Objective:To explore the effect of tyrosine kinase inhibitor (TKI) dose reduction regimen in patients with chronic-phase chronic myeloid leukemia (CML) and its prognostic impact.Methods:A retrospective cohort study was conducted. The clinical data of patients with chronic-phase CML treated with reduced-dose TKI in the First Affiliated Hospital of Soochow University between January 2018 and December 2022 were collected. Patients were divided into groups based on Sokal score, European Treatment and Outcome Study long-term survival (ELTS) score, TKI drug classification and dose reduction, and treatment phase. The overall survival (OS), the cumulative incidence of major molecular response (MMR), the cumulative molecular recurrence rate and event-free survival (EFS) among patients in different strata were compared. Kaplan-Meier method was used for survival analysis.Results:Among 154 patients with chronic-phase CML, the median duration [ M ( IQR)] of reduced-dose TKI therapy was 35.4 months (34.9 months); Sokal score high-risk and low-/intermediate-risk groups comprised 20 cases (12.99%) and 134 cases (87.01%), respectively; ELTS score high-risk and low-/intermediate-risk groups comprised 14 cases (9.09%) and 140 cases (90.91%), respectively. Among 154 patients, 83 cases (53.90%) received imatinib therapy, while 71 cases (46.10%) received second-generation TKI; 138 patients (89.61%) maintained stable TKI dosing at the first dose level, and 16 patients (10.39%) maintained it at the second dose level. The induction therapy group comprised 33 patients (21.43%), while the maintenance therapy group included 121 patients (78.57%). The 3-year OS rate of all 154 patients was 90.6%. Patients in the Sokal score high-risk group demonstrated a lower 3-year OS rate compared to those in the low-/intermediate-risk group (64.1% vs. 96.7%) ( P < 0.001); patients in the ELTS score high-risk group had a lower 3-year OS rate compared to those in the low-/intermediate-risk group (62.9% vs. 95.8%) ( P = 0.002). There was no statistically significant difference in the 3-year OS rate of patients receiving the first dose level and those receiving the second dose level (90.6% vs. 90.0%, P = 0.478); there was no statistically significant difference in the 3-year OS rate of the induction therapy group and the maintenance therapy group (88.9% vs. 91.4%, P = 0.868). Among the 33 patients in the induction therapy group, all received the first dose level. After treatment, 28 achieved MMR, and 2 achieved molecular response 4.0 (MR4.0). The cumulative 1-year MMR rate of all patients in reduction therapy group was 95.8%, with a median time to MMR of 8.4 months; patients in the high-risk Sokal score group had a 1-year cumulative MMR rate of 50.0%, which was lower than that of the low-/intermediate-risk group (95.3%) ( P = 0.014); the median time to MMR was 14.7 months and 7.8 months, respectively. The cumulative 1-year MMR rate of patients treated with first-generation TKI was lower than that in those treated with second-generation TKI (65.0% vs. 100.0%, P = 0.034), and the median time to MMR of patients treated with first-generation TKI was longer than that those treated with second-generation TKI (9.1 months vs. 6.9 months). Among the 149 patients who achieved MMR, 5 experienced molecular relapse, resulting in a 3-year cumulative molecular relapse rate of 8.3%. In the Sokal score low-/intermediate-risk group, the 3-year cumulative molecular relapse rate (1.5% vs. 39.8%, P < 0.001), EFS rate (92.3% vs. 57.1%, P < 0.001), and OS rate (100.0% vs. 62.8%, P < 0.001) were better than those in the Sokal score high-risk group. The 3-year cumulative molecular relapse rate and 3-year EFS rate in patients receiving first dose level therapy were better than those in patients receiving second dose level therapy, and the differences were statistically significant (all P < 0.001). Conclusions:Patients with chronic-phase CML can still obtain good outcomes when receiving dose-reduced TKI, while the prognosis of patients in high-risk group is relatively poor. The choice of TKI and the dosage reduction should be individualized based on patients' characteristics.

In the process of enamel development, premature senescence and apoptosis of ameloblasts are important causes of hereditary enamel hypoplasia. Silence information regulator 2-related enzyme 1 (Sirt1) is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase that has been widely reported to be involved in the regulation of cell senescence. This paper reviews the research progress of Sirt1 regulating epithelial cell senescence, starting with the structural characteristics of Sirt1, and further expounds on the relationship between Sirt1 and senescence. When epithelial cells are stimulated, Sirt1 affects the senescence of epithelial cells in many ways, such as mitochondrial dysfunction. Sirt1 participates in regulating mitochondrial function and metabolic homeostasis, and telomere length is negatively related to senescence. Sirt1 regulates the expression of telomere reverse transcriptase needed for telomere extension, thus positively regulating telomere homeostasis. DNA damage will undergo damage repair, unrepaired DNA damage will cause cell senescence, and the Sirt1/p53 pathway can inhibit epithelial cell senescence by reducing DNA damage. Senescent cells are the source of chronic inflammation, and chronic inflammation can also promote aging in many ways. Sirt1 inhibits epithelial cell senescence by relieving inflammatory symptoms. In future research, we can focus on the effect of Sirt1 on ameloblast senescence and explore its specific mechanism of action on ameloblasts to find a breakthrough in the etiology and treatment of enamel hypoplasia.

Abstract: To investigate the changes of cerebral blood flow(CBF) in patients with type 2 diabetes mellitus(T2 DM) and its correlation with cognitive function and olfactory impairment. Methods: Cognitive function assessment and smell identification test were performed on 83 patients with T2 DM and 62 healthy controls(HC). Three-dimensional pseudo-continuous arterial spin labeling(3 D-pcASL) head images were collected from the two groups. CBF values of the cerebral cortex were compared between the patients and HC after the postprocessing. Correlations between the CBF values and cognitive function assessment and between the CBF values and smell identification test scores were analyzed as well. Results: Compared to the HC, Chinese smell identification test(CSIT), montreal cognitive assessment(MoCA), digit span test(DST), verbal fluency test(VFT) scores were lower in T2 DM patients(P<0.05).The CBF of the bilateral middle frontal gyrus in T2 DM patients was higher than that in HC group(P<0.001). The CBF of the bilateral gyrus rectus and olfactory cortex in T2 DM patients was lower than that in HC group(P<0.001). Conclusion The cognitive and olfactory function of patients with T2 DM decreased. Patients with T2 DM have abnormal perfusion in the bilateral middle frontal gyrus, gyrus rectus and olfactory cortex, revealing that CBF changes in these brain regions may be one of the causes for cognitive impairment and olfactory dysfunction in T2 DM.

OBJECTIVE To understand the present situation of hand hygiene execution rate among clinical medical personnel,and discuss a series of scientific,reasonable and practical hand hygiene intervention methods,in order to elevate the hand hygiene execution rate among medical personnel.METHODS Using the self-designed questionoaires in combination with observation on hand hygiene process and investigation of hand hygiene knowledge level among medical personnel in various departments of different levels of hospitals to assess the hand hygiene execution rate.RESULTS The investigation indicated 76.00% medical personnel have had hand hygienic knowledge training,and referred in the stipulation health drafts,the hand hygiene execution rate was 50.00-70.00%.The hand health execution rate before contact with patients was 59.82%,and after contacts with patients was 77.97%;among department the hand hygiene execution rate before contact with patients was highest in the department of pediatrics(82.78%),the lowest was in emergency department(11.11%),after contact with patients the highest was department of infectiong(100.00%),and the larest was in the internal medicine department(39.93%).CONCLUSIONS Medical personnel's hand hygiene consciousness is still weak,with lacked hand hygiene related knowledge,it is necessary to summarize a set of reasonable effective intervention plans to elevate the hand hygiene execution rate,reduce the hospital infection percentage,and lower the patient pain and the economic loss.