Objective:To evaluate the diagnostic efficiency of hypersensitivity quantitative fecal immunochemical test (hs-qFIT) in colorectal cancer (CRC) and advanced adenoma.Methods:From July to December 2020, consecutive patients aged 50 to 75 years who underwent colonoscopy in Qilu Hospital of Shandong University, and had the Asia-Pacific colorectal screening score of medium or high risk were enrolled. All patients were requested to complete two hs-qFIT before colonoscopy. The diagnostic efficacy of hs-qFIT for CRC and advanced adenoma were assessed. Receiver operating characteristic curve of hs-qFIT in CRC diagnosis was drawn and the area under the curve (AUC) was calculated.Results:A total of 811 patients including 20 (2.5%) cases of CRC, 47 (5.8%) cases of advanced adenoma, 206 (25.4%) cases of non-advanced adenoma, 219 (27.0%) cases of non-adenomatous polyp, 76 (9.4%) cases of other colorectal lesions and 243 (30.0%) cases of non-colorectal lesions were involved. When the fecal hemoglobin cut-off values were 10, 30, 50, 75 and 100 ng/mL, the positive rates of hs-qFIT detection were 17.9% (145/811), 10.9% (88/811), 8.3% (67/811), 7.4% (60/811) and 5.8% (47/811), respectively. When the cut-off value of fecal hemoglobin decreased from 100 ng/mL to 10 ng/mL, the sensitivity of hs-qFIT for CRC diagnosis increased from 90.0% to 100.0%, and the specificity decreased from 96.3% to 84.2%; and the sensitivity of hs-qFIT for the diagnosis of advanced adenoma increased from 19.1% to 66.0%, and the specificity decreased from 95.0% to 85.1%. The AUC of hs-qFIT for the diagnosis of CRC and advanced adenoma were 0.981 (95% confidence interval ( CI) 0.970 to 0.992) and 0.846 (95% CI 0.807 to 0.886), respectively. When the optimal cut-off values were taken, the sensitivity and specificity were 100.0% and 91.2% for the diagnosis of CRC, and 66.0% and 85.3% for the diagnosis of advanced adenoma, respectively. Conclusion:Hs-qFIT can help the early screening of CRC and advanced adenoma.

Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML). In 2007, a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chinese CML patients. This report from the 4-year follow-up revealed that 73% of 59 patients in chronic phase (CML-CP) and 32% of 25 patients in accelerated phase (CML-AP) remained under treatment. The initial dosage of dasatinib for CML-CP and CML-AP patients were 100 mg once daily and 70 mg twice daily (total = 140 mg/ day), respectively. The cumulative major cytogenetic response (MCyR) rate among patients with CML-CP was 66.1% (versus 50.8% at 18 months), and the median time to MCyR was 12.7 weeks. All CML-CP patients who achieved MCyR after a 4-year follow-up also achieved a complete cytogenetic response. The cumulative complete hematological response (CHR) rate among patients with CML-AP was 64% (16/25), with three CML-AP patients achieving CHR between 18 months and 4 years of follow-up; the median time to CHR was 16.4 weeks. The adverse event (AE) profile of dasatinib at 4 years was similar to that at 6 and 18 months. The most frequently reported AEs (any grade) included pleural effusion, headache, and myelosuppression. These long-term follow-up data continue to support dasatinib as a second-line treatment for Chinese patients with CML.

Objective To analyze the therapeutic effects of chemotherapy after chidamide pretreatment in 16 cases of high-risk and refractory lymphoid malignancy. Methods The efficacy and adverse reactions of 16 patients with high-risk and refractory lymphoid malignancy who received chidamide combined with chemotherapy after 3 days pretreatment of chidamide were analyzed. Results Sixteen patients included 6 males and 10 females, and the median age was 49.5 years old (23-88 years old). The median course of previous systemic chemotherapy was 4 (range 0-22). Among 14 patients who received induction chemotherapy, 7 patients achieved complete remission (CR), 7 patients achieved partial remission (PR). Fourteen patients had achieved clinical efficacy, and the overall response rate (ORR) was 100 %. After 2 cases had remission , the patients who entered this regimen for consolidation chemotherapy also had durable CR. The median follow-up time was 13 months (range 2-24 months) until December 2017. Nine cases had overall survival (OS), 7 cases died and 9 cases had progression-free survival. Common adverse effects of the chemotherapy included mild and controllable gastrointestinal reactions after chidamide. Conclusion Chemotherapy after chidamide pretreatment may improve the effect and prognosis of high-risk or refractory lymphoid malignancy.

Objective To evaluate the efficacy and safety of lenalidomide in a real-world clinical practice in Chinese patients with multiple myeloma (MM).Methods It was a prospective,multi-center,observational study.A total of 165 consecutive patients with MM treated with lenalidomide-based regimens were enrolled in 12 hospitals from June 2013 to November 2015.Relevant information was recorded,such as baseline clinical data,cytogenetic abnormalities,treatment regimens,and duration of treatment,safety,and survival.Results (1)There were 126 relapsed and refractory MM (RRMM) patients,25 newly diagnosed patients and 19 maintenance patients.The evaluable RRMM patients accounted for 120 cases,among which 74 cases(61.7％) reached the partial response (PR) or above,and a very good partial response (VGPR) in 16 patients (13.3％),a complete response (CR) in 14 cases (11.7％),a strictly complete response (sCR) in 4 cases (3.3％).Thus,a VGPR or above in 34 patients accounted for 28.3％.(2)The median follow-up was 13 months,the median time to progression 12 months.The median survival after receiving lenalidomide was 19 months,and the median overall survival (OS) was 62 months.(3) The univariate analysis in 120 RRMM patients suggested that prognostic factors for significant improvement in PFS included normal karyotype,international staging system (ISS) Ⅰ-Ⅱ,t(4;14) negative (detected by fluorescence in situ hybridization),non-bortezomib resistance and response to previous regimens.As to OS,nonbortezomib resistance,response to previous regimens and non-primary refractoriness were positive factors.Multivariate analysis showed that the response to previous regimens (PR or better) was an independent good prognostic factor for progress-free survival (PFS),non-bortezomib resistance and non-primary refractoriness for OS.(4) Grade 3 or 4 adverse events that occurred in more than 10％ of all enrolled patients were neutropenia (12.7％),leukocytosis (11.5％) and thrombocytopenia (12.7％).Owing to intolerance of toxic side effects,7 cases withdrew lenalidomide.Conclusions No matter what combination,regimens containing lenalidomide are effective to RRMM patients with overall response rate 61.7％,a time to progression 12 months and an overall survival 62 months.The toxicity is quite tolerable and manageable.In addition,the response to previous treatment (reached PR or above) is the independent good prognostic factor for PFS,non-bortezomib resistance and non-primary refractoriness for OS.Clinical trail registration Clinicaltrials.gov,NCT01947309

AIM:To study the expression of signal transduction molecules in the striatum G protein protein 4 (RGS4) and dopamine D2 receptor (D2) in conditioned place preference (CPP) rats treated with methamphetamine (meth).METHODS:METH dependence CPP model was established (1 week and 2 weeks of METH dependence groups),The protein expression of RGS4 and D2,inhibitory G protein alpha-subunit (Gαi),mitogenactivated protein kinase (MAPK) in striatum were determined by Western blotting (WB).The changes of cyclic adenosine monophosphate (cAMP) content in striatum of rats were determined by enzyme linked immunosorbent assay (ELISA).RESULTS:Compared with saline control group,the average time of rats in the methamphetamine-paired chamber for two groups was increased (P ＜ 0.05).Compared with saline control group,RGS4 protein expressions in the two METH dependent groups were reduced (P ＜0.01);compared with 1 week of METH dependence group,that of 2 weeks group was reduced significantly(P ＜ 0.05).D2,Gαi,MAPK protein and cAMP expressions in the two METH dependent groups were increased (P ＜ 0.01);compared with 1 week of METH dependence group,those of 2 weeks were increased significantly (P ＜ 0.05).CONCLUSION:RGS4 and D2 receptor signaling pathways in striatum have changed in METH dependent rats,RGS4 may be involved in the regulation of METH-dependent D2 receptor signaling pathway in METH dependent rats.

OBJECTIVETo evaluate the early hematologic, cytogenetic and molecular responses in newly diagnosed patients with chronic myelogenous leukemia in chronic phase（CML-CP）and initially treated with a generic imatinib（Xinwei）, manufactured by Jiansu Hansoh Pharmaceutical Group Co., Ltd.

METHODS107 newly diagnosed patients of CML-CP, whose ages were above 18- year- old and who had never received any tyrosine kinase inhibitor（TKI）were treated with Xinwei 400 mg QD. The hematologic, cytogenetic and molecular responses were assessed at 3- and 6-month, and adverse effects were evaluated throughout the study.

RESULTS107 patients were treated with Xinwei for at least 3 months, 54 of them were treated for 6 months or more. At 3- month, the complete hematologic responses（CHR）rate were 98.1%（105/107）; 47/57（82.5%） patients achieved major cytogenetic response（MCyR）, and 20/57 （35.1%） patients complete cytogenetic response（CCyR）; BCR- ABLIS was ≤10% in 77/106 patients （72.6%）, 11 of them（10.4%）achieved major molecular response（MMR, BCR-ABLIS was ≤0.1%）. At 6-month, the CHR rate was 100%（54/54）; 28/39 patients（71.8%）achieved CCyR; BCR-ABLIS was ≤1% in 37/54 patients （68.5% ）, 18 of them （33.3% ） achieved MMR. The grade Ⅲ leukopenia, thrombocytopenia and anemia rates were 19.5%, 23.0% and 13.8%, respectively. No grade Ⅳ hematologic toxicity occurred. The common non- hematologic toxicities were edema（74.7%）, nausea（48.3%）, bone pain（42.5%）, rash（36.8%）, diarrhea（34.5%）, fever（23.0%）, cramp（11.5%）and impaired liver function （3.4%）. No patient experienced grade Ⅳ non- hematologic toxicity. No adverse effects related death occurred.

CONCLUSIONOur results revealed the excellent early haematology, cytogenetic and molecular responses and safety of Xinwei in treating patients with CML-CP.

Anemia ; Antineoplastic Combined Chemotherapy Protocols ; Cytogenetics ; Drugs, Generic ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Prospective Studies ; Protein Kinase Inhibitors ; Remission Induction ; Thrombocytopenia ; Treatment Outcome

OBJECTIVETo construct the P210(T315I-BCR/ABL) transgenic mice model.

METHODSThe transgenic vector in which the P210(T315I-BCR/ABL) gene and eGFP gene was derived by APN/CD13 promoter was constructed and microinjected into the single-cell fertilized eggs of C57 mice. Transgene integration was conformed by PCR genotyping and P210(T315I-BCR/ABL) expression levels was evaluated by RT-PCR. The CML phenotype was confirmed by blood routine examination, Wright's staining for peripheral blood and bone marrow smears, HE staining for organs of transgenic mice.

RESULTSThree transgenic mice lines with high expression of P210(T315I-BCR/ABL) gene and eGFP gene was selected. Compared with the wild type mice, the levels of WBC, platelet and neutrophil granulocyte of transgenic mice began to increase gradually at 2 months, and increase to 23.9×10⁹/L, 4 136×10⁹/L, and 74.6% respectively at 6 months. The remarkable hyperplasia of granulocytes was seen in the peripheral blood and bone marrow smears with splenomegaly infiltrated by leukemic cells.

CONCLUSIONThe P210(T315I-BCR/ABL) transgenic mice was constructed and provided a model to explore the mechanism of T315I CML and screen out the drug for T315 CML patient.

Animals ; Fusion Proteins, bcr-abl ; Genetic Vectors ; Genotype ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Mice ; Mice, Transgenic ; Promoter Regions, Genetic

OBJECTIVETo compare the clinical efficacy of HLA- mismatched related donor (MRD) and HLA-matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies.

METHODS174 patients with hematopoietic malignancies undergoing allogeneic HSCT (allo-HSCT) (82 from MRD and 92 from MUD) between June 2002 and December 2012 were enrolled in this retrospective study. Hematopoietic engraftment, graft versus host disease (GVHD), relapse, overall survival (OS) and disease-free survival (DFS) were compared between MRD and MUD group.

RESULTSThere was no significant difference between MRD and MUD group in terms of age, gender, disease type and disease status before transplantation (all P>0.05). The incidence of Ⅰ-IV acute GVHD (aGVHD) was 62.2% and 54.3% in MRD and MUD group (P=0.295); the incidence of III-IV aGVHD between the two groups was 15.9% and 9.8% (P=0.229). The incidence of chronic GVHD (cGVHD) was 28.4% and 45.1% in MRD and MUD group (P=0.036), but there was no significant difference in the incidence of extensive cGVHD between the two groups (9.0% vs 12.2%, P=0.525). The mortality of GVHD was 8.5% and 10.9% in MRD and MUD group (P=0.605). The 10-year OS and DFS were (50.1±6.1)% and (48.8±6.1)% in MRD group, compared with (50.5±6.7)% and (46.3±6.2)% in MUD group (P=0.501, P=0.873, respectively). The 10-year cumulative relapse rate was (21.5±5.7)% and (37.6±7.3)% in MRD and MUD group (P=0.194).

CONCLUSIONMRD is equivalent to MUD in efficacy and safety. Without HLA- matched related donors, MRD is superior to MUD because donor source is unlimited and transplantation could be made promptly according to disease status.

Adolescent ; Disease-Free Survival ; Graft vs Host Disease ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; Histocompatibility Antigens Class I ; immunology ; Humans ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome ; Unrelated Donors

OBJECTIVETo analyze the association of different types of ABL tyrosine point mutations and imatinib resistance to probe the relation between ABL tyrosine point mutations and the prognosis of patients with chronic myeloid leukemia (CML).

METHODSNested reverse transcriptasepolym erase chain reaction was performed on samples from 70 patients to amplify the ABL kinase domain. Then, the amplified product was purified and sequenced in both direction. The homologous analysis was performed in combination of clinical data.

RESULTSThe ABL domain point mutations were detected in 32 patients (45.7%) including 16 patients in chronic phase (CP), 6 patients in accelerated phase(AP)and 10 patients in blast phase (BP), which were detected as T315I, E255K, C475Y, Y253H, G321W, G250E, F317L, E258K, F359V, E459K and F311I, respectively. Sokal score with intermediate and high risk and Ph+ chromosome with complex karyotype were important risk factors for ABL domain point mutations. The 5-year overall survival (OS) was not significantly different between the patients with or without ABL domain point mutations (78.1% vs 84.2%, P=0.985), while the 5-year cumulative event-free survival (EFS) of two groups were 34.4% and 68.4% (P=0.034), respectively. The rate of complete cytogenetic response was higher in patients treated with allogenic hematopetic stem cell transplantation (allo-HSCT) compared with patients merely treated with second-generation tyrosine kinase inhibitors or chemotherapeutics (P=0.001).

CONCLUSIONPatients with ABL domain point mutations had poor efficacy and prognosis compared to those without ABL domain point mutations. Detection of ABL domain point mutations in CML-CP was helpful for the adjustment of therapeutic options and improvement of prognosis. And allo-HSCT was a more effective therapy for patients with advanced phase.

Adolescent ; Adult ; Aged ; Benzamides ; therapeutic use ; Child ; Drug Resistance, Neoplasm ; Female ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Point Mutation ; Prognosis ; Proto-Oncogene Proteins c-abl ; genetics ; Pyrimidines ; therapeutic use ; Young Adult

Objective To investigate the effect of histone deacetylase inhibitor LBH589 on proliferation,apoptosis and drug resistance of chemoresistant acute myeloid leukemia cells HL60/ADM.Methods HL60/ADM cells were treated with LBH589.Proliferation,apoptosis and adriamycin IC50 were evaluated by MTT assay and AnnexinV-FITC/PI stain.The change in MRP1 expression and intercellular adriamycin accumulatiom were analyzed by flow cytometry.Results Effective proliferative inhibition and apoptotic induction in HL60/ADM cells were observed after treatment with 10-80 nmol/L LBH589 with maximal effect detected after treatment with 70 nmol/L LBH589 for 60 hours.However,inhibition ratio remain unchanged with the further increase of drug dose and incubation time (P ＞ 0.05).Downregulation of MRP1 [(93.90±4.20) ％ vs (76.19±6.53) ％],upregulation of adriamycin accumulation [(8.53±0.68) ％ vs (25.67±1.34) ％] and decrease in adriamycin IC50 [(6.833±0.319) μg/ml vs (1.382±0.104) μg/ml] were induced by the treatment with 20 nmol/L LBH589 (P ＜ 0.01),whose reversal fold was 4.9.The expression of acetylated histone 3 after treatment with LBH589 was higher than that before treatment (P ＜ 0.01).However,relative p-Akt levels after treatment for 24 h and 48 h were 1.07±0.09 and 0.59±0.01,respectively,which were lower than that before treatment (2.03±0.12) (P ＜ 0.01).Meanwhile,expression levels of p53 were 0.57±0.04 and 1.31±0.09,respectively,which were higher than that before treatment (0.21 ±0.02) (P ＜ 0.01).Conclusion Treatment with LBH589 has the capability of inhibiting proliferation and inducing apoptosis,as well as increasing intercellular adriamycin accumulation and sensitivity through downregulation of MRP1 expression and inhibition of PI3K-Akt signaling pathway in HL60/ADM cells.