The prevalence rate of chronic diseases among the floating population is increasing with the acceleration of the aging society. However, factors such as the characteristics of mobility, and the problem of medical insurance reimbursement in different places lead to underutilization of health service and poor health. Therefore, this study analyzed the impact of medical insurance on health service utilization of floating chronic disease patients and the moderating role of health risk perception from the perspective of behavioral economics, such work could shed light on the realization of "Healthy China" strategy and "the Medium- and Long-term Planning for the Prevention and Treatment of Chronic Diseases". We selected the data of China Migrants Dynamic Survey (CMDS) in 2017. A total of 5 640 migrants with chronic diseases were selected. Descriptive statistics was used to describe the basic characteristics of the sample, and binary Logistic regression model was used to analyze the relationship between the different types of medical insurance participation rate and the utilization of medical services, and the moderating role of health risk perception in this relationship. The participation rate of medical insurance was 21.9%. There was still 12.5% migrants with chronic diseases who did not utilize health services when they felt unwell. Only having medical insurance in inflowing area could increase the utilization of health services among migrants with chronic diseases. Health risk perception significantly positively moderated the association of medical insurance for urban employee or public medical insurance with health service utilization among migrants with chronic diseases. The medical insurance and health risk perception can promote the utilization of health services among migrants with chronic diseases. The government should break the barrier of the medical insurance system, improve the level of medical insurance, and strengthen the propaganda and education of chronic diseases prevention and treatment, so as to improve the level of health risk perception of migrants with chronic diseases. In addition, it is necessary to rationally allocate health service supplies and focus more on trans-provincial floating male patients with chronic diseases, who have low health risk perception and limited access to medical services, to improve health service utilization. 流动人口中的慢性病患病率随社会老龄化的加剧不断增长，然而此类慢性病患者因其流动特性和异地就医的医疗保险(简称医保)报销问题，卫生服务利用不足，导致其健康状况较差。本研究从行为经济学角度分析医保对流动慢性病患者卫生服务利用的影响以及健康风险感知在其中的调节作用，以期对实现我国“健康中国”战略、“防治慢性病中长期规划”提供帮助。 根据2017年中国流动人口动态监测调查数据(China Migrants Dynamic Survey，CMDS)，共获得流动慢性病患者有效样本5 640人。采用描述统计方法描述样本基本特征，利用二元Logistic回归模型分析流动慢性病患者不同类型的医保参与率情况与医疗服务利用之间的关联，并且分析健康风险感知在其中的调节作用。 流动慢性病患者流入地的医保参与率为21.9%，仍有12.5%的流动慢性病患者在身体不适时未及时利用卫生服务。只有在流入地参保才能够显著提高流动慢性病患者在流入地的卫生服务利用，健康风险感知能够显著增强公费医保、城镇职工医保与流动慢性病患者卫生服务利用的关联。 参与流入地医保和健康风险感知能够促进流动慢性病患者利用卫生服务，应去除医保制度的区隔阻碍，提高医保统筹层次，同时应加强流动人口慢性病防治的宣传教育，提高其健康风险感知的水平。此外，为提高卫生服务利用率，还应进一步合理配置医疗服务资源，对健康风险感知较低、卫生服务可及性差的跨省流动男性慢性病患者给予更多的关注。
To evaluate the surgical outcomes of maxillary medication-related osteonecrosis of the jaw (MRONJ) at different disease stages and to analyze the comparative efficacy of different surgical techniques on the prognosis of stage Ⅲ patients. A detailed retrospective analysis was conducted on the clinical data of 136 patients with maxillary MRONJ who underwent surgical treatment in the Department of Oral and Maxillofacial Surgery of Peking University School and Hospital of Stomatology from April 2014 to February 2024. All patients were rigorously classified according to the 2022 American Association of Oral and Maxillofacial Surgeons (AAOMS) staging criteria: Stage Ⅰ (n=8), stage Ⅱ (n=30), and stage Ⅲ (n=98). The surgical interventions included local lesion resection with primary direct closure, buccal fat pad packing, and iodoform gauze packing. The patients were systematically followed up for a period of 1 year postoperatively to comprehensively assess several key outcome measures: Complete mucosal healing, resolution of pain, effective infection control, and radiological improvement of maxillary sinus inflammation based on serial computed tomography scans. Statistical analysis was performed using SPSS version 20.0. Continuous variables were expressed as mean±standard deviation and compared using the t-test, while categorical variables were expressed as numbers and percentages and compared using the χ2 test or Fisher' s exact test as appropriate. A P-value < 0.05 was considered statistically significant for all analyses. The overall short-term (3 months) cure rate was 91.2% (124/136), which improved to a long-term (1 year) cure rate of 94.9% (129/136). A stage-stratified analysis revealed excellent long-term cure rates: 100.0% (8/8) for stage Ⅰ, 96.7% (29/30) for stage Ⅱ, and 93.9% (92/98) for stage Ⅲ, with no statistically significant difference in outcomes across the different stages (P=0.611). Among the 98 stage Ⅲ patients, 34 were treated with buccal fat pad transfer (BFPT group) and 64 with iodine strip packing (ISP group), with no significant differences in baseline demographic or clinical characteristics between the two groups, ensuring comparability. The BFPT group demonstrated a statistically significant superior performance in achieving oroantral fistula closure both at the short-term (79.4% vs. 23.4%, P < 0.001) and long-term (85.3% vs. 54.7%, P=0.002) follow-up assessments. In contrast, the ISP group showed a markedly greater degree of improvement in maxillary sinus inflammation, as quantified by a standardized radiographic scoring system, with significantly greater reductions in inflammation scores at both the 3-month (P=0.029) and 12-month (P=0.014) follow-up intervals. Surgical management of maxillary MRONJ results in high rates of success with a favorable complication profile. For advanced (stage Ⅲ) disease, the choice of surgical technique entails a strategic trade-off: The buccal fat pad procedure is more conducive to achieving reliable soft tissue closure and oroantral fistula resolution, whereas iodoform gauze packing provides superior management and resolution of concomitant maxillary sinusitis. Consequently, the selection of surgical technique should be individualized, based on a careful consideration of the patient's specific anatomical defect, the extent of sinus involvement, and their overall clinical condition. 总结上颌药物相关性颌骨坏死(medication-related osteonecrosis of the jaw, MRONJ)的手术治疗效果, 比较不同手术方式治疗Ⅲ期病变患者预后的差异。 回顾性分析2014年4月至2024年2月于北京大学口腔医院颌面外科接受手术治疗的136例上颌MRONJ患者的临床资料。根据美国口腔颌面外科医师协会(American Association of Oral and Maxillofacial Surgeons, AAOMS)2022年发布的分期标准, 将患者分为Ⅰ期(8例)、Ⅱ期(30例)和Ⅲ期(98例)三组。手术方式包括局部病变切除直接缝合、颊脂垫填塞及碘条填塞。患者术后随访1年, 评估黏膜愈合、疼痛、感染控制及上颌窦炎症改善情况。采用SPSS 20.0软件进行统计学分析。 全部患者短期(3个月)总治愈率为91.2%(124/136), 长期(1年)总治愈率为94.9%(129/136)。Ⅲ期患者中, 颊脂垫填塞组在短期和长期随访中的口腔上颌窦瘘消除率均显著高于碘条填塞组(79.4% vs. 23.4%, P < 0.001;85.3% vs. 54.7%, P=0.002)。然而, 碘条填塞组在上颌窦炎症改善方面的表现更优, 其短期和长期炎症评分改善程度均显著高于颊脂垫填塞组(P=0.029, P=0.014)。 手术治疗适宜于Ⅰ~Ⅲ期的上颌MRONJ患者, 对于Ⅲ期上颌MRONJ, 颊脂垫填塞更有利于口腔上颌窦瘘的闭合, 而碘条填塞在上颌窦炎症控制方面更具优势, 临床应根据患者具体情况选择个体化手术方案。
To detect the expression levels of absence in melanoma 2 (AIM2), cysteine aspartate-specific protease-1 (caspase-1), and gasdermin D (GSDMD) in peripheral blood mononuclear cell (PBMC) of patients with idiopathic inflammatory myopathy (IIM) and to explore their role in the pathogenesis of IIM. A total of 30 IIM patients (IIM group) who visited the Department of Rheumatology and Immunology, General Hospital of Northern Theater Command from May 2020 to June 2022 were recruited. Concurrently, 30 healthy volunteers matched by gender and age were recruited from the hospital's Health Examination Center. Clinical information, biochemical and immunological mar-kers, and venous blood samples were collected from the study subjects. Serum double-stranded DNA (dsDNA) levels were detected by fluorescence quantitative method, and the mRNA expression levels of AIM2, caspase-1, GSDMD, interleukin 1β (IL-1β), and IL-18 in PBMC were detected by reverse transcription quantitative real-time PCR (RT-qPCR). The protein expression levels of AIM2, caspase-1, GSDMD, IL-1β, and IL-18 in PBMC were detected using the Western blot (WB) method, and the serum levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay (ELISA). The IIM group included 10 cases of dermatomyositis (DM), 5 cases of polymyositis (PM), 11 cases of overlap syndrome (OM), and 4 cases of immune-mediated necrotizing myopathy (IMNM). Compared with the healthy control group, the serum levels of dsDNA, IL-1β, and IL-18 were significantly increased in the IIM group and its subgroups (P < 0.05). Except for the fact that there was no statistically significant difference in AIM2 mRNA levels in PBMC of the IMNM subgroup compared to the healthy control group, the expression of AIM2, caspase-1, and GSDMD mRNA was significantly increased in the IIM group and other subgroups (P < 0.05); Except for the comparison of IL-1β mRNA levels in PBMC of the IMNM and OM subgroups with the healthy control group showing no statistical difference, the expression of IL-1β and IL-18 mRNA was significantly increased in the IIM group and other subgroups (P < 0.05); Comparisons between subgroups indicated that the expression of IL-1β mRNA in the DM subgroup was significantly higher than that in the OM and IMNM subgroups, and the expression of IL-18 mRNA in the PM subgroup was significantly higher than that in the DM and OM subgroups (P < 0.05). The expression levels of AIM2, caspase-1, GSDMD, IL-1β, and IL-18 proteins in PBMC of the IIM group and its subgroups were significantly higher than those in the healthy control group (P < 0.05); Comparisons among subgroups revealed that the expression of IL-18 protein in the OM subgroup was significantly higher than that in the PM subgroup (P < 0.05). In the IIM group, the mRNA of caspase-1, GSDMD, and IL-18 showed a positive correlation with AIM2 mRNA, and the protein expression of caspase-1, GSDMD, IL-1β, and IL-18 also showed a positive correlation with AIM2 protein expression. The AIM2 inflammasome-mediated pyroptosis pathway may be involved in the pathogenesis of IIM, providing a theoretical basis for further research on the etiology of IIM and the development of new therapies. 检测特发性炎性肌病(idiopathic inflammatory myopathy，IIM)患者外周血单个核细胞(peripheral blood mononuclear cell，PBMC)中黑色素瘤缺失因子2(absent in melanoma 2，AIM2)及其介导的细胞焦亡通路关键组分——半胱氨酸天冬氨酸蛋白酶1(cysteine aspartate-specific protease-1，caspase-1)和焦孔素蛋白D(gasdermin D，GSDMD)的表达，并探讨其在IIM发病机制中的作用。 招募2020年5月至2022年6月于中国人民解放军北部战区总医院风湿免疫科就诊的30例IIM患者(IIM组)，同期于医院体检中心招募30名性别和年龄与IIM患者相匹配的健康志愿者(健康对照组)，收集研究对象临床信息、血液生化和免疫标志物，以及静脉血样本。通过荧光定量法检测血清双链DNA(double-stranded DNA，dsDNA)水平，通过实时荧光定量逆转录PCR(reverse transcription quantitative real-time PCR，RT-qPCR)检测PBMC中AIM2、caspase-1、GSDMD、白细胞介素1β(interleukin 1β，IL-1β)和IL-18的mRNA表达水平，应用蛋白免疫印迹法检测PBMC中AIM2、caspase-1、GSDMD、IL-1β和IL-18的蛋白表达水平，应用酶联免疫吸附(enzyme-linked immuno-sorbent assay，ELISA)法检测血清中IL-1β和IL-18的表达水平。 IIM组包含皮肌炎(dermatomyositis，DM，n=10)、多发性肌炎(polymyositis，PM，n=5)、重叠性肌炎(overlap syndrome，OM，n=11)和免疫介导的坏死性肌病(immune-mediated necrotizing myopathy，IMNM，n=4)4个亚组。与健康对照组相比，IIM组及其各亚组的血清中dsDNA、IL-1β和IL-18水平均显著增加(P＜0.05)。除IMNM亚组PBMC中AIM2 mRNA与健康对照组差异无统计学意义外，IIM组及其他亚组AIM2、caspase-1和GSDMD mRNA表达均显著增加(P＜0.05)；除IMNM和OM亚组PBMC中IL-1β mRNA与健康对照组比较差异无统计学意义外，IIM组及其他亚组IL-1β和IL-18 mRNA表达均显著增加(P＜0.05)；亚组间比较表明，DM亚组PBMC中IL-1β mRNA表达明显高于OM和IMNM亚组，PM亚组IL-18 mRNA表达明显高于DM和OM亚组(P＜0.05)。IIM及其各亚组的PBMC中，AIM2、caspase-1、GSDMD、IL-1β和IL-18蛋白的表达水平均显著高于健康对照组(P＜0.05)；各亚组间比较发现，OM亚组的IL-18蛋白表达显著高于PM亚组(P＜0.05)。相关性分析表明，IIM组caspase-1、GSDMD和IL-18 mRNA与AIM2 mRNA呈正相关，caspase-1、GSDMD、IL-1β和IL-18蛋白与AIM2蛋白表达也呈正相关。 AIM2炎性小体介导的细胞焦亡通路可能参与IIM的发病机制，这一结论可以为研究IIM的病因及开发新的治疗方法提供理论基础。
To propose a novel method for constructing facial smile simulation sequence data based on static three-dimensional (3D) facial data captured at the start and end of smiling, and to preliminarily evaluate the accuracy and feasibility of the proposed method. The 3D dynamic facial data of participants transitioning from a neutral expression to a maximum smile were captured using the 3dMD dynamic facial scanning system. A structured 3D face template was deformed and registered to both the smile starting and ending facial data using the Procrustes analysis non-rigid iterative closest point (PA-NICP) registration algorithm developed by our research group, obtaining two sets of structured homologous data. In MATLAB software, the vertex displacements between the corresponding points of the starting and ending homologous datasets were calculated, and intermediate transitional data with a consistent triangular mesh topology were generated through linear interpolation, thereby constructing the facial smile simulation sequence data. The real 3D dynamic facial data captured from the 3dMD system were used as reference data, and the simulation sequence data constructed in this study were used as test data. The 3D morphological deviations between the reference and test data at multiple time points during the smiling process were calculated to evaluate the accuracy of the constructed smile simulation sequence data. The 3D facial smile simulation sequence data were successfully constructed for one male and one female participants. The average 3D morphological deviation for the simulated sequence of the male participant was (0.31±0.04) mm, and the average 3D morphological deviation for the simulated sequence of the female participant was (0.44±0.08) mm. Based on the PA-NICP registration algorithm, the construction of facial smile simulation sequence data can be achieved. The intermediate transitional data can be parametrically generated and flexibly adjusted using interpolation functions, providing a novel method for 3D dynamic facial data generation that supports esthetic prosthodontic design, treatment outcome evaluation, and communication between clinicians and patients. 建立一种基于微笑静态起始和终止颜面数据构建颜面微笑仿真序列数据的方法, 初步评价该方法的准确性和可行性。 使用动态颜面扫描设备3dMD采集受试者由中性表情进行微笑的颜面动态数据。使用本课题组提出的普氏分析非刚性迭代最近点算法(Procrustes analysis non-rigid iterative closest point, PA-NICP)将结构化的三维人脸模板分别变形配准至微笑起始颜面数据和微笑终止颜面数据上, 获得二者结构化的同源数据。在MATLAB软件中, 计算起始和终止两同源数据间的对应顶点位移量, 通过线性插值生成三角面片拓扑结构一致的中间过渡数据, 从而构建出颜面微笑仿真序列数据。以真实采集的颜面动态数据作为参考数据, 以本方法构建的仿真序列数据作为测试数据, 评价微笑过程中多个时间点的三维形态偏差, 评价本方法构建微笑仿真序列数据的准确性。 本方法构建了男性和女性各1名受试者的三维颜面微笑仿真序列数据, 男性受试者仿真序列数据构建的平均三维形态偏差为(0.31±0.04) mm, 女性受试者仿真序列数据构建的平均三维形态偏差为(0.44±0.08) mm。 基于PA-NICP配准算法, 可实现颜面微笑仿真序列数据的构建, 其中间过渡数据可基于插值函数进行参数化构建和调整, 为口腔美学修复设计、治疗效果评估和医患沟通等提供了一种新的动态颜面数据生成方法。
To analyze the clinical features and virulence gene characteristics of Klebsiella pneumoniae multi-site infections in patients with hospital-acquired pneumonia, as well as the risk factors for death within 30 days in patients with multi-site infections, in order to provide help for clinical anti-infective treatment. The case data of hospital-acquired pneumonia patients with Klebsiella pneumoniae isolated in sputum culture from March 2018 to June 2023 in Peking University Third Hospital were selected for retrospective analysis, and a total of 128 consecutive patients were enrolled, of whom 35 were in the multi-site infection group and 93 were in the lung infection group, and the clinical data, strain sequence typing, and virulence-related genes of the patients in the two groups were analyzed and compared. The differences in age, gender, proportion of the patients with length of hospital stay ≥30 days, antibiotic exposure rate within 90 days and 30-day mortality rate between the two groups were statistically significant (all P < 0.05); the differences in the proportions of combined interstitial lung disease, myocardial infarction, peripheral vascular disease, peptic ulcer, diabetes mellitus and hemiplegia between the two groups were statistically significant (all P < 0.05). The proportions of patients with Glasgow coma scale (GCS) scores < 8 points, the proportion of the patients who underwent peripherally inserted central catheter (PICC) and gastric tube invasive operation, the proportion of the presence of pleural effusion and infectious shock in the multi-site infection group were significantly higher than those of the pulmonary infection group (all P < 0.05). The blood procalcitonin (PCT) level in the multi-site infection group was significantly higher than that of the pulmonary infection group (P=0.004), and the red blood cell count and hemoglobin level were significantly lower than those of the pulmonary infection group (P < 0.001). The proportion of ST11 and the detection rates of virulence genes iroB, ybtA, irp1 and fyuA in Klebsiella pneumoniae strains in the multi-site infection group were significantly higher than those in the pulmonary infection group (P < 0.05). According to the occurrence of death within 30 days, the patients in the multi-site infection group were further divided into the multi-site infection survival group (n=21) and the non-survival group (n=14). Multivariate analysis showed that septic shock was an independent risk factor for death within 30 days of multi-site infection (P=0.045, OR=38.510). Patients with Klebsiella pneumoniae multi-site infection were mainly found in patients with advanced age, female, more comorbidities, performing invasive operation and having history of antimicrobial drug exposure within 90 days. They had lower erythrocyte counts, hemoglobin levels and higher PCT levels, and were prone to pleural effusion, infectious shock. Infectious shock was an independent risk factor for death within 30 days in patients with Klebsiella pneumoniae multi-site infection. ST11 type was the most prevalent type of multi-site infectious strains, and the virulence genes iroB, ybtA, irp1, fyuA were more prevalent. 分析医院获得性肺炎患者肺炎克雷伯菌(Klebsiella pneumoniae)多部位感染的临床特征和毒力基因特征, 以及多部位感染患者30 d内死亡的危险因素, 为临床抗感染治疗提供帮助。 选择北京大学第三医院2018年3月至2023年6月痰培养中分离出肺炎克雷伯菌的医院获得性肺炎患者的病例资料进行回顾性分析, 共连续纳入患者128例, 其中多部位感染组35例, 单纯肺部感染组93例, 分析并比较两组患者的临床资料、菌株序列分型及毒力相关基因。 两组患者年龄、性别、住院时长≥30 d患者比例、90 d内抗菌药物暴露率、30 d死亡率差异均有统计学意义(P均＜0.05), 两组患者合并间质性肺病、心肌梗死、周围血管病、消化性溃疡、糖尿病、偏瘫比例差异亦有统计学意义(P均＜0.05)。多部位感染组格拉斯哥昏迷评分(Glasgow coma scale, GCS)＜8分、行外周静脉置入中心静脉导管(peripherally inserted central catheter, PICC)及胃管侵入操作、出现胸腔积液和感染性休克患者比例均显著高于单纯肺部感染组(P＜0.05);血液降钙素原(procalcitonin, PCT)水平显著高于单纯肺部感染组(P=0.004), 血红细胞计数、血红蛋白水平显著低于单纯肺部感染组(P＜0.001);肺炎克雷伯菌菌株中ST11型占比及iroB、ybtA、irp1、fyuA毒力基因检出率均显著高于单纯肺部感染组(P＜0.05)。根据是否出现30 d内死亡将多部位感染组患者进一步分为多部位感染生存组(n=21)和死亡组(n=14), 多因素分析表明感染性休克是多部位感染30 d内死亡的独立危险因素(P=0.045, OR=38.510)。 肺炎克雷伯菌多部位感染的患者多见于高龄、女性, 多有基础疾病史、侵入性操作史及90 d内抗菌药物暴露史, 且具有更低的红细胞计数、血红蛋白水平及更高的PCT水平, 易出现胸腔积液、感染性休克; 感染性休克是肺炎克雷伯菌多部位感染患者30 d内死亡的独立危险因素; 致多部位感染的菌株中以ST11型为主, iroB、ybtA、irp1、fyuA基因携带率更高。
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 methodology and feasibility of reconstructing soft tissue morphology for fixed implant rehabilitation in edentulous patients using multi-view stereo vision technology, and to conduct a preliminary evaluation of the method's in vitro accuracy. A pair of edentulous resin models were designed and printed, with 6 implant analogs placed in the maxilla and 4 in the mandible. The experimental group (n=10) utilized a self-developed photogrammetric quad-camera system and the automated reconstruction software RealityScan 2.0.1. Self-developed scan bodies were attached to the analogs, and the handheld camera system was used to capture images of the models in vitro. The images were imported into the software to reconstruct the 3D models, and the data were exported as ".stl" files. The control group (n=10) used an intraoral scanner. Scan caps were attached to the analogs, and the models were scanned to generate ".stl" data. Reference data were obtained by scanning the maxillary and mandibular resin models once each with a desktop scanner (EX-PRO). All data were imported into Geomagic Wrap 2021. The root mean square (RMS) was calculated by comparing the 3D morphology of the experimental and control group data against the reference data to represent the magnitude of the 3D morphological deviation and evaluate accuracy. The evaluation was conducted in 4 specific regions: the alveolar ridge, peri-implant soft tissue, buccal, and lingual areas. In the maxilla, the RMS of the experimental group was significantly higher than the control group in the alveolar ridge [(124.89±21.30) μm vs. (53.90±8.93) μm, P < 0.001], peri-implant soft tissue [(157.74±19.13) μm vs. (67.03±3.94) μm, P < 0.001], and lingual areas [(146.01±33.87) μm vs. (46.20±11.19) μm, P < 0.001]. The RMS in the buccal area was lower for the experimental group than the control group [(50.56±8.34) μm vs. (53.83±12.66) μm], but the difference was not statistically significant (P=0.571). In the mandible, the RMS of the experimental group was significantly higher than the control group in the alveolar ridge [(254.04±88.42) μm vs. (58.28±38.96) μm, P < 0.001], peri-implant soft tissue [(165.18±21.30) μm vs. (70.48±28.20) μm, P < 0.001], and lingual areas [(421.75±59.51) μm vs. (54.59±36.77) μm, P < 0.001]. When comparing the buccal and lingual sides, the lingual RMS was significantly higher than the buccal RMS for the experimental group in both the maxilla (P < 0.001) and mandible (P < 0.001). For the control group, the maxillary lingual RMS was significantly lower than the buccal RMS (P < 0.05), while the mandibular lingual RMS was higher than the buccal, but the difference was not statistically significant (P=0.378). The self-developed quad-camera system, combined with multi-view stereo vision reconstruction software, can successfully record the 3D morphology of soft tissue. This study provides a research foundation for the development of extraoral photogrammetric devices capable of simultaneously determining the spatial positions of multiple implant units and acquiring soft tissue morphology. 探索基于多视图立体视觉技术的无牙颌种植固定修复软组织形态重建的方法及其可行性, 初步评价该方法在体外重建软组织形态的正确度。 设计并打印一对无牙颌种植树脂模型, 上颌放置6枚替代体, 下颌放置4枚替代体。以自主研发(简称自研)的摄影测量四目相机组加自动化重建软件RealityScan 2.0.1作为实验组, 将自研扫描杆安装于替代体, 手持自研相机组在体外拍摄模型图像, 每次拍摄数量4×12张, 导入软件重建三维模型, 导出".stl"数据(n=10);以口内扫描仪作为对照组, 将扫描帽安装于替代体, 使用口内扫描仪扫描模型的三维形态, 输出".stl"数据(n=10);使用模型扫描仪EX-PRO获取上、下颌树脂模型的".stl"数据各1例, 作为参考数据。将以上数据导入Geomagic Wrap 2021软件, 分别计算实验组、对照组数据与参考数据三维形态的均方根(root mean squre, RMS), 代表实验组、对照组的三维形态偏差大小, 并评价正确度, 评价范围为牙槽嵴区域、种植体周围软组织区域、颊侧区域和舌侧区域。 在上颌中, 实验组在牙槽嵴区域、种植体周围软组织区域和舌侧区域的RMS均显著高于对照组[(124.89±21.30) μm vs. (53.90±8.93) μm、(157.74±19.13) μm vs. (67.03±3.94) μm、(146.01±33.87) μm vs. (46.20±11.19) μm, 均P < 0.001], 实验组在颊侧区域的RMS略低于对照组[(50.56±8.34) μm vs. (53.83±12.66) μm, P=0.571];在下颌中, 实验组在牙槽嵴区域、种植体周围软组织区域和舌侧区域的RMS均显著高于对照组[(254.04±88.42) μm vs. (58.28±38.96) μm、(165.18±21.30) μm vs. (70.48±28.20) μm、(421.75±59.51) μm vs. (54.59±36.77) μm, 均P < 0.001];颊舌侧两组相比较, 实验组上颌、下颌的舌侧RMS均显著高于颊侧(均P < 0.001), 对照组上颌舌侧RMS显著低于颊侧(P < 0.05), 下颌舌侧RMS高于颊侧(P=0.378)。 自研相机组配合多视图立体视觉重建软件可实现软组织三维形态记录, 为无牙颌种植口外摄影测量设备同步定位多单位种植体空间的位置和获取软组织形态提供了一定的研究基础。
To clarify the diagnostic efficacy of various diagnostic methods through multi-index combined analysis, and to explore the core diagnostic value of direct immunofluorescence (DIF) in oral mucosal pemphigus vulgaris (PV). A total of 53 patients with confirmed oral mucosal PV were included, retrospectively. Their data of DIF, histopathology, serum enzyme-linked immunosorbent assay (ELISA) and clinical diagnosis were systematically analyzed, and diagnostic efficacy of each method was evaluated using indicators, such as sensitivity, specificity, and area under curve (AUC) of the receiver operating characteristic (ROC) curve. The results showed that among the 53 patients, middle-aged and elderly females were predominant, the buccal mucosa was the most common involved site, and most patients had a history of blistering. The positive rate of DIF was 96.23%, mainly manifested as a reticular fluorescent deposition between epithelial spinous cells, demonstrating the highest diagnostic value with a sensitivity of 96.23%, specificity of 100.00%, and AUC of 0.981. Histopathology ranked second, with a sensitivity of 94.34%, a specificity of 100.00%, and an AUC value of 0.972. The ELISA test had a sensitivity of 82.61%, a specificity of 82.35%, and an AUC value of 0.825. Although the sensitivity of clinical diagnosis was acceptable, its specificity was relatively low. Additionally, DIF exhibited complementarity with histopathology, ELISA, and clinical diagnosis, and combined testing could improve diagnostic accuracy. DIF is the "gold standard" for the diagnosis of oral mucosal PV. A comprehensive diagnostic workflow of "clinical manifestation-DIF-histopathology-ELISA" is proposed. This integrated diagnostic system not only significantly improves the accuracy of oral mucosal PV diagnosis but also aligns with the core principles of precision medicine, providing a basis for indivi-dualized treatment. 基于多指标联合分析，探讨直接免疫荧光(direct immunofluorescence，DIF)对口腔黏膜寻常型天疱疮(pemphigus vulgaris，PV)的诊断效能。 回顾性分析53例确诊口腔黏膜PV的患者，收集患者临床资料及DIF、组织病理学、血清学酶联免疫吸附试验(enzyme-linked immunosorbnent assay，ELISA)检测结果，采用灵敏度、特异度、受试者工作特征(receiver operating characteristic，ROC)曲线的曲线下面积(area under curve，AUC)等指标评估各方法的诊断效能。 患者以中老年女性为主，颊黏膜为最常见受累部位，大部分患者伴有起疱史。DIF检测的阳性率为96.23%，主要表现为上皮棘细胞间网状绿色荧光沉积，其诊断价值最高，灵敏度为96.23%，特异度为100.00%，AUC值为0.981；组织病理学次之，灵敏度为94.34%，特异度为100.00%，AUC值为0.972；ELISA检测的灵敏度为82.61%，特异度为82.35%，AUC值为0.825。DIF与组织病理学、ELISA及临床诊断具有互补性，联合检测可提高诊断准确性。 DIF是诊断口腔黏膜PV的核心指标，建议采用“临床表现-DIF-组织病理学-ELISA”综合诊断流程；该综合诊断体系不仅能显著提升口腔黏膜PV诊断的精准度，也契合了精准医疗的核心理念，可为个性化治疗提供依据。
To explore a mathematical method for calculating key articulator parameters based on mandibular movement trajectory data, and to compare the results of this method with reference values provided by existing foreign mandibular movement recording system, thereby establishing an algorithmic basis for developing a domestic mandibular movement recording system. Twenty healthy volunteers (7 males, 13 females) meeting inclusion criteria were recruited, with a mean age of (31±8) years. Mandibular movement data during protrusive and left/right lateral movements were recorded using the JMA Optic foreign mandibular movement recording system. A reference plane coordinate system was established using reverse engineering software, the multi-source maxillofacial data were integrated, and the coordinate systems were then unified. The condylar apex, medial condylar pole, lateral condylar pole, condylar center, empirical hinge axis point, and mandibular incisor point were selected as reference points for mandibular movement trajectories. Three-dimensional movement trajectories were generated for each reference point to calculate the sagittal condylar inclination (SCI), transverse condylar inclination (TCI), immediate side shift (ISS), incisal guidance inclination and canine guidance inclination. The calculation results from different reference points served as distinct experimental groups. Reference values provided by the JMA Optic system were used as the control group for comparative analysis. The SCI values of all the experimental groups were significantly higher than that of the control group (P < 0.001), with a systematic positive bias of approximately 3.1°, though the limits of agreement were relatively narrow. The TCI results varied depending on the reference point: Only the condylar apex group (5.7°±6.1°) was significantly lower than the control group (9.2°±6.6°) (t=5.023, P < 0.001). Differences between the remaining groups and the control group were not statistically significant. The empirical hinge axis point group showed the smallest mean bias and the narrowest limits of agreement, indicating optimal consistency with the control group's TCI. The ISS values were 0.0 (0.0) mm in all the groups. The incisal guidance inclination of the mandibular incisor point group (43.1°±8.6°) was significantly lower than that of the control group (50.6°±13.7°) (t=3.749, P=0.001) with poor consistency. However, the canine guidance inclination of the mandibular incisor point group showed no statistically significant difference compared with the control group (t=-1.873, P=0.069), with acceptable consistency. This study proposed a mathematical method for calculating key articulator parameters based on mandibular movement trajectory data, with a clear and traceable computational pathway. The proposed method showed acceptable consistency with the JMA Optic system algorithm in calculating TCI, ISS, and canine guidance inclination, but poor consistency in calculating SCI and incisal guidance inclination. The selection of reference points directly influenced the results of parameter calculation. This mathematical method provided a reliable theoretical foundation for achieving precise, personalized articulator parameter settings. 探索一套基于下颌运动轨迹数据计算𬌗架关键参数的数学方法, 并将该方法计算结果与现有国外下颌运动记录系统提供的参考值进行比较, 为国产化下颌运动轨迹记录系统的研发奠定相关算法基础。 招募符合纳入标准的20例健康志愿者(男性7例, 女性13例), 平均年龄(31±8)岁。使用JMA Optic下颌运动记录系统采集受试者前伸及左右侧方运动数据。使用逆向工程软件建立参考平面坐标系, 完成受试者颌面部多源数据整合, 再统一坐标系。选取髁突顶点、髁突内极、髁突外极、髁突中心、经验铰链轴点及下颌切点作为下颌运动轨迹参考点, 并生成各参考点的三维运动轨迹, 进而计算前伸髁导斜度(sagittal condylar inclination, SCI)、侧方髁导斜度(transversal condylar inclination, TCI)、迅即侧移(immediate side shift, ISS)、切导斜度和尖导斜度, 以不同参考点的计算结果作为不同实验组。以JMA Optic系统提供的参考值作为对照组进行比较分析。 各实验组的SCI均显著高于对照组(P < 0.001), 且存在约3.1°的系统性正偏差, 但一致性界限较窄。TCI结果因参考点而异, 仅髁突顶点组(5.7°±6.1°)显著低于对照组(9.2°±6.6°)(t=5.023, P < 0.001), 其余组与对照组间差异无统计学意义, 经验铰链轴点组与对照组间表现出最小的平均偏差与最窄的一致性界限, 该组与对照组TCI的一致性最佳。所有组别的ISS均为0.0(0.0) mm。下颌切点组的切导斜度(43.1°±8.6°)显著低于对照组(50.6°±13.7°)(t=3.749, P=0.001), 且一致性欠佳, 而下颌切点组的尖导斜度与对照组间差异无统计学意义(t=-1.873, P=0.069), 且一致性尚可。 提出了一套基于下颌运动轨迹数据计算𬌗架关键参数的数学方法, 其计算路径明确、可追溯。本方法与JMA Optic系统算法在计算TCI、ISS、尖导斜度上一致性尚可, 而在计算SCI和切导斜度上一致性欠佳, 参考点的选择对参数计算结果具有直接影响。该数学方法为实现精准化、个性化的𬌗架参数设置提供了可靠的理论基础。
To digitally measure and analyze the anatomical characteristics of protrusive and intercuspal position (ICP) occlusal contacts in maxillary incisors, thereby establishing a standardized measurement protocol and obtaining characteristic functional data to optimize the incisal guidance design of prostheses. Thirty subjects with stable incisal guidance were recruited. Digital dental mo-dels were acquired via intraoral scanning, and protrusive movement data were captured using a modified patient-specific motion (PSM) technique. Computer-aided design software was used to record the distribution of the occlusal contacts during protrusive movement. Image analysis software was employed to measure the area proportion of guiding locations for each tooth. Reverse engineering software was used to measure and analyze the occlusal contacts in ICP and anatomical characteristics. Measured parameters included the area proportion and distribution of occlusal contacts in ICP, the area proportion of marginal ridges and incisal ridges, radius of curvature of lingual surface, lingual surface inclination, overbite, and overjet. Each parameter was measured twice to calculate the intraclass correlation coefficient for the assessment of test-retest reliability. All measured parameters demonstrated good test-retest reliability. No significant differences were found in any parameters between homologous teeth (P>0.05). During protrusive movement, the area proportion of guiding locations was significantly larger for the central incisors than for the lateral incisors (73.4%±12.3% vs. 26.6%±12.3%, P < 0.001). The frequency of occlusal contacts was significantly higher on the mesial and distal marginal ridges and incisal ridges compared with the lingual fossa and cingulum (P < 0.05). In ICP, no significant difference was observed in the occlusal contact area proportion between the central and lateral incisors (48.8%±20.0% vs. 51.2%±20.0%, P=0.758). The frequency of the occlusal contact was significantly higher on the mesial and distal marginal ridges compared with the incisal ridge, lingual fossa, and cingulum (P < 0.05). Central incisors exhibited significantly higher overbite and overjet than lateral incisors (P < 0.05). The area proportion of mesial and distal marginal ridges was significantly smaller for the central incisors than for the lateral incisors (P < 0.05), but no significant difference was observed in the incisal ridge (P>0.05). No significant differences were observed in the lingual surface inclination or radius of curvature among the incisors (P>0.05). The anatomical characteristics of protrusive and ICP occlusal contacts in maxillary incisors demonstrated bilateral symmetry. Protrusive movement was primarily guided by the maxillary central incisors, with the guiding area of the central incisors being approximately three times that of the lateral incisors. The marginal ridges and incisal ridges were the main guiding locations. Central and lateral incisors exhibited comparable occlusal contact area in ICP. 数字化精准测量分析上颌切牙前伸和正中咬合接触解剖特征, 建立标准化测量流程并获得特征性切导功能相关数据, 为优化修复体的切导设计提供参考。 招募30名切导稳定的正常受试者, 口内扫描获得数字化牙列模型, 并采用改良动态咬合记录法获取前伸运动数据。通过计算机辅助设计软件重现前伸运动中的咬合接触区域并记录其分布, 使用图像分析软件测量各个牙位引导部位面积占比。通过逆向工程软件测量分析牙尖交错位咬合接触与解剖特征, 测量指标包括: 正中咬合接触面积占比与分布、边缘嵴与切嵴面积占比、舌面中央曲率半径、舌面倾斜度与覆牙合、覆盖。以上每项指标重复测量两次, 计算组内相关系数以评价复测信度。 所有指标的复测信度良好, 且在双侧同名牙之间的差异均无统计学意义(P>0.05)。前伸运动时, 中切牙引导部位面积占比显著大于侧切牙(73.4%±12.3% vs. 26.6%±12.3%, P < 0.001), 近远中边缘嵴与切嵴发生咬合接触的频率显著高于舌窝和舌隆突(P < 0.05)。牙尖交错位时, 中切牙与侧切牙咬合接触面积占比差异无统计学意义(48.8%±20.0% vs. 51.2%±20.0%, P=0.758), 近远中边缘嵴发生咬合接触的频率显著高于切嵴、舌窝和舌隆突(P < 0.05)。中切牙的覆牙合、覆盖显著大于侧切牙(P < 0.05), 且近远中边缘嵴面积占比显著小于侧切牙(P < 0.05), 但切嵴面积占比在中切牙和侧切牙之间差异无统计学意义(P>0.05)。不同牙位的舌面倾斜度与舌面中央曲率半径差异均无统计学意义(P>0.05)。 上颌切牙前伸和正中咬合接触解剖特征表现出左右对称性。前伸运动时以上颌中切牙引导为主, 中切牙的引导面积约为侧切牙的3倍, 近远中边缘嵴与切嵴是主要的引导部位; 正中咬合时上颌中切牙与侧切牙有相近的咬合接触面积。
To investigate the association between fat-to-muscle mass ratio (FMR) of whole body, arm, leg and trunk and the risk of benign ovarian neoplasm. A total of 255 412 participants from the prospective cohort study United Kingdom biobank (UKB) were enrolled in the risk-related study of benign ovarian neoplasm. Cox proportional hazard model was used to evaluate the correlation between total and regional FMR and the risk of benign ovarian neoplasm. A priori stratified analysis was performed according to the body mass index (BMI) category to evaluate the correlation between FMR of whole body, arm, leg and trunk and the risk of benign ovarian neoplasm in people with BMI < 25 kg/m2and BMI≥25 kg/m2, respectively. The restricted cubic plot was used to further explore the curve of FMR associated with the risk of benign ovarian neoplasm. Finally, subgroup analysis was performed on the age of the subjects (< 50 years, 50-59 years, ≥60 years) to explore the association between FMR and the risk of benign ovarian neoplasm at different ages. During a median 8.77 years of follow-up, we recruited 1 643 cases of benign ovarian neoplasms. After adjusting for demographic, reproductive, genetic, lifestyle, and hormone-related factors, total, arm, leg and trunk FMR were significantly positively correlated with the risk of benign ovarian neoplasm and higher than BMI with the risk of benign ovarian neoplasm, among which the whole body FMR had the strongest correlation with the risk of benign ovarian neoplasm (HR: 2.16; 95%CI: 1.67-2.79). Stratified analysis of FMR and the risk of benign ovarian neoplasm based on BMI showed that compared with people with BMI≥25 kg/m2, people with BMI < 25 kg/m2 had a stronger association between whole body, arm, leg and trunk FMR and the risk of benign ovarian neoplasm (Pinteraction < 0.05). The restricted cubic plot showed that the association between FMR of the whole body, arm and trunk and the risk of benign ovarian neoplasm had an opposite trend between normal weight and overweight/obese people. Subgroup analysis showed that the association between the whole body and leg FMR and the risk of benign ovarian neoplasm decreased with age (P < 0.05). Among them, leg FMR was associated with benign ovarian neoplasm in people younger than 50 years (HR: 2.38; 95%CI: 1.39-4.08). There is a positive correlation between the total, arm, trunk FMR and the risk of benign ovarian neoplasm, and the correlation is stronger in people with BMI < 25 kg/m2 and women aged 40-50 years. 探讨全身、手臂、腿部及躯干脂肪肌肉比率(fat-to-muscle mass ratio，FMR)与卵巢良性肿瘤风险的关联性。 使用英国生物样本库(United Kingdom biobank，UKB)前瞻性队列研究的数据，在卵巢良性肿瘤风险关联性研究中纳入255 412例研究对象。采用Cox比例风险模型分别评估全身、手臂、腿部及躯干FMR与卵巢良性肿瘤风险的关联性。根据体重指数(body mass index，BMI)进行先验分层分析，评估全身、手臂、腿部及躯干FMR分别在BMI＜25 kg/m2和BMI≥25 kg/m2人群中与卵巢良性肿瘤风险的关联性。采用限制性立方图进一步探讨FMR与卵巢良性肿瘤风险关联的变化趋势，最后根据研究对象的年龄(＜50岁、50~59岁、≥60岁)进行亚组分析，探究在不同年龄组FMR与卵巢良性肿瘤风险关联。 中位随访时间为8.77年，共追踪到卵巢良性肿瘤1 643例。在调整人口学因素、生殖因素、遗传因素、生活方式和激素相关因素后，全身、手臂、腿部和躯干FMR与卵巢良性肿瘤的发病风险均呈显著正相关，且高于BMI与卵巢良性肿瘤的发病风险，其中全身FMR与卵巢良性肿瘤风险关联性最强(HR：2.16; 95%CI：1.67~2.79)。根据BMI分层分析FMR与卵巢良性肿瘤风险显示，相比BM I≥25 kg/m2人群，BMI＜25 kg/m2人群的全身、手臂、腿部和躯干FMR与卵巢良性肿瘤风险的关联更强(Pinteraction＜0.05)。限制性立方图显示全身、手臂、躯干FMR与卵巢良性肿瘤风险关联在BMI＜25 kg/m2和BMI≥25 kg/m2人群间整体呈相反趋势。亚组分析可见全身、腿部FMR与卵巢良性肿瘤风险关联随着年龄组增长而降低(P＜0.05)，其中＜50岁年龄组人群的腿部FMR与卵巢良性肿瘤关联性最强(HR：2.38; 95%CI：1.39~4.08)。 FMR升高会增加卵巢良性肿瘤发病风险，其关联性在BMI＜25 kg/m2人群和40~50岁女性中更强。
To explore the key technical points and value of cell transfer technology in the diagnosis of micro-volume cell fluid. In the study, 32 micro-volume cell fluid samples with the diagnosis of tumor or atypical cells in the Department of Pathology, Peking University First Hospital were collected from September 2024 to June 2025. The cells on the ThinPrep cytology test (TCT) slides were divided into several sections and transferred to corresponding slides for immunocytochemistry (ICC) and special staining. Hematoxylin-eosin (HE) staining slides before and after transfer were compared to evaluate the performance of cell transfer technology in maintaining the consistency of cell morphology. The re-diagnosis referring to the results of ICC and special staining of transfer slides were made. The diagnosis before and after cell transfer was compared to evaluate the value of technology in improving the differential diagnostic accuracy. A total of 140 cell transfer slides were prepared from the 32 samples. Among them, 32 HE-stained slides were consistent with the original TCT slides in terms of staining quality, cell morphology and arrangement, with a success rate of 100%; 99 transfer slides were immuno-stained, of which 91 had accurate color and position of positivity and clear background of negativity, with a success rate of 91.91%; 9 special-stained slides had sharp color contrast and clear background, with a success rate of 100%. With the help of ICC and special staining results of transfer slides, 26 of the 32 samples were accurately diagnosed, including 18 cases of malignant tumors and 8 cases of non-neoplastic lesions; 6 cases remained undiagnosed, including four due to ICC staining failure and two due to too few cells. Compared with the original cytological diagnosis, a definitive differential diagnosis was obtained in 81.25% of cases after cell transfer. The application of cell transfer technology in TCT samples is feasible in clinical practice and is suitable for cases requiring ICC and special staining for auxiliary diagnosis. It can significantly improve the differential diagnostic accuracy for the micro-volume cell fluid samples, which is invaluable for the special cases which pathological diagnosis can only be made based on the micro-volume cell fluid samples because no more tissue sample is available. 探讨细胞转移技术应用于微量细胞液病理诊断的技术关键点及价值。 收集北京大学第一医院病理科2024年9月至2025年6月, 细胞学诊断为肿瘤细胞或非典型性细胞的微量细胞液样本, 共32例, 提取薄层液基细胞学技术(ThinPrep cytology test, TCT)制作的切片, 将切片上的细胞膜分割后分别转移到相应的载玻片上, 进行免疫细胞化学(immunocytochemistry, ICC)及特殊染色。对比转移前后苏木精-伊红(hematoxylin-eosin, HE)染色片, 评估细胞转移技术在维持细胞形态前后一致性方面的表现。对细胞转移后的ICC和特殊染色结果再次诊断, 评估细胞转移技术对提升鉴别诊断准确率的价值。 32例样本共转移140张转移片, 其中HE染色片32张, 无论是染色质量还是细胞形态和排列方式均与原始TCT制片一致, 成功率100%;ICC染色片99张, 其中91张着色定位准确、背景清晰, 成功率91.91%;特殊染色片9张, 色彩对比鲜明, 背景清晰, 成功率100%。借助细胞转移后的ICC和特殊染色结果, 32例样本中26例明确诊断, 包括恶性肿瘤18例和非肿瘤性病变8例, 另6例仍无法确诊, 其中4例ICC染色失败, 2例细胞量过少。与细胞转移前相比, 鉴别诊断准确率提高到81.25%(26/32)。 将细胞转移技术应用于TCT制片在临床实践中具有可行性, 适用于需要ICC及特殊染色辅助诊断的病例。该技术可提高微量细胞液样本鉴别诊断的准确率, 在无法获得组织学样本或只能依靠微量细胞液样本的病理诊断决定治疗策略时, 具有重要的临床价值。
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 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。
To explore the gross classification of gallbladder cancer with primary lesion confined within the gallbladder wall, and its correlation with prognosis and precancerous lesions. A retrospective study was conducted on 123 patients who were admitted to Peking University Third Hospital from January 2006 to December 2020. These patients had preoperative imaging findings suggesting that the primary lesion was confined within the gallbladder wall and had postoperative pathology of adenocarcinoma. Based on CT, MRI, or gross specimens, they were divided into the following four types: Type 1, simple intraluminal lesion: Intraluminal lesions without focal thickening of the gallbladder wall; Type 2, complex intraluminal lesion: Intraluminal lesions associated with focal thickening of the gallbladder wall and/or outer surface dimpling at the tumor base; Type 3, focal wall thickening: Circumferential focal wall thickening with heterogeneous enhancement within 2 continuous parts of the gallbladder; Type 4, diffuse wall thickening: Circumferential diffuse wall thickening extending more than 2 continuous parts of the gallbladder with heterogeneous enhancement. The clinical pathological characteristics, types of precancerous lesions, and survival status were compared among the different types. Both preoperative CT/MRI and intraoperative gross specimens could serve as the basis for gross classification, with gross specimens demonstrating the highest accuracy rate. Among the 123 patients, 13 could not be classified, while the remaining 110 underwent gross classification. The gross classification of gallbladder cancer was strongly or moderately correlated with histopathological parameters such as T-stage (P < 0.001, rs=0.682), lymph node metastasis (P < 0.001, rs=0.478), tissue differentiation degree (P < 0.001, rs=0.484), nerve infiltration (P < 0.001, rs=0.490), and vascular invasion (P < 0.001, rs=0.334). The higher the classification, the more adverse histopathological parameters were observed. Additionally, the gross classification of gallbladder cancer was moderately strongly and highly strongly correlated with residual lesions after surgical treatment (P < 0.001, rs=0.328) and postoperative recurrence (P < 0.001, rs=0.619) in the patients. Survival analysis revealed that the higher the classification, the shorter the median survival time of the patients (Type 1: 96 months, Type 2: 73 months, Type 3: 30 months, Type 4: 14 months, P < 0.001). Multivariate Cox regression indicated that the gross classification of gallbladder cancer was an independent prognostic factor (HR=3.609, 95%CI: 2.177-5.983, P < 0.001). In the patients with the most heterogeneous biological behavior in stage T2, the gross classification of gallbladder cancer was also closely associated with prognosis (median survival times were 72, 70, 29, and 16 months, respectively, P < 0.001). Multivariate Cox regression further demonstrated that the gross classification of gallbladder cancer was an independent prognostic factor (HR=2.723, 95%CI: 1.566-4.736, P < 0.001). In terms of tumor origin, the gross classification of gallbladder cancer was significantly correlated with the type of precancerous lesions: Type 1 mainly originated from intracholecystic papillary neoplasm of the gallbladder, while Types 3 and 4 were mostly high-grade biliary intraepithelial neoplasm or without precancerous lesions. Analysis of the natural history of the tumor suggested that Type 1 progressed slowly, Type 4 progressed rapidly, and Type 2 exhibited greater heterogeneity. The gallbladder cancer with primary lesion confined within the gallbladder wall is closely related to prognosis and precancerous lesions, and can serve as an important reference for surgical decision-making and stratified management. 探讨原发灶局限于胆囊壁内胆囊癌的大体分型及其与预后和癌前病变相关性。 回顾性纳入2006年1月至2020年12月北京大学第三医院收治的123例术前影像提示原发灶局限于胆囊壁内、且术后病理为腺癌患者。依据CT、MRI或大体标本分为如下4型：1型，局限性凸向腔内肿物，不伴肿物附着处胆囊壁增厚；2型，局限性凸向腔内肿物，伴肿物附着处胆囊壁增厚和/或增厚处浆膜皱褶；3型，局限于两个连续部分的胆囊壁环形增厚；4型，延续至两个以上连续部分的胆囊壁环形增厚。比较各分型之间的临床病理特征、癌前病变类型及生存情况。 术前CT/MRI及术中大体标本均可以作为大体分型的依据，大体标本准确率最高。123例患者中13例无法分型，剩余110例完成大体分型。胆囊癌大体分型与T分期(P＜0.001，rs=0.682)呈高强度相关，与淋巴结转移(P＜0.001，rs=0.478)、组织分化程度(P＜0.001，rs=0.484)、神经浸润(P＜0.001，rs=0.490)以及脉管瘤栓(P＜0.001，rs=0.334)等组织病理学参数呈中等强度相关，分型越高，不良组织病理学参数越多。另外，胆囊癌大体分型与患者手术治疗后残余病灶(P＜0.001，rs=0.328)和术后复发(P＜0.001，rs=0.619)呈中等强度和高等强度相关性。生存分析显示，分型越高，患者中位生存时间越短，1型96个月，2型73个月，3型30个月，4型14个月，P＜0.001。多因素Cox回归表明胆囊癌大体分型是患者预后的独立影响因素(HR=3.609，95%CI：2.177~5.983，P＜0.001)。在肿瘤生物学行为异质性最强的T2期患者中，胆囊癌大体分型同样与预后密切相关，中位生存时间分别为72个月、70个月、29个月和16个月， P＜0.001。多因素Cox回归亦表明胆囊癌大体分型是患者预后的独立影响因素(HR=2.723，95%CI：1.566~4.736，P＜0.001)。在肿瘤起源方面，胆囊癌大体分型与癌前病变类型显著相关：1型主要源自胆囊内乳头状肿瘤，3型与4型则多为高级别胆管上皮内瘤变或无癌前病变。肿瘤自然病程分析提示：1型进展缓慢，4型进展迅速，2型表现出较大异质性。 原发灶局限于胆囊壁内胆囊癌大体分型与预后及癌前病变密切相关，可作为手术决策与分层管理的重要参考依据。
To construct a standardized unilateral molar occlusal interference model, to establish a comprehensive surface electromyography (sEMG)-based index system for orofacial muscle function, and to develop an accurate discriminant model, thereby providing an objective electrophysiological basis for occlusal interference diagnosis. Twenty-six healthy adult volunteers were recruited and provided written informed consent. Utilizing advanced digital dental technology, including intraoral scanning, computer-aided design (CAD), and additive manufacturing, a standardized occlusal inter-ference patch with a precise thickness was fabricated. This patch was adhesively bonded to the occlusal surface of the mandibular first molar to create a reversible unilateral occlusal interference model. A self-developed, multi-channel wireless sEMG system was employed to collect high-fidelity electromyographic signals from key bilateral masticatory muscles: the anterior temporal muscles, masseters, and the anterior bellies of the digastric muscles. Data were recorded during 10 standardized mandibular functional activities both before (baseline) and after the induction of interference. From the raw sEMG signals, a multi-dimensional index system comprising 56 distinct indicators across time, frequency, and complexity domains was constructed. Sophisticated statistical analyses, including paired-sample t-tests (or Wilcoxon signed-rank tests), principal component analysis (PCA) for dimensionality reduction, and stepwise Logistic regression analysis, were applied to screen for the most significant feature variables and to build the optimal discriminant model. Forty valid interference models were successfully established. Statistical analysis revealed 253 sEMG indicators showed significant differences following interference induction (P < 0.05), with lateral-movement-related parameters demonstrating particular sensitivity. PCA extracted 19 principal components (PCs) explaining 85.5% of cumulative variance, where PC1 (muscle fatigue level) and PC2 (functional movement amplitude) represented the primary explanatory components. The optimal Logistic regression model incorporated 3 principal components. Cross-validation showed the model achieved a mean accuracy of 0.840, with mean sensitivity and specificity of 0.851 and 0.828, respectively, and a mean area under the curve (AUC) of 0.923. The Logistic regression discriminant model for unilateral molar occlusal interference constructed in this study can effectively identify the occlusal interference state under the experimental conditions, demonstrating promising diagnostic potential. 构建标准化的单侧磨牙咬合干扰模型, 建立基于表面肌电的口颌肌功能指标体系, 并开发咬合干扰的判别模型, 为咬合干扰的客观诊断提供电生理学参考。 招募到26名志愿者, 采用口内扫描、计算机辅助设计及增材制造技术制作标准化咬合干扰贴片, 于下颌第一磨牙处构建可逆性单侧咬合干扰模型。使用自主研发的多通道无线表面肌电系统采集干扰前后10种下颌功能活动时双侧颞肌前束、咬肌及二腹肌前腹的肌电信号, 构建包含56项指标的多维度表面肌电指标体系。通过配对t检验或Wilcoxon符号秩检验、主成分分析和Logistic回归分析, 筛选特征变量并建立判别模型。 共构建40例有效干扰模型, 253项表面肌电信号指标干扰前后比较差异具有统计学意义(P < 0.05), 其中侧方运动相关指标对咬合干扰的敏感性最高。主成分分析共提取19个主成分(principal component, PC), 累计方差贡献率85.5%, 其中PC1(肌肉疲劳程度)和PC2(功能性运动幅度)为主要解释成分。Logistic回归模型最终纳入3项主成分, 交叉验证结果表明模型平均准确率为0.840, 平均灵敏度与特异度分别为0.851和0.828, 平均曲线下面积为0.923。 研究构建的单侧磨牙咬合干扰Logistic回归判别模型能有效识别本实验条件下的咬合干扰状态, 具有较好的诊断潜力。
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。
To compare the composition and structure of extraradicular bacterial communities in periapical lesions of teeth with post-treatment apical periodontitis (PoAP) between cases with and without sinus tracts. Patients requiring apical surgery were recruited from the Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology. Periapical lesion samples were collected from teeth with sinus tracts and without sinus tracts during apical microsurgery. The remaining lesion samples were submitted for pathological examination. Following the extraction of the bacterial DNA, the V3-V4 region of the bacterial 16S rRNA gene was subjected to high-throughput sequencing using Illumina NovaSeq 6000. Bioinformatics analysis was performed using QIIME2 software. α diversity indices (Shannon, Simpson, Chao1) were calculated, and intergroup differences were analyzed using Wilcoxon test. β diversity was assessed by principal coordinate analysis based on Weighted Unifrac test, and community composition differences were analyzed with permutational multivariate analysis of variance (PERMANOVA). Differences in relative abundance between the groups were compared using the Wilcoxon test, followed by Benjamini-Hochberg false discovery rate (FDR) correction to convert P value to q value. A total of 66 subjects were enrolled, including 21 male and 45 female patients, with a mean age of (33.91±9.16) years. Three subjects each had two teeth enrolled. In total, 69 teeth were included. These teeth included 47 cases without sinus tracts and 22 cases with sinus tracts. No significant differences were observed between the two groups in the distribution of obturation quality or pathological types (P>0.05). No statistically significant differences were found in α diversity indices between the two groups (P>0.05). However, β diversity analysis revealed a significant difference between the two groups (P=0.008). At the phylum level, the relative abundance of Bacteroidota was significantly higher in the group with sinus tracts (16.98% vs. 9.22%, q < 0.01), while the relative abundance of Pseudomonadota was significantly lower in the group with sinus tracts (30.70% vs. 42.19%, q < 0.05). At the genus level, Porphyromonas, Tannerella, Segatella, Phocaeicola, and Hoylesella were significantly enriched in the group with sinus tracts (q < 0.05), whereas Bacillus was more abundant in the group without sinus tracts (q < 0.05). The extraradicular bacterial community structure significantly differs between PoAP with and without sinus tracts. Porphyromonas, Tannerella, Segatella, Phocaeicola, and Hoylesella may be associated with the formation and persistence of sinus tracts. 比较无窦型与有窦型根管治疗后慢性根尖周炎(post-treatment apical periodontitis, PoAP)患牙根管外菌群的组成与结构差异。 纳入需要进行显微根尖手术治疗的PoAP患牙。手术中收集患牙根尖周病变组织, 并对细菌进行16S rRNA高通量测序, 测序区域为V3~V4。利用QIIME2软件进行生物信息学分析, 计算样本的α多样性, 采用Wilcoxon秩和检验进行组间差异分析。采用基于Weighted Unifrac距离的主坐标分析评估样本的β多样性, 通过置换多元方差分析(permutational multivariate analysis of variance, PERMANOVA)比较组间差异。采用Wilcoxon秩和检验比较组间物种相对丰度的差异, 并通过Benjamini-Hochberg法进行错误发现率(false discovery rate, FDR)校正, 将P值校正为q值。 共纳入66例受试者, 男性21例, 女性45例, 平均年龄(33.91±9.16)岁。66例受试者中3例各有2颗患牙被纳入, 共纳入69颗患牙, 其中无窦型47颗, 有窦型22颗, 无窦型和有窦型两组在根充质量及病理类型上的分布差异均无统计学意义(P＞0.05)。两组样本的α多样性指数差异无统计学意义(P>0.05), β多样性分析显示两组样本整体菌群结构差异有统计学意义(P < 0.01)。在门水平上, 有窦型组中拟杆菌门(Bacteroidota)的相对丰度显著高于无窦型组(16.98% vs. 9.22%, q < 0.01), 而假单胞菌门(Pseudomonadota)的相对丰度显著低于无窦型组(30.70% vs. 42.19%, q < 0.05);在属水平上, 卟啉单胞菌属(Porphyromonas)、坦纳菌属(Tannerella)、Segatella、Phocaeicola和Hoylesella在有窦型组中丰度更高(q < 0.05), 而芽孢杆菌属(Bacillus)在无窦型组中丰度更高(q < 0.05)。 无窦型与有窦型PoAP的根管外菌群结构存在显著差异, 卟啉单胞菌属、坦纳菌属、Segatella、Phocaeicola和Hoylesella可能与窦道的形成和持续存在相关。