Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Aim To explore the role and mechanism of nuclear receptor subfamily 1,group D,member 1(NR1D1)in the proliferation and migration of mouse adventitial fibroblasts(AFs). Methods Primary AFs isolated from C57BL/6J mice were cultured. Adenovirus carrying Nr1d1 gene was used to overexpress NR1D1 in AFs. The expression of β-catenin was restored by SKL2001. Proliferating cell nuclear antigen(Ki-67)immunofluorescence staining and CCK-8 staining were used to determine cell proliferation,and scratch test was used to determine cell migration. qPCR was used to determine the mRNA level of Nr1d1. Western blot was used to determine the protein levels of NR1D1 and β-catenin. To investigate the role of NR1D1 in intimal hyperplasia,20 male wild type C57BL/6J mice were randomly divided into sham group,carotid artery endothelial injury,sham+SR9009(NR1D1 agonist)group and carotid artery endothelial injury+SR9009(n=5 in each group). They were treated with DMSO or SR9009(100 mg·kg-1·d-1)via intraperitoneal injection for 14 days after operation,respectively. The degree of carotid intimal hyperplasia was measured by HE staining 28 days after operation. Results NR1D1 overexpression significantly reduced the percentage of Ki-67-positive cells(P<0.01),total cell number(P<0.01)and slowed down the rate of wound-healing(P<0.01). NR1D1 overexpression significantly inhibited the expression of β-catenin(P<0.05). After the expression of β-catenin was restored by SKL2001,the inhibitory effects of NR1D1 overexpression on the proliferation and migration of AFs were abolished(P<0.01). Enhanced activity of NR1D1 significantly ameliorated intimal hyperplasia after carotid endothelial injury(P<0.01). Conclusion NR1D1 may inhibit the proliferation and migration of AFs via suppressing the expression of β-catenin.

OBJECTIVE: To explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci. METHODS: A questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke. RESULTS: A total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033). CONCLUSION Decreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.
Aged ; Genome-Wide Association Study ; Humans ; Ischemic Stroke ; Middle Aged ; Sleep/genetics* ; Stroke/genetics* ; Surveys and Questionnaires

Objective: To examine the influence of sacroiliac joint reduction quality on the clinical effect of bionic reduction and internal fixation for pelvic ring injury. Methods: From January 2014 to February 2019,the clinical data of 78 patients diagnosed with pelvic ring injury involving sacroiliac joints and treated with bionic reduction and internal fixation at Honghui Hospital Affiliated to Medical College of Xi'an Jiaotong University were retrospectively analyzed.There were 48 males and 30 females,aged (48.3±8.3)years (range:28 to 68 years).After bionic reduction and internal fixation,the patients were grouped according to the maximum displacement distance (d) of sacroiliac joint residual on the damaged side measured by CT examination. Patients with d≤5 mm were included in anatomical bionic reduction group,and patients with d>5 mm were included in non-anatomical bionic reduction group.In non-anatomical bionic reduction group,according to the direction of residual displacement,the patients were divided into separation displacement group and anterior-posterior displacement group. The X-ray examination was performed immediately and at the last follow-up after operation.If sacroiliac joint was relocated,or internal plant loosening,displacement,fracture and re-displacement of fracture,it was defined as internal fixation failure.Majeed pelvic fracture scoring system was used to evaluate the postoperative functional status of the two groups,and visual analogue scale (VAS) was used to evaluate the postoperative pain.Comparison between groups was performed by completely random design ANOVA,χ² test,Fisher's exact test,Mann-Whitney U and Kruskal-Wallis H test. Results: According to the CT examination,28 cases were included in anatomical bionic reduction group,and 50 cases were included in non-anatomical bionic reduction group.In non-anatomical bionic reduction group,27 cases were divided into separation displacement group and 23 cases were in anterior-posterior displacement group.There was no significant difference in general data among anatomical bionic reduction group,separation displacement group and anterior-posterior displacement group (P>0.05). The follow-up time was (37.8±6.6) months (range:25 to 51 months). At the last follow up,the excellent and good rate of Majeed score in anatomical bionic reduction group was 96.4%(27/28),which was better than that in separation displacement group(74.1%(20/27)) and anterior-posterior displacement group (30.4%(7/23)),the difference was statistically significant (Z=-6.479,P<0.01;Z=-6.256,P<0.01); and the good rate of the separation displacement group was better than that of the anterior-posterior displacement group(Z=-3.607,P<0.01).The VAS of anatomical bionic reduction group (17 cases with 0 point, 11 cases with 1 to 3 points) were lower than that of the displacement group (6 cases with 0 point,16 cases with 1 to 3 points,5 cases with 4 to 6 points) and anterior-posterior displacement group (3 cases with 0 point,7 cases with 1 to 3 points,13 cases with 4 to 6 points),the difference was statistically significant (Z=-3.515,P<0.01;Z=-3.506,P<0.01),and there was no difference between separation displacement group and anterior-posterior displacement group.Total of 8 cases of internal fixation failure occurred,and the failure rate of anatomical bionic reduction group (0,0/28) was lower than that of the separation displacement group (11.1%,3/27) and anterior-posterior displacement group (21.7%,5/23) (P=0.111,P=0.014),and there was no difference between separation displacement group and anterior-posterior displacement group(P=0.444). Conclusions: In the bionic reduction and internal fixation of pelvic fracture involving sacroiliac joint injury,the functional status,pain and internal fixation failure rate of patients with anatomical bionic reduction of sacroiliac joint are significantly better than those in the non-anatomical bionic reduction.The functional recovery of patients with separation displacement is better than that of the patients with anterior and posterior displacement.
Bionics ; Bone Screws ; Female ; Fracture Fixation, Internal ; Fractures, Bone/surgery* ; Humans ; Male ; Retrospective Studies ; Sacroiliac Joint/surgery*

OBJECTIVE: To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL). METHODS: The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy. RESULTS: One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT). The complete remission (CR) rate was 85.7% at d33 of induction remission chemotherapy. The serious adverse event and treatment-related mortality (TRM) rate was 71.4% and 14.3%, respectively. The recurrence rate was 21.4% and the median time of relapse was 12(9.7-18.4) months. Except for 4 patients who gave up treatment, the 5-year event-free survival (EFS) rate in the other 11 patients was (54.5±15.0)%. The 5 years EFS of 4 patients who received consolidation chemotherapy was significantly lower than the 6 patients who received allo-HSCT after CR (25.0%±21.7% vs 83.3%±15.2%, P=0.033). CONCLUSION The CCLG-ALL2008 (for high-risk group) protocol in treatment of children with MPAL can get a high CR rate, but also with a high incidence of SAE. The patients received allo-HSCT after CR may have a good prognosis.
Child ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Phenotype ; Prognosis ; Remission Induction ; Retrospective Studies

OBJECTIVE: To investigate the clinical features and prognostic factors of acute lymphoblastic leukemia (ALL) children with P2RY8-CRLF2 gene rearrangement. METHODS: A total of 108 children with B-cell ALL (B-ALL) were diagnosed and systematically treated according to Chinese Children's Leukemia Group (CCLG) -ALL 2008 in our hospital from January 2016 to December 2016. The 108 patients were divided into two groups according to the result of mutiplex polymerase chain reaction: group with P2RY8-CRLF2 gene rearrangement and group without P2RY8-CRLF2 gene rearrangement. The ALL children with P2RY8-CRLF2 gene rearrangement were all treated by CCLG-ALL 2008 high-risk group (HR) regimens, and the ALL children in group without P2RY8-CRLF2 gene rearrangement received different intensity chemotherapy according to clinical risk classification. RESULTS: Five (4 male and 1 female) out of 108 patients with B-ALL had P2RY8-CRLF2 gene rearrangement. In the 5 B-ALL patients with P2RY8-CRLF2 gene rearrangement, the median age of the was 4 (2-6) years old and the median WBC count was 26.2 (2.46-525.1)×10 CONCLUSION The early treatment response and prognosis of ALL children with P2RY8-CRLF2 gene rearrangement are worse, and more effective protocol is needed for this subtype patients.
Child ; Child, Preschool ; Disease-Free Survival ; Female ; Gene Rearrangement ; Humans ; Male ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Prognosis ; Receptors, Cytokine/genetics* ; Receptors, Purinergic P2Y/genetics*

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; Extracorporeal Membrane Oxygenation ; Humans ; Lung Transplantation ; methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Pulmonary Fibrosis ; mortality ; surgery ; Respiratory Distress Syndrome, Adult ; mortality ; surgery

OBJECTIVE: To investigate the clinical features and prognostic factors of childhood Burkitt Lymphoma/leukemia. METHODS: The clinical data of 35 patients with newly-diagnosed childhood Burkitt lymphoma/leukemia from March 2011 to September 2017 in Fujian Medical University Union Hospital were retrospectively analyzed and summarized. Among 35 patients, 5 gave up treatment and one patient died of multiple organ failure before treatment, and 29 patients received CCCG-BNHL-2010 protocol chemotherapy. RESULTS: The 35 cases of BL/L includsd 31 males and 4 females (M∶F=7.75∶1) with the median age of 5(2.0-11) years. Clinically, the common infiltration sites were as follows: abdominal organs (especially ileocecus, 21/35, 60%), bone marrow (21/35, 60%), faciomaxillary (10/35, 28.57%), and central nervous system (8/35, 22.85%). According to St. Jude staging system, 6 patients were grouped into stage Ⅱ, and 8 into stage Ⅲ and 21 into stage Ⅳ, among which the bone marrow blasts of 17 patients were more than 25%. The analysis of therapeutic efficacy and prognosis showed that in median follow up of 23.4 (5.3-86.4) months, 5 patients relapsed (5/29, 17.24%), the median relapsed time was 5.7 (3.9-7.2) months; tow-year overall survival (OS) rate and progression-free survival (PFS) rate was 79.2%±7.6% and 78.3%±7.9%, respectively. Univariate analysis showed that the 2-year OS and PFS in patients with LDH＞2N, stage Ⅳ (bone marrow infiltration), central nervous system infiltration and no-CR after 2 courses of treatnent all were significantly lower than those in patients with LDH≤2N, stageⅡ-Ⅲ, without central nervous system infiltration as well as CR after 2 course of treatment (P values were 0.015, 0.015, 0.019 and 0.000, respectively). Cox regression analysis showed that no-CR after 2 course was an independent unfavorable prognostic factor (HR 0.34, 95%CI: 0.03-0.407). CONCLUSION The childhood Buruitts lymphoma/leukemia is more freguently seen in males and school-age children, Advanced stage, bone marrow and contral nervous system infitration are common at the first visit to doctor, moreover the Burkitt's lymphoma/leykemia present repid progression and dangerous feature. The current intensive chemotherapy (high dose of drugs and short course) possess the significant therapeutic efficacy for this disease, but the patients should have very poor prognosis if they can not achieve CR after 2 course of chemotherapy.
Antineoplastic Combined Chemotherapy Protocols ; Burkitt Lymphoma ; Child ; Child, Preschool ; Female ; Humans ; Male ; Prognosis ; Retrospective Studies

Background:: Depression and anxiety have been correlated with elevated risks for quality-of-life (QOL), adverse outcomes, and medical expenditure in patients with acute coronary syndrome (ACS). However, the relevant data are lacking for Chinese ACS populations, especially regarding different effects of major depression, anxiety, and comorbidity. The objective of this study was to evaluate the dynamic changes of depression and/or anxiety over 12 months and examine the effects of depression, anxiety, and comorbidity on QOL, adverse outcomes, and medical expenditure in Chinese patients with ACS. Methods:: For this prospective longitudinal study, a total of 647 patients with ACS were recruited from North China between January 2013 and June 2015. Among them, 531 patients (82.1%) completed 12-month follow-ups. Logistic regression model was utilized for analyzing the association of baseline major depression, anxiety, and comorbidity with 12-month all-cause mortality, cardiovascular events, QOL, and health expenditure. Results:: During a follow-up period of 12 months, 7.3% experienced non-fatal myocardial infarction (MI) and 35.8% cardiac rehospitalization. Baseline comorbidity, rather than major depression/anxiety, strongly predicted poor 12-month QOL as measured by short-form health survey-12 (odds ratio [OR]: 1.77, 95% confidence interval [CI]: 1.22–2.52, P = 0.003). Regarding 12-month non-fatal MI and cardiac re-hospitalization, baseline anxiety (OR: 2.83, 95% CI: 1.33–5.89, P < 0.01; OR: 4.47, 95% CI: 1.50–13.00, P < 0.01), major depression (OR: 2.58, 95% CI: 1.02–6.15, P < 0.05; OR: 5.22, 95% CI: 1.42–17.57, P < 0.03), and comorbidity (OR: 6.33, 95% CI: 2.96–13.79, P < 0.0001, OR: 14.08, 95% CI: 4.99–41.66, P < 0.0001) were all independent predictors, and comorbidity had the highest predictive value. Number of re-hospitalization stay, admission frequency within 12 months and medical expenditure within 2 months were the highest in patients with ACS with comorbidity. Conclusions: Major depression and anxiety may predict 12-month non-fatal MI and cardiac re-hospitalization. However, comorbidity has the highest predictive value with greater medical expenditure and worse QOL in Chinese patients with ACS. And depression with comorbid anxiety may be a new target of mood status in patients with ACS.

OBJECTIVE: To analyze the clinical features and to explore the therapeutic efficacy and prognostic factors of children with anaplastic large cell lymphoma (ALCL). METHODS: The clinical data of 18 children with ALCL admitted in Department of Pediatric Hematology, Union Hospital of Fujian Medical University from April 2011 to November 2017 was collected and analyzed. RESULTS: The male to female ratio was 2∶1, the median age of onset was 6 (0.9-11.3) years old, and the B symptom was positive in 13 cases. The most common initial symptom was lymphadenopathy (in 17 cases). All patients were manifested with multiple organ involvements. 4 cases were classified as clinical stage Ⅱ, 11 cases as stage Ⅲ, and 3 cases as stage Ⅳ. Laboratory tests revealed 9 cases with leukocytosis and 8 cases with CRP＞20 mg/L. The pathological results showed all ALK-positive anaplastic large cell lymphoma with Ki-67 rate between 40%-90%. The median follow-up time was 41 months. 2 patients died before treatment, 1 patient was lost to follow-up. 15 patients accepted chemotherapy protocol of CCCG-BNHL-2011. 2 patients relapsed early, the 3 year event-free survival rate was (76.7±10.2)%. Kaplan-Meier survival analysis showed leukocytosis, increased CRP level, bone involvement and clinical stage were factors affecting prognosis. CONCLUSION ALCL is a relatively rare subtype of childhood non-Hodgkin's lymphoma with high invasiveness. Leukocytosis, increased CRP level, bone involvement and clinical stage are poor factors affecting the prognosis of patients.
Antineoplastic Combined Chemotherapy Protocols ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Humans ; Infant ; Lymphoma, Large-Cell, Anaplastic ; Male ; Prognosis