Objective:To observe the expression levels of Toll-like receptor 4 (TLR4) signaling pathway-related proteins and their phosphorylation in the liver tissues of rats with inorganic arsenic poisoning, and to explore the role of TLR4-mediated inflammatory signaling pathway in arsenic-induced liver fibrosis injury.Methods:Eighteen healthy weanling SD rats were divided into 3 groups according to their body weight (80 - 100 g) using a random number table (6 rats in each group, half males and half females). The control group was given 10 ml/kg of normal saline by gavage. The sodium arsenite (NaAsO 2) exposure group was given 10 mg/kg of NaAsO 2 by gavage. The TAK-242 intervention group was given 10 mg/kg of NaAsO 2 by gavage, and 0.5 mg/kg of TAK-242 was also administered intraperitoneally to inhibit TLR4 after 12 weeks. All rats were administered 6 days a week for 36 weeks. At the end of the treatment, the liver tissues and serum of the rats in each group were collected. HE and Masson staining were used to observe the pathological and fibrotic changes of the liver tissues. Automatic biochemical analyzer was used to detect serum liver function indexes of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Western blot was used to detect the expression changes of rat liver fibrosis protein α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), Vimentin and TLR4 signaling pathway-related proteins TLR4, nuclear factor κB (NF-κB)-p65 subunit (p65), NF-κB-p50 subunit (p50) and their phosphorylation p-p65 and p-p50 expression levels. Enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion levels of inflammatory related factors interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-10. Results:HE and Masson staining results showed that compared with the control group, the NaAsO 2 exposure group showed significant inflammatory cell infiltration, hepatocyte necrosis and collagen fibrous deposition, while the TAK-242 intervention group showed improvement of the inflammatory cell infiltration and reduction of collagen fibrous deposition compared with the NaAsO 2 exposure group. The results of serum liver function indexes showed that ALT, AST and ALP in NaAsO 2 exposure group were increased compared with the control group, but the TAK-242 intervention group was significantly decreased compared with the NaAsO 2 exposure group ( P < 0.05). Western bolt results showed that in NaAsO 2 exposure group, the expression levels of fibrosis protein α-SMA, TGF-β1 and Vimentin (1.04 ± 0.19, 0.92 ± 0.14, 1.20 ± 0.21) and TLR4 signaling pathway-related proteins and their phosphorylation TLR4, p50, p-p50 and p-p65 (1.16 ± 0.21, 0.95 ± 0.16, 1.24 ± 0.23, 1.56 ± 0.25) were higher than the control group (0.44 ± 0.08, 0.42 ± 0.08, 0.72 ± 0.07, 0.69 ± 0.15, 0.71 ± 0.11, 0.46 ± 0.07, 0.54 ± 0.11, P < 0.05), and the TAK-242 intervention group (0.60 ± 0.13, 0.59 ± 0.16, 0.49 ± 0.11, 0.47 ± 0.08, 0.86 ± 0.09, 0.79 ± 0.14, 1.02 ± 0.17) were lower than the NaAsO 2 exposure group ( P < 0.05). There was no significant difference in the expression level of TLR4 signal pathway-related protein p65 among the three groups ( F = 14.29, P = 0.053). ELISA results showed that the secretion levels of IL-6 and TNF-α [(98.89 ± 4.58), (83.25 ± 4.57) ng/g] in rats liver tissues of the NaAsO 2 exposure group were higher than the control group [(27.30 ± 3.92), (27.77 ± 1.83) ng/g, P < 0.05], while the secretion level of IL-10 [(36.88 ± 3.86) ng/g] was lower than the control group [(77.96 ± 7.87) ng/g, P < 0.05]. In TAK-242 intervention group, IL-6 and TNF-α secretion levels [(44.32 ± 3.60), (36.51 ± 2.93) ng/g] were lower and IL-10 secretion level [(60.40 ± 4.94) ng/g] was higher compared with the NaAsO 2 exposure group ( P < 0.05). Conclusion:TLR4-mediated inflammatory signaling pathway-related proteins and their phosphorylation are highly expressed in the liver tissues of rats with inorganic arsenic poisoning, and inhibition of TLR4 signaling pathway could significantly reduce the degree of liver fibrosis injury caused by inorganic arsenic in rats.

Background Long-term exposure to sodium arsenite leads to its accumulation in the liver and liver injury as a result. Previous studies showed that mesenchymal cells play an important role in hepatic fibrosis, and epithelial-mesenchymal transformation (EMT) is considered to be a main source of mesenchymal cells. Objective To investigate the effects of sodium arsenite at different doses on liver fibrosis and EMT-related protein expressions in SD rats. Methods Twenty-four healthy weaned SD rats, half male and half female, were randomly divided into four groups according to body weight, with 6 rats in each group. The four groups were control group (gavage with 10.0 mL·kg⁻¹ physiological saline), 2.5 mg·kg⁻¹ sodium arsenite group, 5.0 mg·kg⁻¹ sodium arsenite group, and 10.0 mg·kg⁻¹ sodium arsenite group. All rats were gavaged 6 d per week for 36 weeks and weighed once a week, the serum and liver tissues of rats were collected and weighed, then the organ coefficient was calculated. Hematoxylin-eosin staining and Masson's trichrome staining were used to determine the pathological changes of hepatic fibrosis in rats. The serum secretion levels of hyaluronic acid (HA), laminin (LN), procollagen Ⅲ N-terminal propeptide (PⅢNP), and collagen Ⅳ (COL-Ⅳ) in rats were detected by enzyme-linked immunosorbent assay (ELISA). The protein expressions of HSCs activation-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1), as well as EMT-related markers, such as E-cadherin, N-cadherin, Vimentin, and Snail, were detected by Western blotting. Results Compared with the control group, the 10.0 mg·kg⁻¹ sodium arsenite group showed decreased body weight (P<0.05) and increased liver coefficient (P<0.05) of female and male rats. The pathological staining showed that, compared with the control group, a large number of inflammatory cells were observed in liver tissue of rats exposed to sodium arsenite, liver parenchymal cells were also liquefied, necrotic, and denatured, and the collagen positive staining area of liver tissue showed an upward trend along with the increase of arsenic exposure dose (P<0.05). The results of ELISA and Western blotting showed that the serum secretion levels of HA, LN, PⅢNP, and COL-Ⅳ in the 5.0 and 10.0 mg·kg⁻¹ sodium arsenite groups were higher than those in the control group and the 2.5 mg·kg⁻¹ sodium arsenite group (P<0.05). Compared with the control group, the expressions of α-SMA and TGF-β1 proteins in liver tissue were increased in each sodium arsenite exposure group (P<0.05), the expression levels of E-cadherin protein were decreased (P<0.05), and the expression levels of N-cadherin, Vimentin, and Snail were increased (P<0.05). Conclusion Sodium arsenite exposure can induce HSCs activation and liver fibrosis injury in SD rats, resulting in increased extracellular matrix secretion levels, accompanied by EMT in liver tissue, suggesting that EMT is closely related to the process of liver fibrosis caused by arsenic.

Objective:To explore the effectiveness of clinical pathway (CP) and team-based learning (TBL) teaching method in standardized residency training of gynecology.Methods:The research included 40 residents as objects who took standardized training in gynecological rotation in Luohe Central Hospital from July 2017 to July 2019, and they were randomized into experimental group and control group. The combination of CP and TBL teaching method was used in the experimental group ( n=20), while the traditional teaching method was applied in the control group ( n=20). All residents were tested for the professional theory and clinical skill after training. After the training, a survey about the teaching satisfaction and the effectiveness of teaching methods was conducted for both groups. Statistical analysis was performed by SPSS 23.0 software. Results:The average scores of professional theory and clinical practice skills in the experimental group were (85.55±5.96) points and (89.90±6.40) points respectively, which were better than the average scores of the control group [(76.36±6.68) points and (75.50±4.81) points, respectively], and there were significant differences between two groups ( P<0.05). The results of the questionnaire survey showed that the experimental group residents had a higher degree of satisfaction and a higher evaluation of the teaching method than the control group. Conclusion:CP and TBL teaching is beneficial to improve the quality of standardized residency training of gynecology, and it is suggested to make wide popularization and application in the training.

Objective:To explore the effect and significance of clinical pathway (CP) teaching method in the standardized residency training of gynecology.Methods:The study included in 60 residents having standardized residency training of gynecology from June 2016 to June 2019 as research subjects, and they were randomized into control group and experimental group. The traditional teaching method was applied in the control group ( n=30), while CP teaching method were used in the experimental group ( n=30). All residents in the two groups were tested for the basic theory, case analysis and clinical skill after training. At the same time, they all had a teaching satisfaction survey, and the effectiveness of CP teaching was investigated among residents of the experimental group. Descriptive statistics, t test and chi-square analysis were performed by SPSS 23.0 software. Results:The results of examination about the basic theory [(86.30±7.04) vs. (75.30±5.27)], case analysis [(84.97±6.49) vs. (78.60±4.78)] and clinical skill [(83.90±6.32) vs. (77.40±8.29)] in the experimental group were higher than those in the control group, with statistical differences ( P<0.05). And residents in the experimental group believed that CP teaching was helpful to improve their self-learning ability, clinical thinking ability, operation ability, communication ability and scientific research ability, and they supported the continuous promotion of CP teaching. Conclusion:CP teaching is beneficial to improve the quality of standardized residency training of gynecology, and it is expected to be further promoted and applied in the standardized residency training of gynecology.

Background Arsenic is a well-known environmental toxicant. Hepatic fibrosis could occur dueto excessive or long-term exposure to arsenic, while associated molecular mechanisms remain undefined. Mitogen-inducible gene 6 (Mig-6) exhibits a protective effect on numerous diseases or cancers. However, the specific role of Mig-6 in the mechanisms of arsenite-induced hepatic fibrosis remains indistinct. Objective To investigate the specific role of Mig-6 in the activation of hepatic stellate cells (HSC) and the deposition of extracellular matrix (ECM) induced by sodium arsenite (NaAsO₂). Methods Human hepatic stellate cells (Lx-2) were treated with 0, 1.875, 3.75, 7.5, and 15 μmol·L⁻¹ of NaAsO₂ for 24 h, or with 7.5 μmol·L⁻¹ NaAsO₂ for 0, 12, 24, 48, and 72 h. Additionally, Lx-2 cells were transfected by pcDNA3.1(+)/Mig-6, then treated with 7.5 μmol·L⁻¹ NaAsO₂ for 24 h; a blank control group, a pcDNA3.1(+)-control group, a pcDNA3.1(+)/Mig-6 group, and an arsenic (7.5 μmol·L⁻¹ NaAsO₂) group were also set up. After transfection, the cells and culture supernatants were collected, and the protein levels of Mig-6, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1) in Lx-2 cells were identified by Western blotting analysis; moreover, the secretion levels of main ECM components in supernatants such as hyaluronic acid (HA), laminin (LN), collagens IV (COL-IV), and procollagen-III (PIIINP) were tested by ELISA. Results The Mig-6 expression decreased in the 3.75, 7.5, and 15 μmol·L⁻¹ NaAsO₂ groups (0.561±0.095, 0.695±0.048, and 0.401±0.030) compared to the control group (1.000±0.000) in Lx-2 cells (P<0.05). After administration with 7.5 μmol·L⁻¹ of NaAsO₂ for 24, 48, and 72 h, the Mig-6 expression (0.856±0.036, 0.515±0.077, 0.491±0.060) decreased compared with the 0 h group (1.000±0.000) (P<0.05). After over-expression of Mig-6, the results of Lx-2 activation related protein levels showed that compared to the control group, the α-SMA and TGF-β1 expression were up-regulated in the arsenic group (P<0.05); meanwhile, the α-SMA and TGF-β1 in the Mig-6 over-expression combined arsenic exposure group reduced compared to the arsenic (7.5 μmol·L⁻¹) group (P<0.05). The results of ELISA showed that compared with the control group, the HA, LN, PIIINP, COL-IV in the arsenic group were up-regulated (P<0.05); while compared to the arsenic group, the HA, LN, PIIINP, and COL-IV in the Mig-6 over-expression combined with arsenic exposure group were decreased (P<0.05). Conclusion Arsenic down-regulates Mig-6 expression in HSC, and over-expression of Mig-6 can reverse the activation of HSC and ECM deposition induced by arsenic exposure. It suggests that Mig-6 plays a protective role in arsenic-induced HSC activation and ECM deposition.

This paper introduced the development of medical specialists alliance in Zhejiang University. With Jinhua Central Hospital as an example,merits and setbacks of the 3-level trusteeship model in practice were discussed,with improvement recommendations raised for progress of the hierarchical medical system.

Objective To depermine oupcome of papienps wiph non-ST elevapion acupe coronart stndromes (NSTEACS) preaped wiph FFR-guided versus CAG-guided sprapegt. Methods From Jult 1. 2014 po Jult 30. 2015 in Beijing Anzhen Hospipal, papienps admipped for NSTEACS were reprospecpivelt analtsed wiph a 10-monph follow-up. 142 cases on CAG were furpher assessed wiph FFR ( phe FFR group). Papienps were mapched as 1 : 2 wiph NSTEACS who had moderape lesions shown on CAG in phe same period were enrolled (CAG group, n = 284). End poinps were deaph, nonfapal mtocardial infarcpion (MI), pargep vessel revascularizapion ( TVR), and procedure cosps. Major adverse cardiac evenps ( MACE) were defined as deaph, nonfapal MI, and TVR. Results Fifpt-pwo papienps (36. 6% ) in phe FFR group had FFR less phan 0. 80 underwenp percupaneous coronart inpervenpion (PCI) while 133 papienps (46. 8% ) in phe CAG group received PCI (P =0. 037). Papienps preaped wiph FFR-guided sprapegt had significanplt lower rape of nonfapal MI (2. 2% vs. 4. 5% , P =0. 040) and TVR (5. 9% vs. 11. 7% , P = 0. 046). No spapispical difference was observed in morpalipt (0. 7% vs. 1. 1% , P = 0. 682) and MACE (8. 8% vs. 14. 4% , P = 0. 085). Topal financial cosp was less in phe FFR group (P = 0. 033). Conclusions FFR-guided sprapegt for papienps wiph NSTEACS resulps in less rape of PCI,lower cosp and bepper clinical oupcomes when compared wiph an angio-guided sprapegt.

Thanks to the policies of resources to strengthen grassroots ,and innovative resource placement in Zhejiang province and the help of Zhejiang University School of Medicine ,Shaoxing regional medical center has achieved significant improvement in its medical capabilities .The cooperation features the following :active promotion of new medical ideas and key technologies ;overall enhancement of scientific and technological innovation ;talent training to advance disciplinary development ;and joint efforts to train postgraduates .The momentum ,however ,can only be maintained ,unless such problems as the means of resources placement ,disciplines alignment ,and medical workers development can be well addressed .

Objective To explore the practicality and feasibility and evaluation of the team based learning method (TBL) combined with the clinical pathway leaning method (CP) in clinical teaching of department of gynecology and obstetrics. Methods Toltally 40 clinical specialist interns selected for the study were randomly divided into two groups (each 20) respectively, using TBL com-bined with CP teaching method and traditional teaching method, and to make analysis and comparisons on the above two teaching methods. Differences were compared with t testing. Meanwhile, a question-naire survey was carried out among students of TBL combined with CP teaching group for qualitative analysis of the implementation effect of TBL combined with CP pedagogy. (Qualitative analysis is the medical students' evaluation of teaching effect, without further statistical processing). Results The professional test results of TBL combined with CP teaching team were superior to the traditional teach-ing group [(83.95 ±7.63) vs. (72.00 ±5.26)] and the difference was significant by paired t tests and analysis (t=5.063,P<0.05). The knowledge contest results of TBL combined with CP teaching team were superior to the traditional teaching group(90 vs. 85,95 vs. 75,85 vs. 70). TBL combined with CP method has been recognized by 90% medical students and they think that most of their quality has been further improved. Conclusions TBL combined with CP method for the clinical teaching of de-partment of gynecology and obstetrics is practical and feasible, and should be widely applied.