Salivary Gland Injury Research Articles

TGFβ2-Driven Ferritin Degradation and Subsequent Ferroptosis Underlie Salivary Gland Dysfunction in Postmenopausal Conditions.

Despite the high incidence of dry mouth in postmenopausal women, its underlying mechanisms and therapeutic interventions remain underexplored. Using ovariectomized (OVX) mouse models, here this study identifies ferroptosis, an iron-dependent regulated cell death, as a central mechanism driving postmenopausal salivary gland (SG) dysfunction. In the OVX-SGs, TGFβ signaling pathway is enhanced with the aberrant TGFβ2 expression in SG mesenchymal cells. Intriguingly, TGFβ2 treatment reduces iron-storing ferritin levels, leading to lipid peroxidation and ferroptotic death in SG epithelial organoids (SGOs). Mechanistically, TGFβ2 promotes the autophagy-mediated ferritin degradation, so-called ferritinophagy. A notable overexpression of the type III TGFβ receptor (TβRIII) is found in the OVX-SGs and TGFβ2-treated SGOs, while the silencing of TβRIII mitigates the ferroptosis-mediated deleterious effects of TGFβ2 on SGOs. Finally, administration of ferroptosis inhibitor, Liproxstatin-1 (Lip-1), improves saliva secretion in OVX mice. Present findings collectively suggest a link between TGFβ signaling, ferroptosis, and SG injury, offering new therapeutic avenues for postmenopausal xerostomia.

The single-strand DNA-binding protein SSB1 is involved in the expression of salivary gland radiation injury repair.

Single-strand DNA-binding protein 1 (SSB1) plays a crucial role in the cellular response to DNA damage. This study aimed to explore the expression and regulation of SSB1 in normal rat salivary gland tissues and tissues following radiation, with a specific emphasis on its involvement in the repair of salivary gland injury. A total of 45 adult SD rats were randomly assigned to one control group or eight experimental groups. In the control group, five rats were euthanized without irradiation, and their parotid gland tissues were collected for analysis. The experimental groups received a dose of 6Gy of radiation targeting the head and neck region; subsequently, five rats from each group were euthanized hly to collect parotid gland tissue samples, resulting in a total of eight experimental groups. The expression levels of SSB1, γ-H2AX, and PARP1 in the parotid gland tissues were assessed via immunohistochemistry, while changes in SSB1 gene expression were quantified via RT-qPCR. No significant morphological differences were observed between the two groups following HE staining. In the immunohistochemistry (IHC) analysis, notable tissue-specific variation in SSB1 expression was identified, with higher levels detected in the ducts than in the acini and connective tissue. The expression of SSB1 gene initially increased post-radiation before subsequently decreasing, ultimately returning to baseline levels, as corroborated by the RT-qPCR results. In contrast, γ-H2AX and PARP1 exhibited minimal expression in the control group; however, their expression peaked at 1h in the experimental group before gradually declining to levels comparable to those of the control group. Radiation induces time-dependent upregulation of SSB1 expression in rat salivary glands, indicating that SSB1 may play a role in radiation-induced repair processes.

Transactivation DNA-binding protein-related genes were associated with salivary gland injury in primary Sjögren syndrome.

The purpose was to identify transactivation DNA-binding protein-related genes in salivary gland injury in primary Sjögren syndrome (pSS) in southwest China. We downloaded the datasets of GSE7451, GSE23117, and GSE40611. In order to screen the candidate genes, 2 kinds of machine learning algorithms were used. We collected blood from 28 patients and 20 controls to verify the expression of candidate genes using quantitative real-time polymerase chain reaction. The receiver operating characteristic curve was used to evaluate the diagnostic efficiency. Correlations between candidate genes and immune cells were examined. A total of 31 differentially expressed genes were obtained. Through different algorithms, 6 genes including IFIT1, CSF2RB, TRIM22, PPM1H, VAMP7, and C21orf2 were getted. Validation results suggested that the expression of CSF2RB, VAMP7, IFIT1, C21orf2, and TRIM22 was significantly increased in pSS. The area under the curve of CSF2RB was 0.937 and that of TRIM22 was 0.915. Immune infiltration analysis showed that the percentage of activated mast cells was lower than the controls (P = .025). Correlation analysis suggested that CSF2RB was associated with immune cell infiltration. The expression of CSF2RB was significantly upregulated, which could be related to the increase of γδ T cells. We revealed that CSF2RB could be the candidate gene of pSS. CSF2RB was involved by regulating various immune cells. The expression of CSF2RB was significantly upregulated, which was related to the increase of γδ T cells.

A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation.

The salivary glands are often damaged during head and neck cancer radiotherapy. This results in chronic dry mouth, which adversely affects quality of life and for which there is no long-term cure. Mouse models of salivary gland injury are routinely used in regenerative research. However, there is no clear consensus on the radiation regime required to cause injury. Here, we analysed three regimes of γ-irradiation of the submandibular salivary gland. Transcriptional analysis, immunofluorescence and flow cytometry was used to profile DNA damage, gland architecture and immune cell changes 3 days after single doses of 10 or 15 Gy or three doses of 5 Gy. Irrespective of the regime, radiation induced comparable levels of DNA damage, cell cycle arrest, loss of glandular architecture, increased pro-inflammatory cytokines and a reduction in tissue-resident macrophages, relative to those observed in non-irradiated submandibular glands. Given these data, coupled with the fact that repeated anaesthetic can negatively affect animal welfare and interfere with saliva secretion, we conclude that a single dose of 10 Gy irradiation is the most refined method of inducing acute salivary gland injury in a mouse model.

Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress.

Radiation-induced salivary gland injury (RISGI) is a common complication of radiotherapy in patients with head and neck cancer. Intragland expression of the Sonic Hedgehog (Shh) gene may partially rescue irradiation (IR)-induced hyposalivation by preserving salivary stem/progenitor cells and parasympathetic innervation, maintaining resident macrophages, and maintaining microvascular density. Previous studies have revealed that Ad-Rat Shh transduction through the salivary glands of miniature pigs can ameliorate oxidative stress-induced microvascular dysfunction after radiotherapy. Changes in the parotid salivary flow rate were analyzed, and the parotid tissue was collected at 5 and 20 weeks after IR. Changes in the Hedgehog pathway and vascular function-related markers (vascular endothelial growth factor (VEGF) and CD31) and oxidative stress-related markers were detected via immunohistochemistry, immunofluorescence, and Western blotting. A stable Shh-overexpressing cell line was generated from human umbilical vein endothelial cells (HUVECs) and exposed to 10 Gy X-ray irradiation, after which endothelial cell proliferation, senescence, apoptosis, and vascular function were evaluated. We found that intragland expression of the Shh gene efficiently alleviated IR-induced parotid gland injury in a miniature pig model. Our results indicate that the antioxidative stress and microvascular-protective effects of the Hh pathway are regulated by nuclear factor-erythroid 2-related factor 2 (Nrf2).

Duct ligation/de-ligation model: exploring mechanisms for salivary gland injury and regeneration.

Sialadenitis and sialadenitis-induced sialopathy are typically caused by obstruction of the salivary gland ducts. Atrophy of the salivary glands in experimental animals caused by duct ligation exhibits a histopathology similar to that of salivary gland sialadenitis. Therefore, a variety of duct ligation/de-ligation models have been commonly employed to study salivary gland injury and regeneration. Duct ligation is mainly characterised by apoptosis and activation of different signaling pathways in parenchymal cells, which eventually leads to gland atrophy and progressive dysfunction. By contrast, duct de-ligation can initiate the recovery of gland structure and function by regenerating the secretory tissue. This review summarizes the animal duct ligation/de-ligation models that have been used for the examination of pathological fundamentals in salivary disorders, in order to unravel the pathological changes and underlying mechanisms involved in salivary gland injury and regeneration. These experimental models have contributed to developing effective and curative strategies for gland dysfunction and providing plausible solutions for overcoming salivary disorders.

MiR-34a promotes mitochondrial pathway of apoptosis in human salivary gland epithelial cells by activating NF-κB signaling

To investigate the potential molecular mechanism of miR-34a in Sjögren's syndrome (SS). Transmission electron microscopy was used to observe the salivary gland tissues of mild and severe SS patients. SS mouse model was constructed and injected with miR-34a antagonist. HSGE cells were transfected with miR-34a mimic. Starbase predicted miR-34a binding sites and validated them with dual-luciferase reporter assays. Immunohistochemistry, HE staining, CCK-8, TUNEL assay, flow cytometry, immunofluorescence and Western Blot were used to investigate the effects of miR-34a on NF-κB signaling and mitochondrial pathway of apoptosis in HSGE cells. Severe SS patients showed obvious mitochondrial damage and apoptosis in salivary glands. MiR-34a was overexpressed and NF-κB signaling is activated in salivary glands of severe SS patients. Inhibition of miR-34a alleviated salivary gland injury in SS mice, as well as inhibited the activation of NF-κB signaling and mitochondrial pathway of apoptosis. In conclusion, miR-34a promoted NF-κB signaling by targeting IκBα, thereby causing mitochondrial pathway apoptosis and aggravating SS-induced salivary gland damage.

Cautery excision of oral mucocele in pediatric children: A case report

Introduction: Oral mucocele is a common, oral lesions that mostly present as painless, clear, or bluish cysts on the lower lip of children and young adults. These are harmless, mucus-filled growths usually resulting from a little salivary gland or duct injury. Mucus can leak into surrounding subepithelial tissue when the salivary glands are injured by lip biting, sucking, or trauma. This is known as a mucus extravasation cyst, and it is the most frequent variety of mucoceles. This report presents two cases of mucocele. Case History: Two case studies of oral mucoceles reported that almost all included lip mucoceles were clinically bullous lesions, it was soft, fluctuant, and palpable, which corroborates the hypothesis that lip mucoceles are commonly incited by traumatic injury such as tooth impingement and lip-biting habit. All cases were treated with a simple excision using an electrocautery. Two lesion diagnosis was confirmed by Histopathology anatomy (HPA). Discussion: Mucoceles are common oral lesions often seen in children and adolescents, typically caused by lip biting due to psychological stress. Diagnosis is based on clinical features such as rapid appearance, size variations, and bluish color. Treatments include scalpel excision and electrocautery, with electrocautery providing minimal bleeding and painless wounds. Conclusion: One of the typical salivary gland lesions in the oral cavity is mucocele. The use of electrocautery is known to be beneficial for wound healing. Awareness education for children and parents is necessary to eliminate a lip-biting habit.

PANoptosis induced by inflammatory cytokines promotes salivary glands radiation injury.

Salivary glands are frequently damaged in patients undergoing radiotherapy for head and neck cancer. Whether PANoptosis, which is characterized by pyroptosis, apoptosis, and necroptosis, occurs during radiation injury to the salivary glands and its role remain unclear. Radiation-induced injury models of mouse submandibular gland, as well as primary acinar cells and HSG cell lines were established to determine the presence of radiation-induced PANoptosis. Several programmed cell death inhibitors, PFTα, disulfiram, Nec-1 and zVAD, were used to compare the effects of different cell death pathway on radiation injury. The LEGENDplex™ Human Inflammation Panel was used to characterize the inflammatory landscape secreted by salivary gland cells after radiotherapy. Single 15Gy or 8Gy radiotherapy triggered PANoptosis in mouse submandibular gland or salivary gland cells. Compared to the suppression of pyroptosis, apoptosis, or necroptosis alone, the inhibition of PANoptosis is more effective in preventing radiation injury to the salivary glands (p < 0.0001). The levels of multiple inflammatory cytokines were significantly up-regulated in the supernatants of HSG cells within 48 h after IR. Neutralizing inflammatory cytokines are capable of inhibiting salivary glands PANoptosis. Inhibition of PANoptosis induced by inflammatory cytokines can effectively prevent radiation injury of salivary glands.

Salivary Organotypic Tissue Culture: An Ex-vivo 3D Model for Studying Radiation-Induced Injury of Human Salivary Glands.

An organotypic tissue culture model canmaintain the cellular and molecular interactions, as well as the extracellular components of a tissue ex vivo. Thus, this 3D modelbiologically mimics in vivo conditions betterthan commonly used 2D culture in vitro models. Here, we provide a detailed workflow for generating live 3Dorganotypic tissue slices from patient-derived freshly resected salivaryglandular tissues. We also cover the processing of these tissues for various downstream applications like live-dead viability/cytotoxicity assay, FFPE sectioning and immunostaining, and RNA and protein extraction with a focus on the salivary gland radiation injury model. These procedures can be applied extensively to various solid organs and used for disease modeling for cancer research, radiation biology, and regenerative medicine.

CSF1R-dependent macrophages in the salivary gland are essential for epithelial regeneration after radiation-induced injury.

The salivary glands often become damaged in individuals receiving radiotherapy for head and neck cancer, resulting in chronic dry mouth. This leads to detrimental effects on their health and quality of life, for which there is no regenerative therapy. Macrophages are the predominant immune cell in the salivary glands and are attractive therapeutic targets due to their unrivaled capacity to drive tissue repair. Yet, the nature and role of macrophages in salivary gland homeostasis and how they may contribute to tissue repair after injury are not well understood. Here, we show that at least two phenotypically and transcriptionally distinct CX3CR1+ macrophage populations are present in the adult salivary gland, which occupy anatomically distinct niches. CD11c+CD206-CD163- macrophages typically associate with gland epithelium, whereas CD11c-CD206+CD163+ macrophages associate with blood vessels and nerves. Using a suite of complementary fate mapping systems, we show that there are highly dynamic changes in the ontogeny and composition of salivary gland macrophages with age. Using an in vivo model of radiation-induced salivary gland injury combined with genetic or antibody-mediated depletion of macrophages, we demonstrate an essential role for macrophages in clearance of cells with DNA damage. Furthermore, we show that epithelial-associated macrophages are indispensable for effective tissue repair and gland function after radiation-induced injury, with their depletion resulting in reduced saliva production. Our data, therefore, provide a strong case for exploring the therapeutic potential of manipulating macrophages to promote tissue repair and thus minimize salivary gland dysfunction after radiotherapy.

Metformin Attenuates TGF-β1-Induced Fibrosis in Salivary Gland: A Preliminary Study.

Fibrosis commonly arises from salivary gland injuries induced by factors such as inflammation, ductal obstruction, radiation, aging, and autoimmunity, leading to glandular atrophy and functional impairment. However, effective treatments for these injuries remain elusive. Transforming growth factor-beta 1 (TGF-β1) is fundamental in fibrosis, advancing fibroblast differentiation into myofibroblasts and enhancing the extracellular matrix in the salivary gland. The involvement of the SMAD pathway and reactive oxygen species (ROS) in this context has been postulated. Metformin, a type 2 diabetes mellitus (T2DM) medication, has been noted for its potent anti-fibrotic effects. Through human samples, primary salivary gland fibroblasts, and a rat model, this study explored metformin's anti-fibrotic properties. Elevated levels of TGF-β1 (p < 0.01) and alpha-smooth muscle actin (α-SMA) (p < 0.01) were observed in human sialadenitis samples. The analysis showed that metformin attenuates TGF-β1-induced fibrosis by inhibiting SMAD phosphorylation (p < 0.01) through adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-independent pathways and activating the AMPK pathway, consequently suppressing NADPH oxidase 4 (NOX4) (p < 0.01), a main ROS producer. Moreover, in rats, metformin not only reduced glandular fibrosis post-ductal ligation but also protected acinar cells from ligation-induced injuries, thereby normalizing the levels of aquaporin 5 (AQP5) (p < 0.05). Overall, this study underscores the potential of metformin as a promising therapeutic option for salivary gland fibrosis.

Hong Kong Guangdong Rheumatology Meeting

Sjögren’s syndrome is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Hallmarks of the disease are a loss of salivary and lacrimal gland function as well as lymphocytic infiltration, elevated proinflammatory cytokines, and circulating autoantibodies. The effective treatments are limited. However, new therapies targeting specific immune pathways associated with Sjögren’s syndrome are being developed. Gene transfer to the salivary glands has been considered a promising approach to treating the dysfunction. The application of this treatment on salivary gland injuries has been studied for decades, yet its clinical progress is delayed. This chapter provides a coup d’oeil into gene transfer methods and various gene/vector types for salivary glands. AAV2-LAMP3-treated mice developed an SS-like phenotype with progressive salivary hypofunction and autoantibody production. To confirm the role of TLR4 in the induction of BMP6 following stimulation, AAV2-LAMP3–treated mice with established salivary hypofunction were treated i.p. with the TLR4 antagonist TAK242 for 10 days, and the effect of the drug on salivary gland protein expression and function was tested. We observed that treatment with TAK242 significantly decreased BMP6 expression and increased AQP5 expression in the salivary gland tissues. In agreement with this observation, the saliva flow rate of AAV2-LAMP3–treated mice also increased compared with that in vehicle control–treated mice. Gene therapy using recombinant viruses as gene transfer vectors to deliver a water channel (aquaporin 1, AQP1) to restore membrane water permeability in the salivary gland was shown to be safe and resulted in some patients with radiation-induced xerostomia having a sustained increase in saliva flow. A clinical trial using AAV2 to transfer AQP1 to the salivary glands of radiation-induced xerostomia patients is ongoing (NCT02446249) and results from this study may support application of this treatment in Sjögren’s syndrome. Gene therapy could also be used to deliver immunomodulators locally to the salivary gland resulting in a higher local concentration within the gland that could deliver therapeutics levels of recombinant protein, while minimizing the side effects associated with the drugs. Another study investigated whether a neurturin-expressing adenovirus could be used for gene therapy in vivo to protect parasympathetic neurons and prevent gland hypofunction after irradiation. The results suggest that in vivo neurturin gene therapy prior to irradiation protects parasympathetic function and prevents irradiation-induced hypofunction.

Diffusion-weighted MRI at the Late Stage after Radiotherapy for Evaluating Salivary Gland Injury.

Salivary gland injury is the main complication of radiotherapy for nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the value of diffusion-weighted magnetic resonance imaging (DW-MRI) as a reliable tool to assess salivary gland function in NPC patients after radiotherapy. This study analysed the MR images of 31 NPC patients at different time points within 2-3 years after radiotherapy. The changes in the apparent diffusion coefficient (ADC) and its relationship with radiation dose were analysed. Both the parotid and submandibular gland ADC values increased significantly 3-6 months after radiotherapy and then decreased gradually. The ADC value of the parotid gland was positively correlated with radiation dose at the late stage (P = 0.012, r = 0.359). The submandibular gland ADC change value (P = 0.035) and change ratio (P = 0.027) of the high radiation dose group were significantly lower than those of the low dose group at the late stage. The correlation between ADC values of parotid and submandibular glands and the radiation dose indicated that DW-MRI could be helpful in evaluating salivary gland injury after radiotherapy.

Ductal delivery of extracellular vesicles promote the recovery from salivary gland inflammation

Salivary gland dysfunction worsens the quality of life, but treatment for restoration of salivary gland function is limited. Although previous reports have demonstrated the therapeutic potentials of extracellular vesicles (EVs) in different preclinical models, the role of EVs in salivary glands remains elusive. Furthermore, little is known about the roles of salivary gland-derived EVs in tissue repair or regeneration compared to other EVs. In this study, EVs secreted from salivary gland-derived mesenchymal stem cells (sgMSCs) were comparatively analyzed with those from Wharton's jelly-derived MSC (wjMSCs). sgMSCs secreted more significant amounts of EVs than wjMSCs, and salivary gland epithelial cells showed a more efficient uptake of sgMSC-EVs than wjMSC-EVs. The possibility of immune regulation was tested via macrophage polarization and LPS-induced epithelial inflammation, resulting in an M1-to-M2 shift and reversal of acinar-to-ductal metaplasia by sgMSC-EV. Furthermore, the roles of sgMSC-EV-mediated immune regulation and tissue repair were clarified in vivo via retroductal delivery of sgMSC-EVs in a mouse model of obstructive sialadenitis. Collectively, our data demonstrate the superior role of sgMSC-EVs in the recovery from salivary gland inflammation and injury and suggest EVs as therapeutic tools for salivary gland dysfunction.

Nanonitrator: novel enhancer of inorganic nitrate’s protective effects, predicated on swarm learning approach

Inorganic nitrate is an indispensable nutrient that has been used in experimental studies for the prevention and treatment of several diseases. However, the short half-life of nitrate limits its clinical application. To increase the usability of nitrate and overcome the challenges of traditional combination drug discovery through large-scale high-throughput biological experiments, we developed a swarm learning-based combination drug prediction system that identified vitamin C as the drug of choice to be combined with nitrate. Employing microencapsulation technology, we used vitamin C, sodium nitrate, and chitosan 3000 as the core materials to prepare a nitrate nanoparticle, which we named Nanonitrator. The long-circulating delivery ability of nitrate by Nanonitrator significantly increased the efficacy and effect duration of nitrate in irradiation-induced salivary gland injury, without compromising safety. Nanonitrator at the same dose could better maintain intracellular homeostasis than nitrate (with or without vitamin C), emphasizing its potential for clinical use. More importantly, our work provides a method for incorporating inorganic compounds into sustained-release nanoparticles.

Repair mechanism of radiation-induced salivary gland injury by hypoxia-pretreated human urine-derived stem cell exosomes.

To explore the protective effect of human urine-derived stem cell exosomes (hUSC-Exos) on radiation-induced salivary gland (SG) injuries in Sprague Dawley rats. Fresh adult urine was collected, and primary hUSCs were isolated and identified. The hUSCs were hypoxia-pretreated with 1% oxygen for 24 h and then transferred to a normoxic culture environment for 24 h. The hUSC-Exos were collected and identified for exosomes. A radiation-induced injury model was established in the rats, and exosomes were introduced by local injection in the SG and tail vein. The submandibular gland was excised for morphological observation 1 week later. Immunohistochemical detection of the glandular tissue was conducted by α-smooth muscle actin (a-SMA), stem cell growth factor receptor (c-Kit) staining, and periodic acid-Schiff staining. Qualitative polymerase chain reaction and western blot analysis were adopted to detect the gene and protein expression of Wnt3a, GSK3β, and Axin. In both the normoxic and hypoxic hUSC-Exo groups, microvesicular structures with bilayer membranes of approximately 80 nm in diameter were detected, and the expressions of CD9 and CD63 were detected by nanoflow cytometry. Compared with the control group, in the radiation-induced injury model group, the expression of a-SMA was significantly higher, the expression of c-Kit was significantly lower, and the expressions of Wnt3a, GSK3β, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). Compared with the model group, in the normoxic and hypoxic hUSC-Exo groups, the expression of a-SMA was significantly decreased, the expression of c-Kit was significantly increased, and the expressions of Wnt3a, GSK3β, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). Hypoxia-pretreated hUSC-Exos could repair radiation-induced SG injuries by activating the Wnt3a/GSK3β pathway to suppress the expressions of a-SMA and c-Kit.

Gene Therapeutic Delivery to the Salivary Glands.

The salivary glands, exocrine glands in our body producing saliva, can be easily damaged by various factors. Radiation therapy and Sjogren's syndrome (a systemic autoimmune disease) are the two main causes of salivary gland damage, leading to a severe reduction in patients' quality of life. Gene transfer to the salivary glands has been considered a promising approach to treating the dysfunction. Gene therapy has long been applied to cure multiple diseases, including cancers, and hereditary and infectious diseases, which are proven to be safe and effective for the well-being of patients. The application of this treatment on salivary gland injuries has been studied for decades, yet its clinical progress is delayed. This chapter provides a coup d'oeil into gene transfer methods and various gene/vector types for salivary glands to help the new scientists and update established scientists on the progress that has been made during the past decades for the treatment of salivary gland disorders.

Contribution of military dentists to the development of modern salivalogy

Salivary gland diseases remain one of the most common pathologies of the masticatory apparatus, presenting challenges for the diagnosis and treatment of individuals in practical healthcare settings.&#x0D; AIM: This study aimed to present the contribution of military dentists to modern salivalogy and illuminate their professional journey in maxillofacial surgery and dentistry. The main scientific publications about the life and professional activity of military dentists A.V. Klementov and V.V. Lobeiko were analyzed. Lobeiko devoted to modern salivalogy, and other related aspects of modern stomatology and maxillofacial surgery have been analyzed. We present previously unknown information from the lives of A.V. Klementov and V.V. Lobeiko, military dentists well-known in our country. Lobeiko made a considerable contribution to the study of salivary glands pathology and thus developed a new direction of stomatology and maxillofacial surgery salivalogy. The main directions of their scientific activity in the development and improvement of methods of treatment of diseases, injuries, and tumors of the salivary glands as well as rehabilitation of patients after combined treatment of oncostomatological diseases are considered. A.V. Klementov proposed the classification of inflammation, systemic diseases, and salivary gland tumors, which is used up to now by dentists and maxillofacial surgeons in the Russian Federation and neighboring countries. He improved many diagnostic methods and conservative and surgical treatment of this pathology and suggested treatment methods for salivary gland injuries and their outcomes. For the first time, Lobeiko proposed index methods of the evaluation of the severity of inflammatory, reactive, and dystrophic diseases of the salivary glands, radiation- and drug-induced sialoadenopathies, and evaluation system of the effectiveness of the treatment of the aforementioned diseases in adults, which allowed standardization on the severity of pathologies and objectification of the positive results of complex treatment. He was one of the first who used the endoscopic technique to remove salivary glands. Military dentists were credited for the study of psychophysiological status of adults suffering from different salivary diseases and determination of age-related immunological indices of saliva in adults. Familiarity with the life history of military dentists A.V. Klementov and V.V. Lobeiko, as well as their scientific research in the field of salivalogy, is useful for dentists and maxillofacial surgeons dealing with salivary gland pathology.

Optimal administration time of vitamin C after 131I therapy in differentiated thyroid cancer based on propensity score matching.

ObjectivesThis study aimed to investigate the protection of the salivary glands by vitamin C administration at 2 and 24 h after an initial treatment using iodine-131 (131I) in patients with differentiated thyroid cancer (DTC) and examined the optimal administration time of vitamin C to protect the salivary glands from radiation injury.MethodThe clinical data of patients with differentiated thyroid carcinoma who had been treated with 131I in the Department of Nuclear Medicine in Shanxi Bethune Hospital from January 2014 to December 2020 were retrospectively analyzed. The propensity score matching method was adopted to match patients who received the administration of vitamin C at 2 h with those receiving administration at 24 h. A total of 230 pairs/460 patients were enrolled in the study. The chi-squared (χ2) or Fisher's exact test was used to compare the indicators representing the incidence of salivary gland injury between the two groups.ResultsThe incidence of salivary gland injury (17.39%) with acidic substances at 2 h was lower compared with administration at 24 h (26.96%). The incidence of acute salivary gland injury (15.22%) and chronic salivary gland injury (26.09%) in the 24-h group were higher than those in the 2-h group (4.78% and 18.26%, respectively). The differences in the left submandibular gland concentrate index and right submandibular gland concentrate index were statistically significant before and after treatment in both the 2 and the 24-h groups; these functions had been impaired after treatment.ConclusionsFollowing treatment with 131I, the protective effect of acidic substances administered at 2 and 24 h on the salivary glands were different. The incidence of salivary gland injury in the 2 h acid stimulation group was lower than in the 24 h acid stimulation group. The present study revealed that 131I treatment did cause some injury to the salivary glands and that the protective effect of administering vitamin C at 2 and 24 h may be limited. Accordingly, protection against salivary gland injury should be conducted using comprehensive measures.