Effect of Additional Clostridium butyricum on the Intestinal Flora of Chronic Hepatitis B Patients Treated with Entecavir.

INTRODUCTION: To explore the influence of intestinal flora on the occurrence, development and antiviral therapy of chronic hepatitis B (CHB), 16S rDNA amplification sequencing was performed to investigate the intestinal flora in CHB patients treated with entecavir (ETV) and Clostridium butyricum (CB). METHODS: CHB patients were divided into the ETV group (treatment with ETV alone) and ETV + CB group (treatment with ETV and CB). After 8-week treatment, feces samples were collected and processed for 16S rDNA amplicon sequencing; blood samples were collected for the biochemical, immunologic and virologic evaluations, which were compared between groups. RESULTS: ETV treatment for 8 weeks significantly decreased the serum levels of alanine aminotransferase (ALT), interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and HBV DNA compared to those before treatment, but there were no marked differences between the ETV group and ETV + CB group. The intestinal flora changed significantly in the CHB patients after ETV + CB treatment: there were marked differences in 13 unique species before treatment and 4 unique species after ETV + CB treatment; at the phylum level, the top five bacteria with significant difference between patients before treatment and ETV + CB patients were Firmicutes, Actinobacteria, Cyanobacteria, Euryarchaeota and Synergistetes. There were significant differences in 25 unique species in the ETV group and 4 unique species in the ETV + CB group; at the phylum level, the top five bacteria with significant difference between ETV patients and ETV + CB patients were Actinobacteria, Fusobacteria, Proteobacteria, Saccharibacteria and Synergistetes. CONCLUSION: ETV treatment improves the serum biochemical, immunologic and virologic variables, but additional CB fails to further improve these variables. Of note, additional CB affects the intestinal flora in the CHB patients treated with ETV.

Effect of Entecavir on the Intestinal Microflora in Patients with Chronic Hepatitis B: A Controlled Cross-Sectional and Longitudinal Real-World Study.

INTRODUCTION: This study aimed to analyze the diversity of intestinal flora in patients with chronic hepatitis B (CHB) and investigate the effect of entecavir on the intestinal flora in these patients. METHODS: Thirty patients with CHB and 30 healthy controls were recruited from the Department of Infectious Diseases and Department of Gastroenterology of Shanghai Tongji Hospital between January 2017 and December 2018. Stool samples were collected for the detection of intestinal flora by high-throughput sequencing. Patients with CHB received antivirus therapy with entecavir for 8 weeks. The biochemical and virological responses were assessed and the intestinal flora were compared. RESULTS: After entecavir treatment, the blood levels of alanine aminotransferase (ALT), interleukin-6 (IL-6), IL-8, tumor necrosis factor (TNF), and hepatitis B virus (HBV) DNA reduced significantly in patients with CHB and the species abundance of intestinal flora increased markedly. In patients with CHB, the unique genera included Butyrivibrio, Phaseolus acutifolius, and Prevotellaceae NK3B31 group before treatment and Howardella, Candidatus Stoquefichus, Citrobacter, Dysgonomonas, Faecalicoccus, Methanobrevibacter, Mitsuokella, Mobilitalea, Succinivibrio, Gluconobacter, and Plesiomonas after treatment. The abundance of the following genera increased significantly after entecavir treatment in patients with CHB: Clostridium sensu stricto 1, Erysipelotrichaceae UCG-007, and Intestinibacter. The abundance of Streptococcus, Atopobium, and Murdochiella reduced markedly after entecavir treatment in patients with CHB. CONCLUSION: After 8-week entecavir treatment, the blood biochemical, immunological, and virological responses improved significantly, the species abundance of intestinal flora increased markedly, and there were unique genera in patients with CHB before and after treatment.

[Research advances of leukemia mouse hematopoietic stem cell transplantation model].

Mouse model of leukemia hematopoietic stem cell transplantation is the key platform to study leukemia experimental treatment, which has been widely used in anticancer drug screening and in the studies of leukemia pathogenesis and experimental treatment. Transplantation mouse model has several advantages such as short cycle of model establishment, good repetitiveness, and the more stable biological characteristics of the tumor cell lines. The source of leukemia and tumor cell lines, choice of mouse species, the establishment of transplantation model, the recent advances of GVHD model and other aspects of transplantation mouse model are summarized in this review.

[Detecting minimal residual disease status in allogeneic hematopoietic stem cell transplantation of patients with high-risk acute leukemia].

OBJECTIVE: To explore the relationship between minimal residual disease (MRD) and the outcome of patients with high-risk acute leukemia (AL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: By 4/5-color multi-parameter flow cytometry (MFC, CD45/SSC gating) for detecting MRD at pre-(day-30) and post-transplant (day +30, +60, +100, 6 months, 9 months and 12 months), the investigators retrospectively analyzed the MRD levels and the prognosis of 90 high-risk patients. According to the MRD cutoff value of 0.1%, the low-level and high-level groups were defined. In the high-level group, the patients were divided into two sub groups according to the subsequent treatment (intervention therapy group and non-intervention therapy group). RESULTS: MRD pre-transplant had no predictive value for the clinical outcome. The patients with high levels of MRD post-transplant (+60 d and +100 d) showed higher relapse rates than those of the low-level group. In addition, regarding MRD +100 d post-transplant, differences were significant among 3 groups (high-level MRD and intervention therapy group, high-level MRD and non-intervention therapy group and low-level MRD group) including 1-year relapse-free survival (RFS) (100% vs 60.87% vs 91.30%, P < 0.05) and 3-year RFS (85.71% vs 44.72% vs 68.48%, P < 0.05). The median time from first high level MRD detected to clinical relapse was 2.5 (1 - 26) months. In the high level MRD group (+100 d post-transplant), 7 of 30 patients received intervention therapy without relapse. However another 23 patients had no intervention treatment and 11 of them relapsed latter (P < 0.05). CONCLUSION: The MFC-based quantification of MRD post-transplant reveals important prognostic information in patients with high-risk AL. MRD check point at day +100 (cutoff: 0.1%) may discriminate different risk populations. Those patients with MRD levels ≥ 0.1% should receive early intervention at an early stage and a low tumor burden so as to reduce the relapse rate and boost survival.