Objective·To investigate the bidirectional causal relationships between celiac disease(CeD)and Hashimoto thyroiditis(HT)as well as Graves disease(GD),using a two-sample Mendelian randomization(MR)approach.Methods·Single nucleotide polymorphisms(SNPs)related to CeD,HT and GD were extracted from publicly available Genome-Wide Association Studies(GWAS)databases and used as instrumental variables.The inverse-variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median(WME)and weighted mode(WMO)methods,to evaluate the causal associations between CeD and both HT and GD.Replication analyses using alternative GWAS datasets were conducted to validate the robustness of the results.Heterogeneity was assessed using Cochran's Q test,and pleiotropy was evaluated via MR-Egger intercept test.Leave-one-out analyses were performed to assess the impact of individual SNPs on the results.Results·The IVW analysis results indicated that genetically predicted CeD significantly increased the risk of HT[discovery group:OR=1.186(95%CI 1.114?1.262),P<0.001;replication group:OR=1.218(95%CI 1.090?1.361),P<0.001]and GD[discovery group:OR=1.214(95%CI 1.155?1.276),P<0.001;replication group:OR=1.273(95%CI 1.161?1.396),P<0.001].However,reverse MR analyses did not provide evidence for a causal relationship between HT and CeD,while genetically predicted GD significantly increased the risk of CeD[discovery group:OR=1.259(95%CI 1.006?1.576),P=0.044;replication group:OR=1.387(95%CI 1.233?1.560),P<0.001].Sensitivity analyses suggested that the results were not influenced by horizontal pleiotropy.Conclusion·CeD may be causally associated with a higher risk of HT and GD,while GD may increase the risk of developing CeD.HT does not appear to have an impact on CeD.

Objective·To investigate the bidirectional causal relationships between celiac disease(CeD)and Hashimoto thyroiditis(HT)as well as Graves disease(GD),using a two-sample Mendelian randomization(MR)approach.Methods·Single nucleotide polymorphisms(SNPs)related to CeD,HT and GD were extracted from publicly available Genome-Wide Association Studies(GWAS)databases and used as instrumental variables.The inverse-variance weighted(IVW)method served as the primary analytical approach,supplemented by MR-Egger,weighted median(WME)and weighted mode(WMO)methods,to evaluate the causal associations between CeD and both HT and GD.Replication analyses using alternative GWAS datasets were conducted to validate the robustness of the results.Heterogeneity was assessed using Cochran's Q test,and pleiotropy was evaluated via MR-Egger intercept test.Leave-one-out analyses were performed to assess the impact of individual SNPs on the results.Results·The IVW analysis results indicated that genetically predicted CeD significantly increased the risk of HT[discovery group:OR=1.186(95%CI 1.114?1.262),P<0.001;replication group:OR=1.218(95%CI 1.090?1.361),P<0.001]and GD[discovery group:OR=1.214(95%CI 1.155?1.276),P<0.001;replication group:OR=1.273(95%CI 1.161?1.396),P<0.001].However,reverse MR analyses did not provide evidence for a causal relationship between HT and CeD,while genetically predicted GD significantly increased the risk of CeD[discovery group:OR=1.259(95%CI 1.006?1.576),P=0.044;replication group:OR=1.387(95%CI 1.233?1.560),P<0.001].Sensitivity analyses suggested that the results were not influenced by horizontal pleiotropy.Conclusion·CeD may be causally associated with a higher risk of HT and GD,while GD may increase the risk of developing CeD.HT does not appear to have an impact on CeD.

Objective:To observe the neuroprotective effect of wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) in combination with Panax ginseng total saponin (PNS) on cerebral ischemia-reperfusion rats; To elucidate the mechanism of "wind medicine increasing effect".Methods:Totally 140 male SD rats were divided into sham-operation group, model group, PNS group, Puerariae Lobatue Radix group, Acori Tatarinowii Rhizoma group, Puerariae Lobatue Radix + PNS group, Acori Tatarinowii Rhizoma + PNS group according to the random number table method, with 20 rats in each group. Except for the sham-operation group, the cerebral ischemia/reperfusion rat model was established using the modified Longa line bolus method in the remaining groups. After 7 d of administration of the appropriate pharmacologic intervention in each group, neurological dysfunction was evaluated by Zea-longa score after final administration, cerebral infarct volume was determined by TTC staining; blood brain barrier (BBB) permeability of brain tissue on the ischemic side was detected by Evans blue content; BBB ultrastructure of each group of rats was observed by transmission electron microscopy; Claudin 5 protein expression level was detected by immunohistochemistry; Zonula occludens-1 (ZO-1), major facilitator supeffamily domain-containing protein 2a (Mfsd2a), Occludin, P-glycoprotein (P-gp), Monocarboxylate Transporters-1 (MCT1) and breast cancer resistance protein (BCRP) protein expression levels were detected by Western-blot.Results:Compared with the model group, the rat neurological function scores were reduced in each administration group ( P<0.05), infarct volume was reduced ( P<0.05), EB content of brain tissue decreased ( P<0.05), protein expressions of Claudin 5, ZO-1, Mfsd2a and Occludin in brain tissue were elevated ( P<0.05), the protein expressions of P-gp, BCRP and MCT1 were reduced ( P<0.05), and the protein expressions of Claudin 5, Mfsd2a, and Occludin was higher in the Puerariae Lobatue Radix + PNS group and Acori Tatarinowii Rhizoma + PNS group than that of each group of medication alone ( P<0.05), and the protein expression of MCT1 was lower than that of each group of medication alone ( P<0.05); the protein expression level of ZO-1 in the Puerariae Lobatue Radix + PNS group was higher than that of the group of medication alone ( P<0.05); P-gp protein expression was lower in Acori Tatarinowii Rhizoma + PNS group than in the PNS group and Acori Tatarinowii Rhizoma group ( P<0.05). Conclusion:Wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) may potentiate the neuroprotective effect of PNS on cerebral ischemia-reperfusion rats, and the mechanism may be related to the protection of BBB structural integrity and maintenance of central barrier properties, while regulating substance transport proteins and increasing the intracerebral content of the drug.

Objective:To study the effect of trefoil factor family (TFF) 3 on the expression of tight junctions (TJs) in the nasal mucosa epithelium of eosinophilic chronic rhinosinusitis (eCRS) and its mechanism.Methods:From September to December 2020, eligible patients from the Department of Otorhinolaryngology of the First Affiliated Hospital of Nanchang University were recruited, including 11 control patients and 37 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), from whom nasal mucosa and nasal polyp tissue samples were collected. Immunohistochemistry (IHC) was used to detect the localization and expression intensity of TFFs (TFF1, TFF2 and TFF3) and TJs (occudin, claudin-1 and ZO-1) in nasal mucosa. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) were used to detect the mRNA and protein expression. A cell model of tight junction injury in human nasal epithelial cells (HNECs) through stimulation with interleukin (IL)-13 was also established. The optimal modeling concentration and time for HNECs were determined, which were subsequently treated with TFF3 and/or a phosphoinositide 3-kinase (PI3K)-specific inhibitor (LY294002). Finally, RT-qPCR and WB were used to assess the effects of TFF3 on tight junctions and the PI3K/serine/threonine kinase (Akt) signaling pathway. Data were analyzed statistically using GraphPad Prism 7 software.Results:IHC results showed that the expression of TFF1 and TFF3 in nasal mucosa of eCRS group was significantly higher than that of control group ( t=4.62, P=0.002; t=5.89, P<0.001), respectively, mainly expressed in goblet cell. The expression of occludin, claudin-1 and ZO-1 in the nasal mucosa of the eCRS group was lower than that of the control group (occludin t=3.98, P=0.019; claudin-1 t=5.15, P=0.002; ZO-1 t=5.42, P=0.001), respectively. WB results showed that the expression of TFF3 in non-eosinophilic chronic sinusitis (Non-eCRS) group and eCRS group was higher than that in the control group ( t=3.62, P=0.036; t=5.93, P<0.001). The expression of occludin, claudin-1 and ZO-1 in eCRS group was lower than that in the control group (occludin t=5.14, P=0.002; claudin-1 t=6.35, P<0.001; ZO-1 t=6.64, P<0.001), respectively. The RT-qPCR results showed that compared with the control group, the levels of TFF1 and TFF3 mRNA were increased in the nasal mucosal epithelium of the Non-eCRS and eCRS groups (TFF1 t=3.98, P=0.046, t=4.89, P=0.002; TFF3 t=3.50, P=0.044, t=6.78, P<0.001). There was no statistically significant difference in TFF2 mRNA levels between the Non-eCRS and eCRS groups ( t=1.34, P=0.061; t=3.37, P=0.055). Compared with the control group, Non-eCRS and eCRS groups showed a decrease in the mRNA levels of occludin, claudin-1 and ZO-1 (occludin t=4.27, P=0.011, t=5.61, P=0.007; claudin-1 t=3.62, P=0.036, t=6.80, P<0.001; ZO-1 t=3.47, P=0.047, t=7.86, P<0.001). The mRNA levels of TFF3 and TJs in eCRS nasal mucosa tissue showed a moderate positive correlation (occludin r=0.661, claudin-1 r=0.614, ZO-1 r=0.548, all P<0.001); TFF1 showed a low degree of positive correlation with the expression of occludin, claudin-1 and ZO-1 (occludin r=0.467, P=0.040; claudin-1 r=0.362, P=0.012; ZO-1 r=0.425, P=0.025). The establishment of cell models showed that compared with normal HNECs, the mRNA expression of TFF3 was most significantly increased at a concentration of 50 ng/ml stimulated by IL-13 ( t=3.72, P=0.013); The mRNA expression of occludin, claudin-1 and ZO-1 decreased (occludin t=3.18, P=0.031; claudin-1 t=3.86, P=0.010; ZO-1 t=5.16, P=0.002). The expression of TFF3 mRNA increased most significantly after 15 hours of IL-13 stimulation ( t=3.14, P=0.034); The mRNA expression of occludin, claudin-1 and ZO-1 decreased (occludin t=3.97, P=0.010; claudin-1 t=4.78, P=0.004; ZO-1 t=5.16, P=0.004). TJs damage model could be established by treating HNECs with 50 ng/ml IL-13 for 15 hours. Intervention experiments showed that compared with the IL-13 group, the IL-13+TFF3 group showed an increase in TJs mRNA expression (occludin t=6.10, P=0.009; claudin-1 t=5.90, P=0.013; ZO-1 t=9.44, P=0.007). Compared with the IL-13 group, the expression of TJs protein in the IL-13+TFF3 group increased (occludin t=3.23, P=0.013; claudin-1 t=9.40, P=0.017; ZO-1 t=2.23, P=0.032); The expression of TJs protein decreased in the IL-13+TFF3+LY294002 group (occludin t=4.73, claudin-1 t=8.77, ZO-1 t=3.51, all P<0.001). Compared with the IL-13+TFF3 group, the IL-3+TFF3+LY294002 group showed a decrease in PI3K and p-Akt/Akt protein expression (PI3K t=13.29, p-Akt/Akt t=10.30, all P<0.001). The increased mRNA and protein expression of occludin, claudin-1 and ZO-1 induced by TFF3 were also inhibited by LY294002. Conclusion:TFF3 can up-regulate the expression of occludin, claudin-1, and ZO-1 through PI3K/Akt pathway, and has a certain protective effect on the nasal mucosal epithelial barrier, providing a new idea for treating eCRS.

Objective:To evaluate the safety and efficacy of a Zenith fenestrated aortic stent-graft (ZFEN) system in the treatment of short-necked aneurysms.Methods:The clinical data of 5 patients receiving F-EVAR in Zhongshan Hospital, Fudan University from Mar 2018 to Sep 2019 according to the standards of short-necked abdominal aortic aneurysm and COOK ZFEN custom stent were retrospectively analyzed.Results:Patients' average age was (69±11) years old. The time of stent customization was 4-6 weeks. The average maximum diameter of AAA was (60.8±14.0) mm. The average proximal neck diameter was (26.0±2.6) mm and the average length anchoring zone was (6.4±2.2) mm. The rate of technical success was 100%. There was no intraoperative loss of visceral vessels and stent displacement. The meane follow-up time was 6.8 months. The perioperative mortality was 0, and there were no other major complications. There were 3 patients with simple type Ⅱ endoleak and 1 patient with type Ⅲ endoleak. The endoleaks disappeared in 4 patients during follow-up of 3-12 months. 1 patient suffered with type Ⅱ and type Ⅲ endoleak, and the visceral vessels and branching stents were patent in all patients.Conclusion:The short term result of COOK ZFEN stent-graft system was safe and feasible for the treatment of short-necked AAA.

Objective: To investigate the expression of microRNA-133b (miR-133b) in esophageal squamous cell carcinoma (ESCC), and explore its effect and the underlying molecular mechanisms on cell proliferation and invasion. Methods: Real-time quantitative PCR (qPCR) was used to examine miR-133b expression in 63 ESCC tissues and paired adjacent non-cancerous tissues, several ESCC cells (Eca109, EC9706, EC1, TE1, KYSE70) and normal esophageal epithelial cell Het-1A. MiR-133b mimic, inhibitor and negative control (NC) were transfected into TE1 cells. The effect of miR-133b on cell proliferation and invasion were determined by CCK-8 and Transwell assays, respectively. Subsequently, the target gene of miR-133b was predicted by online tools TargetScan and miRDB, which was verified by dual luciferase reporter assays. Finally, Western blot was utilized to detect the effects of miR-133b overexpression on expression of target gene TAGLN2 as well as EMT-related proteins E-cadherin, N-cadherin, Snail, Slug and Vimentin. Results: Relative levels of miR-133b in ESCC tissues (0.295±0.040) were significantly lower than those in adjacent non-cancerous tissues (1.002±0.011, P<0.001). The expression of miR-133b was tightly associated with clinical staging, lymph node metastasis and prognosis. Moreover, relative levels of miR-133b in ESCC cells Eca109, EC9706, EC1, TE1 and KYSE70 (0.679±0.031, 0.391±0.008, 0.236±0.016, 0.031±0.005 and 0.099±0.020) were evidently lower than that in normal esophageal epithelial cell Het-1A (1.005±0.016, all P<0.001). In TE1 cells, miR-133b mimic significantly increased the level of miR-133b to 6.199±0.627, and suppressed cell proliferation and invasion, whereas miR-133b inhibitor obviously decreased its expression to 0.182±0.023, and promoted cell proliferation and invasion. Most notably, the relative luciferase activities of miR-133b-mimic group (0.320±0.018) in TE1 cells transfected with TAGLN-3′UTR-WT were markedly lower than that in NC group (1.010±0.036, P<0.001), whereas those in TAGLN-3′UTR-MUT transfection cells were 1.019±0.056 and 1.008±0.021, respectively, showing no significantly statistical difference (P>0.05). Furthermore, miR-133b overexpression markedly downregulated TAGLN2, N-cadherin, Snail, Slug and Vimentin levels, and increased E-cadherin expression. Conclusion MiR-133b plays an important role in the proliferation and invasion of ESCC cells by regulating TAGLN2 expression, and it may be a potential therapeutic target for ESCC patients.

Objective: To evaluate the safety and effectiveness of the Endurant stent graft for abdominal aortic aneurysm cases with proximal neck length <10 mm. Methods: This study was a retrospective analysis. From January 2010 to May 2015, 22 consecutive abdominal aortic aneurysm patients with proximal neck length <10 mm were treated with endovascular aortic repair by Endurant stent graft in Department of Vascular Surgery, Zhongshan Hospital, Fudan University. There were 19 (86.3%) male cases, aging from 57 to 84 years. All patients underwent preoperative CT angiography and the anatomic parameters of abdominal aortic aneurysm were measured. All patients performed standard endovascular aortic repair first and if there was obvious proximal typeⅠ endoleak, the CUFF or the chimney technology were applied to observed the perioperative technical and the clinical success rate. During follow-up, the incidence of adverse events and the reintervention rate were observed. Results: These 22 cases had proximal neck length 5 to 9 mm with the average of (7.2±1.4) mm. Immediate endoleak occurred in 5 patients with 4 cases of proximal typeⅠ endoleak, 3 cases were implanted proximal CUFF, 1 case implanted CUFF and left renal artery chimney. One case died perioperatively, the clinical success rate was 95.4%, the technical success rate was 77.3%. During the follow-up of 6 to 54 months, there was 1 case with delayed proximal type-1 endoleak, during operation the patient had no endoleak, but disappeared 6 months later without further intervention. So the incidence of adverse event was 4.5% and reintervention rate was 0. Conclusion The Endurant stent graft for abdominal aortic aneurysm cases with proximal neck length < 10 mm is safe and effective.

Estrogen receptors (ERs) are members of nuclear receptors and related to several diseases such as cancer, inflammation and osteoporosis. ERs have two forms, ERα and ERβ, which have different functions and organism distributions. Compounds selectively targeting ERβ can regulate important physiological functions and avoid the side effects caused by targeting ERα. Therefore, selective ERβ ligands have received considerable research interest in recent years. In this article, different kinds of selective ERβ ligands were summarized and their structure-activity relationships were also analyzed.

Objective To analyze the perioperative mortality,stroke rates and late benefits of carotid artery stenting for the treatment of unilateral severe stenosis of carotid artery with contralateral obliteration in a single medical center.Methods Clinical data of 38 cases were analyzed retrospectively,including postoperative period and follow-up.Results The technical success rate was 100％ ( 38/38 )with no peri-operative 30-day mortality or ischemic stroke.The overall peri-operative complication rate was 34.2％ ( 13/38),including transient ischemic attack (TIA) in 5.3％ (2/38).The average follow-up time was ( 29 ± 13 ) months with follow-up rate of 86.8％ ( 33/38 ).The mortality was 0 and the overall complication rate was 12.1％ (4/33),including TIA in 6.1％ (2/33).No patients had recurrent stroke.Twenty-three cases underwent whole brain CT perfusion evaluation before and after the therapy.A significant improvement of the perfusion parameters was observed in the stenotic side after CAS.Conclusions CAS contralateral to an occluded carotid artery can be performed with acceptable perioperative mortality and stroke risk rates,as well as a satisfactory long-term beneficial effect in stroke prevention.

Objective To evaluate the clinical characteristics and surgical treatment of renal stenosis resulting from fibromuscular dysplasia ( FMD ). Methods 16 cases from 1998 to 2011 were reviewed,the average age was (28 ± 13 ) years old. Among them, all patients suffered refractory hypertension and only one presented renal dysfunction. Aorto-renal bypass was performed in 2 cases.Resection and reconstruction was performed in 2 cases,balloon angioplasty in 10 and stent implantation in 3.Results There was 1 death peri-operatively.13 out of 15 cases were followed-up with no death.Significant decline of blood pressure [ (134 ± 14 )/( 83 ± 8 ) mm Hg vs.( 151 ± 17 )/( 96 ± 16 ) mm H g ( P ＜ 0.01 ) ]and 100％ effective rate were observed.The creatine level were preserved after surgical treatment [ (61 ±22) μmol/L vs.(69 ± 22) μmol/L,(P ＞ 0.05 ) ] with 4 cases improved and the other 9 stable.12 patients received ultrasound surveillance with only one case of 20％ restenosis. Conclusions Renal stenosis due to FMD are most common in children and the youth with hypertension as major presentation. Balloon angioplasty is the first choice of surgical treatment with positive efficacy.