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.

Objectives:Using data from the heart transplant patient dataset of our center,we aimed to develop a preoperative risk scoring model specifically suitable for the Chinese population undergoing heart transplantation.This model was established to predict the likelihood of graft failure within the first year post-surgery and classify recipients according to their risk level.Methods:A retrospective study was conducted at a single center on 1 210 consecutive heart transplant recipients between June 2004 and December 2022.Risk factor screening was performed using univariate and multivariate logistic regression analyses.Variable selection was carried out through a stepwise backward procedure based on the Akaike Information Criterion(AIC).The regression coefficients obtained from the final model were employed as weighting factors in the multifactor analysis.The study utilized the area under the receiver operating characteristic(ROC)area under curve(AUC)as a metric to evaluate the performance of the model.Patients were stratified into low,medium,and high-risk groups based on the distribution of the calculated scores.Survival analysis was conducted on the various risk groups using the Kaplan-Meier method,with statistical comparisons performed using the log-rank test.A significance level of P<0.05 was deemed statistically significant.Results:A risk scoring model,denoted as the heart transplant(HTx)score,was developed,comprising 11 variables and yielding a total score of 20.6 points.In comparison to the low-risk group,the OR for 1-year graft failure in the medium-risk group was 2.0(95%CI:1.1-3.6,P=0.02),while the high-risk group had an OR of 9.8(95%CI:5.4-17.7,P<0.01).The risk scoring model exhibited strong discriminative ability with an AUC of 0.712(95%CI:0.646-0.778)and an internally validated bias-corrected AUC of 0.713.The results of the Hosmer-Lemeshow goodness-of-fit test indicated that the predictive model demonstrated a strong calibration ability(Hosmer-Lemeshow χ2=2.92,P=0.71).Within the cohort,the AUC values for the IMPACT score,UNOS score,RSS score,Mayo score,BO score,and TRS score models were 0.645,0.651,0.632,0.589,0.610,and 0.604,respectively.These findings suggest that the HTx scoring model exhibited superior predictive performance compared to the aforementioned models in forecasting outcomes within our cohort.The Kaplan-Meier survival analysis revealed statistically significant differences in long-term survival rates between the three risk groups,a noticeable decrease in long-term survival rates were observed with increasing levels of HTx risk stratification(P<0.05).Conclusions:Present results indicate a significant association between the developed HTx risk scores and graft failure within the initial year post-surgery,present model effectively categorizes the heart transplant recipients into low,medium,and high-risk groups and is valuable for risk stratification.

Objectives:To assess the situation of retained cardiac implantable electronic device(CIED)leads after cardiac transplantation,the associated factors,and their impact on long-term prognosis.Methods:A retrospective analysis was conducted on 1 096 patients who underwent cardiac transplantation at Fuwai Hospital of the Chinese Academy of Medical Sciences from January 1,2005 to January 1,2022.Among them,204 patients(18.6%)received CIED therapy before cardiac transplantation.Two physicians independently reviewed the pre-and post-transplant chest X-rays to determine the presence of retained CIED leads.Logistic multivariate regression analysis was used to assess factors associated with retained CIED leads,and Kaplan-Meier survival curves were plotted to analyze the impact of retained CIED leads on long-term prognosis.Results:Among the 204 patients who received CIED therapy before cardiac transplantation,the highest proportion were those treated with implantable cardioverter defibrillator(ICD)and cardiac resynchronization therapy-defibrillator(CRT-D),accounting for 47.5%(97/204)and 40.7%(83/204),respectively.The mean duration from CIED implantation to cardiac transplantation was(45.1±40.0)months,and 38 patients(18.6%)had retained CIED leads after cardiac transplantation.The results of the logistic multivariate regression analysis showed that the duration from CIED implantation to cardiac transplantation was the only factor associated with retained CIED leads after cardiac transplantation(OR=1.020,95%CI:1.011-1.030,P=0.000).Cumulative all-cause survival rates among patients without CIED implantation(n=892),those without retained CIED leads(n=166),and those with retained CIED leads(n=38)were 88.5%,93.3%and 84.2%,respectively.Kaplan-Meier survival curve analysis showed no significant difference in cumulative all-cause survival among the three groups(log-rank P=0.643).Conclusions:In patients who received CIED implantation before cardiac transplantation,18.6%had retained leads after surgery.The duration from CIED implantation to cardiac transplantation is the only factor associated with lead retained after cardiac transplantation,but retained leads does not affect the outcome post heart transplantation.

Objectives:When heparin-induced thrombocytopenia(HIT)is diagnosed before heart transplantation,recommendation varies according to small sample observations from other countries.In China,recent HIT is considered as a relative contradiction for heart transplantation and clinical study results is not yet available.Methods:A total of 325 patients who received heart transplantation in Fuwai Hospital from January 1,2022 to July 31,2024 were retrospectively analyzed,124 of whom received instrumental circulation and heparin before transplantation,and 15 of whom had suspected HIT before surgery.Diagnostic strategy was based on clinical investigation,antibody detection and expert opinion.Results:All 15 patients used intra-aortic balloon pump(IABP)preoperatively,6 were diagnosed with HIT,contributing 4.8%of those who used mechanical circulation support before heart transplantation.Three patients were tested positive for HIT-Ab just before surgery.Three different anticoagulation strategies:bivalirudin,heparin,and combined bivalirudin and heparin was used in each of the 3 patients,respectively.Their clinical features varied significantly.The first patient experienced challenging bleeding issue and cervical vein embolization.The second patient experienced low-limb embolization and the third patient experienced spleen artery embolization.Thrombocyte count returned to normal range at day 8,6 and 10 respectively post operation.Conclusions:HIT is not rare in patients using IABP and other mechanical circulation support devices before heart transplantation.Diagnosis and treatment of HIT is challenging for patients awaiting heart transplantation.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objectives:Using data from the heart transplant patient dataset of our center,we aimed to develop a preoperative risk scoring model specifically suitable for the Chinese population undergoing heart transplantation.This model was established to predict the likelihood of graft failure within the first year post-surgery and classify recipients according to their risk level.Methods:A retrospective study was conducted at a single center on 1 210 consecutive heart transplant recipients between June 2004 and December 2022.Risk factor screening was performed using univariate and multivariate logistic regression analyses.Variable selection was carried out through a stepwise backward procedure based on the Akaike Information Criterion(AIC).The regression coefficients obtained from the final model were employed as weighting factors in the multifactor analysis.The study utilized the area under the receiver operating characteristic(ROC)area under curve(AUC)as a metric to evaluate the performance of the model.Patients were stratified into low,medium,and high-risk groups based on the distribution of the calculated scores.Survival analysis was conducted on the various risk groups using the Kaplan-Meier method,with statistical comparisons performed using the log-rank test.A significance level of P<0.05 was deemed statistically significant.Results:A risk scoring model,denoted as the heart transplant(HTx)score,was developed,comprising 11 variables and yielding a total score of 20.6 points.In comparison to the low-risk group,the OR for 1-year graft failure in the medium-risk group was 2.0(95%CI:1.1-3.6,P=0.02),while the high-risk group had an OR of 9.8(95%CI:5.4-17.7,P<0.01).The risk scoring model exhibited strong discriminative ability with an AUC of 0.712(95%CI:0.646-0.778)and an internally validated bias-corrected AUC of 0.713.The results of the Hosmer-Lemeshow goodness-of-fit test indicated that the predictive model demonstrated a strong calibration ability(Hosmer-Lemeshow χ2=2.92,P=0.71).Within the cohort,the AUC values for the IMPACT score,UNOS score,RSS score,Mayo score,BO score,and TRS score models were 0.645,0.651,0.632,0.589,0.610,and 0.604,respectively.These findings suggest that the HTx scoring model exhibited superior predictive performance compared to the aforementioned models in forecasting outcomes within our cohort.The Kaplan-Meier survival analysis revealed statistically significant differences in long-term survival rates between the three risk groups,a noticeable decrease in long-term survival rates were observed with increasing levels of HTx risk stratification(P<0.05).Conclusions:Present results indicate a significant association between the developed HTx risk scores and graft failure within the initial year post-surgery,present model effectively categorizes the heart transplant recipients into low,medium,and high-risk groups and is valuable for risk stratification.

OBJECTIVE To investigate the inhibitory effects of Bruceine A(BA)on colon cancer and its underlying mechanisms.METHODS Human colon cancer HT-29 and HCT116 cells were treated with various concentrations of BA(0,1,2,5,10,20,40,80 μmol·L-1).Cell viability was assessed using the Cell Counting Kit-8(CCK-8).Flow cytometry,wound healing assays,and Transwell assays were employed to evaluate the effects of BA on cell apoptosis,cell cycle,invasion,and migration.Mo-lecular docking simulations were used to assess the binding of BA to GSK-3β protein,and Western blot analysis was used to examine protein expression related to the cell cycle,epithelial-mesenchymal transition,and the Wnt/β-catenin signaling pathway.An HT-29 cell subcutaneous xenograft mouse model was established.After tumor formation,mice were randomly divided into three groups(six mice per group):a blank group,a low-dose BA group(0.1 mg·kg-1),and a high-dose BA group(0.2 mg·kg-1).Mice were ad-ministered the drug for 19 d,then sacrificed,and tumor tissues were collected.Tumor volume changes over time were observed;Ki67 immunohistochemistry was used to assess cell proliferation in tumor tissues;Western blot analysis of Wnt/β-catenin signaling pathway protein expression was conducted.RESULTS Compared with the blank group,BA could significantly inhibit the proliferation of HT-29 and HCT116 cells,with IC50 values of 10.80 μmol·L-1 and 17.96 μmol·L-1,respectively.Flow cytometry results showed that BA significantly induced apoptosis of HT-29 cells(P<0.01,P<0.001),and arrested the cell cycle at the S phase,accompanied by de-creased expression of cycle-related proteins CDK2 and Cyclin A(P<0.05,P<0.01,P<0.001).BA inhibited cell migration and in-vasion ability(P<0.05,P<0.01,P<0.001),reduced the expression of EMT-related proteins Snail,Vimentin,and N-Cadherin(P<0.01,P<0.001),and upregulated the expression of E-Cadherin protein.In addition,BA inhibited the expression of β-catenin and p-GSK3β proteins.Wnt agonist LiCl could significantly antagonize the anti-colon cancer effect of BA;Wnt inhibitor XAV939 could enhance the anti-colon cancer effect of BA.In the in vivo experiment,compared with the blank group,the tumor volume of the low-dose and high-dose BA groups was significantly reduced(P<0.05,P<0.001).Immunohistochemistry results showed that compared with the blank group,the expression of Ki67 in tumor tissues of the low-dose and high-dose BA groups was significantly reduced(P<0.001).Western blot results further proved that BA inhibited the Wnt/β-catenin signaling pathway.CONCLUSION BA inhibits the viability,invasion,and migration of colon cancer HT-29 cells,induces apoptosis,and causes cell cycle arrest.Additionally,it significantly suppresses the growth of subcutaneous HT-29 cell xenografts in vivo,possibly related to the Wnt/β-catenin signaling pathway.

Kirsten rat sarcoma viral oncogene homolog(KRAS)protein inhibitors are a promising class of thera-peutics,but research on molecules that effectively penetrate the blood-brain barrier(BBB)remains limited,which is crucial for treating central nervous system(CNS)malignancies.Although molecular generation models have recently advanced drug discovery,they often overlook the complexity of bio-logical and chemical factors,leaving room for improvement.In this study,we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug effi-cacy and drug absorption properties.Our approach utilizes a variational autoencoder(VAE)generative model integrated with reinforcement learning for multi-objective optimization.This method specifically aims to enhance BBB permeability(BBBp)while maintaining high-affinity substructures of KRAS in-hibitors.To support this,we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models.Additionally,we introduce two novel metrics,the knowledge-integrated reproduction score(KIRS)and the composite diversity score(CDS),to assess structural performance and biological relevance.Retrospective validation with KRAS inhibitors,AMG510 and MRTX849,demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications.This study provides a robust framework for accelerating the structural enhancement of lead compounds,advancing the drug development process across diverse targets.

PURPOSE: To investigate the incidence and influencing factors of bone loss in patients with spinal cord injury (SCI). METHODS: A retrospective case-control study was conducted. Patients with SCI in our hospital from January 2019 to March 2023 were collected. According to the correlation between bone mineral density (BMD) at different sites, the patients were divided into the lumbar spine group and the hip joint group. According to the BMD value, the patients were divided into the normal bone mass group (t > -1.0 standard deviation) and the osteopenia group (t ≤ -1.0 standard deviation). The influencing factors accumulated as follows: gender, age, height, weight, cause of injury, injury segment, injury degree, time after injury, start time of rehabilitation, motor score, sensory score, spasticity, serum value of alkaline phosphatase, calcium, and phosphorus. The trend chart was drawn and the influencing factors were analyzed. SPSS 26.0 was used for statistical analysis. Correlation analysis was used to test the correlation between the BMD values of the lumbar spine and bilateral hips. Binary logistic regression analysis was used to explore the influencing factors of osteoporosis after SCI. p < 0.05 was considered statistically significant. RESULTS: The incidence of bone loss in patients with SCI was 66.3%. There was a low concordance between bone loss in the lumbar spine and the hip, and the hip was particularly susceptible to bone loss after SCI, with an upward trend in incidence (36% - 82%). In this study, patients with SCI were divided into the lumbar spine group (n = 100) and the hip group (n = 185) according to the BMD values of different sites. Then, the lumbar spine group was divided into the normal bone mass group (n = 53) and the osteopenia group (n = 47); the hip joint group was divided into the normal bone mass group (n = 83) and the osteopenia group (n = 102). Of these, lumbar bone loss after SCI is correlated with gender and weight (p = 0.032 and < 0.001, respectively), and hip bone loss is correlated with gender, height, weight, and time since injury (p < 0.001, p = 0.015, 0.009, and 0.012, respectively). CONCLUSIONS The incidence of bone loss after SCI was high, especially in the hip. The incidence and influencing factors of bone loss in the lumbar spine and hip were different. Patients with SCI who are male, low height, lightweight, and long time after injury were more likely to have bone loss.
Humans ; Spinal Cord Injuries/complications* ; Male ; Female ; Retrospective Studies ; Incidence ; Adult ; Bone Density ; Middle Aged ; Case-Control Studies ; Osteoporosis/etiology* ; Lumbar Vertebrae ; Bone Diseases, Metabolic/etiology* ; Aged ; Risk Factors

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.