PCNA Confers the Conversion of Hepatitis B Virus Relaxed Circular DNA to Covalently Closed Circular DNA by Its DNA Binding Domain / 中国生物化学与分子生物学报

Chronic hepatitis B virus (HBV) infection is a primary cause for liver cancer. And the main challenge of curing hepatitis B is the elimination of the stable covalently closed circular DNA (cccDNA) of the viral genome. The formation of HBV cccDNA requires the filling of single-stranded region and the ligation of nicks in relaxed circular DNA (rcDNA) strands. Previously, our group reported that proliferating cell nuclear antigen (PCNA) was involved in the formation of HBV cccDNA. However, the underlying mechanism of the conversion of HBV rcDNA to cccDNA is poorly understood. In the present study, we aim to explore the mechanism by which PCNA contributes to the conversion of HBV rcDNA to cccDNA. Our data showed that PCNA was involved in the process of HBV rcDNA repair. The knockout of PCNA by the CRISPR/Cas9 system remarkably blocked the conversion of HBV rcDNA to cccDNA, while the ectopic expression of PCNA could effectively rescue the event (P<0. 001). Knockout of PCNA significantly slowed down the conversion kinetics of HBV rcDNA to cccDNA (P<0. 01). Mechanically, the DNA binding domain of PCNA was required for the process of HBV rcDNA repair to cccDNA (P<0. 01). Thus, we conclude that PCNA confers the conversion of HBV rcDNA to cccDNA by its DNA binding domain. Clinically, PCNA might serve as a novel target for antiviral therapy.

Outcomes of 138 myelodysplastic syndrome patients with HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ(2)=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ(2)=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ(2)=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ(2)=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions: HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

Hematopoietic Stem Cells Differentiate into the Megakaryocyte Lineage--Review / 中国实验血液学杂志

Abstract　　Hematopoietic stem cells are able to self-renewal and differentiate to all blood lineages. With the development of new technologies, recent studies have proposed the revised versions of hematopoiesis. In the classical model of hematopoietic differentiation, HSCs were located at the apex of hematopoietic hierarchy. During differentiation process, HSCs progressively lose self-renewal potential to be commited to progenitors with restricted differentiation potential. For instance, HSCs first give rise to multipotent progenitor cells, then produce bipotent and unipotent progenitors, and finally differentiate to mature blood cells. For the differentiation of megakaryocytes, common myeloid progenitors derived from HSCs give rise to megakaryocyte-erythrocyte progenitors and then develop to megakaryocytes. However, recent results show that megakaryocytes can be directly generated from HSCs without multipotent or bipotent phases. Alternatively, platelet-biased HSCs produce megakaryocyte progenitors. In this article, recent advances in the hematopoiesis and megakaryocyte differentiation pathway are reviewed.

Emerging role of Mitochondria in Maintenance of Hematopoietic Stem Cells--Review / 中国实验血液学杂志

Mitochondria are double-membrane organelles existing only in eukaryotic cells. Mitochondria perform various important functions，such as producing energy，regulating signal transduction，and contributing to stress response. Recent studies have highlighted an important role of mitochondria in the determination of hematopoietic stem cells （HSC） fate. Limited biogenesis or timely clearance of mitochondria is an important way against oxidative stress，which favors the quiescence of HSC. Accumulation of mitochondria may lead to proliferation of HSC，even the aging of HSC. Mitochondrial signaling regulates Ca concentration，which is essential for HSC differentiation. This review summarizes the current findings of the mitochondrial roles in HSC quiescence，self-renewal，lineage differentiation and aging.

Outcomes and prognostic factors of myelodysplastic syndrome patients with allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the outcomes and prognostic factors of myelodysplasia syndrome (MDS) patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: 165 cases of MDS who underwent allo-HSCT from Jan. 2010 to Mar. 2018 were analyzed retrospectively, focusing on the overall survival (OS) , disease free survival (DFS) , relapse, non-relapse mortality (NRM) and their related risk factors. Results: Of all the 165 cases, 105 were male and 60 were female. The 3-year OS and DFS rate were 72.5% (95%CI 64.9%-80.1%) and 67.4% (95%CI 59.17%-75.63%) , respectively. The 3-year cumulative incidence of relapse and NRM were 12.11% (95%CI 7.03%-18.65%) and 20.44% (95%CI 14.15%-27.56%) , respectively. HCT-comorbidity index (P=0.042, HR=2.094, 95%CI 1.026-4.274) was identified as independent risk factor for OS by the multivariate analysis. Intensive chemotherapy before HSCT or hypomethylation agents treatment had no effects on OS[ (67.0±7.5) %vs (57.7±10.9) %, χ(2)=0.025, P=0.874]. Conclusions: allo-HSCT is a promising means for MDS, and NRM is the major cause of treatment failure. MDS with refractory anemia with excess blasts and secondary acute myeloid leukemia patients may not benefit from intensive chemotherapy or hypomethylation agents treatment before HSCT.

Treatment and surgery of primary hepatic cancer with portal vengus tumor thrombosis / 中华外科杂志

<p><b>OBJECTIVE</b>To study the methods of surgery for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (TTPV).</p><p><b>METHODS</b>To Analyze and summarize the clinical information from 138 HCC patients with tumor thrombi in portal vein collected during January 1990 and January 2003.</p><p><b>RESULTS</b>Thirty-seven patients receiving palliative therapy died from 1 to 8 months, and average survival time is 3.9 months. 101 patients had operation treatment, 23 of them underwent hepatoma resection, and average survival time was 10.9 months; 78 patients underwent hepatoma resection and removal of tumor thrombi, and average survival time was 26.8 months. 52 of whom underwent hepatic artery and portal vein chemoembolization, the 1-, 3-, 5-year survival rates was 96.2%, 51.9%, 11.5%, the 1-, 3-, 5-year survival rates of the 26 patients who didn't undergo chemoembolization were 76.9%, 23.1%, 0%.</p><p><b>CONCLUSIONS</b>Operation treatment can comparatively extend the survival time of hepatocellular carcinoma with tumor thrombi in portal vein patients, and the best choice is hepatoma resection and removal of tumor thrombi, hepatic artery and portal vein chemoembolization after operation can enhance the effect.</p>