Objective To evaluate the application of flipped classroom(FC)approach in endocrine system integrated course for students from 4+4 clinical medicine pilot class at Peking Union Medical College(PUMC).Methods The study included the students of 4+4 clinical medicine pilot class grades 2019-2023 in PUMC.The students of grades 2019-2021(n=77)served as the control receiving traditional teaching method,while the students of grades 2022 and 2023(n=76)were selected as the experimental group,which were taught by FC approach.The selected teaching content is thyroid theme.The scoring rates of thyroid related questions in the final exam were as-sessed and a questionnaire survey was conducted to evaluate teaching satisfaction and effectiveness.Results The scoring rates of experimental group were significantly higher as compared to that of control group(P＜0.05).Over 90％of the students in the experimental group strongly satisfied or satisfied with the teaching content arrangement,design form,classroom atmosphere,teacher-student interaction of FC and expressed willingness to continue with this methodology.In addition,over 90％of the students strongly agreed or agreed that FC stimulated learning inter-est,improved self-learning ability,strengthened the connection between theory and clinical practice,inspired clini-cal reasoning,enhanced the abilities to analyze and solve problems,and cultivated communication and teamwork skills.Conclusions The application of FC approach in endocrine system integrated course achieved excellent teaching outcomes with high satisfaction of the students.

Objective To utilize single-cell and peripheral blood transcriptomic data from 3D brain organoids,combined with machine learning,to analyze the role of mitochondrial autophagy genes in schizophrenia(SCZ).Methods By integrating two machine learning algorithms,we identified differentially expressed mitochondrial autophagy-related genes between schizophrenia patients and healthy controls using peripheral blood RNA sequencing data.The relationship between mitophagy gene,immune cells and inflammatory factors was further explored.Comprehensive single-cell analysis was used to explore the signaling pathways and specific transcription factors based on mitophagy genes.Results Using machine learning,seven key mitophagy genes expressed in schizophrenia patients were identified.Based on Mitoscore analysis,at the single-cell level,neurons with high mitochondrial autophagy activity(Mitohigh_Neuron)formed new interactions with endothelial cells via the SPP1 signaling pathway.Conclusion This study identified two subtypes of mitophagy and seven key mitophagy genes in schizophrenia,providing new insights into the pathogenesis of the disease.

Aim To investigate the effect of Panax no-toginseng saponins(PNS)on the interaction between endometrial cancer cells and macrophages by regulating the epidermal growth factor receptor(EGFR)/heat shock protein 27(HSP27)axis.Methods Ishikawa cells were divided into Control,DDP,PNS-treated,M2-CM,M2-CM+DDP,M2-CM+PNS,M2-CM+PNS+oe-NC,M2-CM+PNS+oe-EGFR,PNS(200 mg·L-1)+oe-NC,PNS(200 mg·L-1)+oe-EG-FR,oe-NC,oe-EGFR,oe-EGFR+si-NC,and oe-EG-FR+si-HSP27 groups.MTT assay was used to detect cell proliferation,Transwell assay for cell invasion,TUNEL assay for cell apoptosis,qRT-PCR for macro-phage polarization markers CD86 and CD163 mRNA levels,ELISA for iNOS and IL-12 levels,and West-ern-blot for EGFR and HSP27 protein expression.A nude mouse xenograft tumor model was established and treated with PNS to evaluate the effect of PNS in vivo.Results Compared with the Control group,PNS and DDP significantly inhibited the proliferation and inva-sion of Ishikawa cells and induced apoptosis.M2-CM treatment inhibited M1 macrophage markers,promoted M2 macrophage markers,and induced Ishikawa cell growth,but this effect was reversed by PNS treatment.EGFR was confirmed as a target of PNS,and compared with the M2-CM+PNS+oe-NC group,EGFR overex-pression promoted M2 macrophage marker levels,in-duced Ishikawa cell proliferation and invasion,and in-hibited apoptosis.Knockdown of HSP27 reversed the effect of EGFR overexpression on the biological behav-ior of Ishikawa cells.Animal experiments showed that PNS could inhibit tumor growth and reduce the positive expression of CD163,EGFR,and HSP27 in tumor tis-sues.Conclusion PNS affects the interaction be-tween macrophages and EC cells by regulating the EG-FR/HSP27 axis,thereby participating in EC progres-sion.

Objective:To evaluate the lung ultrasound characteristics of mycoplasma pneumoniae pneumonia in children and to investigate the value of lung ultrasound monitoring in clinical diagnosis and treatment.Methods:A retrospective analysis of 62 children with mycoplasma pneumoniae pneumonia admitted to Xi'an Chest Hospital from 7 November to 30 November 2023 was performed，and the characteristic parameters of bedside lung ultrasound and their related clinical data were collected. Pathological lung ultrasound features such as interrupted pleural line，well-spaced B-lines，coalescent B-lines，small subpleural patchy pulmonary consolidation，large pulmonary consolidation and pleural effusion in 12 scan areas of both lungs were observed. The maximum upper and lower diameters，right and left diameters，and anterior and posterior diameters of the large pulmonary consolidations were measured，and the changes in the above signs before and after treatment were measured and compared.Results:In sixty-two children with mycoplasma pneumoniae pneumonia，including 32 males and 30 females，with a mean age of（8.18 ± 2.05）years old and a mean hospital stay of（8.79 ± 2.93）days，lung ultrasound showed interrupted pleural line，well-spaced B-lines，coalescent B-lines，small subpleural patchy pulmonary consolidation，large pulmonary consolidation and pleural effusion，with the incidence of 93.5%（58 /62），33.9%（21/62），32.3%（20/62），59.7%（37/62），66.1%（41/62）and 17.7%（11/62），respectively，in which the large pulmonary consolidations presented rich blood supply were more common in the L6 and L4 areas，while the pleural effusions were more common in the L6 area.The signs of interrupted pleural line，coalescent B-lines，large pulmonary consolidation and pleural effusion were significantly improved after treatment compared with before treatment（all P<0.05）. The upper and lower diameters，left and right diameters，and anterior and posterior diameters of large pulmonary consolidations were significantly reduced after treatment compared with before treatment［（4.19 ± 2.42）cm vs.（2.84 ± 2.31）cm， t=2.613， P=0.011；（2.80 ± 1.82）cm vs.（1.96 ± 1.62）cm， t=2.226， P=0.029；（3.41 ± 2.11）cm vs.（2.12 ± 1.82）cm， t=2.972， P=0.004］.With the process of treatment，the dynamic observation of lung ultrasound showed that the well-spaced B-lines/coalescent B-lines gradually decreased until they completely disappeared or a small number of B-lines remained，and the area of the large pulmonary consolidation showed a dynamic downward trend（all P<0.001），and the area of large pulmonary consolidations gradually decreased until they completely disappeared or only small subpleural patchy pulmonary consolidations and well-spaced/coalescent B-lines remained，and at the same time，the pleural effusion gradually absorbed until it disappeared. Conclusions:Lung ultrasound can detect the distribution area of lung lesions，morphology and blood supply characteristics of children with mycoplasma pneumoniae pneumonia，as well as the dynamic changes after treatment，and lung ultrasound can dynamically monitor and evaluate the progression and regression of the disease in real time，providing a reliable imaging evidence for clinical practice.

Traditional scientific research management suffers from problems such as scattered archives,lack of effective dynamic process supervision for projects,weak data analysis capabilities,and low sharing,making it difficult to meet the unified management of multiple hospital areas in medical groups and the independent management of each branch.The group has devel-oped an intelligent scientific research management system based on artificial big data by constructing the framework and designing the content of various demand modules for scientific research management.This system achieves full coverage management of sci-entific research activities,designing interrelated information data networks for scientific research project process management,a-chievement management,academic(specialized)construction management,postdoctoral management,etc.,realizing informa-tionization and refined management of multiple campuses within the group.Analyze the technological values of each hospital,de-partment,and personnel to provide powerful reference for decision-makers.The information-based scientific research manage-ment system is an important guarantee for hospital groups to intelligently manage and efficiently carry out scientific research work.

OBJECTIVE: To propose a new protocol for personalized mandibular reconstruction assisted by three-dimensional (3D) retrieval model based on fully connected neural network (FCNN) and a database of mandibles, and to verify clinical feasibility of the protocol. METHODS: A database of mandibles of 300 normal northern Chinese Han people was established. On the basis of cephalometry, the mandible landmarks with good stability were further screened. Mandibular landmarks were selected and geometric features of the mandible were extracted. A 3D retrieval algorithm was developed, which could retrieve the mandible most similar to a given mandible from the database. A FCNN was built to train the algorithm to improve accuracy of the 3D retrieval model. Using Geomagic Control 2014 software, matching accuracy of the 3D retrieval model was based on aforementioned mandible database and algorithm. From December 2019 to March 2021, a total of 5 patients underwent personalized mandibular reconstruction assisted by a 3D retrieval model based on mandible database and FCNN in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The most similar mandible was retrieved from mandible database through 3D retrieval algorithm. It was used to restore the premorbid morphology of defect area and guide mandibular reconstruction. For the 5 patients, mandible was reconstructed with iliac flap. Virtual surgical plan was transformed using individual surgical guides. RESULTS: Through screening, mandibular landmarks with high reproducibility and stability were identified and composed of mandibular landmarker protocols. After training, the average deviation between most similar mandible retrieved from the 300-case mandible database through 3D retrieval model based on FCNN and given mandible was (1.77±0.44) mm. And the root-mean-square deviation between the most similar mandible retrieved from the database and given mandible was (2.58±0.86) mm. The mandibular reconstruction surgery was successful in all the 5 patients. Their facial symmetry and occlusion were restored. All the patients were satisfied with postoperative appearance. The mean deviation between postoperative mandible and preoperative design was (0.98±0.17) mm. The area with a deviation ≤1 mm accounted for 61.34%±14. 13%, ≤2 mm accounted for 83.82%±7.35%, and ≤3 mm accounted for 93.94%± 2.87%. CONCLUSION The personalized mandibular reconstruction assisted by 3D retrieval model based on the 300-case mandible database and FCNN is feasible clinically.
Humans ; Neural Networks, Computer ; Mandibular Reconstruction/methods* ; Mandible/diagnostic imaging* ; Imaging, Three-Dimensional/methods* ; Adult ; Databases, Factual ; Female ; Male ; Algorithms ; Middle Aged ; Cephalometry

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Background and Aims:According to the Chinese Guidelines for the Diagnosis and Treatment of Colorectal Cancer(2023 Edition),patients with early-stage colorectal cancer who present with high-risk factors require additional radical surgery following endoscopic resection.However,due to the relatively low rate of lymph node metastasis in early colorectal cancer,some patients may not benefit from such supplemental surgery.Therefore,accurately identifying patients who are truly likely to benefit and refining the indications for supplemental surgery are pressing clinical challenges.This study was conducted to investigate the risk factors and distribution patterns of lymph node metastasis following additional radical surgery through retrospectively analyzing a large single-center cohort,thereby providing evidence-based support for clinical decision-making.Methods:Clinicopathologic data were retrospectively reviewed for patients with early-stage colorectal cancer who underwent additional radical surgery at Fudan University Shanghai Cancer Center between 2008 and 2023.Binary Logistic regression and multivariate analyses were performed to identify risk factors associated with lymph node metastasis,and the distribution characteristics of metastatic lymph nodes were further examined.Results:A total of 417 patients were included in the study,with lymph node metastasis confirmed in 36 cases(8.63％)postoperatively.Over time,the number of patients undergoing supplemental surgery increased,while the proportion of cases with residual cancer decreased.Among 243 patients included in the risk factor analysis,univariate analysis indicated that submucosal invasion depth of SM2 or greater,poor tumor differentiation,positive vascular invasion,and tumor location were high-risk factors for lymph node metastasis.Multivariate analysis identified invasion depth(P=0.039)and tumor location(P=0.014)as independent risk factors.Among the metastatic cases,58.3％involved a single lymph node;63.9％of metastases were limited to the first station,and 36.1％extended to the second station,with no metastasis found at the third station.Only four patients had preoperative imaging suggestive of lymph node enlargement.Conclusion:Although the number of supplemental surgeries following endoscopic resection of early-stage colorectal cancer has increased significantly,the actual rate of lymph node metastasis remains low,suggesting a potential risk of overtreatment.Submucosal invasion depth ≥SM2 and tumor location are independent risk factors for metastasis.D2 lymph node dissection is deemed necessary,while the diagnostic value of imaging remains limited.Clinical decisions should prioritize precision and individualized treatment planning.

Chronic heart failure is the terminal stage of various cardiovascular diseases， and cardiomyocyte apoptosis is the turning point of decompensation. Studies have shown that traditional Chinese medicine （TCM） could regulate apoptosis-related signaling pathways and factors and inhibit or up-regulate the expression of apoptosis-related proteins. Thus， TCM can reduce cardiomyocyte apoptosis， protect the myocardial tissue and improve the cardiac function， demonstrating remarkable clinical effects. In recent years， the research on the treatment of chronic heart failure based on the inhibition of cardiomyocyte apoptosis is increasing and becomes the current research hotspot. On the basis of literature review， this paper discovers that TCM regulates apoptosis factors and multiple signaling pathways to inhibit apoptosis and inflammation and delay the progression of chronic heart failure through classical pathways such as the death receptor pathway， the mitochondrial pathway， and the endoplasmic reticulum pathway. At the same time， the studies in this field have the following problems： Repeated studies with shallow， simple， and fragmented contents， treating animal models with TCM prescriptions without syndrome differentiation， treating diseases with drugs at only one concentration which is insufficient to indicate efficacy， and lacking comprehensive， holistic， and systematic studies on the relationships of apoptosis with inflammatory responses， pyroptosis， ferroptosis， and autophagy. In the future， more scientific， reasonable， comprehensive， and feasible experimental schemes should be designed on the basis of comprehensively mastering the research progress in this field， and the communication and cooperation between researchers in different disciplines should be strengthened. The specific pathological mechanism of cardiomyocyte apoptosis in chronic heart failure and the signaling pathways， active components， and action targets of TCM in inhibiting cardiomyocyte apoptosis in chronic heart failure should be elucidated. Such efforts are expected to provide sufficient reference for the clinical treatment of chronic heart failure.