Meta analysis of the application of ERAS concept in orthopedic surgery / 中国医师杂志

Objective:To evaluate the value and effectiveness of the enhanced recovery after surgery (ERAS) theory in orthopedic surgery, and to provide a theoretical basis for optimizing rehabilitation plans during the perioperative period of orthopedic surgery.Methods:Relevant literature on the application of accelerated rehabilitation in orthopedic perioperative period officially published in Pubmed and the Chinese Medical Journal Database From January 2000 to October 2022 was searched and included in randomized controlled and clinical case studies. The patients were divided into the experimental group (ERAS group) and the control group (conventional treatment group). The patients in the experimental group were treated with ERAS mode after surgery, while the patients in the control group were treated with conventional rehabilitation mode after surgery. The hospital stay, postoperative complications, postoperative nausea and vomiting, and postoperative incidence rate of deep vein thrombosis in the two groups were statistically analyzed.Results:Finally, a total of 1 301 patients were included in 9 articles, divided into an experimental group (ERAS group, n=643) and a control group (conventional treatment group, n=652). There was a statistically significant difference in hospital stay between the experimental group and the control group ( MD=-4.11, 95% CI: -6.73 to -1.49, P=0.002); The overall effect tendency of the incidence of complications between the experimental group and the control group was statistically significant ( P=0.005); Compared with the control group, the incidence rate of postoperative nausea and vomiting in the experimental group was lower ( P=0.04); The incidence rate of postoperative deep vein thrombosis in the experimental group was lower than that in the control group ( P=0.02). Conclusions:The application of accelerated rehabilitation concept in orthopedic surgery patients can reduce the length of hospital stay, and reduce the incidence rate of postoperative complications, nausea and vomiting, and deep vein thrombosis.

Identification and optimization of peptide inhibitors to block VISTA/PSGL-1 interaction for cancer immunotherapy

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8+ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8+ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Tryptophan 2,3-dioxygenase 2 controls M2 macrophages polarization to promote esophageal squamous cell carcinoma progression

Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3

A novel cyclic peptide targeting LAG-3 for cancer immunotherapy by activating antigen-specific CD8 T cell responses

PD-1 and CTLA-4 antibodies offer great hope for cancer immunotherapy. However, many patients are incapable of responding to PD-1 and CTLA-4 blockade and show low response rates due to insufficient immune activation. The combination of checkpoint blockers has been proposed to increase the response rates. Besides, antibody drugs have disadvantages such as inclined to cause immune-related adverse events and infiltration problems. In this study, we developed a cyclic peptide C25 by using Ph.D.-C7C phage display technology targeting LAG-3. As a result, C25 showed a relative high affinity with human LAG-3 protein and could effectively interfere the binding between LAG-3 and HLA-DR (MHC-II). Additionally, C25 could significantly stimulate CD8 T cell activation in human PBMCs. The results also demonstrated that C25 could inhibit tumor growth of CT26, B16 and B16-OVA bearing mice, and the infiltration of CD8 T cells was significantly increased while FOXP3 Tregs significantly decreased in the tumor site. Furthermore, the secretion of IFN- by CD8 T cells in spleen, draining lymph nodes and especially in the tumors was promoted. Simultaneously, we exploited T cells depletion models to study the anti-tumor mechanisms for C25 peptide, and the results combined with MTT assay confirmed that C25 exerted anti-tumor effects CD8 T cells but not direct killing. In conclusion, cyclic peptide C25 provides a rationale for targeting the immune checkpoint, by blockade of LAG-3/HLA-DR interaction in order to enhance anti-tumor immunity, and C25 may provide an alternative for cancer immunotherapy besides antibody drugs.