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 design the proficiency testing (PT) project (No. NIFDC-PT-183) for assays of bismuth potassium citrate capsules and organize to assess the proficiency of complexometric titration in laboratories, and provide some technical analyses and advices.
Methods: Two groups of samples with different concentration were prepared. The uniformity was evaluated with one-way analysis of variance and the stability was confirmed with t-test, whose results all conformed the requirements. The samples with three combinations were randomly distributed to 279 laboratories. The determination was performed according to the assays of bismuth potassium citrate capsules in Volume Ⅱ of the Chinese Pharmacopoeia 2015. The median value and normalized interquartile range (NIQR) of robust statistical analysis was adopted and Z-scores were used to evaluate the results from each of laboratories.
Results: Among 279 laboratories, 240 laboratories results were satisfactory, 23 were questionable, and the other 16 were unsatisfied. The satisfaction rate was 86.0%.
Conclusion: The overall capacity of national laboratories for assays of bismuth potassium citrate capsules is good while a portion of participants require further improvement.

Objective To establish a method to qualitatively identify and quantitatively determine a new impurity from beclomethasone propionate inhalation aerasol.Methods Ultra-performance liquid chromatography-Q-exactive orbitrap-mass spectrometry(UPLC-QE-MS)technology and Discovery Studio software were used to identify and predict the toxicity of a new impurity in beclomethasone propionate inhalation aerasol,and the content of this new impurity was determined by UPLC.Results The new impurity in beclomethasone propionate inhalation aerasol was polybutylene terephthalate(PBT)cyclic dimer.Discovery Studio software predicted that PBT dimer had potential developmental toxicity,with no mutagenicity,no ocular and skin irritancy and no rodent carcinogenicity.The content range of PBT dimer in 9 batches of beclomethasone propionate inhalation aerasol was 20.5-116.6 pg per bottle.Conclusion This study can realize the rapid identification and toxicity prediction of the new impurity in the preparation,and provide a theoretical basis for the quality control of the preparation by determining their content.

Objective To construct a predictive model for septic shock based on the propensity score matching (PSM) method and validate its effectiveness. Methods A total of 114 patients with sepsis were enrolled as study objects, and were divided into septic shock group (40 patients) and sepsis group (74 patients) according to whether they developed septic shock. PSM was performed with a ratio of septic shock to sepsis of 1∶2, resulting in the inclusion of 30 patients in the septic shock group and 60 patients in the sepsis group after matching. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), serum amyloid A (SAA), soluble endothelial protein C receptor (sEPCR), endothelial cell-specific molecule 1 (ESM-1), clusterin (CLU), and the Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score and Sequential Organ Failure Assessment (SOFA) score at admission were compared between the two groups. Cox proportional hazards regression analysis was used to identify the factors influencing septic shock, and a predictive model for septic shock was constructed and internally validated using the receiver operating characteristic (ROC) curve. Kaplan-Meier survival curves were plotted to analyze the differences in survival prognosis among patients with different expression levels of the indicators. Results After matching, there were no statistically significant differences in general information between the two groups (P>0.05). At admission, the septic shock group had higher levels of serum PCT, CRP, SAA, IL-6, sEPCR, ESM-1, and higher APACHE Ⅱ and SOFA scores, as well as a lower level of serum CLU compared with the sepsis group (P < 0.05). Cox regression analysis showed that PCT, CRP, SAA, IL-6, sEPCR, ESM-1, APACHE Ⅱ score, and SOFA score were independent risk factors for septic shock (P < 0.05), while CLU was an independent protective factor (P < 0.05). The predictive model for septic shock, constructed based on these factors, showed an internal validation accuracy of 94.44%, an area under the curve of 0.950, a sensitivity of 93.33%, and a specificity of 96.67%. Dead patients had higher levels of PCT, CRP, SAA, IL-6, sEPCR, ESM-1, and higher APACHE Ⅱ and SOFA scores, as well as a lower level of CLU at admission compared with survivors (P < 0.05). Compared with patients with low expression levels or low scores, patients with high expression levels of PCT, CRP, SAA, IL-6, sEPCR, ESM-1, and high APACHE Ⅱ and SOFA scores had higher fatality rates, while patients with high CLU expression levels had a lower fatality rate (P < 0.05). Conclusion The serum biomarkers including PCT, CRP, SAA, IL-6, sEPCR, ESM-1, CLU, and the APACHE Ⅱ and SOFA scores in sepsis patients are closely related to the occurrence of septic shock and survival prognosis. The predictive model constructed by combining these indicators can accurately predict the occurrence of septic shock.

ObjectiveTo explore the role of interleukin-6 （IL-6）/signal transducer and activator of transcription 3 （STAT3） pathway in the balance of T helper 17 （Th17）/regulatory T （Treg） cells in ulcerative colitis （UC） with internal dampness-heat accumulation syndrome and the intervention mechanism of Shaoyaotang. MethodA total of 60 SD rats were randomized into blank group （equivalent volume of normal saline）， model group （equivalent volume of normal saline）， western medicine control group （0.42 g·kg^-1 mesalazine）， and low-dose （11.1 g·kg^-1）， medium-dose （22.2 g·kg^-1）， and high-dose （44.4 g·kg^-1） Shaoyaotang groups. UC with internal dampness-heat accumulation syndrome was induced in rats with the compound method except for the blank group. The administration lasted 14 days for each group. At 24 h after the last administration， rats were killed and the spleen and colon tissues were separated. The histopathological changes of colon were observed based on hematoxylin and eosin （HE） staining and the levels of interleukin-17 （IL-17） and transforming growth factor-β₁ （TGF-β₁） in colon tissue were detected by immunohistochemistry （IHC）. Flow cytometry was employed to determine the levels of Th17/Treg cells in the spleen， and Western blot to measure the levels of IL-6 and STAT3 proteins in colon tissue. ResultCompared with the blank group， the model group had lesions such as congestion and erosion， low percentage of spleen Treg cells （P<0.01）， high percentage of Th17 cells （P<0.01）， and high levels of IL-6 and STAT3 proteins in colon tissue （P<0.01）. Compared with the model group， the administration groups showed alleviation of colon injury， high percentage of spleen Treg cells （P<0.05， P<0.01）， low percentage of Th17 cells （P<0.01）， and low levels of IL-6 and STAT3 proteins in colon tissue （P<0.01）. ConclusionShaoyaotang regulates the balance of Th17/Treg by inhibiting the IL-6/STAT3 pathway， thereby relieving the pathological damage of UC rats with internal dampness-heat accumulation syndrome and affecting their immune function.

Objective:To systematically analyze the efficacy of nasal endoscopic transsphenoidal decompression and glucocorticoid pulse therapy for traumatic optic neuropathy (TON).Methods:PubMed, Web of Science, Cochrane Library, ClinicalTrial.gov, CNKI, Wanfang, China Biomedical and other databases were searched to retrieve clinical studies on endoscopic surgery and hormone therapy for TON since their establishment to November 1, 2020.Two researchers screened the literature and evaluated the quality of the included literatures.The improvement of visual acuity before and after treatment was taken as an effective indicator.RevMan 5.3 statistical software was used for meta-analysis.The sensitivity of the results was analyzed atfer literature exclusion.The publication bias of each study was double checked by funnel plot and Begg test.Results:Eight studies were included, including 7 cohort studies and 1 randomized controlled trial.There was no significant difference between the endoscopic decompression group and glucocorticoid group in the efficiency of visual acuity improvement in the treatment of TON [odds ratio ( OR)=1.65, 95% confidence interval ( CI)∶0.75-3.66, P=0.22], neither in TON patients with residual vision before surgery ( OR=2.17, 95% CI: 0.94-4.98, P=0.07). For nasal endoscopic decompression surgery, early surgery (disease course<7 days) was more effective than late surgery (disease course>7 days) ( OR=4.73, 95% CI: 2.55-8.78, P<0.01). Sensitivity analysis suggested that the results of this literature analysis were not robust.The Begg test showed that there was no literature publication bias. Conclusions:There is no significant difference between nasal endoscopic surgery and glucocorticoid therapy in the treatment of TON.Early endoscopic surgery may help improve visual acuity in patients with residual vision.

Objective:To observe the effects of TCM compounds for eliminating phlegm and removing blood stasis on the ultrastructure of atrial myocardium in atrial fibrillation (AF) rats; To explore its possible mechanism.Methods:Totally 60 male SD rats were divided into blank group (10 rats) and model group (50 rats) according to random number table method. The atrial fibrillation model was established by tail vein injection of ACh-CaCl 2 mixture for 7 consecutive days, and then the rats with successful modeling were divided into model group, verapamil group, TCM compounds high-, medium- and low-dosage groups according to random number table method, with 10 rats in each group. TCM compounds high-, medium- and low-dosage groups were given Chinese herbal decoction 41.25, 20.63, 10.31 g/(kg?d) by gavage, respectively, and the verapamil group was given verapamil solution 25 g/(kg?d). The blank group and the model group were given an equal volume of normal saline by gavage for consecutive 14 days. After 14 consecutive days, electrophysiological recorder was used to measure the duration of atrial fibrillation in each group of rats; the changes of ultrastructure of atrial myocytes in each group were observed under transmission electron microscope; serum ROS, SOD and GSH-Px levels of rats were detected by ELISA. Results:Compared with the model group, the duration of atrial fibrillation in TCM compounds high-, medium- and low-dosage groups and verapamil group decreased ( P<0.05); the ultrastructural damage of atrial myocytes was improved; the content of ROS [(139.20±3.34) ng/ml,(139.00±3.28) ng/ml, (139.25±3.82) ng/ml vs. (155.60±7.32) ng/ml] in TCM compounds high- and medium-dosage groups and verapamil group decreased; the contents of SOD [(2.41±0.26) ng/ml, (2.40±0.12) ng/ml, (2.37±0.06) ng/ml vs.(2.12±0.21) ng/ml] increased ( P<0.05); the content of GSH-Px [(3.61±0.06) ng/ml, (3.60±0.08) ng/ml, (3.47±0.15) ng/ml, (3.51±0.19) ng/ml vs.(3.27±0.12) ng/ml] in TCM compounds high-, medium- and low-dosage groups and verapamil group increased ( P<0.05). Conclusion:TCM compounds for eliminating phlegm and removing blood stasis can shorten the duration of atrial fibrillation in rats, reduce the damage of ultrastructure of atrial myocytes in AF rats, regulate the expressions of serum ROS, SOD and GSH-Px in AF rats, and inhibit oxidative stress, which may be one of its mechanisms of action in the treatment of atrial fibrillation.

Objective To explore the mechanism of the treatment of atrial fibrillation(AF)with traditional Chinese medicine compound of eliminating phlegm and removing blood stasis.Methods Sixty male SD rats were randomly divided into the blank group and the model group.Ach(66 μg·mL-1)-CaCl2(10 mg·mL-1)was injected into the tail vein for 7 consecutive days to establish the rat AF model.The rats with successful modeling were randomly divided into model group,high,medium and low dose groups of Chinese herbal compound and verapamil group.The high,medium and low dose groups of Chinese herbal compound were given 12.38 mg,6.18 mg and 3.10 mg·kg-1·d-1 Chinese herbal compound for removing phlegm and removing blood stasis solution by gavage,while the verapamil group was given 8.31 mg·kg-1·d-1 verapamil solution by gavage,and the blank group and model group were given equal volume distilled water by gavage.During this period,the rats were still given tail vein injection for 14 consecutive days.The duration of atrial fibrillation in lead Ⅱ of rats was measured by electrophysiological recorder,the ultrastructural changes of rat atrial muscle were observed by transmission electron microscope,the relative expression of CAV1.2,CaM,CaMKⅡ mRNA in rat atrial muscle was detected by RT-PCR,and the expression of CAV1.2,CaM,CaMKⅡ and downstream proteins RyR2,P-RyR2 in rat atrial muscle was detected by Western blot.Results Compared with the blank group,the rats in the model group showed typical atrial fibrillation ECG.Compared with the model group,the duration of atrial fibrillation in the compound Chinese medicine group decreased.The arrangement of myofilaments was relatively neat,and the structure of mitochondria was relatively complete;CAV1.2 mRNA and protein expression increased(P<0.05),CaM,CaMKⅡ mRNA and protein expression decreased(P<0.01),downstream protein P-RyR2 expression decreased(P<0.01),RyR2 protein expression had no difference(P>0.05).Conclusion The Chinese herbal compound for removing phlegm and removing blood stasis can shorten the duration of atrial fibrillation in rats,inhibit the ultrastructure damage of atrial myocytes,and its mechanism may be related to regulating the expression of CAV1.2/CaM/CaMKⅡ signal pathway and improving the disorder of calcium regulation.

Objective: To investigate the prevalence of hyperuricemia and its correlation among adolescents aged 13-16 in Hanjiang district of Yangzhou city. Methods: Five hundred and nine adolescents aged 13-16 years in Hangjiang district of Yangzhou city were recruited. Their fasting serum uric acid level were measured by Benecheck premium UA monitoring system. The demographic imformation, family history, eating and living habits of the respondents were collected by questionnaires. Results: The average serum uric acid level of 509 adolescents in Hangjiang district of Yangzhou city was (374±98) μmol/L, and (420±103) μmol/L in males, higher than that of females [(329±70) μmol/L](t=11.69, P<0.05). The overall prevalence of HUA was 36.9%(188/509), and 43.2%(108/250) in males, higher than in females 30.8%(80/259)(χ²=4.16, P<0.05). Multivariate Logistic regression analysis showed that male [OR=1.70, 95%CI(1.18, 2.45)], obese [OR=8.99, 95%CI(4.58, 17.63)], high-salt oily diet [OR=1.67, 95%CI(1.05, 2.61)], soy products [OR=2.66, 95%CI(1.45, 4.88)], animal offal [OR=7.81, 95%CI(3.42, 17.83)], seafood [OR=4.80, 95%CI(2.83, 8.12)], sugary drinks [OR=6.49, 95%CI(3.08, 13.64)] and time spent on electronic products [OR=1.98, 95%CI(1.07, 3.65)] might be risk factors for hyperuricemia (P<0.05), while fruit [OR=0.52, 95%CI(0.32, 0.85)] and outdoor activities [OR=0.55, 95%CI(0.33, 0.92)] might be protective factors for HUA (P<0.05). Conclusion There is a high prevalence of hyperuricemia among adolescents aged 13-16 in Hangjiang district of Yangzhou city. The level of serum uric acid in adolescents significantly increased. Male, obesity, high salt and oily diets, soy products, animal offal, seafood, and sugary drinks may be risk factors for HUA. Fruits and outdoor activities may be protective factors for HUA. Relevant disciplines can take corresponding measures to prevent adolescent HUA.

Objective To analyze the expressions of lymphocytes in the peripheral blood and serum cytokines in the children with secretory otitis media (SOM) and the effects of glucocorticoids interventions.Methods Totally 90 SOM children were selected as case group,and 30 healthy children were selected as control group.The case group was randomly divided into group A (simple oral antibiotic treatment),group B (oral antibiotics combined with local glucocorticoid treatment) and group C (oral antibiotics combined with systemic glucocorticoid treatment),30 cases in each group.The CD4 + T lymphocytes percentage,CD8 + T lymphocytes percentage,the ratio of CD4 +/CD8 + T lymphocytes in peripheral blood and the serum interleukin-2 (IL-2),interferon gamma (IFN-γ),tumor necrosis factor alpha (TNF-α),interleukin-6 (IL-6),interleukin-10 (IL-10) levels were detected and compared between case group and control group.The air conduction auditory thresholds under different frequency of the patients in group A,group B and group C were examined and compared.Results The CD4 + T lymphocytes percentage,the ratio of CD4 +/CD8 + T lymphocytes in peripheral blood and the serum IL-2,IFN-γ,TNF-α,IL-6,IL-10 levels of the patients in the case group were significantly higher than those in the control group (P ＜ 0.0 5).After the treatment,the above indicators of the children in group A,group B and group C decreased,and there were significant differences before and after the treatment between two groups (P ＜ 0.05).The air conduction auditory thresholds under different frequency of the patients in group B or group C were significantly lower than those in group A (P ＜ 0.05),while there were no significant differences in the air conduction auditory thresholds under different frequency between the children in group B and group C (P ＞ 0.05).Conclusion The patients with SOM show imbalanced cell immune function and cytokines expressions in the peripheral blood.The combination of glucocorticoids therapy and routine antibiotic therapy can effectively improve the immune function and the therapeutic effects.