OBJECTIVETo evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL).

METHODSA relapsed B-ALL child after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was treated with CAR-T, and the related literatures were reviewed.

RESULTAn 11-year-old girl with TEL-AML1 fusion gene positive BALL who suffered a bone marrow relapse 28 months after remission from conventional chemotherapy. During the second remission, the patient received haploidentical allo-HSCT. She relapsed with detectable TEL-AML1 fusion gene even after chemotherapy and donor leukocyte infusions. She received an experimental donor-derived fourth generation CD19 CAR-T therapy. After infusion of 1 × 10(6)/kg CAR-T cells, she experienced only mild or moderate cytokine-release syndrome and the minimal residual disease turned negative. Then three maintenance of CAR-T cell infusions [(0.83-1.65)×10(6)/kg] was administered, and the disease-free survival had lasted for 10 months. However, the TEL-AML1 copies in her blood still increased and she died with leukemia relapse after additional CAR-T cell infusion.

CONCLUSIONTreatment of relapsed B-ALL with the fourth generation CAR-T cells directed against CD19 was effective and safe. CAR-T therapy is a novel therapeutic approach that could be useful for patients with relapsed and refractory B-ALL who have failed all other treatment options.

Bone Marrow ; Child ; Core Binding Factor Alpha 2 Subunit ; genetics ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Neoplasm, Residual ; Oncogene Proteins, Fusion ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; therapy ; Receptors, Antigen, T-Cell ; genetics ; Recurrence ; Remission Induction ; T-Lymphocytes ; cytology ; Transplantation, Homologous

Sleep is an important activity of daily life for individuals,and sleep disorders can seriously affect their physical and mental health.This article summarizes the impact of vestibular stimulation on sleep,and reviews feasible and effective intervention methods from swing movement,galvanic vestibular stimulation,and weighted blankets stimulation,in order to provide new ideas and methods for the diagnosis and treatment of sleep disorders.

Objective:To investigate the efficacy and safety of retrograde intrarenal surgery(RIRS) with holmium laser lithotripsy in the management of calyceal diverticular calculi.Methods:A retrospective analysis was performed on 56 patients with calyceal diverticular calculi admitted to Huashan Hospital of Fudan University from January 2017 to May 2020. The 56 cases included 25 males and 31 females. The average age was 37.4 (ranging 22-67) years. Calyceal diverticular stones were located in the upper pole of the kidney in 32 cases, middle pole in 16 case and lower pole in 8 cases, with 32 cases on the left side and 24 cases on the right side. Multiple stones occurred in 46 cases, and single stone in 10 cases. The mean diameter of stones was 11.5 (ranging 3.0-17.5)mm. All 56 patients had different degrees of lumbar pain and/or hematuria preoperatively. Among them, 17 patients received extracorporeal shock wave lithotripsy (ESWL) with failure. Moreover, 9 cases suffered with urinary infection. All 56 patients with calyceal diverticular calculi underwent retrograde flexible ureterorenoscopic Ho: YAG laser lithotripsy under general anesthesia. The flexible ureterorenoscope was advanced into the kidney through the ureteral access sheath, looking for the cervical orifice of calyceal diverticulum. After finding renal diverticulum, holmium laser was used to incise and expand the neck or weak part of the diverticulum. The diverticular calculi were fragmented into particles less than 3 mm. Larger fragments were removed through a nitinol stone basket one by one. A F6 D-J stent was indwelled. The intraoperative conditions, postoperative complication rate and stone free rate were statistically analyzed.Results:The calyceal diverticular calculi in all 56 patients were discovered, and the diverticulum orifice were identified in 48 patients(85.7%). 53 of them underwent calyceal diverticular calculi fragmentation successfully. Lithotripsy failed in 3 cases, as the calculi were incarcerated in the lower pole calyceal diverticulum with a long narrow neck and the limitation of flexure at the end of the flexible ureteroscope. Two of them underwent percutaneous nephrolithotomy instead due to the calculi located in the posterior calyx. In another one case, ESWL was performed as the calculi located in the anterior calyx. Of the 17 cases received unsuccessful ESWL, RIRS was successful in 16 cases (94.1%). The mean operative time was 68.1(ranging 37-105)min, and mean hospitalization was 1.8 (ranging 1-3)d. The complication rate was 15.1%(8/53). All of these complications were mild (Clavien Ⅰ-Ⅱ). No serious complications such as perforation of the renal pelvis and ureter or major bleeding were occurred. After mean postoperative follow-up of 6.3(ranging 3-12) months, the stone-free rate was 83.0% (44/53) after the first procedure. 7 cases with residual stones ≥4mm received a second procedure. Among them, 6 cases received flexible ureterorenoscopy and the other one received ESWL and external physical vibration lithecbole therapy. The stone-free rate and symptom remission rate was 92.5% (49/53) and 96.2% (51/53) respectively after the second procedure, and no recurrence of calyceal diverticular calculi was observed during the stage of fllow-up.Conclusions:RIRS with holmium laser lithotripsy in the treatment of calyceal diverticular calculi, using the body's natural cavities, is a minimally invasive, safe and efficient strategy with slight complications. RIRS with holmium laser lithotripsy is an optional treatment for calyceal diverticular calculi.

Objective: To evaluate the safety and efficacy of chimeric antigen receptors T cells (CAR-T) in childhood acute B lymphoblastic leukemia (B-ALL) to probe the prognosis-related factors. Methods: Forty-eight children, 29 boys and 19 girls, aged 3-17years old (median age was 8 years old) , with recurrent or refractory CD19 positive B-ALL, were treated by the CD19 specific CAR-T cells. A total of 48 cases received 61 infusions. Flow cytometry or real-time quantitative polymerase chain reaction method were used to monitor micro residual disease (MRD) . The follow-up period was from 16 to 1 259 days with the median follow-up of 406 days. SPSS software was used to statistical analysis. Results: No adverse reaction was observed during 61 infusions. The most common adverse reaction after CAR-T cell infusions was cytokine-release syndrome (CRS) . Only 2 cases experienced level 3 CRS performance, including continuous high fever, convulsions, delirium, serous cavity effusion, and decreasing of blood pressure. Tocilizumab was given to release CRS performance. No treatment-related death occurred. Thirty-seven patients showed response during 7 to 28 days after infusions. The early response rate was 77.1%, with MRD before infusion less than 5% group higher than the MRD more than 5% group (87.1% vs 58.8%, χ²=4.968, P=0.036) . For the 37 patients who showed response to CAR-T cell infusions, univariate analysis identified that age, disease status at the time of treatment, MRD before infusion affected 2-year OS rate (P<0.05) . Multivariate prognostic analysis for EFS disclosed that the MRD before infusion more than 5% (RR=3.433, 95% CI 1.333-8.844, P=0.011) and not bridge to HSCT (RR=4.996, 95% CI 1.852-13.474, P=0.001) were the independent risk factors. Conclusion The fourth generation CAR-T cells directed against CD19 could effectively and safely treat relapsed and refractory B-ALL, which implicated that CAR-T therapy as a novel therapeutic approach could be useful for patients with relapsed or refractory B-ALL who have failed all other treatment options. Reducing MRD as far as possible by effective pretreatment chemotherapy was in favor of increasing the response rate. Bridging HSCT after CAR-T cell treatment might be a better therapeutic strategy for the patient with refractory or molecular relapsed B-ALL.

Objective: To investigate the effect of exogenous L-Arg on the survival of extended perforator flap in rats. Methods: Sixteen male Sprague Dawley rats were randomly divided into L-Arg group (n=8) and control group(n=8). The extended dorsal three-vascular territory perforator flaps were made in rats. L-Arg (400 mg·kg^-1·d^-1) was injected intraperitoneally in L-Arg group 1d before operation, immediately and 1-7 d after operation, while the same volume of saline was injected intraperitoneally in control group at the same time points. The appearance and distribution of blood vessels were observed, and the flap survival areas were measured 7d after operation. The tissue samples were harvested from choke zone Ⅱ for histological study and the expression of vascular endothelial growth factor (VEGF) was detected by immunohistochemistry and Western blot, respectively. Results: After 7d, the clearer vascular structure and more new vessels in choke zone Ⅱ were observed in L-Arg group. The survival rate of flap in L-Arg group was (88.42±4.19)%, which was significantly higher than that in control group[(76.52±5.37)%, t=3.707, P<0.01]. The microvessel density and caliber of choke zone Ⅱ in L-Arg group was (29.47±5.28)/mm² and(47.27±5.32)μm, which were significantly higher than those in control group (t=2.694 and 2.389, P<0.05 or P<0.01). The immunohistochemistry and Western blot showed that the expression of VEGF in choke zone Ⅱ of L-Arg group was significantly higher than that in control group (t=9.428 and -3.054,P<0.05 or P<0.01). Conclusion: Exogenous L-Arg can increase the survival rate of extended dorsal perforator skin flap through promoting vascularization and dilatation of vessels in choke zone Ⅱ in rats.
Animals ; Arginine ; pharmacology ; Graft Survival ; drug effects ; Male ; Neovascularization, Physiologic ; drug effects ; Perforator Flap ; blood supply ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; Vascular Endothelial Growth Factor A ; metabolism