[Objective]To explore how hyperthyroidism induces ventricular remodeling via activating β-catenin/FoxO1 in rat cardiomyocytes.[Methods]Hyperthyroidism-induced ventricular remodeling rat models were established by intraperitoneal injection of levothyroxine(T4)at 0.1 mg/kg for 30 days.β-catenin inhibitor MSAB(14 mg/kg)was admin-istrated for 30 days.We used western blot to detect the expression of myocardial hypertrophy marker ANP,β-catenin and FoxO1;immunofluorescence to examine the expression and intracellular distribution of β-catenin and FoxO1.Hyperthy-roidism-induced cardiomyocyte hypertrophy rat models were established by treatment of triiodothyronine(T3)into cul-tured primary neonatal rat cardiomyocytes for 24 hours.β-catenin siRNA(30 nmol/L)was used to down-regulate β-catenin expression in cardiomyocytes.Western blot and immunofluorescence were used to analyze the effects of β-catenin inhibition on the hyperthyroidism-induced cardiomyocyte hypertrophy.[Results]Following Wnt/β-catenin activation,β-catenin was found increased nuclear expression,to bind to the nuclear transcriptional factors and regulate the gene ex-pression.β-catenin nuclear expression was significantly increased in the hyperthyroidism-induced ventricular remodeling rats,but no change was found in the expression of typical transcriptional factor TCF7l2.Our results revealed that inhibiting β-catenin by MSAB attenuated the hyperthyroidism-induced rat ventricular remodeling.Further analysis indicated that β-catenin/FoxO1 expression was significantly increased in hyperthyroidism-induced myocardial hypertrophy which could be attenuated by suppressing β-catenin/FoxO1 in cardiomyocytes.[Conclusions]β-catenin/FoxO1 is activated in hyperthy-roidism-induced myocardial hypertrophy and β-catenin/FoxO1 inhibition attenuates hyperthyroidism-induced cardiomyo-cyte hypertrophy.

Objective:To explore the efficacy of the combination of radiofrequency ablation(RFA) and endoscopic metal stent in the treatment of patients with unresectable cholangiocarcinoma.Methods:From January 3, 2012 to June 30, 2019, at the Department of Endoscopic of the Third Affiliated Hospital of Naval Medical University, the clinical data of 44 patients with unresectable cholangiocarcinoma who were treated by the combination of RFA and endoscopic metal stent were retrospectively collected, which included age, gender, location of cholangiocarcinoma(hilar cholangiocarcinoma and distal cholangiocarcinoma), etc. Postoperative evaluation was conducted based on the follow-up, including clinical success rate, postoperative complication rate, time of stent patency and overall survival time (OS). The Kaplan-Meier method and log-rank test were used to analyze the difference of OS between patients with hilar cholangiocarcinoma and distal cholangiocarcinoma. Mann-Whitney U test was used for statistical analysis. Results:The age of the 44 patients with cholangiocarcinoma was (70.3±11.6) years old, with 20 males (45.5%). There were 22 patients (50.0%) with hilar cholangiocarcinoma and 22 patients (50.0%) with distal cholangiocarcinoma. The clinical success rate of 44 patients was 93.2%(41/44). A total of 5 patients(11.4%) had postoperative complications, which were all improved by appropriate treatment. The median time of follow-up of the 44 patient was 9.2 months(ranged from 3.1 to 57.6 months), the median time of stent patency was 7.0 months (ranged from 5.8 to 8.2 months). Thirty-two patients (72.7%) died during the follow-up, and the median OS was 10.9 months(ranged from 9.0 to 12.8 months). The median OS of patients with hilar cholangiocarcinoma was 7.8 months(ranged from 4.6 to 11.0 months) and that of patients with distal cholangiocarcinoma was 12.5 months(ranged from 5.7 to 19.4 months), and there was no statistically significant difference( P>0.05). Conclusion:RFA combined with endoscopic metal stent is safe and effective in the treatment of patients with unresectable cholangiocarcinoma.

Objective:To assess the therapeutic efficacy and safety of the gemcitabine combined with nedaplatin (GN) chemotherapy for metastatic human epidermal growth factor receptor-2 (HER-2) negative breast cancer patients.Methods:Forty-five patients with HER-2 negative recurrent metastatic breast cancer who had received prior adjuvant or neoadjuvant therapy with anthracycline and/or taxanes were enrolled. All the patients received GN regime from January 2014 to February 2019. The therapeutic efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST) 1.1. The adverse response was evaluated and monitored according to common terminology criteria for adverse events (CTCAE). The progression-free survival (PFS) and overall survival (OS) and prognostic factors were also analyzed.Results:All of the 45 patients received 4 course GN, 1 of them achieved complete response, 21 achieved partial response. The objective response rate was 48.9 (95% CI: 33.7%-64.1%). Grade 3-4 hematological toxicities include leukopenia occurred in 10 (22.2%) of patients, neutropenia in 13 (28.9%) patients, and thrombocytopenia in 8 (17.6%) patients. The grade 3-4 hematological toxicities mainly manifested as nausea and vomiting, and the incidence was 4.4% (2/45). Among the 45 patients, 34 died, the median PFS was 5.1 (95% CI: 3.9-6.1) months and the median OS was 17.6 (95% CI: 13.1-20.9) months. Conclusion:The combination of gemcitabine and nedaplatin is an effective and tolerable treatment for metastatic breast cancer patients previously treated with anthracyclines and/or taxanes.

Objective:To assess the therapeutic efficacy and safety of the gemcitabine combined with nedaplatin (GN) chemotherapy for metastatic human epidermal growth factor receptor-2 (HER-2) negative breast cancer patients.Methods:Forty-five patients with HER-2 negative recurrent metastatic breast cancer who had received prior adjuvant or neoadjuvant therapy with anthracycline and/or taxanes were enrolled. All the patients received GN regime from January 2014 to February 2019. The therapeutic efficacy was evaluated according to response evaluation criteria in solid tumors (RECIST) 1.1. The adverse response was evaluated and monitored according to common terminology criteria for adverse events (CTCAE). The progression-free survival (PFS) and overall survival (OS) and prognostic factors were also analyzed.Results:All of the 45 patients received 4 course GN, 1 of them achieved complete response, 21 achieved partial response. The objective response rate was 48.9 (95% CI: 33.7%-64.1%). Grade 3-4 hematological toxicities include leukopenia occurred in 10 (22.2%) of patients, neutropenia in 13 (28.9%) patients, and thrombocytopenia in 8 (17.6%) patients. The grade 3-4 hematological toxicities mainly manifested as nausea and vomiting, and the incidence was 4.4% (2/45). Among the 45 patients, 34 died, the median PFS was 5.1 (95% CI: 3.9-6.1) months and the median OS was 17.6 (95% CI: 13.1-20.9) months. Conclusion:The combination of gemcitabine and nedaplatin is an effective and tolerable treatment for metastatic breast cancer patients previously treated with anthracyclines and/or taxanes.

Objective To construct a CaME141G fusion protein-expressing plasmid,and to express,purify,and identify the activity of the recombinant protein. Methods The 141st site of the wild type CaM,E (GAG),was mutated to G (GGG),using site-specific mutagenesis technology. Escherichia coli BL-21 was transformed with the mutant plasmid. The GST-CaME141G fusion protein was mass-cultured and induced for expression. Subsequently,the GST-CaME141G fusion protein was purified using GS-4B beads. PreScission protease was applied to remove the GST,the Bradford method used to determine the concentration of purified protein,and SDS-PAGE used to detect its relative molecular weight and purity. The GST pull-down assay was used to study the protein's biological activity. Results The CaME141G protein was successfully purified at a high concentration and purity. The protein could interact with PreIQ protein fragments from the myocardial CaV1. 2 calcium channel C terminal,in a CaME141G concentration-dependent manner. Therefore,CaME141G has the ability to bind with the CaV1. 2 calcium channel. Conclusion This study successfully constructed a CaME141G fusion protein-expressing plasmid and purified the CaME141G protein. This lays a foundation for regulating the function of CaM mutations in the myocardial CaV1. 2 calcium channel,and for the study of its relationship with diseases of the cardiovascular system.

Objective To investigate the effects and mechanism of evodiamine on the proliferation and apoptosis of osteosarcoma MG-63 cells.Methods MG-63 cells were cultured with evodiamine for 24 hours,and the cell proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay.Cell cycle arrest,apoptosis and intracellular Ca2+ accumulation were evaluated by flow cytometry.BALB/C mice model of osteosarcoma was established to investigate the tumor inhibitory effect of evodiamine on human osteosarcoma.Wnt/β-catenin signaling protein expressions in osteosarcoma cells were detected by Western blotting.Results As concentration of evodiamine increasing (0.25 μmol/L,0.5 μmol/L,1.0 μmol/L,2.0 μmol/L and 4.0 μmol/L),the inhibition rate of MG-63 ceils increased [(4.18 ± 1.26)％,(15.49 ± 2.26)％,(40.55 ± 6.57)％,(49.87 ±7.69)％ and (60.42 ±8.29)％].The difference was statistically significant between 2.0 μmol/L group and the control group (t =-2.66,P ＜ 0.05).MG-63 cells were cultured with 2.0 μmol/L evodiamine for 24 hours,and the apoptotic rate was (64.67 ± 8.63) ％,the proportion of S phase cells was (85.33 ± 9.31)％,the fluorescence of Ca2+ was 97.33 ± 21.31.The corresponding data of the control group were (4.94 ± 0.81) ％,(43.67 ± 8.92) ％ and 28.67 ± 8.92,the differences were statistically significant (t =-11.90,P ＜ 0.05;t =-7.22,P ＜ 0.05;t =-6.65,P ＜ 0.05).On mice model,the tumor weight of evodiamine group and the control group was (2.15 ±0.35)g and (4.29 ±0.49)g respectively,the difference was statistically significant (t =7.95,P ＜ 0.05).Comparing with the control group (1.00 ± 0.00),evodiamine decreased the expression of β-catenin protein (0.72 ± 0.36) and increased the expressions of Bax (1.15± 0.27) and Caspase-3 (1.46 ± 0.18) protein,and the differences were statistically significant (t =-3.05,P ＜ 0.05;t =-6.42,P ＜ 0.05;t =-5.85,P ＜ 0.05).Conclusion Evodiamine inhibits proliferation and induces apoptosis of human osteosarcoma MG-63 cells by blocking Wnt/β-catenin signaling.

Objective To investigate the application value of the Perclose Proglide vascular devices in the thoracic endovascular aortic repair (TEVAR) of aortic dissection.Methods Retrospective analysis of 106 patients who underwent TEVAR for Standford B type aortic dissection were performed.The femoral lumen was measured by CTA be fore,1 month and 1 year after TEVAR.Results A total of 223 Perclose Proglide vascular closure devices were used in the 106 patients,including 97 patients with 2 devices,7 patients with 3 devices,2 patients with 4 devices.The puncture femoral artery diameters had no significant differences between before and 1 month,1 year after TEVAR (all P ＞0.05).Conclusion Per close Proglide vascular closure devices can be effectively and safely used in the TEVAR,which has little influence on the femoral artery diameter,and is worth to be applied in the clinics extensively.

Background Keratoconus is a chronic and progressive non-inflammatory ectatic disorder characterized by corneal thinning and irregular corneal topography,and its pathgenesis is a hot topic.A suitable animal model of keratoconus is still lacking,which limits the progress of relevant research.Corneal ectasia is a main anatomical basis of keratoconus,so we assume that keratoconus model could be constructed by simulating corneal ectasia.Objective This study was to investigate the influence of collagenase type Ⅱ on biomechanical responses detected by corneal visualization Scheimpflug technology (Corvis ST) and the feasibility of construction of rabbit model of corneal ectasia using coliagenase type Ⅱ.Methods This study protocol was approved by Ethic Committee of Peking University First Hospital and followed the Statement about experimental animal use and care from Association for Research in Vision and Ophthalmology (ARVO).Keratectasia models were established in 10 right eyes of 10 New Zealand white rabbits by soaking 8 mm-diameter central cornea using collagenase type Ⅱ solution prepared by PBS solution containing 15％ dextran (200 μl of 5 mg/ml) for 30 minutes after epithelial debridement,and only 200 μl PBS solution containing 15％ dextran was used in the same way in the left eyes as controls.The average corneal curvature (Km) and central corneal thickness (CCT) were measured with hand-held electronic corneal curvature meter and corneal ultra-sonic pachymetry respectively before modeling and 14 days after modeling.Corneal biomechanical parameters and intraocular pressure were measured in vivo by using Corvis ST at day 14 after modeling.The rabbits were sacrificed at day 14 after modeling,and corneal sections were prepared for hematoxylineosin staining and transmission electron microscopic examination.Results There were no significant differences in Km and C CT between model group and control group before modeling (Km:[48.28±2.29] D vs.[48.82± 1.63] D;CCT:[356.50± 19.13] μm vs.[356.20±21.66] μm;both at P＞0.05).The Km increased to (48.87±2.27) D and CCT decreased to (340.40±19.84)μm at day 14 after modeling,which were significantly different from (46.86±1.47) D and (367.80±23.38)μm (both at P＜0.01).The maximal deformation amplitude of model group and control group was (1.25±0.07) mm and (1.15 ±0.13) mm,respectively,showing a considerable difference between them (t=2.65,P＜0.05).No significant differences were found in applanation 1/2 time,applanation 1/2 length,applanation velocity,radius of curvature and peak distance between the two groups (all at P＞0.05).The morphology and ultrastructure examinations revealed that the arrangement of collagen fibers was loose and disorder and the interfiber space was enlarged in comparison with control group.Conclusions Collagenase type Ⅱ can lower corneal biomechanical properties.Soaking of cornea with collagenase type Ⅱ may be a potential way to establish a keratectasia animal model.

Objective To further intensify the reform of public hospitals,promote talents team building and scientific research management innovation,enhancing the overall capacity of care delivery,as well as the development of science and technology in grass-roots hospitals.Methods A series of measures were adopted to arouse the enthusiasm of personnel to conduct research and finally increase the research outcomes.Concrete measures include talent training program and scientific research man-agement innovation,construction funding assurance,whole-process dynamic management,clarification of the quantitative evaluation index,research rewards,research funding management,as well as performance management.Results After implementation of such measures,the academic atmosphere changed a lot,medical technology improved,the quality of scientific research,project application and research outcomes increased dramatically which has statistical significance compare to previous situations.Conclusions The establishment of the incentive system plays a significant role.It helps in talent agglomeration during a relatively short period of time,exploring the potential capabilities of scientific research,enhancing the core competitiveness of hospital scientific research,which provide strong intellectual support and talent guarantee for hospitals development.

Objective To evaluate the feasibility and efficacy of catheter-directed thrombolysis (CDT) for the treatment of non-acute (history ＞ 14 days) deep venous thrombosis (DVT) of the lower extremity.Methods Clinical data of 63 patients of non-acute DVT of lower extremities treated by CDT and adjunctive angioplasty and stenting from July 2009 to August 2013 were analyzed retrospectively.Venous recanalization was graded by a thrombus score based on pre-and post-treatment venography.Follow-up was performed by Doppler ultrasound and clinical evaluation.Results A total of 63 limbs with DVT with a mean symptom duration of (22 ± 5) days were treated by a continuous combined with pulse-spray infusion of urokinase of (1.21 ± 0.69) million IU/d for (74 ± 21) hours.Significant recanalization was achieved in 77％ (48 of 63) of the treated limbs.After thrombolysis,percutaneous angioplasty was done for 15 residual lesions and stent placement was performed in 11 iliac veins and 1 femoral vein.Minor bleeding occurred in 6 (10％) patients,no patients suffered from major bleeding or symptomatic pulmonary embolism.During follow up (mean:15 ±6 months),the veins were patent in 45 (71％) limbs.15 (24％) limbs developed mild post-thrombotic syndrome (PTS),and none had severe PTS.Conclusions CDT combined with adjunctive angioplasty and stenting is safe and effective for removal of the clot burden and for restoration of the venous flow in patients with non-acute lower extremity DVT.