Adult ; Aneurysm, False ; etiology ; therapy ; Embolization, Therapeutic ; Humans ; Intracranial Arterial Diseases ; etiology ; therapy ; Male ; Wounds and Injuries ; therapy

BACKGROUNDThe Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway and the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway are the two major independent signal transduction pathways. However, it has recently been found that STAT3 may be negatively regulated by ERK1/2 in gp130-dependent signaling. Cardiotrophin-1 (CT-1), a potent novel hypertrophic cytokine, depends on gp130 to induce signaling and depends on STAT3 to exert hypertrophic effect. In this study, we examined whether STAT3 activity was negatively regulated by ERK1/2 during CT-1-induced signaling in rat cardiomyocytes and, if so, whether such crosstalk interfered with the hypertrophic effect of CT-1 and, furthermore, whether the mechanism underlying the crosstalk involved phosphorylation of serine 727 (S727) in STAT3.

METHODSThe activities of ERK1/2 and STAT3 were assessed by in-gel kinase assay and Western blot analysis, respectively. The role of S727 phosphorylation in the crosstalk between ERK1/2 and STAT3 was determined by a transient transfection study using a STAT3S727A mutant. Cardiomyocyte hypertrophy was evaluated by the cellular protein-to-DNA ratio and [(3)H]-leucine incorporation.

RESULTSCT-1 simultaneously activated both ERK1/2 and STAT3 in rat cardiomyocytes. Inhibition of ERK1/2 by U0126 resulted in an increase of CT-1-induced tyrosine phosphorylation of STAT3 and, consequently, the protein-to-DNA ratio and [(3)H]-leucine incorporation. Transient transfection of the cells with STAT3S727A had no significant effect on CT-1-induced tyrosine phosphorylation of STAT3.

CONCLUSIONSSTAT3 is activated by CT-1 in rat cardiomyocytes, but full activation is mitigated by the simultaneous activation of ERK1/2. The inhibition of ERK1/2 increases the activity of STAT3, which, in turn, enhances the hypertrophic effect of CT-1. The crosstalk between ERK1/2 and STAT3 is independent of the phosphorylation of the S727 in STAT3. Such crosstalk may contribute to the development of adequate cardiac hypertrophy.

Active Transport, Cell Nucleus ; Animals ; Antigens, CD ; metabolism ; Cardiomegaly ; chemically induced ; metabolism ; Cytokine Receptor gp130 ; Cytokines ; toxicity ; DNA-Binding Proteins ; physiology ; Membrane Glycoproteins ; metabolism ; Mitogen-Activated Protein Kinase 1 ; physiology ; Mitogen-Activated Protein Kinase 3 ; physiology ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; STAT3 Transcription Factor ; Trans-Activators ; physiology ; Tyrosine ; metabolism

OBJECTIVETo investigate the health care status of female workers exposed to occupational hazards in Haidian district of Beijing and improve the labor protection of female workers.

METHODSA questionnaire provided by National Center for Women and Children's Health of Chinese CDC was used in the survey conducted to collect information about health care status of female workers in 141 factories with occupational hazards including chemical poisons and physical factors (noise, libration, microwave, high frequency and low temperature).

RESULTS141 factories were investigated, including 53 state-owned enterprises, 21 collective enterprises, 46 joint-stock enterprises, and 21 non-public enterprises. 12 251 female workers were surveyed, 10.19% (1249/12 251) of whom were exposed to occupational hazards. Of 141 factories studied, 16.31% (23/141) had no labor protection management organization.27.66% (39/141) did not provide pre-employment physical examination service to female workers.48.94% (69/141) didn't establish labor protection system for female workers in menstrual period. While, 21.28% (30/141) of the studied institutes deducted some salaries in the pregnancy, and 32.62% (46/141) deducted their wages during the puerperal period. 2.13% (3/141) arranged female workers in the posts which are forbidden by law (continuous heavy work load operation).9.93% (14/141) arranged pregnant female workers on the post forbidden by law.31.91% (45/141) and 33.33% (47/141) would deduct the time of prenatal medical examination and lactation from their working hours, respectively.39.01% (55/141) didn't afford the cost of fertility. 68.09% (96/141) had annual gynecological examination.45 factories were collected occupational examination reports, accounted for 31.91% (45/141). No female workers were found suffering from occupational disease. Of the 1865 occupational hazard factor monitoring points in 34 factories, there were 155 monitoring points, which were all noise monitoring points, did not meet the standard.

CONCLUSIONThe current health-care status of female workers is not optimistic. It is necessary to consistently improve health care legislations, establish coordinated management mechanism and strengthen the publicity of policy to protect female workers.

China ; epidemiology ; Female ; Humans ; Occupational Diseases ; epidemiology ; Occupational Exposure ; statistics & numerical data ; Occupational Health ; Surveys and Questionnaires ; Women's Health Services ; Work Capacity Evaluation ; Workplace

OBJECTIVE: To investigate whether β-globin gene 3'UTR+101G>C (HBB:c.*233G>C) variant has genetic effect and provide basis for gene diagnosis and genetic counseling. METHOD: Whole blood cell analysis and capillary zone electrophoresis (CZE) were used to analyze the hematological indexes. The most frequent 23 mutations in southern Chinese individuals were routinely measured by PCR-flow fluorenscence immunmicrobeads assay. Sanger sequencing was used to detect the other variants of β-globin gene (HBB). RESULTS: In 463 cases, a total of 7 cases with HBB:c.*233G>C variant were detected, among them 4 cases carried other pathogenic variants of HBB gene (2 cases were in trans, 2 cases were in cis), who had typical hematological characteristics of mild β-thalassemia, and 3 cases also carried abnormal hemoglobin variation, but did not have hematological characteristics of β-thalassemia. CONCLUSION The study shows that HBB:c.*233G > C variant has no obvious genetic effect and should be a benign polymorphism.
3' Untranslated Regions ; Hemoglobins, Abnormal/genetics* ; Humans ; Mutation ; beta-Globins/genetics* ; beta-Thalassemia/genetics*

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*