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Objective To investigate the effect of the HtrA serine peptidase 3(HTRA3)gene on choroidal neovascu-larization(CNV)and M2 macrophage polarization.Methods Fasting venous blood was collected from 30 patients with wet age-related macular degeneration(wAMD group)and 30 healthy subjects(normal group).The serum HTRA3 messen-ger ribonucleic acid(mRNA)level was detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR).RF/6A cells were randomly divided into the control group,NC-sh group and HTRA3-sh group.Lentiviral vectors of NC-shRNA and HTRA3-shRNA were transfected into RF/6A cells in the NC-sh group and HTRA3-sh group by Lipo-fectamine2000.HTRA3 transfection was detected by qRT-PCR and Western blot.Then,the RF/6A cells were randomly di-vided into the N group,H group,H+NC-sh group and H+HTRA3-sh group.After cell transfection,RF/6A cells in the N group were cultured in a RPMI 1640 complete medium at a normoxia state,and cells in other groups were cultured in a RP-MI 1640 medium with 200 mmol·L-1 CoCl2 at a hypoxia state.Tubule formation was measured by Matrigel.The C57BL/6J mice were divided into the control group,CNV group,CNV+NC-sh group and CNV+HTRA3-sh group,with 12 mice in each group.Mice in the control group were unmodeled mice,and mice in the other groups were laser-induced CNV model mice.NC-shRNA and HTRA3-shRNA lentiviral vectors with a titer of 1 × 1011 TU·mL-1 were administered to mice in the CNV+NC-sh group and CNV+HTRA3-sh group via intravitreal injection.Mice in the control group and CNV group were in-jected with phosphate buffered saline.After 7 days of treatment,the mice were examined by fundus fluorescein angiogra-phy,and the eyeballs received hematoxylin & eosin staining.The mRNA levels of HTRA3,chitinase-like protein 3(Ym-1),arginase 1(Arg-1),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2)and vascular endothelial growth factor(VEGF)in RF/6A cells or choroidal tissues were detected by qRT-PCR.The protein expression levels of HTRA3,VEGF and nuclear factor kappa B(NF-κB)p65 in RF/6A cells or choroidal tissues were detected by Western blot.Re-sults Compared with the normal group,serum HTRA3 mRNA level of patients in the wAMD group increased(t=11.804,P＜0.001).Compared with the control group and NC-sh group,the expressions of HTRA3 mRNA and protein in RF/6A cells in the HTRA3-sh group decreased(all P＜0.05).Compared with the N group,the number of closed lumen and the mRNA and protein expressions of HTRA3 and VEGF in RF/6A cells in the H group increased(all P＜0.05).Compared with the H+NC-sh group,the number of closed lumen and the mRNA and protein expressions of HTRA3 and VEGF decreased in RF/6A cells in the H+HTRA3-sh group(all P＜0.05).Compared with the control group,the mRNA and protein expression levels of HTRA3 increased,the relative fluorescence intensity of CNV increased,the mRNA levels of Ym-1 and Arg-1 in-creased,the iNOS and COX-2 mRNA levels decreased,and the NF-κB p65 protein expression level increased in mice of the CNV group(all P＜0.05).Compared with the CNV+NC-sh group,the mRNA and protein expression levels of HTRA3 de-creased,the relative fluorescence intensity of CNV decreased,the mRNA levels of Ym-1 and Arg-1 decreased,the mRNA levels of iNOS and COX-2 increased,and the NF-κB p65 protein expression level decreased in mice of the CNV+HTRA3-sh group(all P＜0.05).Conclusion Down-regulation of HTRA3 can inhibit the formation of CNV and the polarization of M2 macrophages.HTRA3 may be an important potential target for the prevention and treatment of wAMD.
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Objective:To explore the clinical application values of a nomogram based on preoperative breast MRI and axillary ultrasonography imaging parameters for predicting the risk of sentinel lymph node (SLN) metastasis in early-stage breast cancer patients.Methods:Three hundred and ninty-seven female patients (mean age 48.0±10.7 years old, range 25-81 years old) who admitted to Sun Yat-sen University Cancer Center from May 2007 to December 2017 were enrolled in this study. All patients were diagnosed as primary unilateral invasive early-stage breast cancer confirmed by surgical pathology. Preoperative breast MRI, axillary ultrasonography and clinical pathological data of enrolled patients were retrospectively analyzed. According to the pathological results of sentinel lymph node biopsy (SLNB), the cases were divided into negative SLN group ( n=200) and positive SLN group ( n=197). Clinicopathologic data, MRI and axillary ultrasound features were analyzed and compared between two groups. Logistic regression analysis was used to select independent risk factors. Then a predictive model was constructed and a nomogram was made for visualizing the associations between the predictive factors and SLN metastasis. Goodness-of-fit of the model was evaluated by using the Hosmer-Lemeshow test. Predictive performance was assessed based on the receiver operating characteristic (ROC) curves. Bootstrap resampling was performed for internal validation. Results:Significant differences were found in patient age, lymphovascular invasion status, PR status, HER2 status and molecular subtype between negative and positive SLN groups (all P<0.05); MRI features including tumor size, mass margin, long and short diameter, as well as the ratio of long to short diameter of LNs, LN margin, presence or absence of LN hilum, and axillary LNs symmetry were found significantly different between negative and positive SLN groups (all P<0.05); as for the axillary LN ultrasonography parameters, the interface between cortex and medulla, presence or absence of cortical thickening, and LN hilum were significantly different between negative and positive SLN groups (all P<0.05). Logistic regression analysis results showed that several factors could be identified as predictors of SLN metastasis, including patient age, MRI features (lymph node margin, presence or absence of lymph node hilum, and lymph node symmetry), axillary ultrasonography descriptors (presence or absence of cortical thickening) and pathological factors (lympovascular invasion, PR and HER2 status). The nomogram with patient age and the above imaging factors showed good,prediction performance with the area under the ROC as 0.778. Combining with the pathological parameters, the prediction performance of the nomogram model was significantly improved, yielding the area under the ROC of 0.866. Conclusions:The nomogram based on breast MRI and axillary ultrasonography can be applied as a noninvasive quantitative tool to predict the risk of SLN metastasis in early-stage breast cancer, which may facilitate decision-making for axillary treament strategy preoperatively.
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Objective@#To summarize the clinical manifestations and treatment of retinal artery occlusion and cerebral infarction caused by facial injection of hyaluronic acid.@*Methods@#Fifteen cases (15 eyes) with vision lose caused by facial cosmetic injection of hyaluronic acid visited Xi＇an No.4 Hospital from December 2010 to January 2017. The clinical data were collected such as general medical history and treatment methods, and follow-up for 1 year.@*Results@#All patients were female, 22-41 years old, with average age of 33. All patients were injected with hyaluronic acid. For 8 patients the fillers were injected in the forehead, 3 patients were in the glabellar region, 3 patients were in the nasolabial fold, and 1 patient was in the temporal of left eye. All patients had vision lose after injection, the visiting time was 1 to 6 hours. 13 patients were central retinal artery occlusion (CRAO). 1 patient was retinal branch artery occlusion (BRAO), 1 patient was ischemic optic neuropathy (ION), 13 patients manifested as no light perception (NLP), 1 patient was 0.6, 1 patient was CF/30 cm, and 14 patients with cerebral infarction, manifested as headache, dizziness. All patients were given emergency treatment, and 9 patients had treated with interventional thrombolysis therapy. After treatment 11 patients, visual acuity had no significant improvement, but 4 patients improved. Headache, dizziness symptoms disappeared, but cerebral infarction lesions still existed on MRI.@*Conclusions@#Human face is a rich blood supply; vision loss and cerebral infarction could occur after injection of hyaluronic acid. After urgent treatment visual acuity is not improved obviously, eventually leading to irreversible visual impairment or even loss.
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Objective To investigate the characteristics of multifocal electroretinogram (mf-ERG) and optical coherence tomography (OCT) in macular edema (ME) secondary to retinal vein occlusion (RVO).Methods Mf-ERG and OCT were performed in 38 patients (38 eyes) of ME secondary from RVO patients and 23 normal persons (23 eyes) in the same period of the control group.OCT was used to detect macular retinal thickness (CMT) at foveal area with diameter 1 mm,mf-ERG was used to evaluate the function of macular retina and analyze the amplitude density of P1 wave and latency of P1,N1 wave from ring 1 to ring 5.Results Compared with the control group,the amplitude densities of P1 in BRVO group were obviously decreased in ring 2 (35.95 ± 17.04)nV · deg-2,ring 3(24.72 ±8.32)nV · deg-2,ring 4(19.28 ±6.38)nV ·deg-2,ring 5 (13.49-± 6.16) nV · deg-2,respectively (all P ＜ 0.05);The latencies of P1 were prolonged significantly in ring 2 (35.74-± 3.72) ms (P ＜ 0.05);The latencies of N1 were prolonged significantly in ring 2 (18.43-± 4.63) ms,ring 3 (18.67-± 2.86) ms (both P ＜ 0.05).Compared with the control group,the amplitude densities of P1 in CRVO group were obviously decreased in ring 1 (81.58 ± 43.15) nV · deg-2,ring 2 (33.71 ±9.81) nV · deg-2,ring 3 (22.15 ± 9.75) nV · deg-2,ring 4 (16.65-± 6.38) nV · deg-2,ring 5 (14.18-± 4.59) nV · deg-2,respectively (all P ＜ 0.05);The latencies of P1 were prolonged significantly in ring 2 (37.56 ± 5.55) ms,ring 3 (37.31 ± 5.22) ms,ring 4 (35.71 ±5.63) ms,ring 5 (37.30 ± 5.37) ms (all P ＜ 0.05);The latencies of N1 were prolonged significantly in ring 1 (21.82 ±5.76) ms,ring 2(19.18 ±4.82) ms,ring3 (19.31 ±4.25)ms,ring 4 (19.05 ± 4.55) ms,ring 5 (19.43 ± 4.12) ms (all P ＜ 0.05).There was negative correlation between CMT and amplitude densities of P1 of ring 1 in CRVO group (r =-0.576,P ＜ 0.05).Conclusion OCT combined with mf-ERG can comprehensively reflect the change of retinal fumction and structure in ME secondary to RVO.
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Objective To compare the efficacy and safety of half-dose verteporfin and half-fluence photodynamic therapy in chronic central serous chorioretinopathy (CSC).Methods The medical records of 42 patients (42 eyes) with chronic CSC were retrospectively reviewed.According to the difference of drug dose and laser parameters in the course of PDT,the patients were divided into two groups:half-dose group and half-fluence group.Half-dose group:22 patients (22 eyes) received half-dose verteporfin(3 mg· m-2)and standard PDT(83 s,50 J · cm-2).Half-fluence group:20 patients (20 eyes) received full-dose verteporfin (6 mg · m-2) and half-fluence PDT (42 s,25 J · cm-2).Patients were followed up at 1 month,3 months,6 months after PDT.The outcome measures was the proportion of eyes with complete resolution of subretinal fluid(SRF),the changes in best corrected visual acuity (BCVA) and central retinal thickness(CMT).Results At 6 months after PDT,22 eyes(100％) that received half-dose PDT showed complete resolution of SRF,19 eyes(95％)that received half-fulence PDT showed complete resolution of SRF.There was no statistical difference between two groups (P ＞ 0.05).At 6 months after PDT,the mean BCVA improved 7.2 letters in half-dose group and 6.7 letters in half-fluence group.There was no statistical difference compared with the improvement of BCVA between two groups(P ＞ 0.05).In half-dose group,mean baseline central retinal thickness was (351 ± 90) μm,which was decreased to (178 ±55) μm after 6 months,respectively (P ＜ 0.05).In half-fluence group,mean baseline central retinal thickness was (322 ± 96) μm,which was decreased to (181 ± 47) μm after 6 months,respectively (P ＜ 0.05).None of the patients developed retinal pigment epithelium atrophy and CNV.Conclusion Half-dose verteporfm PDT and half-fluence PDT are effective and safe in the treatment of chronic CSC.