[Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study].

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

[Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study].

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

[Dasatinib combined with multi-agent chemotherapy regimen in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a prospective study from a single center].

Objective: This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients. Methods: This prospective, single-arm, and open clinical study enrolled 30 adult Ph(+) ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results: All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS (P=0.004) , HRFS (P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS (P=0.030) and EFS (P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions: The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph(+) ALL patients. Clinical trial registration: ClinicalTrials.gov, NCT02523976.

[Effect of genetic polymorphism of TPMT and NUDT15 on the tolerance of 6-mercaptopurine therapy in adult acute lymphoblastic leukemia].

Objective: To investigate the effect of genetic polymorphisms of TPMT*2 rs1800462, TPMT*3B rs1800460, TPMT*3C rs1142345, and NUDT15 rs116855232 on the tolerance of 6-mercaptopurine (6-MP) therapy in adult acute lymphoblastic leukemia (ALL) . Methods: A total of 216 adult patients who were diagnosed with ALL and treated with cyclophosphamide, cytarabine, and 6-MP [complementary and alternative medicine (CAM) regimen] from September 2015 to December 2019 were included. Polymorphisms were detected by TaqMan SNP Genotyping Assay. Combined with clinical data, the influence of genetic polymorphism on the tolerance of 6-MP in the treatment of ALL was analyzed. Results: Among the 216 patients, 185 (85.65%) patients had B-ALL and 31 (14.35%) patients had T-ALL. 216 (100%) patients had CC genotype for both TPMT*2 rs1800462 and TPMT*3B rs1800460. The number of TT and TC genotypes for TPMT*3C rs1142345 was 209 (96.76%) and 7 (3.24%) , respectively. The allele frequency was 1.62% for TPMT*3C rs1142345. The number of CC, CT, and TT genotypes for NUDT15 rs116855232 was 166 (76.85%) , 48 (22.22%) , and 2 (0.93%) , respectively. The allele frequency was 12.04% for NUDT15 rs116855232. The TPMT*3C rs1142345 mutant group (TC+CC genotype) had less transfusion volume of packed red blood cell than the wild group (CC genotype) (P=0.036) , and the mutant group (TC+CC genotype) had a higher risk to develop hepatotoxicity (increased aspartate aminotransferase) than the wild group (CC genotype) (OR=9.559, 95% CI 1.135-80.475, P=0.038) . The durations of white blood cells (WBC) <1×10(9)/L and absolute neutrophil count (ANC) <0.5×10(9)/L in the NUDT15 rs116855232 mutation group (CT+TT genotype) were longer than that in the wild group (CC genotype) (P=0.005, P=0.007) , and the transfusion volume of apheresis-derived platelets in the mutant group (CT+TT type) was greater than that in the wild group (CC genotype) (P=0.014) . Conclusion: Genetic polymorphism of TMPT and NUDT15 has an effect on the tolerance of 6-MP in the treatment of adult ALL. Detecting genotypes of patients with ALL before treatment helps to optimize the dosage of 6-MP, which may help shorten the bone marrow suppression duration and reduce blood transfusion volume.

[Rituximab combined with short-course and intensive regimen for Burkitt leukemia: efficacy and safety analysis].

Objective: This study aimed to explore the efficacy and safety of rituximab combined with short-course and intensive regimens in the treatment of adult patients with Burkitt leukemia. Methods: The clinical data of 11 Burkitt leukemia patients in our hospital from January 30, 2006, to September 12, 2018, were collected. The clinical details, complete remission (CR) rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were evaluated. Results: The median age of 11 patients was 34 (15-54) years, of which six were males and five were females (M∶F, 1.2∶1) . The median white blood cell (WBC) count was 12.28 (2.21-48.46) ×10(9)/L, and the median blast percent of peripheral blood and bone marrow were 40% (3%-76%) and 84.0% (29.5%-94.5%) , respectively. Ten patients were administered with rituximab combined with a short-course and intensive regimens, and two patients underwent autologous hematopoietic stem cell transplantation following consolidation chemotherapy. The CR rate after one cycle of induction therapy was 100%, the four-year OS was 90%, and RFS was 90%. Out of the ten treated patients, only one patient suffered from tumor lysis syndrome during the induction chemotherapy. Consequently, renal function recovered after hemodialysis and other treatments. The regimen is safe with no treatment-related deaths. Conclusions: Rituximab combined with short-course and intensive chemotherapy regimens is effective and well-tolerated in adult Burkitt leukemia.

Regulatory roles of miR-593 in the proliferation and invasion of human hepatic carcinoma.

OBJECTIVE: The aim of this study was to explore the expression manuals of microRNA-593 (miR-593) in hepatocellular carcinoma (HCC), and to investigate its role in mediating the proliferation, migration and invasion of HCC cells. PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect miR-593 expression in HCC tissues and cells. HCC cells were, then, transfected with miR-593 mimic to exogenously overexpress miR-593. Cell counting kit 8 (CCK8) assay was exploited to detect the proliferation ability of HCC cells. In addition, wound healing assay and transwell assay were adopted to determine the migration and invasion abilities of HCC cells, respectively. RESULTS: MiR-593 was abnormally down-expressed in HCC tissues and cells. Up-regulation of miR-593 significantly inhibited the proliferation, migration and invasion of HCC cells. CONCLUSIONS: MiR-593 acted as a tumor suppressor gene in the development of HCC. Hence, we proposed that miR-593 might be a new potential therapeutic target marker for HCC treatment.

[Analysis of follow-up results of chrono-chemotherapy or conventional chemotherapy combined with intensity modulated radiotherapy in locally advanced nasopharyngeal carcinoma].

Objective: To evaluate the long-term effect and safety of chrono-chemotherapy combined with intensity modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma (NPC). Methods: 160 patients with locally advanced NPC were randomly divided into a chrono group and conventional group according to random number table. In the first stage, all patients underwent two cycles of induced chemotherapy, consisting of docetaxel, cisplatin and 5-Fu every 21 days. Notably, patients received chrono-moduated chemotherapy according to circadian rhythm in the chrono group, and conventional chemotherapy in the conventional group. Then, 21 days after the completion of first stage, three cycles of concurrent cisplatin chemotherapy every 21 days were given to all patients during IMRT. The median follow-up after the completion of radiotherapy was 31 months. Long-term side effects and the survival of patients were observed. Results: Patients in the chrono group had significantly lower rates of hearing loss (22.72%), dysphagia (0) and neck fibrosis (4.54%) compared with those in the conventional group (39.13%、8.69%, 15.94%, respectively, all P<0.05). Meanwhile, the 1- year overall survival rates (97.0% vs 92.8%), 3-year overall survival rates (80.3% vs 81.2%), 1-year progression free survival rates (95.5% vs 87.0%), 3-year progression free survival rates (71.2% vs 73.9%), 1-year locoregional relapse-free survival rates (97.0% vs 95.7%), 1-year locoregional relapse-free survival rates (92.4% vs 92.8%), 1-year distant metastasis-free survival rates (97.0% vs 98.6%) and 3-year distant metastasis-free survival rates (90.9% vs 91.3%) between the chrono group and the conventional group were not statistically significant (all P>0.05). Conclusions: Compared with conventional chemotherapy, chrono-chemotherapy combined with IMRT didn't affect long-term survival, but reducing the incidence of adverse events in patients with locally advanced NPC.

Role of imaging biomarkers for prognostic prediction in patients with pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumours. PDAC has a poor prognosis; therefore, it is necessary to perform further risk stratification. Identifying prognostic factors before treatment might help to implement suitable and personalised treatment for individuals and avoid side effects. Conventional staging systems and tumour biomarkers are fundamental to establish prognosis; however, they have obvious limitations. Novel imaging biomarkers extracted from advanced imaging techniques offer opportunities to evaluate underlying tumour physiological characteristics, such as mutational status, cellular composition, local microenvironment, tumour metabolism, and biological behaviour. Thus, imaging biomarkers might help the decision making of oncologists and surgeons. The present review discusses the functions of imaging biomarkers for prognostic prediction in patients with PDAC and their potential value for further translation in clinical practice.

LEF-AS1 participates in occurrence of colorectal cancer through adsorbing miR-505 and promoting KIF3B expression.

OBJECTIVE: To explore the possible role and mechanism of long non-coding ribonucleic acid LEF-AS1 (lncRNA LEF-AS1) in the pathogenesis of colorectal cancer (CRC). PATIENTS AND METHODS: The expression levels of LEF-AS1 in 54 CRC tissue samples and adjacent normal ones were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). In the meantime, CRC cell lines were screened for subsequent in vitro experiments. LEF-AS1 siRNA was transfected into CRC cells using the liposome method. Then, cell counting kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assays were conducted to detect cell proliferation. Thereafter, transwell assay was performed to evaluate the cell migration capacity, as well as invasiveness, Caspase-3 activity was examined to estimate cell apoptosis, and flow cytometry was applied for cell cycle detection. Subsequently, bioinformatics analysis was carried out to predict the target genes of micro RNA (miR)-505 that were predicted to be able to bind to LEF-AS1, while the relative activity of luciferase between miR-505 and KIF3B or LEF-AS1 was examined via luciferase gene reporter assay. In addition, the interaction between KIF3B and miR-505, as well as LEF-AS1, was further verified by RNA knockdown assay and cell reversal experiments. RESULTS: The expression of LEF-AS1 in CRC tissue specimens was found to be markedly higher than that in normal colon tissues. After transfection with LEF-AS1 siRNA, the cell viability, as well as cell migration and invasion capacities, were both attenuated. However, the cell apoptosis rate was conversely elevated. Dual-Luciferase reporter assay revealed that LEF-AS1 could combine with miR-505, which was capable of targeted binding to KIF3B. In addition, LEF-AS1 siRNA transfection attenuated cell proliferation, migration, and invasion capacities, which could be partially reversed by the overexpression of KIF3B. CONCLUSIONS: In this research, LEF-AS1 is highly expressed in CRC tissues and cell lines. However, the down-regulation of LEF-AS1 reduces the proliferation rate and suppresses the invasiveness and metastasis of CRC cells through the LEF-AS1/miR-505/KIF3B axis.

[Myeloid/lymphoid neoplasms with eosinophilia and FGFR1 rearrangement: 5 cases report and literatures review].

Objective: To investigate the clinic-pathological features, diagnosis and treatment of 8p11 myeloproliferative syndrome (EMS) . Methods: Five patients diagnosed as EMS from Jan 2014 to May 2018 at Blood Disease Hospital, Chinese Academy of Medical Sciences were enrolled. The clinical manifestations, laboratory characteristics, treatment and outcome of these patients were summarized. Results: The peripheral blood leukocyte count of 5 patients with EMS increased significantly, accompanied with an elevated absolute eosinophils value (the average as 18.89×10(9)/L) . The hypercellularity of myeloid cells was common in bone marrow, always with the elevated proportion of eosinophils (the average as 17.24%) , but less than 5% of blast cells. The chromosome karyotype of the 5 cases differed from each other, but presenting with the same rearrangement of FGFR1 gene by fluorescence in situ hybridization technology. The average interval between onset and diagnosis was 4.8 months with a median survival of only 14 months. Conclusion: EMS was a rare hematologic malignancy with poor prognosis and short survival. It was commonly to be misdiagnosed. Analysis of cytogenetics and molecular biology were helpful for early diagnosis.

[A single-center, randomized controlled trial of PEG-rhG-CSF and common rhG-CSF to promote neutrophil recovery after induction chemotherapy in newly diagnosed acute myeloid leukemia].

Objective: To compare the time of the recovery of neutrophils or leukocytes by pegylated recombinant human granulocyte stimulating factor (PEG-rhG-CSF) or common recombinant human granulocyte stimulating factor (rhG-CSF) in the myelosuppressive phase after induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients. At the same time, the incidences of infection and hospitalization were compared. Methods: A prospective randomized controlled trial was conducted in patients with newly diagnosed AML who met the enrollment criteria from August 2014 to December 2017. The patients were randomly divided into two groups according to a 1:1 ratio: PEG-rhG-CSF group and rhG-CSF group. The time of neutrophil or leukocyte recovery, infection rate and hospitalization interval were compared between the two groups. Results: 60 patients with newly diagnosed AML were enrolled: 30 patients in the PEG-rhG-CSF group and 30 patients in the rhG-CSF group. There were no significant differences in age, chemotherapy regimen, pre-chemotherapy ANC, WBC, and induction efficacy between the two groups (P>0.05) . The median time (range) of ANC or WBC recovery in patients with PEG-rhG-CSF and rhG-CSF were 19 (14-35) d and 19 (15-26) d, respectively, with no statistical difference (P=0.566) . The incidences of infection in the PEG-rhG-CSF group and the rhG-CSF group were 90.0%and 93.3%, respectively, and there was no statistical difference (P=1.000) . The median days of hospitalization (range) was 20.5 (17-49) days and 21 (19-43) days, respectively, with no statistical difference (P=0.530) . Conclusions: In AML patients after induction therapy, there was no significant difference between the application of PEG-rhG-CSF and daily rhG-CSF in ANC or WBC recovery time, infection incidence and hospitalization time.

[Therapeutic effect of low-temperature radiofrequency coblation on early-stage laryngeal cancer].

Objective: To evaluate the safety,efficacy and prognosis of low-temperature plasma radiofrequency coblation for early-stage laryngeal cancer(Tis, T1 and T2). Method: A retrospective analysis of 202 patients with early-stage laryngeal cancer who underwent the low-temperature radiofrequency coblation surgery, including 34 cases of Tis(16.83%), 49 cases of stage T1aN0M0(24.26%), 50 cases of stage T1bN0M0(24.75%) and 69 cases of stage T2N0M0(34.16%). Surgical patients were followed up closely for 6 to 60 months, with a median follow-up of 29 months. Result: Of the 202 patients,165(81.68%) had no recurrence and achieved good surgical results. None of them suffered severe complications such as post-operative hemorrhage and asphyxia. 37 cases(18.32%) had recurrence, including 1 case(0.50%) in stage Tis, 7 cases(3.47%) in stage T1a,7 cases(3.47%) in stage T1b, and 22 cases(10.89%) in stage T2. Thirteen patients who had recurrence underwent total laryngectomy(5 of which had a recurrence of T3 and 8 of which progressed to T4), including 1 in the stage T1a,2 in the stage T1b, and 10 in the stage T2. Vertical hemilaryngectomy were performed in 4 cases, 3 cases of stage T1a and 1 case of stage T2; 5 cases underwent plasma radiofrequency coblation again, including 3 cases of stage T1b and 2 cases of stage T2,no recurrence was found in all the patients; 1 patient had no obvious recurrence in the larynx but had cervical lymph node metastasis, radical neck dissection was performed; 1 patient with stage T2 recurrence was treated with a tracheotomy to relieve laryngeal obstruction without further treatment;3 cases showed improvement by radiotherapy and chemotherapy treatment after recurrence; 9 death cases,5 patients died after radiotherapy and chemotherapy, and 4 patients stopped getting treatment after recurrence.Conclusion: Low-temperature radiofrequency coblation surgery for patients with early-stage laryngeal cancer has great advantages in the preservation of laryngeal function and reduction of surgical trauma after surgery compared with traditional surgical method, and can obtain satisfactory results, but the selection of surgical indications for some patients with clinical stage T2 is still need to be carefully considered..

[Impact of duration of antibiotic therapy on the prognosis of patients with acute myeloid leukemia who had Gram-negative bloodstream infection in consolidation chemotherapy].

Objectives: To investigate the influence of duration of antibiotic therapy on the prognosis of patients with AML who had Gram-negative bloodstream infection during consolidation chemotherapy. Methods: Data were collected retrospectively from 591 patients enrolled from the registered "A Phase III study on optimizing treatment based on risk stratification for acute myeloid leukemia, ChiCTR-TRC-10001202" treatment protocol between September 2010 and January 2016 in different treatment cycles. Results: A total of 119 episodes of Gram-negative bloodstream infection occurred during consolidation chemotherapy. Excluding the 5 episodes in which fever lasted longer than 7 days, 114 episodes of infection were analyzed. The median neutrophil count was 0 (0-5.62)×10(9)/L, median neutropenia duration was 9 (3-26) days, median interval of antibiotics administration was 7 (4-14) days. Logistic regression analysis showed that there is no significant difference on 3-day recurrent fever rate and reinfection by the same type bacteria between antibiotics administration ≤7 days or >7 days (1.2% vs 3.0%, P=0.522, OR=0.400, 95% CI 0.024-6.591; 18.5% vs 21.2%, P=0.741, OR=0.844, 95% CI 0.309-2.307). Propensity score analysis confirmed there was no significant difference on same pathogen infection rate between antibiotics application time ≤ 7 days or >7 days (P=0.525, OR=0.663, 95% CI 0.187-2.352). No infection associated death occurred within 7 or 30 days in both groups. Conclusion: Discontinuation of therapy until sensitive antibiotics treated for 7 days does not increase the recurrent fever rate and the infection associated death rate. Indicating that, for AML who had Gram-negative bloodstream infection during consolidation chemotherapy, short courses of antibiotic therapy is a reasonable treatment option when the infection is controlled.

[The relationship between physical activity and incident hypertension in rural Chinese].

Objective: To investigate the relationship between physical activity (PA) and the risk of incident hypertension among population in rural areas of China. Methods: The Community Intervention of Metabolic Syndrome in China & Chinese Family Health Study (CIMIC) was conducted in 2007-2008. Data on PA, smoking, drinking, blood pressure and other variables were obtained at baseline. Then the follow-up study of incident hypertension was performed during 2012-2015. A total of 41 457 participants aged ≥18 years and free from hypertension at baseline were included in the final analyses. PA was calculated as metabolic equivalent (MET) for each participant. Cox proportional hazard models were used to explore the relationship of PA with incident hypertension according to the quartiles of PA. Results: A total of 6 780 participants developed hypertension during an average follow up of 5.8 years. The annual incidence of hypertension was 2.80%. Compared to participants in the first quartile of PA, HR (95%CI) of incident hypertension decreased with the level of PA of 0.92 (0.86, 0.99), 0.72 (0.67, 0.77) and 0.70 (0.65, 0.75) for the 2(nd), 3(rd) and 4(th) quartile, respectively (P(trend)<0.001). In subgroup analyses, compared to the first quartile, hazards of hypertension among normotensive participants (systolic blood pressure less than 120 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure less than 80 mm Hg) in the 2(nd), 3(rd) and 4(th) quartile were 0.82 (0.70, 0.95), 0.73 (0.63, 0.85) and 0.78 (0.67, 0.90), respectively (P(trend)=0.002). Among participants with prehypertension (systolic blood pressure from 120 to 139 mmHg and/or diastolic blood pressure from 80 to 89 mmHg), similar trend for the relationship of PA and incident hypertension was also found with HR (95%CI) of 0.94 (0.87, 1.01), 0.71 (0.65, 0.77) and 0.66 (0.61, 0.71) for the 2(nd), 3(rd) and 4(th) quartile, respectively (P(trend)<0.001). Conclusion: There was linear trend association between PA and incident hypertension. Increased PA in daily life may be a protective factor against hypertension.

[Spectrum of somatic mutations and their prognostic significance in adult patients with B cell acute lymphoblastic leukemia].

Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum. The impact of gene mutation on the patients' overall survival (OS) and recurrence free survival (RFS) was analyzed by the putative mutations through Kaplan-Meier, and Cox regression methods. Results: Of the 113 patients, 103 (92.0%) harbored at least one mutation and 29 (25.6%) harbored more than 3 genes mutation. The five most frequently mutated genes in B-ALL are SF1, FAT1, MPL, PTPN11 and NRAS. Gene mutations are different between Ph+ B-ALL and Ph- B-ALL patients. Ph- B-ALL patients with JAK-STAT signal pathway related gene mutation, such as JAK1/JAK2 mutation showed a poor prognosis compared to the patients without mutation (OS: P=0.011, 0.001; RFS: P=0.014,<0.001). Patients with PTPN11 mutation showed better survival than those without mutation, but the difference was not statistically significant (P value > 0.05). Besides, in Ph+ B-ALL patients whose epigenetic modifications related signaling pathway genes were affected, they had a worse prognosis (OS: P=0.038; RFS: P=0.047). Conclusion: Gene mutations are common in adult ALL patients, a variety of signaling pathways are involved. The frequency and spectrum are varied in different types of B-ALL. JAK family gene mutation usually indicates poor prognosis. The co-occurrence of somatic mutations in adult B-ALL patients indicate the genetic complex and instability of adult B-ALL patients.

[Characteristics and prognosis in adult acute myeloid leukemia patients with MLL gene rearrangements].

Objective: To analyze the clinical and laboratory characteristics, and prognosis of adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. Methods: The medical records of 92 adult AML patients with MLL gene rearrangements from January 2010 to December 2016 were retrospectively analyzed. Results: 92 cases (6.5%) with MLL gene rearrangements were identified in 1 417 adult AML (Non-M(3)) patients, the median age of the patients was 35.5 years (15 to 64 years old) with an equal sex ratio, the median WBC were 21.00(0.42-404.76)×10(9)/L, and 78 patients (84.8%) were acute monoblastic leukemia according to FAB classification. Eleven common partner genes were detected in 32 patients, 9 cases (28.1%) were MLL/AF9(+), 5 cases (15.6%) were MLL/AF6(+), 5 cases (15.6%) were MLL/ELL(+), 2 cases (6.3%) were MLL/AF10(+), 1 case (3.1%) was MLL/SETP6(+), and the remaining 10 patients' partner genes weren't identified. Of 92 patients, 83 cases with a median follow-up of 10.3 (0.3-74.0) months were included for the prognosis analysis, the complete remission (CR) rate was 85.5% (71/83), the median overall survival (OS) and relapse free survival (RFS) were 15.4 and 13.1 months, respectively. Two-year OS and RFS were 36.6% and 29.5%, respectively. Of 31 patients underwent allogeneic hematopoietic stem-cell transplantation (allo-HSCT), two-year OS and RFS for patients received and non-received allo-HSCT were 57.9% and 21.4%, 52.7% and 14.9%, respectively (P<0.001). Among patients with partner genes tested, 9 of 32 cases (28.1%) were MLL/AF9(+), the median follow-up was 6.0(4.1-20.7) months. 3 patients with MLL/AF9 underwent allo-HSCT. 23 cases (71.9%) were non- MLL/AF9(+), the median follow-up was 7.8 (0.3-26.6) months. 14 patients (60.1%) with non-MLL/AF9 underwent allo-HSCT. One-year OS for patients with MLL/AF9 and non-MLL/AF9 were 38.1% and 55.5%, respectively (P=0.688). Multivariate analysis revealed that high WBC (RR=1.825, 95% CI 1.022-3.259, P=0.042), one cycle to achieve CR (RR=0.130, 95% CI 0.063-0.267, P<0.001), post-remission treatment with allo-HSCT (RR=0.169, 95% CI 0.079-0.362, P<0.001) were independent prognostic factors affecting OS. Conclusions: AML with MLL gene rearrangements was closely associated with monocytic differentiation, and MLL/AF9 was the most frequent partner gene. Conventional chemotherapy produced a high response rate, but likely to relapse, allo-HSCT may have the potential to further improve the prognosis of this group of patients.

[Characteristics and prognosis in adult patients with early T-cell precursor acute lymphoblastic leukemia].

Objective: To analyze the clinical, laboratory characteristics and prognosis of adult early T-cell precursor acute lymphoblastic leukemia (ETP-ALL). Methods: The clinical data of 13 adult ETP-ALL patients from January 2009 to March 2017 were retrospectively analyzed and compared with non-ETP ALL patients. Results: 13 ETP-ALL patients (17.3%) were identified in 75 adult T-ALL patients, the median age of the patients was 35 years old (15 to 49 years) and 10 patients were male (76.9%). ETP-ALL patients had lower WBC count, LDH level, blasts in peripheral blood, lower incidence of thymic mass and higher PLT count compared to non-ETP ALL patients. The CR rate after one course induction chemotherapy for ETP-ALL and non-ETP ALL patients was 33.3% and 90.1%, respectively (χ(2)=26.521, P<0.001). The median overall survival(OS) was 11.33 (95%CI 0-28.46) and 25.69 (95%CI 11.98-39.41) months, respectively. The 3-year OS was 41.7% and 40.7%, respectively (P=0.699). The median event free survival (EFS) was 1.51 (95%CI 1.23-1.79) and 21.36 (95%CI 4.67-38.04) months, respectively. The 3-year EFS was 16.7% and 39.5%, respectively (P=0.002). The 3-year relapse free survival (RFS) was 53.0% and 52.0%, respectively (P=0.797). Multivariate analysis revealed that CNSL and allo-HSCT were independent risk factors affecting OS of T-ALL and ETP-ALL didn't affect the prognosis of T-ALL. Conclusion: To our knowledge, this study is the first report on characteristics and prognosis of adult ETP-ALL patients in China. At total of 13 T-ALL patients (17.3%) were classified as having ETP-ALL. These patients had a lower leukemia burden and lower CR rate after one course induction compared to non-ETP ALL patients. Allo-HSCT can improve the prognosis of ETP-ALL.

Prognostic significance of downregulated BMAL1 and upregulated Ki-67 proteins in nasopharyngeal carcinoma.

This study assessed the prognostic value of BMAL1 and Ki-67 expression in patients with nasopharyngeal carcinoma. Level of BMAL1 mRNA was assessed in tissue specimens from 36 nasopharyngeal carcinomas and 20 nasopharyngeal chronic inflammations using quantitative reverse transcriptase-polymerase chain reaction. Expression of BMAL1 and Ki-67 proteins was analyzed immunohistochemically in 90 paired nasopharyngeal carcinoma and distant normal tissues. The Kaplan-Meier curves and the Log-rank test were used to calculate prognostic significance stratified by BMAL1 and Ki67 protein expression and the COX regression model was to analyze the multivariate prognosis. BMAL1 mRNA was significantly reduced in nasopharyngeal carcinoma (4.67 ± 0.27 versus 6.64 ± 0.51 in chronic inflammation tissues, p = 0.002). Level of BMAL1 mRNA was associated with tumor distant metastasis (3.37 ± 0.66 versus 5.04 ± 0.27 compared with non-metastasis, p = 0.011). Level of BMAL1 protein was also reduced in tumor tissues and BMAL1 expression was associated with better 1-, 3- and 5-year overall survival (OS) of cancer patients (92.6%, 69.2% and 62.3% versus 59.1%, 40.9% and 0% in patients with low BMAL1 expressed tumors; p = 0.000). BMAL1 expression and age were independent prognostic factors for OS (p = 0.032). Furthermore, Ki-67 expression was high in tumor versus normal tissues and associated with poor OS of cancer patients (p = 0.035). The Pearson correlation analysis showed that there was an inverse association between BMAL1 and Ki-67 protein expression (p = 0.021). This study demonstrated that lost BMAL1 and Ki-67 overexpression were associated with poor OS of nasopharyngeal carcinoma patients.

Effects of low-dose epinephrine on perioperative hemostasis and inflammatory reaction in major surgical operations: a randomized clinical trial.

Essentials Blood loss and immune reaction are closely related to morbidity and recovery after surgery. We studied the effect of epinephrine plus tranexamic acid on blood loss and immune reaction. Epinephrine plus tranexamic acid reduced postoperative total blood loss and immune reaction. Epinephrine plus tranexamic acid did not increase the incidence of complications. SUMMARY: Background Hemostasis, thrombosis and surgical stress-induced immune reactions are important for perioperative morbidity and recovery after major surgical operations. Objectives To evaluate the effects of combined administration of low-dose epinephrine (LDEPI) and tranexamic acid (TXA) on perioperative blood loss, thromboembolic complications and inflammatory responses in patients undergoing total hip arthroplasty (THA). Patients/Methods Patients scheduled for THA (n = 195) were randomized into three interventions: intravenous LDEPI plus TXA (group IV); topical diluted epinephrine plus TXA (group TP); and TXA alone as control (group CT). The primary outcome was perioperative blood loss on postoperative day (POD) 1. Secondary outcomes included perioperative blood loss on POD 3, intraoperative blood loss, volume of drainage, transfusion values, coagulation and fibrinolysis parameters, inflammatory cytokine levels, cases of thrombosis, intravenous fluid on the operation day, and length of hospital stay. Results The mean calculated amounts of total blood loss in groups IV, TP and CT were 631.2 mL, 760.5 mL, and 825.6 mL, respectively, on POD 1; treatment effects (differences) were 194.4 mL (95% confidence interval [CI] 146.7-242.0) and 65.0 mL (95% CI 17.4-112.7). Groups IV and TP had lower levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin [IL]-1ß) and higher levels of the anti-inflammatory cytokine IL-10, and showed faster development of coagulation and fibrinolysis (without change in peak levels), than group CT early postoperation. No differences were observed in transfusion, thromboembolic and other outcomes among the groups. Conclusion The combined administration of LDEPI and TXA was more effective in reducing perioperative blood loss and alleviating the inflammatory response than TXA alone, without increasing the incidence of thromboembolic and other complications.