The Hedgehog (Hh) signaling pathway plays a crucial role in embryo development of drosophila and a variety of vertebrate including humans,via regulating cell differentiation and proliferation.Mutation of Hh and aberrant activation or overexpression of the secreted Hh signaling molecules may induce cancer.Recent studies show that Hh signaling is associatied with invasion and metastasis in multiple types of malignant tumours.The machanisms are correlated with maintaining of cancer stem cells,epithelial-mesenchymal transition ( EMT),tumor cell autocrine/paracrine signaling and promotion of tumor angiogenesis and lymphangiogenesis.The study of mechanisms how Hh signaling promotes cancer metastasis,will provide new directions for molecular diagnosis,prognosis and molecular targeted therapy of cancer.

Objective To evaluate the characteristics of left ventricular structure ,function ,myocardial mechanics ,hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy ( HCM ) using state‐of‐the‐art echocardiography . Methods A consecutive series of 85 adult HCM patients w ho were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected . According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography ,the patients were divided into three groups :patients with non‐obstructive HCM ( n ＝28) ,those with labile‐obstructive HCM ( n ＝27) ,and those with obstructive HCM ( n ＝ 30 ) . In addition ,16 normal family members of HCM patients were included as control group . T wo‐dimensional speckle tracking imaging ,tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states . Results ① As compared with the control group ,left ventricular end‐diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups ( all P ＜ 0 .05 ) . Left ventricular maximum wall thickness and left ventricular mass index were the highest in obstructive HCM , followed by labile‐obstructive and non‐obstructive HCM ,and the lowest in the control group ( all P ＜0 .05) . ②A t rest ,the left ventricular global longitudinal ,circumferential and radial strain ( GLS ,GCS and GRS) ,as well as the twist of obstructive HCM were significantly lower than the other three groups ( all P ＜0 .05) . As compared with the control group ,the GLS and twist decreased in the labile‐obstructive and non‐obstructive HCM ( all P ＜0 .05 ) ,but there were no significant changes of GCS and GRS ( all P ＞ 0 .05 ) . T he obstructive HCM had the lowest mitral annular plane systolic excursion ( M APSE ) and s′,and the longest systolic peaking time standard deviation( T s‐SD) and early diastolic peaking time standard deviation ( Te‐SD) ( all P ＜0 .05) . T he left ventricular diastolic function of obstructive HCM ( e′,the E/e′ratio and the left atrial volume index ) was the worst ,labile‐obstruction and non‐obstructive HCM were better ,and the control group was the best ( all P ＜ 0 .001 ) . ③ During exercise ,the GLS ,GCS ,GRS ,twist of the left ventricle and the M APSE were the lowest in the obstructive HCM ,which increased in the labile‐obstructive and non‐obstructive HCM ,and were best in the control group . T he T s‐SD and Te‐SD were the shortest in the control group ,were prolonged in non‐obstructive and labile‐obstruction HCM ,and were longest in obstructive HCM ( all P ＜ 0 .05 ) . Additionally ,the exercise time of the control group was the longest , followed by non‐obstructive and labile‐obstruction HCM ,and the shortest in the obstructive HCM ( all P ＜0 .05) . T he M ET s of obstructive HCM were significantly lower than the other three groups ( all P ＜0 .05) . Conclusions In obstructive HCM ,the left ventricular systolic strain and synchronization ,as well as the M APSE ,are significantly impaired in patients both at rest and during exercise . T he patients with labile‐obstructive and non‐obstructive HCM have reduced left ventricular GLS , twist ,and e′,but normal left ventricular GCS ,GRS ,synchrony ,and M APSE at rest ,which are all impaired during exercise .

Objective:To investigate the different expression of galectin-10 in nasal polyps with different degrees of eosinophil infiltration, and to explore whether galectin-10 can be used as a new biomarker of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and its possible role in the pathogenesis of ECRSwNP.Methods:A total of 36 patients (20 males, 16 females, aged from 14 to 74 years old) who underwent functional endoscopic sinus surgery at the Second Affiliated Hospital of Nanchang University from November 2018 to April 2019 were enrolled into the retrospective study, including 11 cases of ECRSwNP, 15 cases of non-ECRSwNP and 10 cases in control group (deviation of nasal septum). The patients were divided into allergic rhinitis and non-allergic rhinitis groups, atopy and non-atopy groups according to whether patients in the experimental group and control group had allergic rhinitis and atopy. HE staining was performed for histological assessment of CRSwNP which was classfied as ECRSwNP and non-ECRSwNP. Immunohistochemistry (IHC) was used to determine the positive localization and semi-quantitative expression level of galectin-10 protein in ERSwNP, non-ECRSwNP and control groups. The expression levels of galectin-10 protein in three groups were determined by Western Blot. The expression levels of galectin-10 mRNA in three groups were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Analyzing the correlation between the expression of galectin-10 and clinical factors including the allergic rhinitis and atopy, SPSS 19.0 software and Graphpad prism 7.0 were used for statistical analysis and mapping.Results:By using IHC method, it was found that galectin-10 was mainly localized in eosinophils in the polyp tissues. The semi-quantitative expression of the galectin-10 in the ECRSwNP group (0.051±0.003) was significantly higher than that of non-ECRSwNP (0.028±0.004) and control groups (0.025±0.004, t value was 3.862 and 5.137, both P<0.01). There was no significant difference between the control and non-ECRSwNP groups ( t=0.560, P>0.05). The expression of galectin-10 in the ECRSwNP group was significantly higher than that of non-ECRSwNP and control groups ( t value was 25.351 and 27.376, both P<0.01). However, there was no significant difference between the non-ECRSwNP and control groups ( t=1.071, P>0.05). Compared with the non-ECRSwNP (1.188±0.054) and control groups (1.020±0.142), the expression of galectin-10 mRNA was higher in the ECRSwNP group (2.413±0.303), the differences were significant ( t value was 3.973 and 4.156, both P<0.05). There was no significant difference between the non-ECRSwNP and control groups ( t=1.110, P>0.05). There was no significant difference in the expression of galectin-10 between the allergic rhinitis group and the non-allergic rhinitis group (all P>0.05), so as to the atopy group and non-atopy group(all P>0.05). Conclusion:The expression level of galectin-10 is elevated in ECRSwNP, and not influenced by allergic status, suggesting that galectin-10 may be a new biomarker for ECRSwNP and play an important role in the pathogenesis of ECRSwNP.

Objective:To investigate the role of the CXC chemokine receptor 1 (CXCR1)/CXC chemokine ligand 8 (CXCL8) axis in the abnormal proliferation of bile duct epithelial cells in primary biliary cholangitis (PBC).Methods:30 female C57BL/6 mice were randomly divided into the PBC model group (PBC group), reparixin intervention group (Rep group), and blank control group (Con group) in an in vivo experiment. PBC animal models were established after 12 weeks of intraperitoneal injection of 2-octanoic acid coupled to bovine serum albumin (2OA-BSA) combined with polyinosinic acid polycytidylic acid (polyI:C). After successful modelling, reparixin was injected subcutaneously into the Rep group (2.5 mg · kg -1 · d -1, 3 weeks). Hematoxylin-eosin staining was used to detect histological changes in the liver. An immunohistochemical method was used to detect the expression of cytokeratin 19 (CK-19). Tumor necrosis factor-α (TNF-α), γ-interferon (IFN-γ) and interleukin (IL)-6 mRNA expression were detected by qRT-PCR. Western blot was used to detect nuclear transcription factor-κB p65 (NF-κB p65), extracellularly regulated protein kinase 1/2 (ERK1/2), phosphorylated extracellularly regulated protein kinase 1/2 (p-ERK1/2), Bcl-2-related X protein (Bax), B lymphoma-2 (Bcl-2), and cysteine proteinase-3 (Caspase- 3) expression. Human intrahepatic bile duct epithelial cells were divided into an IL-8 intervention group (IL-8 group), an IL-8+Reparicin intervention group (Rep group), and a blank control group (Con group) in an in vitro experiment. The IL-8 group was cultured with 10 ng/ml human recombinant IL-8 protein, and the Rep group was cultured with 10 ng/ml human recombinant IL-8 protein, followed by 100 nmol/L Reparicin. Cell proliferation was detected by the EdU method. The expression of TNF-α, IFN-γ and IL-6 was detected by an enzyme-linked immunosorbent assay. The expression of CXCR1 mRNA was detected by qRT-PCR. The expression of NF-κB p65, ERK1/2 and p-ERK1/2 was detected by western blot. A one-way ANOVA was used for comparisons between data sets. Results:The results of in vivo experiments revealed that the proliferation of cholangiocytes, the expression of NF-κB and ERK pathway-related proteins, and the expression of inflammatory cytokines were increased in the Con group compared with the PBC group. However, reparixin intervention reversed the aforementioned outcomes (P<0.05). In vitro experiments showed that the proliferation of human intrahepatic cholangiocyte epithelial cells, the expression of CXCR1 mRNA, the expression of NF-κB and ERK pathway-related proteins, and the expression of inflammatory cytokines were increased in the IL-8 group compared with the Con group. Compared with the IL-8 group, the proliferation of human intrahepatic cholangiocyte epithelial cells, NF-κB and ERK pathway-related proteins, and inflammatory indicators were significantly reduced in the Rep group ( P < 0.05). Conclusion:The CXCR1/CXCL8 axis can regulate the abnormal proliferation of bile duct epithelial cells in PBC, and its mechanism of action may be related to NF-κB and ERK pathways.

Objective: To evaluate the characteristics of left ventricular structure, function, myocardial mechanics, hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy (HCM) using state-of-the-art echocardiography. Methods: A consecutive series of 85 adult HCM patients who were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected. According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography, the patients were divided into three groups: patients with non-obstructive HCM (n=28), those with labile-obstructive HCM (n=27), and those with obstructive HCM (n=30). In addition, 16 normal family members of HCM patients were included as control group. Two-dimensional speckle tracking imaging, tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states. Results: ①As compared with the control group, left ventricular end-diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups(all P<0.05). Left ventricular maximum wall thickness and left ventricular mass index were the highest in obstructive HCM, followed by labile-obstructive and non-obstructive HCM, and the lowest in the control group (all P<0.05). ②At rest, the left ventricular global longitudinal, circumferential and radial strain (GLS, GCS and GRS), as well as the twist of obstructive HCM were significantly lower than the other three groups (all P<0.05). As compared with the control group, the GLS and twist decreased in the labile-obstructive and non-obstructive HCM(all P<0.05), but there were no significant changes of GCS and GRS (all P>0.05). The obstructive HCM had the lowest mitral annular plane systolic excursion (MAPSE) and s′, and the longest systolic peaking time standard deviation(Ts-SD) and early diastolic peaking time standard deviation(Te-SD) (all P<0.05). The left ventricular diastolic function of obstructive HCM (e′, the E/e′ ratio and the left atrial volume index) was the worst, labile-obstruction and non-obstructive HCM were better, and the control group was the best (all P<0.001). ③During exercise, the GLS, GCS, GRS, twist of the left ventricle and the MAPSE were the lowest in the obstructive HCM, which increased in the labile-obstructive and non-obstructive HCM, and were best in the control group. The Ts-SD and Te-SD were the shortest in the control group, were prolonged in non-obstructive and labile-obstruction HCM, and were longest in obstructive HCM (all P<0.05). Additionally, the exercise time of the control group was the longest, followed by non-obstructive and labile-obstruction HCM, and the shortest in the obstructive HCM (all P<0.05). The METs of obstructive HCM were significantly lower than the other three groups (all P<0.05). Conclusions In obstructive HCM, the left ventricular systolic strain and synchronization, as well as the MAPSE, are significantly impaired in patients both at rest and during exercise. The patients with labile-obstructive and non-obstructive HCM have reduced left ventricular GLS, twist, and e′, but normal left ventricular GCS, GRS, synchrony, and MAPSE at rest, which are all impaired during exercise.