Chronic myeloid leukemia (CML) is a malignant tumor formed by clonal proliferation of bone marrow hematopoietic stem cells. With the improvement of disease awareness and the introduction of new drugs, more than 90% of CML patients can achieve long-term survival. However, a few patients still show drug resistance. This article reviews the mechanism of drug resistance in CML patients treated with tyrosine kinase inhibitor (TKI) and the characteristics of ABL kinase region mutation.

Objective:To establish a fluorescent reporter human induced pluripotent stem cell line (hiPSCs) for monitoring the expression of visual system homeobox 2 ( VSX2). Methods:VSX2_small guide RNA (sgRNA) was inserted into vector PX459 to construct knockout plasmid, and the P2A-eGFP knock-in donor plasmid was conducted at the same time.The two plasmids were transfected into BC1-hiPSCs.Single cell clones were generated after treatment of puromycin.Correct insertion was confirmed by PCR and Sanger sequencing.The isogenicity of the parental and the reporter hiPSCs was confirmed by STR analysis and karyotyping.Pluripotency capacity of the reporter hiPSCs was analysed by reverse trascription PCR and immunofluorescence.Three-germ-layer formation experiment was carried out to analyse the multi-lineage differentiation ability of the reporter hiPSCs.The reporter hiPSCs were further differentiated to obtain three-dimension (3D) retinal organoids, and immunofluorescence was used to identify the co-localization of the enhanced green fluorescent protein (eGFP) and VSX2.Results:A VSX2 eGFP reporter hiPSC clone was successfully obtained by CRISPR/Cas9 technology, which was consistent with the parental hiPSCs (BC1-hiPSCs) in morphology, without any chromosomal aberrations or cell line cross-contamination.Reverse transcription PCR assay and immunofluorescence showed obvious positive expressions of iPSCs markers in BC1- VSX2 eGFP-iPSCs, including NANOG, OCT4, SOX2, DNMT3B and GDF3 mRNA as well as NANOG, OCT4, SSEA4 and TRA-1-60 protein.The α-fetoprotein (AFP), α-smooth muscle actin (α-SMA) and neuronal class Ⅲ β-tubulin (TUJ1) were expressed in endoderm, mesoderm and ectoderm, respeetively, derived from BC1- VSX2 eGFP-iPSCs, and eGFP and VSX2 were co-stained in the neural retinal layer of 3D retinal organoids derived from BC1- VSX2 eGFP-iPSCs by immunofluorescence. Conclusions:VSX2 fluorescent reporter hiPSCs is successfully generated, which can monitor the temporal and spatial expression changes of VSX2 protein in real time, providing a powerful tool for evaluation of retina development mechanism and cell therapy.

Objective:To explore the application effect of four-track teaching mode (LBL: lecture-based learning; CBL: case-based learning; PBL: problem-based learning) in pediatric teaching of integrated traditional Chinese and Western Medicine.Methods:175 integrated traditional Chinese and Western medical students in seven-year program were divided into experimental group and control group. The experimental group was taught by four-track teaching mode, while students in the control group. Were applied with traditional teaching method ("LBL+CBL").Results:Students in the experimental group highly rated the four-track teaching mode and were better than those in the control group in the following aspects: satisfaction with teaching methods, interest in learning, the ability of creative thinking, the thinking ability of clinical diagnosis and treatment, and memorization ( P<0.05). And students' mid-term, final and comprehensive scores in the experimental group were significantly higher than those in the control group ( P<0.05). Conclusion:Compared with traditional teaching methods, the four-track teaching mode can improve the quality of pediatric teaching of integrated traditional Chinese and Western medical students, which should be further integrated and perfected in the teaching practice.

Objective: To explore the clinical effects of scapular region flaps pedicled with circumflex scapular artery in the reconstruction of axillary burn scar contractures. Methods: From December 2008 to December 2018, 21 patients with axillary burn scar contractures were admitted to our department. There were 12 male patients and 9 female patients, aged 2-48 years, with an average of 17.4 years. According to the characteristics of axillary scar contractures, the patients were divided into type Ⅰ of 5 patients, type Ⅱ of 2 patients, type Ⅲ of 5 patients, and type Ⅳ of 9 patients. The preoperative abduction ranges of shoulder joint were 20-150°, with an average of 68.33°. The wound areas after resection and release of scar contractures ranged from 12 cm×4 cm to 33 cm×11 cm, with an average of 18.13 cm×5.41 cm, and the wounds were repaired with scapular region flaps pedicled with circumflex scapular artery in the areas of 14 cm×5 cm-35 cm×14 cm, with an average of 20.19 cm×7.71 cm. The donor sites of 5 patients were expanded prior to flap repair operation, and the other 16 patients were repaired by direct transfer of flaps. The donor sites were closed directly. The type, number, and transfer way of scapular region flaps were calculated, and the improvement of abduction angle of shoulder joint and condition of the flaps were observed during follow-up after operation. Results: There were 5 ascending scapular flaps, 13 scapular flaps, and 3 parascapular flaps. The flaps were transferred through open wounds in 18 cases, subcutaneous tunnel in 1 case, and trilateral foramia in the remaining 2 cases. All the flaps survived after operation. During follow-up of 3 months to 5 years, with an average of 19.4 months, the abduction angles of shoulder joints were 90-180°, with an average of 137.62°, which showed that the abduction function of shoulder joint improved obviously. The texture of flap was soft, and the color of the flap was close to the surrounding skin. The patients and/or their family members were satisfied with the operation results. Conclusions The scapular region flap pedicled with circumflex scapular artery has a lot of advantages, including a long vascular pedicle, simple technique for flap harvest, a hidden donor site, and flexible and diverse transfer mode of flap. It is an effective option for clinical reconstruction of severe axillary burn scar contracture.

Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.

Objective:To explore the feasibility and technical tips of donor-site reconstruction of the latissimus dorsi myocutaneous flap using the perforator propeller flap technique.Methods:Between July 2012 and January 2019, a total of 24 patients, including 9 males and 15 females, underwent reconstructions of defects in various locations using the latissimus dorsi myocutaneous flap. The average patient age was 43.6 years (range, 4-81 years). Before surgery, perforators adjacent to the latissimus dorsi muscle were explored using an ultrasound Doppler probe and marked on the skin. A latissimus dorsi myocutaneous flap was elevated according to the resultant defect following the removal of the lesion and transferred to reconstruct the defect. The donor-site defects were reconstructed using one, dual, or even triple perforator propeller flap.Results:All the 24 myocutaneous flaps survived completely. The dimension and width of the myocutaneous flaps ranged from 16 cm × 11 cm to 33 cm × 17 cm and 9 cm to 20 cm, respectively. The donor-site defects of the myocutaneous flap were all closed by perforator propeller flaps including 22 pedicled flaps and 2 free flaps. The defect was reconstructed by one perforator propeller flap in 12 patients, two flaps in 11, and three flaps in the remaining one patient. There were 36 posterior intercostal artery perforator propeller flaps and one freestyle perforator propeller flap. The size, pedicle length, and rotation angle of the propeller flaps were 13 cm × 5 cm to 23 cm × 14 cm, 3 cm to 6 cm, and 90 to 180 degrees, respectively. All the donor sites of the perforator propeller flaps were closed primarily. Total necrosis of the propeller flap occurred in one patient and small-sized distal flap necrosis in another one. The remaining propeller flaps survived completely. All patients were followed up for one to 38 months and the mean follow-up time was 7 months. Tumor recurrence was noticed in four patients. All patients were satisfied with the final functional and aesthetic outcomes.Conclusions:Using the perforator propeller flaps could guarantee not only harvesting a wide latissimus dorsi myocutaneous flap, but also primary donor-site closure of the myocutaneous flap, and therefore greatly improve the versatility and capability of the latissimus dorsi myocutaneous in defect reconstruction.

Objective:To explore the indications and technical tips of defect reconstruction in the elbow and upper arm using the radial collateral artery perforator (RCAP) propeller flap.Methods:From October 2016 to December 2019, 6 patients underwent defect reconstruction using the RCAP propeller flaps. All patients were female, aged from 5 to 66 years, with an average of 31 years. All of the defects were repaired with radial collateral artery perforator propeller flap. Before the surgery, the RCAP was thoroughly explored using the hand-held ultrasound Doppler and marked on the skin. According to the size, shape and location of the defect, a RCAP propeller flap was elevated based on the chosen RCAP, rotated in a certain degree with the perforating point as the rotation point. The large paddle was used to repair the defect of the upper extremity, and the small paddle was used to assist in closing the donor site. The donor sites were sutured directly or repaired with free skin graft. Capillary filling test or indocyanine green SPY fluorescence imaging system was used to evaluate the blood supply of the flap immediately. The effect was observed.Results:The defect size ranged from 6.0 cm × 3.0 cm to 10.0 cm × 7.0 cm. The flap size ranged from 6.0 cm × 3.5 cm to 20.0 cm × 8.0 cm. All perforators were septocutaneous perforators. The pedicle of the pedicle ranged from 2.5 cm to 5.0 cm and the mean length was 3.6 cm. The flaps were rotated 180° in 5 patients, and 150° in one patient. The donor sites were sutured directly in 5 patients and repaired with free skin graft in one patient. Five flaps survived completely without any major complications. Wound infection occurred in one flap, which healed after debridement. All donor sites were closed primarily, except one which was covered by free skin grafting. All patients were followed up for 3 months to 3 years and the average follow-up time was 2.4 years. The appearance and texture of the flap were good, and the motion of elbow joint was normal. All patients were satisfied with the functional and aesthetic outcomes of the upper extremities. Tumor recurrence was not noticed in the oncologic patients.Conclusions:For selected patients, the RCAP propeller flap could be an alternative option for soft-tissue defect reconstruction in the upper extremity.

Objective:To explore the feasibility and technical tips of donor-site reconstruction of the latissimus dorsi myocutaneous flap using the perforator propeller flap technique.Methods:Between July 2012 and January 2019, a total of 24 patients, including 9 males and 15 females, underwent reconstructions of defects in various locations using the latissimus dorsi myocutaneous flap. The average patient age was 43.6 years (range, 4-81 years). Before surgery, perforators adjacent to the latissimus dorsi muscle were explored using an ultrasound Doppler probe and marked on the skin. A latissimus dorsi myocutaneous flap was elevated according to the resultant defect following the removal of the lesion and transferred to reconstruct the defect. The donor-site defects were reconstructed using one, dual, or even triple perforator propeller flap.Results:All the 24 myocutaneous flaps survived completely. The dimension and width of the myocutaneous flaps ranged from 16 cm × 11 cm to 33 cm × 17 cm and 9 cm to 20 cm, respectively. The donor-site defects of the myocutaneous flap were all closed by perforator propeller flaps including 22 pedicled flaps and 2 free flaps. The defect was reconstructed by one perforator propeller flap in 12 patients, two flaps in 11, and three flaps in the remaining one patient. There were 36 posterior intercostal artery perforator propeller flaps and one freestyle perforator propeller flap. The size, pedicle length, and rotation angle of the propeller flaps were 13 cm × 5 cm to 23 cm × 14 cm, 3 cm to 6 cm, and 90 to 180 degrees, respectively. All the donor sites of the perforator propeller flaps were closed primarily. Total necrosis of the propeller flap occurred in one patient and small-sized distal flap necrosis in another one. The remaining propeller flaps survived completely. All patients were followed up for one to 38 months and the mean follow-up time was 7 months. Tumor recurrence was noticed in four patients. All patients were satisfied with the final functional and aesthetic outcomes.Conclusions:Using the perforator propeller flaps could guarantee not only harvesting a wide latissimus dorsi myocutaneous flap, but also primary donor-site closure of the myocutaneous flap, and therefore greatly improve the versatility and capability of the latissimus dorsi myocutaneous in defect reconstruction.

Objective:To explore the indications and technical tips of defect reconstruction in the elbow and upper arm using the radial collateral artery perforator (RCAP) propeller flap.Methods:From October 2016 to December 2019, 6 patients underwent defect reconstruction using the RCAP propeller flaps. All patients were female, aged from 5 to 66 years, with an average of 31 years. All of the defects were repaired with radial collateral artery perforator propeller flap. Before the surgery, the RCAP was thoroughly explored using the hand-held ultrasound Doppler and marked on the skin. According to the size, shape and location of the defect, a RCAP propeller flap was elevated based on the chosen RCAP, rotated in a certain degree with the perforating point as the rotation point. The large paddle was used to repair the defect of the upper extremity, and the small paddle was used to assist in closing the donor site. The donor sites were sutured directly or repaired with free skin graft. Capillary filling test or indocyanine green SPY fluorescence imaging system was used to evaluate the blood supply of the flap immediately. The effect was observed.Results:The defect size ranged from 6.0 cm × 3.0 cm to 10.0 cm × 7.0 cm. The flap size ranged from 6.0 cm × 3.5 cm to 20.0 cm × 8.0 cm. All perforators were septocutaneous perforators. The pedicle of the pedicle ranged from 2.5 cm to 5.0 cm and the mean length was 3.6 cm. The flaps were rotated 180° in 5 patients, and 150° in one patient. The donor sites were sutured directly in 5 patients and repaired with free skin graft in one patient. Five flaps survived completely without any major complications. Wound infection occurred in one flap, which healed after debridement. All donor sites were closed primarily, except one which was covered by free skin grafting. All patients were followed up for 3 months to 3 years and the average follow-up time was 2.4 years. The appearance and texture of the flap were good, and the motion of elbow joint was normal. All patients were satisfied with the functional and aesthetic outcomes of the upper extremities. Tumor recurrence was not noticed in the oncologic patients.Conclusions:For selected patients, the RCAP propeller flap could be an alternative option for soft-tissue defect reconstruction in the upper extremity.

Objective: To explore the feasibility and technical points of soft tissue defect reconstruction using the pedicled anterolateral thigh flap based on perforating vessels from the lateral circumflex femoral artery oblique branch. Methods: Between November 2009 and April 2019, 27 pedicled anterolateral thigh flaps were performed to repair the wound of trunk and lower extremity, based on perforating vessels from the lateral circumflex femoral artery oblique branch. 16 flaps were proximally based and 11 were distally based. Results: The proximally based flap ranged from 15 cm×8 cm to 32 cm×12 cm. The mean length of the pedicle was 8.2 cm. The distally based flap ranged from 9 cm×7 cm to 24 cm×8 cm. The mean length of the pedicle was 18.6 cm. All flaps survived after surgery. Venous congestion occurred in one flap and relieved in five days. Conclusions With oblique branch as the pedicle, the vascular dissection was easy and donor site morbidity was minimized while harvesting the proximally based anterolateral thigh flaps; long pedicle could be obtained, and the reconstructive sphere was extended when using the distally based anterolateral thigh flaps.