Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that a phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts a range of anti-tumor activities in lung cancer. Here, we found that upregulation of PGAM1 correlates with increased levels of M2-like tumor-associated macrophages (TAMs) in human colon cancer samples, particularly in liver metastatic tissues. HKB99 suppressed tumor growth and metastasis in cell culture and syngeneic tumor models. M2-polarization, induced by colon cancer cell co-culture, was reversed by HKB99. Conversely, the increased migration of colon cancer cells by M2-TAMs was remarkably restrained by HKB99. Notably, a decrease in TAM infiltration was required for the HKB99-mediated anti-tumor effect, along with an increase in CD8⁺ T cell infiltration. Moreover, HKB99 improved the efficacy of anti-PD-1 treatment in syngeneic tumors. Overall, this study highlights HKB99's inhibitory activity in TAM-mediated colon cancer progression. Targeting PGAM1 could lead to novel therapeutic strategies and enhance the effectiveness of existing immunotherapies for colon cancer.

Neoadjuvant chemotherapy has become an indispensable weapon against high-risk resectable cancers, which benefits from tumor downstaging. However, the utility of chemotherapeutics alone as a neoadjuvant agent is incapable of generating durable therapeutic benefits to prevent postsurgical tumor metastasis and recurrence. Herein, a tactical nanomissile (TALE), equipped with a guidance system (PD-L1 monoclonal antibody), ammunition (mitoxantrone, Mit), and projectile bodies (tertiary amines modified azobenzene derivatives), is designed as a neoadjuvant chemo-immunotherapy setting, which aims at targeting tumor cells, and fast-releasing Mit owing to the intracellular azoreductase, thereby inducing immunogenic tumor cells death, and forming an in situ tumor vaccine containing damage-associated molecular patterns and multiple tumor antigen epitopes to mobilize the immune system. The formed in situ tumor vaccine can recruit and activate antigen-presenting cells, and ultimately increase the infiltration of CD8⁺ T cells while reversing the immunosuppression microenvironment. Moreover, this approach provokes a robust systemic immune response and immunological memory, as evidenced by preventing 83.3% of mice from postsurgical metastasis or recurrence in the B16-F10 tumor mouse model. Collectively, our results highlight the potential of TALE as a neoadjuvant chemo-immunotherapy paradigm that can not only debulk tumors but generate a long-term immunosurveillance to maximize the durable benefits of neoadjuvant chemotherapy.

Objective: To compare the surgical accuracy of the 3D printing surgical guide and traditional occlusal splint in the treatment of skeletal facial asymmetry cases. Methods: 12 facial asymmetric patients underwent joint orthognathic and orthodontics treatments were included in this research. In the 3D printing group (n=6) the pre-surgical CT scan for the skeleton and laser scan for the dentures were performed and 3D orthognathic procedures including Le FortⅠ and BSSRO combined with genioplasty were planned. The 3D printing surgical guides were manufactured and applied during surgeries. Another 6 cases were received same procedures by traditional occlusal splint techniques as the control group. Post-surgical CT reconstruction and 3D superimposition with pre-surgical planning was carried out for outcome comparison. Results: The maximal error of maxillar was 0.65 mm and average error was less than 1 mm in 3D printing group, while the maxillary maximal error was 2.11 mm and average error was greater than 1 mm in traditional group which showed the statistical significance (P<0.05). Conclusions The usage of 3D printing surgical guide could improve the orthognathic surgical precision by controlling the jaw bone in a three-dimensional way.

Objective To develop and validate a new genioplasty templates system for monoblock osseous genioplasty.Methods Thirty-six patients with chin deformities were enrolled in this study.The chin template system included a cutting guide and a repositioning guide for a genioplasty.Chin templates were designed in a computer and fabricated using a three-dimensional printing technique.The accuracy of the genioplasty templates were assessed by comparing the actual postoperative outcomes with the virtual plan.Results All genioplasty was successfully completed by the template system.The largest linear rootmean-square deviation(RMSD) between the planned and the postoperative chin segments was 1.16 mm and the largest angular RMSD was 3.06°.Conclusions The results showed that the chin template system provides a reliable method for transfer of genioplasty planning.The operation precision of the genioplasty can be improved by using the surgical templates system.

Objective To evaluate the results of the orthognathic surgery with computer aided simulation-three-dimensional(3D) printed surgical guide and dental model surgery in the treatmemt of patients with mandibular excess and facial asymmetries.Methods The coordinate system was built in ProPlan CMF 2.0 software,and the horizontal plane consisted of PoL,PoR,OrL,middle sagittal plane through nasion point and basion point and the plane perpendicular to the horizontal plane,coronoid plane through nasion point and the plane perpendicular to the horizontal plane and middle sagittal plane.The orientation of maxilla and mandibular distal segment was calculated by each triangle(U 1-U6L-U6R,L1-L6L-L6R,Me-M5L-M5R) before and after orthognathic surgery.A total of 60 mandibular excess patients with facial asymmetries were enrolled in this retrospective study.They were divided into two groups,group I with computer aided simulation,group Ⅱ with dental model surgery.The difference of maxillary occlusal plane roll and yaw angle,mandibular occlusal plane roll and yaw angle,and mandibular body plane roll and yaw angle were calculated.Statistical analysis was performed with SPSS 17.0 software.Results The yaw angle of mandibular occlusal plane of the dental model surgery and computer aided simulation was 0.36°± 0.48° and 0.84° ±0.36° (P=0.043),respectively.The roll angle of mandibular occlusal plane of the dental model surgery and computer aided simulation was 0.26°±0.79° and 0.54°±0.40°(P=0.032),respectively.The yaw angle of mandibular body plane of the dental model surgery and computer aided simulation was 0.60°± 1.04° and 0.23°±0.52°(P=0.008),respectively.The roll angle of mandibular body plane of the dental model surgery and computer aided simulation was 0.82°± 0.72° and 0.53°± 0.37° (P=0.028),respectively.The changes in computer aided simulation group were more obvious than that in the dental model surgery group,but the difference was not significant in the yaw angle of maxillary occlusal plane and the roll angle of maxillary occlusal plane between the two groups(P ＞ 0.05).Conclusions It was more effective to correct mnandibular asymmetry by computer aided simulation than dental model surgery.