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Objective:To observe the changes of visual acuity and fixation properties of eyes with idiopathic macular hole (IMH) before and after surgery.Methods:A prospective clinical study. From September 2019 to December 2020, 25 patients with 25 eyes of IMH diagnosed in Department of Ophthalmology of The Fourth People's Hospital of Shenyang were included in the study. All patients underwent pars plana vitrectomy (PPV) combined with internal limiting membrane stripping. All eyes underwent best corrected visual acuity (BCVA), optical coherence tomography (OCT), and microperimetry before and after surgery. The BCVA examination was carried out using the Snellen visual acuity chart, which was converted into logarithmic minimum resolution angle (logMAR) visual acuity during statistics. The 12° macular sensitivity (MS) and bivariate contour ellipse area (BCEA) were measured by MP-3 microperimetry. The minimum diameter (MIN) and base diameter (BASE) of the macular hole were measured by OCT; the distance between the preferred retinal location (PRL) and the center of the fovea was measured by Image-proplus 6.0 image processing software. At 1 and 3 months follow-up after surgery, the same equipment and methods as before surgery were used to conduct related examinations. The changes of BCVA, PRL distance from the fovea, MS, BCEA, and macular hole shape before and after surgery were compared and observed. One-way analysis of variance was used to compare the indicators before and after surgery. Pearson correlation analysis was used for the correlation between BCVA and preoperative BCVA, PRL and foveal center distance at 3 months after surgery. The correlation between MIN, BCVA, PRL and foveal center before surgery distance, MS, BCEA and BCVA at 3 months after surgery were analyzed by multiple linear regression.Results:Among 25 eyes of 25 cases, 1 male had 1 eye, and 24 females had 24 eyes. The macular hole in stage Ⅲ and Ⅳ were 11 eyes and 14 eyes, respectively. MIN and BASE were 537.68±200.09 and 905.48±278.79 μm, respectively. One month after surgery, the hiatus was closed. Before surgery and 1 and 3 months after surgery, the logMAR BCVA of the affected eyes were 0.80±0.17, 0.70±0.21, 0.60±0.25, and the MS were 22.20±3.86, 23.60±3.14, 24.38±2.68 dB, the distances between PRL and the center of the fovea were 537.72±426.05, 402.00±395.06, 236.80±219.54 μm, and BCEA were 7.90±3.43, 6.40±2.67, 4.80±2.32 deg 2. Compared with before operation, BCVA ( F=7.047, 20.104) and MS ( F=1.980, 5.390) were significantly improved at different time after operation, the distance between PRL and fovea center ( F=1.265, 9.530), BCEA ( F=2.762, 13.617) were decreased, the difference were statistically significant ( P<0.05). The results of correlation analysis showed that BCVA at 3 months after surgery was significantly associated with preoperative MIN ( r=0.810), BASE ( r=0.664), BCVA before surgery and 1 month after surgery ( r=0.854, 0.940), preoperative and surgical MS at 1 month after surgery ( r=-0.548, -0.578), distance between PRL and foveal center before surgery and at 1 month after surgery ( r=0.833, 0.915), BCEA before surgery and at 1 month after surgery ( r=0.636, 0.732) were significantly correlated ( P<0.05). The results of multiple linear regression analysis showed that the distance between PRL and foveal center before surgery and BCVA were risk factors for poor prognosis of BCVA at 3 months after surgery. Conclusions:The BCVA and MS of eyes with IMH are significantly improved after surgery, and the distance between PRL and foveal center and BCEA decreased. BCVA, PRL and foveal center distance before surgery are risk factors for poor visual acuity after surgery.
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Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS
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Objective To apply color Doppler flow imaging (CDFI) and transcranial Doppler (TCD) to the follow-up observation of the changes of cervical vessel,intracranial hemodynamics and cerebrovascular reserve capacity (CVR) of the patients after carotid artery stent implantation.Methods Totally 96 patients with carotid artery stent implantation underwent CDFI and TCD examinations,and the changes of hemodynamics were compared before and 1 month,6 months,1 a and 2 a after implantation.Results The values of peak systolic velocity (PSV) and resistance index (RI) at the areas of carotid stenosis were lower significantly than those before implantation,while the values of PSV,pulsatility index (PI) and CVR of the middle cerebral artery were obviously higher than those before implantation (P＜0.05).There were no significant differences between the cervical and intracranial hemodynamics indexes 1 month,6 months,1 a and 2 a after treatment.Two-year follow-up found 4 cases of restenoses after implantation,and the rate for restenosis was 4.2％.Conclusion Carotid artery stent implantation improves significantly cervical and intracranial blood supply as well as CVR of the carotid stenosis patient,and CDFI combined with TCD can be used for the accurate evaluation of the efficacy and postoperative follow-up of carotid artery stent implantation.
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Objective To explore the immune property and possible mechanism of the CD71+ CD235a+ nucleated erythroid cells from peripheral blood in elderly,as compared with those of healthy young.Methods Peripheral blood obtained by venipuncture from healthy young(n=59,mean age=28 years) and elderly(n=78,mean age=68 years)donors were measured by flow cytometry to evaluate the frequency of the CD71+ CD235a+ cells in peripheral blood mononuclear cells (PBMC).In vitro assays,CD71+ CD235a+ cells were sorted by flow cytometry and T cells were sorted using CD4+T cell isolation kit,then the T cell proliferation assays were conducted by following groups:T cell + CFSE group;T cell +CFSE co-cultured with CD71+ CD235a+ cells from the young donors;T cell + CFSE co-cultured with CD71+ CD235a+ cells from the older donors.Real-time PCR were used to identify the expression of the immune cytokine secreted by CD71+ CD235a+ cells.Results (1)the results showed a significant increase in the percentage of CD71+ CD235a+ cells in the elderly compared with the young [(9.93± 2.95)％ vs (1.96 ± 1.16)％,t =3.37,P ＜ 0.001];(2)the CD71+ CD235a+ cells from the older donors could suppress the proliferation of the T cells (t =2.91,P＜ 0.05)while from the young group we could not observe this phenomenon(t =0.387,P＞0.05).(3)The results of Real-time PCR revealed that,compared with CD71+ CD235a+ cells from the young,CD71+ CD235a+ cells from the elderly expressed higher levels of Arg-2 (t =9.04,P＜0.01),IL-1β,IL-6 and TGF-β(t =4.51,5.46,6.92,all P＜0.05).Conclusions There are higher frequencies of CD71+ CD235a+ cells in aged samples than the young.And the CD71+CD235a cells from the elderly could secrete more Arg-2,IL-1β,IL-6 and TGF-β to suppress the T cell proliferation.
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Objective To investigate the level of subpopulations of myeloid-derived suppressor cells (MDSCs) in elderly tumor-bearing mice versus elderly tumor-free mice,and to study the difference in immune suppressive functions between different subpopulations and their mechanisms.Methods A total of 20 healthy C57BL/6 elderly mice(aged 18-20 months) were randomly chosen to establish Lewis lung cancer models.The amount of monocytic-MDSCs (MO-MDSCs) and polymorphonuclear granulocytic-MDSCs(PMN-MDSCs) in tumor-free and tumor-bearing elderly mice was evaluated by using flow cytometry.MO-MDSCs and PMN-MDSCs were separated with Magnetic-Activated Cell Sorting (MACS) MicroBeads and their morphological characteristics were observed after May-Grunwald-Giemsa staining.The effects of MO-MDSCs and PMN-MDSCs on the proliferation of T cells were determined by Brdu-enzyme-linked immunosorbent assay(ELISA).And the immune suppressive mediators secreted by the subpopulations were detected by Real-time polymerase chain reaction(PCR).Results Compared to the tumor-free group,the proportion of MO-MDSCs in the spleen of tumorbearing group were increased [(12.44± 1.20) ％ vs.(38.42±3.66) ％,t=5.67,P＜0.001],while PMN-MDSCs were not [(10.34±0.68) ％ vs.(12.18±1.27) ％,t=2.21,P=0.09].The result of Brdu-ELISA showed that MO-MDSCs could suppress the proliferation of T cells [(0.30 ± 0.18) vs.(3.38±0.96),t=8.33,P＜0.001],while PMN MDSCs could not [(2.69±0.45)vs.(3.38±0.96),t =1.72,P=0.11].The result of PCR showed that as compared with PMN-MDSCs,Mo-MDSCs had the increased expression levels of arginase-1 (ARG-1),inducible nitric oxide synthase (iNOS),interleukin-10 (IL-10),interferon-γ(IFN-γ) (t =4.31,8.89,1.70,3.13,respectively,P ＜ 0.01 or 0.05),while the expression levels of interleukin-13 (IL-13),transforming growth factor-β(TGF-β) had no differences (t=4.94 and 2.75,P =0.39 and0.47).Conclusions MO-MDSCs are significantly increased in elderly Lewis lung cancer mice models.MO-MDSCs could mediate lung tumor evasion by suppressing the proliferation of T cells through highly expressing ARG-1,iNOS,IL-10 and IFN-γ.
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Objective To study characteristics and immune mechanisms of CD11b+ GR-1-myeloid-derived suppressor cells (CD11b+ GR 1+ MDSCs) in elderly mice,as compared with those of healthy young mice.Methods Totally 20 healthy C57BL/6 young mice (aged 1-2 months) and 20 elderly mice (aged over 18 months) were randomly chosen and splenetic CD11b+ GR-1+ MDSCs were sorted with the MDSCs Isolation Kit.In vitro assays,the effects of young and elderly CD1 1b+ GR 1+ MDSCs on the proliferation of T cells were determined by Brdu Elisa.Transwell co-culture and real-timePCR were used to identify the mechanisms of different immune suppressive functions of CD11b+GR 1+ MDSCs sorted from young mice and elderly mice.Results Compared with young MDSCs,elderly MDSCs could evidently suppress the proliferation of T cells (t=8.67,P＜0.001),and this function could be reversed by trans-well co-culture (t=6.93,P＜0.001).The results of realtime PCR revealed that,compared with young MDSCs,elderly MDSCs expressed higher levels of arginase-1 (ARG-1),inducible nitric oxide synthase (iNOS),reactive oxygen species (ROS),interleukin 10 (IL-10),IL13 and transforming growth factor (TGF)-β (t=9.04,4.86,7.04,6.92,4.51,5.46,respectively,P＜0.05 or P＜0.01).Conclusions CD11b+GR-1+MDSCs sorted from healthy elderly mice can evidently suppress the proliferation of T cells through cell-cell contact and secretion of suppressive medium.
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Objective To explore the expression of negative costimulatory molecule B7-H1 of myeloid derived suppressor cells(MDSCs) and its roles in age-related immunosuppressive functions.Methods 36 C57BL/6 mice were divided into 2 groups:the elderly group(12-month-old,n=18) and the young group(4-8-week-old,n=18).The expressive level of negative costimulatory molecules of MDSCs in the two groups was measured by flow cytometry(FCM).Besides,MDSCs were sorted by using MDSC isolation kit and T cells were obtained by grinding lymph nodes.To explore the influence of B7-H1 on the MDSCs' immunosuppressive functions,T cell proliferation and intervention assay was conducted using the five following groups:T cells group,T cells + CFSE group [T cells with carboxyfluorescein diacetate succinimidyl ester(CFSE)],T cells +-CFSE cocultured with MDSCs from the young group,T cells + CFSE cocultured with MDSCs from the elderly group,and T cells + CFSE cocultured with MDSCs from elderly group and anti-B7-H1 blocking antibody.The effect of B7-H1 on T cell proliferation in MDSCs were observed.Results The expression level of B7-H1 of the MDSCs was significantly increased in the elderly group as compared with the young group(t=3.27,P＜0.05).T cell proliferation assay revealed that T cells were remarkably suppressed by MDSCs in elderly group as compared to the youth group(t=5.42,P＜0.05).The suppression of T cells by MDSCs was dramatically reversed by anti-B7-H1 blocking antibody in elderly group(t=8.28,P＜0.05).Conclusions B7-H1,a molecule expressed on the surface of MDSCs,plays a key role in the age-related immunosuppressive function of MDSCs.
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Objective To study the effect of Qingfei oral liquid contained serum on the transforming growth factor-?1 (TGF-?1) and platelet-derived growth factor-BB (PDGF-BB) mRNA gene expression of human embryonic lung fibroblast cells infected by adenovirus (ADV) type 3I and 7b. Method TGF-?1 and PDGF-BB mRNA expression of human embryonic lung fibroblast cells infected by ADV type 3I and 7b were determined by in situ hybridization before and after treated with Qingfei oral liquid contained serum. Results ADV could up-regulate TGF-?1 and PDGF-BB mRNA of human embryonic lung fibroblast cells (P
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Objective:To study the effect ofQingfei Oral Liquid medicated serum on the tumor necrosis factor-?(TNF-?) mRNA gene expression ofhuman embryonic lung fibroblasts induced by adenovirus Type3I, 7b.Methods:We determined the TNF-? mRNA ofADV-infected human embryonic lung fibroblasts before and after adding the medicated serum by in situ hybridization.Results:Adenovirus could up-regulate the TNF-?mRNA ofhuman embryonic lung fibroblasts(P