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Gaining a better understanding of autoprotection against drug-induced liver injury(DILI)may provide new strategies for its prevention and therapy.However,little is known about the underlying mechanisms of this phenomenon.We used single-cell RNA sequencing to characterize the dynamics and functions of hepatic non-parenchymal cells(NPCs)in autoprotection against DILI,using acetaminophen(APAP)as a model drug.Autoprotection was modeled through pretreatment with a mildly hepatotoxic dose of APAP in mice,followed by a higher dose in a secondary challenge.NPC subsets and dynamic changes were identified in the APAP(hepatotoxicity-sensitive)and APAP-resistant(hepatotoxicity-resistant)groups.A chemokine(C-C motif)ligand 2+endothelial cell subset almost disappeared in the APAP-resistant group,and an R-spondin 3+endothelial cell subset promoted hepatocyte proliferation and played an important role in APAP autoprotection.Moreover,the dendritic cell subset DC-3 may protect the liver from APAP hepatotoxicity by inducing low reactivity and suppressing the autoimmune response and occurrence of inflammation.DC-3 cells also promoted angiogenesis through crosstalk with endothelial cells via vascular endothelial growth factor-associated ligand-receptor pairs and facilitated liver tissue repair in the APAP-resistant group.In addition,the natural killer cell subsets NK-3 and NK-4 and the Sca-1-CD62L+natural killer T cell subset may promote autoprotection through interferon-y-dependent pathways.Furthermore,macrophage and neutrophil subpopulations with anti-inflammatory phenotypes promoted tolerance to APAP hepatotoxicity.Overall,this study reveals the dynamics of NPCs in the resistance to APAP hepatotoxicity and provides novel insights into the mechanism of autoprotection against DILI at a high resolution.
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Objective: To investigate the clinical characteristics, treatment regimens, and outcomes of patients with primary breast dif-fuse large B-cell lymphoma (PB-DLBCL). Methods: Between January 2010 and January 2018, 21 patients with PB-DLBCL were diag-nosed, treated, and followed up at the First Affiliated Hospital of Zhengzhou University. All patients were female, with a median age of 49 years (ranging from 21 to 77 years) at presentation. All patients received chemotherapy, of which 17 patients received the CHOP regimen and 4 received the EPOCH regimen. Eight patients received chemotherapy followed by radiotherapy, and 13 received chemo-therapy alone. Six patients received prophylactic intrathecal injections. The incidences of refractory and progressive disease between patients who received different regimens were analyzed using the Chi-square test. The overall survival (OS) and progression-free sur-vival (PFS) rates were calculated using the Kaplan-Meier method, and differences in survival were compared using the Log-rank test. Multivariate analysis was performed with the Cox-regression model for those factors that were confirmed as significant in the univari-ate analysis. Results: The most common presentation was a painless mass. The 5-year OS and PFS rates were 74% and 66%, respective-ly. There was no significant difference in the incidence of refractory or progressive disease between the EPOCH and CHOP groups (P=0.603). Six of those who received prophylactic intrathecal injections had no central nervous system recurrence, and 2 patients who did not receive prophylactic intrathecal injections had central nervous system recurrence. Univariate and multivariate analyses showed that both the level of serum β2 microglobulin [P=0.044, hazard ratio (HR)=0.431, 95% confidence interval (CI): 0.432-0.967] and radio-therapy (P=0.002, HR=0.495, 95% CI: 1.073-2.508) were related to the OS of PB-DLBCL. Conclusions: PB-DLBCL often occurs in women, mostly involving the unilateral breast, which manifests mainly as a painless mass. The level of serum β2 microglobulin is a factor of poor prognosis in PB-DLBCL. The treatment modality of chemotherapy combined with radiotherapy can significantly improve the OS of PB-DLBCL. Prophylactic intrathecal injections may be useful to reduce the incidence of refractory disease or recurrence in the central nervous system.
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The incidence of primary intestinal lymphoma (PIL) in primary gastrointestinal lymphoma (PGIL) is much lower than that of primary gastric lymphoma (PGL). Treatment strategies for PGL have been normalized, but there are still controversies concerning about the diagnosis criteria and optimal treatment of PIL. The lesions are mainly found in intestinal tract, and the most common involvement is ileocecal junction. The pathological types are derived from B-cell and diffuse large B-cell lymphoma (DLBCL) is the most common type, followed by extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Surgery, chemotherapy, radiotherapy, antibiotics and monoclonal antibody therapy could be used as the monotherapy or different combined therapies, however, the final conclusion has not been reached in the treatment of PIL, accompanied by various influencing factors for prognosis. This review discusses the diagnosis criteria, clinical features, optimal treatment and prognostic factors of PIL. The diagnosis criteria and the optimal treatment will be put more emphasis.