Based on cancer collateral theory， this paper proposes toxin-stasis accumulation in collaterals and yin deficiency with toxin hyperactivity as the core pathogenesis of postoperative recurrence of triple-negative breast cancer. Impaired qi transformation in collateral and depletion of yin interact， contributing to toxin-stasis binding， inadequate collateral nourishment， and unrestrained yang activity. The temporal dimension emphasizes yin deficiency with toxin hyperactivity and early reactivation of latent toxin； the spatial dimension emphasizes toxin-stasis accumulation and dissemination through collaterals. Treatment follows the principle of regulating qi and resolving collaterals. Before recurrence， emphasis is placed on nourishing collaterals to restrain latent toxin； after recurrence， on resolving binding while protecting collaterals. Herbal combinations are further tailored to disorders of qi， blood， and fluid collaterals and to the sites of dissemination， integrating treatment according to recurrence status and affected collateral systems. These theoretical propositions are intended to inform clinical reasoning and require clinical validation.

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 investigate the clinical characteristics and efficacy of children with acute lymphoblastic leukemia (ALL) and TP53 mutation, and to explore the relationship between TP53 mutation and the prognosis of children with ALL.Methods:The clinical data of 141 children with newly diagnosed ALL from November 2016 to December 2019 in Fujian Medical University Union Hospital were collected, and the whole-exome gene assay was performed in bone marrow samples of the children by using next-generation sequencing technology. The clinical characteristics of children with TP53 mutation were retrospectively analyzed, and the Kaplan-Meier method was used to compare the overall survival (OS) and event-free survival (EFS) of children with or without TP53 mutation.Results:Among the 141 children with newly diagnosed ALL, TP53 mutations were detected in 5 children (3.5%), all of which were B-precursor acute lymphoblastic leukemia (B-ALL). No TP53 mutation was detected in T-cell acute lymphoblastic leukemia (T-ALL) children, and TP53 mutation accounted for 4.0% (5/126) of B-ALL children. The types of TP53 mutation were all single nucleotide variants. Five ALL children with TP53 mutation were male, with a median age of 60 months (16- 156 months). At the time of onset, all children had anemia and elevated lactate dehydrogenase, and 4 children had subcutaneous hemorrhage and hyperuricemia. The immunophenotypes of all children were precursor B-cell type, and 4 children had myeloid antigen expression. Among 4 ALL children with TP53 mutation who received standard treatment, 2 cases relapsed, and the recurrence time was 8.9 months and 12.1 months, respectively. The expected 15-month EFS rate and OS rate of ALL children with TP53 mutation were lower than those of ALL children without TP53 mutation (37.5% vs. 97.7%, χ2 = 29.90, P < 0.001; 37.5% vs.98.3%, χ2 = 24.90, P < 0.001). Conclusions:ALL children with TP53 mutation are more commonly found in male and B-cell type, with high early recurrence rate and poor efficacy. TP53 mutation may become a necessary supplement for prognostic assessment.

Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.

Objective:To investigate the clinical features and prognosis of B-cell acute lymphoblastic leukemia (B-ALL) children with intrachromosomal amplification of chromosome 21 (iAMP21).Methods:The data of 233 children diagnosed with B-ALL who received chemotherapy according to Chinese Children Cancer Group (CCCG) - acute lymphoblastic leukemia -2015 (CCCG-ALL-2015) protocol in the Affiliated Union Hospital of Fujian Medical University from January 2019 to December 2020 were retrospectively analyzed. These patients were divided into iAMP21 group and non-iAMP21 group according to whether iAMP21 was positive in the bone marrow fluid of children before chemotherapy based on ETV6-RUNX1 probe fluorescence in situ hybridization. Children in iAMP21 group received CCCG-ALL-2015 intermediate-risk group regimen induction chemotherapy, while children in non-iAMP21 group received different intensities of chemotherapy according to the clinical risk classification. The clinicopathological characteristics of patients were compared in both groups, the therapeutic efficacy and prognosis of B-ALL children with iAMP21 was analyzed.Results:iAMP21 was found in 5 (2.1%) of 233 B-ALL children. The median hemoglobin concentration in iAMP21 group was higher than that in non-iAMP21 group [99 g/L (71-148 g/L) vs. 74 g/L (30-156 g/L); U = 268.50, P = 0.043]; there were 4 cases (80%) with bone pain in iAMP21 group (5 cases) and 53 cases (23.2%) with bone pain in non-iAMP21 group (228 cases),and the difference in the osteoarticular pain incidence of both groups was statistically significant ( χ2 = 8.53, P = 0.017). There were no significant differences in the proportion of patients with different gender, age, white blood cell counts, platelet counts, hepatosplenomegaly between the two groups (all P > 0.05). Among 5 children with iAMP21, 1 patient was detected with high CRLF2 expression and 1 patient with IKZF1 1-8 exon loss of heterozygosity. The above mentioned two children with iAMP21, whose minimal residual disease (MRD) were still positive after consolidation therapy, and then they received chimeric antigen receptor T-cell treatment and hematopoietic stem cell transplantation. MRD of the other 3 children with iAMP21 turned negative after induction therapy. Up to the last follow-up in October 2021, 5 patients with iAMP21 had disease-free survival. Conclusions:The incidence of B-ALL children with iAMP21 is about 2%. These patients are prone to osteoarticular pain and have relatively mild anemia. The curative effect of some children is still poor after active treatment,which needs to be further clarified with more samples.

Objective:To introduce a newly modified surgical approach and explore the clinical efficacy of en bloc kidney transplantation from deceased infant donors to adults.Methods:Four cases of en bloc kidney transplantation from deceased infant donor to adult were performed with a new modified surgical approach in renal transplantation and dialysis center of the Second People's Hospital of Shanxi Province from January 2017 to September 2019. All 4 cases were cardiac death donors. There were 3 males and 1 female donors, aged (54 ± 22.69) d and weighing (5.6 ± 0.79) kg. There were 1 male and 3 female recipients, aged (41.5 ± 5.97) years and weighing (45 ± 3.56) kg. For lowering operative difficulties and preventing hemodynamic disturbances, bilateral kidneys were sutured and fixed during trimming. Then end-to-side anastomosis was performed between donor kidney abdominal aortic valve and recipient external iliac artery and between donor renal inferior vena cava valve and recipient external iliac vein.Results:All operations were successful without vascular or urinary complication. The average duration of donor kidney repair was 20 min and the average duration of transplantation 68.75 min. The functions of transplanted kidney recovered well during a follow-up period of 12 months. The long-term survivals of recipient and transplanted kidney were satisfactory.Conclusions:The newly modified surgical approach of en bloc kidney transplantation from deceased infant donor to adult has optimized operative handling. With a higher success rate, vascular complications are lowered. A wider popularization is recommended.

Objective:To explore the application value of non-invasive pressure-strain loop (PSL) in evaluating left ventricular systolic function of young strength athletes with different heart rates.Methods:Thirty-five young wrestlers were collected randomly and divided into 2 groups according to the heart rate: group 1 (heart rate of 40-59 beats/min, n=20) and group 2 (heart rate of 60-80 beats/min, n=15). Thirty healthy young males were selected as the control group at the same period. Non-invasive PSL was used to obtain left ventricular global longitudinal strain (GLS), longitudinal peak strain dispersion (PSD), global myocardial work index (GWI), global constructive myocardial work (GCW), global wasted myocardial work (GWW) and global myocardial work efficiency (GWE) in three groups, and the differences between them were measured. Results:Compared with the control group, GWE in the athlete group 1 and 2 reduced, PSD, GWW were increased, and GWI, GCW in the athlete group 1 were decreased, and all differences were statistically significant (all P<0.05). Compared with the athlete group 1, PSD, GWI, GCW, GWW in the athlete group 2 increased and GWE was reduced (all P<0.05). Conclusions:PSL can quantitatively evaluate the left ventricular myocardial work of young strength athletes with different heart rates, and then assess the effect of heart rates on the left ventricular systolic function of athletes.

Objective:To investigate the clinical features and prognosis of ETV6-RUNX1-positive childhood B-precursor acute lymphocyte leukemia (B-ALL) .Methods:The clinical data of 927 newly diagnosed children with B-ALL admitted to the Fujian Medical University Union Hospital from April 2011 to May 2020 were retrospectively analyzed. According to the results of ETV6-RUNX1 gene, the patients were divided into ETV6-RUNX1 + and ETV6-RUNX1 - groups. The clinical features and prognosis between the two groups were compared. Among the 182 children with ETV6-RUNX1 +, 144 patients received the Chinese Childhood Leukemia Collaborative Group (CCLG) -ALL 2008 protocol (CCLG-ALL 2008 group) and 38 received the China Childhood Cancer Collaborative Group (CCCG) -ALL2015 protocol (CCCG-ALL 2015 group) . The efficacy, serious adverse effects (SAE) incidence, and treatment-related mortality (TRM) of the two groups were also compared. Results:Of the 927 B-ALL patients, 189 (20.4% ) were ETV6-RUNX1 +. The proportion of patients with risk factors (age ≥10 years or <1 year, white blood cell count ≥50×10 9/L) in the ETV6-RUNX1 + group was significantly lower than that in the ETV6-RUNX1 - group ( P=0.000, 0.001, respectively) , while the proportion of patients with good early response (good response to prednisone, d15 or d19 MRD <1% , and d33 or d46 MRD<0.01% in induction chemotherapy) in the ETV6-RUNX1 + group was significantly higher than that in the ETV6-RUNX1 - group ( P=0.028, 0.004, respectively) . The 5-year EFS and OS of the ETV6-RUNX1 + group were significantly higher than those of the ETV6-RUNX1 - group (EFS: 89.8% vs 83.2% , P=0.003; OS: 90.2% vs 86.3% , P=0.030) . The incidence of infection-related SAE and TRM was significantly higher than that of CCCG-ALL 2015 group. A statistical difference was observed between the incidence of infection-related SAE of the two groups (27.1% vs 5.3% , P=0.004) , but no difference in TRM (4.9% vs 0, P=0.348) . Conclusion:ETV6-RUNX1 +B-ALL children have fewer risk factors at diagnosis, better early response, lower recurrence rate, and good prognosis than that of ETV6-RUNX1 -B-ALL children. Reducing the intensity of chemotherapy appropriately can lower the infection-related SAE and TRM and improve the long-term survival in this subtype.

Objective:To explore the application value of ultrasonic layer-specific strain technology in evaluating left ventricular systolic function in young male strength athletes.Methods:In October 2018, 30 professional young male wrestlers from Henan Provincial Heavy Sports Management Center (athlete group) and 30 healthy young males matched with age (control group) were randomly selected.Using traditional echocardiography combined with stratified strain technique, heart rate (HR), left ventricular end-diastolic diameter(LVDd), interventricular septal thickness on diastole(IVSTd), postwall thickness on diastole (PWTd), relative wall thickness (RWT), end diastolic volume index(EDVI), end systolic volume index (ESVI), ejection fraction (LVEF), stroke volume index (SVI), cardiac index (CI), spherical index (SPI), endocardial myocardial global longitudinal strain(GLSendo), mid-myocardial global longitudinal strain(GLSmid), epicardial myocardial global longitudinal strain(GLSepi), peak strain dispersion(PSD) and whole myocardial longitudinal strain cross-wall difference (ΔLS) were measured respectively. The differences between the two sets of data were analyzed.ROC curves were plotted to analyze and compare the stratified strain parameters performance to predict left ventricular systolic function or synchrony in athletes.Results:The values of LVDd, PWTd, IVSTd, RWT, SPI, EDVI, ESVI and SVI in athelete group were higher than those of the control group. And the values of HR, GLSendo, GLSmid, GLSepi and ΔLS were lower than those of the control group.The differences were statistically significant (all P<0.05). There was no significant difference in LVEF, CI and PSD between the two groups (all P>0.05). The areas under the ROC curve of GLSendo, GLSmid and GLSepi for athletes′ left ventricular systolic function were 0.753, 0.747 and 0.726, respectively, and the optimal cut-off values were -22.34%, -19.95%, -17.35%, respectively. Conclusions:Long-term high-intensity exercise can lead to subclinical changes in left ventricular systolic function, and ultrasonic layer-specific strain technology can more accurately and specifically evaluate left ventricular systolic dysfunction. Among the GLS parameters, GLSendo is the optimal parameter for testing the left ventricular systolic function of athletes.

Objective:To summarize the clinical experiences of 9 ABO-incompatible kidney transplantation at our center and explore its clinical application value.Methods:Methods From April 2016 to December 2019, there were 9 living kidney transplants of ABO incompatible relatives, including type A to type B (n=3), type B to type O (n=3), type B to type A (n=1) and type AB to type B (n=2). Immunosuppressant plus single membrane plasmapheresis (PE) and/or double filtration plasmapheresis (DFPP) and rituximab were employed for pretreating recipients. Adverse reactions of recipients were observed during and after pretreatment. Blood group antibody titer, complications and other related parameters were recorded before and after transplantation before and after monitoring pretreatment.Results:After pretreatment, IgM, IgG and total titer of blood group antibodies were ≤1: 4 on the day of transplantation and the titer of non-blood group antibodies rebounded within 2 weeks (≤1: 8). During preconditioning, 2 patients experienced oral numbness and involuntary dithering during plasmapheresis and there was 1 case of infusion reaction after rituximab dosing. The early recovery of renal function was all excellent. Renal biopsy was performed in 4 patients with slow elevation of serum creatinine and 1 case developed acute antibody-mediated rejection. The survival rate of all recipients at the last follow-up was 100%.Conclusions:Live kidney transplantation of ABO-incompatible relatives is both safe and feasible so that it may help alleviate some shortage of donor kidney.