Introduction and Aims Ranula is a mucus retention cyst originating from the sublingual gland, and surgical intervention has traditionally been the main treatment. However, surgery is often associated with recurrence, risk of nerve injury, and patient discomfort. Sclerotherapy using polidocanol, a low-toxicity agent, has emerged as a promising minimally invasive alternative. This study aimed to evaluate the clinical outcomes and safety of polidocanol injection therapy in patients with sublingual ranula. Methods This retrospective study included 34 patients with sublingual ranula who underwent intralesional injection of 3% polidocanol between December 2021 and March 2025. Some patients with large or recurrent lesions were additionally treated with pingyangmycin. Clinical data including age, sex, lesion size, symptom duration, number of injections, and follow-up time were collected. Treatment outcomes were categorized as complete resolution or unfavorable outcomes (including partial remission or recurrence). Statistical analyses were performed to identify factors associated with treatment outcomes. Results Among the 34 patients, 30 (88.2%) achieved complete resolution, while 4 (11.8%) had unfavorable outcomes. Maximum lesion diameter was independently associated with treatment outcome (adjusted OR per 1-mm increase = 0.886, 95% CI: 0.742-0.982; P = .018; Firth-penalized logistic regression adjusted for age and lesion site). No serious complications were observed during a mean follow-up of 22.44 ± 14.93 months. Conclusion Polidocanol injection therapy appears to be a safe and minimally invasive option for the management of sublingual ranula, demonstrating favorable clinical outcomes and a high rate of lesion resolution in this retrospective cohort. Clinical Relevance Polidocanol sclerotherapy offers a conservative outpatient treatment option for sublingual ranula, providing favorable clinical outcomes with low morbidity and potentially reducing the need for surgical excision.

Infantile hemangioma (IH), the most common vascular tumor of infancy, relies on hemangioma stem cells (HemSCs) to drive pathological vasculogenesis during the proliferating phase. While beta-blockers are currently first-line treatment for IH, resistance and rebound growth necessitates novel strategies. Here, we identify histone deacetylase inhibitors (HDACi) as a potential epigenetic drug for IH. The pan-HDAC inhibitor SAHA significantly suppresses in vivo vasculogenesis in a murine IH model. Mechanistically, SAHA selectively blocks the differentiation of HemSCs into pericytes by destabilizing NOTCH3 protein through acetylation-primed ubiquitination and proteasomal degradation, thus disrupting perivascular support which is indispensable for IH vasculogenesis. Furthermore, the blockade of pericyte differentiation by SAHA synergizes with propranolol, which inhibits endothelial differentiation of HemSCs, in a complementary manner. Additionally, SAHA promotes adipogenic differentiation of HemSCs and accelerates IH involution. Collectively, our work highlights the clinical significance of cell fate determination during IH progression, and establishes HDAC inhibition as a novel therapeutic option for IH through targeting pericyte differentiation of HemSCs, which provides a promising enhancement to current treatment strategies of refractory IH.

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor that typically presents in infancy or early childhood. As awareness of KHE increases, it is imperative that the management of KHE be updated to reflect the latest evidence-based guidelines. The aim of this study was to integrate the literature and Chinese expert opinions to provide updated recommendations that will guide the diagnosis, treatment, and prognosis of patients with KHE. According to this consensus statement, 28 nationally peer-recognized experts in vascular anomalies and an expert in evidence-based medicine were assembled and formed three consensus subgroups. A series of key themes and questions were developed for each group, including recommendations for diagnosis, treatment, and prognosis. A systematic search was conducted for English-language articles published in PubMed and other relevant studies identified by the expert panel. A diagnosis of KHE necessitates the integration of clinical, imaging, and histologic features. The treatment of KHE should be tailored to the specific characteristics of each patient, including the size of the lesion, the presence of symptoms, the location, and the overall condition of the patient. In addition to focusing on the disease itself, it is also important to consider the complications of KHE and their impact on prognosis. The recommendations presented herein are intended to assist in the guidance of clinical practice and decision-making in patients with KHE, with the objective of improving patient outcomes.

Oral and maxillofacial region is the most common site for the onset of vascular anomalies.Some vascular anomalies can lead to bleeding,which may be the first noticeable symptom.Due to the rich blood supply and the proximi-ty to the respiratory tract,bleeding in this area is particularly challenging to manage.If not treated promptly or if inappro-priate methods are used,they may result in serious complications.To address this issue,we invited a group of domestic experts with extensive experience in diagnosing and treating vascular anomalies in oral and maxillofacial region to formu-late this consensus.The goal is to provide guidance and recommendations for medical professionals on the management of bleeding associated with these vascular lesions.

Infantile hemangioma (IH) affects 5-10% of all infants and up to 30% of premature newborns. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of IH in humans. In this study, we performed single-cell RNA sequencing on hemangioma samples from 3 infants diagnosed with IH. A total of 36,237 high-quality cells were clustered into 10 major cell types, including endothelial cells and hemangioma mural cells. Endothelial cells in IH exhibit strong proliferative capacity and heterogeneity. Furthermore, cell-cell communication analysis and immunofluorescence colocalization revealed that hemangioma mural cells, which constitute >50% of IH, can release ligands such as VEGFA and PGF and act on endothelial cells, thus promoting endothelial cell proliferation and angiogenesis. We also found that the expression levels of VEGFA and Ki-67 are significantly higher in IH than in normal infant skin tissue. Finally, we also found that adrenaline receptor beta 1 is specifically expressed in EC1 and EC2, adrenaline receptor beta 2 is specifically expressed in EC3, and adrenoceptor alpha is specifically expressed in hemangioma mural cells. In summary, our study provides a cellular atlas of proliferative-phase IH and reveals the important roles of endothelial cells and hemangioma mural cells in the development of IH.

Infantile hemangioma (IH) is the most prevalent vascular tumor during infancy, characterized by a rapid proliferation phase of disorganized blood vessels and spontaneous involution. IH possibily arises from a special type of multipotent stem cells called hemangioma stem cells (HemSCs), which could differentiate into endothelial cells, pericytes, and adipocytes. However, the underlying mechanisms that regulate the cell fate determination of HemSCs remain elusive. Here, we unveil KLF2 as a candidate transcription factor involved in the control of HemSCs differentiation. KLF2 exhibits high expression in endothelial cells in proliferating IH but diminishes in adipocytes in involuting IH. Using a combination of in vitro culture of patient-derived HemSCs and HemSCs implantation mouse models, we show that KLF2 governs the proliferation, apoptosis and cell cycle progression of HemSCs. Importantly, KLF2 acts as a crucial determinant of HemSCs' fate, directing their differentiation toward endothelial cells while inhibiting adipogenesis. Knockdown of KLF2 induces a pro-adipogenic transcriptome in HemSCs, leading to impaired blood vessel formation and accelerated adipocyte differentiation. Collectively, our findings highlight KLF2 as a critical regulator controlling the progression and involution of IH by modulating HemSCs' cell fate decisions.

Proline 4-hydroxylase 2 (P4HA2) is known for its hydroxylase activity, primarily involved in hydroxylating collagen precursors and promoting collagen cross-linking under physiological conditions. Although its overexpression influences a wide variety of malignant tumors' occurrence and development, its specific effects and mechanisms in oral squamous cell carcinoma (OSCC) remain unclear. This study focused on investigating the expression patterns, carcinogenic functions, and underlying mechanisms of P4HA2 in OSCC cells. Various databases, including TCGA, TIMER, UALCAN, GEPIA, and K-M plotter, along with paraffin-embedded samples, were used to ascertain P4HA2 expression in cancer and its correlation with clinicopathological features. P4HA2 knockdown and overexpression cell models were developed to assess its oncogenic roles and mechanisms. The results indicated that P4HA2 was overexpressed in OSCC and inversely correlated with patient survival. Knockdown of P4HA2 suppressed invasion, migration, and proliferation of OSCC cells both in vitro and in vivo, whereas overexpression of P4HA2 had the opposite effects. Mechanistically, the phosphorylation levels of the PI3K/AKT pathway were reduced following P4HA2 silencing. The study reveals that P4HA2 acts as a promising biomarker for predicting prognosis in OSCC and significantly affects metastasis, invasion, and proliferation of OSCC cells through the regulation of the PI3K/AKT signaling pathway.

As the most common benign vascular tumor in infants, infantile hemangioma (IH) is characterized by rapid growth and vasculogenesis early in infancy, followed by spontaneous involution into fibrofatty tissues over time. Extensive evidence suggests that IH originates from hemangioma stem cells (HemSCs), a group of stem cells with clonal expansion and multi-directional differentiation capacity. However, the intricate mechanisms governing the cell fate transition of HemSCs during IH development remain elusive. Here we comprehensively examine the cellular composition of IH, emphasizing the nuanced properties of various IH cell types and their correlation with the clinical features of the tumor. We also summarize the current understanding of the regulatory pathways directing HemSC differentiation into endothelial cells (ECs), pericytes, and adipocytes throughout the stages of IH progression and involution. Furthermore, we discuss recent advances in unraveling the transcriptional and epigenetic regulation of EC and adipocyte development under physiological conditions, which offer crucial perspectives for understanding IH pathogenesis.

Geranylgeranyltransferase type I (GGTase-I) significantly affects Rho proteins, such that the malignant progression of several cancers may be induced. Nevertheless, the effect and underlying mechanism of GGTase-I in the malignant progression of salivary adenoid cystic carcinoma (SACC) remain unclear. This study primarily aimed to investigate the role and mechanism of GGTase-I in mediating the malignant progression of SACC. The level of GGTase-I gene in cells was stably knocked down by short hairpin RNA-EGFP-lentivirus. The effects of GGTase-I silencing on the migration, invasion, and spread of cells were examined, the messenger RNA levels of GGTase-I and RhoA genes of SACC cells after GGTase-I knockdown were determined, and the protein levels of RhoA and RhoA membrane of SACC cells were analyzed. Moreover, the potential underlying mechanism of silencing GGTase-I on the above-mentioned aspects in SACC cells was assessed by examining the protein expression of ROCK1, MLC, p-MLC, E-cadherin, Vimentin, MMP2, and MMP9. Furthermore, the underlying mechanism of SACC cells proliferation was investigated through the analysis of the expression of cyclinD1, MYC, E2F1, and p21CIP1/WAF1. Besides, the change of RhoA level in SACC tissues compared with normal paracancer tissues was demonstrated through quantitative reverse-transcription polymerase chain reaction and western blot experiments. Next, the effect after GGTase-I silencing was assessed through the subcutaneous tumorigenicity assay. As indicated by the result of this study, the silencing of GGTase-I significantly reduced the malignant progression of tumors in vivo while decreasing the migration, invasion, and proliferation of SACC cells and RhoA membrane, Vimentin, ROCK1, p-MLC, MMP2, MMP9, MYC, E2F1, and CyclinD1 expression. However, the protein expression of E-cadherin and p21CIP1/WAF1 was notably upregulated. Subsequently, no significant transform of RhoA and MLC proteins was identified. Furthermore, RhoA expression in SACC tissues was significantly higher than that in paracancerous tissues. As revealed by the results of this study, GGTase-I shows a correlation with the proliferation of SACC through the regulation of cell cycle and may take on vital significance in the migration and invasion of SACC by regulating RhoA/ROCK1/MLC signaling pathway. GGTase-I is expected to serve as a novel exploration site of SACC.

Senescence of bone marrow mesenchymal stem cells (BMMSCs) induced by chronic oxidative stress is an important factor contributes to the postmenopausal osteoporosis (PMOP). Mitochondrial quality control takes a pivotal role in regulating oxidative stress and cell senescence. Genistein is a major isoflavone in soy products, which is best known for its ability to inhibit bone loss in both postmenopausal women and ovariectomized (OVX) rodents. Here we show that OVX-BMMSCs displayed premature senescence, elevated reactive oxygen species (ROS) level and mitochondria dysfunction, while genistein rescued these phenotypes. Using network pharmacology and molecular docking, we identified estrogen-related receptor α (ERRα) as the potential target of genistein. Knockdown of ERRα greatly abolished the anti-senescence effect of genistein on OVX-BMMSCs. Further, the mitochondrial biogenesis and mitophagy induced by genistein were inhibited by ERRα knockdown in OVX-BMMSCs. In vivo, genistein inhibited trabecular bone loss and p16INK4a expression, upregulated sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor gamma coactivator one alpha (PGC1α) expression in the trabecular bone area of proximal tibia in OVX rats. Together, this study revealed that genistein ameliorates senescence of OVX-BMMSCs through ERRα-mediated mitochondrial biogenesis and mitophagy, which provided a molecular basis for advancement and development of therapeutic strategies against PMOP.

Most of the patients with oral and maxillofacial malignancy are in the middle and advanced stages at diagnosis and the incidence rate is increasing in recent years. Chemotherapy alone is difficult to benefit the survival of patients with advanced oral and maxillofacial malignancy. Ultrasound hyperthermia is a new and effective treatment for malignant tumor, which is developing rapidly in addition to conventional treatment. However, at present, ultrasound hyperthermia has not been widely used in the treatment of oral and maxillofacial malignancy. Therefore, formation of a guideline on ultrasound hyperthermia for oral and maxillofacial malignancy is mandatory, in order to promote and standardize the clinical practice of ultrasound hyperthermia in this field, and improve the long-term survival rate and quality of life of patients.

脉管异常类疾病是一组疾病的总称,国际脉管异常研究学会(ISSVA)将其分为2大类:脉管肿瘤和脉管畸形.本文结合脉管异常类疾病的分子病理学表现,对其遗传学改变的最新研究成果加以总结.在球形静脉畸形中,突变的球蛋白可能通过与c-met的相互作用激活PI3K信号.此外,它们可能抑制TGF-β介导的平滑肌细胞分化,并诱导所谓的血管球细胞增殖.淋巴管畸形中的PIK3CA突变可能刺激VEGF-C或VEGFR3表达,诱导PIK3CA与细胞膜结合;或通过激活下游Akt/mTOR,促进细胞增殖、趋化性和血管生成.动静脉畸形中的RAS通路突变可能激活MEK/ERK信号,RAS激活可能诱导内皮细胞形态变化、出芽行为增加、血管管腔扩大以及动脉和静脉之间异常连接而不伴有细胞增殖.婴幼儿血管瘤中VEGFR2和TEM8突变导致VEGFR2、TEM8和整合素之间的相互作用增加,由此导致整合素/NFATc2/VEGFR1通路失活,导致VEGFR2磷酸化和内皮活化.

EDITORIAL article Front. Oncol., 16 June 2023Sec. Pediatric Oncology Volume 13 - 2023 | https://doi.org/10.3389/fonc.2023.1229197

Background:Infantile hemangioma (IH) is the most common benign vascular tumor of infancy and is proposed to arise from hemangioma stem cells (HemSCs). Therapies for IH include oral beta-blockers, surgery, and the delivery of novel therapeutic agents, such as bioactive microRNAs (miRNAs). However, in the extracellular environment, miRNA is easily hydrolyzed by RNase. miR-187-3p has previously been confirmed to promote or inhibit various malignancies, but its role in the development and progression of IH remains unclear.Methods:In this study, engineered exosomes (E-exos) were exploited to deliver miR-187-3p into HemSCs. The E-exos were generated by introducing miR-187-3p mimics into human adipose mesenchymal stem cell-derived exosomes (hAMSC-exos) via electroporation. The expression and secretion of miR-187-3p were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis, transmission electron microscopy (TEM), and dynamic light scattering (DLS) were used to characterize the exosomes. The effects of the E-exos on HemSC viability were examined using the tube formation assay and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Western blot analysis was used to evaluate the effects of E-exos on Notch-1, Notch-4, and Jagged-1 expression in HemSCs.Results:E-exos did not differ significantly from hAMSC-exos in terms of morphology, particle size, or surface markers. E-exos could be internalized by HemSCs, and the course of cellular uptake of E-exos was time dependent. After 12 hours of treatment, E-exos significant inhibited tube formation. Notch signaling was also inhibited by miR-187-3p loading by E-exos. E-exos showed excellent inhibitory effects against HemSC proliferation via Notch signaling.Conclusions:This study provides a foundation for using hAMSC-exos to optimize current clinical options to facilitate IH treatment and deliver therapeutic agents in the future.

Background: Sclerotherapy is the first-line therapeutic method for lymphatic malformations (LMs). This retrospective cohort study evaluated the effectiveness and safety of a novel combined foam sclerosant: polidocanol and pingyangmycin foam (PPF), for treating cervicofacial macrocystic LMs.Methods and Results: From July 2018 to October 2020, 51 patients with cervicofacial macrocystic LMs were enrolled in this study. All patients received intralesional 3% polidocanol or PPF injections. The outcome was evaluated regarding demographic and clinical characteristics, degree of treatment response, and post-treatment complications. Overall, 16 patients (31.4%) underwent PPF sclerotherapy. All these patients (100%) showed remarkable reduction in lesion size within three sessions. Excellent responses were shown in 88.5% of these patients within three sessions, which is higher than single polidocanol sclerotherapy (80%). The average sessions (duration) of PPF sclerotherapy were 2.5, which was significantly shorter than the single foam sclerotherapy (p < 0.05). Treatment duration was significantly associated with age, lesion location, lesion size, and number of cysts (p < 0.05). No severe complications were noted in this study. Local or systemic complications, such as swelling and mild fever occurred but subsided without any specific treatment.Conclusions: PPF is a safe, and effective combined foam sclerosant for the treatment of cervicofacial macrocystic LMs. This combined foam can improve treatment response and reduce treatment duration compared with a single sclerosant. It can be broadly used if further large-scale clinical trials verify its efficacy and safety.

目的:探讨selumetinib对神经纤维瘤相关施万细胞中YAP功能状态的影响,分析和评价联合靶向YAP及MEK1/2对施万细胞生长的体外抑制作用.方法:采用慢病毒转染构建NF1敲低的大鼠施万细胞模型,通过Western免疫印迹、RT-PCR方法验证敲低效率,结合免疫荧光染色,评估YAP蛋白的表达水平及功能状态.利用siRNA敲低YAP的表达.通过CCK-8实验检测不同药物(YAP抑制剂veteporfin、MEK1/2抑制剂selumetinib)处理条件下肿瘤细胞的增殖活性,平板克隆和微球形成实验观察不同处理条件下肿瘤细胞的体外肿瘤形成能力.根据Chou-Talalay法开展selumetinib和Veteporfin的联合指数分析.采用GraphPad Prism 8软件包对数据进行统计学分析.结果:成功构建了Nf1基因沉默的施万细胞模型(shNf1-RSC96),证实selumetinib促进神经纤维瘤相关施万细胞的YAP转录活性.进一步抑制YAP基因表达后,selumetinib对shNf1-RSC96细胞增殖的抑制作用得到显著增强.联合靶向抑制YAP及MEK1/2,Veteporfin增强selumetinib对肿瘤细胞活性的抑制并具有协同效应.结论:干预神经纤维瘤相关施万细胞中YAP的核易位及转录激活过程,可增强selumetinib对细胞增殖的抑制作用,联合靶向抑制YAP及MEK1/2可能是NF1相关神经纤维瘤潜在的治疗策略.

目的 对口腔专业本科生提早接触临床与临床前导师制课程进行教学效果的评估与教学反思.方法 调查上海交通大学口腔医学院2013级至2018级口腔医学专业全体学生共279名:2016、2017、2018级学生为试验组(实施《患者与医师》课程),人数依次为48、60、60人;2013、2014、2015级学生为对照组(未实施《患者与医师》课程),人数依次为39、39、33人.分别对两组同学以问卷调查的形式在课程作用、课程设置、学时数安排合理性,两组学生的未来科室选择倾向性,课程的局限性等方面进行反馈.应用SPSS 25.0软件包对数据进行统计学分析.结果 试验组学生对课程的认可度和自主积极性较高,多数学生能在2～3个科室中决定自己未来希望从事和发展的方向.对照组学生均有意愿参与该课程的学习,并认为此课程能为自己的临床实习提供一定帮助.在培养兴趣、建立工作认知和提高人文关怀意识等方面的课程作用评价中,两组学生的反馈差异有统计学意义(P＜0.05);两组学生均认为该课程与其他临床见习课有所区别;两组学生在期望的见习次数上有显著性差异(P＜0.05).结论 依托于《患者与医师》课程的口腔专业提早接触临床与临床前导师制的教学模式是基于临床早接触课程的延伸和拓展,学生对该课程的认可度较高,且比较之下发现在激发学习兴趣、协调临床与科研、增进人文关怀意识等方面的教学效果较为优异,相较基础早接触课程有较大优势.本调研的反馈与已积累的教学经验有利于进一步提高课程质量.

OBJECTIVE:This research investigated the biological role of isoprenylcysteine carboxyl methyltransferase (ICMT) in tongue squamous cell carcinoma (TSCC) progression meanwhile to explore the conceivable mechanism.METHODS:The mRNA and protein expression were measured using real-time PCR and Western blot. Cell proliferation, apoptosis, cycle distribution, migration and invasion were evaluated by CCK-8 assay, flow cytometry, wound-healing assay and transwell assay. The anti-tumor activity of ICMT silencing was observed in nude mice.RESULTS:Our results indicated that silencing of ICMT-mediated methylation effectively inhibited TSCC cells proliferation in vitro and reduced tumor growth in vivo. Moreover, ICMT knockdown also induced cell apoptosis and cell cycle arrest of both CAL-27 and SCC-4 cells. In addition, CAL-27 and SCC-4 cells migration and invasion were weakened by ICMT siRNA. Mechanistically, ICMT deficiency significantly decreased the K-Ras and RhoA membrane targeting localization, leading to the suppression of K-Ras- and RhoA-mediated downstream signaling in CAL-27 and SCC-4 cells.CONCLUSIONS:Altogether, our findings identified a crucial role played by ICMT in the progression of TSCC and the potential mechanisms by which exerted its effects, indicating that targeting ICMT may represent a promising therapeutic strategy for TSCC.

围手术期血糖水平异常现象是影响患者预后的重要因素.目前,已有较多关于外科手术围手术期血糖管理指南,但对于口腔颌面外科手术围手术期血糖异常情况尚未有规范的管理方案.根据已发表的相关指南、共识及文献,并结合颌面外科的特点及我们的经验,本文主要从术前高血糖的筛查、评估,术中血糖安全管理,术后血糖水平的监测及治疗等方面规范了标准化血糖管理操作规程,为颌面外科围手术期血糖管理提供参考.

婴幼儿血管瘤是儿童期最常见的良性肿瘤,目前主张早期予以干预,以减少并发症和对心理发育的负面影响.随着β受体阻滞剂的成功应用,治疗方法发生了革命性变化,治疗效果也随之提高.本文结合文献分析,基于循证医学证据,概述了婴幼儿血管瘤各种治疗方法的适应证、优缺点和选择依据,以期为临床应用提供指导.