Rationale:Acquired hemophilia A is a rare hemorrhagic disease in which the body produces specific antibodies that attack factor VIII, resulting in bleeding that is mainly mucocutaneous and associated with soft tissue and the gastrointestinal system. Approximately 50% of this disease derives from basic diseases, such as autoimmune diseases, cancer, and pregnancy.Patient concerns:We report a 35-year-old postpartum female with acquired hemophilia A who initially presented with pleural hemorrhage.Diagnoses:In this patient activated prothrombin time (PT) and activated partial thromboplastin time (APTT) were found, and the factor VIII activity was 12.6%, furthermore Bethesda assay showed a FVIII antibody titer of 7.4 Bethesda units (BUs).Interventions:The treatment requires a 2-pronged approach: treatment of the bleeding and elimination of the inhibitor.Outcomes:After hemostatic agents were used and inhibitors were eradicated, the patient achieved complete remission without relapse.Lessons:It is essential to recognize the development of disease earlier in pregnant woman.

BackgroundBoth omacetaxine (HHT) and curcumin were shown to exhibit anti-proliferative effect on lymphoma cells. However, the role of combination of HHT with curcumin (HHT/curcumin combination) on lymphoma cells remains unclear. Thus, this study aimed to investigate the effect of HHT/curcumin combination on the proliferation, migration, and angiogenesis of lymphoma cells.MethodsCell counting kit-8 (CCK-8), Ki67 immunofluorescence and transwell assays were used to assess the viability, proliferation and migration of U937 and Raji cells respectively. In addition, tube formation assay was used to determine the effects of HHT/curcumin combination on angiogenesis in human umbilical vein endothelial cells (HUVECs).ResultsIn this study, we found that HHT/curcumin combination significantly inhibited the proliferation, migration and invasion in U937 and Raji cells (all P < 0.01). In addition, combination treatment markedly inhibited the secreted levels of vascular endothelial growth factor (VEGF)-(A-D) (all P < 0.01) in Raji cells. Moreover, combination treatment exhibited anti-tumor effects in Raji cells, as shown by the decreased signals of phosphorylated VEGF receptor 2 (p-VEGFR2) and phosphorylated protein kinase B (p-Akt) (all P < 0.01). Meanwhile, combination treatment inhibited VEGFA levels (P < 0.01) in exosomes derived from Raji cells. Application of exosomes with downregulated VEGF to HUVECs notably inhibited proliferation, migration and tube formation of HUVECs, evidenced by the decreased signals of p-Akt, angiogenin-1, matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) (all P < 0.01).ConclusionOur findings indicated that combination of HHT and curcumin could inhibit lymphoma cell growth and angiogenesis via inhibition of VEGF/Akt signaling pathway. These results suggested that HHT combined with curcumin might be regarded as a promising therapeutic approach for the treatment of lymphoma.

Both homoharringtonine (HHT) and curcumin exhibit anti-proliferative effects on lymphoma cells, but the effects of combined HHT and curcumin treatment remain unclear. Here, we investigated the effects of HHT/curcumin combination on the proliferation, apoptosis, and invasion in lymphoma cells. CCK-8, flow cytometry, and transwell assays were used to assess proliferation, apoptosis, and invasion of U937 and Raji cells. p-Smad3, E-cadherin, and N-cadherin expression were also measured in Raji cells using Western blot assays. Combination of HHT and curcumin synergistically inhibited U937 and Raji cell proliferation and invasion. In addition, the combination treatment markedly increased apoptosis of Raji cells as evidenced by increased Bax, cleaved caspase 3, and cleaved caspase 9 expression. Meanwhile, the combination treatment promoted anti-tumor mechanisms in Raji cells as indicated by decreases in p-Smad3 and N-cadherin and increases in E-cadherin. In vivo experiments showed that the combination treatment suppressed tumor growth in a mouse Raji xenograft model. Our findings indicate that combination of HHT and curcumin inhibited lymphoma cell growth by downregulating the TGF-β/Smad3 pathway. These results suggest that HHT combined with curcumin might be a promising therapeutic approach for the treatment of lymphoma.

Autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) can be observed in Waldenström macroglobulinemia (WM). The autoimmune disorders are primarily mediated by autoimmune monoclonal gammopathy, but druginduced hemolysis should also be considered. Herein, we presented the case of a 63-yearold female WM patient complicated with ITP, who was admitted to our department with a complaint of abdominal pain. After first half of bortezomib/dexamethasone/rituximab (BRD) chemotherapy, her platelet level recovered, but subsequently decreased to extremely low level (around 1-2×10 9 /L), and the patient suffered from platelet transfusion refractoriness. During the management of refractory thrombocytopenia, the patient developed severe hemolytic anemia, and further tests confirmed warm AIHA. FcγRIIα polymorphism test showed that the patient had FcγRIIα-131RH, which implied that the AIHA may not be WMrelated. Given the effects of ibrutinib in controlling WM, secondary AITP and AIHA, ibrutinib single treatment was started, which quickly corrected the thrombocytopenia within five days, but not hemolysis. With a relatively safe platelet level, eltrombopag was stopped, and the hemolysis relieved three days after eltrombopag withdrawal. This is the first report on eltrombopag-induced AIHA in the management of WM-associated ITP.

Resibufogenin (RBG) is an active ingredient of toad venom that also has antitumor potential. The present study aimed to investigate the role of RBG in multiple myeloma (MM) and the underlying action mechanism involving the PI3K/Akt signaling pathway. A human MM cell line, RPMI8226, was treated with RBG and/or insulin-like growth factor 1 (IGF-1; an activator of the PI3K/AKT signaling pathway). Cell viability and apoptosis were detected using Cell Counting Kit-8 and flow cytometry, respectively. Cell migration and invasion were detected using a Transwell assay. In addition, the epithelial-mesenchymal transition (EMT)-associated proteins (E-cadherin, N-cadherin and Vimentin) and the PI3K/AKT pathway-associated proteins [AKT, phosphorylated (p)-AKT, PI3K and p-PI3K] were measured using western blotting. RBG inhibited the viability, migration and invasion, and promoted the apoptosis of RPMI8226 cells in a dose-dependent manner. RBG at concentrations of 4 and 8 µM upregulated E-cadherin, and downregulated N-cadherin and Vimentin in RPMI8226 cells. RBG also decreased the protein expression of p-AKT and p-PI3K in a dose-dependent manner. In addition, the intervention of IGF-1 weakened the inhibitory effects of RBG on the malignant characteristics of MM cells. RBG-induced inhibition of EMT and the PI3K/AKT pathway were also weakened by IGF-1 treatment. In conclusion, RBG inhibited viability, migration, invasion and EMT, and promoted the apoptosis of MM cells by blocking the PI3K/AKT signaling pathway.