Objective To propose a high-precision deep learning-based image assessment method of osteosarcoma chemotherapy efficacy for clinical treatment,as existing methos have low accuracy of osteosarcoma assessment.Methods The low incidence of osteosarcoma led to the small scale of its imaging data and the problem of imbalance in data categories.This study combined deep learning with clinical medical information,combined the bone sarcoma generation module of BoneGAN and the scale lesion information capture module,and proposed OMLA-Net,a deep learning assessment network for chemotherapy effect of bone sarcoma based on multi-scale lesion attention network,which achieved computer-aided bone tumor assessment with integrated data augmentation and focused lesion information through pre-training and generalized loss training.Results In this study,40 cases of osteosarcoma MRI data were used as the basis for the comparison test on the generated dataset,and the OMLA-Net assessment outperformed the SOTA method Conv-LSTM-GAN in terms of the assessment effects such as accuracy and F1 scores,and the difference was statistically significant(Bootstrap statistical method P＜0.05);the subsequent K-fold cross-validation ablation experiments further demonstrated the effectiveness of each module proposed by OMLA-Net.Conclusion OMLA-Net can effectively perform the impact assessment of chemotherapy effect on osteosarcoma,which provides a new idea for subsequent clinical application.

Colorectal cancer(CRC) is one of the most common malignant tumors worldwide, primarily originating from recurrent inflammatory bowel disease(IBD). Therefore, blocking the inflammation-cancer transformation in the colon has become a focus in the early prevention and treatment of CRC. The inflammation-cancer transformation in the colon involves multiple types of cells and complex pathological processes, including inflammatory responses and tumorigenesis. In this complex pathological process, immune cells(including non-specific and specific immune cells) and non-immune cells(such as tumor cells and fibroblasts) interact with each other, collectively promoting the progression of the disease. In traditional Chinese medicine(TCM), inflammation-cancer transformation in the colon belongs to the categories of dysentery and diarrhea, with the main pathogenesis being cold and heat in complexity. This paper first elaborates on the complex molecular mechanisms involved in the inflammation-cancer transformation process in the colon from the perspectives of inflammation, cancer, and their mutual influences. Subsequently, by comparing the pathogenic characteristics and clinical manifestations between inflammation-cancer transformation and the TCM pathogenesis of cold and heat in complexity, this paper explores the intrinsic connections between the two. Furthermore, based on the correlation between inflammation-cancer transformation in the colon and the TCM pathogenesis, this paper delves into the importance of the interaction between inflammation and cancer. Finally, it summarizes and discusses the clinical and basic research progress in the TCM intervention in the inflammation-cancer transformation process, providing a theoretical basis and treatment strategy for the treatment of CRC with integrated traditional Chinese and Western medicine.
Humans ; Colon/pathology* ; Integrative Medicine ; Animals ; Cold Temperature ; Cell Transformation, Neoplastic/drug effects* ; Medicine, Chinese Traditional ; Hot Temperature ; Inflammation ; Drugs, Chinese Herbal/therapeutic use* ; Colonic Neoplasms/drug therapy*

The aim of this study is to explore a new path of empowering ideological and political educa-tion in courses with digital intelligence technology,therefore to improve the teaching quality of biology courses in universities,promote the comprehensive implementation of the fundamental task of cultivating morality and talents,and continuously improve the level of"three pronged education".By using the biol-ogy course"Immunology"as a practical carrier,we have constructed a dual-driven framework of"ideo-logical and political guidance+digital intelligence empowerment"utilizing digital tools to further highlight pedagogical feature enhancement,curricular optimization,innovative teaching models,multidimensional assessment,and enhanced teaching refinement.The empowerment of digital intelligence in the ideological and political construction of the course"Immunology"has achieved notable progress.Students' profes-sional abilities and ideological and political literacy have significantly improved,and the proportion of students with excellent grades has been increasing year by year(81.93％of students with good grades or above in 2024),demonstrating outstanding performance in various social practice activities;The course exhibits excellent demonstration and radiation effects on campus,and the teaching results have been sup-ported by the Ministry of Education and provincial-level education reform projects.This study serves as a practical example for the digital transformation of ideological and political education in higher education courses,providing reference and innovative insights for implementing ideological and political elements in other courses of biology majors.

Objective:To evaluate the clinical feasibility of subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation following transvenous lead extraction (TLE).Methods:This was a retrospective study. Consecutive patients who underwent S-ICD implantation at Peking University People′s Hospital between June 2015 and October 2023 were enrolled. Patients were divided into the TLE group and the newly implanted group based on whether they received TLE prior to S-ICD implantation. Baseline characteristics, S-ICD indication, defibrillation threshold test results, complications, and postoperative follow-up data were collected and compared between the two groups.Results:A total of 27 patients were included, aged (49.2±14.2) years, including 19 males. There were 12 patients in the TLE group and 15 in the newly implanted group. Compared with the TLE group, patients in the newly implanted group were younger ((43.3±13.7) years vs. (55.6±12.0) years, P=0.013). The main S-ICD indication in the TLE group was high infection risk (9/12), whereas in the newly implanted group it was younger age (11/15). All patients underwent successful S-ICD implantation, with 18 patients completing defibrillation threshold testing (all successful). Additionally, the TLE group had longer follow-up duration than the newly implanted group (42 (19, 60) months vs. 12 (3, 28) months, P=0.001). No complications or deaths occurred during follow-up, with normal device function in both groups. A total of 17 ventricular tachycardia or fibrillation events were recorded, of which 7 met defibrillation criteria and all received effective therapy. Conclusion:S-ICD demonstrates safety and efficacy as a therapeutic option for patients after TLE, with comparable device functionality and follow-up outcomes to patients with newly implanted S-ICD.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

The aim of this study is to explore a new path of empowering ideological and political educa-tion in courses with digital intelligence technology,therefore to improve the teaching quality of biology courses in universities,promote the comprehensive implementation of the fundamental task of cultivating morality and talents,and continuously improve the level of"three pronged education".By using the biol-ogy course"Immunology"as a practical carrier,we have constructed a dual-driven framework of"ideo-logical and political guidance+digital intelligence empowerment"utilizing digital tools to further highlight pedagogical feature enhancement,curricular optimization,innovative teaching models,multidimensional assessment,and enhanced teaching refinement.The empowerment of digital intelligence in the ideological and political construction of the course"Immunology"has achieved notable progress.Students' profes-sional abilities and ideological and political literacy have significantly improved,and the proportion of students with excellent grades has been increasing year by year(81.93％of students with good grades or above in 2024),demonstrating outstanding performance in various social practice activities;The course exhibits excellent demonstration and radiation effects on campus,and the teaching results have been sup-ported by the Ministry of Education and provincial-level education reform projects.This study serves as a practical example for the digital transformation of ideological and political education in higher education courses,providing reference and innovative insights for implementing ideological and political elements in other courses of biology majors.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Objective:To evaluate the clinical feasibility of subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation following transvenous lead extraction (TLE).Methods:This was a retrospective study. Consecutive patients who underwent S-ICD implantation at Peking University People′s Hospital between June 2015 and October 2023 were enrolled. Patients were divided into the TLE group and the newly implanted group based on whether they received TLE prior to S-ICD implantation. Baseline characteristics, S-ICD indication, defibrillation threshold test results, complications, and postoperative follow-up data were collected and compared between the two groups.Results:A total of 27 patients were included, aged (49.2±14.2) years, including 19 males. There were 12 patients in the TLE group and 15 in the newly implanted group. Compared with the TLE group, patients in the newly implanted group were younger ((43.3±13.7) years vs. (55.6±12.0) years, P=0.013). The main S-ICD indication in the TLE group was high infection risk (9/12), whereas in the newly implanted group it was younger age (11/15). All patients underwent successful S-ICD implantation, with 18 patients completing defibrillation threshold testing (all successful). Additionally, the TLE group had longer follow-up duration than the newly implanted group (42 (19, 60) months vs. 12 (3, 28) months, P=0.001). No complications or deaths occurred during follow-up, with normal device function in both groups. A total of 17 ventricular tachycardia or fibrillation events were recorded, of which 7 met defibrillation criteria and all received effective therapy. Conclusion:S-ICD demonstrates safety and efficacy as a therapeutic option for patients after TLE, with comparable device functionality and follow-up outcomes to patients with newly implanted S-ICD.

Objectives:To assess the clinical characteristics and lead extraction in patients with venous occlusion related to infection of cardiovascular implantable electronic devices. Methods:Clinical data of 405 patients(147 men,mean age[62.4±13.2]years)who underwent lead extraction from January 2020 to January 2024 in Peking University People's Hospital were reviewed.Contrast venography of the access vein was retrospectively analyzed.The patients were divided into venous occlusion group(n=119)and non-venous occlusion group(n=286)according to the presence or absence of venous occlusion.The clinical characteristics and lead extraction of patients in two groups were analyzed. Results:Occlusion of the access vein occurred in 119 patients(29.4%).The subclavian vein was occluded in 48 cases(40.3%),brachiocephalic vein was occluded in 37 cases(31.1%),axillary vein was occluded in 30 cases(25.2%),superior vena cava was occluded in 4 cases(3.4%).There were no significant differences between venous occlusion group and non-venous occlusion group in terms of age,sex,device type,number of leads,or anticoagulation therapy(all P>0.05).Time from implant of the initial leads was significantly longer in the venous occlusion group than in the non-venous occlusion group([10.4±3.8]years vs.[5.9±4.1]years,P=0.042).Clinical extraction success rate and complications were similar between the venous occlusion group and the non-venous occlusion group(both P>0.05).Procedural duration and fluoroscopy exposure time were significantly lower in non-venous occlusion group than in the venous occlusion group(both P<0.05).Patients in the venous occlusion group required more advanced tools(such as laser sheaths,evolution sheaths,and needle's eye snares)for lead extraction compared to patients in the non-venous occlusion group(84.0%vs.67.1%,P=0.001). Conclusions:The incidence of venous occlusion related to infection of cardiovascular implantable electronic devices is 29.4%.Time from implant of the initial leads is significantly longer and lead extraction is more difficult in patients with venous occlusion,and requires more advanced tools and more time to achieve the successful lead extraction.

ObjectiveThe detection of RNA single nucleotide polymorphism (SNP) is of great importance due to their association with protein expression related to various diseases and drug responses. At present, splintR ligase-assisted methods are important approaches for RNA direct detection, but its specificity will be limited when the fidelity of ligases is not ideal. The aim of this study was to create a method to improve the specificity of splintR ligase for RNA detection. MethodsIn this study, a dual-competitive-padlock-probe (DCPLP) assay without the need for additional enzymes or reactions is proposed to improve specificity of splintR ligase ligation. To verify the method, we employed dual competitive padlock probe-mediated rolling circle amplification (DCPLP-RCA) to genotype the CYP2C9 gene. ResultsThe specificity was well improved through the competition and strand displacement of dual padlock probe, with an 83.26% reduction in nonspecific signal. By detecting synthetic RNA samples, the method demonstrated a dynamic detection range of 10 pmol/L-1 nmol/L. Furthermore, clinical samples were applied to the method to evaluate its performance, and the genotyping results were consistent with those obtained using the qPCR method. ConclusionThis study has successfully established a highly specific direct RNA SNP detection method, and provided a novel avenue for accurate identification of various types of RNAs.