Tricellulin, a key tricellular tight junction (TJ) protein, is essential for maintaining the barrier integrity of acinar epithelia against macromolecular passage in salivary glands. This study aims to explore the role and regulatory mechanism of tricellulin in the development of salivary gland hypofunction in Sjögren's syndrome (SS). Employing a multifaceted approach involving patient biopsies, non-obese diabetic (NOD) mice as a SS model, salivary gland acinar cell-specific tricellulin conditional knockout (Tric^CKO) mice, and IFN-γ-stimulated salivary gland epithelial cells, we investigated the role of tricellulin in SS-related hyposalivation. Our data revealed diminished levels of tricellulin in salivary glands of SS patients. Similarly, NOD mice displayed a reduction in tricellulin expression from the onset of the disease, concomitant with hyposecretion and an increase in salivary albumin content. Consistent with these findings, Tric^CKO mice exhibited both hyposecretion and leakage of macromolecular tracers when compared to control animals. Mechanistically, the JAK/STAT1/miR-145 axis was identified as mediating the IFN-γ-induced downregulation of tricellulin. Treatment with AT1001, a TJ sealer, ameliorated epithelial barrier dysfunction, restored tricellulin expression, and consequently alleviated hyposalivation in NOD mice. Importantly, treatment with miR-145 antagomir to specifically recover the expression of tricellulin in NOD mice significantly alleviated hyposalivation and macromolecular leakage. Collectively, we identified that tricellulin deficiency in salivary glands contributed to hyposalivation in SS. Our findings highlight tricellulin as a potential therapeutic target for hyposecretion, particularly in the context of reinforcing epithelial barrier function through preventing leakage of macromolecules in salivary glands.
Sjogren's Syndrome/complications* ; Animals ; Xerostomia/etiology* ; Mice ; Mice, Inbred NOD ; MARVEL Domain Containing 2 Protein/metabolism* ; Humans ; Mice, Knockout ; Disease Models, Animal ; Interferon-gamma ; Salivary Glands/metabolism* ; Tight Junctions/metabolism* ; MicroRNAs/metabolism* ; Female

Xerostomia (dry mouth) is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren's syndrome, with no permanent cure existing for this debilitating condition. To this end, in vitro platforms are needed to test therapies directed at salivary (fluid-secreting) cells. However, since these are highly differentiated secretory cells, the maintenance of their differentiated state while expanding in numbers is challenging. In this study, the efficiency of three reversible thermo-ionically crosslinked gels: (1) alginate-gelatin (AG), (2) collagen-containing AG (AGC), and (3) hyaluronic acid-containing AG (AGHA), to recapitulate a native-like environment for human salivary gland (SG) cell expansion and 3D spheroid formation was compared. Although all gels were of mechanical properties comparable to human SG tissue (~11 kPa) and promoted the formation of 3D spheroids, AGHA gels produced larger (>100 cells/spheroid), viable (>93%), proliferative, and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins (aquaporin-5, NKCC1, ZO-1, α-amylase) for 14 days in culture. Moreover, the spheroids responded to agonist-induced stimulation by increasing α-amylase secretory granules. Here, we propose alternative low-cost, reproducible, and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact, highly viable 3D-SG spheroids.
Humans ; Hydrogels/chemistry* ; Acinar Cells/cytology* ; Spheroids, Cellular/cytology* ; Salivary Glands/cytology* ; Gelatin/chemistry* ; Collagen/chemistry* ; Alginates/chemistry* ; Cell Culture Techniques/methods* ; Hyaluronic Acid/chemistry* ; Cell Proliferation ; Cell Survival ; Cells, Cultured

The emergence of sialoendoscopy has fundamentally altered and has played a huge role in the diagnosis and treatment of salivary gland diseases. However, nationwide, the number of oral and maxillofacial surgeons skilled in the use of sialoendoscopy is very small, which limits its further promotion and application. No standardized training program is currently available for sialoendoscopy in domestic stomatology colleges, and the content and assessment standards of relevant training needs further improvement. Based on relevant clinical and teaching experience, this paper emphasizes the important role of clinical application and skill training for sialoendoscopy, with the aim of promoting the popularization and development of sialoendoscopic therapy.
Humans ; Endoscopy/methods* ; Clinical Competence ; Salivary Gland Diseases/diagnosis*

Objective:To summarize the clinical characteristics, diagnosis and treatment experience of salivary pleomorphic adenoma in children. Methods:Thirty patients with salivary pleomorphic adenomas treated in Beijing Childrens Hospital from January 2008 to December 2022 were retrospectively reviewed, including 11 boys and 19 girls, with the age ranging from 0.3 to 14.4 years（median age 10.4 years）. Initial presentation, medical history, imaging workups, surgical approaches, complications, rates of recurrence were evaluated. Results:Major salivary gland lesions were most common（n=24, 80%）; 53.3%（16 of 30） arising in the submandibular glands and 26.7%（8 of 30） in the parotid. Minor salivary gland lesions（n=6, 20%） were removed from the palate, tongue, face, trachea, nasopharynx, and upper mediastinumand. Preoperative imaging was reviewed in all patients and consisted of 26 ultrasound exams, 2 computerized tomography（CT） exams, and 15 magnetic resonance imaging（MRI） exams. Fine needle aspiration biopsy was performed in 12 patients. Surgical excision was performed in all patients. Postoperative complications included transient facial paresis（n=3）, Pneumonia and pleural effusion（n=1）. Average length of follow-up was 36.7 months; confirmed recurrence occurred in one patients. Conclusion:The symptoms of salivary gland pleomorphic adenoma in children are different according to the location of the tumor. The treatment is complete surgical resection, and a small amount of normal tissue around the tumor should be removed to reduce recurrence.
Humans ; Male ; Female ; Child ; Adenoma, Pleomorphic/diagnosis* ; Adolescent ; Retrospective Studies ; Salivary Gland Neoplasms/diagnosis* ; Child, Preschool ; Infant ; Neoplasm Recurrence, Local

Objective:Traditional salivary gland surgery involves incisions in the visible facial and cervical regions, leaving postoperative scars that affect cosmesis. This study aims to investigate the clinical efficacy, safety, and application value of robot-assisted endoscopic resection of benign submandibular and parotid gland lesions via a postauricular approach, while clarifying its advantageous differences compared with endoscopic surgery. Methods:Clinical data of 23 patients who underwent robot-assisted endoscopic surgery via a postauricular approach（11 parotid gland cases and 12 submandibular gland cases） from January 2017 to February 2025 were retrospectively analyzed. Meanwhile, A matched control group of patients who received postauricular endoscopic surgery during the same period was selected as the control group in a 1∶1 ratio（11 parotid gland cases and 12 submandibular gland cases）. Indicators such as operation time, intraoperative blood loss, complications, and postoperative aesthetic satisfaction scores（Numeric Satisfaction Scale, NSS） were collected and compared between the two groups. The inclusion criteria were limited to benign lesions of the parotid superficial lobe（diameter ≤5 cm, without deep lobe involvement） and benign submandibular gland lesions（diameter ≤4 cm, without extension through the mylohyoid muscle）. Results:All robot-assisted surgeries were successfully completed without conversion to open surgery. In the robot group, there were 7 male patients（mean age 39.5 years） and 16 female patients（mean age 35.9 years）. For parotid gland surgeries, the mean operation time was （114.00±38.35） minutes. For submandibular gland surgeries, the mean operation time was（140.00±30.75） minutes.Temporary facial paralysis occurred in 0 of patients after robotic submandibular gland surgery （vs.8% in the endoscopic group） and 18% after robotic parotid gland surgery （vs.27 % in the endoscopic group）,all of which resolved within 1 month, with no occurrence of salivary fistula or infection. Patients had high aesthetic satisfaction（NSS scores: 8.90±1.20 for parotid surgeries and 9.00±0.70 for submandibular surgeries）. No tumor recurrence was observed during the 8-77 month follow-up period. Conclusion:Robot-assisted endoscopic salivary gland surgery via a postauricular approach is safe and feasible. With three-dimensional high-definition visualization and precise mechanical manipulation, it outperforms traditional endoscopic surgery in reducing blood loss, lowering the risk of nerve injury, and achieving long-term cosmetic outcomes. It is particularly suitable for young patients and cases with benign lesions of the parotid superficial lobe or submandibular gland that have high aesthetic demands. However, this surgical approach is not suitable for deep parotid lobe tumors, and its long-term efficacy requires verification through large-sample studies.
Humans ; Robotic Surgical Procedures/methods* ; Retrospective Studies ; Endoscopy/methods* ; Submandibular Gland/surgery* ; Parotid Gland/surgery* ; Female ; Male ; Operative Time ; Salivary Glands/surgery* ; Adult ; Middle Aged

A 57-year-old woman with a 2-year history of a left infra-auricular mass with no associated symptoms presented with a 6.0 cm ´ 4.0 cm ´ 3.0 cm firm, non-tender, movable mass. No imaging was done. Fine needle aspiration biopsy (FNAB) revealed sheets of epithelial cells that had abundant dense grayish-blue cytoplasm in a mucinous background with abundant lymphocytes (Figure 1), suggestive of salivary gland neoplasm with oncocytic or oncocytoid features (Category IVB, Salivary Gland Neoplasm of Uncertain Malignant Potential).Total parotidectomy revealed a 4.3 X 3.2 X 3.0 cm deep lobe lesion with a tan-grey to dark brown, smooth and dull external surface. Cut sections showed a cream-white to pink, lobulated, heterogenous cut surfaces. Microscopically, the lesion was unencapsulated with poorly demarcated borders. The neoplastic cells were arranged in haphazard sheets and surrounded by abundant lymphocytes. The tumor cells had abundant eosinophilic and granular cytoplasm compatible with oncocytes with mild to moderate nuclear atypia. There were occasional cystic spaces that contained mucin though mucocytes were not readily apparent. (Figure 2) Necrosis, perineural and lymphovascular space invasion or anaplasia were not evident.
Carcinoma, Mucoepidermoid ; Salivary Gland Neoplasms ; Parotid Gland

Sialolithiasis occurs in approximately 0.45% to 1.20% of the general population. The typical clinical symptom manifests as a painful swelling of the affected glands after a meal or upon salivary stimulation, which extremely affects the life quality of the patients. With the development of sialendoscopy and lithotripsy, most sialoliths can be successfully removed with preservation of the gland. However, sialoliths in the deep hilar-parenchymal submandibular ducts and impacted parotid stones located in the proximal ducts continue to pose great challenges. Our research center for salivary gland diseases (in Peking University School and Hospital of Stomatology) has used sialendoscopy for 17 years and treated >2 000 patients with salivary gland calculi. The success rate was approximately 92% for submandibular gland calculi and 95% for parotid calculi. A variety of minimally invasive surgical techniques have been applied and developed, which add substantial improvements in the treatment of refractory sialolithiasis. Further, the radiographic positioning criteria and treatment strategy are proposed for these intractable stones. Most of the hilar-parenchymal submandibular stones are successfully removed by a transoral approach, including transoral duct slitting and intraductal basket grasping, while a small portion of superficial stones can be removed by a mini-incision in submandibular area. Impacted stones located in the distal third of parotid gland ducts are removed via "peri-ostium incision", which is applied to avoid a cicatricial stenosis from a direct ostium incision. Impacted parotid stones located in the middle and proximal third of the Stensen's duct are removed via a direct mini-incision or a peri-auricular flap. A direct transcutaneous mini-incision is commonly performed under local anesthesia with an imperceptible scar, and is indicated for most of impacted stones located in the middle third, hilum and intraglandular ducts. By contrast, a peri-auricular flap is performed under general anesthesia with relatively larger operational injury of the gland parenchyma, and should be best reserved for deeper intraglandular stones. Laser lithotripsy has been applied in the treatment of sialolithiasis in the past decade, and holmium ∶YAG laser is reported to have the best therapeutic effects. During the past 3 years, our research group has performed laser lithotripsy for a few cases with intractable salivary stones. From our experiences, withdrawal of the endoscopic tip 0.5-1.0 cm away from the extremity of the laser fiber, consistent saline irrigation, and careful monitoring of gland swelling are of vital importance for avoidance of injuries of the ductal wall and the vulnerable endoscope lens during lithotripsy. Larger calculi require multiple treatment procedures. The risk of ductal stenosis can be alleviated by endoscopic dilation. In summary, appropriate use of various endoscopy-assisted lithotomy helps preserve the gland function in most of the patients with refractory sialolithiasis. Further studies are needed in the following aspects: Transcervical removal of intraglandular submandibular stones, intraductal laser lithotripsy of impacted parotid stones and deep submandibular stones, evaluation of long-term postoperative function of the affected gland, et al.
Humans ; Salivary Gland Calculi/surgery* ; Constriction, Pathologic ; Endoscopy ; Salivary Ducts/surgery* ; Lithotripsy ; Treatment Outcome

Objective: To investigate the expression of TRPS1 in salivary gland-type breast carcinoma and its clinical application. Methods: A total of 30 cases of salivary gland-type breast carcinoma diagnosed from May 2015 to November 2022 at the Department of Pathology of the First Affiliated Hospital of Nanjing Medical University were collected. The expression of TRPS1 was detected by immunohistochemistry and compared with that of GATA3. TRPS1 and GATA3 expression in 24 cases of primary salivary gland carcinoma. Results: There were 10 cases of breast secretory carcinoma, aged 21-61 years (median 53.5 years), with the size ranging from 0.9-2.2 cm (median 1.6 cm), 2 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 2-55 months of follow-up (median 29.5 months, mean 29.7 months). There were 20 cases of breast adenoid cystic carcinoma, aged 36-77 years (median 53.5 years), with the size ranging from 1.2-5.5 cm (median 2.5 cm), 3 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 3-92 months of follow-up (median 22.5 months, mean 31.7 months), and 1 patient had lung metastasis 15 months after surgery. The medium/high expression ratio of TRPS1 in breast secretory carcinoma was 10/10, which was higher than that of GATA3 (7/10). TRPS1 was also positive in the 2 cases with lymph node metastases. The medium/high expression rate of TRPS1 in breast adenoid cystic carcinoma was 20/20, which was significantly higher than that of GATA3 (2/20). TRPS1 was highly expressed in both classic and solid subtypes, while GATA3 was only expressed in a few cases of the classic subtype. TRPS1 was also positive in 3 cases with lymph node metastases and 1 case of the pulmonary metastases. The expression level of TRPS1 was the same in 1 case before and after neoadjuvant chemotherapy. In addition, TRPS1 was positive in parotid secretory carcinoma and adenoid cystic carcinoma. The medium/high expression rate of TRPS1 in parotid secretory carcinoma (6/6) was higher than that of GATA3 (2/6), and the medium/high expression rate of TRPS1 in parotid adenoid cystic carcinoma (17/18) was higher than that of GATA3 (2/18). Conclusions: The expression of TRPS1 is highly sensitive to salivary gland-type breast carcinoma, especially in GATA3-negative solid subtype of adenoid cystic carcinoma, which plays an important role in clinical practice.
Humans ; Female ; Carcinoma, Adenoid Cystic/pathology* ; Lymphatic Metastasis ; Salivary Gland Neoplasms/pathology* ; Parotid Neoplasms ; Lung Neoplasms ; Breast Neoplasms ; Parotid Gland ; Repressor Proteins

More than 30 years of rapid development of endoscopic surgery has led to the mainstreaming of this procedure in many surgical departments in China. Since the first report on endoscopy, it has been used in salivary gland resection for more than 20 years. The overall development of endoscopic surgery indicates that its use in oral and maxillofacial surgery is still in the early exploration stage; it has not yet been maturely developed or applied. Owing to the advancement of other disciplines and corresponding widening experiences in those fields, the development of endoscopic technology in oral and maxillofacial surgery will likely achieve a leapfrogging. Learning from the general development pattern of endoscopy, this research explores the application history, current situation, and future direction of the application of endoscopy in salivary gland surgery.
Endoscopy/methods* ; Endoscopes ; Salivary Glands/surgery* ; China

Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the "immuno-privileged" status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient's immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.
Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells ; Quality of Life ; Regeneration ; Salivary Glands ; Stem Cells