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 compare the intestinal injury induced by different intensities of waveshock in rats exposed to extremely cold environment and to preliminarily explore the characteristics of the injury.Methods Sixty healthy male SD rats(2 months old,weighing 200～250 g)were randomly divided into 6 groups(n=10):blank control group,low-temperature control group,5.0 MPa shock control group,and low-temperature+4.0,4.5 and 5.0 MPa shock groups.The rats in the experimental groups were pre-treated in a-10℃low-temperature environment for 30 min and then subjected to intestinal injury by using BST-I biological shock tube with different driving pressures.At 3,8,and 24 h after injury,the serum levels of IL-6,TNF-α,intestinal fatty acid binding protein(I-FABP),and diamine oxidase(DAO)were detected,and the survival of rats within 24 h was recorded.At 24 h after injury,the rats were anesthetized and dissected,the characteristics of intestinal injury were observed,and pathological examination was performed.The differences of intestinal injury were compared among the 6 groups to explore the characteristics of intestinal injuries after different intensities of shockwave in rats after exposure to extremely cold environment.Results Compared with the blank control group,the other 5 groups exhibited different severities of intestinal injury,and the rats in the low-temperature+different shock groups were more prone to intestinal edema and trauma.The mortality rate was significantly increased in the low-temperature+5.0 MPa shock group(P<0.05).Pathological and serological studies found that dual effects of very cold environment and blast injury resulted in intestinal mucosal hemorrhage,edema,and disintegration of lamina propria in the experimental rats.The indicators of intestinal mucosal injury and intestinal inflammatory factors were also significantly increased when compared with the blank control group,and significant differences were among the groups with increment of shock intensity(P<0.05).Conclusion Exposure to very cold environment combined with abdominal blast injury increases mortality rate in rats,manifested by elevated serological indicators and intestinal inflammatory factors,as well as varying severities of intestinal wall edema and submucosal bleeding.Furthermore,the severity of the injury is positively related to the impact intensity,with worsened as the impact intensity increasing.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.

Objective:To construct a predictive model for the risk of major adverse cardiovascular events(MACE) after surgery in patients with symptomatic arteriosclerosis obliterans(ASO) .Methods:From Jan 2018 to Dec 2021, 957 patients with symptomatic ASO admitted to Nanjing Drum Tower Hospital were selected and divided into MACE and non-MACE groups according to whether they had a post-op MACE. A risk prediction model was constructed based on a stepwise regression method with multi-factor COX regression analysis. The model was evaluated using the receiver operating characteristic curve (ROC), the calibration curve to assess the model fit, and the Bootstrap method for internal validation.Results:MACE occurred in 143 patients (14.94%). After COX regression analysis, BMI, creatinine clearance, fibrinogen, rivaroxaban and previous history of surgery were enrolled into model constructing. The ROC curve assessed the model with a C-statistic of 0.690 (95% CI: 0.644-0.736), sensitivity and specificity of 49.2% and 80.7% respectively, a Jorden index of 0.299 and an optimal cut-off value of 0.086. Calibration curves showing agreement between predicted and actual observed values. Internally validated C-statistic of 0.689 (95% CI: 0.672-0.700). The population was divided into high and low risk groups based on the best cut-off value and analysed for survival. The difference between the two groups was statistically different. Conclusion:The risk prediction model for the occurrence of MACE based on clinical parameters is simple and convenient, with good predictability and good discriminatory ability, and can provide reference for the assessment and treatment of MACE in ASO patients.

BACKGROUND: Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth (SHED-exos) in sialadenitis caused by SS. METHODS: SHED-exos were administered to the submandibular glands (SMGs) of 14-week-old non-obese diabetic (NOD) mice, an animal model of the clinical phase of SS, by local injection or intraductal infusion. The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice. Protein expression was examined by western blot analysis. Exosomal microRNA (miRNAs) were identified by microarray analysis. Paracellular permeability was evaluated by transepithelial electrical resistance measurement. RESULTS: SHED-exos were injected into the SMG of NOD mice and increased saliva secretion. The injected SHED-exos were taken up by glandular epithelial cells, and further increased paracellular permeability mediated by zonula occluden-1 (ZO-1). A total of 180 exosomal miRNAs were identified from SHED-exos, and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway might play an important role. SHED-exos treatment down-regulated phospho-Akt (p-Akt)/Akt, phospho-glycogen synthase kinase 3β (p-GSK-3β)/GSK-3β, and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells. Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1, a PI3K agonist. Slug bound to the ZO-1 promoter and suppressed its expression. For safer and more effective clinical application, SHED-exos were intraductally infused into the SMGs of NOD mice, and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and Slug and increased ZO-1 expression. CONCLUSION Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3β/Slug pathway-mediated ZO-1 expression.
Mice ; Animals ; Humans ; Sjogren's Syndrome/therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Tight Junctions/metabolism* ; Glycogen Synthase Kinase 3 beta ; Mice, Inbred NOD ; Phosphatidylinositol 3-Kinases/metabolism* ; Exosomes/metabolism* ; Xerostomia ; Phosphatidylinositol 3-Kinase ; MicroRNAs/genetics*

OBJECTIVE To evaluate the efficacy of the functional dressing of Polygonum capitatum nanofibers （P-PVP-PCL）. METHODS P-PVP-PCL were prepared by electrospinning technology， and the microstructure of P-PVP-PCL was observed. The antibacterial activity and antioxidant activity of P-PVP-PCL and its effects on the survival rate， adhesion and migration rate of mouse fibroblast L929 cells were investigated. The effects of medical gauze dressing， blank nanofiber dressing （PVP-PCL） and P- PVP-PCL on the healing rate of the wound were investigated by establishing the back skin wound model of rats. The pathological changes of the wound tissue and collagen fiber deposition were observed， as well as the number of platelet endothelial cell adhesion molecule-1 （CD31） positive blood vessels and the expression of transforming growth factor-β （TGF-β） protein in wound tissue. RESULTS P-PVP-PCL had a smooth surface and a double-layer structure at the cross-section. The inhibition rates of P-PVP-PCL against Staphylococcus aureus and Escherichia coli were （98.88±0.66）% and （94.75±1.41）% ， respectively. The antioxidant activity of P-PVP-PCL was （83.69±1.56）%， and the cell activity of the P-PVP-PCL group was significantly higher than those of the control group and PVP-PCL group （P＜0.05）. Compared with medical gauze dressings， P-PVP-PCL was more conducive to L929 cell adhesion； at 48 hours， the cell scratches in this group had basically healed. Compared with the medical gauze dressing group， the wound healing rates of the PVP-PCL group and the P-PVP-PCL group were significantly increased （P＜0.05）. On the 14th day of intervention， the wounds in the P-PVP-PCL group had basically healed， there was no dermal necrosis in the wound tissue， and the collagen fibers were arranged relatively neatly and the density was relatively uniform. The number of CD31 positive blood vessels and the expression of TGF-β protein showed a downward trend compared with the 7th day of intervention， and the number of CD31 positive blood vessels was significantly lower than those of the medical gauze dressing group and PVP-PCL group （P＜0.05）， but the protein expression of TGF- β was significantly higher than those of the medical gauze dressing group and the PVP-PCL group （P＜0.05）. CONCLUSIONS P-PVP-PCL has good antibacterial and antioxidant activity in E-mail：444096585@qq.com vitro， and can promote the proliferation， adhesion and migration of L929 cells. It can promote wound healing of rats in vivo.

ObjectiveTo explore the clinical effect of core muscle motor control training on postpartum diastasis recti abdominis. MethodsFrom January, 2021 to January, 2022, 30 outpatients with postpartum diastasis recti abdominis were randomly divided into control group (n = 15) and experimental group (n = 15). Manipulative therapy and breathing training were performed simultaneously in both groups. Besides, the control group received conventional core strength training, and the experimental group received core muscle motor control training, for four weeks. Their distance of diastasis recti abdominis, abdominal circumference and waist circumference were compared before and after treatment. ResultsAfter treatment, the distance of diastasis recti abdominis, abdominal circumference and waist circumference reduced in both groups (Z = 3.408, t > 5.927, P < 0.05). The reduction value of diastasis recti abdominis distance was more in the experimental group than in the control group (t = 2.328, P < 0.05). ConclusionCore muscle motor control training can effectively relieve postpartum diastasis recti abdominis, and the effect is better than conventional core strength training.

Objective:To observe the clinical effect of modern root canal therapy on pulpitis in flying personnel.Methods:A total of 229 patients who were diagnosed as pulpitis from March of 2018 to April of 2020 were divided into 2 groups alternately according to the order of treatment. One hundred and fifteen patients in the study group that received modern root canal therapy and 114 patients in the control group that received the conventional root canal therapy. The clinical symptoms (red and swollen gums, pain and chewing discomfort) score, visual analogue scale (VAS) and masticatory ability score were respectively investigated before treatment and 2 weeks after treatment. The quality of life (QOL) score was investigated before treatment and 1 month after treatment. The total effective rate was evaluated 2 weeks after treatment and the incidences of adverse reactions (local swelling, root canal obstruction and occlusive pain) were analyzed. The recurrence rates by 6-month treatment and the treatment results were compared between 2 groups.Results:The total effective rate of the study group was 93.04%, which was higher than that of the control group (84.21%), and the difference between the 2 groups was statistically significant ( χ2=4.438, P=0.035). There were no differences on clinical symptoms score, QOL score, VAS, inflammatory index and masticatory ability score between 2 groups before treatment (all P>0.05). The clinical symptoms score, VAS, the levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in the study group after treatment were lower than those of the control group, but the masticatory ability score and QOL score were higher than those of the control group after treatment. The differences between the 2 groups were statistically significant ( t=8.229-46.504, all P=0.001). The incidence of adverse reactions and recurrence rate in the study group was 7.83% and 5.22% respectively, which was lower than that of the control group (17.54% and 13.16%, respectively, χ2=4.881, 4.334, P=0.027, 0.037). Conclusions:The modern root canal therapy has better clinical effect on the treatment of pulpitis. It can shorten the treatment courses, reduce the inflammation response, pain degree, adverse reactions and recurrence rate, improve the curative rate and the life of teeth of flying personnel, and reduce the adverse factors in high altitude flight.

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*

In the spirit of curriculum-centered principle, the research group actively explored the content construction, operation mode and teaching method reform of comprehensive experimental course of basic medicine. Guided by diseases and application, experimental teaching courses based on the preparation and intervention process of animal models of diseases were extensively carried out, and "innovative" experimental items were added to ensure that the course contents reflected the frontier and the times. The course construction was guided by the training of biomedical frontier methods, making efforts to cultivate students' learning ability, practical ability and innovative ability. In addition, on the basis of optimizing the course content construction oriented to practical application and innovation, a virtual simulation experiment project is built, combined with online-offline hybrid teaching, to improve the comprehensive practical ability of trainees.