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 characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

From the perspective of transfusion medicine and based on the vision and framework of patient blood management, this article combines the advances in basic science, blood transfusion, laboratory, and clinical medicine. It aims to systematically review the key elements and characteristics of patient fibrinogen management by maintaining and optimizing patients' hemostatic function while reducing blood transfusions. This review enriches the connotation of transfusion medicine, especially patient blood management, and provides valuable insights for clinical practice.

ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

OBJECTIVE To analyze the specific risks and long-term toxicities of four BCR-ABL1 tyrosine kinase inhibitors （TKIs）（imatinib， dasatinib， nilotinib， and bosutinib） in pediatric patients with hematological malignancies. METHODS Adverse drug event （ADE） reports submitted to the the United States FDA Adverse Event Reporting System （FAERS） from January 2012 to December 2024， with imatinib， dasatinib， nilotinib， and bosutinib as the primary suspect drugs， were collected. Data mining was performed using the reporting odds ratio method and proportional reporting ratio method. ADE terms were classified and summarized by system organ class （SOC） and preferred term （PT） according to the Medical Dictionary for Drug Regulatory Activities （MedDRA， version 26.0）. Meanwhile， the ADE reports were divided by age into the adult group （≥18 years） and the pediatric group （＜18 years） to compare the differences in ADE between the two groups. RESULTS A total of 1 512 pediatric ADE reports were included： 993 for imatinib， 391 for dasatinib， 112 for nilotinib， and 16 for bosutinib. Among the reported ADEs， the patients were mainly aged 12-＜18 years； the reports mainly originated from the United States， France， and Japan； and the primary indications were chronic myeloid leukemia and acute lymphoblastic leukemia. A total of 5 256 ADE signals were mined， among which 235 were positive signals， involving 1 103 PT across 27 SOC. The top five PT ranked by the number of positive signals were nausea， febrile neutropenia， abdominal pain， neutropenia， and anemia. The top two SOC were general disorders and administration site conditions， and gastrointestinal disorders. Compared with the adult group， the pediatric group had relatively higher proportions of events related to infections and infestations as well as blood and lymphatic system disorders. Pediatric long-term toxicity signals primarily included growth retardation， accompanied by signals related to endocrine system abnormalities and bone metabolism abnormalities. Specific signals included imatinib-associated septic shock， dasatinib-associated chylothorax， and nilotinib-associated electrocardiographic QT interval prolongation. CONCLUSIONS When pediatric patients use BCR-ABL1 TKIs， priority monitoring of infection risk and hematologic parameters is required， along with long-term follow-up of height， endocrine， and bone metabolism parameters. Targeted screening and management of drug-specific signals should be performed to ensure the long-term safety of pediatric medication.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Abstract： ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 （GLUT1） on the proliferation， migration， adhesion， and angiogenesis of human umbilical vein endothelial cells （HUVECs） under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment （1% O₂， 5% CO₂， 94% N₂）. The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability， proliferation capacity， and examining the expression changes of GLUT1， HIF-1α， and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further， GLUT1 was overexpressed using plasmid transfection and the proliferation， migration， adhesion， and angiogenic capabilities of HUVECs were evaluated through scratch assays， cell adhesion assays， and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy，and oxygen consumption rate （OCR） was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions， the ischemia-hypoxic environment significantly inhibited the proliferation， cell viability， migration， and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1， HIF-1α and VEGFA proteins were also markedly reduced. However， when GLUT1 expression was upregulated， the migration， adhesion， and angiogenic capabilities of HUVECs were significantly improved， and the protein expression levels of HIF-1α， VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage， while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions， potentially through modulating cellular energy metabolism and signal transduction pathways， thereby affecting cell proliferation， migration， adhesion， and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Objective: To explore the network structure of eating behaviors with anxiety, depression and perceived stress in adolescents, so as to provide a basis for effective prevention and intervention of eating behavior problems and negative emotions in adolescents. Methods: Based on the Psychology and Behavior Investigation of Chinese Residents (2021) database, the study was conducted among 3 087 adolescents. Sakata Eating Behavior Scale Short From(EBS-SF) was used to investigate their eating behaviors. The Patient Health Questionnaire-9(PHQ-9), Generalized Anxiety Disorder Scale-7 Item(GAD-7), and Perceived Stress Questionnaire-3 Item (PSQ-3) were used to evaluate their depression, anxiety and perceived stress. Network analysis method was applied to construct a network of eating behaviors and negative emotional symptoms among adolescents, so as to evaluate the centrality, bridge strength, stability and accuracy of each item. Results: The total scores of eating behaviors, depression,anxiety and stress perception in adolescents were 17.41±4.53,6.95±6.08,4.86±5.03,9.34±3.80,respectively. The symptom with the highest intensity and expected impact was "I am only satisfied when I buy more food than I need", with a node intensity and expected impact value of 4.37. The nodes Depression and Anxiety were the most closely connected(weight=0.87). There were no statistically significant differences in the network structure( M =0.13,0.11) and network connection strength(female and male:4.16,4.06, s =0.10;urban and rural areas:4.08,4.07, s =0.01) between different sexes and residents ( P >0.05). Conclusion The negative impact of comorbidities such as anxiety, depression, perceived stress and eating behaviors among adolescents can be reduced through targeted prevention and intervention of core symptoms and bridging symptoms.