Primary plasma cell leukemia (pPCL) is an extremely aggressive and rare subtype of plasma cell neoplasm with extremely poor prognosis, and optimal treatment strategies remain controversial due to its low incidence. This case is unique in that it reports long-term disease-free survival after combination chemotherapy followed by allogeneic peripheral blood hematopoietic stem cell transplantation (allo-PBSCT), which provides valuable real-world evidence supporting the potential curative role of this sequential therapeutic approach for pPCL, a disease where long-term survival is rarely achieved with conventional treatments.

Multiple myeloma (MM) is an intractable hematologic malignancy characterized by clonal growth of malignant plasma cells in the bone marrow. Recent studies have highlighted the role of N6-methyladenosine (m6A) RNA modifications in MM progression; however, the function of the m6A demethylase fat mass and obesity-associated protein (FTO) remains unclear. This study aims to explore the mechanisms by which FTO-mediated m6A demethylation of Serpin Family F Member 1 (SERPINF1) impacts MM progression. SERPINF1 and FTO expressions were assessed via real-time quantitative polymerase chain reaction (RT-qPCR). The impact of such expressions on MM was evaluated using CCK-8, EdU, transwell, and tumor xenograft model assays. Key molecules involved in the Wnt/β-catenin pathway were assessed via Western blotting. The relationship between SERPINF1 and FTO was determined through correlation analysis, methylated RNA immunoprecipitation, luciferase, RT-qPCR, Western blotting, RNA immunoprecipitation, and actinomycin D treatment assays. Finally, the effect of their interaction on MM was assessed through rescue experiments. SERPINF1 expression was reduced in MM samples. SERPINF1 overexpression suppressed the malignant traits of MM cells and reduced the levels of β-catenin, c-Myc, and cyclin D1. In vivo experiments revealed that SERPINF1 overexpression suppressed tumor growth in xenograft models. Mechanistically, FTO expression was upregulated in MM and SERPINF1 expression was negatively regulated by demethylating its m6A sites via IGF2BP1. Rescue experiments demonstrated that SERPINF1 overexpression reversed FTO-induced oncogenic phenotypes. These findings suggest that FTO-mediated m6A demethylation suppressed SERPINF1 expression in MM, whereas SERPINF1 overexpression inhibited tumor progression via the Wnt/β-catenin pathway.

Objective: This study aimed to investigate the effects of 4-Octyl itaconate (4-OI) on immune thrombocytopenia (ITP) mice model and elucidate the underlying mechanism.Methods: An ITP mouse model was established by intraperitoneal injection of the monoclonal antibody MWReg30 and treated by 4-OI with/without chloroquine (CQ). The mice were divided into four groups: Control, ITP, ITP+4-OI and ITP+4-OI + CQ. Platelet (PLT) content was detected and bone marrow megakaryocytes were quantified using Giemsa staining. Apoptosis was evaluated by TUNEL staining, protein expression of Bax and Bcl-2 in bone marrow tissues was detected by western blotting, and megakaryocyte apoptosis ratio was assessed by flow cytometry detection of CD61+ cells. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood, and the mRNA expression of LC3II, Becin-1, and SQSTM1 were detected by qRT-PCR; Immunofluorescence evaluated LC3II, Beclin-1, and SQSTM1 expression in bone marrow, as well as the ratios of CD41+Beclin-1+ and CD41+LC3II+ megakaryocytes.Results: Compared to the ITP group, 4-OI treatment significantly increased PLT counts, while reduced the spleen index and bone marrow megakaryocyte numbers. 4-OI also increased the apoptosis rate of megakaryocytes by increasing Bax protein expression and reducing Bcl-2 expression in the bone marrow. LC3II and Beclin-1 expression increased in PBMCs and bone marrow tissues, whereas SQSTM1 expression decreased. Megakaryocytes exhibited reduced LC3II and Beclin-1. The autophagy inhibitor chloroquine (CQ) suppressed all the 4-OI-induced effects.Conclusion: 4-OI ameliorated ITP-induced thrombocytopenia by modulating autophagy-related proteins in megakaryocytes, inducing autophagy, and promoting apoptosis.

Abstract Background Multiple myeloma (MM), a heterogeneous malignancy originating from plasma cells in bone marrow, represents roughly 1% of total tumors and 10% of all hematopoietic tumors. The treatment of multiple myeloma has advanced rapidly in recent years, and regimens based on carfilzomib have shown significant improvement in survival for MM, but their real-world efficacy and safety profiles require further exploration. Here we evaluated the efficacy and safety of carfilzomib-based combination therapy in patients with MM. This was a retrospective, multicenter observational study. Aims To evaluate the real-world efficacy and safety of carfilzomib-based combination therapies in patients with MM. Methods We retrospectively analyzed clinical data from MM patients treated with carfilzomib-based regimens between August 2022 and June 2025 at two centers in China. Results A total of 103 patients were included. The median age was 62 years (range: 41–79) and 51.5% were male. Among 86 patients with available International Staging System (ISS) staging data, 48 (55.8%) were classified as stage III. Of the 70 patients with available cytogenetic data (locally assessed via fluorescence in situ hybridization), high-risk cytogenetic profile was defined as the presence of t (4;14), t (14;16), t (14;20), or del(17p). 14 (20.0%) patients had high cytogenetic risk, and 5 (7.1%) patients exhibited “double hit”. Only 3 patients were newly diagnosed MM, among the remaining 100 patients, 99 (99.0%) had prior exposure to bortezomib, 41.0% had received prior anti-CD38 monoclonal antibody (mAb), and 10 patients had undergone prior autologous stem cell transplantation (ASCT). The median number of prior treatment lines was 3 (range: 1-7). 16 (15.5%) patients received carfilzomib and dexamethasone (Kd) based therapy with or without anti-CD38 mAb, 46 (44.7%) received Kd combined with an immunomodulatory agent (IMiD) with or without anti-CD38 mAb, 33 (32.0%) received Kd combined with chemotherapy with or without anti-CD38 mAb, and 8 (7.8%) received Kd combined with other regimens. A total of 39 patients received anti-CD38 mAb. Patients received a median of 5 cycles (range: 1-7). Efficacy was assessed in 93 patients with an overall response rate ORR of 61.3%. Complete response (CR) was achieved in 16.1%, very good partial response (VGPR) in 14.0%, partial response (PR) in 31.2%, stable disease (SD) in 2.2%, and progressive disease (PD) in 36.6%. The median time to response was 4.5 months (range: 1-8 months). With a median follow-up of 9 months (range: 1–27), the median progression-free survival (PFS) was 13.6 months, and the median overall survival (OS) was 24.8 months. Elderly patients (≥65 years) demonstrated lower response rates, with an ORR of 49%. In terms of adverse reactions, we paid more attention to the occurrence of cardiovascular adverse events (CVAEs). Prior to carfilzomib treatment, 32 patients (31.1%) had a history of hypertension, 2 (1.9%) had a history of heart failure, and 10 (9.7%) had a history of arrhythmia. During carfilzomib-based combination therapy, a total of 15 patients (14.6%) developed CVAEs, including heart failure, palpitations, arrhythmia, elevated troponin I (TnI) levels, and pericardial effusion. Among these, two patients experienced grade ≥3 CVAEs, one developed atrial fibrillation, which improved following amiodarone administration, and the other experienced heart failure, which was alleviated with diuretic and coronary vasodilator therapy. Hematologic toxicities were the most frequently observed adverse events, including anemia (48.0%), leukopenia (34.3%), and thrombocytopenia (24.5%). The most common non-hematologic treatment-emergent adverse events (TEAEs) were infections (30.1%). A total of 31 patients (20.1%) experienced hematologic toxicities of grade ≥3. Two patients developed grade 3–4 renal toxicity, manifesting as acute kidney failure. Additionally, complications such as pulmonary embolism, oral ulcers, allergic dermatitis, ankle joint swelling, and headache were each observed in one patient, and two patients experienced diarrhea. Conclusion Carfilzomib-based combination regimens demonstrated encouraging efficacy and manageable safety profiles in real-world MM patients. These results support further prospective evaluation to optimize clinical application.

Background: Sepsis is characterized by the simultaneous activation of inflammation and coagulation in response to systemic infection, leading to microvascular dysfunction and consequential multiorgan failure. Previous studies have revealed that TMEM16F is involved in blood coagulation and inflammatory response. However, its detailed regulatory molecular mechanisms and functions in sepsis remain unknown. Objectives: In this study, we aim to investigate the regulatory effects and the underlying mechanism of TMEM16F in sepsis-induced microvascular thrombosis and inflammation. Methods: We used septic patients, lipopolysaccharide (LPS)-induced septic mouse models, and in vitro cellular experiments with LPS-stimulated endothelial cells. Bioinformatical analysis and molecular biological techniques were performed to identify the target genes of TMEM16F. Results and Conclusions: We found that TMEM16F was highly expressed in vivo and in vitro septic model, and its deletion decreased mortality, inflammation, and the microthrombi formations in LPS-induced septic mice. Additionally, silencing NRF2 not only inhibited TMEM16F expression but also improved LPS-induced thrombosis, inflammation, and organ injury, which could be reversed by inhibition of miR-17-5p. By bioinformatics analysis with subsequent chromatin immunoprecipitation-polymerase chain reaction and luciferase activity experiments, we revealed that the transcription factor NRF2 drove TMEM16F transcription through promoter binding while suppressing miR-17-5p, thereby increasing TMEM16F expression in endothelial cells. Furthermore, plasma concentrations of TMEM16F and miR-17-5p were correlated with coagulation activation, inflammation, and disseminated intravascular coagulation scores in septic patients. Overall, these findings identify the NRF2/miR-17-5p/ TMEM16F axis may be a potential therapeutic target for sepsis.

Acute myeloid leukemia (AML) is a kind of heterogeneous hematologic malignancy with high incidence, which is usually treated by intensive and maintenance treatment with large dose of conventional chemotherapy drugs. However, cell resistance is still an unsolved problem. The abnormal expression of miRNAs is closely related to the pathogenesis and progression of AML, and affects the drug resistance of cancer cells. miR-149-3p plays an important role in the resistance of cancer cells to cisplatin, and plays an excellent anti-tumor activity. By studying the function of miR-149-3p, it is expected to find new therapeutic methods to reverse chemotherapy resistance. In order to explore the mechanism of action of miR-149-3p on AML chemotherapeutic drug sensitivity, we explored the relationship between the Warburg effect and AML chemotherapeutic drug resistance. Based on AML cells, transfection of miR-149-3p inhibitor/NC and Warburg effect inhibitor (2DG) and PI3K/AKT pathway inhibitor (LY294002) were used to investigate the mechanism of IFN-γ regulating chemotherapy resistance of AML cells through Warburg effect. Down-regulation of miR-149-3p significantly inhibited drug sensitivity of AML cells. Down-regulation of miR-149-3p significantly promoted proliferation and invasion of AML cells while inhibiting apoptosis by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax. Down-regulation of miR-149-3p significantly promoted the expression of Warburg effect-related proteins hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and Glucose transporter 1 (GLUT1), glucose consumption, lactic acid, and intracellular ATP production. After inhibiting the Warburg effect with 2DG, the effect of miR-149-3p was inhibited, suggesting that upregulation of miR-149-3p reversed AML cell resistance by inhibiting the Warburg effect. In addition, miR-149-3p interacted with AKT1. Down-regulation of miR-149-3p increased the expression of inosine phosphate 3 kinase (PI3K), protein kinase B (AKT), and multi-drug resistance protein (MDR1). LY294002 inhibited the expression of these proteins, and down-regulation of miR-149-3p reversed the effect of LY294002 and improved the drug resistance of cells. Upregulation of miR-149-3p expression may potentially be a therapeutic target for AML resistance. It has been shown to inhibit PI3K/AKT pathway activation, thereby inhibiting the Warburg effect, and affecting cell proliferation, apoptosis, and drug resistance.

Introduction: Carfilzomib has been approved for the treatment of relapsed or refractory multiple myeloma (RRMM) in China1 and become a new trend for the treatment of RRMM in clinical practice. In this study, we retrospectively analyzed the clinical data of 60 RRMM patients in real world to investigate the clinical efficacy and safety of carfilzomib-based therapies, with a view to further optimizing the treatment of RRMM. Methods: we retrospectively collected and analyzed clinical data of 60 RRMM patients treated with carfilzomib based chemotherapy regimens in the Hematology Department of the Second Affiliated Hospital of Harbin Medical University from January 2023 to June 2024. The efficacy was evaluated at the end of each cycle of treatment, and the adverse effects were recorded in detail during the treatment process. The primary endpoint is Overall Response Rate (ORR), while the secondary endpoints are Overall Survival (OS) and Progress Free Survival (PFS) according to 2016 IMWG criteria. Results: Sixty RRMM were available for efficacy and safety assessment. Carfilzomib based therapies includes KRd (carfilzomib, lenalidomide and dexamethasone; 8 cases), KCd (carfilzomib, cyclophosphamide, and dexamethasone; 10 cases), DKd (carfilzomib, daratumumab, and dexamethasone; 8 cases), KPd(carfilzomib, pomalidomide, and dexamethasone; 8 cases), KBd (carfilzomib, bendamustine, cyclophosphamide, and dexamethasone; 4 cases), KDD(carfilzomib, dexamethasone and liposomal doxorubicin; 4 cases) and Kd (carfilzomib and dexamethasone; 20 cases). The median number of cycles was 4 (2-9). The ORR was 83.3%(50/60) of which 6 (10.0%) complete response (CR) in 6 cases, 10 (16.7%) very good partial response (VGPR) , and 34 (56.7%) partial response (PR). Patients of older than 60 years old, R-ISS stage III, high-risk cytogenetic abnormalities, and previous ≥3 lines of therapy account for 60%, 73.3%, 63.3%, and 26.7% respectively. The ORR was significantly lower in patients who previously had received third-line and higher treatment (50%) than in those who had received first- and second-line treatment(95.5%, p＜0.05). Median PFS was 8 months and the data of OS was unmature. The most common hematological and non-hematological adverse effects were thrombocytopenia (50.0%) and upper respiratory tract infection (30%) respectively which were resolved or relieved in vast majority of patients after symptomatic treatment without affecting the course of treatment. Conclusion: The efficacy of carfilzomib-based regimens in RRMM is promising and adverse effects are manageable. References： 1.Carfilzomib (Kyprolis®) label.

Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.

OBJECTIVE:Acute myeloid leukemia (AML) is a form of primary acute leukemia with high mortality. Our previous study demonstrated that miR-149-3p was down-regulated in chemoresistant acute leukemia cells. However, the biological function of miR-149-3p in AML needs to be further explored.METHODS:Herein, the expression of miR-149-3p was overexpressed/silenced in U-937 human AML cells via transfection with miR-149-3p agomir/antagomir. The effect of miR-149-3p on U-937-induced tumor growth was investigated using a xenograft nude mouse model.RESULTS:The results showed that miR-149-3p overexpression inhibited the proliferation and increased the apoptosis of U-937 cells. In addition, miR-149-3p suppressed epithelial-mesenchymal transition in U-937 cells, as demonstrated by the miR-149-3p agomir-induced increase in E-cadherin expression and decrease in vimentin expression. The in vivo experiments demonstrated that miR-149-3p suppressed tumor progression.CONCLUSION:In conclusion, the findings revealed the association of miR-149-3p with the development of AML and suggest that miR-149-3p is a potential therapeutic candidate for AML.

Objective This study was to explore the effect of exosomal miR-155 derived from bone marrow mesenchymal stem cells (BMSCs) on stemness maintenance and drug resistance in MPC-11 multiple myeloma cells. Methods MPC-11 cells were transfected with mimics or inhibitors of miR-155. miR-155 expression was detected by qRT-PCR, cell condition was observed, and the expression of stemness maintenance markers OCT-4 and Nanog was observed by immunofluorescence. The expression of proteins associated with the Hedgehog signaling pathway and drug resistance was evaluated by western blot. To investigate whether exosomes affect cell behavior by horizontal delivery of miR-155, MPC-11 cells were co-cultured with exosomes isolated from BMSCs that were transfected with mimics or inhibitors of miR-155. Cell proliferation and the expression of proteins related to stemness maintenance protein and drug resistance were examined. Results In function assays, after miR-155 mimics transfection, the expression levels of proteins related to stemness maintenance marker, Hedgehog signaling, and drug resistance were increased in MPC-11 cells. BMSC-derived exosomes carrying miR-155 inhibited apoptosis, promoted cell division, and upregulated the expression of protein associated with stemness maintenance, Hedgehog signaling, and drug resistance. Conclusion Therefore, our findings indicate that exosomal delivery of miR-155 exerted the same effect as transfection did on the stemness maintenance and drug resistance of multiple myeloma cells.

目的 探讨成人急性髓系白血病(acute myeloid leukemia,AML)患者首疗程诱导化疗结束时检测微小残留病(minimal residual disease,MRD)的意义.方法 回顾性分析2016年1月～2019年12月经过1个疗程诱导化疗后获形态学无白血病状态(morphologic leukemia-free state,MLFS)且有多参数流式细胞术MRD结果的AML患者233例,其中MRD阳性组135例,MRD阴性组98例.分析首疗程诱导化疗结束时MRD与AML患者总生存时间(overall survival,OS)、无白血病生存时间(leukemia-free surviv-al,LFS)的关系.结果 MRD阴性组5年OS优于MRD阳性组(36.7％vs 21.5％,P =0.002).MRD阴性组5年LFS优于MRD阳性组(37.2％vs 19.6％,P＜0.001).单因素分析表明,年龄≥60岁、初始白细胞(WBC)计数≥100×109是MRD阳性的高危因素(P均＜0.05),首次诱导完全缓解(complete remis-sion,CR)后血小板(Plt)计数≥300×109提示更高的MRD阴性率(P = 0.018).初始Plt计数、预后危险度分级在MRD阴性组和阳性组中差异均无统计学意义(P均＞0.05).结论 首疗程化疗结束获MRD阴性提示更好的预后;CR后Plt计数水平与MRD阴性有一定相关性.

目的 观察改良VTD-PACE方案(硼替佐米、来那度胺、地塞米松、顺铂、脂质体阿霉素、环磷酰胺及依托泊苷)治疗多发性骨髓瘤髓外病变(extramedullary disease,EMD)及浆细胞白血病(plasma cell leukemia,PCL)的疗效和不良反应.方法 选取2017年11月～2018年9月,10例EMD或PCL患者,接受改良VTD-PACE方案治疗.记录患者的临床特征、实验室及影像学检查结果,在每个疗程结束后评估治疗效果及不良反应.结果 接受治疗的患者中位疗程数4(2～6)个,总反应率(overall response rate,ORR)达80％,8例患者达到部分缓解(partial response,PR)及以上.随访时间30个月,中位总生存期(median overall survival,OS)24(5～30)个月,中位无进展生存期(progression-free survival,PFS)18(2～23)个月.主要的不良反应是周围神经病变(peripheral neuropathy,PN)、消化道症状、乏力及骨髓抑制,通过对症干预治疗耐受性良好,无治疗相关性死亡.结论 改良VTD-PACE方案效率高,耐受性好,可作为治疗EMD及PCL患者的新方案.

Not required for Clinical Vignette.

Objectives: Multiple myeloma (MM) is one of the most common types of hematologic malignancy for which the underlying molecular mechanisms remain largely unclear. Dysregulated miRNA expression has been shown to be involved in MM tumorigenesis, progression and drug response. Therefore, a comprehensive analysis based on miRNA-level integrated strategy was performed. Methods: This study aimed to elucidate key miRNA signatures and pathways in MM by integrated bioinformatics analysis. Expression profiles GSE24371, GSE49261 and GSE54156 were obtained from the Gene Expression Omnibus database, and differentially expressed miRNAs (DEMirs) with p < 0.05 were identified. The target genes of these DEMirs were obtained from ENCORI database, and functional enrichment, subpathway enrichment and protein-protein interaction network construction were performed. The key target genes were identified by random walk algorithm and survival verification was performed. Results and discussion: First, six up-regulated and four down-regulated DEMirs shared between any two GSE data sets were identified. Second, target genes (DEMirTGs) by up-regulated and down-regulated DEMirs were obtained. Functional and subpathway enrichment analysis showed that these up-regulated DEMirs are consistently involved in the Wnt signaling pathway. Moreover, enrichment of the down-regulated DEMirs is mainly in the MAPK signaling pathway. Finally, a protein-protein interaction sub-network for these DEMirTGs was constructed, the correlations between the two key genes were identified and survival in MM was evaluated using multiple independent data sets. Conclusion: We identified miRNA signatures and key target genes that were closely related to MM biology, and these genes might serve as potential therapeutic targets for MM patients.

AIMS:We set about to investigate the potential role of microRNA-155-5p (miR-155-5p) in the development of immune thrombocytopenia (ITP), an idiopathic deficiency of blood platelets.MAIN METHODS:Initially, RT-qPCR and Western blot analyses were carried out to determine the expression of miR-155-5p and SOCS1 in peripheral blood mononuclear cells (PBMCs) and macrophages from ITP patients. We undertook gain- and loss- function methods by transfection of macrophages and PBMCs with treated plasmids. The expression patterns of platelet-related factors were measured by ELISA, and the expressions of PD1, PDL1, and macrophage M2 marker CD206 and CD86 were also measured. The relationship between miR-155-5p and SOCS1 was determined using the dual-luciferase reporter gene assay. We also established an ITP mouse model to explore the roles of miR-155-5p and SOCS1 in vivo.KEY FINDINGS:miR-155-5p was up-regulated, while SOCS1 was down-regulated in PBMCs and macrophages from ITP patients. SOCS1 was indicated as a target of miR-155-5p. Inhibition of miR-155-5p or up-regulation of SOCS1 facilitated macrophage M2 polarization as demonstrated by an increased M2/M1 ratio and suppressed expression of platelet-related factors. Furthermore, silencing of SOCS1 promoted ITP progression through blocking the PD1/PDL1 pathway, whilst upregulation of miR-155-5p remarkably increased the platelet abundance and suppressed SOCS1 expression in ITP model mice.SIGNIFICANCE:Silencing of miR-155-5p could promote PD1/PDL1 pathway-mediated macrophage M2 polarization and prevent ITP via up-regulation of SOCS1, thus relieving ITP.

Background/Aims: Multiple myeloma (MM) is a plasma cell neoplasm which constitutes about 10% of all hematologic malignancies. Despite the development and application of novel agents, MM still undergoes an aggressive and incurable course in the vast majority of patients. Ca2+ is one of the critical regulators of cell migration. Ca2+ influx is essential for the migration of various types of cells including tumor cells. However, the role of store-operated calcium entry (SOC) channels, the only Ca2+ channels of non-excitable cells, has not yet been reported in MM cell survival. Methods: We evaluated the expression of Stim1 and Orai1 (two key regulators of SOC) in MM tissues and cell lines by immunohistochemical assay, quantitative real-time PCR assay and western blot. MM cell lines were pretreated with pharmacological blockers and siRNAs, and then MM cell proliferation, cell cycle arrest, and apoptosis were examined by FACS (flow cytometry) assay, and Annexin V-FITC/PI staining. The correlation between the expression of Stim1 (or Orai1) level and outcome in MM were assessed by using Progress Free Survival (PFS). Results: Stim1 and Orai1 were both abundantly expressed in MM tissue and MM cell lines. Inhibition of SOCE reduced MM cell viability, and induced cell cycle arrest and apoptosis. Stim1 or Orai1 silencing also reduced cell viability, caused cell apoptosis and cell cycle arrest in MM cell lines. Over-expression of Stim1/Orai1 in MM patients was closely associated with the clinical outcome of MM. Conclusion: The Stim1/Orai1-mediated signaling participates in the pathogenesis of MM, which represents an attractive target for future therapeutic intervention.

Immune thrombocytopenia purpura (ITP) is characterized by destruction of circulating platelets and the presence of antiplatelet IgG antibodies, which opsonize platelets for splenic clearance resulting in low levels of circulating platelets, and the disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors also play a role. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated, including viral or bacterial infections. C-reactive protein (CRP), a member of the pentraxin family, is a major acute-phase protein in humans and is a clinical marker of infection. We aimed to investigate the correlation between the levels of CRP and the presence of antiplatelet IgG antibodies in adults with newly diagnosed ITP. CRP levels and platelet counts were measured in the blood samples from a 60 ITP patient (with confirmed anti-GPIIb/IIIa antibodies), 60 infection patients (all without anti-GPIIb/IIIa antibodies) and 60 normal individuals. The bleeding score, recover time of intravenous immune globulin (IVIg) therapy and the number of megakaryocytes in bone marrow were recorded in ITP patients. The platelet count, bleeding score, recover time of intravenous immune globulin (IVIG) therapy and the number of megakaryocytes in bone marrow and CRP concentrations were compared in ITP group using Spearman's correlation coefficient. We examined the influence of intraperioneal CRP administration on antibody-mediated platelet destruction in mice. There were no statistical differences in gender, age and body mass index among the three groups (P>0.05). Though CRP levels are significantly elevated in ITP patients and infection patients (P<0.05), the platelet count was markedly lower only in ITP patients. We found that CRP was inert toward platelets without antiplatelet antibodies in this study. There are a significant correlation between CRP levels and platelet counts, bleeding severity and the number of megakaryocytes in bone marrow aspiration (r=-0.5079, r=0.5498, r=0.4172, P<0.001, respectively). Moreover, a significant correlation was observed between the recovery time of platelet count and CRP levels (r=-0.5569, P<0.001). In mice, platelet count was lower in Anti-CD41 (0.75 μg)+, CRP (200 μg) group as compared with Anti-CD41 (0.75 μg)+, CRP(-) group and Anti-CD41 (0.75 μg)-, CRP (200 μg) group (P<0.05). In summary, this study indicated that CRP levels are significantly elevated in ITP patients all with confirmed anti-GPIIb/IIIa antibodies, which is able to predict the clinical bleeding severity of ITP patients. The slower CRP levels reduction after IVIg treatment predicted slower platelet count recovery in ITP.

Quercetin, a natural flavonoid, inhibits the growth of leukemia cells and induces apoptosis. Heat shock protein 27 (HSP27) has been reported to promote the development of leukemia by protecting tumor cells from apoptosis through various mechanisms. The present study investigated the effects of small hairpin (sh)RNA-mediated HSP27 knockdown on the anti‑cancer effects of quercetin in U937 human leukemia cells. Cells were transfected with recombinant lentiviral vector pCMV‑G‑NR‑U6‑shHSP27 (shHSP27), which expressed shRNA specifically targeting the HSP27 gene, alone or in combination with quercetin. The results showed that shHSP27 and quercetin synergistically inhibited U937 cell proliferation and induced apoptosis by decreasing the Bcl2-to-Bax ratio. Furthermore, this combined treatment significantly suppressed the infiltration of tumor cells and the expression of angiogenesis‑associated proteins HIF1α and VEGF. Compared with shHSP27 or quercetin alone, shHSP27 plus quercetin markedly decreased the protein expression of cyclinD1 and thus blocked the cell cycle at G1 phase. The Notch/AKT/mTOR signaling pathway is important in tumor aggressiveness; quercetin plus shHSP27 significantly decreased Notch 1 expression and the phosphorylation levels of the downstream signaling proteins AKT and mTOR. The inhibitory effects of quercetin plus shHSP27 on this pathway may thus have been responsible for the cell cycle arrest, inhibition of proliferations and infiltration as well as enhancement of apoptosis. Therefore, these findings collectively suggested that suppression of HSP27 expression amplified the anti‑cancer effects of quercetin in U937 human leukemia cells, and that quercetin in combination with shHSP27 represents a promising therapeutic strategy for human leukemia.

Silent information regulator type-1 (SIRT1) is the best-studied member of the Sirtuin (Sir2) family of nicotinamide dinucleotide (NAD)-dependent class III histone deacetylases (HDACs). Rrecently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma, but has not yet been explored in Angioimmunoblastic T-cell lymphoma (AITL). Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in AITL. Immunohistochemical expression of SIRT1, p53 were evaluated by using a 2mm core from 45 AITL patients. Positive expression of SIRT1 was seen in 71.11% (32 of 45) of patients and p53 expression were seen in 53.33% (24 of 45). SIRT1 and p53 expression were significantly associated with shorter PFS by univariate analysis (P=0.009 and P < 0.001, respectively), multivariate analysis also shows that SIRT1 expression relate to worse prognosis. We also suggest inferior survival in AITL with the combined expression of SIRT1 and clinical characteristics of high IPI scores, high clinical stage, increased serum LDH, decreased HGB and increased -Globulin. In conclusion, our results indicate that SIRT1 is strongly expressed in AITL and it act as a clinically significant prognostic indicator for AITL patients, may also serve as a therapeutic target in AITL.

目的:探寻脾切治疗原发免疫性血小板减少症的短期、长期疗效,并发症及影响疗效的相关因素.方法:本文选取了2001年06月至2011年06月于哈尔滨医科大学附属第二医院行脾切术治疗的ITP患者100例,分析患者术后缓解率及其相关并发症,而且对术后患者进行了短期、长期随访,评估其影响疗效的预后因素.结果:100例患者中,脾切除术后短期有效率为84.0％,长期有效率76.0％.其中年龄、病程、性别、有无副脾、骨髓巨核细胞计数、术前血小板计数、术前有无出血没有统计学意义,术后血小板峰值有统计学价值,术前对激素的反应可以作为重要的预后参考因素.结论:脾切治疗原发免疫性血小板减少症是一种安全且十分有效的治疗方法,术前激素的反应效果和术后血小板峰值可作为术后的评估指标.而且切脾有效率随着随访时间的延长未见明显降低.