Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

Objective:To investigate the application value of cardiac magnetic resonance imaging(CMR) in evaluating the perioperative risk of surgical treatment in patients of coronary artery disease and heart failure with reduced ejection fraction.Methods:A total of 78 patients diagnosed with CAD and HFrEF who underwent CABG in Beijing Anzhen Hospital from January 2018 to October 2021 were retrospectively enrolled. All patients underwent CMR examination before CABG. The perioperative data of the two groups were compared, and the risk factors that may lead to perioperative MACCE were analyzed by LASSO regression. Then, logistic regression was used to establish a prediction model and internal validation was performed to evaluate the diagnostic efficiency and accuracy of the model by Bootstrap method. Results:There were 24 patients(30.8%) with perioperative MACCE and 54 patients(69.2%) without perioperative MACCE. LASSO regression was used to screen out three factors related to the outcome. Multivariate logistic regression analysis showed that LGE in the third and eighth segment of left ventricle and diastolic radial strain rate were independent risk factors for perioperative MACCE. The area under the curve of the prediction model constructed with CMR was 0.799(95% CI: 0.696-0.901), so the discrimination was good. The calibration curve showed that the prediction curve was basically fit to the standard curve, and the Hosmer- Lemeshow test P=0.797, indicating high prediction accuracy. Conclusion:CMR is a valuable test for evaluating perioperative risk in patients with coronary heart disease complicated with HFrEF. To establish the risk prediction model combined with CMR can provide some reference for the assessment of perioperative risk in these patients undergoing surgical treatment.

Objective:To investigate the application value of cardiac magnetic resonance imaging(CMR) in evaluating the perioperative risk of surgical treatment in patients of coronary artery disease and heart failure with reduced ejection fraction.Methods:A total of 78 patients diagnosed with CAD and HFrEF who underwent CABG in Beijing Anzhen Hospital from January 2018 to October 2021 were retrospectively enrolled. All patients underwent CMR examination before CABG. The perioperative data of the two groups were compared, and the risk factors that may lead to perioperative MACCE were analyzed by LASSO regression. Then, logistic regression was used to establish a prediction model and internal validation was performed to evaluate the diagnostic efficiency and accuracy of the model by Bootstrap method. Results:There were 24 patients(30.8%) with perioperative MACCE and 54 patients(69.2%) without perioperative MACCE. LASSO regression was used to screen out three factors related to the outcome. Multivariate logistic regression analysis showed that LGE in the third and eighth segment of left ventricle and diastolic radial strain rate were independent risk factors for perioperative MACCE. The area under the curve of the prediction model constructed with CMR was 0.799(95% CI: 0.696-0.901), so the discrimination was good. The calibration curve showed that the prediction curve was basically fit to the standard curve, and the Hosmer- Lemeshow test P=0.797, indicating high prediction accuracy. Conclusion:CMR is a valuable test for evaluating perioperative risk in patients with coronary heart disease complicated with HFrEF. To establish the risk prediction model combined with CMR can provide some reference for the assessment of perioperative risk in these patients undergoing surgical treatment.

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) as a preoperative planning strategy for lymphaticovenous anastomosis (LVA) in improving the quality of LVA and the outcome of short-term limb volume reduction in patients with secondary upper limb lymphedema.Methods:Patients with breast cancer-related upper extremity lymphedema who underwent LVA at the Department of General Surgery Cancer Center Division of Breast Surgery of Zhejiang Provincial People’s Hospital from August 2021 to August 2023 were enrolled retrospectively. According to whether preoperative ultrasound lymphography was performed, the patients were divided into CEUS assisted group and control group. In the CEUS assisted group, preoperative CEUS lymphography combined with high-frequency ultrasound color Doppler imaging was utilized for precise localization of lymphatic vessels and recipient veins, as well as surgical target planning for LVA. In the control group, preoperative indocyanine green lymphography was employed to guide surgical exploration. Mann-Whitney U test was used to compare the number of LVA surgical exploration incisions per limb and the number of successful anastomoses per limb between the two groups. The success rate of anastomosis (total number of successful anastomoses/total number of surgical exploration incisions) was compared by the chi-square test. The duration of single anastomosis, mean arm circumference, and the difference between preoperative and postoperative mean arm circumference were compared by independent sample t-test. Paired-sample t-test was used to compare the improvement of the mean arm circumference of the operated limb of the two groups after 3 months of follow-up. P < 0.05 was considered statistically significant. Results:A total of 47 female patients were enrolled, including 27 patients in the CEUS assisted group, with an average age of (57.1±9.0) years and a median edema course of 2 years. There were 20 cases in the control group, with an average age of (58.1±9.6) years and a median duration of edema of 2 years. The CEUS group, compared with the control group, exhibited a higher number of surgical exploration incisions per limb [6.0 (4.0, 7.0) cases vs. 5.0 (3.0, 6.0) cases], a greater number of successful anastomoses per limb [5.0 (3.0, 6v0) cases vs. 3.0 (2.0, 3.0) cases], and a significantly increased overall success rate of anastomosis [82.8% (125/151) vs. 61.4% (54/88)]. Additionally, there was a significant increase in the preoperative and postoperative mean arm circumference difference [(6.2±3.3) cm vs. (3.9±1.9) cm]. The duration of single anastomosis was significantly shortened [(57.4±16.0) min vs. (92.8±18.5) min], with statistically significant differences observed in all comparisons (all P < 0.05). The preoperative and postoperative mean arm circumference were compared between the CEUS group [(31.4±4.6) cm vs. (25.3±4.7) cm] and the control group [(31.3±4.3) cm vs. (27.5±3.8) cm], respectively, with statistically significant differences observed in both groups (both P < 0.01). Conclusion:CEUS lymphography, as a preoperative planning strategy for LVA, can significantly increase the number and success rate of LVA anastomosis in patients with secondary upper limb lymphedema, shorten the duration of single anastomosis, and improve the short-term effect of limb volume reduction after LVA.

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) as a preoperative planning strategy for lymphaticovenous anastomosis (LVA) in improving the quality of LVA and the outcome of short-term limb volume reduction in patients with secondary upper limb lymphedema.Methods:Patients with breast cancer-related upper extremity lymphedema who underwent LVA at the Department of General Surgery Cancer Center Division of Breast Surgery of Zhejiang Provincial People’s Hospital from August 2021 to August 2023 were enrolled retrospectively. According to whether preoperative ultrasound lymphography was performed, the patients were divided into CEUS assisted group and control group. In the CEUS assisted group, preoperative CEUS lymphography combined with high-frequency ultrasound color Doppler imaging was utilized for precise localization of lymphatic vessels and recipient veins, as well as surgical target planning for LVA. In the control group, preoperative indocyanine green lymphography was employed to guide surgical exploration. Mann-Whitney U test was used to compare the number of LVA surgical exploration incisions per limb and the number of successful anastomoses per limb between the two groups. The success rate of anastomosis (total number of successful anastomoses/total number of surgical exploration incisions) was compared by the chi-square test. The duration of single anastomosis, mean arm circumference, and the difference between preoperative and postoperative mean arm circumference were compared by independent sample t-test. Paired-sample t-test was used to compare the improvement of the mean arm circumference of the operated limb of the two groups after 3 months of follow-up. P < 0.05 was considered statistically significant. Results:A total of 47 female patients were enrolled, including 27 patients in the CEUS assisted group, with an average age of (57.1±9.0) years and a median edema course of 2 years. There were 20 cases in the control group, with an average age of (58.1±9.6) years and a median duration of edema of 2 years. The CEUS group, compared with the control group, exhibited a higher number of surgical exploration incisions per limb [6.0 (4.0, 7.0) cases vs. 5.0 (3.0, 6.0) cases], a greater number of successful anastomoses per limb [5.0 (3.0, 6v0) cases vs. 3.0 (2.0, 3.0) cases], and a significantly increased overall success rate of anastomosis [82.8% (125/151) vs. 61.4% (54/88)]. Additionally, there was a significant increase in the preoperative and postoperative mean arm circumference difference [(6.2±3.3) cm vs. (3.9±1.9) cm]. The duration of single anastomosis was significantly shortened [(57.4±16.0) min vs. (92.8±18.5) min], with statistically significant differences observed in all comparisons (all P < 0.05). The preoperative and postoperative mean arm circumference were compared between the CEUS group [(31.4±4.6) cm vs. (25.3±4.7) cm] and the control group [(31.3±4.3) cm vs. (27.5±3.8) cm], respectively, with statistically significant differences observed in both groups (both P < 0.01). Conclusion:CEUS lymphography, as a preoperative planning strategy for LVA, can significantly increase the number and success rate of LVA anastomosis in patients with secondary upper limb lymphedema, shorten the duration of single anastomosis, and improve the short-term effect of limb volume reduction after LVA.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

OBJECTIVE To prepare Neuritic acid oral emulsion ，to optimize its formulation and preparation technology ，and to investigate its stability. METHODS Neuritic acid oral emulsion was prepared by mechanical method. On the basis of single factor experiment ，the appearance ，centrifugal stability ，centrifugal stability constant （Ke）and particle size of the emulsion as indexes，the formulation was optimized by orthogonal design ，taking the dosage of oleic acid ，octylphenol polyoxyethylene ether-10 and propylene glycol as factors ，the preparation technology was optimized by taking emulsification temperature ，shear time，pressure of high-pressure homogenization and cycle times of high-pressure homogenization as factors. The content of neuritic acid was determined by high performance liquid chromatography. The stability of Neuritic acid oral emulsion was investigated by high temperature test ，accelerated test and long-term test. RESULTS The optimal formulation and preparation technology were as follows：neuritic acid of 1 g，oleic acid of 5％ ，octylphenol polyoxyethylene ether- 10 of 4％ ，propylene glycol of 2％ ， emulsification temperature of 60 ℃ ，shear time of 2 min，homogenization pressure of 40 MPa and cycle times of twice. After three experiments ，the average particle size of Neuritic acid oral emulsion was 158.05 nm（RSD＝1.58％，n＝3），the average Ke was 0.39（RSD＝1.49％，n＝3），and the appearance was uniform milky white ，there was no stratification. The results of high temperature test showed that Neuritic acid oral emulsion was prone to stratification in high temperature environment ，and the content of neuritic acid increased. The results of accelerated test and long-term test showed that there was no significant change in the appearance or the content of neuritic acid when Neuritic acid oral emulsion was placed at room temperature for 6 months. CONCLUSIONS The formulation and preparation technology are stable and feasible ，and can be used for the preparation of Neuritic acid oral emulsion. Neuritic acid oral emulsion should not be placed in high temperature environment. It has good stability at room temperature for 6 months.

Objective To investigate the occurrence of deep venous thrombosis (DVT) in the perioperative period of patients with fracture distal to the knee,so that clinicians have a better understanding of the occurrence of DVT in the perioperative period of the fracture distal to the knee.Methods A retrospective analysis of the clinical data of 365 patients with distal knee fractures who underwent surgery in the Department of Orthopaedics Trauma,Xi'an Jiaotong University Medical College Red Cross Hospital from June 2014 to March 2018 was conducted.There were 213 males and 152 females,aged (45.05 ± 15.24) years,with an age range of 17-83 years.Classification of fracture sites:177 cases of tibiofibular shaft fracture,130 cases of ankle fracture,and 58 cases of foot fracture.According to whether thrombosis occurred or not,the patients were divided into thrombotic group and non-thrombotic group before and after operation.There were 66 patients with thrombosis before operation,299 patients without thrombosis before operation,88 patients with thrombosis after operation,and 277 patients without thrombosis after operation.The incidence of thrombosis and the location of the thrombus were recorded.The sex,age,fracture site,ASA score,operation time,the time from injury to admission,the time from injury to surgery,intraoperative tourniquet time,intraoperative blood transfusion volume,intraoperative blood loss,intraoperative transfusion volume,hemoglobin volume at admission and 1 day after operation,D-dimer level at admission and 1 day after operation,multiple injuries,chronic hepatitis and medical diseases were analyzed.The measuremernt data of normal distribution and homogeneity of variance were expressed as mean ± standard deviation (Mean ± SD),the t test was used for comparison between two groups.The comparison of count data was performed by x2 test or Fisher exact probability method,and multivariate logistic regression analysis was performed on the risk factors affecting the occurrence of DVT in both lower extremities.Results The preoperative DVT rate was 18.1％ (66/365).In patients with thrombosis,distal thrombosis accounted for 93.94％ (62/66),and mixed thrombosis accounted for 6.06％ (4/66).The incidence of postoperative DVT was 24.1％ (88/365).In patients with thrombosis,distal thrombosis accounted for 94.32％ (83/88),proximal thrombosis accounted for 1.14％ (1/88),and mixed thrombus accounted for 4.55％ (4/88).Fracture site,ASA score,operation time,intraoperative tourniquet time,intraoperative blood transfusion volume,intraoperative blood loss,intraoperative transfusion volume were not statistically significant(P ＞0.05).Age ≥ 40 years (OR =2.691,95％ CI:1.422-5.093,P =0.002),the time from injury to admission ＞ 3 days (OR =1.927,95 ％ CI:1.072-3.463,P =0.028)were independent risk factors for DVT formation in fracture distal to the knee before operation.Age ≥ 40 years (OR =3.925,95 ％ CI:2.161-7.129,P =0.000),the time from injury to surgery ＞ 5 days (OR =1.835,95 ％ CI:1.080-3.119,P =0.025),D-dimer level at 1 day after operation (OR =1.191,95％ CI:1.096-1.293,P =0.000),combined with multiple injuries (OR =1.981,95％ CI:1.006-3.902,P =0.048),combined with coronary atherosclerotic heart disease (OR =2.692,95％ CI:1.112-6.517,P =0.028) were independent risk factor for DVT formation after operation for fracture distal to the knee.Conclusions The occurrence of DVT before and after the fracture of the knee is mainly caused by distal thrombosis,and proximal thrombosis also occurs.Those patients aged≥40 years,combined with multiple injuries and coronary heart disease,should focus on preventing the occurrence of DVT.After the injury,the patient is immediately admitted to the hospital for DVT screening,and when the general condition allowed,shortening the preoperative waiting time can reduce the occurrence of DVT.

OBJECTIVE To summarize the clinical features of the acquired immunodeficiency syndrome-related Kaposi's sarcoma(AIDS-KS) in head and neck. METHODS The clinical data of 20 inpatients with AIDS-KS in head and neck from June 2009 to September 2016 in Beijing Ditan Hospital were retrospectively analyzed. RESULTS All 20 patients were male, median age 38.50±10.98. One case was Manchu, 1 case was of Uygur, and others were Han nationality. There were 7 cases with homosexuality history, 2 cases with blood transfusion history, and 1 case with prostitution history. Mass in head and face was the first symptom in 10 cases. The head and neck skin and mucosa were involved, including 2 cases with nasal mucosa involvement, 4 cases with auricle skin involvement, 8 cases with oral mucosal involvement, 3 cases with facial skin involvement, 1 case with neck skin involvement, 1 case with eyelid conjunctiva involvement. Four cases had disseminated lesions. When diagnosed, the CD4+T lymphocyte were 52.55±47.87/mm3. The CD4+T were less than 200/mm3 in all of the patients, including CD4+T＜50/mm3 in 15 cases(75％). After treatment with highly active antiretroviral therapy combined with or without chemotherapy, 12 cases were discharged. Eight cases died due to respiratory failure or septic shock or other reasons. CONCLUSION Kaposi's sarcoma of the head and neck might be the first visit of AIDS patients. Some of the patients get partial remission after highly active antiretroviral therapy and the overall prognosis is poor.