Objective : To establish an interleukin-1β (Il-1β) induced inflammatory model of rat articular chondro- cytes (ACs) , and to investigate the relationship between the expression of lysine acetyltransferase 7 (KAT7) under inflammatory stimulation and the senescence of ACs. Methods: Primary ACs were obtained by digestion of rat knee cartilage with collagenase type Ⅱ and identified. The inflammatory model of ACs was induced by IL-1β . KAT7 was over-expressed or knocked down in ACs by adeno-associated virus infection or small interfering RNA transfection , respectively. A negative control group was set up. Transwell assay was used to detect cell migration ability. Senes- cent cells were stained with senescence-associated β-galactosidase (SA-β-Gal) . Western blot ( WB) was used to detect the protein expression levels of KAT7 , collagen type II (Col Ⅱ ) , matrix metalloproteinase 13 (MMP13) , tumor protein p53 (p53) and cyclin-dependent kinase inhibitor 1A (p21) . The cells of negative control group and KAT7 over-expression group were performed for RNA sequencing , and WB was used to verify the related signaling pathways obtained by Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Results: Compared with the control group , the SA-β-Gal staining was enhanced , the protein expression of Col Ⅱ decreased , the pro- tein expression of MMP13 and p53 increased , the cell migration ability decreased , and the expression of KAT7 also increased in the ACs of rats after IL-1β stimulation. Compared with the negative control group , the SA-β-Gal stai- ning was enhanced , the protein expression of Col Ⅱ decreased , the protein expression of MMP13 , p53 and p21 in- creased , and the cell migration ability decreased in the KAT7 over-expression group. Compared with the negative control group , the SA-β-Gal staining was weakened , the protein expression of Col Ⅱ increased , the protein expres- sion of MMP13 , p53 and p21 decreased , and the cell migration ability was enhanced in the KAT7 knockdown inflammatory model of ACs. KEGG enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway was activated. Compared with the negative control group , the relative protein ex⁃pression levels of phosphorylated protein kinase B (p⁃AKT)/AKT and phosphorylated mammalian target of rapamy⁃cin (p⁃mTOR)/mTOR in KAT7 over⁃expression group increased. The relative protein expression levels of p ⁃AKT/AKT and p ⁃mTOR/mTOR in KAT7 knockdown cells decreased. Conclusion Rat ACs with high expression of KAT7 exhibit senescence and osteoarthritis phenotype , and the mechanism may be related to the activation of PI3K/AKT/mTOR signaling pathway by KAT7.

Wet age-related macular degeneration(wARMD)emerges as a primary contributor to irreversible vision impairment in the aging demographic. In clinical practice, anti-vascular endothelial growth factor(VEGF)therapies exhibit pronounced success in managing wARMD. However, in the actual clinical application, there are significant individual differences in the prognosis of anti-VEGF drug therapy, and some patients show poor response to the treatment, which may be related to the morphological differences of retinal layers in macular area, genetics, systemic conditions and other factors. It will help develop a more rational and individualized treatment plan to judge the prognosis of patients according to their different clinical manifestations in advance, so as to reduce overtreatment and the risk of retinal damage. In recent years, most studies on treatment response mainly focus on fundus morphology, genetics and so on. In this study, the relevant factors affecting adverse response to wARMD were reviewed, aiming to provide with more accurate treatment and prognostic monitoring programs for clinicians.

Objective To investigate the effect of LAG-3 deficiency (LAG3^-/-) on natural killer (NK) cell function and hepatic fibrosis in mice infected with Echinococcus multilocularis. Methods C57BL/6 mice, each weighing (20 ± 2) g, were divided into the LAG3^-/- and wild type (WT) groups, and each mouse in both groups was inoculated with 3 000 E. multilocularis protoscoleces via the hepatic portal vein. Mouse liver and spleen specimens were collected 12 weeks post-infection, sectioned and stained with sirius red, and the hepatic lesions and fibrosis were observed. Mouse hepatic and splenic lymphocytes were isolated, and flow cytometry was performed to detect the proportions of hepatic and splenic NK cells, the expression of CD44, CD25 and CD69 molecules on NK cell surface, and the secretion of interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin (IL)-4, IL-10 and IL-17A. Results Sirius red staining showed widening of inflammatory cell bands and hyperplasia of fibrotic connective tissues around mouse hepatic lesions, as well as increased deposition of collagen fibers in the LAG3-/-group relative to the WT group. Flow cytometry revealed lower proportions of mouse hepatic (6.29% ± 1.06% vs. 11.91% ± 1.85%, P < 0.000 1) and splenic NK cells (4.44% ± 1.22% vs. 5.85% ± 1.10%, P > 0.05) in the LAG3^-/- group than in the WT group, and the mean fluorescence intensity of CD44 was higher on the surface of mouse hepatic NK cells in the LAG3^-/- group than in the WT group (t = −3.234, P < 0.01), while no significant differences were found in the mean fluorescence intensity of CD25 or CD69 on the surface of mouse hepaticNK cells between the LAG3^-/- and WT groups (both P values > 0.05). There were significant differences between the LAG3^-/- and WT groups in terms of the percentages of IFN-γ (t = −0.723, P > 0.05), TNF-α (t = −0.659, P > 0.05), IL-4 (t = −0.263, P > 0.05), IL-10 (t = −0.455, P > 0.05) or IL-17A secreted by mouse hepatic NK cells (t = 0.091, P > 0.05), and the percentage of IFN-γ secreted by mouse splenic NK cells was higher in the LAG3^-/- group than in the WT group (58.40% ± 1.64% vs. 50.40% ± 4.13%; t = −4.042, P < 0.01); however, there were no significant differences between the two groups in terms of the proportions of TNF-α (t = −1.902, P > 0.05), IL-4 (t = −1.333, P > 0.05), IL-10 (t = −1.356, P > 0.05) or IL-17A secreted by mouse splenic NK cells (t = 0.529, P > 0.05). Conclusions During the course of E. multilocularis infections, LAG3^-/- promotes high-level secretion of IFN-γ by splenic NK cells, which may participate in the reversal the immune function of NK cells, resulting in aggravation of hepatic fibrosis.

Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor microenvironment (TME). They have been shown to play an important immunosuppressive role in the development of TME and promote tumor immune escape, growth and metastasis. It is a current research hotspot to regulate the functional polarization of TAMs through trained immunity (metabolic reprogramming, epigenetic remodeling) to affect the occurrence and development of tumors. Therefore, in-depth research in this field not only presents a more comprehensive perspective on the pathogenesis of immune-mediated diseases, but also can provide new strategies for clinical anti-tumor immunotherapy. This paper outlines the origin of TAMs and the phenotypes and mechanisms of TAMs polarization, discusses the mechanisms by which metabolic reprogramming and epigenetic remodeling regulate TAMs, summarizes the regulation of TAMs activation and polarization by them, and provides an overview of the progress in TAMs at the current stage of clinical practice, hoping to provide reference for the development of new immunoprevention and treatment strategies.

Objective:To assess the effectiveness of robot-assisted mandibular angle osteotomy using the FACE-Q questionnaire.Methods:A randomized controlled clinical study was conducted in the Second Affiliated Hospital of Zhengzhou University from January 2022 to June 2023. Patients with mandibular angle hypertrophy aged 18 to 40 years old were recruited as research objects, and a randomization and supply management system (Clinflash IRT 2.0) was used to randomly assign the experimental group and control groups in a 1∶1 ratio. Before surgery, Mimics 21.0 software was used to plan the surgical approach and determine the osteotomy plane based on the head CT data of the two groups. The experimental group underwent robot-assisted mandibular angle osteotomy according to the preoperative osteotomy plan, while the control group underwent traditional manual mandibular angle osteotomy according to the preoperative design. Six months after surgery, patients filled in the FACE-Q craniofacial module scale to evaluate the surgical effect, covering 12 indicators in four aspects: appearance satisfaction (including face, jaw and smile), health-related quality of life (including appearance anxiety, psychology, social interaction and speech), postoperative function (including breathing, diet, face and pronunciation), and adverse reactions. Each indicator was scored from 0 to 100 points, with higher scores indicating better evaluation. SPSS 27.0 software was used to process the data, and the measurement data of normal distribution were expressed by Mean±SD, and t-test was used for comparison between groups. The measurement data of non-normal distribution were expressed by M ( Q1, Q3), and Mann-Whitney U test was used for the comparison between groups. P<0.05 was considered statistically significant. Results:The experimental group included 20 patients, 3 males and 17 females, with an age of (27.6±4.4) years (19 to 38 years); the control group included 20 patients, 4 males and 16 females, with an age of (27.4±3.9) years (19 to 35 years). Six months postoperatively, all patients in both groups had good wound healing, and the mandibular hypertrophy was improved to varying degrees. There were no complications such as facial paralysis, facial deviation, or pain. The FACE-Q questionnaire results showed that in terms of appearance satisfaction, the scores for the three indicators of face, mandible, and smile in the experimental group were (72.2±11.7), 86(77, 92), and (63.2±9.5) points, respectively, all higher than those in the control group, which were (49.2±9.9), 43(35.5, 50), and (48.0±7.7) points, respectively, with statistically significant differences ( P<0.01 for all); in terms of health-related quality of life, except for speech, the scores for the three indicators of appearance anxiety, psychology, and social interaction in the experimental group were higher than those in the control group [(71.0±11.5) points vs.(49.1±10.3) points, (66.7±11.7) points vs.(45.4±10.5) points, (75.0±9.7)points vs.(56.4±8.5) points], with statistically significant differences ( P<0.01 for all); in terms of postoperative function, the score for eating in the experimental group was higher than that in the control group [(83.4±10.7) points vs.(71.0±14.9) points] ( P<0.01), but there were no statistically significant differences in the other three indicators ( P>0.05 for all); in terms of adverse reaction, there was no statistically significant difference between the two groups ( P>0.05). Conclusion:The result of the FACE-Q questionnaire assessment confirmed that robot-assisted mandibular angle osteotomy can significantly improve patients’ postoperative appearance satisfaction, psychological state, social adaptability, and eating function without increasing the incidence of complications.

Objective:To assess the effectiveness of robot-assisted mandibular angle osteotomy using the FACE-Q questionnaire.Methods:A randomized controlled clinical study was conducted in the Second Affiliated Hospital of Zhengzhou University from January 2022 to June 2023. Patients with mandibular angle hypertrophy aged 18 to 40 years old were recruited as research objects, and a randomization and supply management system (Clinflash IRT 2.0) was used to randomly assign the experimental group and control groups in a 1∶1 ratio. Before surgery, Mimics 21.0 software was used to plan the surgical approach and determine the osteotomy plane based on the head CT data of the two groups. The experimental group underwent robot-assisted mandibular angle osteotomy according to the preoperative osteotomy plan, while the control group underwent traditional manual mandibular angle osteotomy according to the preoperative design. Six months after surgery, patients filled in the FACE-Q craniofacial module scale to evaluate the surgical effect, covering 12 indicators in four aspects: appearance satisfaction (including face, jaw and smile), health-related quality of life (including appearance anxiety, psychology, social interaction and speech), postoperative function (including breathing, diet, face and pronunciation), and adverse reactions. Each indicator was scored from 0 to 100 points, with higher scores indicating better evaluation. SPSS 27.0 software was used to process the data, and the measurement data of normal distribution were expressed by Mean±SD, and t-test was used for comparison between groups. The measurement data of non-normal distribution were expressed by M ( Q1, Q3), and Mann-Whitney U test was used for the comparison between groups. P<0.05 was considered statistically significant. Results:The experimental group included 20 patients, 3 males and 17 females, with an age of (27.6±4.4) years (19 to 38 years); the control group included 20 patients, 4 males and 16 females, with an age of (27.4±3.9) years (19 to 35 years). Six months postoperatively, all patients in both groups had good wound healing, and the mandibular hypertrophy was improved to varying degrees. There were no complications such as facial paralysis, facial deviation, or pain. The FACE-Q questionnaire results showed that in terms of appearance satisfaction, the scores for the three indicators of face, mandible, and smile in the experimental group were (72.2±11.7), 86(77, 92), and (63.2±9.5) points, respectively, all higher than those in the control group, which were (49.2±9.9), 43(35.5, 50), and (48.0±7.7) points, respectively, with statistically significant differences ( P<0.01 for all); in terms of health-related quality of life, except for speech, the scores for the three indicators of appearance anxiety, psychology, and social interaction in the experimental group were higher than those in the control group [(71.0±11.5) points vs.(49.1±10.3) points, (66.7±11.7) points vs.(45.4±10.5) points, (75.0±9.7)points vs.(56.4±8.5) points], with statistically significant differences ( P<0.01 for all); in terms of postoperative function, the score for eating in the experimental group was higher than that in the control group [(83.4±10.7) points vs.(71.0±14.9) points] ( P<0.01), but there were no statistically significant differences in the other three indicators ( P>0.05 for all); in terms of adverse reaction, there was no statistically significant difference between the two groups ( P>0.05). Conclusion:The result of the FACE-Q questionnaire assessment confirmed that robot-assisted mandibular angle osteotomy can significantly improve patients’ postoperative appearance satisfaction, psychological state, social adaptability, and eating function without increasing the incidence of complications.

Bone graft materials have mixed effects of bone repair in the field of oral maxillofacial surgery. The qualitative analyses performed by previous studies imply that autogenous odontogenic materials and autogenous bone have similar effects on bone repair in clinical jaw bone transplantation. This retrospective systematic assessment and network metaanalysis aimed to analyze the best effect of clinical application of autogenous odontogenic materials and autogenous, allogeneic, and xenogeneic bone grafts in bone defect repair. A systematic review was performed by searching the PubMed, Cochrane Library, and other journal databases using selected keywords and Medical Subject Headings search terms. 10 Papers (n = 466) that met the inclusion criteria were selected. The assessment of heterogeneity did not reveal any overall statistical difference or heterogeneity (P = 0.051 [ 0.05), whereas the comparison between autogenous and allogeneic bone grafts revealed local heterogeneity (P = 0.071 0.1). Risk of bias revealed nine unclear studies and one high-risk study. The overall consistency was good (P = 0.065 [ 0.05), and the local inconsistency test did not reveal any inconsistency. The publication bias was good. The confidence regarding the ranking of bone graft materials after GRADE classification was moderate. The effects on bone repair in the descending order were as follows: autogenous odontogenic materials, xenogeneic bone, autogenous bone, and allogeneic bone. This result indicates that the autogenous odontogenic materials displayed stronger effects on bone repair compared to other bone graft materials. Autogenous odontogenic materials have broad development prospects in oral maxillofacial surgery.

Objective:To describe a prospective study of pre-operative tumor-bed boost performed at the 1.5 T MR-Linac in combination with adjuvant whole breast irradiation, and a first case, with an accentuation on clinical feasibility and safety.Methods:A phase II, single arm study recruiting early stage patients follows a paradigm that first boosts the tumor bed and then undergoes breast conservative surgery in 2 weeks, and last irradiates the whole breast in 6 weeks. The primary endpoint is ≥ grade 2 acute breast toxicity. A 43 years old patient affected by a breast carcinoma, not special type of the right-sided lateral quadrant, staged cT 2N 0M 0, was planned and treated. The dose, 8 Gy for one time, was calculated by Monaco on CT simulation images. Both the air electron stream effect (ESE) and the electron return effect (ERE) at the presence of 1.5 T magnetic field were evaluated. During the pre-treatment evaluation, we carried out adaptation-to-position adjustment. Results:The normal organ dosimetry is within toleration. The Dmax to the skin, the chin and the right upper arm was 8.44 Gy, 28.5 cGy and 17.8 cGy, respectively. There was no increased toxicity from ERE and ESE, and the treatment was well tolerated without > grade 1 acute toxicity. The patient received breast conservative surgery on day 7 without delayed wound healing.Conclusions:This is the first case successfully treated within a clinical trial by pre-operative tumor-bed boost under 1.5 T MR-Linac in our institution. More participants are needed to validate and optimize the paradigm.

Objective:To analyze locoregional recurrence (LRR) pattern of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, with and without adjuvant radiotherapy (RT). Methods:A total of 5442 eligible patients with breast cancer from 12 Chinese centers were included. The LRR sites and the effect of RT at different sites on recurrence in patients with and without RT were analyzed. The Kaplan-Meier method was used to calculate the cumulative LRR rate, and the difference was compared by the log-rank test.Results:With a median follow-up time of 63.8 months for the entire cohort, 395 patients developed LRR. The chest wall and supraclavicular fossa were the most common LRR sites, regardless of RT or molecular subtypes. The 5-year chest wall recurrence rates for patients with and without chest wall irradiation were 2.5% and 3.8%( P=0.003); the 5-year supraclavicular lymph nodal recurrence rates for patients with and without supraclavicular fossa irradiation were 1.3% and 4.1%( P<0.001); the 5-year axillary recurrence-free rates for patients with and without axillary irradiation were 0.8% and 1.5%( HR=0.31, 95% CI: 0.04-2.23, P=0.219); and the 5-year internal mammary nodal recurrence-free rates for patients with and without internal mammary nodal irradiation were 0.8% and 1.5%( HR=0.45, 95% CI: 0.11-1.90, P=0.268). Conclusions:The chest wall and supraclavicular fossa are the most common LRR sites of patients with pT 1-2N 1 breast cancer after modified radical mastectomy, which is not affected by adjuvant RT or molecular subtypes. The chest wall and supraclavicular fossa irradiation significantly reduce the risk of recurrence in the corresponding area. However, axillary and internal mammary nodal irradiation has no impact on the risk of recurrence in the corresponding area.

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68⁺ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.