<0.01). The proliferation inhibition rate and apoptosis rate of the combined treated group were significantly higher than that in control and single treated groups (P<0.05, P<0.01), TAK1 silencing and 3.5 µmol/L of As2O3 could decrease the expression of TAK1, p-JNK, c-Fos, c-Jun and BCL-2 in different degrees, and increase the expression levels of BAX and the activated (cleaved) caspase-3, 9 with statistically significant differences as compared with control group (P< 0.05). When Kasumi-1 cells were treated with TAK1 specific siRNA plus As2O3 for 24 h, protein expression levels were all significantly greater than that in the single-treated groups (P< 0.05). CONCLUSION: TAK1 silencing and As2O3 can separately and synergistically inhibit Kasumi-1 cell proliferation which probably relates with the inducing apoptosis via the JNK and mitochondrial pathway. Meanwhile, TAK1 silencing enhances the inhibitory effect of As2O3 on Kasumi-1 cell proliferation.

[Clinical Efficacy of EPOCH±R Followed by DICE±R Regimen for Primary Breast Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the clinical efficacy and safety of EPOCH±R followed by DICE±R regimen for primary breast diffuse large B-cell lymphoma. METHODS: Forty-three patients with primary breast diffuse large B-cell lymphoma were admitted in our hosptial from January 2000 to April 2016. Among them 24 patients were treated with CHOP±R regimen, 19 patients were treated with EPOCH±R followed by DICE±R regimen. The clinical efficacy, survival rate and adverse effects were observed and compared between them. RESULTS: The complete rate in EPOCH±R followed by DICE±R regimen group was higher than that in the CHOP±R group (84.2% vs 70.8%), and the relapsed rate was lower in EPOCH±R followed by DICE±R regimen group than that in the CHOP±R group (6.25% vs 35.3%). Progression-free survival (PFS) and overall survival (OS) rates of 5 years after diagnosis in the EPOCH±R followed by DICE±R group were significantly higher as compared with that in CHOP±R group (PFS, 75% vs 47.4%, P=0.035; OS, 73.3% vs 45.2%, P= 0.043). Treatment-related hematologic adverse events were more serious in the EPOCH±R followed by DICE±R group(63.2% vs 25%). However, these adverse events were controlled and no treatment-related deaths were observed. Multivariate analysis showed that age (P=0.008; 95% CI, 0.026 to 0.579), radiotherapy (P=0.045; 95% CI, 1.028 to 14.719) and LDH level (P=0.007; 95% CI, 0.017 to 0.531) were independent prognostic factors for 5 year overall survival. CONCLUSION: EPOCH±R followed by DICE±R regimen is an effective and safe treatment regimen for PB-DLBCL. Prognostic factors for survival are age, LDH level and radiotherapy.

[Rituximab and Dexamethasone Combined with Cyclophosphamide for Treatment of Relapsed and Refractory Immune Thrombocytopenia].

OBJECTIVE: To evaluate the efficiency and safety of rituximab and dexamethasone combined with cyclophosphamide for treating patients with relapsed and refractory immune thrombocytopenia (ITP). METHODS: Twelve patients with relapsed and refractory immune thrombocytopenia were prospectively enrolled in this study, and received rituximab 375 mg/m(2) once a week for 4 weeks, dexamethasone 40 mg once a day for consecutive 4 days, and cyclophosphamide 500 mg/m(2) biweekly for 2 weeks. The levels of IFN-r and IL-4 in peripheral blood of patients were measured by enzyme-linked immunosorbent assay (ELISA), and the percentages of Breg, Treg and Th17 cells were detected by flow cytometry before and after treatment. Efficiency was evaluated according to platelet counts, and side effects were observed. RESULTS: Six out of 12 patients reached to complete remission and 4 patients reached to partial remission, with the total response rate 83.33%. The platelet counts [(115.42 ± 76.60) × 10(9)/L] after treatment were significantly higher than that before treatment [(115.42 ± 76.60) × 10(9)/L] (P < 0.001). The ratio of IFN-r/ IL4 after treatment (5.89 ± 2.30) was very significantly lower than that before treatment (7.00 ± 2.73) (P = 0.002). The percentage of Breg cells after treatment [(21.27 ± 4.28)%] were much significantly higher than that before treatment [(15.48 ± 1.67)%] (P < 0.001). The ratio of Treg/Th17 after treatment (3.07 ± 1.50) was significantly higher than that before treatment (0.98 ± 0.45) (P < 0.001). Infusion reaction was observed in 1 patient, secondary hypertension and hyperglycemia were in 1 patient, and pneumonia in 2 patients. CONCLUSION: Rituximab and dexamethasone combined with cyclophosphamide can improve the outcomes of patients with relapsed and refractory immune thrombocytopenia patients and they were well tolerated, its mechanism may be related with the balance between T cell sunsets and Treg cells.