Objective:To investigate the clinical characteristics and prognostic factors of TCF3-PBX1 fusion gene-positive childhood B-cell precursor acute lymphoblastic leukemia (B-ALL).Methods:The clinical data of 1 287 newly diagnosed children with B-ALL who were admitted to five hospital in Fujian province (Fujian Medical University Union Hospital, the First Affiliated Hospital of Xiamen University, Zhangzhou Affiliated Hospital of Fujian Medical University, Quanzhou First Hospital Affiliated to Fujian Medical University, Nanping First Hospital of Fujian Province) from April 2011 to December 2020 were retrospectively analyzed. According to the results of TCF3-PBX1 fusion gene testing, all the patients were divided into TCF3-PBX1-positive group and TCF3-PBX1-negative group. The clinical characteristics, early treatment response [minimal residual disease (MRD) at middle stage and end of induction chemotherapy] and long-term efficacy [overall survival (OS) and event-free survival (EFS)] of the patients in both groups were compared. Kaplan-Meier method was used for survival analysis. The prognostic factors of TCF3-PBX1-positive B-ALL were analyzed by using Cox proportional hazards model. Among 83 children with TCF3-PBX1-positive B-ALL, the treatment regimens, risk stratification and efficacy evaluation of 62 cases were performed by using Chinese Children's Leukemia Group (CCLG)-ALL 2008 regimen and 21 cases were performed by using Chinese Children's Cancer Group (CCCG)-ALL 2015 regimen, and the efficacy and incidence of serious adverse events (SAE) between the two groups compared.Results:Among 1 287 B-ALL patients, 83 patients (6.4%) were TCF3-PBX1-positive. The proportion of patients with initial white blood cell count (WBC)≥50×10 9/L in the TCF3-PBX1-positive group was higher than that in the TCF3-PBX1-negative group, while the proportions of patients with MRD ≥1% on induction chemotherapy day 15 or day 19, and MRD ≥0.01% on induction chemotherapy day 33 or day 46 in the TCF3-PBX1-positive group were lower than those in the TCF3-PBX1-negative group (all P < 0.05). Univariate Cox regression analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 and TCF3-PBX1 ≥0.01% on induction chemotherapy day 33 or day 46 were risk factors for OS and EFS (all P < 0.05). Multivariate analysis showed that MRD ≥1% on induction chemotherapy day 15 or day 19 was an independent risk factor for OS ( HR = 10.589, 95% CI 1.903-58.933, P = 0.007) and EFS ( HR = 10.218, 95% CI 2.429-42.980, P = 0.002). TCF3-PBX1≥0.01% on induction chemotherapy day 33 or day 46 was an independent risk factor for EFS ( HR = 6.058, 95% CI 1.463-25.087, P = 0.013) but not for OS ( HR = 3.550, 95% CI 0.736-17.121, P = 0.115). The 10-year EFS and OS rates of the TCF3-PBX1-positive group were 84.6% (95% CI 76.9%-93.1%) and 89.1% (95% CI 82.1%-96.6%), and the differences between the two groups were not statistically significant (both P > 0.05). Among 80 children who received standardized treatment, compared with children who were treated with CCLG-ALL 2008 regimen, the incidence of infection-related SAE was lower in children who were treated with CCCG-ALL 2015 regimen [0 (0/21) vs. 20.3% (12/59), χ2 = 5.22, P = 0.022], but there were no statistical differences in treatment-related mortality, relapse rate, EFS and OS between the two groups (all P > 0.05). Conclusions:Children with TCF3-PBX1-positive B-ALL have a good prognosis, and MRD≥1% at middle stage of induction chemotherapy and TCF3-PBX1≥0.01% at the end of induction chemotherapy may be influencing factors for poor prognosis. CCCG-ALL 2015 regimen can reduce infection-related SAE while achieving good efficacy.

Objective To evaluate the effect of regional hypothermia on limb ischemia-reperfusion (I/R) injury in a rabbit model of hemorrhagic shock.Methods Eighteen healthy adult New Zealand white rabbits of both sexes,weighing 2.0-2.5 kg,were divided into 3 groups (n=6 each) using a random number table:sham operation group (S group),limb I/R group (I/R group) and regional hypothermia group (RH group).Rabbits were shot with 0.25 g steel ball with a 7.62 mm smoothbore at the middle and lower 1/3 of the left hindlimb in I/R and RH groups.When the blood pressure was stable for 30 min after injury,blood was drawn via the right femoral artery at a rate of 2 ml/min until mean arterial pressure decreased to 45-50 mmHg.Then a rubber tourniquet was used to ligate left hindlimbs 10 min later.The injured limb was cooled down for 4 h after applying tourniquet to maintain the subcutaneous temperature at 9-11 ℃ in group RH.After tourniquet was applied for 4 h,perfusion was restored and lasted 6 h.After catheterization (T0) and at 2,4 and 6 h of reperfusion (T1-3),blood samples were collected from the right femoral artery for blood gas analysis and for determination of tumor necrosis factor-α (TNF-α),interleukin-2 (IL-2) and IL-6 concentrations in serum (by enzyme-linked immunosorbent assay).The animals were sacrificed at T3,and tissues around the margin of the inferior lobe of right lung were obtained for examination of the pathological changes which were scored and for determination of wet to dry weight ratio (W/D ratio).Results Compared with group S,the respiratory rate was significantly increased and PaCO2 was decreased at T2,3,the pathological score and W/D ratio were increased,and the concentrations of TNF-α,IL-2 and IL-6 in serum were increased at T1-3 in I/R and RH groups (P＜0.05).Compared with group I/R,the respiratory rate was significantly decreased and PaCO2 was increased at T2,3,the pathological score and W/D ratio were decreased,and the concentrations of TNF-α,IL-2 and IL-6 in serum were decreased at T1-3 (P＜0.05),and the pathological score was significantly attenuated in group RH.Conclusion Regional hypothermia can reduce limb I/R injury in a rabbit model of hemorrhagic shock,and the mechanism may be related to inhibiting systemic inflammatory responses.