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Background and Aims: The annual incidence of early‐onset colorectal cancer (EOCRC) is increasing at an alarming rate. The prognosis of EOCRC remains controversial, and whether the early onset is a risk factor for colorectal cancer remains unclear. Methods: We searched four electronic bibliographic databases from database inception to April 25, 2022 for studies that included both early‐ and later‐onset patients and performed a prognostic analysis. Random‐effects models were used to summarize the prognostic information extracted by the investigators, including overall survival (OS), cancer‐special survival (CSS), and disease‐free survival (DFS). Network meta‐analysis (NMA) was used to compare patients' long‐term prognoses in different age subgroups. Results: After 694 reports were screened, 13 studies were included in the final analysis, with a total of 448,781 CRC cases. In the meta‐analysis of the 5‐year OS, EOCRC had a better prognosis compared to LOCRC (hazard ratio [HR] 0.87, 95% confidence interval [CI], 0.74–0.99; relative risk [RR] 0.83, 95% CI, 0.78–0.89). No difference in prognosis was found between the two groups in terms of 5‐year CSS (RR 0.99, 95% CI, 0.93–1.05), 5‐year DFS (RR 0.90, 95% CI, 0.74–1.09), and short‐term OS. In the NMA, patients aged <30 years had the worst outcome (surface under the cumulative ranking curve [SUCRA], 15.8%) in 5‐year OS; consistent results were observed in the analysis of 5‐year CSS (<30 years, SUCRA 4.5%), but the difference was not statistically significant. Conclusion: Although patients with early‐onset CRC had better OS than those with later‐onset CRC, there was no difference in the CSS. Meanwhile, the trend for survival was worse in younger patients, especially in those ages 18–29 years. Thus, more attention should be paid to early diagnosis and treatment of EOCRC. Systematic Review and Meta‐Analysis Registration: The systematic review and Meta‐analysis protocol was registered with PROSPERO (registration number CRD42022334697). [ABSTRACT FROM AUTHOR]

Splenomegaly is a prominent clinical manifestation of malaria and the causes remain incompletely clear. Anemia is induced in malaria and extramedullary splenic erythropoiesis is compensation for the loss of erythrocytes. However, the regulation of extramedullary splenic erythropoiesis in malaria is unknown. An inflammatory response could facilitate extramedullary splenic erythropoiesis in the settings of infection and inflammation. Here, when mice were infected with rodent parasites, Plasmodium yoelii NSM, TLR7 expression in splenocytes was increased. To explore the roles of TLR7 in splenic erythropoiesis, we infected wild-type and TLR7 -/- C57BL/6 mice with P. yoelii NSM and found that the development of splenic erythroid progenitor cells was impeded in TLR7 -/- mice. Contrarily, the treatment of the TLR7 agonist, R848, promoted extramedullary splenic erythropoiesis in wild-type infected mice, which highlights the implication of TLR7 on splenic erythropoiesis. Then, we found that TLR7 promoted the production of IFN-γ that could enhance phagocytosis of infected erythrocytes by RAW264.7. After phagocytosis of infected erythrocytes, the iron metabolism of RAW264.7 was upregulated, evidenced by higher iron content and expression of Hmox1 and Slc40a1 . Additionally, the neutralization of IFN-γ impeded the extramedullary splenic erythropoiesis modestly and reduced the iron accumulation in the spleen of infected mice. In conclusion, TLR7 promoted extramedullary splenic erythropoiesis in P. yoelii NSM-infected mice. TLR7 enhanced the production of IFN-γ, and IFN-γ promoted phagocytosis of infected erythrocytes and the iron metabolism of macrophages in vitro , which may be related to the regulation of extramedullary splenic erythropoiesis by TLR7., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Liu, Xing, Chen, Fang, Mo, Gong, Tan, Liang, Xiao, Tang, Wei, Zhao, Xie, Pan, Yin and Huang.)