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: To investigate the effects and molecular mechanisms of mechano-growth factor (MGF) on the proliferation and differentiation of periodontal ligament stem cells (PDLSCs). Methods: PDLSCs were obtained using magnetic bead sorting. Flow cytometry was performed to identify biomarkers. The clonogenicity and multidifferentiation potential of PDLSCs were identified by colony-forming unit, osteogenic and adipogenic differentiation assays. A CCK8 assay was used to detect the cell activity under different concentrations of mechano-growth factors (MGF-Ct24E). Western blot was used to detect the protein expression of proliferating cell nuclear antigen(PCNA), Scleraxis, collagen type I alpha 1 (COL1A1）, Osterix, Yes-associated protein (YAP) and phosphorylation Yes-associated protein (P-YAP）in PDLSCs. YAP protein expression was observed by immunofluorescence. Knockdown of YAP expression by a siRNA, detected the expression of PCNA, Scleraxis and COL1A1under MGF-Ct24E in PDLSCs. Results : PDLSCs showed high expression of stem cell markers (CD29, CD90 and CD105) and low expression of hematopoietic markers (CD34 and CD45). PDLSCs also have a strong ability to clone. Red calcium junctions were observed by Alizarin red staining, and red lipid droplets were observed by Oil red O staining. After treatment with 50 ng/mL and 100 ng/mL MGF-Ct24E for 24 h, the cell activity of periodontal ligament stem cells was significantly enhanced (P<0.05). The protein expression of PCNA, Scleraxis and COL1A1 was significantly upregulated, and the protein expression of Osterix was significantly downregulated (P<0.05). After treatment with 50 ng/mL mechano-growth factor for 24 h, the phosphorylation of YAP protein was significantly enhanced (P<0.05), and YAP protein was observed to accumulate in the nucleus by immunofluorescence. Following inhibition of YAP expression, PCNA and Scleraxis had significantly downregulated expression caused by MGF-Ct24E (P<0.05). Conclusion MGF promotes proliferation and fibrogenesis via upregulation of YAP activities.

BACKGROUND: Although newly formed constructs of feasible pressure-preadjusted bone marrow mesenchymal stem cells (BMSCs) and platelet-rich fibrin (PRF) showed biomechanical flexibility and superior capacity for cartilage regeneration, it is still not very clear how BMSCs and seed cells feel mechanical stimuli and convert them into biological signals, and the difference in signal transduction underlying mechanical and chemical cues is also unclear. METHODS: To determine whether mechanical stimulation (hydrostatic pressure) and chemical cues (platelet-rich fibrin, PRF) activate canonical or noncanonical Wnt signaling in BMSCs, BMSCs cocultured with PRF were subjected to hydrostatic pressure loading, and the activation of the Wnt signaling molecules and expression of cartilage-associated proteins and genes were determined by western blotting and polymerase chain reaction (PCR). Inhibitors of canonical or noncanonical Wnt signaling, XVX-939 or L690,330, were adopted to investigate the role of Wnt signaling molecules in mechanically promoted chondrogenic differentiation of BMSCs. RESULTS: Hydrostatic pressure of 120 kPa activated both Wnt/b-catenin signaling and Wnt/Ca2+ signaling, with the the maximum promotion effect at 60 min. PRF exerted no synergistic effect on Wnt/b-catenin signaling activation. However, the growth factors released by PRF might reverse the promotion effects of pressure on Wnt/Ca2+ signaling. Real-time PCR and Western blotting results showed that pressure could activate the expression of Col-II, Sox9, and aggrecan in BMSCs cocultured with PRF. Blocking experiment found a positive role of Wnt/b-catenin signaling, and a negative role of Wnt/ Ca2+ signaling in chondrogenic differentiation of the BMSCs. Mutual inhibition exists between canonical and noncanonical Wnt signaling in BMSCs under pressure. CONCLUSION Wnt signaling participates in the pressure-promoted chondrogenesis of the BMSCs co-cultured with PRF, with canonical and noncanonical pathways playing distinct roles during the process.

Objective:To translate the English version of the health enhancement lifestyle profile-screener into Chinese and assess its reliability and validity based on classical test theory(CTT) and Rasch model among the elderly.Methods:A total of 447 older adults from rural and urban areas in Sichuan Province from December 2020 to March 2021 were selected by convenience sampling, and were surveyed with the revised Chinese version of health enhancement lifestyle profile-screener(HELP-CS). Rasch and CTT-based approaches were used to evaluate the unidimensionality data-model fit, internal consistency, test-retest reliability, criterion validity and discriminant validity of the questionnaire.Results:According to the results of the initial test questionnaire, the ninth question was deleted, and 14 items were retained to form a formal questionnaire. The formal test results showed that HELP-CS met the unidimensionality, and the residual mean square error for item 2 and 14 were within the acceptable range, which were 1.49 and 1.41. Item 10 and 12 had the highest logits, which were 1.87 and 1.91 respectively. There were gender differences in some topics. The Cronbach′s α of the scale was 0.719, and the test-retest reliability was 0.704 after two months. The criterion correlations with HPLP-CE were 0.581.Conclusion:HELP-CS has good adaptability, reliability and validity in the elderly, and can be used as a quick and effective screening tool in the study of the lifestyle of the elderly.

Objective To explore and construct specialist nursing practice of safety management of sedation and analgesia in interventional surgery in China.Methods From February 2016 to November 2017, literature analysis, semi-structured interviews and cross-sectional survey were used to establish the practice scope of specialized nursing in the safety management of sedation and pain relief in interventional surgery. Delphi expert advice consultation method was used to consult and screen related items, and the weight was determined by analytic hierarchy process.Results The positive coefficient of the two rounds of expert consultation was 100％, the expert authority coefficient Cr was 0.85. The coordination coefficients of the second round from the recognition degree, correlation degree and operability were 0.204, 0.228 and 0.215 respectively (P<0.01). Finally, a total of 3 dimensions (46 items), including preoperative evaluation (8 items), intraoperative management (36 items), and postoperative evaluation and monitoring (2 items).Conclusions In order to promote the safety management of sedation and pain relief in interventional surgery, a set of specialized nursing practice areas suitable for nurses were constructed.

Objective To observe the clinical effect of 0.9％ sodium nasal irrigation to adjuvant treatment of allergic rhinitis with postnasal drip symptoms.Methods Fifty-eight patients of allergic rhinitis with postnasal drip symptoms were divided into two groups by random number table method,29 cases in each.The treatment group was treated on the basis by antihistamine drugs in the specification,nasal steroid and nasal decongestants,given 0.9％ sodium to nasal irrigation before nasal steroid;the control group was not given 0.9％ sodium to nasal irrigation before nasal steroid,treatment for 6 weeks,improvement of allergic rhinitis symptoms and postnasal drip symptoms were observed in two groups.Results The clinical efficacy of allergic rhinitis:the total effective rate in treatment group was higher than that in control group [96.6％ (28/29) vs.72.4％ (21/29)],which reached statistical significance (P ＜ 0.05).The clinical efficacy of postnasal drip symptoms:the effective rate in treatment group was higher than that in control group [89.7％ (26/29) vs.58.6％(17/29)],which reached statistical significance(P＜ 0.05).Conclusions 0.9％ sodium nasal irrigation can improve the nasal symptoms of allergic rhinitis,reduce postnasal drip symptoms at the same time.It is a safe and effective treatment method.