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

Salivary glands mucosa-associated lymphoid tissue lymphoma (SGML) is a distinct subtype of marginal zone B-cell type non-Hodgkin′s lymphoma (NHL), which is commonly seen in middle aged females. SGML is usually associated with autoimmune diseases such as Sjögren's syndrome or with chronic infection such as hepatitis C virus (HCV) infection. Chromosomal abnormalities are frequently seen in SGML, which usually activate nuclear factor-κB molecular pathway to modulate cell survival and proliferation, resulting in lymphoma occurrence. SGML tends to arise from parotid gland, presenting frequently as a localized and indolent lesion, a long-term follow-up and biopsy are needed for accurate diagnosis. Surgery, radiotherapy and chemotherapy are usually effective disseminated diseases at multiple sites need combined treatment. SGML has a relatively better prognosis with a higher relapse rate than other types of NHLs, dissemination or higher degree of malignant transformation may occur. Thus, a long-term and close follow-up is essential for patients with SGML.

Autologous submandibular gland (SMG) transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously. This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients' glands 4-6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.
Animals ; Autonomic Pathways ; growth & development ; Fascia ; innervation ; Female ; Humans ; Keratoconjunctivitis Sicca ; surgery ; Male ; Models, Animal ; Rabbits ; Recovery of Function ; Secretory Rate ; Submandibular Gland ; innervation ; transplantation ; Transplantation, Autologous

OBJECTIVE:To observe therapeutic efficacy and safety of Milrinone injection in the treatment of hypertensive heart disease complicated with heart failure. METHODS:A total of 120 patients with hypertensive heart disease complicated with chronic heart failure were randomized into control group and observation group according to random number table,with 60 cases in each group. Control group received routine therapy,including blood pressure controlling,anti-heart failure and other symptomatic treatment;observation group was additionally given Milrinone injection 0.3 mg/kg,continuous pump,qd. A treatment course lasted for 5 d. Both groups received one course of treatment each month for consecutive 6 months. Both groups were followed up for one year. 6 min walking distance(6MWD),BNP,LVEF,CI,LVEDD,heart rate,sitting systolic blood pressure(SiSBP)and sitting diastolic blood pressure(SiDBP),re-hospitalization rate and cardiovascular mortality were observed in 2 groups before treatment, after 3,6 months and 1 year of treatment;therapeutic efficacy of heart function and the incidence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in 6MWD,BNP,LVEF,CI,heart rate,SiSBP and SiDBP between 2 groups;after 3 months,6 months and 1 year of treatment,6MWD,LVEF and CI of 2 groups were increased significantly,while BNP,LVEDD,resting heart rate,SiSBP and SiDBP were decreased significantly;the observation group was significantly better than the control group,with statistical significance(P<0.05). Total response rate of heart function was 90.00%in observation group,which was significantly higher than 63.33% in control group,with statistical significance(P<0.05). After 1 year of follow-up,re-hospitalization rate of observation group was significantly lower than that of control group,with statistical sig-nificance (P<0.05);there was no statistical significance in cardiovascular mortality (P>0.05). There were no statistical signifi-cance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Milrinone injection shows good efficacy in the treatment of hypertensive heart disease complicated with heart failure,can significantly reduce BNP and re-hospitalization rate as well as improve prognosis with good safety.

Massive open online courses (MOOCs) , which has caused a large scale of medical edu-cation in recent years, has led to an exploration boom in medical education. By the end of November 2014, on four large domestic and foreign MOOCs platform, a total of 178 medical related MOOCs were found, accounting for 12.2% of the total number of courses, among which public health MOOCs accounted for 44.9%. In terms of medical education, MOOCs are not only a powerful supplement of existing medical ed-ucation and can assist dissemination of medical knowledge, they can also promote pedagogy innovation and improve teaching quality to a certain extent. Moreover, the huge amounts of data collected by MOOCs can also be used to develop research of students' learning behavior. In addition, by recruiting study objects, the researchers have begun to use MOOCs supporting scientific research. As a novel educational development, MOOCs face many challenges while they bring opportuni-ties for medical education. However, active prac-tice and exploration will bring more powerful vitality for its development in the medical field.

OBJECTIVETo observe the immune reaction in the mixed culture of host lymphocytes with allogenic and host endothelial cells.

METHODSThe host epithelial cells and lymphocytes from burn patients and allogenic epithelial cells were mix-cultured in different ratios, so as to simulate the local immune micro-environment of host skin island in intermingled skin grafting. In addition, the cells from normal human subjects were also mix-cultured as control. The lymphocyte cpm values were detected by (3)H-TdR and HLA molecules and T cell subgroup were determined by immunohistological technique.

RESULTS(1) The lymphocyte proliferation reaction could be effectively inhibited by the epithelial cells from burn patients but not from normal control. (2) The inhibition of host lymphocyte proliferation could not be mediated by the HLA-DQ molecules of epithelium from burn patients. (3) The positive expression rate of HLA-DR of epithelia from burn patients was evidently higher that that from normal control (P < 0.05), (4) The CD8 expression of lymphocyte in burn patients was significantly higher than that in normal control (P < 0.01), while the CD4 expression in burn patients was lower than that in normal control (P < 0.01). But there was no obvious difference of the CD3 expression between patients and normal subjects (P > 0.05).

CONCLUSIONThe lymphocyte proliferation reaction could be obviously inhibited by the host epithelium, which might be related to the specific immune state of the host lymphocytes and epithelium of burn patients.

Cell Communication ; immunology ; physiology ; Cell Culture Techniques ; Cell Division ; Epithelial Cells ; immunology ; physiology ; Humans ; Lymphocytes ; immunology ; physiology ; Skin Transplantation ; immunology