Despite worldwide promising clinical outcome of CD19 CART therapy, relapse after this therapy is associated with poor prognosis and has become an urgent problem to be solved. We conducted a CD22 CAR T-cell therapy in 34 relapsed or refractory (r/r) BALL pediatric and adult patients who failed from previous CD19 CAR T-cell therapy. Complete remission (CR) or CR with incomplete count recovery (CRi) was achieved in 24 of 30 patients (80%) that could be evaluated on day 30 after infusion, which accounted for 70.5% of all 34 enrolled patients. Most patients only experienced mild cytokine-release syndrome and neurotoxicity. Seven CR patients received no further treatment, and 3 of them remained in remission at 6, 6.6, and 14 months after infusion. Eleven CR patients were promptly bridged to transplantation, and 8 of them remained in remission at 4.6 to 13.3 months after transplantation, resulted in 1-year leukemia-free survival rate of 71.6% (95% CI, 44.2-99.0). CD22 antigen loss or mutation was not observed to be associated with relapsed patients. Our study demonstrated that our CD22 CAR T-cells was highly effective in inducing remission in r/r BALL patients, and also provided a precious window for subsequent transplantation to achieve durable remission.

Gastrointestinal (GI) tract graft-versus-host disease (GvHD) is a major cause of post-allo-HSCT (hematopoietic stem cell transplantation) morbidity and mortality. Patients with steroid-refractory GI-GvHD have a poor prognosis and limited therapeutic options. FMT2017002 trial (#NCT03148743) was a non-randomized, open-label, phase I/II clinical study of FMT for treating patients with grade IV steroid-refractory GI-GvHD. A total of 55 patients with steroid-refractory GI-GvHD were enrolled in this study. Forty-one patients with grade IV steroid-refractory GI-GvHD were included in the final statistical analysis. Of them, 23 patients and 18 patients were assigned to the FMT group and the control group, respectively. On days 14 and 21 after FMT, clinical remission was significantly greater in the FMT group than in the control group. Within a follow-up period of 90 days, the FMT group showed a better overall survival (OS). At the end of the study, the median survival time was >539 days in the FMT group and 107 days in the control group (HR=3.51; 95% CI, 1.21–10.17; p=0.021). Both the event-free survival time (EFS) (HR=2.3, 95% CI, 0.99–5.4; p=0.08) and OS (HR=4.4, 95% CI, 1.5–13.04; p=0.008) were higher in the FMT group during the follow-up period. Overall, the mortality rate was lower in the FMT group (HR=3.97; 95% CI, 1.34–11.75; p=0.013). No differences in the occurrence of any other side effects were observed. Our data suggest that the diversity of the intestinal microbiota could be affected by allo-HSCT. Although its effectiveness and safety need further evaluation, FMT may serve as a therapeutic option for grade IV steroid-refractory GI-GvHD.Clinical Trial Registration[ClinicalTrials.gov], identifier [NCT03148743].

Abstract. Low-dose ionizing radiation (LDIR) may increase the mortality of solid cancers in nuclear industry workers, but only few individual cohort studies exist, and the available reports have low statistical power. The aim of the present study was to focus on solid cancer mortality risk from LDIR in the nuclear industry using standard mortality ratios (SMRs) and 95% confidence intervals. A systematic literature search through the PubMed and Embase databases identified 27 studies relevant to this meta-analysis. There was statistical significance for total, solid and lung cancers, with meta-SMR values of 0.88, 0.80, and 0.89, respectively. There was evidence of stochastic effects by IR, but more definitive conclusions require additional analyses using standardized protocols to determine whether LDIR increases the risk of solid cancer-related mortality.

The reproductive system is vulnerable to ionizing radiation, which is a hot research topic at present. We tested the effect of polydatin on spermatocytes(GC-1 cells) after X-ray irradiation. The reproductive damage model of C.elegans was established by 60Coγ-ray, and the protective effect of polydatin on reproductive damage caused by ionizing radiation was evaluated. We quantified the ROS levels of GC-1 cells and C.elegans after irradiation with polydatin and evaluated the anti-apoptosis effect of polydatin at proper concentration. Differential genes of C.elegans reproductive damage were screened out from transcriptome sequencing results and comparable GEO datasets. It was proved that 100μM polydatin significantly reduced the apoptosis of GC-1 cells induced by 2 Gy X-ray. In addition, the longevity, reproductive capacity, germ cell apoptosis and spawning and hatching capacity of polydatin were tested. The results showed that 100 μM polydatin content significantly increased the influence of 50 Gy 60Coγ-ray on reproductive capacity of C.elegans. Quantitative analysis of mRNA and protein levels of apoptosis-related genes and reproductive-related genes by qRT-PCR and Western blotcon firmed that polydatin with appropriate dosage had good protective effects on reproductive damage caused by radiation, which laid a foundation for the application research of polydatin in radiation protection.

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Objective: This study aimed to analyze the mechanism by which long-term occupational exposure of workers to low-dose ionizing irradiation induces epithelial mesenchymal transition (EMT) of the human bronchial epithelial cells using transcriptome profiling.Methods: RNA-seq transcriptomics was used to determine gene expression in blood samples from radiation-exposed workers followed by bioinformatics analysis. Normal bronchial epithelial cells (16HBE) were irradiated for different durations and subjected to immunofluorescence, western blotting, scratch healing, and adhesion assays to detect the progression of EMT and its underlying molecular mechanisms.Results: Transcriptomics revealed that exposure to ionizing radiation led to changes in the expression of genes related to EMT, immune response, and migration. At  increased cumulative doses, ionizing radiation-induced significant EMT, as evidenced by a gradual decrease in the expression of E-cadherin, increased vimentin, elevated migration ability, and decreased adhesion capability of 16HBE cells. The expression of fibronectin 1 (FN1) showed a gradual increase with the progression of EMT, and may be involved in EMT.Conclusion: Ionizing radiation induces EMT. FN1 may be involved in the progression of EMT and could serve as a potential biomarker for this process.

BackgroundGastrointestinal (GI) tract graft-vs-host disease (GvHD) is a major cause of post-allo-HCT morbidity and mortality. Patients with steroid-refractory GI-GvHD face a poor prognosis and limited therapeutic options. Here, we report an interim analysis on the safety and efficacy of fecal microbiota transplantation (FMT) in treating steroid-refractory GI-GvHD.MethodsWe did a non-randomized, open-label, phase 1 clinical study on patients with grade IV steroid-refractory GI-GVHD. FMT efficacy was evaluated using indexes of abdominal pain, diarrhea and bloody purulent stool at 14 and 21 days after the diagnosis of steroid-refractory GI-GvHD. The primary outcomes referred to clinical complete remission or partial remission. Secondary outcomes referred to PFS and OS at Day 90 and the end of the research. Safety was evaluated according to adverse events during FMT and the whole follow-up period. The study was registered with ClinicalTrials.gov as #NCT03148743.ResultsA total of 56 patients with steroid-refractory GI-GvHD were enrolled. Of them, 24 patients with grade IV steroid-refractory GI-GvHD were assigned to FMT and 18 to the control group. The characteristics of the two group patients at baseline were similar. At Day 14 after FMT, 13 (54.2%) patients in FMT group and none (0%) of 18 control group achieved clinical remission (p<0.05), while 20(83%) patients in FMT group and 7(39%) in control group showed effective response (clinical remission+partial remission) (RR 7.86, 95% CI 1.88–32.9; p=0.005). At Day 21, the clinical remission was significantly greater in FMT group than in control group (14 (58.3%) of 24 vs 3(16%) of 18; RR 6.0, 95% CI 1.22–29.45; p=0.027). Within a follow up of 90 days, the FMT group showed better OS (HR, 7.0; 95% CI, 1.53-32.08; p=0.012). At the end of the research, the median survival time was >600 days in FMT group and 107 days in control group (HR, 4.73; 95% CI, 1.58-14.14; p=0.005). Both the PFS (HR, 0.24; 95% CI, 0.06-0.95; p=0.055) and OS (HR, 5.97; 95% CI, 1.52-23.43; p=0.01) kept increasing during the follow-up in FMT group. Overall, the mortality rate was lower in FMT group (HR, 5.97; 95% CI, 1.52-23.43; p=0.01). No difference was observed in the occurrence of other side effects, such as hemorrhagic cystitis, infection of bacteria & fungi, CMV&EBV, septicemia, TMA, cardiac events, thrombocytopenia and epilepsy.ConclusionsThe diversity of intestinal microbiota can be affected by allo-HSCT. FMT is effective and safe in treating grade IV steroid refractory GI–GvHD.

The health of radiation workers has always been our focus. Epidemiological investigation shows that long-term exposure to low-dose ionizing radiation can affect human health, especially cancer and cardiovascular disease, and there are many studies on it. However, up to now, there have been few reports on the research of blood and biological samples from radiation workers. In this study, radiation workers and healthy control groups were strictly screened, and the transcriptome of mRNA and circRNA was sequenced by extracting their peripheral venous blood. At the same time, appropriate data sets were selected in the GEO database for bioinformatics analysis, and circRNA-miRNA-mRNA network was constructed. We identified 9 different circular ribonucleic acids, 3 tiny ribonucleic acids, and 2 central genes (NOD 2 and IRF 7). These differentially expressed genes and non-coding RNA are closely related to ionizing radiation damage, and play an important role as biological markers. In conclusion, this study may provide new insights into the role of the circRNA-miRNA-mRNA regulatory network in the health of radiation workers, and provides a new strategy for the future study of radiation biology.