Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective:To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) .Methods:Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed.Results:Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients’ autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0–2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively ( P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions:CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

Objective:To explore the relationship between intolerance of uncertainty and internet addiction among college students, as well as the mediating roles of negative cognitive bias and difficulties in emotion regulation.Methods:In September 2022, 1 762 college students were assessed with intolerance uncertainty scale, negative cognitive process bias questionnaire, difficulties in emotion regulation scale and internet addiction test. SPSS 24.0 software was used for descriptive statistics and correlation analysis. AMOS 23.0 was used to construct a multiple mediation model, and Bootstrap method was used for mediation effects testing.Results:(1) The score of intolerance of uncertainty was 34.00 (28.00, 40.00), the score of negative cognitive bias was 42.00 (34.00, 50.00), the score of difficulties in emotion regulation was 26.00 (20.00, 32.00), and the score of internet addiction was 36.00 (28.00, 46.00). (2)The Spearman correlation analysis showed that intolerance of uncertainty, negative cognitive bias, difficulties in emotion regulation, and internet addiction were significantly positively correlated with each other ( r=0.343-0.626, P<0.01). (3) The results of the path analysis indicated that the direct effect of intolerance of uncentainty on internet addiction was not significant, and the total indirect effect was 0.402(95% CI=0.354-0.451).The indirect effect of negative cognitive bias was 0.253(95% CI=0.200-0.305), accounted for 62.94%(0.253/0.402) of the total indirect effect.The indirect effect of difficulties in emotion regulation was 0.052 (95% CI=0.033-0.076), accounted for 12.93%(0.052/0.402) of the total indirect effect.And the chain mediating effect of negative cognitive bias and difficulties in emotion regulation was 0.097(95% CI=0.068-0.131), accounted for 24.13%(0.097/0.402) of the total indirect effect. Conclusion:Intolerance of uncertainty is significantly positively correlated with internet addiction, and its effects on internet addiction are individually mediated by negative cognitive bias and difficulties in emotion regulation, as well as their chain mediating effects.

Objective:To explore the role of mindfulness and negative cognitive bias between behavioral inhibition system and social anxiety among college students.Methods:From October 12th to November 8th of 2012, a total of 747 college students from a university in Tianjin were sampled and assessed using the behavioral inhibition system scale (BIS), the mindful attention awareness scale (MAAS), the negative cognitive processing bias questionnaire (NCPBQ), and the social avoidance and distress scale (SAD). Descriptive statistics, correlation analysis, and tests for mediating effects were performed by SPSS 20.0 and Mplus 8.0.Results:The scores of behavioral inhibition system, social anxiety, mindfulness and negative cognitive bias were (15.3±2.4), (12.7±7.2), (3.4±0.8) and (45.6±11.5), respectively. The scores of BIS, NCPBQ, and SAD were positively correlated with each other ( r=0.27-0.49, all P<0.001). The scores of MAAS were negatively correlated with the scores of BIS, NCBPQ, and SAD ( r=-0.33--0.28, all P<0.001). The behavioral inhibition system exerted its influence on social anxiety through three pathways. The mediating effect size of mindfulness was 0.04, accounting for 16.0% of the total effect. The mediating effect size of negative cognitive bias was 0.17, accounting for 68.0% of the total effect. And the chain mediating effect size of mindfulness and negative cognitive bias was 0.04, accounting for 16.0% of the total effect. Conclusion:The effects of behavioral inhibition system on social anxiety in college students are individually mediated by mindfulness and negative cognitive biases, as well as their chain mediating effects.

Inhibition of human cytochrome P450 (CYP) can lead to drug-drug interactions, resulting in serious adverse reactions.It is therefore crucial to accurately predict the inhibitory power of a given compound against a particular CYP isoform.This study compared 11 machine learning methods and 2 deep learning models based on different molecular representations.The experimental results showed that the CatBoost machine learning model based on RDKit_2d+Morgan outperformed other models in terms of accuracy and Mathews coefficient, and even outperformed previously published models.Moreover, the experimental results also showed that the CatBoost model not only had superior performance, but also consumed less computational resources.Finally, this study combined the top 3 performing models as co_model, which slightly outperformed the CatBoost model alone in terms of performance.

Objective: To propose reasonable suggestions to promote the standardization of clinical studies by reviewing the systematic reviews and meta-analyses of acupuncture-moxibustion treatment of essential hypertension (EH). Methods: Computer retrieval was conducted through Excerpta Medica Database (EMBASE), PubMed, China National Knowledge Infrastructure (CNKI), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), and Wanfang Academic Journal Full-text Database (Wanfang) to collect systematic reviews and meta-analyses relevant to treating EH with acupuncture-moxibustion therapy. The time range was from the database's inception till July, 2020. The studies were screened based on the inclusion and exclusion criteria and then data-extracted. The study's quality and evidence ratings were performed by referring to the preferred reporting items for systematic review and meta-analysis (PRISMA), a measurement tool to assess systematic reviews 2 (AMSTAR 2), and the grading of recommendations, assessment, development, and evaluation (GRADE). Results: A total of 14 studies, 10 in Chinese and 4 in English, published between 2012 and 2019, were included, involving 70 outcome measures. The methodological quality was rated as critically low, the reporting was relatively complete or had certain flaws, and the evidence strength was rated as low or very low. Conclusion: Regarding the acupuncture-moxibustion treatment of EH, the methodological quality and outcome measure evidence of existing systematic reviews and meta-analyses are relatively low, and the reporting quality also expects further improvements.

Objective:To observe the efficacy and safety of decitabine combined with chemotherapy in treatment of relapsed/refractory T lymphoblastic lymphoma/leukemia (T-LBL/ALL) with TP53 mutation.Methods:The clinical data of a T-LBL/ALL patient with TP53 mutation who had recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) treated with decitabine combined with chemotherapy in the First Affiliated Hospital of Soochow University in June 2018 were retrospectively analyzed and the relevant literature was reviewed.Results:The patient, a 42-year-old male, diagnosed as T-LBL/ALL with TP53 mutation by comprehensive examination underwent sibling-matched donor allo-HSCT after a second complete remission. The patient relapsed 8 months later and was treated with decitabine combined with CLAG regimen to achieve complete remission again. And then, he had leukemia-free survival until now through maintenance treatment with decitabine.Conclusion:Decitabine combined with chemotherapy may be a safe and effective treatment option for relapsed T-LBL/ALL patients with TP53 mutation after allo-HSCT.

Objective: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL. Methods: The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without. Results: The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) . Conclusions Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.

Objective To explore the efficacy of hematopoietic stem cell transplantation (HSCT) for 5 patients with Ph-like acute lymphoblastic leukemia (ALL).Methods Fluorescent in situ hybridization (FISH) was performed for detecting the rearrangement of susceptibility genes.Combined therapy of chemotherapy and ruxolitinib were applied,followed by HSCT.Those failing to achieve complete remission (CR) received an infusion of chimeric antigen T-cells (CAR-T),followed by HSCT once CR was achieved.Four patients accept allogenic HSCT while another auto HSCT.Results Three of them achieved CR after chemotherapy and ruxolitinib.The remaining 2 patients got CR after CAR-T.Four patients remained in CR after HSCT.Early relapse occurred in 1 patient after HSCT.Conclusions Combined therapy of chemotherapy,ruxolitinib and CAR-T are necessary for Phlike ALL patients.HSCT after an initial CR improve patient prognosis.

Objective To improve the understanding of the diagnosis and treatment of Philadelphia (Ph) chromosome-like acute lymphoblastic leukemia (ALL) with EBF1-PDGFRB-positive. Methods One case of Ph-like ALL with EBF1-PDGFRB-positive from the First Affiliated Hospital of Soochow University was reported. Whole exome sequencing was applied to detect the EBF1-PDGFRB fusion gene. Fluorescence in situ hybridization (FISH) was used to detect minimal residual disease. Comprehensive treatments including chemotherapy, imatinib and chimeric antigen T-cell (CAR-T) therapy were utilized. Results EBF1-PDGFRB fusion gene in the bone marrow samples was detected by using whole exome sequencing at early diagnosis. The rearrangement of PDGFRB showed continuous negative after comprehensive therapy. The patient achieved continuous molecular remission for 22 months. Conclusions The comprehensive treatments include combined chemotherapy, CAR-T therapy and tyrosine kinase inhibitor can promote the continuous of major molecular remission for EBF1-PDGFRB-positive Ph-like ALL patients.