Mantle cell lymphoma (MCL) is a rare, aggressive, and heterogeneous subtype of B-cell non-Hodgkin lymphoma. Emerging evidence suggests that epigenetic abnormalities play a critical role in its pathogenesis. Histone deacetylase inhibitors (HDACi) have demonstrated potential as therapeutic agents, either alone or in combination with other treatments, offering a promising avenue for MCL management. In our previous study, proteomic and pathological analyses revealed elevated expression levels of HDAC1 in MCL cell lines and tissues. Transcriptomic analysis of MCL cell lines treated with chidamide demonstrated that the drug could induce transcriptional activation of downstream BET family proteins. Building on these findings, we aim to further explore synergistic effects of BET Inhibitors combine with chidamide in mantle cell lymphoma. Over the past decade, pathological samples from more than 50 MCL patients were collected to evaluate the expression of HDAC1, HDAC2, and HDAC6 antigens. Comprehensive clinical and pathological data were gathered, including laboratory results, imaging findings, initial treatment regimens, treatment responses, remission status, and overall survival outcomes. The expression levels of HDAC1, HDAC2, and HDAC6 antigens in MCL tissues were assessed by experienced pathologists using professional evaluation criteria. The results revealed that while both HDAC1 and HDAC2 are expressed in mantle cell lymphoma tissue samples—with strong expression observed for HDAC1—HDAC6 was not expressed. Mantle cell lymphoma cell line (Maver-1) was treated with varying doses of chidamide (0–30 μM) for 24, 48, and 72 hours. The cytotoxicity of the HDAC inhibitor was assessed using the CCK-8 assay. Results showed that the half-maximal inhibitory concentration (IC50) of chidamide at 48 hours was determined to be 0.9 μM, providing an optimal time point and dosage for subsequent omics and mechanistic studies. Furthermore, it was observed that chidamide exhibited a time- and dose-dependent cytotoxic effect on Maver-1 cells. The cells with chidamide (0.9 μM) for 48 hours, Western blot analysis was performed to evaluate the expression levels of HDAC1, HDAC2, and HDAC6 proteins. The results indicated that all three proteins were expressed at the cellular level. Consistent with clinical findings, HDAC1 showed high expression in Maver-1 cells. Notably, treatment with chidamide significantly reduced the expression levels of HDAC1. The cytotoxic effects of varying doses (0–20 μM) of the BET inhibitor JQ1 on the mantle cell lymphoma cell line (Maver-1) were assessed, and its half-maximal inhibitory concentration (IC50) was determined. Following treatment with chidamide (0.9 μM) for 48 hours, combined treatment with JQ1 at 14.2 μM was applied to evaluate cell cycle arrest in Maver-1 cells. The results showed that combination therapy significantly enhanced G2/M phase arrest, indicating a synergistic effect on disrupting the cell cycle. The synergistic effects of BET inhibitors may be linked to the proliferation of tumor-associated macrophages and modulation of the immune microenvironment. In future we would focus on the underlying mechanisms involving immune microenvironment regulation. This study represents the first exploration of dual epigenetic therapy in MCL. Our goal is to elucidate the mechanisms by which chidamide exerts its therapeutic effects in MCL through regulation of the BET signaling pathway, ultimately providing a theoretical foundation for dual epigenetic therapy in B-cell lymphoma.

BACKGROUND AND AIMS:The efficacy of transient elastography (TE) in the differential diagnosis between porto-sinusoidal vascular disease (PSVD) and compensated cirrhosis has not been sufficiently studied. We aimed to investigate the diagnostic performance of TE and identify histological lesions associated with liver stiffness.METHODS:We conducted a retrospective cohort study including patients with PSVD and cirrhosis (Child-Turcotte-Pugh class A) and healthy subjects. Both the PSVD and cirrhotic patients had at least one sign of PH. The area under the receiver operating characteristic curve (AUROC) was used for differentiation.RESULTS:Ninety-two patients with PSVD (median age: 53 years, 33% male), 100 patients with compensated cirrhosis and 101 healthy subjects were included. The median TE-LSM in the PSVD patients (10.0 [7.0-13.0] kPa) was significantly lower than that in the cirrhotic patients (21.0 [15.0-28.0] kPa, p < .001) but was significantly higher than that in the healthy subjects (5.1 [4.6-6.0] kPa, p < .001). The AUROCs of TE-LSM for the discrimination of PSVD from the cirrhosis and healthy subjects were 0.886 (95% CI: 0.833-0.928) and 0.913 (95% CI: 0.864-0.949), respectively. The sensitivity and specificity to discriminate PSVD from compensated cirrhosis were 78.3% and 82.0%, respectively, at a cut-off of 13.6 kPa. Furthermore, portal fibrosis and aberrant cytokeratin 7 expression of centrilobular hepatocytes were significantly associated with higher TE-LSM (≥10.0 kPa).CONCLUSION:TE-LSM can be used to differentiate PSVD from compensated cirrhosis. Pathological features in association with increased liver stiffness are identified.

Objective. This study aims to compare the electrocardiogram (ECG) abnormalities and QT interval prolongation in 2,886 patients with viral hepatitis cirrhosis and 643 patients with alcoholic cirrhosis in order to understand the characteristics of ECG in patients with cirrhosis and provide information and evidence for clinical diagnosis and treatment. Methods. The ECG data of patients with viral hepatitis cirrhosis and alcoholic liver cirrhosis in the outpatients and inpatients of our hospital from August 2012 to July 2018 were reviewed. The ECG data were recorded, and the ECG report was issued by ECG experts to analyze the abnormal ECG and QT interval of patients in these two groups. Results. In the present study, 1,132 (39.22%) of the 2,886 patients with viral liver cirrhosis and 322 (50.08%) of the 643 patients with alcoholic liver cirrhosis had an abnormal ECG (P < 0.001). Among patients with QT prolongation, 388 patients had viral liver cirrhosis (13.44%) and 170 patients had alcoholic liver cirrhosis (26.44%, P < 0.001). Conclusion. The hemodynamics and electrophysiology of the myocardium are often changed in patients with cirrhosis, and ECG changes may also occur. QT interval prolongation is one of the most common electrophysiological abnormalities in patients with cirrhosis, and QT prolongation is more common in patients with alcoholic liver cirrhosis. Prolonged QT is associated with severe arrhythmia and sudden death and can warn of malignant arrhythmia and sudden death. Therefore, the routine detection of abnormal ECG and QT interval in patients with liver cirrhosis is of significant importance for preventing malignant events.

Extramedullary blast crisis (EBC) is a special kind of blast crisis of chronic myelogenous leukemia (CML). It is more likely to be misdiagnosed as lymphoma when EBC cells are of lymphoid cell lineage and lymphadenopathy is the only symptom before the final diagnosis. In this study, we presented a patient with an unusual presentation of CML transformation as a rapid growth of generalized lymphadenopathy that appeared 5 months after the initial diagnosis of CML. The patient underwent the left supraclavicular lymph node biopsy and repeat bone marrow aspiration. The revealed CD3+, terminal deoxynucleotidyl transferase (TdT)+, CD5+, CD23+, myeloperoxidase (MPO)-, CD20-, cyclin D1-, CD10-, which was consistent with the diagnosis of T-cell lymphoblastic lymphoma (T-LBL). Fluorescence in situ hybridization (FISH) verified the BCR-ABL rearrangement, and T-cell EBC of CML was finally diagnosed. Our report suggested that FISH was necessary to distinguish isolated lymphoid extramedullary blast crisis from secondary NHL in CML.

Background: Non-Hodgkin T/NK cell lymphoma is a rare and widely variable type of lymphoma with the most dismal prognosis. This study aimed to investigate varied impact of the clinical indicators to the overall survival (OS). Methods: We conducted a retrospective study to identify the non-invasive clinical features of T cell lymphoma that can predict prognosis with an innovative analysis method using quantile regression. A total of 183 patients who visited a top-tier hospital in Beijing, China, were enrolled from January 2006 to December 2015. Demographic information and main clinical indicators were collected including age, erythrocyte sedimentation rate (ESR), survival status, and international prognostic index (IPI) score. Results: The median age of the patients at diagnosis was 45 years. Approximately 80% of patients were at an advanced stage, and the median survival time after diagnosis was 5.1 months. Multivariable analysis of the prognostic factors for inferior OS associated with advanced clinical staging [HR=3.16, 95%C1 (1.39-7.2)], lower platelet count [HR =2.57, 95%CI (1.57-4.19), P < 0.001] and higher IPI score [HR =1.29, 95%CI (1.01-1.66), P=0.043]. Meanwhile, T cell lymphoblastic lymphoma [HR =0.40, 95%Cl (0.20-0.80), P=0.010], higher white blood cell counts [HR =0.57, 95%CI (0.34-0.96), P=0.033], higher serum albumin level [I IR =0.6, 95%Cl (0.37-0.97), P=0.039], and higher ESR [I IR =0.53, 95%C[ (0.33-0.87), P=0.0111 were protective factors for OS when stratified by hemophagocytic lymphohistiocytosis (HLH). Multivariable quantile regression between the OS rate and each predictor at quartiles 0.25, 0.5, 0,75, and 0.95 showed that the coefficients of serum beta 2-microglobulin level and serum ESR were statistically significant in the middle of the coefficient curve (quartile 0.25-0.75). The coefficient of 111 was negatively associated with OS. The coefficients of hematopoietic stem cell transplantation (HSCT) and no clinical symptoms were higher at the middle of the quartile level curve but were not statistically significant. Conclusions: The IPI score is a comparatively robust indicator of prognosis at 3 quartiles, and serum ESR is stable at the middle 2 quartiles section when adjusted for I 1111. Quantile regression can be used to observe detailed impacts of the predictors on OS.

Objective To investigate arterial endothelial dysfunction in stable chronic obstructive pulmonary disease (COPD) patients and the correlation between the degree of endothelial dysfunction and the severity of COPD.Methods Forty stable COPD patients were enrolled in a COPD group and 30 non-COPD individuals in a control group.The endothelium-dependent flow-mediated vasodilatation (FMD) of the brachial artery and serum eNO value were measured in both groups.Forced expiratory volume in 1 second (FEV1)/prediction of FEV1 was determined and expressed as FEV1 (％ pred).Results The mean FMD was significantly lower in the COPD group (11.21±5.19) ％ than in the control group (19.86±5.24)％ (t=6.090,P=0.001).The Pearson's correlation analysis showed FMD was positively correlated with FEV1 (％pred) in COPD patients (r=0.440,P＜0.05).The mean serum eNO level in the COPD group (108.58 ± 42.22) μmol/L was significantly lower than in the control group (151.17 ± 97.40)μmol/L (t =2.242,P =0.039).Conclusions The endothelium-dependent flow-mediated vasodilatation is significantly impaired in stable COPD patients,and the degree of impairment is proportional to the FEV1 (％ prediction of FEV1) in COPD patients.

Post-transplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of lymphoid neoplasms associated with immunosuppression following transplantation. Among PTLDs, monomorphic PTLD (m-PTLD) is the largest category; however, its characteristics and survival outcome are not fully understood because of low incidence. This study enrolled 30 adult patients with m-PTLD after kidney-transplantation (KT, n = 17) and hematopoietic stem cell transplantation (HSCT, n = 13) from January 1998 to December 2014. The incidence rates of m-PTLD were 0.74 and 3.63% in the KT and HSCT groups, respectively. M-PTLD patients in the HSCT group were younger and showed earlier onset, with EBV-encoded small RNAs (EBER) more frequently identified. Diffuse large B cell lymphoma (DLBCL) was the main pathological type, and the digestive system was the most extranodal involvement site in m-PTLD after KT and HSCT. Among the 28 patients with DLBCL m-PTLD,the complete remission rate after rituximab treatment was higher than in patients not administered rituximab treatment (P = 0.038). With a median follow-up of 46 months after m-PTLD diagnosis, the estimated 5-year overall survival (OS) was 59.2 ± 9.1% in all patients, and 64.2 ± 11.8 and 52.7 ± 14.1% in the KT and HSCT groups, respectively (P = 0.741). ECOG PS, Ann Arbor stage, and CD68 IHC expression were independent prognostic factors for OS. M-PTLD is a rare but serious complication after transplantation. Ongoing efforts to standardize safe and effective treatment protocols would improve the poor overall survival. The independent prognostic factors contributed to risk-stratified treatment, and might be validated by larger studies.

Objective To comparatively analyze the clinical characteristics of adult hemophagocytic lymphohistiocytosis(HLH) with adult acute myeloid leukemia(AML) receiving haploidentical donor hematopoietic stem cell transplantation(HID HSCT).Methods We retrospectively reviewed 20 adult patients with HLH and 21 adult patients with AML between August 2009 and August 2015.Conditioning regimens consisted of TBI/VP-16/CTX or Bu/VP-16/Cy in HLH and modified Bu/Cy in AML.The stem cell source was from peripheral blood stem cell.The clinical features and outcomes of the patients were comparatively analyzed.Results HLH had a higher incidence of mixed chimerism(P=0.048) and EB virus(EBV) reactivation(P=0.012) compared with AML.All patients in two groups engrafted.The estimated 2-years overall survival(OS) rate of HLH was(60.0±11.0)% with a median follow-up of 20 months while the estimated 2-years OS rate of AML was(71.4±9.9)% with a median follow-up of 39 months.Transplant-related mortality within 100 days following HSCT in HLH was higher than in AML(P=0.045).Conclusion There is an increased incidence of mixed chimerism,EBV reactivation and early transplant-related mortality in HLH patients who received HID HSCT compared to AML patients.So it is important to precisely seize the transplantation window,improve the condition regimen and early monitor the chimerism status.

Objective To explore the clinical effect and toxicity of daunorubicin combined with cytarabine (DA regimen) and idarubicin combined with cytarabine (IA regimen) for the treatment of patients with acute myeloid leukemia (AML) as induction chemotherapy. Methods The clinical data of 84 newly diagnosed AML patients (except M3) treated with DA or IA regimen were analyzed retrospectively. DA regimen group included 32 patients (17 males and 15 females with median age of 46 years), while IA regimen group included 52 patients (29 males and 23 females with media age of 49 years). Efficacy index was complete remission (CR), total efficiency and adverse reactions after one course of chemotherapy rate. Results In DA regimen group,the CR rate was 65.6 %(21/32), and the total efficiency rate was 75.0 %(24/32), while in IA regimen group, the CR rate was 71.2 %(31/52), and the total efficiency rate was 80.8 %(42/52), respectively, but, the differences of media survival and 5-year survival rate were not statistically significant (16.8 months vs. 24.9 months, 26 % vs. 44 %, both P>0.05). The main side effect in the two groups included hematologic (bone marrow suppression) and non-hematologic adverse reactions, with no significant difference between the two groups (all P>0.05). Conclusion For newly diagnosed AML patients, remission rate and total efficiency of DA regimen are same as IA regimen after one course treatment, and adverse events between the two regimens do not differ significantly.

Objective To explore the clinical efficacy and safety of low-dose decitabine combined with cytarabine for myelodysplastic syndromes (MDS). Methods Clinical data of 15 patients with MDS who took the therapeutic regimen with decitabine combined with cytarabine were collected from January 2012 to January 2015. The clinical efficacy and adverse effects were assessed. Results Among the 15 patients, 4 cases were complete remission (CR), 5 cases were partial remission (PR) and 6 cases were stable disease (SD) and progressive disease (PD). The total effective rate was 60.0 % (9/15). Grade Ⅲ-Ⅳ bone marrow depression occurred in 11 cases with incidence rate of 73.3 % (11/15), and the total incidence rate of infection was 40.0 % (6/15), including lung infection of 26.7 % (4/15). All the infections were controlled after active supportive treatment and anti-infection therapy. No patient died of chemotherapy. Conclusions Low-dose decitabine combined with cytarabine can effectively treat MDS and delay the progress of disease. The patients can tolerate the adverse effects in chemotherapy with a low mortality rate.

OBJECTIVE:To investigate the clinical characteristics, therapeutic outcomes and prognostic factors of primary central nervous system lymphoma (PCNSL).METHODS:Clinical records of 31 cases of PCNSL were collected, the clinical charactenstics were analyzed retrospectively. Survival curves were estimated using Kaplan-Meier survival methodology and statistical significance of continuous variables was assessed via the Cox proportional hazard model.RESULTS:The median age was 52 years, with a ratio of male to female 1:1. Headache/dizzy/limb numbness were the most common presentation and the lesions of PCNSL were primarily located at the frontal, parietal, temporal lobes and corpus callosum. All the cases were pathologically diffuse large B cell lymphoma (DLBCL), 6 cases were the type of germinal center (GC) and 25 cases of non-GC type, after craniotomy operation and biopsy. Among 31 cases, 17 patients accepted the combined treatment, 3 patients underwent simple chemotherapy, 8 patients received simple radiotherapy, the other patients accepted support therapy. The median follow-up for surviving patients was 24 months. The 1-, 3-, and 5-year survival rates were 80.6%, 55.1%, and 36.4%, respectively. The median overall survival time in the combined treatment group was significantly longer than that in simply radiotherapy. There was no significant difference in OS between the groups with and without rituximab. ECOG PS≥2 and elevated serum LDH predicted inferior survival.CONCLUSION:The clinical manifectation of PCNSL is various and complicated, and for the time being there is no optimal treatment scheme. The overall survival time of the combined treatment is longer than that in simply radiotherapy. ECOG PS≥2 and elevated serum LDH often are poor prognostic factors.

OBJECTIVE:To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH).METHODS:Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations.RESULTS:The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a).CONCLUSION:Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.

Objective Rituximab could enhance the efficacy and improve the prognosis in the treatment of non - Hodgkinˊs lymphoma. Meanwhile it could increase the opportunity of lung infection because of its immunosuppression effects. To explore the relationship between remedy containing rituximab and Pneumocystis jiroveci pneumonia(PCP),a rare opportunistic infection. Methods Two cases of PCP after rituximab -containing regimen were reported and the literatures were also reviewed. Results Two reported patients were presented with acute fever with dry cough,shortness of breath,progressive hypoxia and diffuse ground - glass shadows on chest CT scanning films. PCP were treated with high dosage trimethoprim - sulfamethoxazole with or without caspofungin. Conclusion One should be alert to the occurrence of PCP when hypoimmunity pa-tients with rapidly progressive hypoxemia,early diagnosis and treatment rational prophylaxis are the key to improve survival in these patients.

目的:探讨原发性噬血细胞综合征(HLH)合并中枢神经系统病变诊断要点以及异基因造血干细胞移植(Allo-HSCT)治疗情况.方法:对1例原发性HLH合并中枢神经系统病变患者的临床特点进行分析,完善基因测序、免疫学指标检测和家系调查,进行Allo-HSCT.结果:11岁男性病例,表现为反复发热、全血细胞减少,脾大、骨髓中可见噬血现象,自然杀伤(NK)细胞活性下降(10.39％) 基因检测和家系调查显示患者携带分别来自父系和母系的PRF1基因的复杂杂合改变,两位胞姐各自携带不同突变位点;全家成员穿孔素蛋白表达量均有不同程度下降.病程中出现癫痫,头颅核磁共振提示多发病变.确诊原发性HLH合并中枢神经系统病变.给予HLH-2004方案治疗后,接受胞姐HLA 5/10相合Allo-HSCT.目前移植后14个月,一般情况良好.结论:对于合并中枢神经系统病变的原发性HLH,尽早进行Allo-HSCT是获得长期生存及治愈的唯一方法

Objective To investigate the efficacy of rituximab-containing regimen in Epstein-Barr virus associated hemophagocytic lymphohistiocytosis (EBV-HLH). Methods A retrospective analysis involving 6 EBV-HLH patients who had received treatment with rituximab-containing regimen was performed. The patients who were diagnosed with lymphoma or primary HLH subsequently were not included in the analysis. Results All patients were males. The median age was 27.5 years (range 20-61 years). Two patients received rituximab-containing regimen as primary therapy, and got partial remission (PR) within 2 weeks after the first course of rituximab, but relapsed within 4 weeks. Four patients received rituximab-containing regimen as salvage therapy, but none achieved remission. The 6 patients died due to HLH and complications, such as infection and hemorrhage. Laboratory data including white blood cell count, haemoglobin concentration, platelet count ferritin, alanine transaminase, aspartate transaminase,total bilirubin, fibrinogen and EBV-DNA did not show statistical significance (all P>0.05). Conclusion The efficacy of rituximab as a treatment for EBV-HLH is not as good as that in the previous study, and a prospective clinical trial of rituximab-based monotherapy is needed to answer the question.

Myeloablative conditioning-based allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the treatment of adult and adolescent hemophagocytic lymphohistiocytosis (HLH) is rarely reported. We conducted a retrospective study of 30 adult and adolescent HLH transplanted for primary HLH (n = 4), tumor-HLH (n = 8), EBV-HLH (n = 14), and underlying disease-unknown (UDU)-HLH (n = 4). Peripheral blood stem cells (PBSCs) were the stem-cell source in all patients. Twenty-three patients were transplanted from HLA-haploidentical family donors, six from HLA-identical sibling donors, and one from a matched unrelated donor. Four patients appeared with mixed chimerism (MC), and no patient presented with graft failure. There was a high risk for EBV reactivation with an incidence of 47 %. Two patients developed post-transplant lymphoproliferative disorder (PTLD) and three were considered primary disease recurrent. With a median follow-up of 26 months, 19 patients survived and 11 patients died. The estimated 2-year overall survival (OS) was 63.3 ± 8.8 % in all patients, 100 % in primary HLH, 64.3 ± 12.8 % in EBV-HLH, 50.0 ± 17.7 % in tumor-HLH, and 50.0 ± 25.0 % in UDU-HLH. Myeloablative conditioning-based allo-HSCT is an effective treatment for adult and adolescent HLH to achieve complete remission and long-term survival.

目的 探究自体造血干细胞移植(AHSCT)治疗复发难治性朗格汉斯组织细胞增多症(LCH)的疗效。 方法 报道1例AHSCT治疗复发难治性LCH患者的治疗经过，并复习相关文献。 结果 患者经过多次化疗后疗效欠佳，进行AHSCT治疗后完全缓解。 结论 AHSCT治疗可作为复发难治性LCH的有效治疗方案。

Objective To elucidate the curative effects and toxicity of bortezomib in combination with CHOP for patients with angioimmunoblastic T cell lymphoma (AITL).Methods The charts of 14 patients with AITL who received bortezomib 2 mg/m2 d1 plus CHOP regimen were reviewed.Results Among 14 patients including 12 initial and 2 refractory patients, 12 cases got remission (complete remission in 6 cases and partial remission in 6 cases).The anticipated 3-year overall survival rate was 55 ％.The median progression-free survival was 9.4 months.The anticipated 3-year progression-free survival rate was 38 ％.Grade Ⅲ-Ⅳ leucopenia was the most frequent hematological toxicity (6 cases).All of non-hematological toxicities were Ⅰ-Ⅱ grade including peripheral neurotoxicity (8 cases), nauseating and vomiting (6 cases), diarrhea (4 cases) and infection (4 cases).Conclusion The combination of bortezomib and CHOP is an effective and feasible regimen for AITL with acceptable toxicity.