Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

With the advancement of space exploration missions,space station operations have entered a routine phase,where single-flight missions last up to six months.Previous studies indicate that the spaceflight environment severely compromises the immune system,increasing the susceptibility to diseases.As primary responders to pathogenic challenges,immune cells exhibit exceptional sensitivity to gravitational alterations and background ionizing radiation in space,with their dysfunction being a critical health risk.For innate immunity,the complex space environment disrupts macrophage polarization and phagocytosis,neutrophil chemotaxis and killing,natural killer(NK)cell cytotoxicity,and dendritic cell maturation,leading to functional impairment of innate immune defenses.For adaptive immunity,microgravity and radiation induce cellular immune dysregulation by suppressing T cell proliferative capacity and perturbing Th1/Th2/Treg subset balance,while simultaneously undermining humoral immunity through interference with B-lymphocyte protein synthesis,blockade of developmental maturation,and reduction of effector B cell populations.This review summarizes recent advances in understanding space environment-induced immune perturbations and protection options using traditional Chinese medicine,focusing on microgravity and radiation.It not only deciphers molecular mechanisms underpinning immune cell dysfunction but also provides a theoretical foundation and drug-targeting strategies for developing countermeasures against spaceflight-specific immune dysfunction.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.

Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.

Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.

Objective:To explore effect of Glioma-associated oncogene family zinc finger 1(GLI1)on hypoxia induced trans-formation of NR8383 to M1 phenotype and development of pulmonary hypertension(PH).Methods:Fifteen adult male Wistar rats were randomly divided into control group,hypoxia PH model group and hypoxic PH with GANT61 treatment group,with 5 rats in each group.PH related indexes of rats were detected by small animal ultrasound and right cardiac catheter experiment to determine effect of GLI1 specific inhibitor GANT61 on progression of PH.Pulmonary arterial thickness was measured by HE staining.α-SMA and M1 polarization markers TNF-α and IL-1β expressions were determined by immunohistochemistry.M1 polarization markers CD86 and TNF-α expressions were determined by immunofluorescence.GLI1 expression and NF-κB protein were detected by Western blot.mRNA expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 were detected by qRT-PCR.CHIP-PCR verified that GLI1 regulates NF-κB promoter activity.IL-12 content was detected by ELISA.Rat pulmonary artery smooth muscle cells proliferation was detected by CCK-8.Results:GLI1 inhibitor GANT61 could alleviate symptoms of PH in hypoxic rats(P<0.05).Compared with hypoxic group,inhibition of GLI1 reduced expressions of TNF-α and IL-1β in rat lung tissue(P<0.05).In cell experiments,hypoxia induced M1 polarization of NR8383 by up-regulating GLI1 to activate NF-κB pathway,GLI1 overexpression increased expressions of iNOS,CD86,TNF-α,IL-1β and IL-12 in M1 macrophages(P<0.05).NR8383 culture supernatants could stimulate pulmonary artery smooth muscle cell proliferation(P<0.05)and contribute to development of PH.Conclusion:Hypoxia activates NF-κB pathway by up-regulating GLI1 to induce M1 polarization of macrophages contributes to development of PH.