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18 October 2025, Volume 57 Issue 5
  • Development strategy of stomatology industry
    Guangyan YU
    2025, (5):  817-820.  doi: 10.19723/j.issn.1671-167X.2025.05.001    
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    Stomatology is a first-level discipline mainly focusing on maintaining and promoting oral health, as well as preventing and treating diseases of oral and maxillofacial system. Through the great efforts of generations of stomatologists, China's stomatologic causes has achieved remarkable results and rapid development. The number of stomatologists has reached 334 000, and the ratio of stomatologists to the population is 1:4 600, which have made China a major country in stomatology. However, compared with developed countries, there is still a considerable gap in the overall oral health level of our people. Strengthen the construction of stomatologist team, especially the training of stomatologists at the basis level; Optimize medical education in stomatology and improve the quality of graduates; Strengthen primary oral care and lay a solid foundation for oral care service; Regulate private dental institutions and strengthen their construction; Popularize knowledge about oral health, enhance public awareness of oral health, and improve public oral health behaviors; Give full play to the leading role of new ideas, knowledge and technologies in stomatology is a key link in developing stomatology and building a strong country in stomatology.
    Artificial intelligence in stomatology: Innovations in clinical practice, research, education, and healthcare management
    Xuliang DENG, Mingming XU, Chenlin DU
    2025, (5):  821-826.  doi: 10.19723/j.issn.1671-167X.2025.05.002    
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    In recent years, China has continued to face a high prevalence of oral diseases, along with uneven access to high-quality dental care. Against this backdrop, artificial intelligence (AI), as a data-driven, algorithm-supported, and model-centered technology system, has rapidly expanded its role in transforming the landscape of stomatology. This review summarizes recent advances in the application of AI in stomatology across clinical care, biomedical and materials research, education, and hospital management. In clinical settings, AI has improved diagnostic accuracy, streamlined treatment planning, and enhanced surgical precision and efficiency. In research, machine learning has accelerated the identification of disease biomarkers, deepened insights into the oral microbiome, and supported the development of novel biomaterials. In education, AI has enabled the construction of knowledge graphs, facilitated personalized learning, and powered simulation-based training, driving innovation in teaching methodologies. Meanwhile, in hospital operations, intelligent agents based on large language models (LLMs) have been widely deployed for intelligent triage, structured pre-consultations, automated clinical documentation, and quality control, contributing to more standardized and efficient healthcare delivery. Building on these foundations, a multi-agent collaborative framework centered around an AI assistant for stomatology is gradually emerging, integrating task-specific agents for imaging, treatment planning, surgical navigation, follow-up prediction, patient communication, and administrative coordination. Through shared interfaces and unified knowledge systems, these agents support seamless human-AI collaboration across the full continuum of care. Despite these achievements, the broader deployment of AI still faces challenges including data privacy, model robustness, cross-institution generalization, and interpretability. Addressing these issues will require the development of federated learning frameworks, multi-center validation, causal reasoning approaches, and strong ethical governance. With these foundations in place, AI is poised to move from a supportive tool to a trusted partner in advancing accessible, efficient, and high-quality stomatology services in China.
    Biological characteristics and translational research of dental stem cells
    Qianmin OU, Zhengshi LI, Luhan NIU, Qianhui REN, Xinyu LIU, Xueli MAO, Songtao SHI
    2025, (5):  827-835.  doi: 10.19723/j.issn.1671-167X.2025.05.003    
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    Dental stem cells (DSCs), a distinct subset of mesenchymal stem cells (MSCs), are isolated from dental tissues, such as dental pulp, exfoliated deciduous teeth, periodontal ligament, and apical papilla. They have emerged as a promising source of stem cell therapy for tissue regeneration and autoimmune disorders. The main types of DSCs include dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), and stem cells from apical papilla (SCAP). Each type exhibits distinct advantages: easy access via minimally invasive procedures, multi-lineage differentiation potential, and excellent ethical acceptability. DSCs have demonstrated outstanding clinical efficacy in oral and maxillofacial regeneration, and their long-term safety has been verified. In oral tissue regeneration, DSCs are highly effective in oral tissue regeneration for critical applications such as the restoration of dental pulp vitality and periodontal tissue repair. A defining advantage of DSCs lies in their ability to integrate with host tissues and promote physiological regeneration, which render them a better option for oral tissue regenerative therapies. Beyond oral applications, DSCs also exhibit promising potential in the treatment of systemic diseases, including type Ⅱ diabetes and autoimmune diseases due to their immunomodulatory effects. Moreover, extracellular vesicles (EVs) derived from DSCs act as critical mediators for DSCs' paracrine functions. Possessing regulatory properties similar to their parental cells, EVs are extensively utilized in research targeting tissue repair, immunomodulation, and regenerative therapy—offering a "cell-free" strategy to mitigate the limitations associated with cell-based therapies. Despite these advancements, standardizing large-scale manufacturing, maintaining strict quality control, and clarifying the molecular mechanisms underlying the interaction of DSCs and their EVs with recipient tissues remain major obstacles to the clinical translation of these treatments into broad clinical use. Addressing these barriers will be critical to enhancing their clinical applicability and therapeutic efficacy. In conclusion, DSCs and their EVs represent a transformative approach in regenerative medicine, and increasing clinical evidence supports their application in oral and systemic diseases. Continuous innovation remains essential to unlocking the widespread clinical potential of DSCs.
    Current situation and exploration of clinical transformation of plasmatrix in oral implantology
    Yulan WANG, Hao ZENG, Yufeng ZHANG
    2025, (5):  836-840.  doi: 10.19723/j.issn.1671-167X.2025.05.004    
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    With the rapid development of implant dentistry, increasing attention has been paid to the long-term stability and aesthetic outcomes of dental implants, among which sufficient volume and quality of soft and hard tissues are considered crucial contributing factors for successful treatment outcomes. Among the various available tissue regeneration strategies, plasmatrix, an autologous biomaterial derived from the patient ' s own peripheral blood, has demonstrated unique and significant clinical value in the regeneration and augmentation of both soft and hard tissues associated with dental implant therapy in recent years. This notable potential is primarily attributed to its rich content of multiple growth factors, viable cells, and a supportive fibrin scaffold, along with its excellent biocompatibility, tunable biodegradation profile, and a relatively simple and rapid preparation process that does not require complex laboratory equipment. As a result, its clinical applications have been continuously expanding across a wide range of indications. Based on a comprehensive review of the existing literature and current research evidence, this article provides an in-depth summary of the advancements in both basic science and clinical applications of plasmatrix in the context of implant dentistry. Particular attention is given to its classification from a materials science perspective, underlying molecular mechanisms, biological effects in promoting tissue regeneration, and its implementation under different clinical scenarios. Furthermore, the article discusses unresolved technical challenges and existing controversies, and outlines potential future directions for research and technological innovation, aiming to provide robust evidence-based guidance for clinical practice as well as a theoretical and methodological reference for future scientific investigations.
    Establishment and application of key technologies for periodontal tissue regeneration based on microenvironment and stem cell regulation
    Baojin MA, Jianhua LI, Yuanhua SANG, Yang YU, Jichuan QIU, Jinlong SHAO, Kai LI, Shiyue LIU, Mi DU, Lingling SHANG, Shaohua GE
    2025, (5):  841-846.  doi: 10.19723/j.issn.1671-167X.2025.05.005    
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    The prevalence of periodontitis in China is as high as 74.2%, making it the leading cause of tooth loss in adults and severely impacting both oral and overall health. The treatment of periodontitis and periodontal tissue regeneration are global challenges of significant concern. GE Shaohua' s group at School and Hospital of Stomatology, Shandong University has focused on the key scientific issue of "remodeling the periodontal inflammatory microenvironment and optimizing tissue repair and regeneration". They have elucidated the mechanisms underlying the persistence of periodontitis, developed bioactive materials to enhance stem cell regenerative properties, and constructed a series of guided tissue regeneration barrier membranes to promote periodontal tissue repair, leading to the establishment of a comprehensive technology system for the treatment of periodontitis. Specific achievements and progress include: (1) Elucidating the mechanism by which key periodontal pathogens evade antimicrobial autophagy, leading to inflammatory damage; developing intelligent antimicrobial hydrogels and nanosystems, and creating metal-polyphenol network microsphere capsules to reshape the periodontal inflammatory microenvironment; (2) Explaining the mechanisms by which nanomaterial structures and electroactive interfaces regulate stem cell behavior, developing optimized nanostructures and electroactive biomaterials, thereby effectively enhancing the regenerative repair capabilities of stem cells; (3) Creating a series of biphasic heterogeneous barrier membranes, refining guided tissue regeneration and in situ tissue engineering techniques, stimulating the body' s intrinsic repair potential, and synergistically promoting the structural regeneration and functional reconstruction of periodontal tissues. The research outcomes of the group have innovated the fundamental theories of periodontal tissue regeneration, broken through foreign technological barriers and patent blockades, established a cascade repair strategy for periodontal regeneration, and enhanced China' s core competitiveness in the field of periodontal tissue regeneration.
    Construction and application of oral squamous cell carcinoma organoid bank
    Shang XIE, Luming WANG, Xinyuan ZHANG, Qiushi FENG, Yangyang XIA, Ziwei DAI, Xiaofeng SHAN, Zhigang CAI
    2025, (5):  847-851.  doi: 10.19723/j.issn.1671-167X.2025.05.006    
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    Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies, with more than 370 000 new cases and approximately 188 000 deaths annually worldwide. In China, there are roughly 65 000 new cases and 35 000 deaths each year, showing a significant upward trend compared with 2015 statistics. Despite continuous advancements in treatment modalities, the 5-year survival rate remains stagnant at 50%-60%, where tumor heterogeneity and therapy resistance persist as fundamental barriers to precision oncology. To address these critical challenges, this study established a standardized bioban-king protocol for OSCC patient-derived organoids (PDOs) (Patent: Method for constructing an oral squamous cell carcinoma organoid bank, ZL202311378598.3). Through groundbreaking optimization of culture media, enzymatic digestion kinetics, and stepwise cryopreservation, we achieved a biobanking success rate exceeding 95% and pioneered synchronous cultivation of matched primary tumors, lymph node metastases, and adjacent normal mucosa from individual patients, preserving spatial heterogeneity and stromal interactions. Leveraging this platform, we developed high-throughput drug screening: Quantified heterogeneity-driven differential chemoresponse using adenosine triphosphate (ATP)-based viability assays; We discovered resistance mechanisms: Identified sialylated cancer IgG (SIA-cIgG)-mediated cis-platin resistance (primary/secondary) through PTPN13 suppression, with anti-SIA-cIgG combination therapy demonstrating synergistic efficacy. Besides, we elucidated metastatic drivers: CRISPR-Cas9-edited organoids revealed WDR54 promoted metastasis via H3K4me3/H4K16ac epigenetic reprogramming, activating epithelial-mesenchymal plasticity (EMP) and inducing partial epithelial-mesenchymal transition (pEMT). This "holographic patient-mirroring" platform provided unprecedented resolution for OSCC precision therapy and had been formally incorporated into the Chinese Stomatological Association Technical Guidelines (Technical guideline for establishing patient-derived oral squamous cell carcinoma organoid banks, CHSA 2024-08). Future integration of immune-competent organoids, 3D-bioprinted vasculature, and multi-omics-AI systems will accelerate personalized oncology. These innovations will accelerate clinical translation of personalized therapeutic regimens, ultimately bridging the gap between bench research and bedside application.
    Periodontitis and systemic diseases: Thinking and explorations
    Pei CAO, Qingxian LUAN
    2025, (5):  852-858.  doi: 10.19723/j.issn.1671-167X.2025.05.007    
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    Periodontitis has become one of the most widespread chronic inflammatory diseases worldwide, affecting roughly 11% of the adult population. In China, periodontal health is notably poor, with less than 10% of individuals over the age of 35 maintaining periodontal health, while the prevalence of periodontitis in middle-aged and elderly populations reaches as high as 82.6%. From a public health perspective, periodontitis not only seriously compromises oral health but is also closely linked to multiple chronic systemic diseases, including cardiovascular disease, diabetes mellitus, and cognitive impairment. A substantial body of cohort studies and meta-analyses consistently demonstrate that patients with periodontitis are at a significantly increased risk of cardiovascular events. Moreover, periodontitis tends to progress more rapidly in individuals with diabetes, highlighting a bidirectional causal relationship between these two conditions. Our research team has maintained a long-term focus on elucidating the relationship between periodontitis and systemic diseases within Chinese community populations. In this review, we comprehensively summarize epidemiological findings on the associations between periodontitis and cardiovascular disease, metabolic syndrome, and cognitive decline, specifically drawing on data from Chinese cohorts. Complementing these observations, animal experiments provide evidence that experimental periodontitis can induce glucose intolerance and accelerate the development of atherosclerotic lesions. At the mechanistic level, we preliminarily validate that mitochondrial DNA efflux and the hematogenous spread of periodontal pathogens may act as biological conduits bridging local periodontal inflammation with systemic pathologies. We also address current challenges in the field, including difficulties in disentangling causal relationships due to confounding comorbidities like diabetes and cardiovascular diseases, which often coexist and influence each other. To advance understanding, there is an urgent need for well-designed longitudinal and interventional studies employing advanced causal inference methods. Ultimately, this work aims to deepen the current knowledge of periodontitis ' systemic effects and to support the development of evidence-based public health strategies for integrating oral health into chronic disease prevention efforts in China.
    Application of salivary micro-ecosystem in early prevention and control of oral and systemic diseases
    Xiangyu SUN, Chao YUAN, Xinzhu ZHOU, Jing DIAO, Shuguo ZHENG
    2025, (5):  859-863.  doi: 10.19723/j.issn.1671-167X.2025.05.008    
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    Saliva is an important body fluid in the oral cavity containing lots of biomarkers, whose inherent micro-ecosystem holds significant value for early diagnosis and monitoring of oral diseases. Simultaneously, saliva has particular advantages, such as ease of sampling, painless and non-invasive collection, and suitability for repeated sampling, making it highly appropriate for surveillance and follow-up of diseases. In a series of studies conducted by the research group for preventive dentistry in Peking University School and Hospital of Stomatology, we compared different segments of saliva and those samples collected via different sampling methods using proteomic/peptidomic and microbiomic technologies to explore the stability of saliva samples. Besides, the significance of applying representative salivary biomarkers in early prevention and control of representative oral diseases (e.g. dental caries, periodontal diseases) and systemic conditions (e.g. type 2 diabetes mellitus, chronic kidney disease) was confirmed as well.
    Development and dissemination of precision medicine approaches in gastric cancer management
    Zhemin LI, Jiafu JI, Guoxin LI, Ziyu LI, Zhaode BU, Xiangyu GAO, Di DONG, Lei TANG, Xiaofang XING, Shuqin JIA, Ting GUO, Lianhai ZHANG, Fei SHAN, Xin JI, Anqiang WANG
    2025, (5):  864-867.  doi: 10.19723/j.issn.1671-167X.2025.05.009    
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    Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
    Cross-century process of mental health surveys in China
    Junjie HUANG, Zhaorui LIU, Tingting ZHANG, Yueqin HUANG
    2025, (5):  868-874.  doi: 10.19723/j.issn.1671-167X.2025.05.010    
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    The epidemiological research on mental health in China has undergone decades of development, transitioning from multi-regional surveys to nationally representative studies. In 1982, Academician Shen Yucun led a team to complete the first national survey in 12 regions, revealing a point prevalence rate of 10.54‰. In 1993, the point prevalence rate in the second national survey in 7 regions rose to 11.18‰. In 2002, the Composite International Diagnostic Interview (CIDI)-3.0 and Diagnostic and Statistical Manual of Mental Disorders, Fouth Edition (DSM-Ⅳ) standards were first applied in the surveys in urban Beijing and Shanghai to achieve international standards, but the representativeness of urban samples was limited. Subsequent regional studies contributed methodological insights toward a nationally representative survey. From 2013 to 2015, a research team led by Professor Huang Yueqin, in collaboration with 43 institutions, completed the China Mental Health Survey (CMHS), covering 32 552 community adults in 157 counties/districts in 31 provinces/autonomous. This study represents the first nationally representative epidemiological survey of mental disorders in China. The main results showed that the lifetime prevalence of mental disorders among adults in Chinese communities with depressive disorders was 16.6%, including 7.4% for mood disorders and 7.6% for anxiety disorders. Only 9.5% of patients with depressive disorders received treatment, and the full treatment rate was as low as 0.5%. Further surveys based on the CMHS framework in regions such as Ningxia, Urumqi, and Inner Mongolia confirmed the high risk of disease among rural women in western China and the widespread phenomenon of inadequate treatment. The results of CMHS methodology was transformed into the national Guidelines and Technical Standards for Epidemiological Investigation of Community Mental Disorders (2015 Edition) and software copyright, and the main data had been published in The Lancet Psychiatry. It has been used to guide the formulation of policies such as the Healthy China Action (2019-2030). CMHS establishing a complete process from scientific investigation to policy translation, filling the data gap at the national level, providing a replicable paradigm for the world, especially for developing countries, and marking a new stage of evidence-based decision-making in China's mental health epidemiological research.
    Effect of aquaporin 5 on TLR4/MyD88/NF-κB signaling pathway in Sjögren syndrome rats
    Lixiu ZHU, Renli CHEN, Sujuan ZHOU, Ye LIN, Yirong TANG, Zhen YE
    2025, (5):  875-883.  doi: 10.19723/j.issn.1671-167X.2025.05.011    
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    Objective: To investigate the effect of aquaporin 5 (AQP5) on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in Sjögren syndrome (SS) rats. Methods: The SS gene expression data sets GSE406611 and GSE84844 were extracted from the Gene Expression Omnibus (GEO), and the AQP5 mRNA expression was analyzed by R software. The rat SS model was constructed. The successfully modeled rats were divided into SS group, SS+NC group, and SS+pc group, 10 rats in each group; and 10 rats were set as Normal group. The rats in the SS+NC group were injected with 10 μg of rno-pcDNA3.1-AQP5-NC at the submandibular gland, subcutaneously every day for 28 days. The rats in the SS+pc group were injected with 10 μg of rno-pcDNA3.1-AQP5 at the submandibular gland, subcutaneously every day for 28 days. The enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum. High-throughput sequencing was used to identify the target genes. Quantitative real-time PCR (qPCR) and Western blot were used to detect the mRNA and protein expressions of AQP5, TLR4, MyD88, and NF-κB in the rat submandibular gland tissue. Results: In the SS dataset GSE406611 and GSE84844, the mRNA expression of AQP5 in SS was significantly reduced. Compared with the Normal group, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS group were significantly increased, the mRNA and protein expressions of AQP5 were significantly decreased. After overexpression of AQP5, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS+pc group were significantly decreased, the mRNA and protein expressions of AQP5 were significantly increased. The differences were statistically significant (all P < 0.05). Conclusion: The expression of AQP5 is involved in the progression of SS. Increasing the expression of AQP5 can significantly inhibit inflammatory stress and reduce the pathological damage of submandibular gland tissue. This may be related to the inhibition of TLR4/MyD88/NF-κB conduction.
    HDAC2-mediated H3K27 acetylation promotes the proliferation and migration of hepatocellular carcinoma cells
    Shaohai TANG, Baoming YANG, Jiankun LI, Lili ZHAO, Yifan WANG, Shunxiang WANG
    2025, (5):  884-894.  doi: 10.19723/j.issn.1671-167X.2025.05.012    
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    Objective: To explore the specific mechanism of histone deacetylase 2 (HDAC2) mediated histone H3 lysine 27 acetylation (H3K27ac) modification in promoting the proliferation and migration of hepatocellular carcinoma cells. Methods: Samples of 40 cases of hepatocellular carcinoma and paracancerous tissues resected from January 2021 to January 2023 were collected. The expressions of HDAC2 and H3K27ac in hepatocellular carcinoma, paracancerous tissues and cell lines were detected by immunohistochemistry and Western blotting. The correlation between the expression levels of HDAC2 and H3K27ac and the relationship between HDAC2 expression and clinicopathological characteristics of patients with hepatocellular carcinoma were analyzed. The proliferation, migration and invasion of Hep3B and HepG2 cells were determined by MTS, clone formation, scratch and Transwell experiments. The acetylation of H3K27 mediated by HDAC2 was verified by Western blotting, real-time fluorescence quantitative PCR (qRT-PCR) and chromatin immunoprecipitation high-throughput sequencing (ChIP-seq). In vivo xenotransplantation experiment, the tumorigenicity of cells in each group was measured, and the expression of proteins related to phosphoinositide 3-kinases/phosphatase and tensin homolog deleted on chromosome ten/protein kinase B/mammalian target of rapamycin (PI3K/PTEN/AKT/mTOR) signal pathway was detected. Results: High expression of HDAC2 and low expression of H3K27ac were found in hepatocellular carcinoma tissues and cell lines (P < 0.05), and there was a negative correlation between them (r=-0.477, P=0.002). The expression of HDAC2 was related to tumor size, hepatitis B virus infection, TNM stage and portal vein tumor thrombus (P < 0.05). Compared with the sh-NC group of Hep3B and HepG2 cells, the proliferation, clone formation, migration and invasion ability of sh-HDAC2 group were decreased (P < 0.05). Compared with the Empty group, the HDAC2 group exhibited increased expression levels and activity of HDAC2, as well as enhanced cell proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and elevated expression levels of p-PI3K, p-AKT, and p-mTOR (P < 0.05). Conversely, the enrichment and expression levels of H3K27ac, along with the expression level of PTEN, were decreased (P < 0.05). In the iHDAC2 group, the expression levels and activity of HDAC2, as well as the proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and expression levels of p-PI3K, p-AKT, and p-mTOR were reduced (P < 0.05). Additionally, the expression levels of H3K27ac and PTEN were increased (P < 0.05). To validate the involvement of the PI3K/PTEN/AKT/mTOR signaling pathway in HDAC2-mediated regulation of malignant behaviors in liver cancer cells through H3K27ac, the PI3K activator 740Y-P was introduced. Compared with the iHDAC2 group, the iHDAC2+740Y-P group exhibited increased proliferation, clone formation, migration, invasion ability, tumor volume and mass in vivo, and elevated expression levels of p-PI3K, p-AKT, and p-mTOR (P < 0.05). Conversely, the expression level of PTEN was decreased (P < 0.05). Conclusion: HDAC2 initiates PI3K/PTEN/AKT/mTOR signal pathway by mediating H3K27 acetylation, which promotes the occurrence and development of hepatocellular carcinoma.
    Protein biomarker screening and functional analysis of salivary exosomes in patients with ulcerative colitis
    Congyi YANG, Xiaowen ZHENG, Jingyi CHEN, Jun XU, Feng CHEN, Yang CHEN, Ning CHEN
    2025, (5):  895-902.  doi: 10.19723/j.issn.1671-167X.2025.05.013    
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    Objective: To identify protein markers that may be associated with ulcerative colitis (UC) by analyzing differential proteins in the salivary exosomes from newly diagnosed patients with active UC and healthy controls (HC), and to investigate the function of salivary exosome-specific high-expression proteins in UC patients and their potential role in the pathogenesis of UC. Methods: All patients and healthy controls were recruited from Peking University People' s Hospital. Whole saliva was obtained from 37 patients with newly diagnosed active ulcerative colitis (n=37) and apparently healthy controls (n=10). Salivary exosomes were extracted from samples, and the proteins within the exosomes were identified by liquid chromatograph-mass spectrometer (LC-MS/MS). The differentially expressed protein genes underwent gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis using the DAVID tool. In vitro, macrophages were co-cultured with salivary exosomes from UC group and those from HC group, respectively, and real-time quantitative polymerase chain reaction (qPCR) was used to detect levels of CD80+ and CD86+. Additionally, ELISA was performed to measure secretion levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in the cell supernatant. Results: A total of 259 proteins were co-expressed in saliva exosomes from UC group and HC group, among which 11 proteins were highly expressed in the UC group, including PDIA4, A2M, EEF2, C3, PSMA2, PSMB6, PSMA1, IGHG1, IGHG3, IGHG4 and SERPING1, while 4 proteins were lowly expressed in UC group, including TCN1, SLPI and SERPING. Functional analysis of these 15 proteins, along with 129 specific proteins found only in the UC patients and 69 specific proteins found only in HC patients, respectively, was conducted using GO/KEGG. The results revealed that in the UC group, proteasome-related proteins such as PSMA1, PSMA2 and PSMB6 expressions were increased in salivary exosomes while many key molecules involved in complement cascade pathways, such as C3 were up-regu-lated. In vitro co-culture experiments demonstrated that compared with healthy controls, the salivary exosomes of the UC patients in active stage could play a pro-inflammatory role by promoting the transformation of macrophages into M1 type cells that secrete inflammatory factors IL-1β, IL-6 and TNF-α. Conclusion: Salivary exosomes in the UC patients may have the function of promoting inflammation. Analysis of protein levels in the saliva of the UC patients and healthy controls revealed significant differences in the expression levels of 15 co-expressed proteins between the two groups. Among them, C3, PSMA2, PSMB6 and PSMA1 were found to be mainly related to immune and inflammatory reactions in the UC group. These findings suggest that proteins with high specific expression in salivary exosomes of the UC patients have the potential to be used as a disease marker for UC diagnosis and may contribute to the pathogenesis of UC.
    Pathogenesis and mechanism of serine protease 23 in skin fibrosis of systemic sclerosis
    Xiandun YUAN, Zhaohua LI, Dan XU, Ting LI, Dan FANG, Rong MU
    2025, (5):  903-910.  doi: 10.19723/j.issn.1671-167X.2025.05.014    
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    Objective: It has been reported that the mRNA expression of serine protease 23 (PRSS23) was increased in skin fibroblasts from systemic sclerosis patients (SSc). The purpose of this study is to explore the pathogenetic effect and mechanism of PRSS23 in skin fibrosis of SSc. Methods: The expression of PRSS23 in skin tissues from the SSc patients and healthy controls was detected by immunohisto-chemistry. Fibroblasts isolated from fresh skin tissue were used to detect the expression of PRSS23 by real-time quantitative PCR (RT-qPCR) and Western blot. Overexprssion of PRSS23 in BJ, the fibroblasts cell line of skin, was constructed by lentivirus. After stimulation with 400 μmol/L hydrogen peroxide for 12 h, Annexin V/7-AAD staining was used to detect apoptosis of fibroblasts; flow cytometry and Western blot were used to detect the expression of apoptosis-related protein cleaved Caspase-3. The expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in fibroblasts was detected by RT-qPCR and enzyme linked immunosorbent assay (ELISA). Results: Compared with the healthy controls, the expression of PRSS23 in skin tissues of the SSc patients was significantly increased [4.952 (3.806-5.439) vs. 0.806 (0.395-1.173), P < 0.001], and fibroblast was the main cell that expressed PRSS23. The mRNA [27.59 (25.02-30.00) vs. 1.00, P < 0.001] and protein [0.675 (0.587-0.837) vs. 0.451 (0.342-0.502), P=0.029] of PRSS23 in skin fibroblasts isolated from the SSc patients were significantly up-regulated. Compared with the control group, the anti-apoptotic ability of skin fibroblasts overexpressing PRSS23 was enhanced, and the proportion of apoptotic cells was significantly reduced after hydrogen peroxide induction [(5.043±1.097)% vs. (17.480±3.212)%, P=0.022], the expression of apoptosis-related protein cleaved Caspase-3 was also markedly reduced [(0.718±0.022) vs. (1.422±0.105), P=0.003]. In addition, the mRNA [(99.780±1.796) vs. (1.000±0.004), P < 0.001] and protein [(211.600±2.431) ng/L vs. (65.930±1.768) ng/L, P < 0.001] of IL-6 in the fibroblasts overexpressing PRSS23 were significantly up-regulated; the mRNA[(3.555±0.555) vs. (1.000±0.004), P < 0.001] and protein levels [(41.190±0.949) ng/L vs. (31.150±0.360) ng/L, P < 0.001] of TNF-α in the fibroblasts overexpressing PRSS23 were also significantly up-regulated. Conclusion: The expression of PRSS23 is increased in skin fibroblasts of SSc patients. PRSS23 can inhibit cell apoptosis, promote the secretion of inflammatory factors such as IL-6 and TNF-α, and regulate the process that skin fibroblasts transform into pro-inflammatory type. So, PRSS23 is associated with the development of skin fibrosis.
    Expression of lumican protein in serum of patients with rheumatoid arthritis and its correlation with disease and immune activities
    Ju YANG, Jing XU, Juhua DAI, Lianjie SHI
    2025, (5):  911-918.  doi: 10.19723/j.issn.1671-167X.2025.05.015    
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    Objective: To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA). Methods: The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples t test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-t test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at P < 0.05. Results: The levels of LUM were elevated in the RA patients than in the HCs (P < 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all P < 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (P>0.05). The levels of serum LUM were elevated in the RF positive patients (P < 0.000 1), and in the RF and anti-CCP positive patients (P < 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (P>0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (P < 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (P < 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (P < 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (P>0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (P>0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (P < 0.05). Conclusion: LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activity and immune activity in RA.
    Role and mechanism of ubiquitin-specific protease 35 in ferroptosis of rheumatoid arthritis-fibroblast like synoviocytes
    Lianghua FENG, Lirong HONG, Yujia CHEN, Xueming CAI
    2025, (5):  919-925.  doi: 10.19723/j.issn.1671-167X.2025.05.016    
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    Objective: To elucidate the role and underlying mechanism of ubiquitin-specific protease 35 (USP35) in ferroptosis of rheumatoid arthritis-fibroblast like synoviocytes (RA-FLS), thereby enhancing our comprehension of the pathogenesis of RA and identifying potential therapeutic targets for its treatment. Methods: (1) RA-FLS were cultured in vitro and transduced with lentiviral vectors to establish stable cell lines: A USP35-knockdown line (short hairpin ribonucleic acid of USP35, shUSP35) and its control (negtive control of short hairpin ribonucleic acid, shNC), as well as a overexpression of USP35 line (USP35 OE) and its control (Vector). To investigate the role of USP35 in ferroptosis regulation, a ferroptosis model was induced in RA-FLS by treatment with 1 μmol/L Erastin. The cells were divided into six groups: shNC, shNC + Erastin, shUSP35 + Erastin, Vector, Vector + Erastin, and USP35 OE + Erastin. (2) Cell viability was detected using the cell counting kit-8 (CCK-8). (3) Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione/glutathione disulfide (GSH/GSSG) ratios, and Ferrous ion (Fe2+) levels were measured using specific assay kits to evaluate oxidative stress, lipid peroxidation, and glutathione redox status in the cells. (4) Protein expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were detected using Western blotting to investigate their potential involvement in USP35-mediated ferroptosis regulation. Results: (1) Compared with the shNC +Erastin group, the cell viability of the shUSP35+Erastin group was significantly decreased (P < 0.001), while it was notably increased in the USP35 OE+Erastin group compared with the Vector+Erastin group (P < 0.001). These findings indicated that USP35 could alleviate the inhibitory effect of Erastin on RA-FLS cell viability. (2) In comparison to the shNC+Erastin group, the levels of ROS (P < 0.001), MDA (P < 0.05), and Fe2+ (P < 0.001) were significantly elevated, and the GSH/GSSG ratio was increased (P < 0.05) in the shUSP35+Erastin group. Conversely, the levels of ROS (P < 0.001), MDA (P < 0.05), and Fe2+ (P < 0.05) were significantly decreased, and the GSH/GSSG ratio was decreased (P < 0.05) in the USP35 OE+Erastin group compared with the Vector+Erastin group. These results suggested that USP35 could inhibit Erastin-induced oxidative stress and lipid peroxidation in RA-FLS. (3) In Erastin-induced RA-FLS, the expression of USP35 was positively correlated with the protein levels of SLC7A11 and GPX4, indicating a potential mechanism by which USP35 regulated ferroptosis in these cells. Conclusion: USP35 inhibits ferroptosis in RA-FLS, potentially through the increased expression of SLC7A11 and GPX4.
    Effect of the combination of alkaloids from Euodiae Fructus and berberine in Zuojin Pill on cytotoxicity in HepG2 cells
    Yadong GAO, An ZHU, Ludi LI, Yingzi LI, Qi WANG
    2025, (5):  926-933.  doi: 10.19723/j.issn.1671-167X.2025.05.017    
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    Objective: To investigate the hepatotoxicity of alkaloids from Euodiae Fructus combined with berberine (BBR) in Zuojin Pill, and to preliminarily explore the possible detoxification mechanism of the combination components. Methods: The combination ratio of components was determined by the maximum concentration (Cmax) of the chemical components in Zuojin Pill. HepG2 cell model was used to investigate the combined toxicity of the hepatotoxic components from Euodiae Fructus, such as evodiamine (EVO) or dehydroevodiamine (DHED), with BBR for 48 h. The experimental groups were set as follows: the vehicle control group, the EVO group, the DHED group, the BBR group, and the combination group of EVO or DHED with BBR. The cell counting kit-8 (CCK-8) method was used to determine the cell viability, and the combination index (CI) was used to determine the combined toxicity of the components. The alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydroge-nase (LDH), and alkaline phosphatase (ALP) activities as well as total bilirubin (TBIL) content in the cell culture supernatant were detected. The protein expression levels of bile acid transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2), were detected by Western blot. The intracellular malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in HepG2 cells were detected. Results: Compared with EVO or DHED group, the combination of EVO 1 μmol/L with BBR 10 μmol/L or DHED 50 μmol/L with BBR 35 μmol/L significantly increased cell viability of HepG2 cells (P < 0.01), with CI values of 77.89 or 4.49, respectively, much greater than 1. Significant decreases in the activities of ALT, AST, LDH, ALP, and TBIL content in the cell culture supernatant were found in both combination groups (P < 0.05, P < 0.01). Compared with the EVO group, the combination of EVO with BBR upregulated the protein expression levels of BSEP and MRP2. Compared with the DHED group, the combination of DHED with BBR significantly downregulated the protein expression levels of BSEP and MRP2 (P < 0.01). Compared with EVO or DHED group, the combination of EVO or DHED with BBR significantly reduced the MDA content in HepG2 cells (P < 0.05, P < 0.01). Conclusion: A certain ratio of BBR combined with EVO or DHED had an antagonistic effect on HepG2 cytotoxicity, which might be related to regulating the expression of bile acid transpor-ters, and reducing lipid peroxidation damage.
    Influence of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis
    Xiangxian LIU, Yi LIN, Jinzhu GUO
    2025, (5):  934-940.  doi: 10.19723/j.issn.1671-167X.2025.05.018    
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    Objective: To assess the impact of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis patients. Methods: The study included patients over 18 years old who had been treated by biological agents for at least 24 weeks for moderate to severe plaque psoriasis from Novermber 2015 to January 2024. According to the biological agents the patients used, they were divided into three groups: interleukin-17 (IL-17) inhibitor group, IL-23 and IL-12/23 inhibitor group and tumor necrosis factor-α (TNF-α) inhibitor group. The metabolic biochemical parameters of each group were evaluated and compared before and after the administration of the biologic therapies. Results: A total of 174 patients with moderate to severe plaque psoriasis were included in the long-term treatment with biologics, including 127 males (73.00%), 47 females (27.00%), with a median age of 38.00 (31.50, 49.00) years and a median duration of psoriasis of 12.00 (10.00, 20.00) years. The median duration of biologic treatment was 61.00 (49.00, 96.25) weeks, ranging from 26 to 301 weeks. There were 101 patients in the IL-17 inhibitor group, 38 patients in the IL-23 and IL-12/23 inhibitor group, and 35 patients in the TNF-α inhibitor group. After long-term treatment with IL-17 inhibitors, no statistically significant changes were observed in body weight, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose (GLU), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with baseline measurements (P>0.05). However, low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced [(2.90±0.75) mmol/L vs. (3.05±0.79) mmol/L, t=-2.100, P=0.038], while uric acid (UA) levels showed a significant increase [(401.13±99.13) μmol/L vs. (364.94±91.11) μmol/L, t=5.215, P < 0.001]. The group with normal UA levels before treatment showed a significant increase after long-term application of biological agents compared with before treatment [(370.69± 89.59) μmol/L vs. (324.66±64.50) μmol/L, t=5.856, P < 0.001]. Following long-term application of IL-23 and IL-12/23 inhibitors, no statistically significant differences were observed in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C and UA levels when compared with baseline measurements (P> 0.05). However, LDL-C levels exhibited a significant reduction from baseline [(2.85±0.74) mmol/L vs. (3.12±0.68) mmol/L, t=-2.082, P=0.045]. After long-term treatment with TNF-α inhibitor, there were no significant differences in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C, LDL-C and UA compared with baseline measurements (P>0.05). Conclusion: Long-term application of IL-17 inhibitors in moderate to severe plaque psoriasis patients may result in elevated uric acid levels, particularly in patients with normal uric acid levels before treatment. The long-term use of IL-17 inhibitors, IL-23 inhibitors or IL-12/23 inhibitors might reduce LDL-C levels.
    Establishment and validation of a risk prediction model for scoliosis after Nuss procedure in children and young adults with pectus excavatum
    Bowen LI, Qiang ZHANG, Yixin SUN
    2025, (5):  941-946.  doi: 10.19723/j.issn.1671-167X.2025.05.019    
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    Objective: To identify the risk factors associated with the development of post-Nuss procedure scoliosis in pectus excavatum patients and to establish a relevant predictive model. Methods: A retro-spective review was conducted on pectus excavatum patients who underwent Nuss procedure in Department of Thoracic Surgery at Beijing Jishuitan Hospital between January 2018 and February 2023. We gathered the patient demographic information (including age, sex, height, weight, and body mass index) and diagnostic imaging results (echocardiogram, chest CT scan, full-spine radiography, and PA/lateral chest X-rays), and measurements of Haller index, asymmetry index, sternal torsion angle (STA) index, and Cobb angle changes. The risk of post-Nuss procedure scoliosis was assessed. Cox regression analysis was performed to identify independent risk factors for scoliosis development in the pectus excavatum patients. Based on the results of the Cox regression analysis, a risk prediction model was established, and its specific predictive performance was assessed through internal cross-validation. Results: A total of 59 pectus excavatum patients who underwent Nuss procedure were included after applying inclusion and exclusion criteria. The median follow-up duration was 6.84 months, and the follow-up results showed significant improvements in Haller index, STA index, and asymmetry index postoperatively. Twelve patients developed scoliosis 3 months after Nuss procedure, while 47 patients did not, the incidence of scoliosis was 20.3%. Cox regression analysis identified preoperative pulmonary artery hypertension and preoperative asymmetry index as independent risk factors for post-Nuss procedure scoliosis. A predictive model was constructed based on single-factor Cox regression analysis results, incorporating age, height, weight, body mass index, preoperative pulmonary artery hypertension, preoperative Haller index, STA index, asymmetry index, and Cobb angle. The receiver operating characteristic (ROC) curve was plotted, and the area under the curve (AUC) for the overall predictive model was calculated to be 0.995. A calibration curve demonstrated good alignment between predicted values and actual values. Conclusion: Nuss procedure achieved favorable clinical outcomes. However, postoperative scoliosis emerged as a significant complication with a high incidence rate. Pulmonary artery hypertension and asymmetry index were independent predictors of post-Nuss procedure scoliosis. The predictive model developed in this study demonstrated robust performance in estimating the risk of postoperative scoliosis.
    Clinical efficacy of arthroscopic medial patellofemoral complex reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia
    Fengyi HU, Qingyang MENG, Nayun CHEN, Jianing WANG, Zhenlong LIU, Yong MA, Yuping YANG, Xi GONG, Cheng WANG, Ping LIU, Weili SHI
    2025, (5):  947-955.  doi: 10.19723/j.issn.1671-167X.2025.05.020    
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    Objective: To investigate the midterm clinical efficacy of medial patellofemoral complex (MPFC) reconstruction for recurrent patellar dislocation with high-grade trochlear dysplasia. Methods: A retrospective analysis was carried out among adult patients who underwent arthroscopically assisted MPFC reconstruction between January 2014 and December 2020. Dejour classification was evaluated to grade trochlear dysplasia; tibial tubercle-trochlear groove (TT-TG) distance and Insall-Salvati index were measured. Preoperative and postoperative patient-reported outcome measures (PROMs) were compared, including International Knee Documentation Committee (IKDC) score, Kujala score, Lysholm score and Tegner score. Information regarding returning-to-sport rate, re-instability events and complications was collected. Patellar tilt (PT), lateral patellar displacement (LPD) and bisect offset (BSO) ratio were measured based on axial computed tomography before and after surgery to assess the patellofemoral congruence. Results: A total of 46 MPFC reconstructions in 43 patients were enrolled, including 16 male and 27 female. Mean age at surgery was (22.2±7.6) years (range: 14-44 years). Mean follow-up was (49.9±22.6) months (range: 18-102 months). The percentages of Dejour B, C and D dysplasia were 37.0% (17/46), 43.5% (20/46), and 19.6% (9/46), respectively. Mean Insall-Salvati index was 1.2±0.2 (range: 0.85-1.44), and mean TT-TG distance was (19.6±3.5) mm (range: 10.6-28.7 mm). At latest follow-up, there were significant improvements in all PROMs (P < 0.001): IKDC score, from 56.3±15.1 to 86.2±8.1; Kujala score, from 58.9±15.6 to 92.6±5.4; Lysholm score, from 63.7±15.0 to 94.0±5.7; Tegner score, from 3.1±1.4 to 4.7±1.4, and there were no significant differences in the improvements of the scores between the patients with Dejour B, C and D dysplasia. Overall, ninety percent of the patients returned to their preoperative sports level. One patient reported a postoperative subluxation, while no cases of infection, limited range of motion or patella fracture were observed. PT, LPD and BSO ratio were all significant altered (P < 0.001) after MPFC reconstruction. Conclusion: Arthroscopically assisted MPFC reconstruction yielded satisfactory midterm clinical results for recurrent patellar dislocation with high-grade trochlear dysplasia. No significant differences of improvements in knee function were observed among the three types of high-grade trochlear dysplasia.
    Clinical characteristics and influencing factors of extraglandular invasion of prostatic ductal adenocarcinoma
    Xiaoyong YANG, Fan ZHANG, Lulin MA, Cheng LIU
    2025, (5):  956-960.  doi: 10.19723/j.issn.1671-167X.2025.05.021    
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    Objective: To explore the differences in perioperative clinical and pathological characteristics of patients with different pathological types of prostate cancer undergoing radical prostatectomy, and to analyze the influencing factors that may affect the extraglandular invasion of ductal adenocarcinoma of the prostate. Methods: Retrospective collection was made of the radical prostatectomy patients who were admitted to Peking University Third Hospital from December 2011 to April 2021. The patients were screened based on inclusion criteria to obtain basic clinical features and postoperative pathological results. According to the pathological results, the patients were divided into ductal adenocarcinoma group (mixed with ductal adenocarcinoma) and acinar adenocarcinoma group, and a 1 ∶1 propensity score matching was performed to compare the differences in clinical characteristics between the two groups. Univariate and multivariate analyses of the factors related to extraglandular invasion were performed in the matched ductal adenocarcinoma groups. Results: A total of 764 patients with prostate cancer were enrolled in this study, of which 62 patients were confirmed to have ductal adenocarcinoma components by postoperative pathology. There was a statistically significant difference in the proportion of the patients with a history of diabetes in baseline characteristics between the two groups before propensity score matching (29.5% vs. 17.7%, P=0.027). A total of 61 patients with simple acinar adenocarcinoma were successfully matched with the patients with ductal adenocarcinoma, and there was no statistically significant difference in baseline characteristics between the two groups after matching (P>0.05). The comparison of perioperative clinical and pathological features showed that International Society of Urology Pathology (ISUP) grade (P=0.003), pT stage (P=0.004), extraglandular invasion rate (P=0.018) and vascular thrombus rate (P=0.019) in ductal adenocarcinoma group were significantly higher than those in simple acinous adenocarcinoma group. Univariate analysis of the influence factors of extraglandular invasion showed that prostate-specific antigen (PSA) level, prostate volume, ISUP grade, seminal vesicle invasion and perineural invasion might be the influencing factors of extraglandular invasion (P < 0.10). Binary Logistic regression analysis showed that perineural invasion was an independent factor of extraglandular invasion (OR=11.78, 95%CI: 1.97-70.56, P=0.007). Conclusion: Prostatic ductal adenocarcinoma has a worse prognosis than simple acinar adenocarcinoma. Perineural invasion is the influencing factor of extraglandular invasion of ductal adenocarcinoma.
    Prognostic analysis of laparoscopic simultaneous radical cystectomy and nephroureterectomy
    Shenmo LI, Dandan SU, Jiyu LIN, Haodong SONG, Lulin MA, Xiaofei HOU, Guoliang WANG, Hongxian ZHANG, Jianfei YE, Shudong ZHANG
    2025, (5):  961-966.  doi: 10.19723/j.issn.1671-167X.2025.05.022    
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    Objective: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). Methods: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. Results: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). Conclusion: The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.
    Imaging study of osteogenesis in maxillary sinus segment of zygomatic implants
    Ziyang YU, Houzuo GUO, Xi JIANG, Weihua HAN, Ye LIN
    2025, (5):  967-974.  doi: 10.19723/j.issn.1671-167X.2025.05.023    
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    Objective: To assess the osteogenesis height in maxillary sinus segment one year after zygomatic implantation by imaging methods, and evaluate the influence of patient factors, maxillary sinus anatomical factors and surgical factors on postoperative osteogenesis height. Methods: This study is a retrospective study, including patients who underwent zygomatic implantation and whose zygomatic implants passed through the maxillary sinus at the Department of Implantology, Peking University School and Hospital of Stomatology from July 2017 to January 2022. Preoperative and postoperative cone beam CT (CBCT)was taken to measure and calculate the average osteogenesis height (AOH) in maxillary sinus segment of the zygomatic implants, then the residual bone height, the width and morphology of the maxillary sinus floor in the buccal and palatal directions were measured. Besides, the integrity of Schneiderian membrane during implant surgery, and the general information of the patients and zygomatic implants were recorded. By comparing anatomical situations and surgical characteristics, the differences of AOH under different conditions were analyzed. Then AOH was divided into two groups (obvious osteogenesis group and non-obvious osteogenesis group) using the median as the threshold, and the influencing factors of osteogenesis were evaluated using mixed effect generalized linear model univariable and multivariable analysis. Results: A total of 47 zygomatic implants were implanted in 24 patients. During the average follow-up period of 12.1 months, there was no implant failure, and the implant survival rate was 100%. Postoperative CBCT showed that 43 zygomatic implants had osteogenic images in the maxillary sinus segment, most of which originated from the floor of the maxillary sinus, and the median AOH was 3.1 mm [interquartile range (IQR): 4.0 mm]. In terms of maxillary sinus width, there were 31 cases (66.0%) of wide type and 16 cases (34.0%) of narrow type. In the aspect of buccal and palatal morphology, 17 cases were taper (36.2%), 20 cases were round (42.6%), and 10 cases were flat (21.3%). The median of residual bone height was 2.8 mm (IQR: 2.2 mm) before operation. Univa-riate analysis of mixed effect generalized linear model showed that postoperative obvious osteogenic rate was related to the residual bone height (OR=2.09, P=0.006). Multivariate analysis showed that the resi-dual bone height (OR=2.55, P=0.022) and the shape of a taper maxillary sinus (OR=11.44, P=0.040) had a significant impact on the postoperative obvious osteogenic rate. Conclusion: The maxillary sinus floor showed osteogenic images 1 year after the zygomatic implantation surgery. Larger residual bone height and the shape of a taper maxillary sinus may be favorable factors for osteogenesis.
    Comparison of efficacy and safety of oral mucosa grafts and acellular dermal matrix grafts in the treatment of long-segment urethral stricture
    Wenyuan LENG, Duan GAO, Xiaoyu LI, Wei ZUO, Weimin HU, Zhenpeng ZHU, Chunru XU, Jian LIN, Xuesong LI
    2025, (5):  975-979.  doi: 10.19723/j.issn.1671-167X.2025.05.024    
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    Objective: To investigate the differential efficacy and safety profiles of oral mucosa (OM) grafts compared with acellular dermal matrix (ADM) grafts in the surgical management of long-segment urethral strictures. Methods: A retrospective cohort study was conducted involving 27 patients who underwent graft urethroplasty for long-segment urethral strictures in Peking University First Hospital, spanning from May 2010 to September 2023. The patient cohort comprised 14 individuals who received OM grafts and 13 who underwent ADM grafts. The participants were stratified into two groups based on the type of grafts material utilized during surgery. The demographic and clinical baseline characteristics included an average age of (43.3±14.0) years in the OM group and (54.2±15.9) years in the ADM group. The mean body mass index (BMI) for the respective groups were (24.7±4.3) kg/m2 for OM and (25.4±4.8) kg/m2 for ADM. Etiological differences were noted, with idiopathic causes predominantly in the OM cohort and lichen sclerosus in the ADM cohort. Results: The surgical interventions were successfully executed for all the patients. The median stricture length was 4.5 (2.5, 9.0) cm for the OM group and 5.0 (2.0, 14.0) cm for the ADM group (P=0.555). The median operative duration was 160 (71, 221) min for the OM group and 134 (112, 274) min for the ADM group (P=0.065). The catheterization durations was 1.5 (1.0, 6.0) months for the OM group and 3.0 (1.0, 3.0) months for the ADM group. The median postoperative follow-up duration was 12.5 (1.0, 170.0) months for the OM group and 59.0 (3.0, 142.0) months for the ADM group. The surgical success rates were 50.00% in the OM group and 53.85% in the ADM group. No statistically significant differences were observed in postoperative quality of life (QoL) or international prostate symptom score (IPSS) at the final follow-up. The stricture-free survival rates did not differ significantly (HR=0.875, 95%CI: 0.507-1.511, P=0.6). In terms of safety, three patients in the OM group experienced sexual dysfunction, and two had oral complications, whereas the ADM group had one case of postoperative infection. Conclusion: The findings suggest that ADM grafts are comparable to OM grafts in terms of efficacy and safety for the treatment of long-segment urethral strictures, including complex cases attributed to lichen sclerosus. However, given the small sample size of this study, the above conclusions may have certain limitations. Larger cohort studies will be needed in the future to further validate these findings.
    Comparation of anterior maxilla and whole maxilla clockwise rotation to improve paranasal aesthetic defects of skeletal Class Ⅲ maxillofacial deformity
    Fengqi SONG, Xinyu XU, Xiaojing LIU, Zili LI
    2025, (5):  980-988.  doi: 10.19723/j.issn.1671-167X.2025.05.025    
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    Objective: To compare the aesthetic effects of anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy and whole maxilla clockwise rotation on improving paranasal concavity in patients with Class Ⅲ maxillofacial deformity. Methods: A non-randomized controlled trial was designed, and 21 patients diagnosed with skeletal Class Ⅲ maxillofacial deformity were included. In the study, 11 patients in the test group were treated by segmental Le Fort Ⅰ osteotomy combined with anterior maxilla clockwise rotation, and 10 patients in the control group were treated by whole maxilla clockwise rotation. The CBCT and 3D photography of preoperative (T0), 2 weeks postoperative (T1), and 6 months postoperative (T2) were collected respectively, and the three-dimensional cephalometry was carried out. The differences of specific parameters between the two groups were compared by independent sample t-test, including saggital displacement of the cheek mass point (CK) and subalare point (SA), nasolabial angle, occlusal plane angle and labial inclination angle of the upper incisor. Results: There were no significant differences of the parameters on T0 between the two groups. The average sagittal displacement of the upper incisors of the test group was (-0.71±1.67) mm and smaller than that of control group [(2.26±1.68) mm], t=-4.052, P < 0.05. The average angle of the occlusal plane clockwise rotation of the test group was 1.46°±2.38° and smaller than that of the control group (4.31°±1.83°), t=-3.047, P < 0.05. The angle of anterior maxilla clockwise rotation was 11.73°±2.81° during the surgery. The average saggital displacement of the paranasal soft tissue landmarks of the test group from T0 to T2 was larger than that of the control group [CK point, (4.96±1.18) mm vs. (2.01± 1.50) mm, P < 0.05;SA point, (5.19±1.17) mm vs. (2.69±1.45) mm, P < 0.05]. The labial inclination angle of the upper incisor of the test group was 112.15°±5.40° in T2 and significantly smaller than that of the control group (122.38°±8.83°), t=-3.237, P < 0.05. The nasolabial angle of the test group was 106.54°±12.82° in T2 and significantly larger than that of the control group (93.90°±12.46°), t=2.288, P < 0.05. Conclusion: Compared with whole maxilla clockwise rotation, anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy can increase the saggital displacement of the paranasal soft tissue, correct labial inclination of the upper incisors and the acute naso-labial angle and better improve the paranasal aesthetic defects in patients with Class Ⅲ maxillofacial deformity with less changing on the saggital orientation of the upper incisors and the occlusal plane angle.
    Three-dimensional morphological analysis of posed smile
    Yujia XIAO, Bochun MAO, Yanheng ZHOU
    2025, (5):  989-995.  doi: 10.19723/j.issn.1671-167X.2025.05.026    
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    Objective: To investigate the changes and symmetry of facial soft tissue during posed smile, to analyze the feature of posed smile in different gender, and verify the reproducibility of posed smile. Methods: Three-dimensional (3D) facial images of 41 adults (16 males and 25 females with an average age of 26.76±2.70 years) which were taken by FaceScan three-dimensional sensor, including one rest position and two posed smile images. Then these images were imported into 3D soft tissue analysis software for model repositioning. 3D morphable model method (3DMM) was carried out to automatic landmarks setting. After that, the measurement of the eyes, cheeks, nose and perioral area were carried out for 3D soft tissue analysis. Finally, the changes and symmetry of the soft tissues between the two expression states and the gender differences during the posed smiles were compared. Meanwhile, the reproducibility of posed smile was statistically tested. Results: Compared with the rest position, except for nasolabial angle (1.45°±7.65°), the measurements of 3D soft tissue in other region were changed in posed smile (P < 0.001). It should be noted that the eye region was also significantly changed (P < 0.001). Furthermore, the prominent feature of posed smile was that the alar base length became longer, the upper and lower vermilions were narrow and thin, and the mentolabial furrows became shallow. Meanwhile the chin extended anteriorly while the mouth retracted; During posed smile, the labial fissure asymmetry [2.78 (1.73, 3.49) mm], mid-infraorbital asymmetry [2.36 (1.22, 3.27) mm] and outercanthal asymmetry [2.31(1.29, 2.80) mm] were most apparent. Compared with the rest position, the asymmetry was not significantly increased except for cheilion and alar curvature points during the posed smile (P>0.05). In the posed smile, the changes of the right palpebral fissure height and the thickness of lower vermilion (|Li-Stoi| z) of males were greater than those of females (P < 0.05), and asymmetry of exocanthion and cheekbone increased more than that of females (P < 0.05). There was no obvious difference between the two posed smiles. Conclusion: In this study, during the posed smile the soft tissues of the eyes, cheeks, nose, lips and chin changed in different degrees, and the asymmetry of cheilion and alar curvature point was greater than that of the rest position; In addition, the reproducibility of posed smile was excellent, which can be a reference for clinical aesthetics and functional research of smile.
    Impact of palliative care on medication use and medical utilization in patients with advanced cancer
    Dingyi CHEN, Haoxin DU, Yichen ZHANG, Yanfei WANG, Wei LIU, Yuanyuan JIAO, Luwen SHI, Xiaodong GUAN, Xinpu LU
    2025, (5):  996-1001.  doi: 10.19723/j.issn.1671-167X.2025.05.027    
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    Objective: To evaluate the effect of palliative care on drug use, medical service utilization and medical expenditure of patients with advanced cancer. Methods: A cohort of patients including pal-liative care and standard care was constructed using the medical records of the patients in Peking University Cancer Hospital from 2018 to 2020, and coarsened exact matching was used to match the two groups of patients. The average monthly opioid consumption, hospitalization rate, intensive care unit (ICU) rate and operation rate, and the average monthly total cost were selected to evaluate drug use, medical service utilization and medical expenditure. Chi-square test and Wilcoxon signed rank test were used to compare the differences between the two groups before and after exposure and the change in the palliative care group. The net impact of palliative care on the patients was calculated using the difference-in-differences analysis. Results: In this study, 180 patients in the palliative care group and 3 101 patients in the stan-dard care group were finally included in the matching, and the matching effect of the two groups was good (L1 < 0.1). Before and after exposure, the average monthly opioid consumption in the palliative care group was significantly higher than that in the standard care group (Before exposure: 0.3 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; After exposure: 0.7 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; DDD refers to defined daily dose), palliative care significantly increased the average monthly opioid consumption in the patients (0.3 DDD/person-month, P < 0.01). The hospitalization rate (48.9% vs. 74.3%, P < 0.01) and operation rate (3.9% vs. 8.8%, P < 0.01) of the patients in palliative care group were significantly lower than those in standard care group, and the ICU rate became similar between the two groups (1.1% vs. 1.6%, P=0.634). Palliative care significantly reduced the patients ' hospitalization rate (-25.6%, P < 0.01), ICU rate (-4.9%, P < 0.01) and operation rate (-14.5%, P < 0.01). Before and after exposure, the average monthly total costs of pal-liative care group were slightly higher than those of standard care group (Before exposure: 20 092.3 yuan vs. 19 132.8 yuan, P=0.725; After exposure: 9 719.8 yuan vs. 8 818.8 yuan, P=0.165). Palliative care increased the average monthly total cost by 2 208.8 yuan, but it was not statistically significant (P=0.316). Conclusion: Palliative care can increase the opioid consumption in advanced cancer patients, reduce the rates of hospitalization, ICU and surgery, but has no significant effect on medical expenditure.
    Left sided sternocleidomastoid interosseous intravascular papillary endothelial hyperplasia: A case report
    Xiaodi XIAO, Youchen XIA, Jianying LIU, Peng FU
    2025, (5):  1002-1004.  doi: 10.19723/j.issn.1671-167X.2025.05.028    
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    Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson tumor, is a rare vascular benign tumor of blood vessels. It may occur in any part of the body, especially the deep dermis and subcutaneous tissue of the head, neck, fingers and trunk. The imaging and histopathology of IPEH are similar to hemangiosarcoma, especially in the case of active vascular endothelial hyperplasia. IPEH is a reactive proliferative lesion of vascular intima. The etiology is still unclear. After some studies showed that IPEH was a benign lesion, few reports on the etiology of it were reported. IPEH is usually limited to the thrombotic vessels or lumens of vascular malformations, usually accompanied by a clear history of trauma. IPEH usually does not cause any symptoms. It looks like a slow-growing lump. Some cases have been reported with pain and swelling. Although IPEH is relatively rare, its accurate diagnosis is crucial because it may be similar to malignant angiogenic lesions in clinical practice. There were few reports of cases related to intravascular papillary endothelial hyperplasia located in the sternocleidomastoid muscle after reviewing the domestic and foreign literature in recent 10 years. This case reports that a young male, who was admitted to the hospital one month after finding a subcutaneous tumor in the left neck. After admittance, relevant preoperative examinations were completed. After multi-disciplinary discussion and elimination of surgical contraindications, a specific surgical plan was formulated. The tumor was removed under local anesthesia on the second day after admission. During the operation, it was found that the tumor was located between the sternocleidomastoid muscle bundles, and it was sent for pathologic examination. Paraffin section pathology was reported after operation. Histological examination showed that the morphology was consistent with vascular endothelial papillary hyperplasia. There were no related surgical complications and recurrence in the 3-month follow-up. The purpose of this paper is to provide clinicians with a certain understanding of this rare disease through the report of this case of IPEH, and to identify it in later clinical work, and at the same time, to avoid confusion with malignant diseases, such as hemangiosarcoma, leading to unnecessary treatment and increase the cost of treatment.
    Neuroendocrine carcinoma with significantly vacuolar nucleus at the esophagogastric junction: A case report
    Weihua HOU, Shujie SONG, Zhongyue SHI, Lu LIU, Mulan JIN
    2025, (5):  1005-1009.  doi: 10.19723/j.issn.1671-167X.2025.05.029    
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    Neoplasms characterized by the expression of markers of neuroendocrine differentiation in neoplastic cells are defined as neuroendocrine neoplasms. A case of neuroendocrine carcinomas (NECs) with a small amount of papillary adenocarcinoma and significantly vacuolar nucleus at the esophagogastric junction was reported in this article. A 77-year-old male had dysphagia for one week. Endoscopy revealed early-stage esophagogastric junction carcinoma, and biopsy was diagnosed as poorly differentiated carcinoma. Endoscopic submucosal dissection was performed. Histologically, the papillary adenocarcinoma progresses from typically branching papillary structures (well-differentiated) to hyperplasia of the lining epithelium of the papilla to form a cribriform structure (moderately differentiated), to solid area lacking papillary structures (poorly differentiated). There was a continuous process, and during this process, the vacuoles in the nuclei of tumor cells showed progressive changes from mild to obvious and finally to significant vacuoles. The tumor was mainly composed of solid areas (about 95%), with single cell, large cell, round or oval to irregular nuclei, and significantly vacuolar nuclei, nuclei with larger vacuoles appeared in a loop, a few thin weakly basophilic or weakly eosinophilic fine particles could be seen in the vacuoles, and the vacuoles had rough edges. The nucleus chromatin at the outer edge of the vacuoles was fine particles, and mitosis was common (20-30/mm2), atypical mitosis could be seen, and nucleoli could be seen easily, the cytoplasm was weakly eosinophilic, and the boundaries of cells were unclear. The cells were arranged in a nested, trabecular, or diffuse sheet shape, with some arranged in a glandular tube shape. Tumor thrombus was found in the vein of submucosa; the interstitial tissue rich in capillaries within the tumor was accompanied by a large number of neutrophil infiltration. Immunohistochemical staining showed that the solid area of the tumor was positive for synaptophysin (Syn) and chromogranin A (CgA), while papillary adenocarcinoma was negative. Mucin 5AC (MUC5AC) was diffusely positive in papillary adenocarcinoma, while the proportion of positive cells in the solid area of the tumor was about 10% to 15%. In a word, this case showed the extreme situation of the vacuolar nuclear characteristics of NECs, extremely rare, in a sense, this case expanded the boundary of the morphological spectrum of NECs. Understanding the extreme vacuolar features of this nucleus is helpful to make a correct pathological diagnosis.

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Sponsor: Peking University
Editor-in-Chief: ZHAN Qi-min
Executive Editor-in-Chief: ZENG Gui-fang
Editing and Publishing: Editorial Department of Journal of Peking University (Health Sciences)
ISSN: 1671-167X
CN: 11-4691/R