Objective:To investigate the role of hypoxia-induced angiopoietin-like protein 4 (ANGPTL4) expression in experimental choroidal neovascularization (CNV).Methods:Twenty-seven SPF male C57BL/6J mice aged 6-8 weeks were selected.Eighteen of the mice were used to establish a laser-induced CNV model.On the 7th day after laser photocoagulation, success of the modeling was verified using optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA). The retinal pigment epithelium (RPE)-choroid-sclera complex was extracted for protein analysis before modeling and on the 3rd and 7th days after modeling.The relative expression levels of ANGPTL4 and vascular endothelial growth factor (VEGF) at different time points were detected by Western blot.Additionally, frozen sections of mouse eyeballs on day 7 after modeling were prepared and the expression and cellular localization of ANGPTL4 were observed by immunofluorescence.RF/6A cells, derived from monkey choroidal retinal endothelial cells, were treated with 200 μmol/L cobalt chloride (CoCl 2) in the culture medium for 0, 3, 6, and 12 hours.RF/6A cells were also divided into a normal control group, a hypoxia group, and a hypoxia+ si-ANGPTL4 group, and cells were transfected with a plasmid containing si-ANGPTL4 sequence.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot, and the differences in tube formation among the groups were observed by tube formation assay.A total of 27 male C57BL/6J mice were randomly divided into CNV group, CNV+ si-NC group, and CNV+ si-ANGPTL4 group, with 9 mice in each group.In the CNV+ si-NC and CNV+ si-ANGPTL4 groups, si-NC and si-ANGPTL4 were respectively injected into the vitreous cavity after the CNV model was established.Fluorescence leakage in mice was observed by FFA, and the length, thickness and area of CNV was observed using OCTA and immunofluorescence staining of choroidal flat mounts.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot.All animal experiments were conducted in accordance with ARVO Statement on the Use of Animals in Ophthalmic and Vision Research.The experimental protocol was approved by the Affiliated Hospital of Nantong University (No.S20220822-902). Results:Before modeling and on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 protein were 1.00±0.00, 1.58±0.05, and 1.90±0.04, respectively, and the relative expression levels of VEGF protein were 1.00±0.00, 1.31±0.05, and 1.84±0.04, respectively, with statistically significant overall differences ( F=528.934, 390.424, both P<0.05). Among them, on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 and VEGF proteins were significantly higher in CNV group than in the control group (all P<0.05). The tissues of each layer of the retina were clear in the control group, while neovascularization could be seen growing under the retinal neuroepithelial layer in the CNV group.Compared with the control group, ANGPTL4 expression was significantly increased and colocalized with vascular endothelial cells in the CNV group.After CoCl 2 treatment of RF/6A cells for 3, 6, and 12 hours, the relative expression levels of ANGPTL4 and VEGF proteins were higher than at 0 hour, with statistically significant differences (all P<0.05). Compared with the control group, the relative ANGPTL4 protein expression was increased in the hypoxia group and significantly decreased in the hypoxia+ si-ANGPTL4 group, showing statistically significant differences (both P<0.05). The number of tube formations in the control group, hypoxia group, and hypoxia+ si-ANGPTL4 group were 12.67±1.53, 19.64±1.56, and 17.01±1.04, respectively, with a statistically significant overall difference ( F=33.091, P<0.01). The number of tube formations increased in the hypoxia group and hypoxia+ si-ANGPTL4 group compared with the control group, and the number of tube formations decreased in the hypoxia+ si-ANGPTL4 group compared with the hypoxia group, with statistically significant differences (all P<0.05). Relative expression levels of ANGPTL4 and VEGF proteins were significantly lower in the CNV+ si-ANGPTL4 group than those in the CNV group (both P<0.05). The CNV area was significantly lower in the CNV+ si-ANGPTL4 group than in the CNV group and CNV+ si-NC group (both P<0.05). Conclusions:Hypoxia-induced ANGPTL4 promotes experimental CNV formation in vivo and in vitro.Inhibiting ANGPTL4 can reduce CNV formation and leakage.

Objective:To investigate the role of hypoxia-induced angiopoietin-like protein 4 (ANGPTL4) expression in experimental choroidal neovascularization (CNV).Methods:Twenty-seven SPF male C57BL/6J mice aged 6-8 weeks were selected.Eighteen of the mice were used to establish a laser-induced CNV model.On the 7th day after laser photocoagulation, success of the modeling was verified using optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA). The retinal pigment epithelium (RPE)-choroid-sclera complex was extracted for protein analysis before modeling and on the 3rd and 7th days after modeling.The relative expression levels of ANGPTL4 and vascular endothelial growth factor (VEGF) at different time points were detected by Western blot.Additionally, frozen sections of mouse eyeballs on day 7 after modeling were prepared and the expression and cellular localization of ANGPTL4 were observed by immunofluorescence.RF/6A cells, derived from monkey choroidal retinal endothelial cells, were treated with 200 μmol/L cobalt chloride (CoCl 2) in the culture medium for 0, 3, 6, and 12 hours.RF/6A cells were also divided into a normal control group, a hypoxia group, and a hypoxia+ si-ANGPTL4 group, and cells were transfected with a plasmid containing si-ANGPTL4 sequence.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot, and the differences in tube formation among the groups were observed by tube formation assay.A total of 27 male C57BL/6J mice were randomly divided into CNV group, CNV+ si-NC group, and CNV+ si-ANGPTL4 group, with 9 mice in each group.In the CNV+ si-NC and CNV+ si-ANGPTL4 groups, si-NC and si-ANGPTL4 were respectively injected into the vitreous cavity after the CNV model was established.Fluorescence leakage in mice was observed by FFA, and the length, thickness and area of CNV was observed using OCTA and immunofluorescence staining of choroidal flat mounts.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot.All animal experiments were conducted in accordance with ARVO Statement on the Use of Animals in Ophthalmic and Vision Research.The experimental protocol was approved by the Affiliated Hospital of Nantong University (No.S20220822-902). Results:Before modeling and on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 protein were 1.00±0.00, 1.58±0.05, and 1.90±0.04, respectively, and the relative expression levels of VEGF protein were 1.00±0.00, 1.31±0.05, and 1.84±0.04, respectively, with statistically significant overall differences ( F=528.934, 390.424, both P<0.05). Among them, on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 and VEGF proteins were significantly higher in CNV group than in the control group (all P<0.05). The tissues of each layer of the retina were clear in the control group, while neovascularization could be seen growing under the retinal neuroepithelial layer in the CNV group.Compared with the control group, ANGPTL4 expression was significantly increased and colocalized with vascular endothelial cells in the CNV group.After CoCl 2 treatment of RF/6A cells for 3, 6, and 12 hours, the relative expression levels of ANGPTL4 and VEGF proteins were higher than at 0 hour, with statistically significant differences (all P<0.05). Compared with the control group, the relative ANGPTL4 protein expression was increased in the hypoxia group and significantly decreased in the hypoxia+ si-ANGPTL4 group, showing statistically significant differences (both P<0.05). The number of tube formations in the control group, hypoxia group, and hypoxia+ si-ANGPTL4 group were 12.67±1.53, 19.64±1.56, and 17.01±1.04, respectively, with a statistically significant overall difference ( F=33.091, P<0.01). The number of tube formations increased in the hypoxia group and hypoxia+ si-ANGPTL4 group compared with the control group, and the number of tube formations decreased in the hypoxia+ si-ANGPTL4 group compared with the hypoxia group, with statistically significant differences (all P<0.05). Relative expression levels of ANGPTL4 and VEGF proteins were significantly lower in the CNV+ si-ANGPTL4 group than those in the CNV group (both P<0.05). The CNV area was significantly lower in the CNV+ si-ANGPTL4 group than in the CNV group and CNV+ si-NC group (both P<0.05). Conclusions:Hypoxia-induced ANGPTL4 promotes experimental CNV formation in vivo and in vitro.Inhibiting ANGPTL4 can reduce CNV formation and leakage.

Objective:To compare the mid-term clinical effects of AngioJet rheolytic thrombectomy assisted catheter-directed thrombolysis (ART+CDT) with catheter-directed thrombolysis (CDT) in the treatment of acute deep venous thrombosis of lower extremities.Methods:Ninety-one patients admitted to the Department from Jan 2016 to Dec 2017 were placed with inferior vena cava filters and divided into ART+CDT group (30 cases)and CDT group (61 cases). Total urokinase dosge, thrombolytic time, operative cost, length of hospital stay, detumescence rate, thrombus clearance rate, cumulative patency rate of lower limb veins, Villalta score at 2 years and 5 years, thrombosis recurrence rate and chronic venous insufficiency quality of life questionnaire were compared between the two groups.Results:The success rate of surgery was 100% in both groups, there was no mortality. There were significant differences in the short-term postoperative outcomes between the two groups in terms of total dosage of urokinase, thrombolysis time, total cost of surgery, length of hospital stay, detumescence rate, venous patency scores before and after treatment, and venous patency rate (all P<0.05). For the mid- and long-term postoperative outcomes of 2 and 5 years, there were no significant differences in the incidence of PTS, recurrence rate of thrombus, chronic venous function scale, and cumulative patency rate at 2 years (all P>0.05). Conclusions:ART+CDT has a significant advantage over CDT alone in terms of early efficacy and early reopening of blood flow in patients. Both ART+CDT and CDT have a low incidence of PTS and a low recurrence rate of thrombus in the mid-term follow-up, and both have satisfactory performance in the mid- and long-term efficacy of interventional treatment of deep venous thrombosis of lower limbs.

Advanced technology not only brings good news to patients, but also causes a series of ethical issues. Subject risk/benefit assessment is the core of ethical review in clinical research. By combing the development status of China ethics review committee, analyzing the problems existing in the current ethical review, this paper proposed to standardize the establishment and independence of ethics review committee, improve the relevant laws and regulations of the ethics review committee, establish the administrative access and evaluation mechanism of the ethics review committee, build a multi-center mutual recognition alliance, improve the standardized operating procedures of the ethics review committee, set up an ethical personnel training system, and strengthen the review capacity building of the ethics review committee, so as to provide new ideas for the review work of the committee, then better protect the rights and interests of subjects and promote the development of medical science.

BACKGROUND: AND PURPOSE: Previous studies have explored the association between retinal vascular changes and cognitive impairment. The retinal vasculature shares some characteristics with the cerebral vasculature, and quantitative changes in it could indicate cognitive impairment. Hence, a comprehensive meta-analysis was performed to clarify the potential relationship between retinal vascular geometric changes and cognitive impairment. METHODS: Relevant databases were scrupulously and systematically searched for retinal vascular geometric changes including caliber, tortuosity, and fractal dimension (FD), and for cognitive impairment. The Newcastle-Ottawa Scale was used to evaluate the methodological quality of included studies. RevMan was used to perform the meta-analysis and detect publication bias. Sensitivity analyses were also performed. RESULTS: Five studies that involved 2,343 subjects were finally included in the meta-analysis. The results showed that there was no significant association between central retinal artery equivalents (Z=1.17) or central retinal venular equivalents (Z=1.74) and cognitive impairment (both p>0.05). Similarly, no significant difference was detected in retinal arteriolar tortuosity (Z=0.91) and venular tortuosity (Z=1.31) (both p>0.05). However, the retinal arteriolar FD (mean difference: −0.03, 95% CI: −0.05, −0.01) and venular FD (mean difference: −0.03, 95% CI: −0.05, −0.02) were associated with cognitive impairment. CONCLUSIONS A smaller retinal microvascular FD might be associated with cognitive impairment. Further large-sample and well-controlled original studies are required to confirm the present findings.

In this paper, we lay down a homogenization training standard for resident standardized training through a joint discussion among experts from three national resident standardized training bases. The aim of the homogenization of resident standardized training quality shall be reached through the synchronous implementation of tutorial system and comprehensive formative evaluation, the strengthening of training quality process management and the promotion and advancement of training quality of resident standardized training.

Objective To analyze the clinical efficacy of AngioJet mechanical thrombus aspiration system for patients with acute pulmonary embolism (PE).Methods Clinical data of 28 cases of acute pulmonary embolism (PE) patients was retrospectively analyzed,8 cases (AngioJet group) were treated with AngioJet + CDT,20 cases were treated by pigtail catheter thrombolysis(CDT group)alone,the total amount of urokinase,thrombolytic time,related detection index and the occurrence of complications were compared between the two groups.Results The dosage of urokinase in the two groups was (72.5 ± 44.4) × 104U and (169.0 ± 59.3) × 104 U respectively,P ＜ 0.05.The catheter indwelling time was (1.0 ± 0.89) days and (2.65 ± 0.86) days respectively (P ＜ 0.05).There were no statistically significant differences in SBP,PaO2,SpO2 and D-dimer between the two groups before and after operation (P ＞ 0.05).Conclusion Both AngioJet and CDT are effective methods for the treatment of acute PE.The combination of the two methods can accelerate the improvement of clinical symptoms,reducing the dosage of thrombolytic drugs and the occurrence of surgery-related complications.

Objective To evaluate clinical outcome of patients treated with endovascular dilation and stent placement for ilio-femoral venous postthrombotic syndrome (PTS).Methods 42 PTS cases were enrolled in our group from June 2003 to December 2011.Dilation and stent placement in stenosis/ occlusion of ilio-femoral veins were performed in all cases,temporary femoral arteriovenous fistula was established in 24 cases.Results These were not severe perioperative complications.All patients were followed up for 8-75 months.Preoperative limb ulcers in 5 cases were healed.Early thrombosis in stents found in 3 cases was cleared by catheter directed thrombolysis (CDT).Severe in-stent restenosis (＞ 50％)was found in 10 cases,treated with dialation or re-stenting.Primary patency,assisted primary patency and secondary patency rates were 75％,78％,80.1％;64.1％,67.1％,69.6％;63.8％,65.3％,66％;61.7％,65％,65.2％,respectively,at 6 months,12 months,24 months and 36 months.Postoperative Venous Clinical Severrity Score (VCSS) decreased (P =0.000).There was statistical significant improvement in every dimension evaluated by the MOS item short from health survey(SF-36) after operation (P =0.000).Conclusion Ilio-femoral venous stenting is a safe and effective treatment for PTS and with good clinical midterm results.

Objective To evaluate the surgical and interventional therapy in patients with acute superior mesenteric vein thrombosis.Methods In this series,31 acute superior mesenteric vein thrombosis(SMVT) cases were reviewed from Oct 2006 to Feb 2012.According to varied clinical presence,patients received superior mesenteric vein thrombectomy with necrotic bowel resection or indirected catheter thrombolysis through superior mesenteric artery.Results 6 of 9 cases undergoing surgery were cured and other 3 still complained abdominal distension when discharged for not being able to bear anticoagulation and thrombolysis after operation due to alimentary tract hemorrhage,and residual thrombus was shown in superior veins by venography.17 of 22 treated by interventional therapy gained obvious relief within 72 hours after intervention,others gained symptomatic relief in 5-7 days.Indirected catheter thrombolysis were interrupted in 2 due to alimentary tract hemorrhage.One patient was shifted to surgery 48 hours after catheter thrombolysis due to deterioration.Mean duration of follow-up after hospital discharge was (19 ± 5) months in 25 cases,20 had no abdominal distension and pain,3 with postcibal abdominal distension.Conclusions Indirected thrombolytic therapy by way of the superior mesenteric artery is a technically simple,safe and effective therapy for patients with acute SMVT.

Objective To evaluate a combination of interventional treatment and surgical exploration for acute lower limb ischemic disease.Methods We reviewed 42 cases admitted from July 2007 to January 2010,all patients complained pain,paralysis,pulselessness,pallor and paresthesia.After Fogarty thrombectomy angiography was taken in DSA room.Patients with angiostenosis greater than 50％ were then managed by interventional treatment(CDT,PTA,Stenting).Results Lives were saved in all patients,40 lower limbs were saved,and 2 patients received below knee amputation.The amputation rate was 4.76％.Dorsal or(and)posterior tibial artery of foot was felt in 33 patients,symptoms significantly improved.The other 7 patients still had painful and paralysis on the diseased limb.Conclusions The interventional treatment and surgical operation in acute lower limb ischemic disease is safe and result is satisfactory,which can improve the long-term patency and salvage rate of the lower limb.