Multiple myeloma (MM) is an incurable malignancy. The treatment mainly includes induction therapy, minimal residual disease (MRD) clearance therapy, and maintenance therapy. For high-risk/ultra-high-risk (UHR) or relapsed/refractory MM, optimizing the eradication of MRD and sustaining long-term suppression of MRD at low levels are a formidable challenge. Ixazomib (I) is a reversible proteasome inhibitor (PI) that is available orally as the prodrug ixazomib citrate. Lisaftoclax is a novel, potent, selective BCL-2 inhibitor under clinical development for the treatment of patients with hematologic malignancies or solid tumors and has shown clinical antitumor benefit. Herein, we report two patients with relapsed/refractory UHR MM who achieved durable disease control with MRD negativity after receiving ixazomib, lisaftoclax, and dexamethasone (ILD) as maintenance therapy following B Cell Maturity Antigen BCMA-chimeric antigen receptor (CAR)-T cell therapy. Regarding the treatment regimen, all drugs were administered orally: ixazomib 4 mg d1, d8, and d15; lisaftoclax 400 mg d1-d14; and dexamethasone 20 mg d1, d8, and d15. One treatment cycle is defined as 28 days. Treatment will be discontinued in the event of uncontrollable active infection or organ injury. These cases demonstrate that the ILD combination therapy can optimize MRD eradication and sustain long-term MRD suppression, offering a promising therapeutic option for patients with limited treatment choices. Formal evaluations of this regimen in patients with high-risk/ultra-high-risk or relapsed/refractory MM may be meaningful. This study was supported by the China Cancer Foundation (Project No.: CFC2023WJZD003).

Background: Acute myeloid leukemia (AML) is an aggressive and molecularly diverse hematologic malignancy with unfavorable clinical outcomes and limited options for targeted therapy. This study investigated whether polypyrimidine tract-binding protein 1 (PTBP1), an RNA-binding protein (RBP), affects AML progression by binding to WNK lysine-deficient protein kinase 1 (WNK1). Methods: We first determined the level of WNK1 in AML using the Gene Expression Profiling Interactive Analysis‌ (GEPIA) database and verified it by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB) assay. AML cell migration and invasion were analyzed using Transwell assays following WNK1 modulation. Epithelial-to-mesenchymal transition (EMT) marker level was confirmed by WB assay. The influence of WNK1 on the in vivo metastasis of AML was verified via tail vein injection of WNK1-knockdown AML cells into Non-Obese Diabetic/Severe Combined Immunodeficiency (NOD/SCID) mice. Mechanistically, RNA pull-down and RNA immunoprecipitation (RIP) assays were utilized to interpret the relationship between PTBP1 and WNK1 and to determine whether PTBP1 affects AML cell migration and invasion by regulating WNK1, using rescue experiments. Results: WNK1 was highly expressed in AML. WNK1 inhibition hindered AML cell migration, invasion, and the expression of EMT markers. WNK1 depletion markedly suppressed the metastasis of AML cells in vivo. Mechanistically, PTBP1 directly bound to WNK1 and increased its mRNA stability. Furthermore, PTBP1 facilitated AML cells migration, invasion, and the expression of EMT markers via WNK1. Conclusion: We demonstrate that PTBP1 promotes AML progression by modulating WNK1. PTBP1 may therefore represent a potential therapeutic target in AML.

Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is the most common histological subtype of PTCL. PTCL-NOS has a relatively low incidence, and its pathogenesis and mechanisms of drug resistance remain unclear, leading to lagging research progress. The aim of the present study was to summarize the clinical features and outcomes of patients with PTCL-NOS. A total of 30 patients with treatment-naive PTCL-NOS who were admitted to The Second Hospital of Hebei Medical University (Shijiazhuang, China) between September 2013 and September 2023 were retrospectively analysed. The median age at diagnosis was 59 years (range, 17-70 years), and the male-to-female ratio was 2.75:1. The median follow-up duration was 59 months. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 50.4 and 28.9%, respectively. Multivariate analysis showed that an Eastern Cooperative Oncology Group performance status >1, bone marrow involvement and a platelet count <150×109/l were independent risk factors for OS, whereas bone marrow involvement and albumin levels <35 g/l were independent risk factors for PFS. There was no significant difference between the cyclophosphamide, doxorubicin, vincristine, prednisone and etoposide regimen and the cyclophosphamide, vincristine, doxorubicin and prednisone regimen, whereas combinations with chidamide showed a trend toward an improved PFS. Within the cohort, 2 patients with relapsed and refractory CD30-positive PTCL-NOS received salvage chemotherapy with brentuximab vedotin (BV), a monoclonal antibody, and achieved complete metabolic remission, followed by sequential allogeneic haematopoietic stem-cell transplantation, resulting in long-term sustained remission. In conclusion, patients diagnosed with PTCL-NOS generally have a poor prognosis. Nevertheless, the use of innovative targeted therapies, such as chidamide and BV, shows potential to improve treatment outcomes in these patients.

Background:Multiple myeloma (MM) is a common hematologic malignancy characterized by high tumor cell heterogeneity, which significantly impacts the clinical prognosis of patients. Angiogenesis and the molecular features of tumor cells play a critical role in tumor progression and drug resistance. This study aims to explore the impact of tumor cell heterogeneity and angiogenesis-related genes on the prognosis of MM. Methods:We collected transcriptomic data and single-cell RNA sequencing data from MM patients through the Xena and GEO databases. The data were processed and analyzed using bioinformatics methods, including differential gene expression analysis, single-cell clustering, CNV analysis, transcription factor analysis, screening of angiogenesis-related genes, cell communication analysis, and immune infiltration analysis. Results:Through integrative analysis of transcriptomic data and single-cell RNA sequencing data, we identified significant genomic copy number variations in the tumor cells of MM patients. Additionally, different tumor subgroups exhibited differences in angiogenic activity, gene expression, and tumor progression. Notably, high expression of the transcription factor cAMP-responsive element-binding protein 3-like 2 (CREB3L2) in the C1 subgroup was associated with the inhibition of angiogenesis and tumor cell proliferation and migration. Furthermore, the prognostic model based on angiogenesis and transcription factors demonstrated high accuracy in predicting the prognosis of MM patients. Conclusion:This study highlights the critical roles of tumor cell heterogeneity and angiogenesis-related genes in MM. By constructing a prognostic model, it provides new theoretical insights for the precise diagnosis and personalized treatment of MM.

Acute Myeloid Leukemia (AML) carries a high mortality rate in elderly patients who often face limited treatment options and a poor overall prognosis. The combination of Venetoclax (VEN) and Decitabine (DEC) is recommended for treatment, yet there is insufficient evidence to fully support its efficacy. This study aims to perform a meta-analysis to evaluate the effectiveness and safety of the VEN + DEC regimen in treating elderly patients with AML. We systematically searched PubMed, EMBASE, the Cochrane Library, CNKI, and WanFang. Efficacy was evaluated using complete remission (CR), composite response rate, overall response rate, and median overall survival. Safety was assessed based on adverse events. The fixed/random effect model was employed to evaluate the effect sizes. Seven articles were included in this meta-analysis. VEN + DEC group (OR 1.90, 95

PurposeThis study aimed to assess the effectiveness of anti-CD20 monoclonal antibody and hetrombopag for relapsed/refractory immune thrombocytopenia (ITP) following glucocorticoid treatment.MethodsWe retrospectively included four patients with relapsed/refractory ITP. The median disease duration is 9 months. Their prior lines of therapy numbered 4, 2, 4, and 2, respectively. They were treated with a combination of anti-CD20 monoclonal antibody and hetrombopag, followed by maintenance therapy with hetrombopag and monitoring of platelet (PLT) changes.ResultsAll four patients achieved complete response (CR), with the time to response ranging from 2 to 9 days and the duration of response (DoR) ranging from 3 to 27 months. CR was defined as a PLT count >100 × 109/L and the absence of bleeding. The treatment was well tolerated. Only the first patient’s PLT count decreased to 31 × 109/L following discontinuation of therapy after 6 months of DoR. Accordingly, the patient was treated with avatrombopag monotherapy, which maintained the PLT count at normal levels. The third patient presented with secondary ITP. After treatment with ripertamab-hetrombopag, the patient received combination therapy with hetrombopag, glucocorticoids, tacrolimus, and hydroxychloroquine, with the PLT count being maintained within the normal range. The other two patients remained in sustained CR throughout the follow-up period.ConclusionCombining anti-CD20 monoclonal antibody with hetrombopag may offer therapeutic benefits in patients with relapsed/refractory ITP.

Background: cervical squamous cell carcinoma (CSCC) is the second gynecological tumors that seriously threaten women's life quality. Circular RNA (circRNA) is related with cervical cancer carcinogenesis and radiosensitivity. Aim: To investigate the performance of hsa_circ_0007905 (circSTX6) on regulating cellular activities and radiosensitivity in CSCC. Methods: The relative expression of circSTX6 in different tissue samples was detected by RT-qPCR. The cellular activity influence of circSTX6 in cervical cancer cells was measured by CCK-8 and Transwell assays. The survival fractions of cancer cells were detected after the radiation treatment to explore the relationship between circSTX6 and radiosensitivity of cervical cancer. The downstream miRNAs were predicted and analyzed. Rescue experiments confirmed their targeting relationship. Bioinformatic analysis was performed to identify the potential targets of miR-203a-3p. Results: circSTX6 was increased and miR-203a-3p was decreased in cervical cancer tissues and radio-resistant tissues. CircSTX6 expression was related to the patient's survival rates. CircSTX6 absence decreased cervical cancer cell proliferation and invasion while enhancing the sensitivity of cervical cancer cells to radiotherapy by regulating miR-203a-3p. RAB27B may be a target of miR-203a-3p. Conclusion: circSTX6 may be a clinical prognostic biomarker in CSCC. The absence of circSTX6 inhibits cellular behaviors and increases the sensitivity of cervical cancer cells to radiation by modulating miR-203a-3p/RAB27B axis.

Abstract Selinexor is an oral, reversible, potent Selective Inhibitor of Nuclear Export / SINE TM compound that specifically blocks the protein Exportin 1 (XPO1), also known as chromosomal region maintenance 1 (CRM1). Selinexor induces cell cycle arrest, inhibits DNA damage repair and modulates the expression of NF-κB in cancer cells lines and has demonstrated broad activity across several hematologic malignancies including AML. In preclinical studies, AML cells, when treated with selinexor, exhibited sensitivity to chemotherapy, in part, by blocking the nuclear export of topoisomerase II (Clin Cancer Res 2016;22(24):6142-6152). This, when coupled with the presence of an anthracycline antibiotic, resulted in an increased number of DNA strand breaks. In May 2019, the FDA approved the use of selinexor in combination with dexamethasone for adults with relapsed or refractory multiple myeloma who received at least four prior therapies with disease refractory to at least two immunomodulatory agents, at least two proteasome inhibitors, and a CD38-targeting monoclonal antibody. The aim of this study is to evaluate the efficacy and safety of the combination therapy of Decitabine, Venetoclax， and Selinexor (DVS) in the treatment of newly diagnosed AML and MDS patients who are not suitable for intensified chemotherapy, as well as in patients with relapsed/refractory AML and high-risk MDS. Method: This multicenter, single arm, prospective clinical study conducted at multiple research centers in China. A total of 96 patients will be enrolled in the study. The patients were treated with Decitabine 20 mg/m2, d1-5；Venetoclax 100 mg d1, 200 mg d2, 400 mg d3-21; Selinexor 60 mg/d, d4, 11, 18. Every 28 days are one cycle. The primary endpoints are complete remission(CR)/complete remission with incomplete count recovery (CRi) / incomplete recovery of peripheral blood cell count/ANC>0.5X109/L (500/uL) and platelet count ≥ 50 × 109/L (50000/uL), meeting other CR criteria(CRh)/ morphologic leukemia-free state (MLFS) (CR/CRI/CRh/MLFS). Secondary endpoints include objective response rate (ORR) (complete response rate/incomplete recovery of peripheral blood cell count, partial response rate) ，safety. Result: Until July, 2024, there are 14 patients(AML/MDS：12/2) included this study. The median age of the patients is 63.5（24-76）years. The male and female are 5 and 9. Among them, The median of white blood cell count (WBC) is 3.3×10^9/L, platelet count (Platelets) is 41.5×109/L, and the percentage of blast cells in bone marrow is 29.25%. During the first course of treatment, 2 patients discontinued the treatment due to adverse events. 9 patients were evaluated for efficacy, the other three cases did not enter the first course of evaluation due to short follow-up time. With a median follow-up of survivors of 40(27-117) days, 9 patients' efficacy can be evaluated. The complete remission rate was 55.56%（5/9），One （11.11%）patient has stable disease. Five patients experienced adverse events, including two cases of pulmonary infection, one case of thrombocytopenia, one case of pancytopenia, and one case of diarrhea. All were mild or moderate in severity. Conclusion：Combination therapy of Decitabine, Venetoclax，and Selinexor (DVS) has a manageable safety profile and showed activity in AML and MDS.

This study aimed to verify a novel potential indicator of disease progression in acute myeloid leukemia (AML) patients. Bone marrow samples were collected from 27 AML patients and 27 controls without hematological malignancies. Polypyrimidine tract-binding protein 1 (PTBP1) expression in bone marrow samples was measured, and the association of PTBP1 with the French-American-British (FAB) classification, cytogenetics, risk stratification, and complete remission (CR) rate was analyzed. The correlation between PTBP1 and Ki-67/p53 expression in AML patients was ultimately evaluated. The results showed that PTBP1 mRNA and protein levels were greater in AML patients than in controls. PTBP1 expression was able to distinguish between AML patients and controls (area under the curve, 0.8601; 95% confidence interval, 0.7632-0.9570). Furthermore, PTBP1 expression was associated with an increased frequency of internal tandem duplication mutations within FMS-like tyrosine kinase-3 (FLT3) and a complex karyotype, while PTBP1 expression was not correlated with FAB classification, monosomal karyotype, isolated biallelic CCAAT/enhancer-binding protein α (CEBPA) mutation, or nucleophosmin 1 (NPM1) mutation in patients with AML. Moreover, PTBP1 expression was associated with a poorer prognosis according to risk stratification and a lower CR rate in AML patients. In addition, PTBP1 expression was positively correlated with the expression of the proliferation marker Ki-67 and negatively correlated with the expression of the apoptosis marker p53 in AML patients. Overall, PTBP1 is a viable biomarker that contributes to the risk prediction and the determination of potential drug targets for AML.

The occurrence of acute myeloid leukemia (AML) with a simultaneous diagnosis of breast cancer (BC) is rarely reported in the literature. The present study reports the case of a 50-year-old female patient diagnosed with AML coexisting with metastatic BC. Following one cycle of treatment with azacytidine in combination with oral venetoclax for AML, the patient achieved complete remission with incomplete hematological recovery. In addition, the mass in the left breast was smaller following adjuvant chemotherapy. However, due to a refusal from the patient to accept an allogeneic hematopoietic stem cell transplantation (allo-HSCT), the patient succumbed 3 months after diagnosis due to septic shock from neutropenia following the third cycle of chemotherapy. Altogether, the present case report highlighted the application of venetoclax, an oral selective B-cell lymphoma-2 inhibitor, both in hematologic malignancies and solid neoplasms, as an effective therapeutic regimen. Considering the fatality rate associated with AML, allo-HSCT is the only available strategy that can be used to achieve the long-term survival of patients with AML and BC.

This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL (n=60) and patients with reactive lymphoproliferative disease (RLD; n=20) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in patients with RLD compared to those with DLBCL, but the difference was not statistically significant (P>0.05). p62 levels in patients with DLBCL were significantly higher than those in patients with RLD (P<0.05). Beclin-1 expression was associated only with the Ann Arbor stage (P<0.05), whereas p62 expression was associated with the Ann Arbor stage, International Prognostic Index score, extranodal involvement, and Ki-67 index (P<0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in patients with DLBCL. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (P>0.05). However, high p62 expression in patients with DLBCL was associated with reduced 2-year PFS compared with that of patients with low p62 expression (P<0.05); the 2-year OS was not affected (P>0.05). Our results demonstrate that autophagic activity affects the prognosis of patients with DLBCL; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of patients with DLBCL.

Background: PTCL-NOS is the most common histological subtype of PTCL, characterized by high heterogeneity in clinical presentation, immunophenotype, and genetic features. The incidence of PTCL-NOS is regional distributed, with PTCL accounting for 23-27% of non-Hodgkin lymphomas in China, significantly higher than the 10% in Western countries. In terms of treatment, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) like regimens are still the first-line therapy; However, due to the high invasiveness and recurrence rate of the disease, the five-year progression free survival (PFS) rate is only 29%. In recent years, with the application of new drugs such as histone deacetylase (HDAC) inhibitor Chidamide and antibody conjugated drugs brentuximab-vedotin (BV) etc, certain clinical benefits have been brought to PTCL patients, however these patients still faces significant survival challenges. Aim:The aim of this study was to explore the clinical features of Chinese patients with PTCL-NOS in a single institution, to identify potential prognostic factors, and to provide references for early diagnosis and improvement of long-term survival Methods: Thirty patients with treatment-naïve PTCL-NOS admitted to the Second Hospital of Hebei Medical University from January 2015 to 2023 were analyzed retrospectively. Results: A total of 30 patients were included.The median age of the patients at diagnosis was 59 years old (range: 17~70) , and the male to female ratio was 2.75:1. Most patients were an advanced stage at diagnosis, with intranodal primary as the main type; in terms of immunophenotype, there was a variable loss of pan-T cell markers, most commonly seen in abnormal expression of CD5 and CD7. The CD30 positivity rate in this study was 53.8%, which is higher than previous literature reports, or may be related to the different cutoff values of CD30 positive and a relatively small sample size of this study. This suggests that these patients with CD30 positive can use BV as a preferential therapy choice.The follow-up period ended in September 2023, with a median follow-up time of 59.0 months. The 3-year OS and PFS were 50.4% and 28.9%, respectively. The overall 5-year overall survival (OS) and 5-year PFS were 44.8% and 21.7%, respectively. Multivariate analysis showed that ECOG score >1, bone marrow involvement, and PLT <150×109/L were independent risk factors for OS, while bone marrow involvement and ALB <35g/L were independent risk factors for PFS. In terms of treatment, there was no significant difference between the CHOPE regimen and the CHOP regimen, and the combination with Chidamide showed a trend towards improved OS and PFS. Two relapsed and refractory patients wtith CD30 positive had received salvage chemotherapy based on BV monoclonal antibody and achieved complete metabolic remission, followed by sequential allogeneic hematopoietic stem cell transplantation and obtained long-term sustained remission. Conclusion: Patients with PTCL-NOS in China have a poor prognosis, and the conventional CHOP-like regimens has limited efficacy. Several novel drugs such as Chidamide and BV may improve patient prognosis in some individual patients. Future research should focus on the development of effective clinical prediction tools and treatment strategies, particularly accelerating the development of novel drugs for PTCL

Genetic association between SUMO-specific protease 1 (SENP1) and acute myeloid leukemia (AML) has been validated. However, the mechanism by which SENP1 affects AML proliferation, apoptosis, and autophagy remains unknown. The levels of SENP1 and polypyrimidine tract-binding protein 1 (PTBP1) were measured in AML patients, AML cell lines, and xenograft tissues. The effects of SENP1 on AML proliferation, apoptosis, and BECN1-dependent autophagy were assessed through in vitro and in vivo loss- or gain-of-function experiments. SUMOylation analysis using immunoprecipitation (IP), RNA pull-down, RIP, and RNA stability assays were used to explore the molecular mechanism of SENP1 in AML development. The SENP1 level was elevated in AML samples. Silencing SENP1 impeded the development of AML, as evidenced by the inhibition of proliferation and promotion of G1 phase arrest and apoptosis resulting from SENP1 depletion in AML cells. Moreover, silencing of SENP1 restrained BECN1-depentent autophagy in AML cells. In addition, the overexpression of BECN1 or PTBP1 partially neutralized the effect of SENP1 knockdown on AML cell behavior. Mechanistically, SENP1 mediated PTBP1 deSUMOylation, which then directly interacted with BECN1 mRNA and enhanced its stability. In vivo experiments further confirmed the repressive effects of SENP1 suppression on AML development. Collectively, the SENP1/PTBP1/BECN1 signaling axis has been identified as a significant therapeutic target for enhancing AML treatment.

心脏毒性,是抗肿瘤药物严重的并发症.近年来,随诊抗肿瘤药物的发展,多药联合治疗可显著延长患者的生存期,但此方式加重心脏毒性.了解心脏毒性的发生机制,及时发现并进行预防,可减少心血管意外的发生.本文就抗肿瘤药物的心脏毒性预防及管理进行综述.

Background. It is well known that microRNAs (miRNAs) interfere with the progression of various human malignancies. This article is aimed at exploring the regulating role of miR-342-3p in acute myeloid leukemia (AML) and its mechanism. Methods. We used the Gene Expression Omnibus (GEO) database to determine miR-342-3p differential expression patterns in AML patients’ plasma and cells as well as healthy individuals’ plasma and T cells. Quantitative real-time PCR and Western blotting were performed for plasma and cell miR-342-3p and SRY-related high-mobility-group box (SOX12) expression quantification, and cell counting kit-8 assay and flow cytometry were used for the determination of AML cell growth, cycle, and apoptosis. A dual-luciferase reporter gene assay was further carried out to identify the targeted association between miR-342-3p and SOX12 mRNA 3′UTR after prediction by a bioinformatics website. Pearson’s correlation analysis was performed to analyze the connection between miR-342-3p and SOX12 expressions. The LinkedOmics database was utilized to explore the downstream pathways in which SOX12 was enriched. Results. Evidently downregulated plasma miR-342-3p and markedly elevated SOX12 were observed in AML patients versus healthy individuals. miR-342-3p mimics suppressed AML cell growth, enhanced apoptosis, and induced G0/G1 phase arrest; conversely, enhanced capacity of AML cells to proliferate, suppressed apoptosis, and accelerated cell cycle were observed after treatment with miR-342-3p inhibitors. SOX12 was confirmed as miR-342-3p’s target gene. Overexpressing or knocking down SOX12 reversed miR-342-3p’s impacts on AML cell growth, apoptosis, and cycle. Upregulated SOX12 was positively related to DNA replication and RNA polymerase signaling pathways. Conclusion. miR-342-3p affects apoptosis of AML cells and their ability to proliferate via targeted regulation of SOX12.

目的:探讨miR-335调控Survivin和NF-κB表达对B细胞淋巴瘤细胞侵袭、迁移和凋亡的影响.方法:取对数生长期的B细胞淋巴瘤细胞株SU-DHL-4,分为对照组(不做任何处理)、空转染组(转染空载体)和过表达组(转染miR-335).转染48 h后采用RT-PCR和Western blot分别检测各组细胞miR-335水平和Survivin、NF-κB蛋白的相对表达量.采用划痕实验和Transwell侵袭实验检测细胞迁移和侵袭能力.流式细胞仪检测细胞凋亡率.结果:与对照组相比,空转染组miR-335表达水平、Survivin蛋白表达水平、细胞迁移率、侵袭细胞数和细胞凋亡率差异无统计学意义(P>0.05),过表达组miR-335表达水平和细胞凋亡率明显升高(P<0.05),Survivin和NF-κB蛋白表达水平、细胞迁移率和侵袭细胞数明显降低(P<0.05).与空转染组相比,过表达组miR-335表达水平和细胞凋亡率明显升高(P<0.05),Survivin和NF-κB蛋白表达水平、细胞迁移率和侵袭细胞数明显降低(P<0.05).结论:miR-335可通过调控Survivin表达,下调NF-κB信号通路,诱导肿瘤细胞凋亡,并抑制B细胞淋巴瘤细胞的迁移和侵袭.

Objective: This study intended to investigate the therapeutic effect of decitabine and thalidomide on myelodysplastic syndrome (MDS), immunological effect and effective mesenchymal stem cells (MSCs). Methods: Altogether 62 patients with MDS diagnosed in our hospital were selected. Patients who received 5-day treatment mainly and received decitabine from the 1st day to the 5th day were collected as group A (A), while patients who received thalidomide 1st to 5th day as in group A were collected as group B (B). The immunologic effects, blood and bone marrow index levels, clinical effects and adverse reactions of group A and group B before and after intervention were observed. Results: Th17 in the two groups after intervention were evidently lower than that before intervention, and the decrease of Th17 cells in group B after intervention was more obvious than that in group A (P<0.001). Th22 cells in the two groups after intervention were evidently down-regulated compared with those before intervention, and the down-regulation of Th17 cells in group B after intervention was more obvious than that in group A (P<0.001). However, compared with group A, the levels of CD3+, CD4+, CD4+/CD8+ in serum of group B increased more obviously and CD8+ decreased more obviously after intervention. The white blood cell count of group B after intervention was evidently higher than that of group A (P<0.001). The hemoglobin concentration after intervention in group B was evidently higher than that in group A (P<0.001). The platelet count after intervention in group A was evidently higher than that in group B (P<0.001). The total effective rate in group B was evidently higher than that in group A (P<0.05). Conclusion: The combination of decitabine and thalidomide has a better regulatory role in the immunological mechanism and bone marrow mesenchymal stem cells of patients with MDS than the single decitabine therapy on the premise of ensuring clinical efficacy.

目的 探讨自噬相关蛋白Beclin-1和p62在弥漫大B细胞淋巴瘤(DLBCL)中的表达情况,分析两者表达水平与DLBCL患者预后的关系.方法 回顾性分析2015年1月至2018年12月60例DLBCL患者的临床资料,并选取20例反应性淋巴增殖性疾病(RLD)患者作为对照.采用免疫组化法检测Beclin-1和p62蛋白的表达水平,对比分析两者表达水平与预后的关系.结果 Beclin-1在DLBCL及RLD组织中的高表达率分别为63.3％(38/60)和90.0％(18/20),差异有统计学意义(P=0.026).p62在DLBCL及RLD组织中的高表达率分别为70.0％(42/60)和30.0％(6/20),差异有统计学意义(P=0.003).Beclin-1表达水平仅与Ann Arbor分期有关(P=0.000),与年龄、性别、B症状、结外浸润、IPI积分、Bcl-2表达、Ki-67指数和分子亚型等均无关(P>0.05).p62表达与Ann Arbor分期、IPI积分、结外浸润、Ki-67指数有关(P<0.05),与年龄、性别、Bcl-2表达和分子亚型均无关(P>0.05).Beclin-1高低表达组(89.4％vs.59.1％,P=0.009)之间有效率的差异有统计学意义,而p62高低表达组之间(83.3％vs.76.2％,P=0.736)的差异无统计学意义.全组2年无进展生存率为58.3％,2年生存率为91.7％.进一步分析显示,Beclin-1高表达组和低表达组2年无进展生存率(48.1％vs.34.5％,P=0.311)和2年生存率(97.5％vs.95.5％,P=0.914)的差异均无统计学意义.p62高表达组和低表达组2年无进展生存率的差异有统计学意义(39.8％vs.66.3％,P=0.036),而2年生存率的差异无统计学意义(91.7％vs.100.0％,P=0.163).结论 肿瘤细胞的自噬状态影响DLBCL患者的预后,自噬水平越低,其PFS越短.

BACKGROUND:Chimeric antigen receptor T cell (CART) therapy has benefited many refractory lymphoma patients, but some patients experience poor effects. Previous studies have shown that programmed cell death protein-1 (PD-1) inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY:A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema. A large mass was detected in the pelvis, and pathology indicated non-Hodgkin diffuse large B-cell lymphoma. After three cycles of the R-CHOP chemotherapeutic regimen, the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine. Pathological examination of the nodules indicated DLBCL again. The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma. We recommended CAR-T cell treatment. Before treatment, the patient's T cell function and expression of immune detection points were tested. Expression of PD-1 was obviously increased (52.7%) on cluster of differentiation (CD)3+ T cells. The PD-1 inhibitor (3 mg/kg) was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide. CAR-CD19 T cells of 3 × 106/kg and CAR-CD22 T cells 1 × 106/kg were infused, respectively. The therapeutic effect was significant, and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable. Presently, the patient has been disease-free for more than 12 mo.CONCLUSION:This case suggests that the combination of PD-1 inhibitors and CAR-T cells improved therapeutic efficacy in B-cell lymphoma.

Previous research has revealed the involvement of microRNA-212-5p (miR-212-5p) and cyclin T2 (CCNT2) in acute myeloid leukemia (AML). However, whether the miR-212-5p/CCNT2 axis is required for the function of decitabine in AML has not been well elucidated. Quantitative reverse transcription-polymerase chain reaction was used to examine enrichment of miR-212-5p. The relationship between CCNT2 and miR-212-5p was verified by the luciferase reporter assay. Cell apoptosis was evaluated by flow cytometry and western blot. CCK-8 assay was performed to determine cell viability. Decitabine significantly repressed cell viability, while promoted cell apoptosis. Meanwhile, the expression levels of cyclinD1, CDK4, and Bcl-2 were suppressed in cells with decitabine exposure, but Bax and caspase-3 expression levels were upregulated. Besides, miR-212-5p upregulation had the similar function with decitabine in AML cell proliferation and apoptosis. Subsequently, restoration of CCNT2 attenuated miR-212-5p overexpression-induced effects in Kasumi-1 and SKNO-1 cells. In addition, miR-212-5p depletion reversed decitabine-induced CCNT2 downregulation. The miR-212-5p/CCNT2 axis had an implication in the anti-leukemic effect of decitabine in AML.