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Objective:To observe the clinical features of cytomegalovirus (CMV) retinitis (CMVR)- related uveitis after hematopoietic stem cell transplantation (HSCT).Methods:A retrospective clinical study. From October 2015 to May 2020, 14 cases of 21 eyes of CMVR patients with CMVR after HSCT confirmed by the ophthalmological examination of The First Affiliated Hospital of Soochow University were included in the study. Among them, there were 5 males with 8 eyes and 9 females with 13 eyes. The average age was 35.12± 12.24 years old. All the affected eyes were examined by slit lamp microscope combined with front lens and fundus color photography. At the same time, fluorescein fundus angiography (FFA) was performed to examine 10 eyes of 5 cases; 3 cases of 3 eyes were examined for inflammatory cytokines in aqueous humor. All eyes received intravitreal injection of ganciclovir; patients with a history of systemic CMV infection received intravenous infusion of ganciclovir/foscarnet. The retinal lesions in the eye were completely resolved or the aqueous CMV-DNA was negative as a cure for CMVR. The uveitis symptoms, signs, FFA manifestations and the test results of inflammatory factors in aqueous humor before and after the CMVR cure was observed. The follow-up time after CMVR was cured was 3-42 months, and the average follow-up time was 14.28±13.12 months.Results:All eyes with CMVR were diagnosed with retrocorneal dust and/or stellate keratic precipitates (KP), anterior chamber flare and cells, and varying degrees of vitreous flocculent opacity; the retina was typical of a mixture of hemorrhage and yellow-white necrosis like "scrambled eggs with tomatoes". After CMVR was cured, there were 16 eyes (71.4%, 10/14) in 10 cases with KP, anterior chamber flare, cell and vitreous opacity. FFA examination revealed that the majority of retinal leakage during the active period of CMVR was necrotic foci and surrounding tissues; after CMVR was cured, the majority of retinal leakage was the retina and blood vessels in the non-necrotic area. The test results of inflammatory factors in aqueous humor showed that interleukin (IL)-6, IL-8, and vascular endothelial cell adhesion molecules were significantly increased in the active phase of CMVR; after 3 months of CMVR cured, inflammatory factors did not increase significantly.Conclusion:CMVR-associated uveitis after HSCT show as chronic panuveitis, with no obvious eye congestion, KP, anterior chamber flare, cell and vitreous opacity, and retinal vessel leakage which could exist for a long time (>3 months).
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OBJECTIVE： To systematically evaluate therapeutic efficacy of sodium hyaluronate combined with Compound betamethasone versus sodium hyaluronate in the treatment of knee osteoarthritis （KOA）， and to provide evidence-based reference for clinical drug use. METHODS： Randomized controlled clinical trials （RCTs） about sodium hyaluronate combined with Compound betamethasone （observation group） versus sodium hyaluronate （control group） in the treatment of KOA were collected from Cochrane Library， PubMed， Embase， Web of Science， CNKI， Wanfang database and Baidu academics database， etc. By literature screening， data extraction and quality evaluation of included literatures with Jadad scale， Meta-analysis was carried out by using Rev Man 5.3 software. RESULTS： Totally 24 RCTs were included， involving 2 929 patients. Meta-analysis showed that total response rate [OR＝5.33， 95％CI（3.85， 7.38）， P＜0.000 01]， knee joint score of American Special Surgical Hospital [SMD＝1.63， 95％CI（1.32， 1.93）， P＜0.000 01]， knee function score [SMD＝1.22， 95％CI（0.84， 1.59）， P＜0.000 01] of the observation group were significantly higher than those of the control group； visual analogue score was significantly lower than that of control group [SMD＝－1.44， 95％CI（－1.76，－1.11）， P＜0.000 01]. CONCLUSIONS： In the treatment of KOA， therapeutic efficacy of sodium hyaluronate combined with Compound betamethasone is significantly better than sodium hyaluronate， and it can significantly improve knee function.
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Objective To observe the clinical characteristics and treatment of cytomegalovirus retinitis (CMVR) in leukemia patients.Methods This is a retrospective analysis. Seven leukemia patients (13 eyes) with CMVR were studied. All patients underwent examinations of visual acuity, slit lamp microscope, ophthalmoscope, color fundus photography, peripheral blood CD4+T cell count and serum/aqueous CMV-DNA test. All patients were treated with ganciclovir or zoledronic acid combined with intravitreal injection of ganciclovir. The follow-up period was 3-14 months.Results Six patients were treated with hematopoietic stem cell transplantation and 1 patient was with chronic leukemia. All patients were CMV-DNA positive for serum, and 18.5％ (2/7) for aqueous humor. CMVR in leukemia patients showed mild anterior segment inflammation, ocular fundus with irregular yellowish-white retinal necrosis and radial hemorrhage (7 eyes). Some (2 eyes) also shoed gray and white granular retinal infiltrates. Intravenous ganciclovir/zoledronic acid combined with intravitreal injection of high concentration ganciclovir was an effective treatment, while systemic corticosteroids were effective in reducing vitreous opacity.Conclusions CMVR is characterized by progressive necrotic retinitis with hemorrhage and vasculitis. Intravenous ganciclovir/zoledronic acid combined with intravitreal injection of ganciclovir is effective in the treatment of CMVR with leukemia.
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DNA damage response (DDR) is essential for maintaining genome stability and protecting cells from tumorigenesis. Ubiquitin and ubiquitin-like modifications play an important role in DDR, from signaling DNA damage to mediating DNA repair. In this report, we found that the E3 ligase ring finger protein 126 (RNF126) was recruited to UV laser micro-irradiation-induced stripes in a RNF8-dependent manner. RNF126 directly interacted with and ubiquitinated another E3 ligase, RNF168. Overexpression of wild type RNF126, but not catalytically-inactive mutant RNF126 (CC229/232AA), diminished ubiquitination of H2A histone family member X (H2AX), and subsequent bleomycin-induced focus formation of total ubiquitin FK2, TP53-binding protein 1 (53BP1), and receptor-associated protein 80 (RAP80). Interestingly, both RNF126 overexpression and RNF126 downregulation compromised homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs). Taken together, our findings demonstrate that RNF126 negatively regulates RNF168 function in DDR and its appropriate cellular expression levels are essential for HR-mediated DSB repair.
Subject(s)
Humans , Carrier Proteins , Metabolism , Cell Line, Tumor , DNA Breaks, Double-Stranded , DNA Repair , Genetics , DNA-Binding Proteins , Metabolism , Genomic Instability , HeLa Cells , Histones , Metabolism , Nuclear Proteins , Metabolism , RNA Interference , RNA, Small Interfering , Genetics , Signal Transduction , Tumor Suppressor p53-Binding Protein 1 , Metabolism , Ubiquitin , Ubiquitin-Protein Ligases , Genetics , Metabolism , UbiquitinationABSTRACT
Summary: The efficiency and safe range of LipofectamineTM2000 (LF2000)/bcl-xl applied in human keratocytes, the optimal ratio of LF2000/bcl-xl and the bcl-xl gene expression in human keratocytes were investiaged. By using trypan-blue staining, the effects of LF2000 and bcl-xl on the survival rate of the cultured human keratocytes were measured respectively. By using semi-quantitative RT-PCR, the efficiency and the expression of LF2000-mediated bcl-xl transfection into keratocytes were examined. The results showed that the survival rate of human keratocytes had no signficant change in the presence of LF2000 (20 μg/ml) or bcl-xl (10 μg/ml) for 24 h. LF2000 could effectively mediate the transfection of exogenous gene bcl-x1 into human keratocytes. The best transfection efficiency could be obtained when the ratio of bcl-xl/LF2000 was 1:8. One day after transfection, the positive cells for bcl-x1 could be detectable, and the positive rate reached the peak on the post-transfection day 3 (48.3 %), then gradually decreased. Fifteen days after transfection, there were few positive cells. It was suggested that LF2000 could effectively transfer the exogenous gene bcl-xl into human keratocytes without obvious toxicity during a concentration range. LF2000/bcl-xl may be likely to play an important role in gene therapy of human keratocytes.
ABSTRACT
The efficiency and safe range of Lipofectamine2000 (LF2000)/bcl-xl applied in human keratocytes, the optimal ratio of LF2000/bcl-xl and the bcl-xl gene expression in human keratocytes were investiaged. By using trypan-blue staining, the effects of LF2000 and bcl-xl on the survival rate of the cultured human keratocytes were measured respectively. By using semi-quantitative RT-PCR, the efficiency and the expression of LF2000-mediated bcl-xl transfection into keratocytes were examined. The results showed that the survival rate of human keratocytes had no signficant change in the presence of LF2000 (20 microg/ml) or bcl-xl (10 microg/ml) for 24 h. LF2000 could effectively mediate the transfection of exogenous gene bcl-xl into human keratocytes. The best transfection efficiency could be obtained when the ratio of bcl-xl/LF2000 was 1:8. One day after transfection, the positive cells for bcl-xl could be detectable, and the positive rate reached the peak-on the posttransfection day 3 (48.3%), then gradually decreased. Fifteen days after transfection, there were few positive cells. It was suggested that LF2000 could effectively transfer the exogenous gene bcl-xl into human keratocytes without obvious toxicity during a concentration range. LF2000/bcl-xl may be likely to play an important role in gene therapy of human keratocytes.
Subject(s)
Cations/administration & dosage , Cornea/cytology , Genetic Therapy , Keratinocytes/cytology , Keratinocytes/metabolism , Liposomes , Transfection , bcl-X Protein/biosynthesis , bcl-X Protein/geneticsABSTRACT
The role of catecholamine (CA) in the pathogenesis and development of macular edema of central serous chorioretinopathy (CSC) was studied, and its relations with visual acuity were investigated. Plasma concentrations of epinephrine (E) and norepinephrine (NE) were determined in 30 consecutive eyes with CSC. Central macular thickness analysis was done by RTA and all the data were compared with normal eyes and analyzed with SAS software package. Plasma concentrations of E and NE were increased to (569 +/- 123) ng/L and (721 +/- 104) ng/L respectively in active CSC patients, significantly higher than those in normal subjects (P < 0.01), and decreased to normal in convalescent stage. RTA analysis revealed that the retinal thickness of CSC patients was increased at active and recovery stage as compared with normal subjects; and the plasma concentration of E was significantly correlated with central macular thickness (t = 2.173, P < 0.05). Also, central macular thickness measured by RTA was significantly correlated with the visual acuity (r = -0.8046, P < 0.001) in CSC eyes. RTA analysis might be useful to quantitatively detect and evaluate prognosis in CSC patients. The plasma concentration of E, which was highly correlated with macular edema, might play an important role in the early damage and the pathogenesis of CSC.