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*

The“14th Five-Year” National Eye Health Plan has been released and national eye health has risen as a national strategy. Cataract is the primary blinding eye disease in our country, which seriously affects the national eye health. Shaanxi Province, an old revolutionary base area in the western of China, has a relative lower socioeconomic level and about millions of people need to undergo cataract surgery. In 1996, multi-cooperation built the mobile ophthalmic operation vehicle — “Fuming No.1” to contribute the poverty alleviation initiative in Shaanxi Province. In the past 25a, “Fuming No.1” has taken the advantage of the convenience of mobile operation vehicles, implementing operations in rural, mountainous and old areas with weak medical services in Shaanxi Province. A total of more than 480 trips have been made, with a total mileage of more than 200 000 kilometers,covering 104 counties and districts in the province, and nearly 60 000 cases of cataract operations have been completed. “Fuming No.1” bring the light, relieve the pain for cataract patients and help them better fit the world. Furthermore, “Fuming No.1” also offers free operation and intraocular lens for more than 30 000 poor rural patients and reduces medical expenses by nearly 10 million yuan, which has obtained high praise and support from the patients and all walks of life. In addition, “Fuming No.1” is also a mobile training vehicle, which could improve the operation skills of ophthalmologists. In the process of teaching and training, the operations had also been completed with high quality. In view of the unbalanced economic development in our country, “Fuming No.1” will expand service projects, innovate work models, and continue to construct eye healthy in Shaanxi province, making greater contributions to consolidating the achievements of poverty alleviation.

OBJECTIVE: To investigate the age distribution of Mongolian patients with cerebral infarction caused by thrombosis and the correlation and consistency between thromboelastography (TEG) and four parameters of coagulation. METHODS: The age distribution of 298 Mongolian patients with cerebral infarction treated in Affiliated Hospital of Inner Mongolia Minzu University from January 2020 to December 2021 and their TEG, four items of routin coagulation and platelet count were analyzed retrospectively. The correlation and consistency of above-mentioned two detection methods were statistically analyzed. RESULTS: The onset age of 298 Mongolian patients with cerebral infarction was mainly 61-70 years old, accounting for 38.3%, followed by 51-60 years old, accounting for 26.8%. The R time detected by TEG was linearly correlated with PT and APTT（r=0.186，r=0.152）. K value, MA value and α-Angle measured by TEG was linearly correlated with Fib (r=-0.364，r=0.616，r=0.359), K value, MA value and α-Angle measured by TEG was linearly correlated with Plt (r=0.318，r=0.519，r=0.301). The R time detected by TEG was consistent with PT and APTT, and the Kappa values were 0.252 (P<0.001), 0.336 (P<0.001). K, MA, and α-Angle measured by TEG was consistent with Fib, the Kappa values were 0.265 (P<0.001), 0.289 (P<0.001) and 0.290 (P<0.001), respectively; K、MA and α-Angle measured by TEG was consistent with Plt, the Kappa values were 0.276 (P<0.001), 0.285 (P<0.001) and 0.302 (P<0.001), respectively. CONCLUSION The onset age of Mongolian patients with cerebral infarction caused by thrombosis is mainly 61-70 years old, followed by 51-60 years old. The onset age shows a younger trend. There is a significant correlation between TEG and coagulation, but the consistency is weak, therefore, the two methods can not be replaced each other.
Aged ; Blood Coagulation ; Blood Coagulation Tests/methods* ; Cerebral Infarction ; Humans ; Middle Aged ; Retrospective Studies ; Thrombelastography/methods* ; Thrombosis

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPA CONCLUSION AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPA
DNA-Binding Proteins/genetics* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins/genetics* ; Remission Induction

OBJECTIVE: To analyze the clinicobiological heterogeneity of NPM1 mutated (NPM1 METHODS: The NGS data based on 112 genes related to blood disease in 238 newly diagnosed patients with NPM1 RESULTS: Among all the patients, at least one co-mutation was detected out. The median number per case of the mutated genes, including NPM1 CONCLUSION Prognoses of AML involving less common NPM1 missense mutations should be stated on a case by case basis. The mutational landscape and co-occurrence and mutual exclusivity correlations of NPM1
Base Sequence ; High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Nuclear Proteins/genetics*

Objective:To explore systematic implementation of World Health Organization Family International Classifications (WHO-FICs) in the field of rehabilitation: the theoretical and policy framework at macro level, governance and management mechanism at meso level, and implementation modules at micro levels, respectively. Methods:The policy and theoretical framework of rehabilitation development was discussed based on the international rehabilitation policy documents of WHO, mainly as World Report on Disability, Global Action Plan on Disability and Rehabilitation in Health Service System. Protocol and roadmap of systematic implementation of WHO-FICs, including International Classification of Diseases (ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHIβ-2) was proposed. Results:With the use of WHO-FICs, the theoretical and policy framework of rehabilitation was constructed, and the contents and principles of modern rehabilitation services were clarified at macro-level. Rehabilitation is an important part of health service, there are six building blocks: i.e. leadership and governance, financing, human resources for health, service providing, medical technology and health information system. It proposed to use knowledge management system of WHO-FICs, including the classification, nomenclature, definitions, descriptions, terminology and coding systems, to standardize rehabilitation evaluation and statistics. The management and governance system of rehabilitation should be implemented using WHO-FICs. Rehabilitation services are based on the bio-psycho-social model and implemented the principles of people-centered and functioning-oriented. The systematic implementation of WHO-FICs in rehabilitation abide by the model of "Evaluation (ICHI)－Evaluation, Description, Classification and Coding of Functioning (ICF)－Disease Classification, Diagnosis and Coding (ICD)－Rehabilitation Intervention (ICHI)", and with the standardized process of "Evaluation (Functioning and unmet needs)－Diagnose (Disease and Functioning)－Planning of Rehabilitation－Intervention－Evaluation of Outcome". The mic-modules of implementation of WHO-FICs in rehabilitation had been constructed. There were 28 categories of diseases, 7 categories of functioning and 6 categories of rehabilitation interventions in rehabilitation proposed by International Society of Physical and Rehabilitation Medicine. According to ICD-11 and ICF, it proposed to use WHO Disability Assessment Schedule 2.0 (WHODAS 2.0), Brief Model Disability Survey (MDS-B) and VB40 Generic Functioning Domains (VB40), and the ICF core-sets in evaluation of functioning and rehabilitation outcome. The implementation of WHO-FICs in management of medical records and reporting realized the standardized management of medical record, encoding of diseases, functioning and intervention, reporting of performance, and provided tools for billing, reimbursement and payment management of rehabilitation. It proposed to develop WHO-FICs based clinical data sets and big data to implement functioning-related Diagnosis Related Groups and case-mix statistics. Conclusion:With the systematic implementation of WHO-FICs in rehabilitation, the policy and theoretical framework at macro level had been developed. The mechanism of management and governance at meso level had been explored. The application modules and approaches at micro level had been established. A scientific and effective overall solution had been proposed to enhance the scientific, standardized, refined and informatization level, strengthen the level and governance capacity, and improve the quality, safety and the coverage of rehabilitation services.

This paper explored the background, framework and approach, contents and implementation of WHO Rehabilitation in Health System using approaches of ICF and WHO Handbook for Guideline Development. The actions and significances of implementations of seven recommendations and one good practice statements on assistive products had been discussed.

Objective To use World Health Organization Family International Classifications (WHO-FICs) to explore the framework and approaches of development and research of guidelines of rehabilitation at levels of policies, community and services.Methods The important documents and tools of rehabilitation at international level, including United Nations Convention on the Rights of Persons with Disabilities, WHO World Report on Disability, Community-based Rehabilitation Guideline, Rehabilitation in Health Service System, and International Classification of Diseases (ICD), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Intervention (ICHI) of WHO-FICs, had been discussed.Results The framework, classifications, diagnosis and description of diseases and functioning, coding, intervention and functioning evaluation based on ICD-11, ICF and ICHI-β-2 had been established for development and implementation of rehabilitation guidelines and Cochrane rehabilitation.Conclusion The framework and systematic approaches of ontology, classification, terminology, coding, diagnosis and description of diseases and functioning, interventions and evaluations for the development and implementation of rehabilitation guidelines had been developed.

OBJECTIVE: To investigate the effect of other gene mutations outside the fusion gene on the first complete remission (CR) induced by one course of induction chemotherapy in patients with core binding factor-associated acute myeloid leukemia (CBF-AML). METHODS: DNA was extracted from bone marrow or peripheral blood samples of newly diagnosed CBF-AML patients admitted to the Hematology Department of the Second Hospital of Shanxi Medical University from January 2015 to January 2019. Next-generation sequencing was used for detection of 34 kinds of hematologic malignancy-related gene mutations in patients with CBF-AML, the effect of related gene mutations on the first complete remission (CR) rate in one course of induction chemotherapy was analyzed by combineation with clinical characteristics. RESULTS: 34 kinds of genes in bone marrow or peripheral blood of 43 patients were detected by high throughput sequencing and the gene mutations were detected in 16 out of 34 genes. The mutation rate of KIT gene was the highest (48.8%), followed by NRAS (16.3%), ASXL1 (16.3%), TET2 (11.6%), CSF3R (9.3%), FLT3 (9.3%), KRAS (7.0%). The detection rates of mutations in different functional genes were as follows: genes related with signal transduction pathway (KIT, FLT3, CSF3R, KRAS, NRAS, JAK2, CALR, SH2B3, CBL) had the highest mutation frequency (72.1% (31/43); epigenetic modification gene mutation frequency was 30.2% (13/43), including ASXL1, TET2, BCOR); transcriptional regulation gene mutation frequency was 7.0% (3/43), including ETV6, RUNX1, GATA2). Splicing factor related gene mutation frequency was 2.3% (1/43), including ZRSR2). The CR rate was 74.4% after one course of induction chemotherapy. At first diagnosis, patients with low expression of WT1 (the median value of WT1 was 788.9) were more likely to get CR (P=0.032) and the RFS of patients who got CR after one course of induction chemotherapy was significantly longer than that of patients without CR [7.6 (2.2-44.1) versus 5.8 (1-19.4), (P=0.048)]. The rate of CR in the signal transduction pathway gene mutation group was significantly lower than that in non-mutation group (64.5% vs 100%) (P=0.045), while the level of serum hydroxybutyrate dehydrogenase (HBDH) was significantly higher than that in non-mutation group [(418 (154-2702) vs 246 (110-1068)] (P=0.032). There was no difference in CD56 expression between the two groups (P=0.053), which was limited to the difference between (≥20%) expression and non-expression. (P=0.048). CONCLUSION CBF-AML patients with signal transduction pathway gene mutation are often accompanied by high HBDH level and CD56 expression, moreover, the remission rate induced by one course of treatment is low.
High-Throughput Nucleotide Sequencing ; Humans ; Leukemia, Myeloid, Acute ; Mutation ; Prognosis ; Signal Transduction

OBJECTIVETo compare the expression of pinopodes, the marker of endometrial receptivity, during the implantation window in Kunming mice stimulated with two different doses of raloxifene (RAL).

METHODSForty-eight 8-week-old female Kunming mice were randomly divided into 4 groups (n=12), namely saline group, clomiphene citrate (CC, 18 mg/kg) group, RAL (33 mg/kg) group and RAL (44 mg/kg group). In each group, the mice received intragastric administration of 1 mL of normal saline containing CC or RAL at the specified doses or saline only as indicated for ovulation induction, once daily for 2 days. The mice received then injection with 5 IU human chorionic gonadotropin (HCG) and mated and on day 4.5 of gestation, the pregnant mice were sacrificed for examination of the uterus with scanning electron microscopy.

RESULTSAbundant and well developed pinopodes were observed in the endometrium of the mice in the 2 RAL groups and in the saline control group. The mice in CC group showed obviously reduced endometrial pinopodes with poor development.

CONCLUSIONSRAL at two different doses does not obviously affect the expression of pinopodes in the uterine epithelium of mice, suggesting the safety of RAL at these two doses for ovulation induction without causing adverse effects on endometrial receptivity.