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.

To systematically analyzed the reporting status of core elements in publicly available clinical practice guideline(hereafter referred to as "guideline") protocols published domestically and internationally over the past decade, identified existing problems, and provided evidence to inform the standardized writing and publication of future guideline protocols.

Patients with sudden deafness encounter greater psychological challenges and communication barriers after experiencing sudden hearing loss， and traditional medical models often fail to adequately address their unique needs. This paper analyzed the current situation of emotional and behavioral changes in patients with sudden deafness， and the gap between their expectations and the reality of medical care. From the perspective of narrative medicine， the theory and characteristics of the reconstruction of the doctor-patient relationships in patients with sudden deafness were explored. The results showed that narrative medicine can enhance patients’ emotional resonance and understanding， improve the efficiency and quality of doctor-patient communication， promote the formulation of personalized treatment plans， and enhance treatment adherence and satisfaction. Based on these results， strategies and pathways for the reconstruction of doctor-patient relationships for patients with sudden deafness were proposed， including building empathetic bridges and tapping into mechanisms of emotional resonance within narrative medicine； optimizing communication strategies and promoting the application of narrative techniques in doctor-patient dialogues； connecting narrative pathways and advocating the exploration of stories and strategies in personalized treatments； as well as facilitating treatment adherence and making full use of the psychodynamic effects of narrative medicine. Narrative medicine， as a patient-centered medical practice， can effectively promote the reconstruction of doctor-patient relationships， enhance treatment effectiveness， and offer a more humane treatment experience for patients.

With the continuous advancement of internet technology and the improvement of internet literacy among the general population, the concept of online-offline integration in internet hospitals has gradually gained acceptance and has been applied and developed both domestically and internationally. In thoracic surgery, the applicability of this model lies in enhancing efficiency and delivering comprehensive, diversified, and personalized medical services to address complex and severe conditions. However, challenges such as hardware limitations and diagnostic/treatment risks persist during the implementation of internet hospitals. Through future in-depth and localized research, the online-offline integration of internet hospitals is expected to undergo further development and refinement. This progress will facilitate its integration into clinical practice in thoracic surgery, ultimately providing patients with improved medical care services.

Diabetic retinopathy(DR)is one of the most common and severe microvascular complications in diabetic patients and has become one of the leading causes of blindness worldwide. With the continuous rise in the prevalence of diabetes, in-depth exploration of the pathogenesis of DR and effective intervention measures is of great clinical significance. The mechanistic target of rapamycin(mTOR), as a protein kinase, is widely involved in cellular processes such as growth, metabolism, and autophagy. Research indicates that the mTOR signaling pathway plays a crucial regulatory role in the pathological progression of DR, and its abnormal activity can disrupt retinal cell autophagy function, thereby accelerating cellular damage and disease progression. Autophagy, as an important regulatory mechanism for cellular homeostasis, maintains cellular functional balance by clearing damaged organelles and protein aggregates. This article provides a systematic review of the structural and functional aspects of the mTOR signaling pathway, the molecular regulatory mechanisms of autophagy, and their roles in retinal pathological changes. By summarizing current research findings, the article aims to clarify the key regulatory role of the mTOR-autophagy axis in DR, providing theoretical support for elucidating the molecular pathogenesis of DR and offering potential targets and research directions for developing novel targeted therapeutic strategies, thereby holding significant scientific and clinical value.

OBJECTIVE To construct a classification prediction model for vancomycin blood concentration， and to optimize its precision dosing strategies. METHODS Patient records meeting inclusion criteria were extracted from the Medical Information Mart for Intensive Care database. Following data cleaning and preprocessing， a final cohort of 9 902 patient was analyzed. Feature selection was performed through correlation analysis and the Boruta feature selection algorithm. Vancomycin blood concentrations were discretized into three categories based on clinical therapeutic windows： low （＜10 μg/mL）， intermediate （10-20 μg/mL）， and high （≥20 μg/mL）. Six machine learning algorithms were employed to construct classification models： tabular prior-data fitted network （TabPFN）， logistic regression （LR）， random forest （RF）， extreme gradient boosting （XGBoost）， support vector machine （SVM）， K-nearest neighbors （KNN）. Model performance was evaluated using 10-fold cross-validation （10-CV）， with primary metrics including： accuracy， balanced accuracy， precision macro， recall macro， macro F1， area under the receiver operating characteristic curve （OvR-AUC）. Shapley Additive Explanations （SHAP） was adopted to analyze the direction and magnitude of the impact that different features had on the model’s predictive outcomes. RESULTS The results showed that the RF and TabPFN models performed the best （with accuracy of 0.741 4 and 0.737 7， and OvR-AUC of 0.907 0 and 0.895 8， respectively）. XGBoost model exhibited moderate performance， while LR， SVM， and KNN models demonstrated relatively poor performance. Confusion matrix heatmap analysis revealed that both RF and TabPFN achieved higher accuracy in predicting high- concentration cases but exhibited slightly lower performance in the low and medium concentration categories. Bootstrap with 10-CV revealed that the RF model demonstrated stable performance across various evaluation metrics （accuracy： 0.741 4； balanced accuracy： 0.740 3； precision macro： 0.732 1； recall macro： 0.736 0； macro F1： 0.736 0； OvR-AUC： 0.907 0）， indicating good classification performance and generalization ability. SHAP analysis revealed that creatinine， urea nitrogen， daily cumulative dose and administration frequency of vancomycin， which were key predictors， had a significant impact on the prediction results. CONCLUSIONS RF and TabPFN models demonstrate certain advantages in the classification prediction of vancomycin trough blood concentrations； however， their performance in the low to moderate concentration categories still requires improvement.

Objective To establish radioresistant human non-small cell lung cancer NCI-H460R model cells and evaluate the sensitivity of these radioresistant cells to a ferroptosis inducer. Methods Radioresistant cell lines, designated as NCI-H460 R20Gy and NCI-H460 R116Gy, were generated by subjecting parental NCI-H460 cells to fractionated irradiation with varying cumulative doses. Both parental cells and the established radioresistant cell lines were each randomly divided into four groups and exposed to irradiation at 0, 2, 4, and 6 Gy, respectively. Successful establishment of the radioresistant cell lines was confirmed by colony formation assay. Subsequently, cells were treated with increasing concentrations of the ferroptosis inducer RSL-3 to assess differential sensitivity between parental and radioresistant cells to ferroptosis. Results In comparison to the parental NCI-H460 cells (D_0WT=1.2), both NCI-H460 R116Gy and NCI-H460 R20Gy cells exhibited radioresistance, with NCI-H460 R116Gy demonstrating a stronger radioresistance (D_0R116Gy=1.5) than NCI-H460 R20Gy (D_0R20Gy=1.4). Furthermore, NCI-H460 R116Gy cells exhibited increased sensitivity to RSL-3 relative to the parental cells (P < 0.001), while NCI-H460 R20Gy cells did not display a significant difference in sensitivity to RSL-3. Conclusion Human non-small cell lung cancer cells with radioresistance induced by a high cumulative irradiation dose exhibit increased sensitivity to the glutathione peroxidase 4-specific ferroptosis inducer RSL-3. This finding provides an experimental basis for optimizing combined treatment regimens involving radiotherapy and RSL-3 for non-small cell lung cancer patients with radiotherapy resistance.

[摘 要] 目的：探讨白蛋白结合型紫杉醇联合PD-1抑制剂用于治疗一线化疗失败的骨与软组织肉瘤的疗效及安全性。方法：回顾性分析北京积水潭医院骨肿瘤科2017年8月至2020年8月收治的一线化疗失败的晚期骨与软组织肉瘤患者。患者接受白蛋白结合型紫杉醇（125~140 mg/m2，第1天和第8天）与PD-1抑制剂（信迪利单抗或特瑞普利单抗，每21 d一次）联合治疗。每2个治疗周期评估1次疗效，按RECIST 1.1标准评估肿瘤疗效，按NCI-CTCAE5.0标准评估不良反应。结果：共20名患者纳入研究，完成1至8个治疗周期，中位治疗周期数为3个。所有患者均可评估疗效，完全缓解4例（20%），部分缓解0例，稳定9例（45%），疾病进展7例（35%）。客观缓解率（ORR）为20%，疾病控制率（DCR）为65%。中位无进展生存期（PFS）为3.0个月。治疗期间主要不良反应包括2级白细胞减少（40%）、1-2级神经毒性反应（20%），以及2级甲状腺功能减退（10%）。结论：白蛋白结合型紫杉醇联合PD-1抑制剂治疗为一线化疗失败的晚期骨与软组织肉瘤患者提供了一种潜在的治疗选择，其不良反应可控，值得开展更大样本的前瞻性研究进一步验证其疗效。

BACKGROUND: The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis. RESULTS: Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P  <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P  = 0.027; P  = 0.003; P  = 0.035; P  = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P  <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival. CONCLUSION Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology* ; Neoplasm, Residual ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; Risk Factors ; Adolescent ; Adult ; Child ; Child, Preschool ; Young Adult ; Middle Aged ; Infant ; Transplantation, Homologous ; Proportional Hazards Models ; Retrospective Studies