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

Objective:To analyze the association between daily physical activity patterns and dyslipidemia among people receiving physical examination aged 40-65 years.Methods:This cross-sectional study consecutively enrolled 864 participants aged 40-65 years and met the inclusion and exclusion criteria who underwent health check-ups at the Physical Examination Center of Fuquan First People′s Hospital from March to November in 2022. The data of general characteristics, physical activity, physical examination findings, and lipid profiles were collected. The daily physical activity patterns were identified using K-means clustering analysis. The unconditional binary logistic regression was employed to explore the associations between these activity patterns and dyslipidemia, followed by subgroup analyses.Results:The physical activity of the 864 study participants (517 males and 347 females) included in the analysis was divided into 4 patterns (G1: low physical activity; G2: active commuting; G3: housework; G4: leisure exercise). Using G1 as a reference, after adjusting for confounders, G4 was negatively associated with low high density lipoprotein cholesterol (HDL-C) ( OR=0.37, 95% CI: 0.14-1.00) ( P=0.05). In the male, G3 was negatively associated with dyslipidemia ( OR=0.44, 95% CI: 0.21-0.93) and low HDL-C ( OR=0.25, 95% CI: 0.10-0.68) (both P<0.05). In the subjects aged 50 years and above, G2 was negatively associated with dyslipidemia ( OR=0.52, 95% CI: 0.30-0.90), hypertriglyceridemia ( OR=0.50, 95% CI: 0.28-0.90) and low HDL-C ( OR=0.47, 95% CI: 0.24-0.91) (all P<0.05). In those who never or occasionally stayed up late, G2 was negatively associated with hypertriglyceridemia ( OR=0.31, 95% CI: 0.13-0.75) ( P<0.05); in those who stayed up late often, G4 was negatively associated with dyslipidemia ( OR=0.33, 95% CI: 0.13-0.85) and low HDL-C ( OR=0.19, 95% CI: 0.04-0.84) (both P<0.05). In the centrally obese population, G2 was negatively associated with dyslipidemia ( OR=0.55, 95% CI: 0.35-0.88) and hypertriglyceridemia ( OR=0.54, 95% CI: 0.33-0.86) (both P<0.05). Conclusions:Association between different physical activity patterns and dyslipidemia varied among adults aged 40-65 years undergoing health check-ups. Leisure-time exercise is associated with a reduced risk of dyslipidemia, while household activities also emerges as a beneficial factor linked to lower dyslipidemia risk particularly in the male population.

Objective:To analyze the association between daily physical activity patterns and dyslipidemia among people receiving physical examination aged 40-65 years.Methods:This cross-sectional study consecutively enrolled 864 participants aged 40-65 years and met the inclusion and exclusion criteria who underwent health check-ups at the Physical Examination Center of Fuquan First People′s Hospital from March to November in 2022. The data of general characteristics, physical activity, physical examination findings, and lipid profiles were collected. The daily physical activity patterns were identified using K-means clustering analysis. The unconditional binary logistic regression was employed to explore the associations between these activity patterns and dyslipidemia, followed by subgroup analyses.Results:The physical activity of the 864 study participants (517 males and 347 females) included in the analysis was divided into 4 patterns (G1: low physical activity; G2: active commuting; G3: housework; G4: leisure exercise). Using G1 as a reference, after adjusting for confounders, G4 was negatively associated with low high density lipoprotein cholesterol (HDL-C) ( OR=0.37, 95% CI: 0.14-1.00) ( P=0.05). In the male, G3 was negatively associated with dyslipidemia ( OR=0.44, 95% CI: 0.21-0.93) and low HDL-C ( OR=0.25, 95% CI: 0.10-0.68) (both P<0.05). In the subjects aged 50 years and above, G2 was negatively associated with dyslipidemia ( OR=0.52, 95% CI: 0.30-0.90), hypertriglyceridemia ( OR=0.50, 95% CI: 0.28-0.90) and low HDL-C ( OR=0.47, 95% CI: 0.24-0.91) (all P<0.05). In those who never or occasionally stayed up late, G2 was negatively associated with hypertriglyceridemia ( OR=0.31, 95% CI: 0.13-0.75) ( P<0.05); in those who stayed up late often, G4 was negatively associated with dyslipidemia ( OR=0.33, 95% CI: 0.13-0.85) and low HDL-C ( OR=0.19, 95% CI: 0.04-0.84) (both P<0.05). In the centrally obese population, G2 was negatively associated with dyslipidemia ( OR=0.55, 95% CI: 0.35-0.88) and hypertriglyceridemia ( OR=0.54, 95% CI: 0.33-0.86) (both P<0.05). Conclusions:Association between different physical activity patterns and dyslipidemia varied among adults aged 40-65 years undergoing health check-ups. Leisure-time exercise is associated with a reduced risk of dyslipidemia, while household activities also emerges as a beneficial factor linked to lower dyslipidemia risk particularly in the male population.

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.
Cellular Senescence/genetics* ; Humans ; Immunoglobulin G/metabolism* ; Interleukin-13/pharmacology* ; Mitochondria/metabolism* ; Sialadenitis/metabolism*

Objective: To make a preliminery research of comobidity in oral squamous cell carcinoma (OSCC) patients who resides in Beijing area and investigate whether comorbidity affect the surviving rate independently. Compare the similarities and differences between Chinese and foreign OSCC patients. Methods: The medical records of 313 patients who undertaken operation in Peking University Stomatology School from January 2007 to Delember 2009 were retrospectively reviewed. Adult comorbidity evaluation-27 Chinese edition index was used to estimate the comorbidity severity. COX proportional hazards model was used to analyze whether the TNM stage, comobidity, age and gender affected 5-year survival rate. Results: TNM stage and comorbidity have a significant impact on survival rate, the postoperative survival rate decreased significantly with the increasing level of TNM staging and the complexity of comorbidity disease. In this study, the proportion of patients with none, mild, moderate and severe comorbidity diseases was 24%, 48%, 18% and 10%. The five-year survival rates of patients with moderate and severe comorbidity disease were 50% (29/58) and 13% (4/30) respectively. Conclusions The comorbidity disease information can help assess the overall health of OSCC patients, and it is recommended to improve the clinical staging and overall evaluation of oral cancer patients with comorbidity disease information.

Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10⁻⁸~10⁻⁶ mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10⁻⁹ mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α₂-adrenoceptor and nitric oxide synthase.
Arteries ; Dexmedetomidine* ; Endothelium ; Humans ; Indomethacin ; Lung ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Nitric Oxide Synthase Type III* ; Pulmonary Artery ; Serotonin ; Vasoconstriction* ; Yohimbine

Objective To translate the adult comorbidity evaluation-27(ACE-27) index authored by professor JF Piccirillo into Chinese and for the purpose of assessing the possible impact of comorbidity on survival of oral cancer patients and improving cancer staging. Methods The translation included the following steps, obtaining permission from professor Piccirillo, translation, back translation, language modification, adjusted by the advice from the professors of oral and maxillofacial surgery. The test population included 154 patients who were admitted to Peking University of Stomatology during March 2011. Questionnaire survey was conducted on these patients. Retest of reliability, internal consistency reliability, content validity, and structure validity were performed. Results The simplified Chinese ACE-27 index was established. The Cronbach'sαwas 0.821 in the internal consistency reliability test. The Kaiser-Meyer-Olkin (KMO) value of 8 items was 0.859 in the structure validity test. Conclusions The simplified Chinese ACE-27 index has good feasibility and reliability. It is useful to assess the comorbidity of oral cancer patients.

Objective:To investigate the defect types and reconstruction methods of maxillary defects. Methods:The database of 1 107 cases with maxillary defects in Peking University School and Hospital of Stomatology from January 1985 to December 2010 was established. There construction methods were re-viewed. The defect types were classified according to Brown classification system. Results: In the 1 107 cases, 1 104 cases could be classified according to Brown classification system. The most common type was 2a with 559 cases (50. 6%). Among all the 1 107 cases, 349 cases were reconstructed with auto-transplantation, 443 cases with prosthesis, 107 cases untreated, and 208 patients lost to the follow-up. There was a significant growing trend over time for the application of free flaps and a downward trend of prosthesis. The most popular free flaps were fibular flap (88 cases) and radial forearm flap (75 cases) . Rectus abdominis flap and anterolatreal thigh flap were fit for extensive maxillary defects. Conclusion:The most common defect type is 2a. Free flap has become the dominant option for maxillary reconstruc-tion. Free flaps could be selected according to the maxillary defect types.

BACKGROUND:Prefabricated customized bone flaps have the advantages of few trauma, good vascularization, ossification with predetermined shape, and can be used to restore bone defects with compromised blood bed.
OBJECTIVE:To establish animal models of mandibular reconstruction with prefabricated, customized bone flaps.
METHODS:After computed tomography scanning of nine rhesus’ head, customized meshes were made. After loading with recombinant human bone morphogenetic protein-2-incorporated demineralized freeze-dried bone al ograft (DFDBA) or coral ine hydroxyapatite (CHA), the constructs were implanted in latissimus dorsi muscle. Meanwhile, segmental mandibular defects were created, and the customized meshes loaded with DFDBA, CHA, or recombinant human bone morphogenetic protein-2-incooperated DFDBA and CHA were implanted in situ. At 13 weeks, prefabricated bone flaps with recombinant human bone morphogenetic protein-2-incorporated DFDBA or CHA were transferred to repair segmental mandibular defects. Clinical and histological analyses were used to evaluate the ossification and vascularization of the prefabricated implants in ectopic and orthotopic sites.
RESULTS AND CONCLUSION:Segmental mandibular defects were successful y restored with prefabricated bone flaps and recombinant human bone morphogenetic protein-2-incorporated CHA in situ, but other segmental mandibular defects remained with recombinant human bone morphogenetic protein-2-incorporated DFDBA, DFDBA and CHA in situ. Moreover, mandibles reconstructed with prefabricated bone flaps revealed more regenerated and homogeneous bone formation than other reconstructions. These findings suggest that the animal model of mandibular reconstruction with prefabricated, customized bone in rhesus monkey is applicable.

OBJECTIVETo summarize operation key points, prevention and management of complications in vascularized autotransplantation of submandibular gland for treatment of severe keratoconjunctivitis sicca.

METHODS23 patients with severe keratoconjunctivitis sicca were treated by this procedure. Postoperative (99m)Tc images, follow-up studies, and management of complications were performed.

RESULTSThe transplantations were successful in 19 cases, whose symptoms of xerophthalmia disappeared. The patients could stop applying artificial tears. In 4 patients the transplanted glands did not survive. Epiphora occurred in 5 cases. They were successfully treated by reducing the size of the graft. Obstruction of the Wharton's duct took place in one case and was treated by reconstructing the duct. When the superficial temporal vein was too small, venous bridging was applied. To select a relevant vein for anastomosis, blood oozing from the three veins was carefully inspected prior cutting off the gland when the external maxillary artery was preserved and was infused with heparin after the gland had been freed.

CONCLUSIONSIf every point has been properly managed, the successful rate of operation could be warranted.

Adolescent ; Adult ; Child ; Female ; Humans ; Keratoconjunctivitis Sicca ; surgery ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Submandibular Gland ; blood supply ; transplantation ; Transplantation, Autologous ; Treatment Outcome