Composite B-cell and T-cell lymphomas: clinical, pathological, and molecular features of three cases and literature review / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Composite lymphoma (CL) involving B-cell lymphoma and T-cell lymphoma is extremely rare. Herein, we report three such cases using immunohistochemistry, flow cytometry, and the next-generation sequencing (NGS) to identify the pathological and molecular characteristics of CL. In the first case, the patient was admitted to hospital for generalized pruritic maculopapular rash over the whole body. An excisional biopsy of the skin lesions showed T-cell lymphoma. At the same time, the staging bone marrow (BM) biopsy revealed a diffuse large B-cell lymphoma (DLBCL). After R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapies, the patient produced a good response with substantial dissipation of the rashes and relief of skin. The other two patients were admitted to hospital due to lymphadenopathy and were diagnosed with DLBCL and follicular lymphoma (FL) after core needle biopsy of lymph nodes, BM biopsy, BM aspiration, and flow cytometry. Following R-CHOP and R-COP (rituximab, cyclophosphamide, vincristine, and prednisone) therapies, they achieved complete remission unconfirmed (CRu) and complete remission (CR). However, one or two years later, they suffered a relapse of lymphadenopathy. The shocking fact was that re-biopsy of lymphadenopathy revealed peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL). NGS findings identified DNA methyltransferase 3a (DNMT3a), isocitrate dehydrogenase 2 (IDH2), Ras homolog gene family, member A (RHOA), splicing factor 3B subunit 1 (SF3B1), and tumor protein p53 (TP53) mutations. After immunochemotherapy, these patients achieved CRu and CR again. Nevertheless, they suffered a second relapse of T-cell lymphoma. Finally, they died due to progression of disease. We found that the occurrence of CL is associated with Epstein-Barr virus infection and DNMT3a, IDH2, and TP53 mutations, and the prognosis of the disease is closely related to the T-cell lymphoma components.

δ-opioid receptor activation by protein kinase C pathway inhibits acid-induced liver cell apoptosis / 中华肝胆外科杂志

Objective To study the inhibitory effects of δ-opioid receptor activation in serumdeprivation induced apoptosis of human liver cells and the proposed protein kinase C(PKC)pathway mechanism.Methods MTT assay was used to detect the survival rate of human liver cells in vitro and Annexin V-FITC/PI double staining was used to detect the cell apoptosis rate.Flow cytometry was used to analyze cell cycle,RT PCR used to analyze the PKC mRNA and Western Blot analysis was used for detecting the protein expression of PKC and Caspase-3.Results After serum-deprivation for 48h of cultured human liver cells in vitro,significant liver cell apoptosis occurred.The apoptosis was suppressed by δ-opioid receptor activation,which manifested as a slower rate of apoptosis,decreased expression of Caspase-3and increased expression of PKC.After GF109203X was added,the inhibitory effects of DADLE decreased markedly.Conclusion Activation of δ-opioid receptor on the membrane of human liver cells has inhibitory effects on serum-deprivation induced apoptosis of liver cells.The underlying mechanism may be associated with PKC pathway activation.