[Efficacy and Safety of Venetoclax-Based Induction Therapy in Acute Myeloid Leukemia].

AbstractObjective: To investigate the efficacy and safety of venetoclax-based induction chemotherapy in newly diagnosed (ND) patients ineligible for intensive therapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML). METHODS: The clinical data of 51 newly diagnosed patients ineligible for intensive therapy and patients with R/R AML treated in the Department of Hematology of Xijing Hospital from February 1, 2021 to April 30, 2022 were retrospectively analyzed. The incidence of complete remission (CR)/CR with incomplete hematological recovery (CRi), objective remission rate (ORR), minimal residual disease (MRD) status, advense events (AE), overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: Among 51 patients, 32 patients were newly diagnosed patients unfit for intensive therapy, with a median age of 60 (29-88) years, and 19 patients were R/R patients, with a median age of 49 (22-92) years. The median cycles of VEN-based treatment in the two groups were both 2. The CR/CRi rates in the ND-AML and R/R-AML group after one course of induction treatment were 65.6% and 36.9%, respectively, and the ORR were 81.3% and 42.1%, respectively. The cumulative CR/CRi rates after 1-3 courses of VEN-based treatment were 71.9% and 47.4%, respectively. The MRD negativity rates of patients achieving CR/CRi were 69.6% and 33.3%, respectively. In the ND-AML and R/R-AML group, the median PFS were 8(5-11) and 3(1-5) months, and the median OS were 13 (6-20) and 5 (3-7) months, respectively. The median OS of patients achieving CR/CRi in both groups was significantly better than that of patients not achieving CR/CRi (13 months vs 4 months; OS not reached vs 4 months). During the first induction cycle, the incidence of grade 3 or higher granulocytopenia, anemia and thrombocytopenia was 96%, 90.2% and 84.3%, respectively. 30 patients (58.8%) had granulocytopenia with fever. The most common non-hematological AE was infection (12/51, 23.5%), followed by gastrointestinal symptoms (6/51, 11.8%). CONCLUSION: The VEN-based strategy has good treatment response and tolerance in newly diagnosed patients unfit for intensive therapy and R/R AML. The most common AEs are hematological toxicities and infection.

[Clinicopathological Characteristics and Prognosis Analysis of the Patients with Plasmablastic Lymphoma].

OBJECTIVE: To evaluate the clinicopathological characteristics, treatment and prognosis of the patients with plasmablastic lymphoma(PBL). METHODS: The clinical and pathological data of 21 patients with PBL diagnosed and treated in our center between January 2009 and September 2017 were retrospectively analyzed. The clinical and pathological features, treatment and therapentic outcome were summarized and the high risk factors affecting the prognosis of patients were investigated. RESULTS: The 21 PBL patients included 12 males and 9 females, and their median age was 52 years old. The human immunodeficiency virus (HIV) was negative in all patients. The primary involved sites of 16 patients were extranodal, and the patients staged in III-IV accounted for 81%; 18 patients receved first-line chemotherapy with standard CHOP(E) (cyclophosphamide +epirubicin +vincristine +prednisone±etoposide). After treatment, only 1 patient achieved complete response (CR), and 8 patients achieved partial response (PR). The median overall survival time was 6.3 months. Multivariate analysis showed the America Eastern Cooperative Oncology Group (ECOG) physical score and bone marrow infiltration were significant prognostic factors (P<0.01). CONCLUSION: Plasmablastic lymphoma frequently occurrs in the middle-old aged persons with all HIV negative. Primary extranodal lesions are frequent. Most patients were in advanced stage with poor treatment response. ECOG score≥2 and bone marrow infiltration are independent prognostic factors related with worse prognosis.

Isolated myeloid sarcoma in the pancreas and orbit: A case report and review of literature.

Myeloid sarcoma (MS) is a type of extramedullary solid haematological tumour. Myeloid sarcoma is classified into two types based on whether onset of the disease is complicated by haematologic diseases: extramedullary infiltration of leukaemia (leukaemic MS) and isolated myeloid sarcoma. The incidence of isolated myeloid sarcoma is low. In particular, isolated myeloid sarcoma involving the pancreas is extremely rare and prone to misdiagnosis. This case report describes the long and eventful diagnostic process of a case of myeloid sarcoma involving the pancreas and orbit. Due to a lack of typical clinical manifestations and imaging characteristics, the patient underwent several rounds of treatment without a confirmed diagnosis. Eventually, the final diagnosis was pathologically confirmed using several types of biopsies and immunohistochemical detection. To date, this type of disease has not been reported in the literature. This case report describes the detailed diagnostic process and discusses the strategies used for diagnosis, which will facilitate the diagnosis of such diseases in the future.

[Effects of spatial structure on predator-prey interactions: A review.] / ç©ºé—´ç»“æž„å¯¹æ•é£Ÿå ³ç³»å½±å“ç ”ç©¶è¿›å±•.

With increasing human disturbances (e.g., spatial fragmentation), drastic changes have taken place in spatial structure, which further affects the structure and function of ecosystem. The consequences of spatial changes on ecological processes are significantly associated with change in predator-prey interactions. Thus, exploring the relationships between spatial structure andpredator-prey interactions was of significance in understanding the underlying mechanisms of ecological changes in fragmented landscapes. This paper summarized current studies about the effects of typical spatial structures on predator-prey interactions, including the spatial size, spatial shape, spatial orientation, spatial distribution and spatial connectivity. Researches indicated that the stability and continuation of predator-prey system generally decreases with decreasing spatial size and connectivity, and excessive increase in the fragmentation of space, as well as changes in spatial shape and orientation which result in excessive increase in the grazing rate of predators. Effect of complicated spatial structure (coupled from above-mentioned structures) on predator-prey interactions, especially multispecies predator-prey interactions, should be focused on in the future.

Successful treatment of liver aspergilloma by caspofungin acetate first-line therapy in a non-immunocompromised patient.

Aspergillosis remains to be a life-threatening complication in immunocompromised patients. However, Aspergillus infection can be observed in non-immunocompromised individuals in rare cases. We report a case of liver aspergilloma in a chronic aplastic anemia patient under relatively intact immune status. Therapeutic strategy for this rare condition was extensively discussed and caspofungin acetate single agent first-line therapy was applied after careful consideration. Encouraging clinical and radiologic improvements were achieved in response to the antifungal salvage. Our long-term follow-up study also revealed a favorable prognosis. Based on this experience, we suggest caspofungin acetate as first-line therapy for treatment plans of liver aspergilloma.

[Effects of triptolide on bortezomib-induced apoptosis in multiple myeloma cells].

This study was purposed to investigate the effect of triptolide on bortezomib-induced apoptosis in multiple myeloma cell line NCI-H929(H929). MTT assay was applied to detect the inhibitory effects of triptolide and bortezomib alone or combined at different concentrations on H929 cells, the cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining. The results showed that both triptolide (10 - 100 ng/ml) and bortezomib (10 - 100 nmol/L) alone or combination inhibited the proliferation of MM cell line H929 in a concentration-dependent manner. The apoptotic rate of H929 cells in group of triptolide combined with bortezomib was much higher than that in groups of single drug or control; moreover, the apoptotic rate of H929 cells treated by non-inhibitory concentration of triptolide (10 ng/ml) combined with bortezomib (40 nmol/L) for 24 h was significantly higher than that by bortezomib alone (P < 0.05). It is concluded that triptolide can significantly enhance the pro-apoptotic activity of bortezomib in MM cells.

[Effects of xbp-1 gene silencing on bortezomib-induced apoptosis in human multiple myeloma cells].

This study was purposed to investigate the effect of xbp-1 gene silencing on bortezomib-induced apoptosis in multiple myeloma cell line NCI-H929 (H929). After xbp-1 gene expression was interfered by small hairpin RNA, the cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining, and the expression level of XBP-1 protein was detected by Western blot. The results showed that XBP-1 protein level of H929 cells was inhibited effectively by the PLL3.7 lentiviral vector mediated expression xbp-1 shRNA. The apoptosis rate was significantly higher in xbp-1 shRNA-expressing cells than in untreated control group [(10.13±0.61)% vs (2.5±0.2)%, p<0.05]. After treatment with bortezomib, the apoptosis rate of XBP-1 protein functionally deficient H929 cells was significantly higher than those in vector control group [(45.07±1)% vs (19.53±0.8)%, p<0.05]. It is concluded that xbp-1 gene silencing can significantly enhance the pro-apoptotic activity of bortezomib in multiple myeloma cells.

[PI3-kinase mediates thrombin-induced platelet aggregation through mDia1 pathway.].

OBJECTIVE: To investigate the expression of mDia1 (mammalian diaphanous 1)in platelet and the role of mDia1 or phosphatidylinositol 3-kinase (PI3K) in the process of thrombin-induced platelet aggregation. METHODS: The extent of platelet aggregation was measured by a platelet aggregation system and the expression of mDia1 and its relation with F-actin in quiescent, spreading or aggregated platelets by Western blot. RESULTS: There was no significant difference in mDia1 expression level between quiescent and activated platelets. mDia1 moved from a Triton-X100-soluble cytosolic fraction to insoluble cytoskeleton fraction after thrombin induced platelets aggregation. Anti-mDia1 antibody could inhibit this aggregation. PI3K inhibitor Wortmannin or Ly294002 inhibited the thrombin induced platelet aggregation and the above mentioned mDia1 translocation. CONCLUSION: PI3-kinase mediates the thrombin-induced platelet aggregation through mDia1 pathway.

[PI3-kinase mediates activity of RhoA and interaction of RhoA with mDia1 in thrombin-induced platelet aggregation].

The aim of this study was to investigate the role of RhoA/mDia1 pathway in the process of thrombin-induced platelet aggregation and regulatory effect of PI3K inhibitor on this process. The human platelets were isolated from peripheral blood, the activation of RhoA, Rac1 and Cdc42 in the platelet aggregation was detected by GST pull-down assay and immune co-precipitation, the interaction of RhoA, Rac1 and Cdc42 with mDia1 and the formation of complex in the process of platelet aggregation were determined by immune coprecipitation, and the effect of PI3K inhibitor (wortmannin) on above-mentioned process was assayed. The results showed that thrombin elevated the activity of RhoA and the binding capability of RhoA with mDia1 during thrombin-induced platelet aggregation and spreading on Fg coated coverslips. Wortmannin inhibited the rising of RhoA activity and the binding level of RhoA with mDia1 induced by thrombin. Thrombin elevated the activity of Rac1 and Cdc42 during thrombin-induced platelet aggregation, but could not induce binding of Rac1 or Cdc42 with mDia1. Wortmannin could not inhibit the rising of Rac1 and Cdc42 activity induced by thrombin. It is concluded that the PI3-kinase regulates the thrombin-induced actin cytoskeleton reconstitution in platelets by RhoA-mDia1 pathway.

[Bortezomib-induced BiP expression and apoptosis in multiple myeloma cells].

This study was aimed to explore the effect of bortezomib on the apoptosis and expression of the molecular chaperone BiP in human multiple myeloma cell line NCI-H929 (H929). After treatment of H929 cells with different concentrations of bortezomib for 24 hours, cell apoptosis was assayed by flow cytometry with Annexin V-FITC/PI staining, and the expression levels of BiP mRNA and protein were detected by RT-PCR and Western blotting analysis. The results showed that bortezomib of different concentrations (20, 40 and 80 nmol/L) induced apoptosis of H929 cells in dose-dependent manner, with apoptotic rates (15.73 +/- 0.67)%, (27.83 +/- 1.26)% and (44.17 +/- 2.25)% respectively, which were significantly higher than that in control (1.21 +/- 0.07%) (p < 0.05). Bortezomib-induced up-regulation of BiP mRNA levels was almost on a parallel with BiP protein when compared with control. Under the similar apoptosis-stimulating conditions with apoptotic rates varying from 40% to 50%, expression levels of BiP mRNA and BiP protein induced by the classical endoplasmic reticulum stressor Brefeldin A (500 ng/ml, 24 h) were almost consistent with those by bortezomib (80 nmol/L, 24 h). It is concluded that bortezomib-induced apoptosis in H929 cells correlates closely with endoplasmic reticulum stress.