1.Progression and challenge of therapeutic strategies in neovascular age-related macular degeneration
Chinese Journal of Ocular Fundus Diseases 2016;32(1):3-7
Choroidal neovascularization (CNV) is the key characteristic of neovascular age-related macular degeneration (nAMD),and the effective therapy is intravitreal injection of anti vascular endothelial growth factor (VEGF) agents based on clinical and basic research.In the meantime the challenge is how to further improve the inhibiting effect for CNV and visual function of anti-VEGF treatment on nAMD.The new strategy and drug delivery devices for anti-VEGF treatment will optimize the clinical scheme.From bench to bedside,the research on targeted treatment of angiogenesis brings the bloom of nAMD medical therapy.
2.Promoting effect of p75NTR receptor overexpression on oxidative stress injury in human retinal pigment epithelium cells
Yun, QI ; Yujing, BAI ; Xiaoxin, LI ; Xuan, SHI
Chinese Journal of Experimental Ophthalmology 2016;34(1):17-23
Background Choroidal neovascularization (CNV) is the primary pathogenic cause of many fundus diseases.Oxidative stress injury of retinal pigment epithelial (RPE) cells plays important role in angiogenesis of choroid new blood vessels.Oxidative stress injury can active p75NTR receptor, a member of tumor necrosis factors family,resulting in the proliferation of vascular endothelial cells.However, the mechanisms of vascular endothelial cell proliferation remain unclear.Objective This study was conducted to investigate the effect of p75NTR overexpression on CNV and the relative mechanism.Methods The ARPE-19 cell line was used in this study.RPE cells were transfected with p75NTR receptor overexpressed plasmid, and untransfected cells served as the control group.The transfected results were verified by reverse transcription-PCR and Western blot assay.Viability of the cells over time was determined in the p75NTR receptor plasmid transfected group by using BrdU assay.The percentage of apoptotic cells was detected by flow cytometry using Annexin V-FITC/PI fluorescence staining.The percentage of reactive oxygen species (ROS) expression in the cells was detected by using H2 DCFDA fluorescence and flow cytometry.Mitochondrial membrane potential and cytochrome C expression were examined under the confocal microscope.The protein expressions of cleaved caspase-3, Fas and VEGF were determined by Western blot assay.Results The relative expression level of p75 NTR receptor mRNA was (6.11 ±0.77) times higher than that of the control group, and relative expression level of p75NTR receptor protein in the cells in the p75NTR receptor plasmid transfected group was (7.42±0.48) times higher than that in the control group (t=11.49 and 23.17 ,both at P<0.01).The absorbency values of the p75NTR receptor plasmid transfected group were (93.12±0.56) % , (86.30±0.66) % , (72.53-±0.86) % and (60.77 ±2.81) % in 12,24,36 and 48 hours after plasmid transfection, which were significantly lower than 100% in the control group, and the apoptotic percentages were evidently higher than that in the control group (all at P<0.05).The relative fluorescence intensity of ROS fluorescence in the p75NTR receptor plasmid transfected group was 2.4 times higher than that in the control group,showing significant difference (t=16.45, P<0.01).The positive expressing rate of mitomarker (mitochondrial membrane potentials) was 100% in the control group and (37.30± 2.06)% in the p75NTR receptor plasmid transfected group, with significant difference between them (t =57.71,P<0.01).The fluorescence intensity of cytochrome C expression was elevated in the p75NTR receptor plasmid transfected group compared with the control group.Compared with the control group,the expressing levels of cleaved caspase-3 ,Fas and VEGF165 proteins in the cells were significantly raised in the p75NTR receptor plasmid transfected group (all at P<0.01).Conclusions Overexpression of p75NTR receptors in RPE cells leads to mitochondrial damage and cellular apoptosis and the secretion of VEGF protein, which sequentially promote CNV.P75NTR receptor may be another important regulation pathway in RPE oxygen damage.
3.Evaluating the relationship between intracranial atherosclerotic plaque stability and stroke recurrence risk with high-resolution MRI
Sijin HE ; Yingbin LI ; Yanting ZHANG ; Xiaoxin BAI
Chinese Journal of Cerebrovascular Diseases 2017;14(7):351-355
Objective To investigate the relationship between intracranial atherosclerotic plaque stability and stroke recurrence risk.Methods Forty-eight patients with acute ischemic stroke caused by intracranial atherosclerosis in Guangdong Province Hospital of TCM were analyzed retrospectively.After the Essen Stroke Risk Scale (ESRS) was used to assess the risk factors for the patients,they were divided into either an ESRS ≥3 group (n=21 in the high-risk recurrence group) or an ESRS <3 group (n=27 in the low-risk recurrence group).Both groups of patients underwent high-resolution MR imaging (HR-MRI) examinations of the intracranial guilty vessels (basilar artery or unilateral middle cerebral artery).According to the signal intensity of HR-MRI on the T1-weighted imaging,T2-weighted imaging,and T1 fat suppression sequences,the intracranial atherosclerotic stable plaques and unstable plaques were distinguished.The stabilization of intracranial atherosclerotic plaques was compared in patients of both groups.Results There were significant differences in the age and incidences of hypertension,diabetes mellitus,and unstable plaques in patients of both groups (P<0.05).Further multivariate logistic regression analysis of the four factors showed that the age,hypertension,diabetes,and intracranial atherosclerotic unstable plaques were the high-risk factors for recurrent ischemic stroke (ORs,87.114,159.423,8.942,and 11.551,respectively;95%CIs 4.218-1 799.078,3.235-7 855.957,1.054-75.857,and 1.011-132.043,respectively;all P<0.05).Conclusion In addition to the traditional risk factors such as age,hypertension,and diabetes,the intracranial atherosclerotic unstable plaque is an independent risk factor for high-risk recurrence of ischemic stroke.
4.Using hyperbaric oxygen with mesenchymal stem cells to treat traumatic brain injury
Huiping PENG ; Zhifeng BAI ; Rumi WANG ; Xiaoxin LU
Chinese Journal of Physical Medicine and Rehabilitation 2017;39(8):561-565
Objective To investigate any therapeutic effect of combining hyperbaric oxygen with mesenchymal stem cells (MSCs) in treating traumatic brain injury (TBI).Methods Eighty healthy adult rats were randomly divided into a control group,a hyperbaric oxygen group,a stem cell group and a combination group,each of 20.TBI was introduced into the rats of all 4 groups.Twenty-four hours after the modelling,the hyperbaric oxygen group received hyperbaric oxygen therapy,the stem cell group received MSCs transplantation,the combination group was given the hyperbaric oxygen therapy an hour after the MSCs transplantation,while the control group was not given any treatment.All of the rats were evaluated using neurological severity scores (NSSs) after the modeling and again after the treatment.They were then sacrificed for HE staining and the expression of nuclear factor kappa B (NF-kB) and brain-derived neurotrophic factor (BDNF) were observed.Results On the 3rd,5th,10th and 20th day after the modeling,the average NSS of the combination group was significantly lower than those of the other three groups.However,the average NSS of the combination group on the 20th day was significantly superior to that on the 3rd and the 5th days.Compared with the control group,the edema of brain cells was less severe in the other 3 groups.The average expression of NF-kB and BDNF in the combination group was significantly higher than in the other 3 groups on the 3rd,5th,10th and 20th day after the modeling.Conclusion Hyperbaric oxygen,especially long term treatment combined with stem cell transplantation,can significantly improve nerve function in the brain after trauma,relieve inflammation and edema in and around the damaged area,and promote the expression of the NF-kB and BDNF.
5.Treatment of symptomatic cerebral artery stenosis and occlusion with Xenon CT guided cerebral revascularization
Yingbin LI ; Wenjing XU ; Yanting ZHANG ; Xiaoxin BAI
Chinese Journal of Cerebrovascular Diseases 2017;14(5):240-244
Objective To investigate the roles of Xenon-CT cerebral blood flow perfusion imaging in cerebral revascularization before surgery and efficacy evaluation.Methods The clinical data of 15 patients with symptomatic cerebral artery stenosis/occlusion of anterior circulation were analyzed retrospectively.Eight patients were treated with endovascular stenting,1 was treated with internal carotid endarterectomy,and 6 were treated with superficial temporal artery-middle cerebral artery bypass grafting.The regional cerebral blood flow (rCBF) detected by Xenon CT within 2 weeks before and after procedure and the modified Ranking scale (mRS) scores at 6 months after procedure were compared.Results (1) The mean rCBF value of 12 patients with abnormal blood perfusion of target vessels before procedure was 30±10 ml/(100 g·min) and that was 32±14 ml/(100 g·min) after procedure.Compared with before procedure,the difference was statistically significant (P<0.05).The mean rCBF value of 3 patients with normal blood perfusion of target vessels before procedure was 48±6 ml/(100 g·min) and that was 50±7 ml/(100 g·min) after procedure.Compared with before procedure,the difference was not statistically significant (P>0.05).(2) The postoperative mRS score was decreased in 8 cases and stable in 7 cases.Compared with before procedure,there were significant differences in mRS scores after procedure in 15 cases (P<0.05).During the follow-up period,none of the patients had new neurological impairment.Conclusion Revascularization can improve the presence of hemodynamic disorders in patients with symptomatic anterior circulation cerebral artery stenosis or occlusion of the target blood vessels in the distal local cerebral perfusion and neurological deficit symptoms.The patients with abnormal perfusion of preoperative Xenon-CT cerebral blood flow perfusion imaging may be more beneficial than those with normal perfusion.
6.Concentrations of different isoforms of VEGF in aqueous humor in patients with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy
Min, ZHAO ; Yujing, BAI ; Bin, WANG ; Jianhong, LIANG ; Mingwei, ZHAO ; Xiaoxin, LI ; Xuan, SHI
Chinese Journal of Experimental Ophthalmology 2014;32(12):1084-1087
Background There remains some controversy over whether polypoidal choroidal vasculopathy (PCV) represents a subtype of neovascular age-related macular degeneration (nAMD).Anti-vascular endothelial growth factor (VEGF) therapies are important in the treatment of PCV and nAMD.It has been identified that VEGF-A was differentially spliced from exons 8 and formed two isoforms families:the pro-angiogenic VEGFxxx family and the anti-angiogenic VEGFxxxb family.However,the role of the two VEGF families in PCV and nAMD was still unclear.Objective This study was to measure the contents of pro-angiogenic VEGFxxx family and the anti-angiogenic VEGFxxxb family in aqueous humor of nAMD and PCV patients and explore their effect on nAMD and PCV.Methods Thirty-four nAMD patients and 26 PCV patients were enrolled in Peking University People's Hospital during March to December,2013,and 16 age-related cataract patients served as controls.The aqueous humor samples 0.1 ml was collected before the introvitreous injection of anti-VEGF drug.The contents of pro-angiogenic VEGFxxx family and the anti-angiogenic VEGFxxx b family in the aqueous humor were measured by enzyme-linked immunosorbent assay(ELISA).Results The concentrations of VEGF in the aqueous humor in the nAMD group,PCV group and control group were (4 210.00±998.40),(387.00±51.31) and (377.40 ±69.97)pg/ml,respectively,showing a significant difference among the three groups (F =12.851,P =0.000).The concentrations of VEGF165 b in the aqueous humor in the nAMD group,PCV group and control group were (205.50±12.59),(159.40±16.25) and (347.90±29.18) pg/ml,with a significant difference among them (F=23.752,P=0.000).Compared with the control group,VEGF content in the aqueous humor was elevated and the VEGF165b content was declined in the nAMD group,and VEGF165b was lowed in the PCV group,with significant differences between them(all at P=0.000).However,no significant difference was seen in the change of VEGF between the PCV group and the control group (P=0.992).The VEGF content in the aqueous humor was higher in the nAMD group than that in the PCV group (P =0.001),but VEGF165b content was insignificantly different (P =0.097).Conclusions The downregulation of VEGFxxx b may be associated with nAMD and PCV.The different role of VEGFxxx b in the development of PCV and nAMD needs to be verified in further studies.
7.Regulation of Fengxiaofang on Expression of Gene Gob-5 in Asthmatic Mice
Genben BAI ; Yang LIU ; Youlin LI ; Xiaoxin MA ; Shi YAN ; Changzheng FAN ; Yahong GUO
Chinese Herbal Medicines 2010;2(1):68-71
Objective To observe the regulation of Fengxiaofang on the expression of gene Gob-5 in ovalbumin-challenged asthmatic mice. Methods The murine model of allergic asthma established by ovaibumin was used. The model mice were treated experimentally with Fengxiaofang and Dexamethasone as a positive control. The quantitive expression of gene Gob-5 in lung of mice was detected by real-time quantitative PCR. Results The expression of gene Gob-5 in lung of mice was down-regulated by Fengxiaofang. In the experiment, there were no significant differences between the one-fold or ten-fold dosage groups and the normal control group. Gene Gob-5 expression in five-fold dosage was significantly lower than that in the normal control group. Conclusion Fengxiaofang has the effect of lowering the expression of gene Gob-5 which maybe related to the potency on asthmatic disease.
8.Angiographic features and clinical significance of kinking of extracranial internal carotid artery
Yingguang ZHANG ; Jixiang ZHU ; Guifu LI ; Xiaoxin BAI ; Wenyan ZHU ; Shengping HUANG ; Tielin LI ; Hao LIN ; Wangchi LUO
Chinese Journal of Radiology 2009;43(2):181-184
Objective To investigate the clinical manifestations, angiographic features and clinical significance of kinking of extracranial internal carotid artery (ICA). Methods The clinical and radiological data of 21 patients with kinking of extracranial ICA were retrospectively reviewed in our hospital from April 2003 to July 2007. Fisher exact test was performed. Results Of the 21 patients, 7 hod no clinical symptoms, the other 14 showed manifestations of cerebral iachemia with varying degree. One of the characteristic clinical manifestations that neck rotation or specific positions of head and neck might induce the occurrence of clinical symptoms was found in 5 cases. The whole-brain coverage DSA accurately showed the location of kinking of extracranial ICA and the degree of vascular stenosis. In patients with α < 66%, 80% > α≥ 66% and α≥ 80%, clinical symptoms were found in 3 out of 5,7 out of 10 and 4 out of 6 patients, respectively. Fisher exact test revealed that the positive rates of clinical symptoms in three groups had no significant difference (P > 0. 05). Conclusion Kinking of extracranial ICA is a frequent vascular morphologic variation, and it is also a kind of potential disease. The whole-brain coverage DSA is a relatively reliable method to detect this variation.
9.The clinical observation of local intraarterial thrombolysis in acute ischemic stroke of the anterior circulation
Xiaoxin BAI ; Shengping HUANG ; Tielin LI ; Hao LIN ; Wangchi LUO ; Xuelian LI ; Wenyan ZHU ; Yefeng CAI ; Yan HUANG
Clinical Medicine of China 2008;24(12):1210-1213
Objective To evaluate the short-term outcome of local intraarterial thrombolysis in patients with acute ischemic stroke of the anterior circulation. Methods 24 patients with acute ischemic stroke of the anterior cir-culation within 8 hours were treated by local intraarterial thrombolysis. Arterial recanalization was divided into total, partial and occlusive respectively according to angiography. Evaluation of clinical outcome was performed on the 30th day after thrombolysis,and was classified as good for Modified Rankin Scale (MRS) scores of 0 to Ⅲ and poor for MRS scores of Ⅳ to Ⅵ. Results Total recanalization was obtained in 54.2 % of patients, partial recanalization in 25.0%. Clinical outcome was good in 15 patients (62.5%). Cerebral hemorrhage occurred in 4 patients (16.7%). Four patients died (16.7%). Conclusion Local intraarterial thrombolysis is an effective method for treatment of a-cute iachemic stroke of the anterior circulation. It needs further practice and long-term follow-up study on safety and long-term efficacy.
10.Role of balloon occlusion test in the treatment of permanent internal carotid artery occlusion
Shaoxue LI ; Jinhua CHEN ; Yanting ZHANG ; Zhimin ZOU ; Yingbin LI ; Shiwan LIU ; Jun CAI ; Ruicong CHEN ; Xiaoxin BAI
Journal of Regional Anatomy and Operative Surgery 2016;25(8):603-605
Objective To investigate the relation between the balloon occlusion test ( BOT) and the anatomy of the circle of Willis ( CW) , and to explore the role of balloon occlusion test in the treatment of internal carotid artery permanent occlusion. Methods Selected the clinical data of 49 patients (52 sides) who had BOT in our hospital from October 2009 to June 2015,and analyzed the relationship be-tween the occurrence rate of anterior communicating artery ( AcoA) / posterior communicating artery ( PcoA) and the positive rate of BOT retrospectively. Results The occurrence rate of the AcoA was 97. 9%, and the occurrence rate of PcoA in one side was 82. 7%. Negative rate BOT accounted for 92. 3% and AcoA occurred in all, while the positive rate accounted for 7. 7%, including 2 cases of right superior ar-teria cerebri anterior combined with ipsilateral PcoAs absence, 1 case of left superior arteria cerebri anterior combined with ipsilateral PcoAs absence, and 1 case of AcoA and PcoAs absence. Conclusion Before the permanent occlusion of the internal carotid artery, it’ s necessary to clarify the redistribution of the compensatory way of blood flow in the AcoA-absent cases. Implementing permanent occlusion for cases with complete circle of Willis would cause less ischemic risk.