To investigate the effect of long non-coding RNA (LncRNA) differentiation antagonizing non-protein coding RNA (DANCR) on the immune microenvironment of glioma cells by regulating the miR-656/bone morphogenetic protein receptor type 1A (BMPR1A) axis. The expression levels of DANCR, miR-656 and BMPR1A in glioma cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The U87 cells were transfected or co-transfected to form the following groups: sh-DANCR (transfected with sh-DANCR), overexpression (pcDNA 3.1) DANCR (transfected with pcDNA 3.1 DANCR), NC sh (transfected with negative control sh), pcDNA 3.1 (transfected with pcDNA 3.1 vector), sh-DANCR + miR-656 inhibitor (co-transfected with sh-DANCR and miR-656 inhibitor), sh-DANCR + NC inhibitor (co-transfected with sh-DANCR and NC inhibitor), sh-DANCR + pcDNA 3.1 BMPR1A (co-transfected with sh-DANCR and pcDNA 3.1 BMPR1A), and sh-DANCR + pcDNA 3.1 (co-transfected with sh-DANCR and pcDNA 3.1 BMPR1A). The untreated U87 cells were used as the blank group. The proliferation of U87 cells was detected by CCK-8; invasion and migration were detected by Transwell assay; apoptosis was detected by flow cytometry; the expression of DANCR, miR-656, and BMPR1A mRNA in cells was detected by qRT-PCR; the targeting relationship between DANCR and miR-656 was verified by dual-luciferase; and BMPR1A and immune escape factors [programmed death receptor 1 (PD-1) and programmed death-ligand 1 (PD-L1)] were detected by Western blot. The mRNA expressions of DANCR and BMPR1A in U87, A172, LN229 and U251 cells were significantly increased, while the expression of miR-656 was significantly decreased compared with those in NHA cells (P < 0.05). Compared with the blank group and sh-DANCR group, the proliferation rate, invasion, migration number, DANCR, BMPR1A mRNA, BMPR1A, PD-1, PD-L1 expression of U87 cells in the sh-DANCR group were obviously reduced, while the apoptosis rate and miR-656 expression were obviously increased (P < 0.05). Compared with the pcDNA 3.1 group, the proliferation rate, invasion, migration number, DANCR, BMPR1A mRNA, BMPR1A, PD-1, and PD-L1 expression of U87 cells in the pcDNA 3.1 DANCR group were obviously increased, while the apoptosis rate and miR-656 expression were obviously reduced (P < 0.05). Compared with the sh-DANCR +NC inhibitor group, the proliferation rate, invasion, migration number, BMPR1A mRNA, BMPR1A, PD-1, and PD-L1 expression of U87 cells in the sh-DANCR+miR-656 inhibitor group were obviously increased, and the apoptosis rate and miR-656 expression were obviously reduced (P < 0.05), while the expression of DANCR was not obvious (P>0.05). Compared with the sh-DANCR+pcDNA 3.1 group, the proliferation rate, invasion, migration number, BMPR1A mRNA, BMPR1A, PD-1, and PD-L1 expression of U87 cells in the sh-DANCR+pcDNA 3.1 BMPR1A group obviously increased, and the apoptosis rate obviously decreased (P < 0.05), while here was no statistically obvious difference in miR-656 expression and DANCR expression (P>0.05). DANCR and miR-656 had a targeted negative regulatory relationship. LncRNA DANCR improves the immune microenvironment of glioma cells and inhibits the malignant behavior development of cancer cells by regulating the miR-656/BMPR1A axis. 探讨长链非编码RNA(long non-coding RNA，LncRNA)分化拮抗非蛋白编码RNA(differentiation antagonizing non-protein coding RNA，DANCR)调节微小RNA-656(miR-656)/骨形态发生蛋白受体1A(bone morphogenetic protein receptor type 1A，BMPR1A)轴对脑胶质瘤细胞免疫微环境的影响。 实时荧光定量聚合酶链式反应(quantitative real-time polymerase chain reaction，qRT-PCR)检测脑胶质瘤细胞中DANCR、miR-656、BMPR1A的表达水平。通过转染或共转染至U87细胞，分为沉默(short hairpin, sh)-DANCR组、过表达(plasmid cytome galoirus, pc)DNA 3.1DANCR组、阴性对照(negative control, NC)sh组、pcDNA 3.1组、sh-DANCR+miR-656抑制剂组、sh-DANCR+NC抑制剂组、sh-DANCR+pcDNA 3.1 BMPR1A组、sh-DANCR+pcDNA 3.1组，并以未处理的U87细胞为空白组。CCK8检测U87细胞增殖；Transwell实验检测侵袭与迁移；流式细胞仪检测细胞凋亡；qRT-PCR检测细胞中DANCR、miR-656、BMPR1A mRNA表达；DANCR与miR-656靶向关系通过双荧光素酶验证；BMPR1A及免疫逃逸因子[程序性死亡受体1(programmed death-1，PD-1)和程序性死亡配体1(programmed death-ligand 1, PD-L1)]通过Western blot检测。 U87、A172、LN229和U251细胞较NHA细胞中DANCR、BMPR1A mRNA表达显著增加，miR-656表达显著降低(P＜0.05)；与空白组、sh-DANCR组相比，sh-DANCR组U87细胞增殖率，侵袭、迁移数，DANCR、BMPR1A mRNA、BMPR1A、PD-1、PD-L1表达显著降低，凋亡率、miR-656表达显著增加(P＜0.05)；与pcDNA 3.1组相比，pcDNA 3.1 DANCR组U87细胞增殖率，侵袭、迁移数，DANCR、BMPR1A mRNA、BMPR1A、PD-1、PD-L1表达显著增加，凋亡率、miR-656表达显著降低(P＜0.05)；与sh-DANCR+NC抑制剂组相比，sh-DANCR+miR-656抑制剂组U87细胞增殖率，侵袭、迁移数，BMPR1A mRNA、BMPR1A、PD-1、PD-L1表达显著增加，凋亡率、miR-656表达显著降低(P＜0.05)，DANCR表达的差异无统计学意义(P>0.05)；与sh-DANCR+pcDNA 3.1组相比，sh-DANCR+pcDNA 3.1 BMPR1A组U87细胞增殖率，侵袭、迁移数，BMPR1A mRNA、BMPR1A、PD-1、PD-L1表达显著增加，凋亡率显著降低(P＜0.05)，miR-656表达、DANCR表达差异无统计学意义(P>0.05)。DANCR、miR-656具有靶向负调节关系。 LncRNA DANCR调节miR-656/BMPR1A轴改善脑胶质瘤细胞免疫微环境，抑制癌细胞恶性行为发展。
To examine the impact of effective health information acquisition on hemophilia-related health literacy among adult caregivers of children and adolescents with hemophilia in China, and to provide evidence-based recommendations for improving adult caregivers' hemophilia-related health literacy. Data were derived from the 2024 nationwide multicenter cross-sectional survey, "Health Literacy Survey of Hemophilia Patients in China". A total of 856 adult caregivers of children and adolescents with hemophilia were recruited through convenience sampling. To explore the differences in hemophilia-related health literacy and effective health information acquisition levels among caregivers across different demographic characteristics, univariate ANOVA and independent-samples t test were adopted for statistical analysis. The bootstrap method was employed to test the mediating role of effective health information acquisition in the relationship between hemophilia-related health literacy and its influencing factors. The overall level of hemophilia-related health literacy among caregivers of minor patients with hemophilia was relatively low, with an average score of 11.87±2.92. Only 20.68% of the caregivers for underage patients with hemophilia had acquired hemophilia-related health literacy. Univariate ANOVA analysis indicated that marital status, educational attainment, annual household income, registered residence location, and employment status significantly influenced adult caregivers ' hemophilia-related health literacy (P < 0.05). The utilization rate of various health information channels by caregivers of underage hemophilia patients exceeded 70%. Over 95% of the caregivers reported obtaining hemophilia-related health information from medical staff and hemophilia patient organizations. While, the caregivers demonstrated relatively low overall effective health information acquisition (34.43±16.50). The level of effective health information acquisition was related to educational attainment, place of household registration and employment status. Caregivers with higher educational attainment, urban household registration and full-time employment had a higher level of effective health information acquisition, and the differences were statistically significant (P < 0.05). The mediation analysis showed that the level of effective health information acquisition was positively correlated with hemophilia health literacy (P < 0.01), and effective health information acquisition played a partial mediating role between "education attainment" and "hemophilia health literacy", "employment status" and "hemophilia health literacy", and "place of household registration" and "hemophilia health literacy" (P < 0.05). Higher educational attainment and favorable employment status not only directly improved health literacy, but also indirectly enhanced it by promoting effective information acquisition. Compared with urban household registration, rural household registration had a negative impact on health literacy in patients with hemophilia. Meanwhile, effective information acquisition also exerted a partial mediating effect between registered residence location and health literacy. The hemophilia-related health literacy among caregivers of underage hemophilia patients is relatively low. Enhancing adult caregivers' effective health information acquisition of health information will improve their hemophilia-related health literacy. Tailored strategies to optimize effective health information acquisition for adult caregivers with varying sociodemographic characteristics could indirectly contribute to improved health literacy outcomes. 探讨我国未成年血友病患者照护者的有效健康信息获取水平对其血友病健康素养的影响，为提升照护者健康素养提供建议。 基于2024年全国多中心横断面调查《中国血友病患者健康素养调查》数据，采用方便抽样法纳入856例未成年血友病患者的成年照护者。通过单因素ANOVA分析或独立样本t检验了解不同人口学特征下照护者健康素养和有效健康信息获取水平的差异，并采用Bootstrap法检验有效健康信息获取在健康素养与其影响因素之间的中介作用。 未成年血友病患者照护者的血友病健康素养水平整体较低，平均得分为11.87±2.92。仅有20.68 %的照护者具备血友病健康素养，婚姻状况、受教育程度、家庭年收入、户籍所在地和就业状况是照护者血友病健康素养的影响因素(P＜0.05)。未成年血友病患者照护者对各类健康信息获取渠道的使用率均超过70%，超过95%的照护者报告从医护人员、血友病患者组织获取血友病相关健康信息。未成年血友病患者照护者有效健康信息获取水平整体偏低(34.43±16.50)，有效健康信息获取水平与受教育程度、户籍所在地、就业状况相关，受教育程度越高、户籍所在地为城市及有全职工作的照护者有效健康信息获取水平更高，差异有统计学意义(P＜0.05)。中介效应分析表明，有效健康信息获取水平与血友病健康素养呈正相关(P＜0.01)，且有效健康信息获取在“受教育程度”与“血友病健康素养”、“就业状况”与“血友病健康素养”，以及“户籍所在地”与“血友病健康素养”之间均存在部分中介作用(P＜0.05)。 未成年血友病患者照护者的血友病健康素养水平较低，提升照护者的有效健康信息获取水平有助于改善其血友病健康素养；针对不同社会人口学特征的人群，可通过优化有效健康信息获取路径，间接提升其健康素养水平。
To assess the spatial accessibility of pediatric healthcare resources in Beijing and to develop an optimization model for resource allocation under a fixed additional resource constraint, with the aim of exploring optimal allocation strategies for 2025 and 2030. Using communities as the unit of analysis, this study integrated data on Beijing ' s child population in 2020 and pediatric healthcare resources in 2022. An improved two-step floating catchment area (2SFCA) method was applied to measure spatial accessibility. Based on projected child population data for 2025 and 2030, an optimization model was constructed to minimize regional disparities in accessibility. Under the constraint of a fixed total number of additional resources, optimal spatial allocation schemes were derived and compared with a conventional population-based allocation approach. In 2022, Beijing had 4 704 pediatric beds and 4 011 pediatric physicians. The mean spatial accessibility for pediatric beds and pediatric physicians was 1.17 and 0.97, respectively, with a standard deviation of 2.78 for bed accessibility, exhibiting a clear spatial pattern of higher accessibility in central districts and lower accessibility in suburban districts. In the same year, the number of pediatric physicians per 1 000 children in Beijing reached 1.52, already exceeding the targets for 2025 and 2030; therefore, no additional increase in total physician numbers was required. Under the 2025 optimization scenario, the mean accessibility of pediatric beds increased to 1.68, with the standard deviation declining to 2.45, indicating a reduction in regional disparities. Under the 2030 scenario, the mean accessibility further increased to 2. 31, with a standard deviation of 2.56, reflecting continued improvement in accessibility. The optimization model identified Daxing District, Tongzhou District, and Mentougou District as priority districts for additional bed allocation, whereas the conventional population-based approach allocated more resources to Daxing District, Haidian District, and Tongzhou District. While the two approaches showed general consistency in overall spatial allocation, the optimization model more effectively addressed inter-district disparities in accessibility. Significant spatial disparities were identified in the distribution of pediatric healthcare resources in Beijing. The accessibility-oriented optimization approach, under a fixed resource constraint, improved the alignment between supply and demand and reduced regional inequities. It served as a useful complement to conventional population-based allocation methods and provided quantitative evidence to support refined planning and dynamic adjustment of pediatric healthcare resources. Given that the total number of pediatric physicians has already met national targets, leveraging integrated medical consortium and multi-site practice policies to promote the mobility of qualified pediatric physicians toward underserved areas represents a promising pathway toward structural optimization of spatial resource distribution. 评估北京市儿科医疗资源空间可及性，并构建儿科资源优化模型，探索2025年与2030年儿科医疗资源的优化方案。 基于北京市2020年儿童人口数据及2022年儿科执业(助理)医师、床位数据，采用改进的两步移动搜寻法测算儿科医疗资源空间可及性。在此基础上，结合2025年与2030年儿童人口预测结果，构建以最小化可及性差异为目标的优化模型，在新增资源总量固定的情况下求解床位分配方案，并与基于人口规模分配的传统方案进行比较。 2022年北京市共配置儿科床位4 704张、儿科执业(助理)医师4 011名，儿科床位与儿科执业(助理)医师空间可及性平均值分别为1.17和0.97，床位可及性标准差为2.78，可及性呈现中心城区高、外围地区低的空间格局。2022年北京市每千名儿童儿科执业(助理)医师数达到1.52人，已超过2025年及2030年国家目标，在总量层面不涉及新增。按照2025年目标优化儿科床位后，床位空间可及性平均值提升至1.68，标准差2.45，地区间差异程度明显下降；按照2030年目标优化后，可及性平均值进一步提升至2.31，标准差为2.56，可及性水平持续改善。优化模型显示，大兴区、通州区与门头沟区为新增床位重点配置地区；传统按人口规模分配则将新增资源主要投向大兴区、海淀区和通州区。两种方案在总体布局方向上具有一致性，优化模型可更有效地缓解地区间可及性的不均衡。 北京市儿科医疗资源存在空间分布不均衡现象。基于可及性差异最小化的优化方案在资源总量固定条件下，有助于改善空间可及性并缓解地区间差异，可作为传统按人口规模配置资源的有效补充，将可及性指标纳入资源配置过程，为儿科医疗资源精细化规划与动态调整提供量化依据。在医师总量已达标的背景下，应充分发挥医联体协同机制与多点执业政策，推动优质儿科医师资源向可及性不足地区流动与下沉，以实现空间配置的结构性优化。
To explore the relationship between family trauma, school bullying and adolescent suicidal behavior, and the regulatory role of DRD2 gene polymorphism. A total of 98 adolescent patients with depressive disorders who visited our hospital from June 2022 to June 2024 were selected. They were divided into the non-suicide group (n=62) and the suicide group (n=36) based on their suicide behavior in the previous 6 months and their attitudes towards suicide behavior. The general data of the two groups were compared. The relationship between each genotype and suicide behavior, the influencing factors of suicide behavior, the interaction between family trauma and school bullying on suicide behavior, and the regulatory effects of depression and genetic polymorphisms were analyzed. The possible regulatory effects of depression and genetic polymorphisms were also investigated. Compared with the non-suicide group, the duration of illness, non-suicidal self-harm behavior, family trauma, school bullying, anxiety, depression scores in the suicide group increased, while the life meaning score decreased (P < 0.05). The genotype A2A2 was associated with an increased risk of suicidal behavior compared to genotype A1A1 (P < 0.05). In the recessive model, the genotype A2A2 was associated with an increased risk of suicidal behavior compared to genotype A1A1 and A1A2 (P < 0.05); in the additive model, there were significant associations between the genotypes A1A1, A1A2, A2A2 and suicidal behavior (P < 0.05). Non-suicidal self-harm behavior, family trauma, school bullying, depression, and the A2A2 genotype were independent risk factors for suicidal behavior, while life meaning was an independent protective factor. Family trauma > 54.78 points and school bullying > 10.37 points had a multiplicative (OR=6.585, 95%CI: 5.478-7.367) and additive (OR=7.849, 95%CI: 7.231-8.294) interaction effect on adolescent suicidal behavior. Depression exerted a regulatory effect between family trauma (β=0.092, 95%CI: 0.084-0.103), school bullying (β=0.090, 95%CI: 0.081-0.098) and suicidal behavior. In the additive genetic model, the TaqⅠA gene had a significant regulatory effect on "family trauma, school bullying → depression → suicidal behavior" in adolescents with the A1A2/ A2A2 genotype. The risk of suicidal behavior is higher in adolescents with both family trauma and school bullying, and depression plays a part of the mediating effect. The TaqⅠA polymorphism of DRD2 gene has a significant regulatory effect on adolescents carrying A2 allele. 探究家庭创伤、校园霸凌与青少年自杀行为的关系，以及DRD2基因多态性的调节作用。 连续选择2022年6月—2024年6月于宁夏回族自治区宁安医院就诊的确诊为青少年抑郁障碍患者98例，根据就诊前6个月是否有自杀行为和对自杀行为态度得分分为非自杀组(n=62)和自杀倾向组(n=36)。比较两组患者一般资料。分析各基因型与自杀行为的关系、自杀行为的影响因素、家庭创伤和校园霸凌对自杀行为的交互作用。分析基因多态性对抑郁障碍可能存在的调节效应。 与非自杀组比较，自杀倾向组病程、非自杀性自伤行为、家庭创伤、校园霸凌、焦虑、抑郁评分增加，生命意义评分降低(P＜0.05)。基因型A2A2较A1A1可增加自杀行为风险(P＜0.05)。隐性模式中，基因型A2A2较A1A1和A1A2增加自杀行为风险(P＜0.05)；加性遗传模式中，基因型A1A1、A1A2、A2A2与自杀行为之间均有重要关联(P＜0.05)。非自杀性自伤行为、家庭创伤、校园霸凌、抑郁障碍以及A2A2基因型是自杀行为的独立危险因素，生命意义是独立保护因素。家庭创伤＞54.78分和校园霸凌＞10.37分对青少年自杀行为存在相乘(OR=6.585，95%CI：5.478~7.367)及相加(OR=7.849，95%CI：7.231~8.294)的交互作用。抑郁障碍在家庭创伤(β=0.092，95%CI：0.084~0.103)、校园霸凌(β=0.090，95%CI：0.081~0.098)与自杀行为间发挥调节效应。加性遗传模式下，TaqⅠA基因在携带A1A2 / A2A2分型的青少年中对“家庭创伤、校园霸凌→抑郁障碍→自杀行为”的调节效应显著。 家庭创伤和校园霸凌同时存在时青少年自杀行为风险更高，抑郁障碍在其中发挥调节效应，DRD2基因TaqⅠA位点多态性对携带A2等位基因的青少年具有显著的调节效应。
To investigate the etiology of chronic sialadenitis, and to analyze their clinical and imaging characteristics. This retrospective analysis reviewed the clinical and imaging data of patients with chronic sialadenitis who underwent sialendoscopy at the Peking University Hospital of Stomatology between January 2021 and August 2023. (1) with a history of recurrent swelling of major salivary glands; (2) complete medical records with detailed information about potential causes; (3) sialography images were available; and (4) patients had undergone interventional endoscopy. (1) salivary stones; (2) juvenile recurrent parotitis; (3) IgG4-related sialadenitis; (4) Sjögren syndrome; and (5) neoplastic diseases. Based on the latest research results and clinical data, chronic sialadenitis was classified into radioactive iodine-induced sialadenitis (RAIS), allergy-related sialodochitis (ARS), adult chronic recurrent parotitis (ACRP), sialadenosis with sialodochitis, and idiopathic sialadenitis. Idiopathic sialadenitis was defined as a type of chronic sialadenitis with duct stenosis of unknown etiology (allergic causes, autoimmune disorders, radioactive iodine exposure, history of "parotitis" in childhood, etc.). The proportions of five types of sialadenitis were calculated, and their relationships with age, gender, type of affected glands, number of affected glands, duration of symptoms, and imaging characteristics were statistically analyzed. A total of 544 consecutive patients diagnosed with chronic sialadenitis were enrolled in this study. They consisted of 192 males and 352 females, and their ages ranged from 14 to 83 years [mean age: (47.44±13.52) years]. Idiopathic sialadenitis accounted for the largest proportion (71.7%, 390 cases), followed by ARS (12.5%, 68 cases), RAIS (6.4%, 35 cases), ACRP (4.8%, 26 cases), and sialadenosis with sialodochitis (4.6%, 25 cases). Among the 2 176 available glands of the 544 patients, 1 120 (51.5%) glands were affected, including 880 (78.6%) parotid glands and 240 (21.4%) submandibular glands. These five types of sialadenitis exhibited significant differences in gender, age, type and number of affected glands, and duration of symptoms (P < 0.05). Among them, RAIS patients showed the lowest male to female ratio (male ∶ female=1 ∶ 4.83), ARCP patients were the youngest [(32.50±8.60) years], and RAIS and ARS patients had relatively higher number of affected glands. Sialography showed ductal atresia in 23.2% of affected glands with ARIS, "snowflake" pattern in 46.5% of affected glands with ARS, "punctate and globular" ectasia of terminal ducts in 80.4% of affected glands with ARCP, and clustered branch ducts in 71.4% of affected glands with sialadenosis with sialodochitis. Moreover, stenosis and/or dilatation of the main and branch ducts represented the most typical sialography appearance of idiopathic sialadenitis. Idiopathic sialadenitis, RAIS, ARS, ACRP, and sialadenosis with sialodochitis are the five common types of chronic sialadenitis. Among these, idiopathic sialadenitis is the most common type of chronic sialadenitis. Clarification of the etiology, clinical manifestations and imaging characteristics of chronic sialadenitis is important for clinicians to develop personalized treatment plans and improve treatment outcomes. 探索临床上常见的几类不同病因导致的慢性唾液腺炎的占比，并分析其临床和影像学特点。 回顾性分析2021年1月至2023年8月就诊于北京大学口腔医院并行唾液腺内镜治疗的各类慢性唾液腺炎患者的临床及影像资料，除外干燥综合征伴感染、IgG4相关唾液腺炎、结石病伴感染等，根据现有研究结果和资料，初步将唾液腺炎分为131I相关唾液腺炎、过敏相关唾液腺炎、成人复发性腮腺炎、腮腺良性肥大伴管炎、原发性导管狭窄性唾液腺炎(指未发现目前已知的可能病因，并存在导管狭窄的慢性唾液腺炎)，统计分析各类慢性唾液腺炎的占比和主要临床、影像学特点。 共纳入544例患者，男性192例、女性352例，平均年龄(47.44±13.52)岁(14~83岁)。其中，原发性导管狭窄性唾液腺炎最多，占71.7%(390例)；过敏相关唾液腺炎次之，占12.5%(68例)；131I相关唾液腺炎占6.4%(35例)，成人复发性腮腺炎占4.8%(26例)，腮腺良性肥大伴管炎占4.6%(25例)。544例患者共1 120侧腺体受累，包括腮腺880侧(78.6%)及下颌下腺240侧(21.4%)。这五类唾液腺炎在性别、年龄、受累腺体类别、受累腺体数目及病程上差异均存在统计学意义(P < 0.05)，131I相关唾液腺炎患者的女性占比最高(男∶女=1 ∶ 4.83)，成人复发性腮腺炎患者的平均年龄最小[(32.50±8.60)岁]，131I相关唾液腺炎和过敏相关唾液腺炎的受累腺体数目相对较多。从造影表现看，131I相关唾液腺炎中23.2%的受累腺体发生导管闭锁，过敏相关唾液腺炎中46.5%的受累腺体分支导管呈“雪花样”扩张表现，成人复发性腮腺炎中80.4%的受累腺体可见末梢导管“点球状扩张”，腮腺良性肥大伴管炎的受累腺体分支导管呈丛簇状表现者占71.4%，原发性导管狭窄性唾液腺炎的造影表现以主导管(主导管和分支导管)狭窄和(或)扩张为主。 原发性导管狭窄性唾液腺炎、131I相关唾液腺炎、过敏相关唾液腺炎、成人复发性腮腺炎、腮腺良性肥大伴管炎是临床上常见的五类慢性唾液腺炎，其中原发性导管狭窄性唾液腺炎占比最大。明确各类慢性唾液腺炎的病因、临床及影像学特征，将有利于临床医师制定个性化治疗方案，改善治疗效果。
Cranio-maxillofacial bone defects resulting from trauma, tumors, infection, or congenital malformations not only severely impair patients' physiological functions, but also impose a profound psychological burden, constituting a major public health issue that affects overall health and quality of life. Conventional reconstructive approaches, including autologous grafting and allogeneic implantation, can partially restore tissue morphology; however, limitations, such as donor-site morbidity, immune rejection, and long-term resorption prevent the achievement of true biological functional reconstruction. These challenges are particularly pronounced in the repair of complex and large-scale bone defects. The underlying cause lies in the insufficient understanding of the complex cellular behaviors, signaling networks, and material-host interactions involved in bone regeneration, which hampers precise regulation of the repair process. Therefore, the development of new theories, technologies, and materials grounded in mechanistic insights has become a key strategic direction in cranio-maxillofacial bone regeneration research. Supported by the National Natural Science Foundation of China, the Beijing Natural Science Foundation, and National and Provincial Major Talent Programs, our research group has addressed critical clinical challenges in cranio-maxillofacial bone defect repair by proposing an innovative concept of "regulating cell fate, designing intelligent biomaterials, and achieving functional reconstruction". Centered on this key scientific question, we have systematically carried out a full-chain research strategy spanning "fundamental theory-technological breakthroughs-product translation", overcoming multiple bottlenecks and achieving a series of original outcomes. (1) At the level of fundamental theory, we elucidated the epigenetic and ubiquitination regulatory networks governing skeletal stem cell fate determination, and precisely defined functional stem cell subpopulations using single-cell technologies. We also pioneered apoptotic vesicles as a new paradigm for cell-free therapy and clarified their functional diversity. (2) In terms of technological breakthroughs, we established 4D printing technologies with dynamically tunable morphology and function, developed metal surface engineering strategies that integrate controllable degradation with biofunctional regulation, and built artificial intelligence-driven intelligent design and manufacturing platforms. (3) Regarding translational applications, we developed a series of apoptotic vesicle-based biotherapeutics, smart responsive bone-repair scaffolds, and next-generation biofunctionalized biodegradable metal implants. Collectively, these achievements have advanced the fundamental theory of regenerative medicine, overcome key technological barriers, established new clinical strategies for cranio-maxillofacial tissue defect repair, and significantly enhanced core competitiveness in this field. 口腔颅颌面骨缺损由创伤、肿瘤、感染及先天畸形等多种因素引起，严重影响患者生理功能与生活质量。传统的骨修复方法(如自体或异体移植)在复杂、大范围缺损修复中仍面临供区损伤、免疫排斥及远期吸收等局限，其内在原因是缺乏对骨组织再生过程中复杂的细胞行为、信号网络及材料-宿主相互作用的深入解析，导致现有治疗策略难以精准调控修复进程。因此，发展基于机制探索的新理论、新技术和新材料，是目前口腔颅颌面骨再生研究的重要战略方向。本文系统综述了本课题组围绕“调控细胞命运-构建智能材料-实现功能重建”这一核心理念，在口腔颅颌面骨再生领域取得的系列原创性研究进展。从骨骼干细胞命运调控机制入手，阐明了表观遗传修饰、泛素化系统和单细胞水平下功能性干细胞亚群在骨再生中的关键作用，提出了凋亡囊泡作为新型无细胞治疗载体的再生机制及其工程化增强策略；在材料层面，发展了可降解镁、锌金属的生物功能化设计和增材制造技术，并构建了形态与功能双重动态可调的4D打印智能支架，同时引入人工智能，实现精准设计和数字化制造，构建了从机制到转化的系统性创新体系。
Currently, oral health field in our country faces numerous challenges, such as the persistently high prevalence of oral diseases, the heavy burden on medical insurance payments and there are significant regional differences in the level of dental care, so far the full medical equity across society has not yet been achieved. Health management is a key strategy to cope with these challenges. Health management consists of four components: information collection, risk factor assessment, health education and health intervention.The collection of information is the foundation of health education and health interventions. Effective health education and interventions, in turn, promote the conduct of information collection. Health management and medical care overlap in terms of service recipient, practitioner, location, and means of service, but there are different goal, focus point, service model and time span between them. The real rise of health management in our country has appeared since the year 2000. The oral health management is just beginning in our country. It is of significant realistic importance to set up an oral health system in China. It is recommended to carry out top-level design for oral health management and promote its progress from four aspects: changing concepts, cultivating talent, strengthening policy intervention and developing appropriate technique. 当今我国口腔健康领域面临众多挑战，如口腔疾病的患病率居高不下、医保支付不堪重负、口腔医疗水平地域差异大、无法实现医疗公平等，健康管理是应对上述挑战的关键举措。健康管理由信息采集、风险因素评估、健康教育和健康干预四部分组成。信息的采集是健康教育和健康干预的基础，有效的健康教育和健康干预反过来也会促进信息采集的开展。健康管理与医疗在服务对象、实施者、实施地点、服务的手段等方面有交叉，但两者的目标不同，关注的焦点不同，服务模式和时间跨度也不同。健康管理在我国真正兴起于2000年以后，当前，口腔健康管理在我国刚刚起步，因此，构建我国的口腔健康管理体系具有十分重要的现实意义。建议做好口腔健康管理的顶层设计，从转变观念、人才培养、强化政策干预和开发适宜的技术四个方面着手推进。
To explore the promotion of dynamic distraction on osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMMSCs) in three-dimensional culture. Dynamic stretching in a three-dimensional culture for hBMMSCs was achieved with proportions set at 5%, 10%, and 20%, a frequency of 0.5 Hz, and a dynamic stretching duration of 2 hours per day. Static culture was used as the control group. Deformation of hBMMSCs induced by dynamic stretching was observed through cytoplasmic fluorescence staining. After 7 days of dynamic stretching culture, the impact of dynamic stretching on the viability of hBMMSCs was observed through cell live/dead staining. The effect of dynamic stretching on the osteogenic differentiation of hBMMSCs was observed through alkaline phosphatase (ALP) staining and the expression of osteogenic related genes and proteins after 7 days of dynamic stretching culture. Dynamic stretching in a three-dimensional culture for hBMMSCs was successfully constructed, which could achieve different durations, frequencies, and ratios of dynamic stretching. Dynamic stretching led to deformation of hBMMSCs, and the greater the stretching ratio, the more pronounced the cell deformation, transitioning from a circular to a flat oval shape. After 7 days of dynamic stretching culture, hBMMSCs in the static control group and dynamic stretching groups were mostly green stained live cells, with only a few red stained dead cells. The difference in the proportion of live cells between the groups was not statistically significant (P>0.05). The ALP staining in the dynamic stretching group was deeper than that in the static control group, and the number of ALP staining positive cells observed under the microscope was higher. The expression of osteogenic related genes and proteins increased after 7 days of dynamic stretching culture, and the difference was statistically significant (P < 0.05). Among them, the dynamic stretching group with 10% had the deepest ALP staining, the highest number of positive cells, and the most significant increase in the expression of osteogenic related genes and proteins compared with the static control group. Dynamic stretching caused deformation of hBMMSCs without a significant impact on cell viability, and it could effectively promote the osteogenic differentiation of hBMMSCs. 探究动态牵张对人骨髓间充质干细胞(human bone marrow mesenchymal stem cells，hBMMSCs)三维培养中成骨分化的促进作用。 对载有hBMMSCs的三维培养体系进行动态牵张，设置动态牵张的比例(5%、10%、20%)、频率(0.5 Hz)和时间(2 h/d)，以静态培养为对照组；通过胞质荧光染色观察动态牵张引起的hBMMSCs形变；动态牵张培养7 d后，通过细胞活死染色观察动态牵张对hBMMSCs活性的影响，通过碱性磷酸酶(alkaline phosphatase，ALP)染色及定量实验，成骨相关基因和蛋白的表达观察动态牵张对hBMMSCs成骨分化的影响。 成功构建动态牵张三维培养hBMMSCs，可实现不同持续时间、频率和动态牵张的比例；动态牵张使得hBMMSCs发生形变，牵张比例越大，细胞形变越明显，从圆形向扁椭圆形变化；动态牵张培养7 d后，静态对照组和动态牵张各实验组中hBMMSCs基本为绿染的活细胞，仅有个别红染的死细胞，活细胞比例各组之间的差异无统计学意义(P＞0.05)；动态牵张各组较静态对照组ALP大体染色深，显微镜下ALP染色阳性细胞数量多，成骨相关基因和蛋白的表达增加，差异具有统计学意义(P＜0.05)，其中动态牵张10%组ALP大体染色最深，阳性细胞数量最多，成骨相关基因和蛋白的表达较静态对照组增加最为显著。 动态牵张使得hBMMSCs发生形变，对细胞活性无明显影响，能够有效促进hBMMSCs成骨向分化。
To provide empirical evidence for optimizing meal assistance policies and strengthening their role in supporting the health of older adults, this study took Shandong Province as a case to examine the policy logic and practical challenges of meal assistance services for older adults. A combination of policy tool text analysis and qualitative interviews was employed. For the policy tool analysis, 59 policy documents related to meal assistance for older adults at the central and Shandong provincial levels from 2013 to 2024 were selected and categorized using a three-part framework, with policy provisions coded and analyzed as units. Qualitative interviews were conducted in two rounds, from August to October 2023 and again in January 2026, across eight urban and rural sample sites within Shandong' s three major economic circles, involving 17 providers of meal assistance services for older adults; the interview data were coded and analyzed using thematic analysis. Finally, the two sets of data, including policy tools and implementation themes, were integrated through a comparative approach. The development of meal assistance policies for older adults in Shandong Province can be broadly divided into three stages: The initial stage, the growth stage, and the deepening stage. Overall, policy tools exhibited a balanced emphasis on supply-oriented and environment-oriented instruments, while demand-oriented instruments remained relatively insufficient. Interview findings indicated that urban areas had primarily adopted a "government subsidy + market operation" model, while rural areas mainly relied on happiness homes, village collective resources, and public welfare positions to deliver meal assistance services. However, both urban and rural areas faced common challenges, including a mismatch between financial subsidies and operational costs, a shortage of professional staff, weak motivation for social participation, insufficient expression of demand and sustained spending by older adults, and limited implementation capacity at the grassroots level. Meanwhile, some meal assistance sites showed early signs of health-oriented meal assistance practices, such as adjusting menus according to older adults 'dietary preferences, chewing ability, and chronic disease conditions, reducing oil and salt in meal preparation, and exploring meal delivery and health education activities. Nevertheless, these efforts remained largely experience-based and fragmented, and had not yet developed into a standardised model. Meal assistance services for older adults are not only a livelihood initiative to ensure access to warm meals for older adults, but also a crucial entry point for promoting balanced diets, maintaining functional capacity, and achieving healthy aging. Future efforts should focus on refining a tiered and categorized subsidy mechanism, optimizing the differentiated supply structure between urban and rural areas, enhancing demand-side mobilization and social collaboration, strengthening grassroots governance and quality supervision, and facilitating the transition of meal assistance services from project-based provision to an institutionalized and sustainable model. 以山东省为案例分析老年助餐服务的政策逻辑与实践困境，为优化助餐服务政策、更好发挥其健康支撑作用提供实证依据。 运用政策工具文本分析法对筛选出的2013—2024年中央及山东省老年助餐相关59份政策文本进行三分法划分，并以政策条款为单元编码分析；于2023年8至10月及2026年1月在山东省三大经济圈8个城乡样本点，对17名老年助餐服务供给方人员进行定性访谈，采用主题分析法进行编码归类；最后，通过政策工具与实践主题对照方式整合政策和访谈两类资料。 山东省老年助餐政策大体经历萌芽期、上升期和深化期三个阶段，政策工具总体呈现供给型与环境型并重、需求型相对不足的特征。访谈显示，城市地区主要形成“政府补贴+市场运营”模式，农村地区主要依托幸福院、村集体资源和公益岗位开展助餐服务；但两类地区均面临财政补贴与运营成本错配、专业人员不足、社会参与动力偏弱、老年人需求表达和持续消费不足、基层执行能力有限等问题。部分助餐点已初步体现健康助餐取向，如根据老年人口味偏好、咀嚼能力和慢性病情况调整菜谱，控制油盐摄入，探索高龄送餐、健康知识讲座等做法，但总体仍以经验性探索为主，尚未形成制度化、规范化的健康助餐模式。 老年助餐服务不仅是保障老年人“一餐热饭”的民生工程，也是促进合理膳食、维护功能能力和实现健康老龄化的重要抓手。建议完善分层分类补贴机制，优化城乡差异化供给结构，增强需求侧动员与社会协同，强化基层治理和质量监管，推动老年助餐服务由项目化供给转向制度化，以便可持续发展。
To independently evaluate the discrimination of the light version of biological age (Light BioAge) model for predicting all-cause mortality, to explore the association of the difference on Light BioAge and chronological age (AgeDiff) with the composite outcomes of cardiovascular disease (CVD), and to assess the performance of CVD risk prediction using the Light BioAge instead of chronological age in a large Chinese population-based cohort. Participants aged 40-79 years without a history of CVD at baseline were drawn from the CHinese Electronic health Records Research in Yinzhou (CHERRY) study. Harrell' s concordance index (C-index) was employed to assess the discrimination of Light BioAge in predicting all-cause mortality across the overall population and sex-specific subgroups. Cox proportional hazards models were used to assess the association between AgeDiff and the composite outcome of CVD onset and death, adjusting for chronological age, sex, education, region, smoking status, body mass index, systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. Restricted cubic spline (RCS) regression was used to further analyze the potential nonlinear association between AgeDiff and CVD outcomes. Light BioAge was introduced to replace chronological age in the World Health Organization (WHO) non-laboratory CVD risk model to evaluate the discrimination and calibration in predicting 10-year CVD risk. A total of 226 406 adults were included, with a mean age of 55.0 years at baseline, 53.2% of whom were women. During a median follow-up of 7.39 years (cumulative 1 562 141 person-years), 11 703 deaths (7.49 per 1 000 person-years) and 9 815 CVD events (6.30 per 1 000 person-years) occurred. The median Light BioAge and AgeDiff were 49.31 and -5.19 years, respectively, suggesting an underestimation of chronological age. Although the Light BioAge model demonstrated good discrimination for predicting all-cause mortality in the overall population (C-index: 0.742, 95% CI: 0.738-0.746), discrimination was lower in men (0.722, 95%CI: 0.714-0.730) than in women (0.755, 95%CI: 0.749-0.761). After adjusting for confounders, the risk of CVD events showed an elevated trend with increasing AgeDiff (Ptrend < 0.001). Compared with the lowest quartile of AgeDiff, the risk of CVD events in the highest quartile increased by 21% in men (HR=1.21, 95%CI: 1.12-1.30) and 27% in women (HR=1.27, 95%CI: 1.17-1.38). RCS regression further indicated that in the overall population, the risk of CVD events increased with AgeDiff. Besides, no significant thre-shold effect was observed in sex-specific subgroups (P for non-linearity >0.05). Replacing chronological age with the Light BioAge in the WHO model did not improve discrimination; however, it significantly enhanced calibration. Calibration improvement was especially evident in women: while chronological age overestimated risk by 20.5% [expected/observed ratio (EOR)=1.205, 95%CI: 1.167-1.246), the Light BioAge reduced this to a marginal 2.1% underestimation (EOR=0.979, 95%CI: 0.948-1.012). The discrimination of the Light BioAge in predicting all-cause mortality seems good, and a wider AgeDiff indicates higher cardiovascular risk in this large population-based Chinese cohort. Replacing chronological age with biological age in the WHO non-laboratory model significantly improved calibration for women. 在大样本社区人群队列中独立验证Light BioAge模型计算的简易生物学年龄预测全因死亡的区分度，并探索其与时序年龄的差值和心血管病发病及死亡结局事件的关联，以及生物学年龄对心血管病风险预测的实际应用价值。 研究对象为中国鄞州电子健康档案研究(CHinese Electronic health Records Research in Yinzhou，CHERRY)队列中40~79岁基线无心血管病史的人群，利用C统计量(Harrell’s concordance index，C-index) 评估仅通过空腹血糖、血清肌酐和超敏C反应蛋白三个临床常用指标构建的Light BioAge模型在全人群及不同性别亚组中预测全因死亡的外部验证区分度，采用Cox比例风险模型分析年龄差值与首次发生的心血管病发病和心血管病死亡复合终点的关联，调整时序年龄、性别、教育水平、居住地、吸烟状态、体重指数、收缩压、总胆固醇及高密度脂蛋白胆固醇等影响因素后计算风险比(hazard ratio，HR)及其95%置信区间(confidence interval，CI)。采用限制性立方样条回归方法进一步分析年龄差值与心血管病结局事件的潜在非线性关联。在2019年世界卫生组织(World Health Organization，WHO)开发的心血管病风险预测简易模型中采用生物学年龄替换时序年龄，评估对10年心血管病风险预测区分度和校准度的影响。 共纳入226 406名研究对象，人群的基线平均年龄为55.0岁，53.2%为女性。在中位7.39年(累计1 562 141人年)的随访期间，共有11 703人(7.49/1 000人年)发生死亡，9 815人(6.30/1 000人年)发生心血管病发病和死亡复合结局事件。Light BioAge模型计算的生物学年龄及年龄差值的中位数分别为49.31和-5.19，提示其整体上低于时序年龄；虽然Light BioAge模型在全人群中预测全因死亡的区分度较好(C统计量：0.742，95%CI：0.738~0.746)，但在男性中的区分度低于女性[C统计量分别为0.722(95%CI：0.714~0.730)和0.755(95%CI：0.749~0.761)]。调整其他影响因素后，心血管病结局事件的风险呈现随年龄差值增大而增高的趋势(Ptrend < 0.001)；年龄差值处于上四分位数组与下四分位数组相比，男性心血管病结局事件的风险增加了21%(HR=1.21，95%CI：1.12~1.30)，女性增加了27%(HR=1.27，95%CI：1.17~1.38)。限制性立方样条回归的结果进一步显示，总人群的心血管病结局事件的风险随年龄差值的增加而升高，且男性、女性亚组中并未发现明显的阈值效应(非线性关联P>0.05)。在WHO模型中采用生物学年龄替换时序年龄后，预测心血管病风险的区分度无改善，但校准度有明显提升，尤其是在女性人群中从时序年龄模型整体风险高估的20.5%[预测/观察比(expected/observed ratio，EOR)=1.205，95%CI：1.167~1.246]改善为生物学年龄替换后的整体风险仅略微低估2.1%(EOR=0.979，95%CI：0.948~1.012)。 Light BioAge模型构建的简易生物学年龄在大样本社区人群中预测全因死亡的区分度较好，生物学年龄和时序年龄的差值增大将增加心血管病结局事件的风险，在WHO心血管病风险预测模型中用生物学年龄替换时序年龄后，模型的校准度明显改善，特别是在女性人群。
To explore differences in the Big Five personality traits among patients with type 2 diabetes mellitus (T2DM) in relation to demographic characteristics and health education preferences and to provide evidence for personalized health education strategies. In September 2023, a cluster sampling method was used to recruit patients with T2DM from seven community health service centers in Shandong Province, China. Data were collected using a questionnaire survey. The 10-item Big Five Inventory (BFI-10) and a self-developed health education preference questionnaire were used for the assessment. Latent profile analysis (LPA) was conducted to identify personality classifications among the patients. Chi-square tests were applied to compare differences in health education preferences across personality groups, and stratified binary Logistic regression analysis was performed to examine the association between personality classification and health education preferences. A total of 612 patients were included and categorized into three personality groups: Regular-balanced type (69.8%), introverted-sensitive type (6.4%), and proactive-adaptive type (23.8%). In the univariate analysis, the proportion of patients in the proactive-adaptive group who preferred peer patients as health education providers was significantly lower than that in other personality groups (χ2=6.123, P=0.047). In contrast, patients in the introverted-sensitive group showed a significantly higher preference for health education content that included psychological support than other personality groups (χ2=8.566, P=0.014). In the Logistic regression analysis, using the regular-balanced type as the reference group, proactive-adaptive patients were less likely to prefer peer patients with diabetes as health education providers (OR=0.491, 95%CI: 0.279-0.866, P=0.014). Regarding health education content, proactive-adaptive patients demonstrated a lower preference for research-frontier information (OR=0.565, 95%CI: 0.376-0.848, P=0.006). In terms of educational delivery settings, introverted-sensitive patients were less likely to prefer mobile applications as a means of receiving health education (OR=0.374, 95%CI: 0.165-0.848, P=0.019). When the proactive-adaptive type as the reference group, introverted-sensitive patients showed a significantly higher preference for psychological support content (OR=2.122, 95%CI: 1.029-4.380, P=0.042). Personality traits exhibit substantial heterogeneity among patients with T2DM, and different personality classifications are associated with distinct health education preferences. Personality traits may serve as an important reference for developing individualized health education strategies; however, their effectiveness in improving intervention outcomes requires further validation through future studies. 探讨老年2型糖尿病(type 2 diabetes mellitus，T2DM)患者大五人格特质在人口学特征及健康教育偏好上的差异，为个性化健康教育提供依据。 于2023年9月采用整群抽样的方法，抽取山东省7个社区卫生服务中心的T2DM患者，采用简版大五人格量表和自行设计的健康教育偏好问卷进行测量，基于大五人格特质得分使用潜剖面分析来识别患者的人格分类，通过卡方检验和分层二元Logistic回归分析人格分类与健康教育偏好的关联。 纳入的612例患者可分为3种人格分类：常规平衡型(69.8%)、内向敏感型(6.4%)和积极适应型(23.8%)。在单因素分析中，积极适应型患者希望糖尿病病友是健康教育提供者的比例低于其他人格分类(χ2=6.123，P=0.047)，内向敏感型患者希望包含心理疏导内容的比例高于其他人格分类(χ2=8.566，P=0.014)。在Logistic回归分析中，以常规平衡型为参照，在健康教育提供者方面，积极适应型患者更不倾向于选择糖尿病病友作为提供者(OR=0.491，95%CI：0.279~0.866，P=0.014)；在健康教育内容方面，积极适应型患者对研究前沿内容的偏好较低(OR=0.565，95%CI：0.376~0.848，P=0.006)；在健康教育地点方面，内向敏感型患者不倾向于选择手机应用程序作为健康教育获取途径(OR=0.374，95%CI：0.165~0.848，P=0.019)。以积极适应型为参照，在健康教育内容方面，内向敏感型患者对心理疏导的偏好更高(OR=2.122，95%CI：1.029~4.380，P=0.042)。 老年T2DM患者存在明显的人格特质异质性，不同人格分类的患者在健康教育偏好上存在差异；在对T2DM患者开展健康教育时，可将人格特质作为制定个体化干预策略的重要参考因素之一，但其实际干预效果仍有待进一步研究验证。
To evaluate the genetic nurture effect of parental genotypes on the risk of ischemic stroke (IS) in offspring and to elucidate the parental origin-specific differences in this effect. This study utilized data from the "Family Cohort of Common Chronic Non-communicable Diseases in Rural Areas of Northern China". A total of 530 core families and sibling pairs were selected, comprising 1 005 offspring. Single nucleotide polymorphisms (SNPs) within the CTNNA gene family (CTNNA1, CTNNA2 and CTNNA3) were detected. Using offspring as the unit of analysis, parental non-transmitted alleles were inferred based on Mendelian inheritance principles. Rigorous quality control was implemented for genotype imputation, ensuring high reliability of the inferred data. Linear mixed-effects models were constructed to estimate the genetic nurture effect of non-transmitted alleles on offspring IS. These models compared differences between genetic nurture effects and individual genetic effects, distinguished between paternal and maternal effects, and calculated the statistic η to assess the relative magnitude of parental effects. A total of 1 005 offspring from 530 families were included, comprising 308 IS patients (30.6%) with a mean age of 56.3 years. Sixteen independent SNPs associated with IS genetic nurture effects were identified (9 in CTNNA2, 6 in CTNNA3, and 1 in CTNNA1). The effect sizes ranged from -0.282 to 0.480, with rs117741773 (CTNNA2) showing the strongest effect (0.480, 95%CI: 0.278-0.682). Only four of these SNPs exhibited concurrent individual genetic effects, which acted in the opposite direction to the genetic nurture effects. Parent-of-origin specific analysis revealed that 12 SNPs exhibited genetic nurture effects from a single origin: 4 showed exclusively paternal effects (effect size: -0.298 to 0.945; η: 1.21 to 63.83), and 8 showed exclusively maternal effects (effect size: -0.489 to 0.602; η: 0.03 to 0.44). This study provides evidence that multiple IS susceptibility loci within the CTNNA gene family exhibit significant genetic nurture effects. The findings highlight the complex interplay between inherited genetics and the family environment. The heterogeneity of these effects based on parental origin underscores the significant role of parent-specific genetic nurture in the etiology of IS, offering new insights for understanding the missing heritability in stroke genetics. 评估亲代基因型对子代缺血性脑卒中(ischemic stroke, IS)风险的遗传培育效应，并解析该效应的父源与母源差异。 依托“北方农村地区居民常见慢性非传染性疾病家系队列研究”，选取核心家系、同胞对等，检测CTNNA基因家族(CTNNA1、CTNNA2、CTNNA3)的单核苷酸多态性(single nucleotide polymorphisms, SNPs)。以子代为单位推断亲代未传递给子代的等位基因，构建线性混合效应模型，评估亲代未传递等位基因对子代IS的遗传培育效应，并对比其与个体遗传效应的差异，区分父源、母源效应，同时构建统计量η评估两者的相对大小。 共纳入530个家系的1 005名子代，其中IS患者共308例(30.6%)，平均年龄56.3岁。共识别了16个具有IS遗传培育效应的独立SNPs(9个位于CTNNA2，6个位于CTNNA3，1个位于CTNNA1)，效应值为-0.282~0.480，rs117741773(CTNNA2)的效应最强(0.480，95%CI: 0.278~0.682)；其中，仅4个SNPs兼具个体遗传效应，且方向与遗传培育效应相反。亲本特异性分析显示，12个SNPs呈单一亲本遗传培育效应，4个仅表现为父源效应(效应值：-0.298~0.945，η：1.21~63.83)，8个仅表现为母源效应(效应值：-0.489~0.602，η：0.03~0.44)。 CTNNA基因家族中存在多个具有遗传培育效应的IS易感位点，且不同亲本来源效应存在异质性，提示亲本特异性遗传培育效应在IS病因中具有重要作用。
Tumors in the oral and maxillofacial region present significant clinical challenges due to anatomical complexity and high individual variability, with the traditional experience-dependent model often lacking three-dimensional visualization, precise intraoperative navigation, and quantitative postoperative assessment. This article comprehensively reviews over a decade of research and clinical advances in "digital and intelligent surgery" developed by our team at Peking University School and Hospital of Stomatology, systematically documenting its transformative impact on tumor management. In digital surgery, we have established multimodal image fusion techniques integrating CT, MRI, and PET/CT to achieve detailed three-dimensional preoperative visualization, enabling accurate delineation of tumor boundaries and relationships with critical anatomical structures, such as nerves and vessels. We further developed personalized surgical planning methods including virtual design for jaw reconstruction using vascularized fibula or iliac crest flaps, computer-aided pre-forming of orbital titanium mesh, 3D-printed patient- specific plates manufactured via electron beam melting, soft-tissue flap simulation and volumetric planning for the anterolateral thigh flap, and implant-guided rehabilitation for complex maxillary defects. For surgical execution, navigation systems and mixed reality technologies have been implemented to enable accurate tumor resection, osteotomy guidance, and precise positioning of reconstructed bone segments, thereby enhancing surgical accuracy and safety while reducing operative time. In parallel, artificial intelligence has been integrated to enhance diagnostic and planning efficiency through deep learning-based tumor segmentation and classification from enhanced CT and MRI, automated reconstruction planning based on shape completion and morphometric descriptors, postoperative facial contour prediction using surface mesh deformation models, and machine learning-driven prognostic modeling for salivary gland malignancies based on clinicopathological data. The synergistic integration of these digital and intelligent technologies, collectively termed "digital and intelligent surgery", has shifted clinical practice from an experience-driven to a data-driven paradigm, significantly improving precision, safety, and efficiency while enabling truly personalized treatment pathways. This review also identifies current limitations such as the need for further automation in soft-tissue simulation and broader clinical validation of AI tools, and outlines future directions including the development of integrated surgical platforms and real-time adaptive planning systems, emphasizing the role of intelligent surgical systems in shaping the next generation of oral and maxillofacial oncology care toward more predictive, preventive, and patient-centered outcomes. 发生于口腔颌面部的肿瘤因解剖结构复杂且个体差异大, 传统"经验依赖型"诊疗模式存在术前规划无法三维可视化、术中缺少精准导航、术后缺乏量化评估等局限性。本文系统综述了本课题组十余年来在口腔颌面部肿瘤"数智化外科"领域的探索与临床应用成果。在数字化外科方面, 课题组建立了基于CT、MRI、PET/CT等多模态数据融合的术前三维可视化技术, 开发了颌骨缺损重建、眶底钛网预成形、3D打印个性化钛板、软组织皮瓣虚拟设计与种植修复等个性化手术方案设计方法, 并将外科导航系统、混合现实技术应用于术中精准定位与肿瘤切除。在人工智能应用方面, 课题组探索了基于深度学习的肿瘤影像自动分割与分类、颌骨重建方案自动生成、术后面型预测及唾液腺恶性肿瘤预后评估等智能化技术。通过数字化与智能化技术的深度融合, "数智化外科"实现了从经验驱动到数据驱动的诊疗模式转型, 显著提升了口腔颌面部肿瘤诊疗的精准性、安全性和效率, 为患者提供了更加个性化、可预测的治疗方案。本课题组还展望了未来"数智化外科"在口腔颌面部肿瘤诊疗中的发展方向。
To investigate the associations between maternal exposure to cold and heat exposure during the three months before pregnancy and early pregnancy and the risk of congenital heart disease (CHD) in offspring, and to identify critical exposure windows and modifying factors. This nationwide cohort study included women aged 20-49 years with complete pregnancy outcome follow-up from the National Free Pre-pregnancy Check-ups Project (NFPCP) database between January 1, 2014 and April 21, 2020. Meteorological data from the European Centre for Medium-Range Weather Forecasts Reanalysis v5 (ERA5) dataset were linked to residential addresses. Cold and heat exposure were defined based on relative thresholds stratified by climate zone: heat and cold were defined as temperatures above the 90th percentile or below the 10th percentile, respectively, of the location-specific temperature distribution during each exposure window. Cox proportional hazards models were used to analyze the associations between cold and heat exposure during the three months before pregnancy and early pregnancy and the risk of CHD, and to calculate hazard ratios (HR) and 95% confidence intervals (CI) after adjusting for maternal age, body mass index (BMI), education level, geographical region, conception season, and relative humidity. Stratified analyses were performed to examine the effects of age, BMI, and fetal sex on the associations between cold and heat exposure and the risk of CHD. A total of 6 322 635 women aged 20-49 years with complete pregnancy outcome follow-up were included, and 1 478 cases of CHD were diagnosed among their offspring. The analysis showed that heat exposure during the three months before pregnancy was significantly associated with an increased risk of CHD in offspring (HR=1.49, 95%CI: 1.23-1.80); while no significant association was found for heat exposure during early pregnancy. No significant association was observed for cold exposure during the three months before pregnancy and early pregnancy (three months before pregnancy: HR=0.93, 95%CI: 0.77-1.14; early pregnancy: HR=0.95, 95%CI: 0.79-1.16). Stratified analyses showed that the risk of CHD associated with heat exposure during the three months before pregnancy was increased in women aged ≥30 years (HR=2.18, 95%CI: 1.54-3.10) and in male fetuses (HR=1.73, 95%CI: 1.31-2.29); the risk of CHD associated with heat exposure during early pregnancy was significantly increased in women with BMI ≥24 kg/m2 (HR=1.86, 95%CI: 1.21-2.87). Heat exposure during the three months before pregnancy might increase the risk of congenital heart disease in offspring, and this risk was elevated in both women aged ≥30 years and male fetuses. Furthermore, heat exposure during early pregnancy significantly increased the risk of congenital heart disease in offspring among women with BMI ≥24 kg/m2. No significant association was observed between cold exposure and the risk of congenital heart disease. 系统评估母亲在孕前3个月及孕早期冷热暴露对子代先天性心脏病发病风险的影响，并识别潜在的暴露敏感窗口及影响因素。 研究对象为2014年1月1日至2020年4月21日纳入国家免费孕前优生健康检查项目队列中20~49岁有完整妊娠结局追踪的女性。气象数据来源于欧洲中期天气预报中心第五代再分析数据集，根据研究对象居住地匹配孕期温度。为反映区域热适应性，冷热暴露采用相对阈值法定义：依据气候带对研究人群进行分层，计算每位个体在特定暴露时间窗内的平均温度；热暴露定义为该温度高于其所在气候带所有个体温度分布的第90百分位数；冷暴露则定义为低于第10百分位数。采用Cox比例风险模型分析孕前3个月及孕早期冷热暴露与先天性心脏病发病风险的关联，校正母亲年龄、体重指数(body mass index, BMI)、教育水平、地理区域、受孕季节、相对湿度等混杂因素后计算风险比(hazard ratio, HR)及其95%置信区间(confidence interval, CI)。通过分层分析探讨年龄、体重指数、胎儿性别因素对冷热暴露与先天性心脏病发病风险关联的影响。 共纳入6 322 635例20~49岁有完整妊娠结局追踪的女性，其子代共确诊先天性心脏病1 478例。分析显示，在孕前3个月，热暴露与子代先天性心脏病发病风险升高显著相关(HR=1.49，95%CI：1.23~1.80)；而孕早期热暴露与子代先天性心脏病发病风险无显著关联。孕前3个月及孕早期的冷暴露均未发现与先天性心脏病发病风险存在显著关联(孕前3个月：HR=0.93，95%CI：0.77~1.14；孕早期：HR=0.95，95%CI：0.79~1.16)。分层分析显示，孕前3个月热暴露导致先天性心脏病发病风险在30岁及以上孕产妇(HR=2.18，95%CI：1.54~3.10)和男性胎儿(HR=1.73，95%CI：1.31~2.29)中更高；孕早期热暴露导致先天性心脏病发病风险在BMI≥24 kg/m2的孕产妇中显著升高(HR=1.86，95%CI：1.21~2.87)。 孕前3个月热暴露可增加子代先天性心脏病的发病风险，该风险在30岁及以上孕产妇和男性胎儿中更高。此外，孕早期热暴露导致先天性心脏病发病风险在BMI≥24 kg/m2的孕产妇中显著升高。未发现冷暴露与先天性心脏病发病风险存在显著关联。
To investigate the expression of the fatty acid binding protein 6 (FABP6) long transcript in clear cell renal cell carcinoma (ccRCC), its correlation with tumor biological behavior, and further analyze its potential as a biomarker and therapeutic target. Following bioinformatics analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, the FABP6 gene associated with ccRCC development and prognosis was screened. The existence and expression patterns of FABP6 long and short transcripts were further confirmed experimentally. In the experimental section, reverse transcription quantitative real-time PCR (RT-qPCR) and Western blot were used to detect the differential expression levels of the FABP6 long and short transcripts in ccRCC cell lines and tissue samples. ccRCC cell lines with overexpression and knockdown of the FABP6 long transcript were constructed. The impact of the FABP6 long transcript on the proliferation capacity of ccRCC cells was assessed using the 5-ethynyl-2'-deoxyuridine proliferation assay and the colony formation assay, respectively. Bioinformatics database analysis revealed that the expression of the FABP6 gene was higher in ccRCC cell lines and tissue samples compared with their normal counterparts (P=0.02), with FABP6 long transcript being the predominant form (P=0.02). RT-qPCR and Western blot results further confirmed that the expression level of the FABP6 long transcript was higher than that of the FABP6 short transcript in ccRCC cell lines such as 769P, A498, CAKI1, OSRC2, and 786O. In in vitro functional experiments, overexpression of the FABP6 long transcript promoted the proliferation of ccRCC cells. Conversely, knockdown of the FABP6 long transcript significantly inhibited the proliferation of ccRCC cells. This suggested that the FABP6 long transcript might play an oncogenic role in the development and progression of ccRCC, potentially by driving cell cycle progression or regulating related proli-ferative signaling pathways. This study systematically reports the specific high expression of the FABP6 long transcript in ccRCC. Gain-of-function and loss-of-function experiments confirmed its crucial role in promoting ccRCC cell proliferation. This reveals an important new function of the FABP6 gene, particularly FABP6 long transcript, in the malignant progression of ccRCC. 探讨脂肪酸结合蛋白6(fatty acid binding protein 6，FABP6)基因长转录本在肾透明细胞癌(clear cell renal cell carcinoma，ccRCC)中的表达情况及其与肿瘤生物学行为的关系，进一步分析其作为潜在生物标志物和治疗靶点的可能性。 通过基因表达汇编(Gene Expression Omnibus，GEO)和癌症基因组图谱(The Cancer Genome Atlas，TCGA)数据库进行生物信息学分析后，筛选得到与ccRCC发生发展和预后相关的FABP6基因，并通过实验进一步确认其长短转录本的存在情况及表达模式。利用实时荧光定量逆转录PCR(reverse transcription quantitative real-time PCR，RT-qPCR)和蛋白免疫印迹实验检测FABP6基因长短转录本在ccRCC细胞系和组织样本中的表达水平差异。构建FABP6基因长转录本过表达和敲低的ccRCC细胞系，并分别通过5-乙炔基-2’-脱氧尿苷(5-ethynyl-2’-deoxyuridine, EdU)增殖实验和克隆形成实验，评估FABP6基因长转录本对ccRCC细胞增殖能力的影响。 生物信息学数据库分析显示，FABP6基因在ccRCC细胞系和组织样本中的表达高于其正常对照细胞和组织样本(P=0.02)，并且其长转录本为主要表达形式(P=0.02)。RT-qPCR和蛋白免疫印迹实验结果进一步证实，FABP6基因长转录本在ccRCC细胞系769P、A498、CAKI1、OSRC2、786O等中的表达水平高于短转录本。体外功能实验中，过表达FABP6基因长转录本促进ccRCC细胞的增殖能力；相反，敲低FABP6基因长转录本显著抑制ccRCC细胞的增殖能力，提示FABP6基因长转录本可能通过驱动细胞周期进程或调控相关增殖信号通路，在ccRCC的发生发展中扮演了癌基因样的促进作用。 系统报道了FABP6基因长转录本在ccRCC中特异性高表达，并通过功能增益和功能缺失实验证实了其促进ccRCC细胞增殖的关键作用，揭示了FABP6基因，尤其是其长转录本在ccRCC恶性进展中的重要新功能。
Pancreatic adenosquamous carcinoma (PASC) is a rare exocrine malignancy of the pancreas with an increasing incidence, histologically defined by the coexistence of adenocarcinoma and squamous carcinoma components. Current pathological diagnosis typically requires the squamous component to comprise at least 30% of the tumor. However, this threshold remains controversial given the unconfirmed independent prognostic value of the extent of squamous differentiation. Compared with pancreatic ductal adenocarcinoma (PDAC), PASC exhibits greater aggressiveness and heterogeneity, contributing to a poorer prognosis with a median survival of approximately 9 months. Despite its distinct biological behavior, specific preoperative diagnostic methods and targeted therapeutic strategies remain elusive. Diagnostically, while PASC lacks specific molecular markers, the ring-enhancement sign observed in the arterial phase of contrast-enhanced CT may aid distinction from PDAC. Owing to the lack of standardized therapeutic strategies, treatment largely follows guidelines established for PDAC, offering limited survival benefits, though platinum-based chemotherapy and radiotherapy show potential efficacy. Notably, the rationale for immunotherapy lies in the high programmed death-ligand 1 (PD-L1) expression in the squamous component and an immunosuppressive microenvironment characterized by specific checkpoint interactions, such as the TIGIT-CD155 axis. Furthermore, the cellular origin and evolutionary trajectory of PASC remain debated. While monoclonal origin is the prevailing theory, it remains unclear whether the squamous component arises from adenocarcinoma transdifferentiation or from pancreatic pluripotent stem cells. At the molecular level, PASC shares genomic and transcriptomic features with PDAC yet maintains a distinct identity. Concurrently, its tumor microenvironment (TME) displays unique landscapes, differing significantly from PDAC in immune and stromal components like T cells, macrophages, and fibroblasts. Moreover, marked intratumoral heterogeneity is observed between the adenocarcinoma and squamous carcinoma regions within the same tumor. Future efforts should prioritize multi-omics and laser microdissection technologies to establish a refined molecular classification system, alongside the integration of liquid biopsy and artificial intelligence (AI)-assisted radiomics for accurate preoperative diagnosis. This comprehensive strategy is essential to shift clinical practice from empirical treatment to personalized precision medicine, ultimately improving outcomes for this refractory disease. This article systematically reviews the epidemiology and clinicopathological features of PASC, and specifically explores the therapeutic potential of platinum-based chemotherapy, radiotherapy, and immunotherapy. Furthermore, special attention is given to recent advances in monoclonal origin patterns, unique genomic and transcriptomic alterations, and TME heterogeneity. 胰腺腺鳞癌(pancreatic adenosquamous carcinoma, PASC)是一种罕见的胰腺外分泌恶性肿瘤，兼具腺癌与鳞癌双重特征。相较于胰腺导管腺癌(pancreatic ductal adenocarcinoma，PDAC)，PASC表现出更强的侵袭性与异质性，且患者预后更差。PASC的生物学行为特殊，目前临床缺乏特异性的术前诊断方法和针对性的治疗策略，临床治疗多沿用PDAC方案，患者生存获益有限。此外，PASC的细胞起源与演化路径、分子分型图谱也有待阐明。本文系统综述了PASC的流行病学与临床病理特征，并探讨含铂化疗方案、放疗及免疫治疗在改善患者预后方面的潜在价值，同时，总结了PASC在克隆起源模式、独特的基因组和转录组改变以及肿瘤微环境异质性等方面的最新研究进展。
Malignant tumors, a class of diseases characterized by abnormal proliferation and aggressive growth, pose a severe threat to human health. A hallmark of tumor cell biology is the pervasive presence of the Warburg effect, wherein cells undergo high-rate glycolysis leading to substantial lactate production, even under aerobic conditions. Traditionally regarded merely as a metabolic waste product, lactate has been re-evaluated through recent research, which reveals it to be not only a crucial metabolite but also a significant signaling molecule. It exerts core regulatory functions in gene expression and cellular activity through a novel post-translational modification: Protein lactylation. The seminal discovery of histone lactylation unveiled a direct and novel mechanistic link between cellular metabolic states and epigenetic regulation. Subsequent proteomic studies have substantiated that lactylation is a widespread modification existing across various types of non-histone proteins, establishing it as an important regulatory mechanism. The process of lactylation modification is dynamic and reversible, orchestrated by specific "writer" enzymes that catalyze its addition and "eraser" enzymes that facilitate its removal. Within the context of malignant tumors, lactylation modification participates extensively in tumorigenesis and progression by targeting two primary classes of substrate proteins: Histones and non-histone proteins. At the epigenetic level, histone lactylation remodels chromatin state and reprograms gene expression profiles. At the functional level, lactylation of non-histone proteins directly modulates the activity of key signaling pathway components, metabolic enzymes, and DNA repair factors. The synergistic action of these two facets collectively drives core malignant phenotypes, including remodeling of the tumor immune microenvironment, facilitation of metastasis and dissemination, induction of therapy resistance, and dysregulation of metabolism. This review provides a systematic overview of the discovery, molecular mechanisms, and recent advances concerning the roles of lactylation in tumor metabolism, immunity, and treatment resistance. It further explores potential therapeutic strategies targeting lactylation, such as modulating lactate metabolism, intervening in the enzymatic machinery of the modification system, and developing specific blocking agents. Although challenges remain regarding the specificity of the involved enzymes and the functional validation of these modifications, in-depth research on lactylation offers a fresh perspective for understanding the crosstalk between tumor metabolism and epigenetics. It also lays a theoretical foundation for the development of innovative strategies for cancer diagnosis and therapy. 恶性肿瘤是一类以异常增殖和侵袭性生长为特征的疾病，严重威胁人类健康。肿瘤细胞普遍存在瓦博格效应(Warburg effect)，即在有氧条件下仍进行高速糖酵解，产生大量乳酸。乳酸传统上被视为代谢废物，近年研究发现其不仅是重要的代谢物，更可作为信号分子，通过新型蛋白质翻译后修饰——乳酸化修饰，在基因表达和细胞功能调控中发挥核心作用。组蛋白乳酸化修饰的发现，揭示了细胞代谢状态与表观遗传调控间直接相连的全新机制。随后的蛋白质组学研究证实，乳酸化修饰广泛存在于各类非组蛋白中，成为一种重要的调控方式。乳酸化修饰是由写入酶催化、消除酶去除的动态可逆过程。在恶性肿瘤中，乳酸化修饰通过作用于组蛋白和非组蛋白两大类底物，广泛参与肿瘤的发生发展，在表观遗传层面，组蛋白乳酸化重塑染色质状态，重编程基因表达；在功能层面，非组蛋白乳酸化直接调控信号通路关键蛋白、代谢酶和DNA修复因子的活性，二者协同驱动肿瘤免疫微环境重塑、转移扩散、治疗抵抗及代谢异常等核心恶性表型。本文系统综述了乳酸化修饰的发现历程、分子机制，并重点阐述了其在肿瘤代谢、免疫及治疗抵抗中的最新研究进展。同时，探讨了针对乳酸化修饰的潜在治疗策略，包括调控乳酸代谢、干预修饰酶系统，以及开发特异性阻断工具。尽管该领域在酶的特异性和功能研究方面仍面临挑战，但针对乳酸化修饰的深入研究，为理解肿瘤代谢-表观遗传交叉对话提供了全新视角，并为开发创新的肿瘤诊断与治疗策略奠定了理论基础。
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and lethal malignancy in China and other East Asian countries. For patients with locally advanced disease, neoadjuvant chemotherapy or chemoradiotherapy followed by surgery has become the standard treatment paradigm. However, despite improvements in local tumor control and surgical outcomes, long-term survival remains unsatisfactory, largely due to the high incidence of distant metastasis and systemic disease progression. Therefore, optimizing perioperative systemic therapy represents a critical unmet clinical need in ESCC. In recent years, the introduction of immune checkpoint inhibitors (ICIs) has profoundly reshaped the perioperative treatment landscape of ESCC. This review comprehensively summarizes recent clinical advances in perioperative immunotherapy for ESCC, including neoadjuvant immunotherapy alone, neoadjuvant immunotherapy combined with chemotherapy, neoadjuvant immunotherapy combined with chemoradiotherapy, and postoperative adjuvant immunotherapy. Current data indicate that neoadjuvant chemoradiotherapy remains highly effective in improving local control, downstaging tumors, and increasing the rate of R0 resection. Nevertheless, its ability to translate these advantages into durable survival benefit is limited, and distant recurrence remains a major cause of treatment failure. In contrast, neoadjuvant immunotherapy combined with chemotherapy has demonstrated a marked improvement in pathological complete response (pCR) rates across multiple early-phase trials. More importantly, this strategy appears to provide supe-rior systemic disease control, thereby reducing the risk of distant metastasis and offering a promising avenue for improving long-term survival. Neoadjuvant immunotherapy combined with chemoradiotherapy has shown further enhancement of local response and tumor regression; however, this approach is asso-ciated with increased treatment-related toxicity, and robust evidence supporting a clear survival advantage is still lacking. As a result, the optimal integration of radiotherapy into immunotherapy-based perioperative regimens remains an area of active investigation. Given the heterogeneity of ESCC, perioperative treatment strategies should evolve toward individualized, risk-adapted approaches. For patients with a high local tumor burden (advanced T stage), the incorporation of radiotherapy may be beneficial to reinforce local control and improve resectability. Conversely, for patients with extensive lymph node involvement (advanced N stage) and a high risk of distant relapse, immunotherapy-based systemic treatment should be prioritized. In the postoperative setting, adjuvant immunotherapy has been shown to improve outcomes in patients who fail to achieve pCR after neoadjuvant chemoradiotherapy. Looking forward, the integration of dynamic biomarkers, such as circulating tumor DNA (ctDNA), along with the identification of novel immune targets and predictive biomarkers, is expected to further refine patient selection and optimize precision perioperative treatment strategies for ESCC. 食管鳞状细胞癌(esophageal squamous cell carcinoma, ESCC)是中国高发的恶性肿瘤，以手术为核心的新辅助化疗或放化疗虽已成为局部晚期患者的标准治疗模式，但由于远处转移风险高，患者的远期生存获益仍遭遇瓶颈。近年来，免疫检查点抑制剂的引入显著改变了ESCC的围手术期治疗格局。本文综述了ESCC新辅助免疫治疗单药、免疫联合化疗、免疫联合放化疗及术后辅助免疫治疗的最新临床研究进展。现有证据表明，新辅助联合放疗在提高局部控制率及根治性切除率方面优势明显，但在转化为远期生存获益方面仍存在局限；与之相比，新辅助免疫联合化疗在显著提高病理完全缓解(pathological complete response，pCR)率的同时，亦通过更强的全身控制有效降低了远处转移风险。尽管新辅助免疫联合放化疗进一步提升了局部缓解率，但毒性负担增加，且远期生存获益尚待证实。因此，围手术期治疗策略应趋向个体化分层：对于局部肿瘤负荷大(T分期高)者，推荐引入放疗以强化局部控制，提高根治性切除率；对于淋巴结转移负荷较重(N分期高)、远处复发风险高者，应侧重以免疫为基础的全身治疗。在术后辅助治疗方面，免疫治疗可改善新辅助放化疗后非pCR患者的预后。结合循环肿瘤DNA(circulating tumor DNA，ctDNA)等动态生物标志物的检测以及对新型免疫靶点的探索，将有助于ESCC围手术期精准治疗的进一步优化。
Systemic lupus erythematosus (SLE) and lymphoma are two different diseases. However, they might mimic each other sometimes. Here, we reported a case of bone marrow infiltration as initial manifestation of large B-cell lymphoma that mimiced SLE. The patient was an elderly female whose chief complaints were edema and bilateral lower limb fatigue for one month. Initially, she was prescribed thyroid hormone supplementation and albumin infusion for hypothyroidism and hypoproteinemia, respectively. The edema was improved, but fatigue worsened and the patient was bedridden. Then further examinations revealed anemia, thrombocytopenia, elevated lactate dehydrogenase (LDH), abnormal coagulation function, positive urinary protein, reduced complement C3 and C4, and positive antinuclear antibodies. Based on the above manifestations and laboratory findings, the diagnosis of SLE was considered. After administering 40 mg/d of methylprednisolone, the patient' s edema, platelet count and LDH levels were improved, whereas her fatigue worsened to the point where she had difficulty turning in bed. When the dose of glucocorticoid tapered to 40 mg/d of prednisone, the LDH levels elevated and platelet counts decreased. The treatment response was inconsistent with SLE. In order to clarify and confirm the diagnosis, bone marrow puncture was performed and showed large B-cell lymphoma with bone marrow infiltration of 27.5% tumor cells. Enlargement of superficial lymph node or visceral organ is common clinical manifestation of lymphoma. However, our present case was bone marrow infiltration lonely without enlargement of lymph node and organ, and it is referred to as bone marrow lymphoma (BML). BML can be classified into primary bone marrow lymphoma (PBML) and secondary bone marrow lymphoma (SBML). PBML is a rare and primary tumor in the bone marrow without involvement of lymph nodes, liver, spleen and any other organs. It is easy to be misdiagnosed or missed diagnosis due to the absence of specific clinical presentation. Bone marrow examination is required and important to make the diagnosis of PBML. Diffuse large B-cell lymphoma is the most common type of PBML. SBML is caused by lymphoma in other parts of the body and invasion of bone tissue. Most of BML patients have a poor prognosis and require rapid diagnosis and treatment. The patient we reported only took two months from onset of symptoms to death. This case indicated that it was crucial to revisit the diagnostic and therapeutic strategies when treatment response was not consistent with the diagnosis. 淋巴结或脏器肿大是淋巴瘤的常见临床表现，当患者无上述异常，仅以水肿、乏力等非特异性表现为主诉时易被误诊、漏诊。本例患者就诊期间发现贫血、血小板减少、乳酸脱氢酶升高、凝血功能异常、尿蛋白阳性、补体C3和C4降低、抗核抗体阳性，经影像学检查未见肿瘤迹象，初诊为系统性红斑狼疮，经激素治疗后部分症状及实验室指标有所改善，但乏力症状进行性加重，乳酸脱氢酶一过性下降后再次升高，血小板、凝血指标无改善，系统性红斑狼疮不能解释疾病的全貌。为进一步确定病因，行骨髓穿刺检查，明确诊断为大B细胞淋巴瘤骨髓受累。临床诊疗中，系统性红斑狼疮的诊断需充分排除其他疾病，特别是存在不能解释的临床表现或对治疗应答不佳，以避免误诊、误治。
To analyze the incidence of small intestinal bacterial overgrowth (SIBO) in patients with asymptomatic hyperuricemia (HUA) and the serum levels of C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in patients with asymptomatic HUA and SIBO. A total of 87 asymptomatic HUA patients and 40 healthy controls from Shanxi Fenyang Hospital from June 2023 to June 2024 were selected as the study subjects, and the baseline data, laboratory indicators were collected. Lactulose methane-hydrogen breath test (LHBT) was used to detect the occurrence of SIBO, and the asymptomatic HUA patients was divided into SIBO-positive group and SIBO-negative group according to the test results of LHBT. The positive rate of SIBO in the asymptomatic HUA patients was analyzed, and the concentrations of H2 and CH4, the levels of CRP, IL-1β, IL-6 and TNF-α at each time point between the asymptomatic HUA patients and the healthy controls were compared, and the levels of CRP, IL-1β, IL-6 and TNF-α were compared between the SIBO-positive group and the SIBO-negative group. Multivariate Logistic regression analysis was performed to analyze the influencing factors of SIBO in asymptomatic HUA. Spearman rank correlation analysis was used to analyze the correlation between CRP, IL-1β, IL-6 and TNF-α levels and SIBO in asymptomatic HUA patients. The positive rate of SIBO in the asymptomatic HUA patients was 58.62%, which was higher than that in the healthy controls (20.00%), and the difference was statistically significant (χ2=16.431, P < 0.001). There were significant differences in exhaled H2 concentration between the asymptomatic HUA patients and the healthy controls at 0, 30, 60 and 90 min (P < 0.05), and there was no significant difference in exhaled CH4 concentration at each time point (P>0.05). The levels of CRP, IL-1β, IL-6 and TNF-α in the asymptomatic HUA patients were significantly higher than those in the healthy controls (P < 0.05). The serum levels of CRP, IL-1β and IL-6 in the SIBO-positive group were significantly higher than those in the SIBO-negative group (P < 0.05), while the levels of TNF-α were not significantly different between the two groups (P>0.05). Multivariate Logistic regression ana-lysis of the influencing factors of SIBO in the asymptomatic HUA showed that increased IL-1β (OR=1.332, 95%CI: 1.005-1.764, P=0.046) and increased IL-6 (OR=1.586, 95%CI: 1.216-2.069, P=0.001) were independent risk factors for SIBO in the HUA patients. In asymptomatic HUA patients with SIBO, the LHBT set value was positively correlated with serum IL-1β (r=0.594, P < 0.001). Asymptomatic HUA patients are more likely to develop SIBO than healthy people, and SIBO in asymptomatic HUA patients is closely related to the level of inflammatory factors, so attention should be paid to the detection and intervention of SIBO in asymptomatic HUA patients. 分析无症状高尿酸血症(hyperuricemia, HUA)患者小肠细菌过度生长(small intestinal bacterial overgrowth, SIBO)发生情况及无症状HUA合并SIBO患者血清中C-反应蛋白(C-reactive protein, CRP)、白细胞介素(interleukin, IL)-1β、IL-6和肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)表达水平。 选取山西省汾阳医院2023年6月至2024年6月的87例无症状HUA患者和40例健康对照者为研究对象, 收集基线资料和实验室指标。采用乳果糖甲烷-氢呼气试验(lactulose methane-hydrogen breath test, LHBT)检测SIBO的发生情况, 并根据LHBT的检测结果将无症状HUA患者分为SIBO阳性组及SIBO阴性组, 分析无症状HUA患者SIBO阳性率, 比较无症状HUA患者与健康对照者各个时间点(0、30、60和90 min)H2和CH4浓度及CRP、IL-1β、IL-6、TNF-α水平, 以及SIBO阳性组和SIBO阴性组之间的CRP、IL-1β、IL-6、TNF-α水平。采用多因素Logistic回归分析无症状HUA患者发生SIBO的影响因素, 采用Spearman秩相关分析无症状HUA患者CRP、IL-1β、IL-6、TNF-α水平与SIBO的相关性。 无症状HUA患者SIBO阳性率高于健康对照者, 差异有统计学意义(58.62% vs. 20.00%, χ2=16.431, P＜0.001)。无症状HUA患者与健康对照者呼出H2浓度在各时间点差异均有统计学意义(P＜0.05), 但呼出CH4浓度在各时间点差异均无统计学意义(P＞0.05)。无症状HUA患者CRP、IL-1β、IL-6、TNF-α水平高于健康对照者, 差异有统计学意义(P＜0.05)。无症状HUA患者SIBO阳性组血清CRP、IL-1β、IL-6水平均明显高于SIBO阴性组(P < 0.05), 但TNF-α水平在两组间差异无统计学意义(P＞0.05)。多因素Logistic回归分析分析表明, IL-1β升高(OR=1.332, 95%CI: 1.005~1.764, P=0.046)、IL-6升高(OR=1.586, 95%CI: 1.216~2.069, P=0.001)是无症状HUA患者发生SIBO的独立危险因素。无症状HUA合并SIBO患者中, LHBT集值与血清IL-1β成正相关(r=0.594, P＜0.001)。 无症状HUA患者较健康人群更容易发生SIBO, 且SIBO的发生与炎症因子水平密切相关, 应重视无症状HUA患者SIBO的检测和干预。