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.

Objective:To develop an air transfer stretcher for severely injured patients,so as to meet the requirements of severely injured patients for rapid transport of aviation medical treatment.Methods:The guide rails of hatch of mainstream civil airliner models were analyzed through investigation.Based on the principles of modularization,integration and intelligence,a highly universal and portable aviation stretcher with the functions of rapid transport and life support was designed and developed.The design of the stretcher was verified through simulation analysis and calculation,as well as tests in laboratory,which should meet the requirements of the standards from China Civil Aviation Regulations(CCAR)-25.Results:The results of simulation analysis and tests of laboratory showed that the aviation transport stretcher,and the strength and stiffness of its structure reached to requirement of CCAR-25 standard,which was suit to the portable aviation evacuation of severely injured patients on civil airliners,and the rapid transfer between air and ground.It has the function of supporting life,and the aviation transport stretcher with high universality and convenience can enhance the safety and rescue capability of aviation evacuation system of medical treatment of aviation.Conclusion:The portable aviation stretcher with high-versatility that was researched and developed by this study can effectively solve the problems of life support,injury monitoring,and emergently rescue and treatment during the transport for severely injured patients,which improve the support ability of air-ground transportation for severely injured patients.

The air-ground transfer device for patients with serious injury is one kind of medical equipment and system that can realize the safe and efficient transfer for patients with serious injury between the air and the ground under scenarios of emergency medical rescue,which plays an important role in the process of aviation rescue.At present,a variety of air-to-ground transport devices for patients with serious injury have been developed abroad,such as the trauma life support and transportation system of United States,the medical transport aircraft of Israel and so on.In China,it has also been developed,such as general-purpose airborne stretcher supports,life support system for patients with serious injury in moving,cross-platform and etc..However,there are still many challenges in current research and development of air-to-ground transfer devices,including technical stability,intelligent level,the application of new materials and so on.Based on this,this paper systematically reviewed the domestic and international development status of air-to-ground transport devices for patients with serious injury,and analyzed the facing problems and technical challenges of these devices,and discussed their development trends in future.Through the research and analysis for existing devices,this study aimed to provide references for the research and development of air-to-ground transport devices for patients with serious injury,so as to improve the efficiency and quality of emergency medical rescue.

The air-ground transfer device for patients with serious injury is one kind of medical equipment and system that can realize the safe and efficient transfer for patients with serious injury between the air and the ground under scenarios of emergency medical rescue,which plays an important role in the process of aviation rescue.At present,a variety of air-to-ground transport devices for patients with serious injury have been developed abroad,such as the trauma life support and transportation system of United States,the medical transport aircraft of Israel and so on.In China,it has also been developed,such as general-purpose airborne stretcher supports,life support system for patients with serious injury in moving,cross-platform and etc..However,there are still many challenges in current research and development of air-to-ground transfer devices,including technical stability,intelligent level,the application of new materials and so on.Based on this,this paper systematically reviewed the domestic and international development status of air-to-ground transport devices for patients with serious injury,and analyzed the facing problems and technical challenges of these devices,and discussed their development trends in future.Through the research and analysis for existing devices,this study aimed to provide references for the research and development of air-to-ground transport devices for patients with serious injury,so as to improve the efficiency and quality of emergency medical rescue.

Objective:To develop an air transfer stretcher for severely injured patients,so as to meet the requirements of severely injured patients for rapid transport of aviation medical treatment.Methods:The guide rails of hatch of mainstream civil airliner models were analyzed through investigation.Based on the principles of modularization,integration and intelligence,a highly universal and portable aviation stretcher with the functions of rapid transport and life support was designed and developed.The design of the stretcher was verified through simulation analysis and calculation,as well as tests in laboratory,which should meet the requirements of the standards from China Civil Aviation Regulations(CCAR)-25.Results:The results of simulation analysis and tests of laboratory showed that the aviation transport stretcher,and the strength and stiffness of its structure reached to requirement of CCAR-25 standard,which was suit to the portable aviation evacuation of severely injured patients on civil airliners,and the rapid transfer between air and ground.It has the function of supporting life,and the aviation transport stretcher with high universality and convenience can enhance the safety and rescue capability of aviation evacuation system of medical treatment of aviation.Conclusion:The portable aviation stretcher with high-versatility that was researched and developed by this study can effectively solve the problems of life support,injury monitoring,and emergently rescue and treatment during the transport for severely injured patients,which improve the support ability of air-ground transportation for severely injured patients.

Objective:To explore the clinical application pathway of the CT generative adversarial networks (CTGANs) algorithm in mandibular reconstruction surgery, aiming to provide a valuable reference for this procedure.Methods:A clinical exploratory study was conducted, 27 patients who visited the Department of Oral and Maxillofacial Surgery, Xiangya Hospital of Central South University between January 2022 and January 2024 and required mandibular reconstruction were selected. The cohort included 16 males and 11 females, with the age of (46.6±11.5) years; among them, 7 cases involved mandibular defects crossing the midline. The CTGANs generator produced 100 images, and the mean squared error (MSE) was calculated for differences between any two generated images. Preoperative cone-beam CT data from 5 patients were used to construct a labeled test database, divided into groups: normal maxilla, normal mandible, diseased mandible, and noise (each group containing 70 cross-sectional images). The CTGANs discriminator was used to evaluate the loss values for each group, and one-way ANOVA and intergroup comparisons were performed. Using the self-developed KuYe multioutcome-option-network generation system (KMG) software, the three-dimensional (3D) completion area of the mandible under cone-beam CT was defined for the 27 patients. The CTGANs algorithm was applied to obtain a reference model for the mandible. Virtual surgery was then performed, utilizing the fibular segment to reconstruct the mandible and design the surgical expectation model. The second-generation combined bone-cutting and prebent reconstruction plate positioning method was used to design and 3D print surgical guides, which were subsequently applied in mandibular reconstruction surgery for the 27 patients. Postoperative cone-beam CT was used to compare the morphology of the reconstructed mandible with the surgical expectation model and the mandibular reference model to assess the three-dimensional deviation.Results:The MSE for the CTGANs generator was 2 411.9±833.6 (95% CI: 2 388.7-2 435.1). No significant difference in loss values was found between the normal mandible and diseased mandible groups ( P>0.05), while both groups demonstrated significantly lower loss values than the maxilla and noise groups ( P<0.001). All 27 patients successfully obtained mandibular reference models and surgical expectation models. In total, 14 162 negative deviation points and 15 346 positive deviation points were observed when comparing the reconstructed mandible morphology with the surgical expectation model, with mean deviations of -1.32 mm (95% CI:-1.33- -1.31 mm) and 1.90 mm (95% CI: 1.04-1.06 mm), respectively. Conclusions:The CTGANs algorithm is capable of generating diverse mandibular reference models that reflect the natural anatomical characteristics of the mandible and closely match individual patient morphology, thereby facilitating the design of surgical expectation models. This method shows promise for application in patients with mandibular defects crossing the midline.

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.
Humans ; Carcinoma, Squamous Cell/therapy* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/therapy* ; Head and Neck Neoplasms ; Tumor Microenvironment

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Objective:To compare the therapeutic effect of one-stage versus two-stage percutaneous transhepatic biliary fistulation lithotripsy in treatment of complex hepatolithiasis.Methods:A retrospective study was conducted on 145 patients with complex hepatolithiasis who were treated at the First Affiliated Hospital of Guangzhou Medical University between September 2013 and June 2018. There were 60 males and 85 females, aged 21 to 91 (56.5±14.1) years. According to the method of fistula establishment, patients were divided into the percutaneous transhepatic one-step biliary fistulation (PTOBF) group ( n=94) or the two-stage percutaneous transhepatic choledochoscopic lithotripsy (PTCSL) group ( n=51). The success rates of one-time puncture and fistula dilation, operation time of lithotripsy, operative conversion rate (PTCSL was converted to laparotomy and laparoscopic surgery), postoperative complications (including catheter dislodgement), residual stone rates and stone recurrence rates were compared between groups. Results:In the PTOBF group, operation time (105.8±43.6) min, success rate of one puncture 73.4% (69/94), and success rate of one fistula dilation 93.6% (88/94), the rate of operative conversion 0. All these results were significantly better than the corresponding results of the two-stage PTCSL group of (130.0±70.0) min, 54.9% (28/51), 68.6% (35/51), and 13.7%(7/51) respectively (all P<0.05). There were no significant differences in stone residual rate [17.0%(16/94) vs. 15.7% (8/51)] and stone recurrence rate [14.9%(14/94) vs. 17.6% (9/51)] between groups (both P>0.05). The postoperative complications rate was 7.4%(7/94) in PTOBF group, which was 39.2% (20/51) in two-stage PTCSL group (χ 2=22.02, P<0.001). The catheter dislodgement rate of PTOBF group was 2.1% (2/94), lower than that of two-stage PTCSL group 27.4% (14/51), the difference was statistically significant (χ 2=21.59, P<0.001). Conclusion:One-stage PTOBF and two-stage PTCSL were both safe and effective in treatment of complex hepatolithiasis. However, PTOBF had shorter operative times, lower catheter dislodgement and operative conversion rates than PTCSL.

Objective:To explore the relationship between level of urinary iodine excretion (UIE) before 131I treatment and excellent response (ER) in low-to-intermediate risk differentiated thyroid carcinoma (DTC) patients. Methods:A retrospective analysis was performed with 432 DTC patients (124 males, 308 females, age: (42.1±11.0) years) who were treated with 131I for the first time after total thyroidectomy from June 2017 to October 2018 in Department of Nuclear Medicine, the Second Hospital of Shandong University. All patients were divided into 4 groups: G1, group 1, UIE<50 μg/L; G2, group 2, 50 μg/L≤UIE<100 μg/L; G3, group 3, 100 μg/L≤UIE<200 μg/L; G4, group 4, UIE≥200 μg/L. Patients were given 131I with a fixed dose (3 700 MBq). Response was evaluated 6 to 8 months after 131I treatment: ER, indeterminate response (IDR), biochemical incomplete response (BIR), and structural incomplete response (SIR). χ2 test and Kruskal-Wallis rank sum test were used to analyze the data. The adjusted standardized residual (residual) and Cramer′s V between G1-G4 and different treatment reactions were calculated to judge the difference among groups. IDR, BIR and SIR were classified into non-ER (NER) group, and binary logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to find the influencing factors of treatment reactions. Results:There were 51.9%(41/79), 64.9%(98/151), 53.8%(63/117), 30.6%(26/85) patients achieved ER in G1-G4, and the proportion of G4 was significantly lower than that of G1-G3 ( χ2 values: 7.695-25.697, all P<0.05), and there was no significant difference among G1-G3 ( χ2 values: 0.072-3.667, all P>0.05). The UIE level of patients in ER, IDR, BIR, SIR group was 87.5(57.0, 129.0), 97.0(55.7, 211.5), 141.0(74.0, 231.0), 148.0(68.5, 221.0) μg/L( H=15.977, P=0.001), and there was significant difference between those of patients in ER and SIR groups ( χ2=8.729, P=0.019). There was a certain correlation between UIE levels and different treatment reactions (Cramer′s V=0.151, P=0.001). UIE (≥200 μg/L), gender and preablative stimulated thyroglobulin could be used as independent factors affecting ER ( Wald values: 4.029, 7.185, 56.301, all P<0.05). Conclusion:Among DTC patients with low-to-intermediate risk, 131I treatment does not affect ER when the UIE level is less than 200 μg/L, while 131I treatment should be performed carefully when the UIE level is more than 200 μg/L.