Colorectal adenoma is a definite precancerous lesion,and the"inflammation-cancer transformation"is a key pathological link in the process of colorectal adenoma-cancer evolution.Under the guidance of the theory of"preventive treatment of diseases"in TCM,prevention before disease onset and preventing the development of the occurred disease has become the consensus and the important subject of clinical research to block the"inflammation-cancer transformation"and prevent the precancerous lesions of colorectal cancer.This article discussed the effectiveness of TCM in preventing and treating the"inflammation-cancer transformation"from different aspects.Its advantages are reflected in improving the symptoms of TCM and improving the quality of life,etc.Its mechanism may be related to inhibiting the activation of cancer-promoting signals,regulating inflammation,maintaining intestinal microbial homeostasis,and protecting the intestinal barrier.By explaining the pathogenesis of adenoma-cancer transformation in TCM,this article discussed the efficacy and advantages of TCM to block"inflammation-cancer transformation",analyzed its intervention targets and pathways,providing references for the intervention of TCM in the management of precancerous lesions of colorectal cancer and the synergistic prevention and treatment of traditional Chinese and Western medicine.

Chimeric antigen receptor (CAR) T-cell therapy has achieved breakthroughs in treating relapsed/refractory B-cell malignancies. However, it still faces challenges, including complex manufacturing processes, limited indications, T-cell exhaustion, and insufficient durability of therapeutic efficacy. CRISPR/Cas9, a highly efficient and relatively simple gene-editing technology, offers new avenues for overcoming these limitations. This review briefly outlines the working mechanism of CRISPR/Cas9 and focuses on its recent applications and clinical practices in developing universal CAR T-cells, enhancing T-cell function, and extending CAR T-cell therapy to T-cell and myeloid leukemias. Furthermore, this review highlights optimization strategies developed over the past two years to enhance the editing precision, delivery efficiency, and safety of the CRISPR/Cas9 system, aiming to provide insights for the optimal design and clinical application of CAR T-cell therapy.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Chimeric antigen receptor (CAR) T-cell therapy has achieved breakthroughs in treating relapsed/refractory B-cell malignancies. However, it still faces challenges, including complex manufacturing processes, limited indications, T-cell exhaustion, and insufficient durability of therapeutic efficacy. CRISPR/Cas9, a highly efficient and relatively simple gene-editing technology, offers new avenues for overcoming these limitations. This review briefly outlines the working mechanism of CRISPR/Cas9 and focuses on its recent applications and clinical practices in developing universal CAR T-cells, enhancing T-cell function, and extending CAR T-cell therapy to T-cell and myeloid leukemias. Furthermore, this review highlights optimization strategies developed over the past two years to enhance the editing precision, delivery efficiency, and safety of the CRISPR/Cas9 system, aiming to provide insights for the optimal design and clinical application of CAR T-cell therapy.

Colorectal adenoma is a definite precancerous lesion,and the"inflammation-cancer transformation"is a key pathological link in the process of colorectal adenoma-cancer evolution.Under the guidance of the theory of"preventive treatment of diseases"in TCM,prevention before disease onset and preventing the development of the occurred disease has become the consensus and the important subject of clinical research to block the"inflammation-cancer transformation"and prevent the precancerous lesions of colorectal cancer.This article discussed the effectiveness of TCM in preventing and treating the"inflammation-cancer transformation"from different aspects.Its advantages are reflected in improving the symptoms of TCM and improving the quality of life,etc.Its mechanism may be related to inhibiting the activation of cancer-promoting signals,regulating inflammation,maintaining intestinal microbial homeostasis,and protecting the intestinal barrier.By explaining the pathogenesis of adenoma-cancer transformation in TCM,this article discussed the efficacy and advantages of TCM to block"inflammation-cancer transformation",analyzed its intervention targets and pathways,providing references for the intervention of TCM in the management of precancerous lesions of colorectal cancer and the synergistic prevention and treatment of traditional Chinese and Western medicine.

Objective:To investigate the efficacy and toxicity of blinatumomab in the first-line and second-line treatment of pediatric B-cell acute lymphoblastic leukemia (B-ALL).Methods:A multi-center retrospective cohort study was conducted to analyze clinical data from 323 pediatric B-ALL patients treated with blinatumomab across 14 hospitals in China from May 2021 to July 2023. Patients were divided into four groups based on the treatment phase and disease status when blinatumomab was used: relapsed/refractory group, post-consolidation minimal residual disease (MRD)-positive group, early MRD-positive group, and MRD-negative group. Blinatumomab for the relapsed/refractory group was considered as second-line treatment, while the other 3 groups as first-line treatment. The MRD negativity rate after treatment, the survival rates and the incidence of severe adverse events were compared across these groups. Patients who received blinatumomab for more than 7 days were included in the efficacy analysis. Survival analysis was performed using the Kaplan-Meier method, and Log-Rank test was used to compare the survival rates among groups.Results:Among the 323 patients, 191 (59.1%) were male, with the age of 6.2 (3.9, 10.5) years. There were 117 patients in the relapsed/refractory group, 62 cases in the post-consolidation MRD-positive group, 43 cases in the early MRD-positive group, and 101 cases in the MRD negative group. In the relapsed/refractory group, the complete remission rate and MRD negativity rate after one course of blinatumomab were 71.4% (35/49) and 81.5% (75/92) for the 49 children without complete remission and the 92 children with flow cytometry-positive MRD, respectively. In the post-consolidation MRD-positive group, the MRD negativity rates after one course of blinatumomab were 100.0% (27/27), 12/16 and 9/19 for patients with MRD positivity detected by flow cytometry, polymerase chain reaction and next-generation sequencing, respectively. In the early MRD-positive group, the MRD negativity rates were 96.7% (29/30) and 9/9 for flow cytometry and next-generation sequencing, respectively. The 2-year overall survival rate and event-free survival rate for the 319 children evaluable for efficacy were (90.6±1.7)% and (87.6±1.9)%, respectively, with the relapsed/refractory group showing significantly lower overall survival rates and event-free survival rate compared to the other groups ( χ2=21.40, 26.21,both P<0.001). Grade 3 or higher adverse events occurred in 128 cases (39.6%), with hematological toxicity observed in 101 cases, while cytokine release syndrome (CRS), infection, and neurotoxicity occurred in 11, 26 and 8 cases, respectively. In addition, there were statistically significant differences in the grade 3 or higher CRS among the four groups ( χ2=8.03, P<0.05). Conclusion:Blinatumomab can clear MRD more effectively and achieve superior survival outcomes when used as first-line treatment for pediatric B-ALL, with less CRS.

Objective To summarize our experience and the early and midterm outcomes of stented elephant trunk procedure for right-sided aortic arch (RAA) with Kommerell's diverticulum (KD). Methods From April 2013 to July 2020, patients with RAA and KD who underwent stented elephant trunk procedure at our center were collected. Surgery was performed under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy. Results A total of 8 patients were included, including 7 males and 1 female with a mean age of 51.88±9.61 years. All patients had an aneurysmal KD and aberrant left subclavian artery. Preoperative comorbidities included acute Stanford type B aortic dissection in 1 patient, aortic arch pseudoaneurysm in 1 patient, acute type B intramural hematoma in 2 patients, and coronary artery disease in 1 patient. Concomitant procedures included reconstruction of the left subclavian artery in all patients and coronary artery bypass grafting in 1 patient. The mean time of operation, cardiopulmonary bypass, aortic cross-clamping, and selective cerebral perfusion was 6.25±1.16 h, 157.75±40.07 min, 77.75±33.10 min, and 28.50±5.55 min, respectively. No intraoperative death occurred. There was 1 in-hospital death. Follow-up was completed in all patients with a mean period of 3.58±2.08 years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in 1 patient, but reintervention was not performed because neither aortic dilatation nor symptoms of tracheal and esophageal compression were observed during the follow-up. The remaining 6 patients showed positive aortic remodeling with complete thrombosis of the aneurysmal KD, and neither aortic event nor tracheal and esophageal compression occurred. Conclusion Stented elephant trunk procedure is a safe and feasible technique for selected patients with RAA and KD, which can achieve favorable early and midterm outcomes.

Objective To investigate the changes in interleukin-34 (IL-34)levels in serum and bronchoalveolar lavage fluid (BALF) of patients with severe pneumonia and their prognostic value. Methods A total of 66 patients with severe pneumonia (severe pneumonia group), 35 patients with non-severe pneumonia (non-severe pneumonia group), and 27 healthy adults (control group) were enrolled. The severe pneumonia group was further divided into survival group of 38 patients and non-survival group of 28 patients based on 28-day survival. Clinical data of all subjects were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive power of serum IL-34 and relative IL-34 gene expression in BALF for 28-day mortality in patients with severe pneumonia, as well as the predictive power of serum IL-34 for severe pneumonia. Kaplan-Meier survival curves were plotted, and the Log-rank test was used to compare cumulative survival rates. Cox regression analysis was conducted to explore risk factors for 28-day mortality in patients with severe pneumonia. Pearson correlation analysis was used to assess the correlation between serum IL-34 levels and relative IL-34 gene expression in BALF of patients with severe pneumonia. Results Serum IL-34 levels were higher in the severe pneumonia group than those in the non-severe pneumonia group, and were higher in the non-severe pneumonia group than in the control group (P < 0.05). Serum IL-34 levels and relative IL-34 gene expression in BALF were higher in the non-survival group than in the survival group (P < 0.05). ROC curve analysis showed that the areas under the curve for predicting 28-day mortality in patients with severe pneumonia were 0.908 for serum IL-34 levels and 0.878 for relative IL-34 gene expression in BALF. The optimal cutoff value for serum IL-34 levels in predicting severe pneumonia was 129.9 pg/mL. Multivariate Cox regression analysis showed that increased serum IL-34 levels and increased relative IL-34 gene expression in BALF were independent risk factors for 28-day mortality in patients with severe pneumonia (P < 0.05). The Kaplan-Meier survival analysis results indicate that, with a cutoff value of 129.9 pg/mL, patients with severe pneumonia who had high serum levels of IL-34 exhibited a lower cumulative survival rate compared to those with low IL-34 level(Log-rank P < 0.001). Conclusion Serum IL-34 levels are significantly increased in patients with severe pneumonia, and relative IL-34 gene expression in BALF is positively correlated with serum IL-34 levels. Both can be used as indicators for predicting the prognosis of 28-day mortality in patients with severe pneumonia.

Objective:To summarize our experience and outcomes of surgical repair of type Ⅱ right-sided aortic arch(RAA) with Kommerell's diverticulum(KD).Methods:From May 2010 to August 2020, a total of 13 patients with type Ⅱ RAA and KD underwent surgery at our center. Mean age was(50.46±10.31) years, 10 were male, and 3 were female. All patients had an aneurysmal KD and aberrant left subclavian artery(ALSA). Preoperative comorbidities included type B aortic dissection in 1 case, aortic arch pseudoaneurysm in 2 cases, and type B intramural hematoma in 2 cases, respectively. Eight(61.5%) patients underwent stented elephant trunk procedures under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy, and all of them had ALSA reconstruction. Five(38.5%) patients underwent distal arch and descending thoracic aortic replacement through a right posterolateral thoracotomy, the ALSA was reconstructed or ligated in 1 each, and ALSA embolization was performed before surgery in the other 3 cases.Results:No operation deaths occurred. Recurrent laryngeal nerve injury occurred in 2 cases. There was 1(7.69%) in-hospital death. Follow-up was complete in 100 % at mean(5.28±3.84) years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in a patient who underwent stented elephant trunk procedure, but no aortic dilatation or tracheal and esophageal compression was observed during follow-up. Meanwhile, aortic events, limb ischemia, or symptoms of tracheal and esophageal compression were not observed in the remaining 11 patients.Conclusion:Surgical repair of type Ⅱ RAA with KD can achieve favorable early and midterm outcomes. Surgical strategies should be chosen based on the anatomy of the aorta and whether it is combined with compression symptoms.

Objective:To analyse the long-term efficacy in childhood T-cell acute lymphoblastic leukemia (T-ALL) cases enrolled in the national protocol of childhood leukemia in China-acute lymphoblastic leukemia (NPCLC-ALL) 2008.Methods:Clinical data of 96 patients diagnosed as T-ALL and treated with NPCLC-ALL2008 protocol between January 2009 and December 2017 in the Department of Hematology-Oncology, the Children′s Hospital, Zhejiang University School of Medicine were analyzed retrospectively. Predictive value of minimal residual disease (MRD) monitored by flow cytometry was analyzed. Kaplan-Meier method was used for long-term survival analysis.Results:A total of 96 evaluable patients with newly diagnosed T-ALL were analysed, including 72 males and 24 females. The age was 9.5 (ranged from 1.0 to 16.0) years. The follow-up time was 5.7 (ranged from 1.0 to 9.7) years. Among 96 patients, 92 (96%) achieved complete remission. The 5-year event free survival (EFS) and overall survival (OS) rates were (61±6) % and (70±5) %, respectively. Relapse occurred in 18 cases and the 5-year cumulative incidence of relapse was (27±6) %. Twenty-four patients died. The 5-year OS rates of patients with MRD>5% on day 15 of induction therapy was significantly worse than those with MRD≤5% ((60±12) % vs. (72±6) %, χ 2=3.904, P=0.048) . The 5-year EFS and OS rates were obviously lower in patients with MRD>10% before the consolidation therapy ((50±35) %). The 5-year OS rates of patients with relapsed disease was significantly worse than those without ((26±13) % vs. (81±5) %, χ 2=18.411, P<0.01). The earlier the relapse, the worse the prognosis. The 5-year OS rates for patients relapsed within 6 months, within 3 years and more than 3 years, were (25±22) %, (30±14) % and (50±35) % respectively (χ 2=13.207, P<0.01). Conclusions:NPCLC-ALL2008 protocol is effective for childhood T-ALL. The MRD guided accurate risk stratification and individualized treatment can reduce the relapse and improve the survival rate of pediatric T-ALL.