T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To identify clinical features,possible risk factors and treatment related to rituximab-associated interstitial pneumonia(RTX-IP). Methods:The clinicopathological characteristics,immune phenotype and treatment of six patients with diffuse large B-cell lymphoma(DLBCL)develped after receiving R-CDOP treatment were retrospectively analyzed. Results:Six patients had agranulocytosis or granulocytopenia within 1 week before RTX-IP diagnosis,and the median interval time was 3 courses of treatment.All six patients had double-expressor lymphoma(DEL)or triple-expressor lymphoma(TEL).Of the six patients,four had germinal-center B-cell-like lymphoma(GCB),and two had non-GCB.The expression of Ki-67 was＞70％,except for one patient with transformed lymphoma(TL).After treatment with methylprednisolone for about 1 week,all patients'chest CT showed inflammatory absorption.However,one patient developed pneumocystis carinii pneumonia during the process of hormone reduction,and recovered after 27 days of comprehensive treatment with hormones and anti-pneumocystosis therapy.All patients received CDOP regimen(a total of 8 courses)for the treatment of the primary disease,and the process was smooth. Conclusion:R-CDOP regimen may lead to a high incidence of RTX-IP in DLBCL patients(30.0％).The DLBCL patients with DEL or TEL,GCB subtype,TL and high Ki-67 expression were more liable to develop RTX-IP,and the recovery of agranulocytosis may be related to the pathogenesis of RTX-IP.High-resolution CT scan can provide valuable evidence for early diagnosis of RTX-IP.Metagenomic next-generation sequencing(mNGS)helps to distinguish IP from pathogen infections.High dose of glucocorticoids is effective treatment strategy.At the same time,it is necessary to strengthen the prevention and treatment of infection in the process of glucocorticoids application.

Objective:This study aimed to observe whether the treatment-free remission (TFR) of second-generation tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) is better than imatinib (IM) .Methods:The clinical data of 274 CML patients who discontinued treatment and with complete clinical data were retrospectively studied from June 2013 to March 2021. Using both univariate and multivariate Cox proportional hazards regression models, risk factors influencing TFR outcomes after drug withdrawal in CML patients were assessed.Results:A total of 274 patients were enrolled, 140 patients were women (51.1%) , with a median age of 48 (9-84) years at the time of TKI discontinuation. Prior to TKI discontinuation, 172 (62.8%) patients were treated with IM, and 102 (37.2%) had received second-generation TKI treatment, including 73 patients who had shifted from IM to a second-generation TKI and 29 patients who used second-generation TKI as the first-line treatment. The rationale for converting to a second-generation TKI are as follows: 37 patients aimed deep molecular response (DMR) to achieve TFR, seven patients changed due to IM intolerance, and 29 patients changed because of failure to achieve the optimal treatment response. The use of the last type of TKI included 96 patients (94.1%) with nilotinib, three patients (2.9%) with dasatinib, and two patients (2%) with flumatinib, including one patient who changed to IM due to second-generation TKI intolerance. No statistical differences were found in the median age at diagnosis and TKI discontinuation, sex, Sokal score, IFN treatment before TKI, median time of TKI treatment to achieve DMR, and the reasons for TKI discontinuation between the second TKI and IM ( P>0.05) .The median cumulative treatment time of TKI (71.5 months vs 88 months, P<0.001) , the last TKI median treatment time (60 months vs 88 months, P<0.001) , and the median duration of DMR (58 months vs 66 months, P=0.002) were significantly shorter in the second-generation TKI compared with IM. In the median follow-up of 22 (6-118) months after TKI discontinuation, 88 patients (32.1%) had lost their MMR at a median of 6 (1-91) months; of the 53 patients (60.2%) who lost MMR within 6 months, the overall TFR rate was 67.9%, and the cumulative TFR rates at 12 and 24 months were 70.5% and 67.5%, respectively. Withdrawal syndrome occurred in 26 patients (9.5%) . For patients who restarted TKI treatment, 72 patients (83.7%) achieved DMR again at a median treatment of 4 (1 to 18) months. The univariate analysis showed that the TFR rate of patients treated with second-generation TKI was significantly higher than those who were treated with IM (77.5% vs 62.2%, P=0.041) . A further subgroup analysis found that the TFR rate of the second-generation TKI patients was significantly higher than those treated with IM (80.8% vs 62.2%, P=0.026) . No significant difference was found in the second-generation TKI used as the first line treatment compared with those who were treated with IM (69.0% vs 62.2%, P=0.599) . The multivariate analysis results showed that second-generation TKI treatment was an independent prognostic factor affecting TFR in patients who discontinued TKI ( RR=1.827, 95% CI 1.015-3.288, P=0.044) . Conclusion:In the clinical setting, more CML patients rapidly achieved TFR using second-generation TKI than IM treatment.

Objective:To explore the effect of intervention based on adaptive leadership theory in rectal cancer patients with permanent enterostomy.Methods:A total of 118 rectal cancer patients who underwent radical resection and permanent enterostomy in a ClassⅢ Grade A hospital in Yantai from July 2018 to June 2019 were recruited as the research subjects by convenience sampling method. All the subjects were assigned to control group (from July to December 2018) and observation group (from January to June 2019) according to the time of hospitalization, with 59 cases in each group. The control group was given routine nursing, while the observation group was given nursing intervention based on adaptive leadership theory. The effects of interventions were compared using the Colostomy Patient Colostomy Knowledge Attitude and Practice Scale (CPCKAPS) and Social Impact Scale (SIS) .Results:Finally, 54 patients were included in the control group and 52 patients in the observation group. After the intervention, the scores of stoma knowledge, attitude and behavior of the observation group were (11.15±2.33) , (44.53±3.94) and (25.21±3.19) respectively, which were higher than those of the control group, and the differencs were statistically significant ( t=-5.377, -4.575, -2.422; P<0.05) . After the intervention, the scores of SIS social exclusion, intrinsic shame, and social isolation of the observation group were (17.62±3.94) , (10.78±2.49) and (15.81±3.49) points, which were lower than those of the control group, and the differencs were statistically significant ( t=3.143, 2.102, 3.024; P<0.05) . Conclusions:The intervention program based on the adaptive leadership theory can better promote the changes of patients' knowledge, attitudes and behaviors, effectively reduce the stigma of patients with enterostomy.

OBJECTIVE：To prepar e Celastrol oral u lcer film ，and to evalute its quality primarily. METHODS ：The comprehensive scores of the appearance ，film formation and toughness of the drug film were used as indicators ，and the amount of celastrol was controlled to 0.05％. Orthogonal test was used to optimize the amount of excipients as starch ，sodium carboxymethyl cellulose，glycerol and condensed honey ，so as to optimize the formulation ；the validation test was performed. The adhesion force of the film prepared by the optimal formulation were determined. UV spectrophotometer was used to detect the content of celastrol in the film. RESULTS ：The optimal dosage of each excipient in Celastrol oral ulcer film was starch 1.0 g，sodium carboxymethyl cellulose 0.2 g，glycerin 0.4 g，condensed honey 1.5 g. In 3 times of validation tests ，the appearance of the prepared film was good. The average adhesion of the film prepared by the optimal formulation was 4.2 g，and the average content of celastrol was 0.135 3 mg/cm2（RSD＝1.90％，n＝3）. CONCLUSIONS ：In this study ，the best formulation of Celastrol oral ulcer film was optimized，and the film forming ability of the prepared film is good and the quality is stable and uniform.

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.

December 2019 witnessed the outbreak of COVID-19 in Wuhan and spread of the epidemic across the country. As a provincial designated hospital for critical patients, the First Affiliated Hospital of Zhejiang University responded rapidly since then by advocating the four-concentration principles, namely " concentrating patients, experts, resources and treatment" . In its rescue of critical patients, the hospital formulated comprehensive emergency plans, optimized hospital-wide resources, effectively arranged rescue spacing, established medical echelons, and implemented multi-disciplinary strategy. These efforts ensured efficient rescue and treatment, achieving a cure rate up to 98.7% of such patients, with no deaths.

Objective: To explore the availability and safety of fecal microbiota transplantation for patients with refractory diarrhea after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Four acute leukemia patients suffered from refractory diarrhea after allo-HSCT. One of them was refractory intestinal infection, the others were intestinal graft versus host disease. One or two doses of fecal microbiota, 3.4-6.0 U for one dose, were infused via nasal-jejunal tube. The curative effect and side effects were reviewed. Results: Three cases achieved complete remission while 1 was stable disease. The side effects included fever, abdominal pain and diarrhea, which all were Ⅰ grade. Conclusion Fecal microbiota transplantation was effective and safe for refractory diarrhea after allo-HSCT.

Objective: To evaluate the efficacy and safety of mesenchymal stem cells in allogeneic hematopoietic stem cell transplantation for patients with refractory severe aplastic anemia (R-SAA) . Method: The clinical data of 25 R-SAA patients receiving co-transplantation of mesenchymal stem cells combined with peripheral blood stem cells from sibling donors (10 cases) and unrelated donors (15 cases) from March 2010 to July 2018 in Zhengzhou University Affiliated Tumor Hospital were retrospectively analyzed. Antithymocyte globulin (ATG) treatment was ineffective/relapsed in 11 cases, and cyclosporine (CsA) treatment ineffective/relapsed in 14 cases. Results: There were 13 male and 12 female among these patients. One patient had a primary graft failure, one patient had a poorly engraftment of platelets, and the remaining 23 patients achieved hematopoietic engraftment. The median time of granulocyte engraftment was 12.5 (10-23) days and 15 (11-25) days for megakaryocyte. Incidences of grade Ⅰ/Ⅱ acute graft-versus-host disease (aGVHD) and chronic graft-versus-host disease (cGVHD) were 37.5% (9/24) and 21.7% (5/23) , respectively. There was no severe GVHD and no severe complications that related to transplantation. 21 of 25 (84%) patients were alive with a median follow-up of 22.9 (1.6-107.8) months. The 5-year overall survival rate after transplantation was (83.6±7.5) %. Conclusion The combination of mesenchymal stem cells is reliable and safe in the treatment of R-SAA in peripheral blood stem cell transplantation of unrelated donors and sibling donors, which could significantly reduce the incidence of GVHD and severe transplantation-related complications.

Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration. Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed. Results: The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy. Conclusion CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.