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Guided Cavity Preparation to Access an Invagination and Preserve Pulp Vitality of an Immature Maxillary Lateral Incisor With Type IIIa Dens Invaginatus: Technical Overview and a Case Report With 3-Year Follow-Up. 引导空腔预备治疗未成熟上颌侧切牙iia型牙槽内陷并保留牙髓活力:技术综述及3年随访1例。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-26 DOI: 10.1111/iej.70088
Francesc Abella Sans, Venkateshbabu Nagendrababu, Nandini Suresh, Marc Garcia-Font, Paul M H Dummer

Aim: Dens invaginatus (DI) is a developmental anomaly often associated with caries and periapical pathosis. This report describes guided access and filling of an infected invagination in a maxillary lateral (tooth #22) with long-term preservation of pulp vitality.

Summary: A 9-year-old male presented with a palatal sinus tract associated with immature tooth 22. Based on clinical and radiographic examination, a type IIIa DI with a pseudo-foramen midway along the mesial aspect of the root was identified. The tooth had a healthy pulp and peri-invagination periodontitis. A guided endodontic cavity was prepared to selectively access the invagination without compromising the pulp and the invagination filled with a bioceramic calcium silicate-based material. At 36 months the tooth was asymptomatic, and the pulp tested positive. Radiographically, root development was complete with bony healing of the lesion. This case report highlights the effectiveness of guided cavity preparation to access an invagination in an immature tooth with DI while preserving pulp vitality.

目的:凹牙是一种发育异常,常伴有龋病和根尖周围病变。本报告描述了上颌侧牙(22号牙)感染内陷的引导下进入和填充物,并长期保持牙髓活力。摘要:一名9岁男性,因腭窦道与未成熟牙齿相关22。根据临床和影像学检查,确定了一种IIIa型DI,其沿根内侧方向的中间有假孔。牙髓健康,并有牙周炎。在不损害牙髓的情况下,制备了一个有选择地进入内陷的引导根管腔,并填充了生物陶瓷硅酸钙基材料。36个月时,牙齿无症状,牙髓检测呈阳性。x线片显示病灶骨愈合,根发育完全。本病例报告强调了在保留牙髓活力的同时,引导空腔准备在未成熟牙齿内凹处的有效性。
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引用次数: 0
Restoring Cell-Cell Junctions in DSPP-Deficient Odontoblasts Through Nanofibrous Topography and Wnt5a-Cdc42 Activation: A Laboratory Investigation. 通过纳米纤维形貌和Wnt5a-Cdc42激活恢复dspp缺陷成牙细胞的细胞连接:一项实验室研究。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-24 DOI: 10.1111/iej.70086
Jieun Bae, Jung-Wook Kim, Kyung Mi Woo

Aim: Biomaterial-based strategies offer therapeutic potential for inherited disorders such as Dentinogenesis imperfecta type II (DGI-II). DGI-II, a hereditary dental disorder caused by dentine sialophosphoprotein (Dspp) gene mutations, results in fragile, discoloured teeth susceptible to wear and decay. This study investigates the structural alterations in the dentine matrix induced by mutant DSPP and the underlying molecular mechanisms. Furthermore, we evaluated a therapeutic strategy combining nanofibrous substrates with molecular activation of the Wnt5a-Cdc42 pathway, aiming to mitigate these structural defects and restore dentine integrity.

Methodology: A maxillary first premolar extracted from a patient with dentinogenesis imperfecta type II (DGI-II) carrying a known DSPP frameshift mutation was analysed using micro-computed tomography and scanning electron microscopy. MDPC-23 mouse dental pulp pre-odontoblasts were cultured in vitro on electrospun nanofibrous scaffolds with tunable fibre diameters. Dspp expression was silenced to investigate its regulatory role in cell-cell contact formation, while the Wnt5a-Cdc42 pathway was activated via recombinant Wnt5a protein and a small molecule. Data were analysed using Student's t-test or one-way ANOVA with a significance threshold of p < 0.05.

Results: Decalcified or freeze-fractured samples exhibited thick fibres, sparse dentinal tubules, and a disorganised, non-layered dentine matrix, indicating that disrupted cell-cell junctions impair directional appositional dentine formation. Silencing Dspp expression in dental pulp cells led to reduced expression of junctional proteins, Zona occludens-1 (ZO-1) and Connexin43 (Cx43), which are essential for vectorial matrix apposition. Modulating fibre thickness and activating the Wnt5a-Cdc42 signalling axis restored both the expression and cellular localisation of ZO-1 and Cx43, thereby re-establishing cell-cell junctions and paracellular permeability in Dspp-silenced dental pulp cells.

Conclusion: The results provide evidence that Dspp contributes to the structural integrity of dentine by modulating ZO-1 and Cx43 expression and suggest that biomaterial and molecular interventions may offer supportive strategies to restore dentine structure and function in DGI-affected teeth, though they do not address the underlying genetic defect.

目的:基于生物材料的策略为遗传性疾病如牙本质发育不全II型(DGI-II)提供了治疗潜力。DGI-II是一种由牙本质唾液磷蛋白(Dspp)基因突变引起的遗传性牙齿疾病,导致脆弱、变色的牙齿容易磨损和腐烂。本研究探讨了DSPP突变体诱导牙本质基质的结构改变及其分子机制。此外,我们评估了将纳米纤维底物与Wnt5a-Cdc42途径的分子激活相结合的治疗策略,旨在减轻这些结构缺陷并恢复牙本质完整性。方法:用微计算机断层扫描和扫描电镜分析从牙本质发育不全II型(DGI-II)患者中取出的上颌第一前磨牙,该患者携带已知的DSPP移码突变。采用纤维直径可调的电纺丝纳米纤维支架体外培养MDPC-23小鼠牙髓前成牙细胞。我们沉默Dspp表达以研究其在细胞-细胞接触形成中的调控作用,而通过重组Wnt5a蛋白和一个小分子激活Wnt5a- cdc42通路。使用学生t检验或单向方差分析分析数据,显著性阈值为p。结果:脱钙或冷冻断裂的样品显示出粗纤维,稀疏的牙本质小管,无序的,无层状的牙本质基质,表明破坏的细胞-细胞连接损害了定向同位牙本质的形成。在牙髓细胞中沉默Dspp的表达导致连接蛋白,Zona occluden -1 (ZO-1)和Connexin43 (Cx43)的表达减少,这些蛋白是载体基质附着所必需的。通过调节纤维厚度和激活Wnt5a-Cdc42信号轴,可以恢复ZO-1和Cx43的表达和细胞定位,从而在dspp沉默的牙髓细胞中重建细胞间连接和细胞旁通透性。结论:Dspp通过调节ZO-1和Cx43的表达来促进牙本质的结构完整性,并提示生物材料和分子干预可能为修复dgi影响牙齿的牙本质结构和功能提供支持策略,尽管它们不能解决潜在的遗传缺陷。
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引用次数: 0
Feasibility and Precision of Robot-Assisted Autotransplantation of Teeth: An In Vitro Study. 机器人辅助牙齿自体移植的可行性和精度:体外研究。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-17 DOI: 10.1111/iej.70082
Guangwei Chen, Zuwen Ma, Zixin Luo, Huilin Wu, Weifa Li, Jinglin Kuang, Ping Li, Libin Zhou

Aim: This in vitro study evaluated the feasibility, precision and efficiency of robot-assisted tooth autotransplantation compared with static template-guided and freehand techniques.

Methodology: A total of 120 mandibular resin-bone models were randomly assigned to robot-assisted (RA), template-guided (TG) or freehand (FH) socket preparation (n = 40 each). Preoperative CBCT and intraoral scans were merged for virtual planning. In RA, a Yakebot integrated autonomous drilling and dynamic navigation. Accuracy and efficiency were assessed by 10 metrics (CDD, IPDD-C, IPDD-R, LAD, MDAD, BLAD, RAD, Hausdorff distance, Dice coefficient and socket preparation time). Statistical analyses were performed using the Kruskal-Wallis test followed by Dunn's post hoc tests with Bonferroni correction.

Results: RA achieved the smallest deviations across all parameters. Mean CDD was 0.49 ± 0.25 mm in RA, significantly lower than TG (0.63 ± 0.22 mm) and FH (0.69 ± 0.33 mm; p = 0.005). RA also showed the lowest angular errors (LAD 3.81° vs. TG 6.10° and FH 9.54°; p < 0.001) and highest reproducibility. Hausdorff and Dice analyses confirmed superior 3D congruence in RA. Mean socket preparation time was shortest in RA (5.59 ± 0.32 min; p < 0.001).

Conclusion: Under standardised in vitro conditions, robot-assisted autotransplantation achieved higher preparation accuracy, reproducibility and procedural efficiency than template-guided and freehand methods. By integrating robot-guided drilling with dynamic navigation, the system enabled precise socket preparation and may help reduce the technical demands of the procedure. These findings provide preliminary evidence of feasibility and support further validation in clinical studies.

目的:比较机器人辅助牙齿自体移植与静态模板引导和徒手移植的可行性、精确性和有效性。方法:120个下颌骨树脂骨模型随机分为机器人辅助(RA)、模板引导(TG)和徒手(FH)三组(各40个)。术前CBCT和口内扫描合并进行虚拟规划。在RA中,Yakebot集成了自主钻井和动态导航。采用10项指标(CDD、IPDD-C、IPDD-R、LAD、MDAD、BLAD、RAD、Hausdorff距离、Dice系数、窝孔准备时间)评价准确性和效率。采用Kruskal-Wallis检验进行统计分析,随后采用Dunn事后检验进行Bonferroni校正。结果:RA在所有参数上的偏差最小。RA组平均CDD为0.49±0.25 mm,显著低于TG(0.63±0.22 mm)和FH(0.69±0.33 mm; p = 0.005)。RA的角度误差最小(LAD 3.81°,TG 6.10°,FH 9.54°)。p结论:在标准化的体外条件下,机器人辅助自体移植比模板引导和徒手方法具有更高的制备精度、重现性和程序效率。通过将机器人导向钻井与动态导航相结合,该系统可以实现精确的套管准备,并有助于降低作业的技术要求。这些发现提供了初步的可行性证据,并支持在临床研究中进一步验证。
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引用次数: 0
NLRP1 as a Novel Pyroptosis Biomarker in Irreversible Pulpitis: A Laboratory Investigation and Animal Model Study. NLRP1作为不可逆性牙髓炎的新型焦亡生物标志物:实验室调查和动物模型研究。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-16 DOI: 10.1111/iej.70084
Jilin Wu, Churen Zhang, Jiaqi Chen, Yuzi Yu, Zhenhao Xue, Siyi Liu, Jingyi Li, Yanmei Dong

Aim: Irreversible pulpitis poses a significant clinical burden due to progressive inflammatory pulp damage. While inflammatory mechanisms are central to its pathogenesis, they remain incompletely characterised. This study aims to elucidate the role of Nod-like receptor thermal domain associated protein 1 (NLRP1) in irreversible pulpitis pathogenesis.

Methodology: Transcriptomic analysis of public dataset GSE77459 identified dysregulated pyroptosis-related genes (PRGs), with machine learning prioritising hub genes for experimental validation. Key targets were experimentally verified through an integrated approach: in vitro models using lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs) analysed by qRT-PCR, ELISA and Western blot and specific pyroptosis assays (PI uptake, Caspase-1 cleavage); in vivo rat pulpitis models; and clinically validation with human irreversible pulpitis tissues analysed via H&E staining, immunohistochemistry (IHC) and immunofluorescence (IF). Functional roles were further assessed via NLRP1 knockdown and overexpression in hDPCs.

Results: Bioinformatics identified 11 differentially expressed PRGs, with machine learning highlighting six hub genes including unreported NLRP1. Specific pyroptosis assays confirmed that LPS induces membrane pore formation and Caspase-1 activation in hDPCs. Significant post-transcriptional regulation of NLRP1 was demonstrated by pronounced protein upregulation in LPS-stimulated hDPCs despite unaltered mRNA. Functional studies established NLRP1 as a positive regulator, where its knockdown attenuated the LPS-induced inflammatory-pyroptotic response, while its overexpression alone was sufficient to upregulate key mediators. Consistently, elevated NLRP1 expression was observed in rat models and human tissues, where IHC/IF localised prominent expression to inflammatory infiltrates.

Conclusion: NLRP1 is highlighted as a novel pyroptosis biomarker for irreversible pulpitis, with its dysregulation offering diagnostic value for inflammation. These findings suggest its potential involvement in the inflammatory mechanisms of pulpitis, providing a new molecular target for future therapeutic exploration.

目的:不可逆性牙髓炎由于进行性的炎症性牙髓损伤而造成显著的临床负担。虽然炎症机制是其发病机制的核心,但它们仍然不完全表征。本研究旨在阐明nod样受体热结构域相关蛋白1 (NLRP1)在不可逆牙髓炎发病机制中的作用。方法:对公共数据集GSE77459进行转录组学分析,确定了失调的热解相关基因(PRGs),并使用机器学习优先考虑中心基因进行实验验证。通过综合方法对关键靶点进行实验验证:使用脂多糖(LPS)刺激的人牙髓细胞(hDPCs)的体外模型,通过qRT-PCR, ELISA和Western blot和特异性焦解实验(PI摄取,Caspase-1裂解)进行分析;大鼠牙髓炎模型;并通过H&E染色、免疫组织化学(IHC)和免疫荧光(IF)分析人类不可逆牙髓炎组织的临床验证。在hDPCs中,通过NLRP1敲低和过表达进一步评估其功能作用。结果:生物信息学鉴定了11个差异表达的PRGs,机器学习突出了6个中心基因,包括未报道的NLRP1。特异性焦亡实验证实,LPS诱导hDPCs的膜孔形成和Caspase-1激活。在lps刺激的hDPCs中,尽管mRNA没有改变,但显著的蛋白上调证明了NLRP1的转录后调控。功能研究证实NLRP1是一个正调节因子,其敲低可减弱lps诱导的炎症-焦亡反应,而其过表达则足以上调关键介质。在大鼠模型和人体组织中,NLRP1的表达一致升高,其中IHC/IF将突出表达定位于炎症浸润。结论:NLRP1作为不可逆性牙髓炎的一种新型热凋亡生物标志物,其表达异常具有诊断炎症的价值。这些发现提示其可能参与牙髓炎的炎症机制,为未来的治疗探索提供了新的分子靶点。
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引用次数: 0
Exploring Persistent Apical Periodontitis in Humans: Integrative Genetic, Histological and Microbiological Perspectives for Translational Research 探索人类持续性根尖牙周炎:综合遗传学、组织学和微生物学角度的转化研究。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-12 DOI: 10.1111/iej.70070
Igor Bassi Ferreira Petean, Alice Corrêa Silva-Sousa, Rafael Verardino de Camargo, Yara Terezinha Corrêa Silva-Sousa, Fernanda Gonçalves Basso, André Pitondo-Silva, Francisco Wanderley Garcia de Paula-Silva, Erika Calvano Kuchler, Raquel Assed Bezerra da Silva, Lea Assed Bezerra da Silva, Jardel Francisco Mazzi-Chaves, Fabiane Carneiro Lopes-Olhê, Manoel Damião Sousa-Neto
<div> <section> <h3> Aim</h3> <p>To evaluate the impact of polymorphisms in <i>SOCS-1, TNF-α</i> and <i>RANKL</i> on gene expression of <i>RANK</i>, <i>RANKL</i>, <i>TNFRSF1, SOCS-1, IL-10</i>, <i>IL-1β</i> and <i>TNF-α</i>, and to evaluate the histopathological, immunohistochemical and microbiological aspects of persistent apical periodontitis (PAP) after root canal treatment (RCT) in Brazilian individuals.</p> </section> <section> <h3> Methodology</h3> <p>Patients with pulp necrosis and apical periodontitis at the time of the non-surgical RCT (NSRCT) were followed up for at least 1 year after NSRCT. In view of the need for surgical intervention (cases assessed with a CBCTPAI score of 4 and 5, with the presence of symptoms), 20 patients were selected for endodontic surgery, which was planned using cone beam computed tomography images. Initially, saliva was collected as a source of genomic DNA, and the individuals were genotyped for <i>SOCS-1</i>, <i>TNF-α</i> and <i>RANKL</i> polymorphisms by real-time PCR. After collecting the biological material, the periapical lesions obtained were subjected to analysis of gene expression levels for <i>RANK</i>, <i>RANKL</i>, <i>TNFRSF1, SOCS-1, IL-10</i>, <i>IL-1β</i> and <i>TNF-α</i>, and histopathological evaluation for characterisation and differentiation into periapical granulomas and cysts; immunohistochemical evaluation for SOCS-1 and IL-1β protein labeling; and microbiological analysis to identify the microorganisms involved in persistent periapical infection. The relative mRNA expression values of each gene in each group, according with genotypes in different SNPs, were analysed using one-way analysis of variance followed by Tukey's post-test or <i>T</i>-test (<i>α</i> = 5%).</p> </section> <section> <h3> Results</h3> <p>Different expression values of the genes evaluated were observed according to the genotypes of the polymorphisms evaluated in relation to PAP (<i>p</i> < 0.05). Among the cases submitted for histopathological evaluation, 66.7% were diagnosed as periapical granuloma and 33.3% as periapical cyst. Immunohistochemical analysis showed strong positivity for SOCS-1 and IL-1β in the lesions classified as periapical cyst, while the lesions diagnosed as periapical granuloma were not labelled. In the microbiological analysis, four different species of bacteria were isolated: <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus epidermidis</i>, <i>Enterococcus faecalis</i> and <i>Bacillus cereus</i>.</p> </section> <section> <h3> Conclusions</h3> <p>This exploratory study indicates that genetic pol
目的:评估SOCS-1、TNF-α和RANKL基因多态性对RANK、RANKL、TNFRSF1、SOCS-1、IL-10、IL-1β和TNF-α基因表达的影响,并评估巴西个体根管治疗后持续性根尖牙周炎(PAP)的组织病理学、免疫组织化学和微生物学方面的影响。方法:对非手术RCT (NSRCT)时牙髓坏死和根尖牙周炎患者进行至少1年的随访。考虑到手术干预的必要性(CBCTPAI评分为4分和5分的病例,并存在症状),选择20例患者进行牙髓手术,计划使用锥束计算机断层扫描图像。最初,收集唾液作为基因组DNA的来源,并通过实时PCR对个体进行SOCS-1、TNF-α和RANKL多态性的基因分型。收集生物材料后,对获得的根尖周病变进行RANK、RANKL、TNFRSF1、SOCS-1、IL-10、IL-1β和TNF-α基因表达水平分析,并进行组织病理学鉴定,鉴别为根尖周肉芽肿和囊肿;免疫组化评价SOCS-1和IL-1β蛋白标记;并进行微生物学分析,鉴定与持续性根尖周感染有关的微生物。各组各基因mRNA的相对表达量根据不同snp的基因型,采用单因素方差分析,并进行Tukey后验或t检验(α = 5%)。结果:PAP相关基因多态性的基因型不同,被评估基因的表达值也不同(p)。结论:本探索性研究表明,基因多态性可以调节PAP基因表达和蛋白活性,塑造宿主的炎症和修复反应。这些发现突出了它们作为生物标志物的潜力,并为未来的转化研究奠定了基础。
{"title":"Exploring Persistent Apical Periodontitis in Humans: Integrative Genetic, Histological and Microbiological Perspectives for Translational Research","authors":"Igor Bassi Ferreira Petean,&nbsp;Alice Corrêa Silva-Sousa,&nbsp;Rafael Verardino de Camargo,&nbsp;Yara Terezinha Corrêa Silva-Sousa,&nbsp;Fernanda Gonçalves Basso,&nbsp;André Pitondo-Silva,&nbsp;Francisco Wanderley Garcia de Paula-Silva,&nbsp;Erika Calvano Kuchler,&nbsp;Raquel Assed Bezerra da Silva,&nbsp;Lea Assed Bezerra da Silva,&nbsp;Jardel Francisco Mazzi-Chaves,&nbsp;Fabiane Carneiro Lopes-Olhê,&nbsp;Manoel Damião Sousa-Neto","doi":"10.1111/iej.70070","DOIUrl":"10.1111/iej.70070","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Aim&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To evaluate the impact of polymorphisms in &lt;i&gt;SOCS-1, TNF-α&lt;/i&gt; and &lt;i&gt;RANKL&lt;/i&gt; on gene expression of &lt;i&gt;RANK&lt;/i&gt;, &lt;i&gt;RANKL&lt;/i&gt;, &lt;i&gt;TNFRSF1, SOCS-1, IL-10&lt;/i&gt;, &lt;i&gt;IL-1β&lt;/i&gt; and &lt;i&gt;TNF-α&lt;/i&gt;, and to evaluate the histopathological, immunohistochemical and microbiological aspects of persistent apical periodontitis (PAP) after root canal treatment (RCT) in Brazilian individuals.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methodology&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Patients with pulp necrosis and apical periodontitis at the time of the non-surgical RCT (NSRCT) were followed up for at least 1 year after NSRCT. In view of the need for surgical intervention (cases assessed with a CBCTPAI score of 4 and 5, with the presence of symptoms), 20 patients were selected for endodontic surgery, which was planned using cone beam computed tomography images. Initially, saliva was collected as a source of genomic DNA, and the individuals were genotyped for &lt;i&gt;SOCS-1&lt;/i&gt;, &lt;i&gt;TNF-α&lt;/i&gt; and &lt;i&gt;RANKL&lt;/i&gt; polymorphisms by real-time PCR. After collecting the biological material, the periapical lesions obtained were subjected to analysis of gene expression levels for &lt;i&gt;RANK&lt;/i&gt;, &lt;i&gt;RANKL&lt;/i&gt;, &lt;i&gt;TNFRSF1, SOCS-1, IL-10&lt;/i&gt;, &lt;i&gt;IL-1β&lt;/i&gt; and &lt;i&gt;TNF-α&lt;/i&gt;, and histopathological evaluation for characterisation and differentiation into periapical granulomas and cysts; immunohistochemical evaluation for SOCS-1 and IL-1β protein labeling; and microbiological analysis to identify the microorganisms involved in persistent periapical infection. The relative mRNA expression values of each gene in each group, according with genotypes in different SNPs, were analysed using one-way analysis of variance followed by Tukey's post-test or &lt;i&gt;T&lt;/i&gt;-test (&lt;i&gt;α&lt;/i&gt; = 5%).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Different expression values of the genes evaluated were observed according to the genotypes of the polymorphisms evaluated in relation to PAP (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Among the cases submitted for histopathological evaluation, 66.7% were diagnosed as periapical granuloma and 33.3% as periapical cyst. Immunohistochemical analysis showed strong positivity for SOCS-1 and IL-1β in the lesions classified as periapical cyst, while the lesions diagnosed as periapical granuloma were not labelled. In the microbiological analysis, four different species of bacteria were isolated: &lt;i&gt;Pseudomonas aeruginosa&lt;/i&gt;, &lt;i&gt;Staphylococcus epidermidis&lt;/i&gt;, &lt;i&gt;Enterococcus faecalis&lt;/i&gt; and &lt;i&gt;Bacillus cereus&lt;/i&gt;.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This exploratory study indicates that genetic pol","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 3","pages":"486-501"},"PeriodicalIF":7.1,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145742372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Melatonin and the Dental Pulp: A Scoping Review. 褪黑素和牙髓:范围综述。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-09 DOI: 10.1111/iej.70081
Jasmin Schäfer, Konrad Kleszczynski, Edgar Schäfer

Background: In general medicine, melatonin is known to enhance wound healing and promote stem cell differentiation. Its potential relevance in endodontics, however, remains underexplored.

Objectives: This scoping review aimed to systematically assess the available evidence on the effects of melatonin (a) on dental pulp tissue and (b) on human dental pulp stem cells (hDPSCs), particularly regarding cell proliferation and differentiation with regard to endodontics.

Methodology: A comprehensive literature search was conducted in PubMed, Clarivate Analytics' Web of Science and Scopus from inception to July 1, 2025, using Medical Subject Headings (MeSH terms) and supplemented by hand searching and screening of major subject journals.

Results: The initial search yielded 252 records, with one additional record identified through citation mining and relevant journal screening. A total of 22 studies met the inclusion criteria: 11 investigated melatonin's effect on dental pulp tissue regarding anti-inflammatory properties, treatment of pulpitis, wound healing and pulp capping and 11 examined its impact on hDPSCs in terms of cell proliferation and differentiation.

Discussion: The limited evidence obtained from laboratory and animal studies suggests a dose- and time-dependent influence of melatonin, though evidence is insufficient to establish optimal concentrations.

Conclusions: (a) Melatonin demonstrates anti-inflammatory, antioxidant and anti-fibrinolytic effects on dental pulp tissue. (b) Melatonin has potential as a stem cell modulator by promoting odontogenic differentiation and may improve migration and proliferation of hDPSCs.

背景:在一般医学中,褪黑素被认为可以促进伤口愈合和促进干细胞分化。然而,其在牙髓学中的潜在相关性仍未得到充分探讨。目的:本综述旨在系统评估褪黑素(a)对牙髓组织和(b)对人牙髓干细胞(hDPSCs)影响的现有证据,特别是在牙髓学方面的细胞增殖和分化方面。方法:从研究开始到2025年7月1日,在PubMed、Clarivate Analytics的Web of Science和Scopus中进行了全面的文献检索,使用医学主题词(MeSH terms),并辅以人工检索和筛选主要学科期刊。结果:最初的搜索产生了252条记录,通过引文挖掘和相关期刊筛选确定了一条额外的记录。共有22项研究符合纳入标准:11项研究了褪黑素对牙髓组织的影响,包括抗炎特性、治疗牙髓炎、伤口愈合和牙髓覆盖,11项研究了褪黑素对hdpsc细胞增殖和分化的影响。讨论:从实验室和动物研究中获得的有限证据表明褪黑激素具有剂量和时间依赖性影响,尽管证据不足以确定最佳浓度。结论:(a)褪黑素对牙髓组织具有抗炎、抗氧化和抗纤溶作用。(b)褪黑素有潜力作为干细胞调节剂,促进牙源性分化,并可能改善hdpsc的迁移和增殖。
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引用次数: 0
Progress and Perspectives in Allogeneic Cell-Based Pulp Regeneration. 同种异体细胞牙髓再生研究进展与展望。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-05 DOI: 10.1111/iej.70080
Yihan Chen, Mingxin Hu, Yan Lam Lee, Leyi Chen, Shulan Lin, Xin Li, Jianguang Xu, Chengfei Zhang

Background: Cell-based regenerative endodontic procedures (REPs) using dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHEDs) and those from apical papillae have shown great potential for authentic pulp regeneration, as evidenced by reports from preclinical studies and limited clinical trials. However, challenges, such as low cell survival rates, immune rejection during allogeneic transplantation and inconsistent protocols, hinder their widespread clinical implementation.

Objectives: This review aimed to summarise the regenerative methodologies widely used in studies involving autologous and allogenic DPSC/SHED transplantation and their clinical outcomes, analyse the discrepancies between preclinical and clinical studies, explore the potential mechanisms underlying alloimmune responses in allogeneic cell transplantation and provide possible strategies to minimise this type of immune rejection.

Methods: A comprehensive search was conducted on clinicaltrials.gov using keywords '(dental pulp stem cells) OR (dental pulp mesenchymal cells) OR (DPSCs) OR (human deciduous teeth stem cells) OR (stem cells from human exfoliated teeth) OR (SHED),' followed by inputting keywords '(NestaCell) OR (Cellavita HD).' Clinical trials not registered on the website and case reports were also included via advanced search on PubMed using keywords '(dental pulp stem cells) OR (dental pulp mesenchymal cells) OR (DPSCs) OR (human deciduous teeth stem cells) OR (stem cells from human exfoliated teeth) OR (SHED)' with filters '(Case reports) AND (Clinical trial).'

Results: Twenty-seven clinical trials and 11 case reports were included. Whereas these studies related to endodontic diseases revealed favourable outcomes for teeth treated with pulp regeneration approaches, preclinical studies observed limited cell survival in vivo, indicating that DPSCs exhibit environment-dependent immunogenicity and immunoregulatory properties under favourable conditions but become immunogenic in stressful microenvironments such as cell passage and differentiation, hypoxia and inflammation. Potential strategies have been developed to prolong DPSC survival.

Conclusions: Despite encouraging preliminary results, significant limitations remain in the establishment of standardised protocols and the development of reliable techniques for longitudinal cell tracking. In future research, optimised delivery systems, immune-evasive cell engineering and rigorous clinical trial designs should be optimised to advance REPs towards predictable, clinically viable therapies.

背景:基于细胞的再生牙髓治疗(REPs)使用牙髓干细胞(DPSCs)、人类脱落乳牙(SHEDs)和根尖乳头的干细胞已经显示出巨大的牙髓再生潜力,临床前研究报告和有限的临床试验都证明了这一点。然而,挑战,如低细胞存活率,免疫排斥在异体移植和不一致的协议,阻碍了其广泛的临床应用。目的:本综述旨在总结在自体和异体DPSC/SHED移植研究中广泛使用的再生方法及其临床结果,分析临床前和临床研究之间的差异,探讨异体细胞移植中同种免疫反应的潜在机制,并提供可能的策略来减少这种免疫排斥反应。方法:在clinicaltrials.gov网站上输入关键词“(牙髓干细胞)或(牙髓间充质细胞)或(DPSCs)或(人乳牙干细胞)或(人去角质牙齿干细胞)或(SHED)”进行全面搜索,然后输入关键词“(NestaCell)或(Cellavita HD)”。未在网站上注册的临床试验和病例报告也包括在PubMed上使用关键词“(牙髓干细胞)或(牙髓间充质细胞)或(DPSCs)或(人类乳牙干细胞)或(人类脱落牙齿干细胞)或(SHED)”(带过滤器)(病例报告)和(临床试验)进行高级搜索。结果:纳入27项临床试验和11例病例报告。尽管这些与牙髓疾病相关的研究揭示了牙髓再生方法治疗牙齿的有利结果,但临床前研究观察到体内细胞存活有限,表明DPSCs在有利条件下表现出环境依赖性免疫原性和免疫调节特性,但在细胞传代和分化、缺氧和炎症等应激微环境中会变得免疫原性。已经开发出延长DPSC存活的潜在策略。结论:尽管初步结果令人鼓舞,但在建立标准化方案和开发可靠的纵向细胞跟踪技术方面仍然存在重大局限性。在未来的研究中,优化的递送系统、免疫逃避细胞工程和严格的临床试验设计应该得到优化,以推动REPs朝着可预测的、临床可行的治疗方向发展。
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引用次数: 0
Intentional Negotiation and Filling of Accessory Canals: A Case Series With Three-Dimensional Segmentation and Volumetric Healing Assessment. 有意协商和填充副管:一个三维分割和体积愈合评估的病例系列。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-04 DOI: 10.1111/iej.70079
Lucas Pinto Carpena, Gabriel Lima Braz, Henrique Timm Vieira, Nadia de Souza Ferreira

Introduction: Accessory canals (ACs) are anatomical features that may harbour residual infected tissue and contribute to persistent periradicular inflammation. Although filling of these structures is occasionally achieved passively, their intentional mechanical negotiation remains rarely documented in clinical practice. This case series aims to describe the clinical approach, outcomes and imaging strategies used in the intentional debridement and filling of ACs.

Methods: Six teeth with identifiable ACs on cone-beam computed tomography (CBCT), in association with bone resorption, were included. All cases underwent chemomechanical preparation using rotary instrumentation with 2% chlorhexidine gel, active saline irrigation and final EDTA activation with passive ultrasonic irrigation. Intentional mechanical debridement of ACs was performed using small-diameter hand files. All fillings were performed with gutta-percha and AH Plus Jet sealer. Follow-up was performed using CBCT and periapical radiographs after a mean period of 10.16 months. Three-dimensional segmentation was used to aid localization and planning.

Results: All ACs were successfully negotiated and filled with endodontic sealer. Tomographic analysis confirmed evidence of partial or complete periradicular healing in all six cases. No patients presented with clinical symptoms at follow-up.

Conclusion: This case series presents successful intentional instrumentation and obturation of ACs, supported by CBCT-based planning and follow-up. Although limited by the lack of a control group, the findings highlight the potential role of CBCT imaging and segmentation in identifying and accessing complex anatomy. Further prospective studies are needed to determine the impact of this approach on long-term clinical outcomes.

副管(ACs)是一种解剖学特征,可能含有残留的感染组织,并导致持续的根周炎症。虽然这些结构的填充偶尔是被动实现的,但在临床实践中,它们的有意机械协商仍然很少有记录。本病例系列旨在描述有意清创和填充ACs的临床方法,结果和影像学策略。方法:采用锥束计算机断层扫描(CBCT)对6颗与骨吸收相关的可识别ACs的牙齿进行分析。所有病例均采用旋转仪器进行化学力学准备,2%氯己定凝胶,活性生理盐水冲洗,最终EDTA活化被动超声冲洗。采用小直径手锉对ACs进行有意机械清创。所有的填充都是用杜仲胶和AH Plus喷气式封口机进行的。随访时间平均为10.16个月,采用CBCT和根尖周x线片。三维分割用于帮助定位和规划。结果:所有牙髓孔均顺利通断并充填根管封闭剂。断层扫描分析证实了所有6例根周部分或完全愈合的证据。随访时无患者出现临床症状。结论:本病例系列展示了在基于cbct的计划和随访的支持下,ACs的有意置入和封闭成功。尽管由于缺乏对照组,研究结果强调了CBCT成像和分割在识别和获取复杂解剖结构方面的潜在作用。需要进一步的前瞻性研究来确定这种方法对长期临床结果的影响。
{"title":"Intentional Negotiation and Filling of Accessory Canals: A Case Series With Three-Dimensional Segmentation and Volumetric Healing Assessment.","authors":"Lucas Pinto Carpena, Gabriel Lima Braz, Henrique Timm Vieira, Nadia de Souza Ferreira","doi":"10.1111/iej.70079","DOIUrl":"https://doi.org/10.1111/iej.70079","url":null,"abstract":"<p><strong>Introduction: </strong>Accessory canals (ACs) are anatomical features that may harbour residual infected tissue and contribute to persistent periradicular inflammation. Although filling of these structures is occasionally achieved passively, their intentional mechanical negotiation remains rarely documented in clinical practice. This case series aims to describe the clinical approach, outcomes and imaging strategies used in the intentional debridement and filling of ACs.</p><p><strong>Methods: </strong>Six teeth with identifiable ACs on cone-beam computed tomography (CBCT), in association with bone resorption, were included. All cases underwent chemomechanical preparation using rotary instrumentation with 2% chlorhexidine gel, active saline irrigation and final EDTA activation with passive ultrasonic irrigation. Intentional mechanical debridement of ACs was performed using small-diameter hand files. All fillings were performed with gutta-percha and AH Plus Jet sealer. Follow-up was performed using CBCT and periapical radiographs after a mean period of 10.16 months. Three-dimensional segmentation was used to aid localization and planning.</p><p><strong>Results: </strong>All ACs were successfully negotiated and filled with endodontic sealer. Tomographic analysis confirmed evidence of partial or complete periradicular healing in all six cases. No patients presented with clinical symptoms at follow-up.</p><p><strong>Conclusion: </strong>This case series presents successful intentional instrumentation and obturation of ACs, supported by CBCT-based planning and follow-up. Although limited by the lack of a control group, the findings highlight the potential role of CBCT imaging and segmentation in identifying and accessing complex anatomy. Further prospective studies are needed to determine the impact of this approach on long-term clinical outcomes.</p>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":" ","pages":""},"PeriodicalIF":7.1,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparing the Bioactive Effects of Ethylenediaminetetraacetic Acid and Maleic Acid on TGF-β1 Release From Dentine and Dental Pulp Stem Cell Activity 比较乙二胺四乙酸和马来酸对牙本质TGF-β1释放和牙髓干细胞活性的生物活性影响。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-04 DOI: 10.1111/iej.70075
Adithya Subramanya, Sundeep Mata, Rajkumar Narkedamalli, Vijetha Shenoy Belle, Anandh Dhanushkodi, Henry F. Duncan, Vinutha Bhat, Nidambur Vasudev Ballal

Aim

The success of vital pulp treatment (VPT) has been linked to the release of growth factors (GFs) from the dentine matrix, which stimulate dental pulp stem cell (DPSC) activities. Ethylenediaminetetraacetic acid (EDTA) is a commonly used chelating agent that induces the release of GFs bound in the dentine matrix. A 7% Maleic acid (MA) solution has been shown to have better smear layer removal capability and less cytotoxicity compared with 17% EDTA. However, no study has evaluated the effect of 7% MA on the release of GFs from circumpulpal dentine and subsequent DPSC behaviour. This study aimed to evaluate the effect of 17% EDTA and 7% MA conditioning of circumpulpal dentine on the release of transforming growth factor-β1 (TGF-β1), as well as the DPSC activities.

Methodology

Dentine slices treated with phosphate-buffered saline (PBS) acted as the control, while the experimental groups comprised 17% EDTA and 7% MA. The release of TGF-β1 was quantified using ELISA following treatment with the experimental solutions. DPSC proliferation was evaluated with the MTT assay, cell migration was assessed through scratch wound and transwell migration assays. Osteogenic differentiation potential of DPSCs was verified using Alizarin Red staining and an alkaline phosphatase (AP) activity assay.

Results

7% MA induced the highest release of TGF-β1 compared with 17% EDTA and PBS (p < 0.001). 7% MA at 1/1000 dilution significantly increased DPSC proliferation compared with 17% EDTA and PBS (p < 0.001). The scratch wound healing and transwell migration assays demonstrated superior DPSC migration in the 7% MA compared with the 17% EDTA group (p < 0.001). Alizarin Red staining and quantification indicated the highest formation of mineralized nodules in the 7% MA compared with the 17% EDTA group (p < 0.0001). The AP activity assay showed similar enzyme activity in 7% MA and 17% EDTA treated samples.

Conclusions

Within the limitations of this study 7% MA performed better than 17% EDTA in promoting TGF-β1 release from dentine, as well as increased DPSC responses related to cell proliferation, migration, and mineralisation. These findings indicate that 7% MA may be a promising dentine conditioning agent during VPT procedures.

目的:重要牙髓治疗(VPT)的成功与牙本质基质中生长因子(GFs)的释放有关,生长因子可以刺激牙髓干细胞(DPSC)的活性。乙二胺四乙酸(EDTA)是一种常用的螯合剂,可诱导结合在牙本质基质中的GFs释放。与17% EDTA相比,7%马来酸(MA)溶液具有更好的涂抹层去除能力和更低的细胞毒性。然而,没有研究评估7% MA对牙髓周围牙本质中GFs释放和随后的DPSC行为的影响。本研究旨在评价17% EDTA和7% MA调理牙髓周围牙本质对转化生长因子-β1 (TGF-β1)释放及DPSC活性的影响。方法:以磷酸盐缓冲盐水(PBS)处理的牙本质切片为对照,实验组为17% EDTA和7% MA。实验溶液处理后,用ELISA法定量检测TGF-β1的释放。MTT法检测DPSC增殖,划痕法和transwell法检测细胞迁移。采用茜素红染色和碱性磷酸酶(AP)活性测定验证了DPSCs的成骨分化潜力。结果:与17% EDTA和PBS相比,7% MA诱导TGF-β1的释放最高(p结论:在本研究的局限性内,7% MA在促进TGF-β1从牙本质释放方面优于17% EDTA,并增加了与细胞增殖、迁移和矿化相关的DPSC反应。这些结果表明,7% MA可能是一种很有前途的牙本质调理剂。
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引用次数: 0
δ-Bismuth Oxide Responsible for Tooth Discolouration—A Laboratory Investigation δ-氧化铋导致牙齿变色的实验室研究。
IF 7.1 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Pub Date : 2025-12-01 DOI: 10.1111/iej.70077
J. Camilleri, P. Zaslansky, N. Ramanan

Aims

To investigate the phase changes of bismuth oxide in contact with sodium hypochlorite responsible for tooth discolouration.

Methodology

Bismuth oxide (monoclinic α−phase; C) was mixed with sodium hypochlorite at 20°C, 37°C, and 60°C (B20, B37, B60) for a period of 24 weeks with weekly refreshing of solutions. The products were imaged by scanning electron and optical microscopy and characterized by thermographic analysis (TGA), phase analysis by X-ray diffraction (XRD) using Bragg Brentano geometry and Pilatus detector, infrared spectroscopy (FT-IR), and X-ray absorption fine structure (XAFS).

Results

The interaction of bismuth oxide with sodium hypochlorite resulted in a change in microstructure and colour. The thermographic assessment showed a change in mass (5%–10% weight change) and colour reversal to the yellow bismuth oxide at ~450°C. Phase changes dependent on temperature were demonstrated with δ-bismuth oxide, sodium bismuthate and bismuth oxychloride formed as by-products at the different temperatures.

Conclusions

The δ-phase bismuth oxide formation led to the material darkening which will cause tooth discolouration in a clinical setting. Due to the phase changes, the material chemistry after the interaction is different from that of the material placed in the tooth. The by-products of the reaction have not been tested for use in patients. It is recommended to ban the use of bismuth oxide from dental materials and other clinical use due to its instability. The clinical guidance for endodontic treatment needs to be changed to reflect this.

目的:研究氧化铋与次氯酸钠接触后引起牙齿变色的物相变化。方法:将氧化铋(单斜α-相;C)与次氯酸钠在20°C、37°C和60°C (B20、B37、B60)下混合24周,每周更换溶液。采用扫描电子显微镜和光学显微镜对产物进行了成像,并采用热分析(TGA)、Bragg Brentano几何和Pilatus探测器的x射线衍射(XRD)、红外光谱(FT-IR)和x射线吸收精细结构(XAFS)对产物进行了表征。结果:氧化铋与次氯酸钠的相互作用导致了微观结构和颜色的变化。热成像评估显示质量变化(5%-10%的重量变化),并且在~450°C时颜色逆转为黄色氧化铋。在不同的温度下生成了δ-氧化铋、铋酸钠和氯化氧化铋等副产物。结论:δ相氧化铋的形成导致材料变暗,在临床上会导致牙齿变色。由于相变,相互作用后的材料化学性质与放置在牙齿中的材料不同。该反应的副产物尚未在患者身上进行试验。由于氧化铋的不稳定性,建议禁止在牙科材料和其他临床用途中使用。牙髓治疗的临床指导需要改变以反映这一点。
{"title":"δ-Bismuth Oxide Responsible for Tooth Discolouration—A Laboratory Investigation","authors":"J. Camilleri,&nbsp;P. Zaslansky,&nbsp;N. Ramanan","doi":"10.1111/iej.70077","DOIUrl":"10.1111/iej.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the phase changes of bismuth oxide in contact with sodium hypochlorite responsible for tooth discolouration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methodology</h3>\u0000 \u0000 <p>Bismuth oxide (monoclinic α−phase; C) was mixed with sodium hypochlorite at 20°C, 37°C, and 60°C (B20, B37, B60) for a period of 24 weeks with weekly refreshing of solutions. The products were imaged by scanning electron and optical microscopy and characterized by thermographic analysis (TGA), phase analysis by X-ray diffraction (XRD) using Bragg Brentano geometry and Pilatus detector, infrared spectroscopy (FT-IR), and X-ray absorption fine structure (XAFS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The interaction of bismuth oxide with sodium hypochlorite resulted in a change in microstructure and colour. The thermographic assessment showed a change in mass (5%–10% weight change) and colour reversal to the yellow bismuth oxide at ~450°C. Phase changes dependent on temperature were demonstrated with δ-bismuth oxide, sodium bismuthate and bismuth oxychloride formed as by-products at the different temperatures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The δ-phase bismuth oxide formation led to the material darkening which will cause tooth discolouration in a clinical setting. Due to the phase changes, the material chemistry after the interaction is different from that of the material placed in the tooth. The by-products of the reaction have not been tested for use in patients. It is recommended to ban the use of bismuth oxide from dental materials and other clinical use due to its instability. The clinical guidance for endodontic treatment needs to be changed to reflect this.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"59 3","pages":"538-548"},"PeriodicalIF":7.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12884216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145648493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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International endodontic journal
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