Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Objective:In the context of the"dual-channel"management of national medicine,it analyzes the drug purchase selection and influencing factors of local employees in retail pharmacies,and puts forward policy suggestions for optimizing the"dual-channel"of national negotiation drugs.Methods:Using the fsQCA method,it analyzes the combination of individual factors(economic level,health status,et al.)and policy factors(policy promotion efforts,policy implementation degree)on patients'retail pharmacy purchasing selects.Results:Three combinations of conditions were obtained,namely"the type of individual and policy factors working together","the type of policy promotion and implementation driving together",and"the type of policy implementation leading".Conclusion:Firstly,improving the ability of prescription circulation and drug supply in designated retail pharmacies;secondly,strengthening the information release of the"dual-channel"management policy;thirdly,building a collaborative management system centered on insured individuals.

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.
Female ; Humans ; Pregnancy ; Blood Glucose/metabolism* ; Diabetes, Gestational/metabolism* ; Glucose/metabolism* ; Melatonin/metabolism* ; Polymorphism, Genetic ; PPAR gamma ; Receptor, Melatonin, MT2/genetics*