Objectives:To investigate the incidence of tyrosine kinase inhibitor (TKI) withdrawal syndrome and psychological issues, and their associated factors, in patients with chronic-phase chronic myeloid leukemia (CML-CP) after TKI discontinuation.Methods:We retrospectively analyzed the clinical data of CML-CP patients who discontinued TKI therapy at Peking University People's Hospital after September 2012. Logistic regression models were used to identify independent factors associated with the occurrence of TKI withdrawal syndrome and psychological issues.Results:A total of 158 patients were included, of whom 92 (58%) were female. The median age at discontinuation was 50 ( IQR, 35-60) years. With a median follow-up of 25 ( IQR, 11-49) months, the 4-year rate of sustained major molecular response (MMR) was 60% (95% CI: 51%-70%) . Fifty-one (32%) patients experienced TKI withdrawal syndrome at a median of 1.3 ( IQR, 0.5-2.0) months after TKI discontinuation. Fifty-one (32%) patients reported psychological issues such as anxiety. These concerns stemmed from fears of fluctuating BCR::ABL1 levels or disease relapse, and, for those who discontinued TKI for pregnancy, worries about adverse fetal effects and/or the fetus inheriting CML. Multivariable analyses revealed that older age at discontinuation [ P=0.003 when adjusting for TKI therapy duration; P=0.002 when adjusting for deep molecular response (DMR) duration], longer TKI therapy duration ( P=0.010) , and longer DMR duration before discontinuation ( P=0.005) were significantly associated with a higher risk of TKI withdrawal syndrome; a university degree or higher ( P=0.010) and TKI discontinuation due to pregnancy or adverse events ( P=0.001) were significantly associated with psychological issues after discontinuation. The occurrence of TKI withdrawal syndrome or psychological issues had no impact on the probability of major molecular response loss after discontinuation. Conclusion:TKI withdrawal syndrome and psychological issues are common in CML patients who discontinue TKI therapy. Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.

Objectives:To investigate the incidence of tyrosine kinase inhibitor (TKI) withdrawal syndrome and psychological issues, and their associated factors, in patients with chronic-phase chronic myeloid leukemia (CML-CP) after TKI discontinuation.Methods:We retrospectively analyzed the clinical data of CML-CP patients who discontinued TKI therapy at Peking University People's Hospital after September 2012. Logistic regression models were used to identify independent factors associated with the occurrence of TKI withdrawal syndrome and psychological issues.Results:A total of 158 patients were included, of whom 92 (58%) were female. The median age at discontinuation was 50 ( IQR, 35-60) years. With a median follow-up of 25 ( IQR, 11-49) months, the 4-year rate of sustained major molecular response (MMR) was 60% (95% CI: 51%-70%) . Fifty-one (32%) patients experienced TKI withdrawal syndrome at a median of 1.3 ( IQR, 0.5-2.0) months after TKI discontinuation. Fifty-one (32%) patients reported psychological issues such as anxiety. These concerns stemmed from fears of fluctuating BCR::ABL1 levels or disease relapse, and, for those who discontinued TKI for pregnancy, worries about adverse fetal effects and/or the fetus inheriting CML. Multivariable analyses revealed that older age at discontinuation [ P=0.003 when adjusting for TKI therapy duration; P=0.002 when adjusting for deep molecular response (DMR) duration], longer TKI therapy duration ( P=0.010) , and longer DMR duration before discontinuation ( P=0.005) were significantly associated with a higher risk of TKI withdrawal syndrome; a university degree or higher ( P=0.010) and TKI discontinuation due to pregnancy or adverse events ( P=0.001) were significantly associated with psychological issues after discontinuation. The occurrence of TKI withdrawal syndrome or psychological issues had no impact on the probability of major molecular response loss after discontinuation. Conclusion:TKI withdrawal syndrome and psychological issues are common in CML patients who discontinue TKI therapy. Older age at discontinuation and longer TKI therapy duration or DMR duration are significantly associated with TKI withdrawal syndrome. Higher education level and TKI discontinuation due to pregnancy or adverse events are significantly associated with psychological issues.

Objective:To evaluate the role of ferroptosis in hypoxia-reoxygenation (H/R) injury in cardiomyocytes cultured in high-fat high-glucose (HFHG) medium.Methods:Cardiomyocytes H9c2 cells were commonly cultured and divided into 3 groups ( n=20 each) using a random number table method: control group (C group), HFHG-H/R group and Ferrostatin-1 (Fer-1) plus HFHG-H/R group (Fer-1+ HFHG+ H/R group). H9c2 cells were cultured in a HFHG medium for 12 h and then exposed to 1%O 2-5%CO 2-94%N 2 for 4 h, followed by 2 h reoxygenation in a cell incubator.Fer-1 at a final concentration of 10 μmol/L was added while the cells were cultured in the HFHG medium in group Fer-1+ HFHG+ H/R.At 2 h of reoxygenation, the cell viability was measured using CCK-8 assay, the activity of lactate dehydrogenase (LDH) in the supernatant was measured using 2, 4-dinitrophenylhydrazine color method, the activity of reactive oxygen species (ROS) was measured by fluorescent probe DCFH-DA flow cytometry, and the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), nuclear receptor coactivator 4 (NCOA4), and glutathione peroxidase 4 (GPX4) was detected by Western blot. Results:Compared with group C, the cell viability was significantly decreased, the activities of LDH release and ROS were increased, and the expression of ACSL4 and NCOA4 was up-regulated ( P<0.05), and no significant change was found in the expression of GPX4 in group HFHG+ H/R ( P>0.05). Compared with group HFHG+ H/R, the cell activity was significantly increased, the activities of LDH and ROS were decreased, and the expression of ACSL4 and NCOA4 was down-regulated ( P<0.05), and no significant change was found in the expression of GPX4 in Fer-1+ HFHG+ H/R group ( P>0.05). Conclusions:Ferroptosis is involved in the process of H/R injury in cardiomyocytes cultured in HFHG medium.

Objective To study the effect of interlocking intramedullary nail on fixing transverse olecranon fracture. Methods Nine pairs of fresh ulna specimens were collected and the transverse fracture model of olecranon was established. Kirschner wire tension band and interlocking intramedullary nail were used to repair the fracture. Cyclic dynamic tension loads with amplitude of 25 N, mean value of 45 N and frequency of 05 Hz were applied to the triceps tendon under simulated elbow flexion conditions of 30°, 45° and 60°, respectively. The fracture displacements of specimens within 300 cycles were recorded in three groups. ResultsAt 30° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.831±0.333) mm and (3.723±2.390) mm, respectively. At 45° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.167±0.374) mm and (2.455±0.609) mm, respectively. At 60° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.407±0.342) mm and (3.112±1.025) mm, respectively. The fracture displacement of interlocking intramedullary nail was smaller. Conclusions The mechanical properties of interlocking intramedullary nail are better than those of Kirschner wire tension band, and the interlocking intramedullary nail is more stable and firmer for fixing transverse olecranon fracture. Moreover, the interlocking intramedullary nail is installed with the operating tool, thus the operation is more accurate and faster, and the operation efficiency is greatly improved.

Objective:To determine the mechanical properties of our self-designed novel cross-locking intramedullary nails and the impact of number of conical locking nails on the fixation through a finite element analysis and specimen experiments.Methods:Mimics 19.0 and SolidWorks 2014 were used to create transverse fracture models of the olecranon which were subjected to fixation with respectively K-wire tension band (KTB) and our self-designed novel cross-locking intramedullary nails (NIN). The strengths of KTB and NIN fixation were analyzed by Ansys. Fifteen human ulna specimens were used to construct a transverse fracture model of the olecranon; an Instron E10000 mechanical testing machine was used to determine mechanical properties in fixation respectively with KTB, one NIN (NIN-1) and 3 NINs (NIN-3).Results:In the finite element analysis, in simulation of the forearm flexed at 45° under a 100 N load, the deformation of the fracture surface of the olecranon in fixation with KTB, NIN-1 and NIN-3 was respectively 0.131 mm, 0.123 mm and 0.121 mm. In the specimen experiments, in simulation of the forearm flexed at 45°, the maximum failure loads for fixation with KTB, NIN-1 and NIN-3 were (313.38±27.68) N, (528.56±53.58) N and (871.04±94.95) N, respectively, showing significant differences among the 3 groups ( P<0.05). The maximum failure load for NIN-3 fixation was significantly greater than that for KTB or NIN-1 fixation, and the maximum failure load for NIN-1 fixation was significantly greater than that for KTB fixation ( P<0.05). Conclusions:Compared with KTB fixation, NIN fixation is more convenient in operation and has better mechanical properties. NIN-3 fixation has the best mechanical properties.