Background: To study the corresponding strategies to control inflammatory bowel disease (IBD), a comprehensive assessment of the disease burden is required. Herein, we present long-term trends in the burden of IBD in China over the last three decades, as well as its epidemiological features.Methods: We characterized the burden of IBD in China using the GBD 2019 methods and results, based on prevalence, incidence, mortality, years lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) estimated using the DisMod-MR 2-1. We also used joinpoint and age-period-cohort (apc) analysis methods to interpret IBD epidemiological characteristics and compare them to global prevalence trends.Results: The age-standardized incidence and mortality rates in both sexes changed from 1.47 (95% CI: 1.24, 1.74) to 3.01 (95% CI: 2.59, 3.50) and from 0.86 (95% CI: 0.59, 1.16) to 0.30 (95% CI: 0.24, 0.35) per 100,000 people in China from 1990 to 2019. The age-standardized DALY rate in China decreased from 24.47 (95% CI: 17.88, 30.19) per 100,000 people in 1990 to 13.10 (95% CI: 10.29, 16.31) per 100,000 people in 2019. The average annual percentage change (AAPC) in age-standardized incidence, prevalence, and mortality rates for IBD in China were 2.51 (95% CI: 2.44, 2.57), 2.53 (95% CI: 2.41, 2.66), and −3.62 (95% CI: −3.85, −3.39). The effects of age, period, and cohort on incidence and mortality rates differed.Conclusions: The increasing age-standardized prevalence rates are contributed to by the reduction in age-standardized mortality rates and DALYs, compounded by the rise in the age-standardized incidence rates between 1990 and 2019 in China. The burden of IBD in China will be a major public health challenge, given the country's large population base and aging population.

Radiotherapy (RT)-induced tumoricidal immunity is severely limited when tumors are well-established. Here, we report that depleting SIRPα on intratumoral macrophages augments efficacy of RT to eliminate otherwise large, treatment-resistant colorectal (MC38) and pancreatic (Pan02 and KPC) tumors, inducing complete abscopal remission and long-lasting humoral and cellular immunity that prevent recurrence. SIRPα^-deficient macrophages activated by irradiated tumor-released DAMPs exhibit robust efficacy and orchestrate an anti-tumor response that controls late-stage tumors. Upon RT-mediated activation, intratumoral SIRPα^-deficient macrophages acquire potent proinflammatory features and conduct immunogenic antigen presentation that confer a tumoricidal microenvironment highly infiltrated by tumor-specific cytotoxic T cells, NK cells and inflammatory neutrophils, but with limited immunosuppressive regulatory T cells, myeloid derived suppressor cells and post-radiation wound-healing. The results demonstrate that SIRPα is a master regulator underlying tumor resistance to RT and provide proof-of-principle for SIRPα^-deficient macrophage-based therapies to treat a broad spectrum of cancers, including those at advanced stages with low immunogenicity and metastases.

Damage to the intestinal mucosal barrier play an important role in the pathogenesis of ulcerative colitis (UC). Discovering the key regulators and repairing the disturbed barrier are crucial for preventing and treating UC. Traditional Chinese medicine (TCM) has been proved to be effective on treating UC and has exhibited its role in repairing the intestinal mucosal barrier. We summarized the evidence of TCM against UC by protecting and repairing the physical barrier, chemical barrier, immune barrier, and biological barrier. Mechanisms of increasing intestinal epithelial cells, tight junction proteins, and mucins, promoting intestinal stem cell proliferation, restoring the abundance of the intestinal microbiota, and modulating the innate and adaptive immunity in gut, were all involved in. Some upstream proteins and signaling pathways have been elucidated. Based on the existing problems, we suggested future studies paying attention to patients’ samples and animal models of UC and TCM syndromes, conducting rescue experiments, exploring more upstream regulators, and adopting new technical methods. We hope this review can provide a theoretical basis and novel ideas for clarifying the mechanisms of TCM against UC via repairing the intestinal mucosal barrier.

Macrophage functional plasticity plays a central role in responding to proinflammatory stimuli. The molecular basis underlying the dynamic phenotypic activation of macrophages, however, remains incompletely understood. In this article, we report that SIRPα is a chief negative regulator of proinflammatory macrophage polarization. In response to TLR agonists, proinflammatory cytokines, or canonical M1 stimulation, Src family kinases (SFK) excluding Lyn phosphorylate SIRPα ITIMs, leading to the preferential recruitment and activation of SHP-1, but not SHP-2. Solely extracellular ligation of SIRPα by CD47 does not greatly induce phosphorylation of SIRPα ITIMs, but it enhances proinflammatory stimuli–induced SIRPα phosphorylation. Examination of downstream signaling elicited by IFN-γ and TLR3/4/9 agonists found that SIRPα-activated SHP-1 moderately represses STAT1, NF-κB, and MAPK signaling but markedly inhibits Akt2, resulting in dampened proinflammatory cytokine production and expression of Ag presentation machinery. Pharmacological inhibition of SHP-1 or deficiency of SIRPα conversely attenuates SIRPα-mediated inhibition and, as such, augments macrophage proinflammatory polarization that in turn exacerbates proinflammation in mouse models of type I diabetes and peritonitis. Our results reveal an SFK–SIRPα–SHP-1 mechanism that fine-tunes macrophage proinflammatory phenotypic activation via inhibition of PI3K–Akt2, which controls the transcription and translation of proinflammatory cytokines, Ag presentation machinery, and other cellular programs.

Differential analysis of intestinal microbiota and metabolites in mice with dextran sulfate sodium-induced colitis