Muramidase-released protein(MRP)is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis(S.suis).However,the identification of viable therapeutics for S.suis infection was hindered by the absence of an explicit mechanism for MRP-actuated inflammation.Dihydroartemisinin(DhA)is an artemisinin derivative with potential anti-inflammatory activity.The modulatory effect of DhA on the inflammatory response mediated by the virulence factor MRP remains obscure.This research aimed to identify the signaling mechanism by which MRP triggers the innate immune response in mouse spleen and cultured macrophages.With the candidate mechanism in mind,we investigated DhA for its ability to dampen the pro-inflammatory response induced by MRP.The innate immune response in mice was drastically triggered by MRP,manifesting as splenic and systemic inflammation with splenomegaly,immune cell infiltration,and an elevation in pro-inflammatory cyto-kines.A crucial role for Toll-like receptor 4(TLR4)in coordinating the MRP-mediated inflammatory response via nuclear factor-kappa B(NF-κB)activation was revealed by TLR4 blockade.In addition,NF-KB-dependent transducer and activator of transcription 3(STAT3)and mitogen-activated protein kinases(MAPKs)activation was required for the inflammatory signal transduction engendered by MRP.Intriguingly,we observed an alleviation effect of DhA on the MRP-induced immune response,which referred to the suppression of TLR4-mediated actuation of NF-KB-STAT3/MAPK cascades.The inflam-matory response elicited by MRP is relevant toTLR4-dependent NF-κB activation,followed by an increase in the activity of STAT3 or MAPKs.DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade,highlighting the therapeutic potential of DhA in targeting S.suis infection diseases.

Objective : To investigate the effect of standardized lymph node sorting on postoperative results of gas- troesophageal junction malignant tumors． Methods : The data of all patients with malignant gastroesophageal junc- tion in gastric cancer database were analyzed retrospectively．Lymph nodes were sorted according to whether sur- geons were present immediately after surgery．Patients were divided into lymph node sorting group (sorting group) and lymph node unsorting group (unsorting group) ．General data included gender，age，body mass index (BMI) ， carcinogenic antigen ( CEA) ，postoperative albumin level，preoperative hemoglobin，etc．Perioperative and patho- logical data included operation time，intraoperative blood loss，postoperative hospital stay，tumor differentiation， distance from superior incisal margin，total number of lymph nodes，number of positive lymph nodes，etc．Kaplan- Meier curve and Log-rank test were used for survival analysis，and propensity score matching analysis adjusted for confounding factors between groups. Results : A total of 386 patients were included，including 133 in lymph node sorting group and 253 in non-sorting group．The median follow-up time was 40. 18 months．The total number of lymph nodes and the number of positive lymph nodes in the sorting group were (26. 38 ± 12. 18) and (6. 63 ± 10. 14) ，respectively，while the total number and the number of positive lymph nodes in the non-sorting group were ( 12. 25 ± 7. 06) and (3. 07 ± 3. 77) ，respectively．There were statistically significant differences in the total num- ber of lymph nodes and the number of positive lymph nodes between the sorting group and the non-sorting group (P ＜0. 05) ．There was no statistically significant difference in survival between the sorting group and the non-sorting group before matching．There were 112 and 203 patients with advanced gastric cancer in the two groups，respec- tively．The overall survival curve of patients in the sorting group was better than that in the non-sorting group，and the difference in median survival time was statistically significant (P＜0. 05) ．The caliper value was set to 0. 02， and 94 pairs of patients were preferentially matched．After matching，the total number of lymph nodes and the num- ber of positive lymph nodes in the sorting group were (24. 71 ± 12. 03) and (5. 70 ± 9. 95) ，respectively，while the total number and the number of positive lymph nodes in the non-sorting group were ( 13. 05 ± 7. 63) and (3. 37 ± 4. 32) ，respectively．The difference between the two groups was statistically significant (P＜0. 05) ．The overall survival curve of patients in the sorting group was better than that in the non-sorting group，and the median survival time was statistically significant (P＜0. 05) ． Conclusion Postoperative lymph node sorting for gastric cancer can significantly increase the number of total lymph nodes and positive lymph nodes，reduce lymph node migration，and improve postoperative survival time.