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Patients benefit greatly from early detection of colorectal cancer, but present diagnostic procedures have high costs, low sensitivity, and low specificity. However, it is still difficult to develop a strategy that can effectively detect cancer early using high-throughput blood analysis. Fano resonance-boosted SERS platform label-free serum creates an effective diagnostic system at the point of care. We obtained 220 high-quality SERS serum spectral datasets from 88 healthy volunteers and 132 patients with colorectal cancer. The biomarker detected in serum was further evaluated using 100 colorectal cancer tissues and adjacent normal intestinal tissues collected from West China Biobanks, West China Hospital, Sichuan University. The results showed that in 97 out of 100 paired samples, the biomarkers were successfully detected using the SERS platform. This demonstrates that Fano resonance-based SERS is highly effective for diagnosing colorectal cancer.
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In psoriasis, keratinocytes are triggered by factors, such as infection or tissue damage, to release DNA, which thereby activates plasmacytoid dendritic cells and macrophages to induce inflammation, thickened epidermis, and parakeratosis. The recognition of double-stranded (ds)DNA facilitates the activation of cytoplasmic DNA sensors absent in melanoma 2 (AIM2) inflammasome assembly and cyclic guanosine monophosphate adenosine monophosphate (cGAMP) synthase (cGAS) - stimulator of interferon gene (STING) pathway, both of which play a pivotal role in mediating the inflammatory response and driving the progression of psoriasis. Additionally, secreted proinflammatory cytokines can stimulate further DNA release from keratinocytes. Notably, the activation of AIM2 and cGAS-STING signaling pathways also mediates programmed cell death, potentially enhancing DNA overproduction. As a result, excessive DNA can activate these pathways, amplifying persistent inflammatory responses that contribute to the maintenance of psoriasis. Several studies have validated that targeting DNA and its mediated activation of AIM2 and cGAS-STING offers promising therapeutic strategies for psoriasis. Here, we postulate a hypothesis that excessive cytosolic DNA can activate AIM2 and cGAS-STING, mediating inflammation and programmed cell death, ultimately fostering DNA accumulation and contributing to the development of psoriasis.
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We report a fatal case of disseminated herpes zoster in a patient with multiple myeloma, illustrating the severe risks immunocompromised individuals face from viral infections. By combining a detailed case report with an extensive literature review, the paper seeks to shed light on the underlying susceptibility factors for varicella-zoster virus infection in multiple myeloma patients. We further evaluate effective prophylactic protocols for herpes zoster, aiming to equip clinicians with improved therapeutic strategies. The case underscores the critical need for vigilant clinical assessments and tailored patient management to mitigate infection risks and enhance patient outcomes.
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A 64-year-old female presented with acute painless vision loss in the left eye was diagnosed with neovascular age-related macular degeneration. During the 20-year follow-up, the patient experienced subretinal fluid, subretinal hemorrhage, pigmentary epithelium detachment, intraretinal fluid, subretinal scar formation and macular atrophy. A total of 3 PDT treatments, 3 intravitreal bevacizumab and 16 ranibizumab injections were performed in the left eye. At the last visit, she remained best-corrected visual acuity of 20/200 with foveal macular atrophy and subfoveal fibrotic scar.
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Degeneração Macular , Fotoquimioterapia , Feminino , Humanos , Pessoa de Meia-Idade , Ranibizumab , Bevacizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Cicatriz/tratamento farmacológico , Resultado do Tratamento , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Degeneração Macular/tratamento farmacológico , Atrofia/tratamento farmacológico , Injeções Intravítreas , Tomografia de Coerência ÓpticaRESUMO
Background: Thyroid function abnormality (TFA) is one of the most common toxicities in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors. However, the risk factors related to TFA and the relationship between TFA and prognosis in NSCLC are not fully clarified. Methods: We conducted a retrospective study of patients with advanced NSCLC who were treated with PD-1 inhibitors in Huzhou Central Hospital. Thyroid function test was carried out using electrochemiluminescent bridging immunoassay. The association between TFA and clinical outcome was investigated. Results: A total of 273 patients were included in this study. Patients who experienced TFA had longer progression-free survival (21.9 vs 6.4 months; p < 0.001) and overall survival (44.6 vs 24.1 months; p = 0.02) than patients without TFA. After multivariate analysis, TFA was an independent prognostic factor for progression-free and overall survival (p < 0.05). Conclusion: TFA is associated with better outcome in NSCLC patients who receive immunotherapy.
Many patients with non-small-cell lung cancer are treated with immunotherapy, a type of treatment that uses the body's natural immune system to fight diseases. We conducted a retrospective study of advanced non-small-cell lung cancer patients who were treated with PD-1 inhibitors (a type of immunotherapy) in Huzhou Central Hospital. Thyroid function abnormality (TFA) is one of the common toxicities in patients receiving PD-1 inhibitors. Our study showed that patients who experienced TFA have longer survival times compared with patients without TFA (overall survival, 44.6 vs 24.1 months; p = 0.02). TFA could be an effective predictor of outcome in non-small-cell lung cancer cases being treated with immunotherapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia , Prognóstico , Estudos Retrospectivos , Glândula TireoideRESUMO
RATIONALE: Aortic arch interruption is a type of congenital vascular malformation that is often observed in childhood. Most children die of congestive heart failure due to rapid deterioration. Children can only survive to adulthood if they have extremely rich collateral circulation. Cases of acute cerebral infarction with large vessel occlusion receiving interventional treatment in adult patients with interrupted aortic arch have not been reported. PATIENT CONCERNS: A 55-year-old man with a history of atrial fibrillation and smoking but without a family history of stroke was admitted to our hospital with a 5-hour history of left limb weakness and speech difficulties. DIAGNOSES: Emergency brain computed tomography showed a large cerebral infarction in the right frontal temporal parietal lobe. He was suspected to have aortic arch interruption in the early stage of endovascular interventional therapy through the femoral artery approach, and was converted to the transradial artery pathway. The aortic arch was disconnected, and the right internal carotid artery was occluded. INTERVENTIONS: Considering the possibility of cardiogenic embolism, a middle catheter was used for thrombus aspiration of the right internal carotid artery. After removal of the dark red thrombus was removed, the right internal carotid artery was successfully recanalized. OUTCOMES: The patient recovered well after the operation. However, the patient and his family refused further treatment for aortic arch interruption. The modified Rankin Scale score was 0 at 3âmonths and 1âyear of follow-up which meant that he recovered quite well. LESSONS: Adult patients with acute cerebral infarction with large vessel occlusion are rarely complicated with aortic arch interruption, and emergency thrombectomy via the radial artery approach is feasible.
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Aorta Torácica/cirurgia , Coartação Aórtica/cirurgia , Arteriopatias Oclusivas/cirurgia , Infarto Cerebral/tratamento farmacológico , Procedimentos Endovasculares/métodos , Adulto , Aorta Torácica/diagnóstico por imagem , Coartação Aórtica/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Trombose , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Circular RNAs (circRNAs) are involved in a variety of biological processes, including tumorigenesis. However, the exact role and molecular mechanisms of circ_0000043 in endometrial carcinoma (EC) remain largely unknown. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the expression levels of circ_0000043, microRNA-1271-5p (miR-1271-5p) and catenin delta 1 (CTNND1). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to measure cell proliferation, cell apoptosis and cell cycle distribution, respectively. Cell migration and invasion were assessed by transwell assay. Western blot assay was performed to examine the protein expression of matrix metalloproteinase 2 (MMP2), MMP9 and CTNND1. The interaction between miR-1271-5p and circ_0000043 or CTNND1 was predicted by starBase and confirmed by dual-luciferase reporter assay. The mice xenograft model was established to investigate the role of circ_0000043 in vivo. RESULTS: Circ_0000043 and CTNND1 were highly expressed and miR-1271-5p was lowly expressed in EC tissues and cells. Knockdown of circ_0000043 inhibited the progression of EC by inhibiting cell proliferation, migration, invasion and tumor growth (in vivo) and promoting apoptosis. MiR-1271-5p was a direct target of circ_0000043 and its inhibition reversed the inhibitory effect of circ_0000043 knockdown on the progression of EC cells. In addition, CTNND1 was a downstream target of miR-1271-5p, and miR-1271-5p overexpression inhibited EC cell proliferation, migration and invasion and induced apoptosis by targeting CTNND1. Moreover, circ_0000043 positively regulated CTNND1 expression by sponging miR-1271-5p. CONCLUSION: Circ_0000043 knockdown inhibited the progression of EC by regulating miR-1271-5p/CTNND1 axis, which might provide a promising circRNA-targeted therapy for EC.
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Cateninas/metabolismo , Neoplasias do Endométrio/genética , MicroRNAs/metabolismo , RNA Circular/análise , Animais , Ciclo Celular , Proliferação de Células , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase em Tempo Real , delta CateninaRESUMO
PURPOSE: To investigate whether triptolide-nanoliposome-APRPG (TP-nanolip-APRPG), a novel sustained-release nano-drug delivery system that targets vascular endothelial cells, could enhance the inhibition of triptolide (TP) on laser-induced choroidal neovascularization (CNV). METHODS: TP was encapsulated with or without APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified nanoliposomes. CNV was induced by laser photocoagulation in C57BL/6J mice. One microliter of 10⯵g free TP monomer, TP-nanolip containing 10⯵g TP, TP-nanolip-APRPG containing 10⯵g TP, or an identical volume of PBS was intravitreally injected in mice immediately after laser photocoagulation. Seven days after laser photocoagulation, CNV volumes were calculated in each group. Infiltration of M2 macrophages as well as protein levels of vascular endothelial growth factor (VEGF) and inflammatory factors including ICAM-1 and MCP-1 in the RPE-choroid complex were determined. In vitro assays for cell proliferation, migration, and tube formation were also performed. RESULTS: TP-nanolip-APRPG was successfully synthesized and exhibited good TP delivery and enhanced the cellular uptake of TP in vitro. In vitro studies showed that TP-nanolip-APRPG was a better inhibitor of cell proliferation (31.34⯱â¯3.89 % vs 41.25⯱â¯4.67 % vs 53.55⯱â¯5.76 %), migration (62.60⯱â¯8.88 vs 104.60⯱â¯13.32 vs 147.00⯱â¯13.15), and tube formation (681.26⯱â¯108.15 vs 926.75⯱â¯54.01 vs 1189.84⯱â¯157.14) than TP-nanolip or free TP (all Pâ¯<â¯0.05). Intravitreal injections of free TP (77588.10±7719.28 µm3), TP-nanolip (64628.23⯱â¯5857.96 µm3), and TP-nanolip-APRPG (50880.34⯱â¯6606.56 µm3) inhibited the development of CNV compared with the PBS control group (120338.07⯱â¯17428.90 µm3) (Pâ¯<â¯0.01, n=6). TP-nanolip-APRPG and TP-nanolip significantly down-regulated the protein levels of VEGF (152.76±19.55 vs 182.24±19.98 vs 208.55±21.93 pg/mg total protein) and inflammatory factors including ICAM-1 (61.69±3.49 vs 72.04±3.49 vs 81.92±4.09 ng/mg total protein) and MCP-1 (40.14±3.50 vs 50.75±4.18 vs 60.27±5.23 pg/mg total protein) compared with the free TP monomer group (all Pâ¯<â¯0.05, n=8), which paralleled the decreased infiltration of M2 macrophages in the CNV lesions. Moreover, no influence on retinal morphology and function was observed before or after treatment in each group (Pâ¯>â¯0.05, n=6). CONCLUSIONS: TP-nanolip-APRPG, a novel sustained-release drug delivery system targeting endothelial cells of CNV lesions, could enhance TP inhibition of the development of CNV without toxicity in the retina, suggesting therapeutic potential for CNV-related diseases in future clinical practice.
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Neovascularização de Coroide/prevenção & controle , Diterpenos/administração & dosagem , Células Endoteliais/efeitos dos fármacos , Lipossomos/química , Nanopartículas/química , Oligopeptídeos/química , Fenantrenos/administração & dosagem , Animais , Movimento Celular/efeitos dos fármacos , Neovascularização de Coroide/etiologia , Preparações de Ação Retardada , Diterpenos/química , Diterpenos/farmacocinética , Liberação Controlada de Fármacos , Compostos de Epóxi/administração & dosagem , Compostos de Epóxi/química , Compostos de Epóxi/farmacocinética , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenantrenos/química , Fenantrenos/farmacocinética , Retina/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
BACKGROUND: To evaluate the anatomical and functional responses in eyes with diabetic macular edema (DME) treated with ranibizumab under "1 + pro re nata (PRN)" regimen. METHODS: This prospective interventional case series included 69 eyes of 69 patients with DME treated with intravitreal injections of 0.5 mg ranibizumab followed by repeated injections as needed. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), and predictive factors for final visual outcomes were assessed. RESULTS: Logarithm of minimal angle of resolution (logMAR) BCVA improved from 0.64 ± 0.23 at baseline to 0.56 ± 0.27, 0.53 ± 0.26, 0.47 ± 0.25, 0.44 ± 0.32, 0.47 ± 0.26 and 0.46 ± 0.26 at time-point of months 1, 2, 3, 6, 9, and 12, respectively (P < 0.05 for any follow-up time-point except month 1). CFT decreased from 478.23 ± 172.31 µm at baseline to 349.74 ± 82.21 µm, 313.52 ± 69.62 µm, 292.59 ± 61.07 µm, 284.67 ± 69.85 µm, 268.33 ± 43.03 µm, and 270.39 ± 49.27 µm at above time-points, respectively (P < 0.05). The number of injections was 6.83 times over 12 months' follow-up under "1 + PRN" regimen. Multivariate analysis showed that the factors including age, BCVA at baseline, disruption of ellipsoid zone, posterior vitreous detachment (PVD), and vitreomacular traction (VMT) were correlated with the final BCVA. CONCLUSIONS: Intravitreal injections of ranibizumab under "1 + PRN" regimen is a not only effective but also safe way to improve visual acuity of DME patients. And older age, lower baseline BCVA, VMT, and disruption of ellipsoid zone are predictors for final poor BCVA while PVD is a positive predictive factor for good final BCVA. TRIAL REGISTRATION: The trial was registered retrospectively in ClinicalTrials.gov on 2 June 2019 (NCT03973138).
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Retinopatia Diabética/complicações , Edema Macular/tratamento farmacológico , Ranibizumab/administração & dosagem , Acuidade Visual , Inibidores da Angiogênese/administração & dosagem , China/epidemiologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Angiofluoresceinografia/métodos , Humanos , Injeções Intravítreas , Edema Macular/epidemiologia , Edema Macular/etiologia , Masculino , Estudos Prospectivos , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
PURPOSE: To investigate whether triptolide has inhibitory effects on the development of choroidal neovascularization (CNV), together with its underlying anti-angiogenic mechanisms. METHODS: CNV was induced in C57BL/6 J mice using laser photocoagulation. Triptolide at concentrations of 0.035 and 0.07 mg/kg body weight (BW) or the same volume of phosphate-buffered saline (PBS) was intraperitoneally injected into mice 2 days before laser photocoagulation, which was continued daily till the end of the experiment. CNV areas were measured on day 7. The numbers of M1, M2, and F4/80+ macrophages were detected on day 1, 3, and 7 in each group. The levels of vascular endothelial growth factor (VEGF) and inflammatory molecules,including intercellular adhesion molecule (ICAM)-1,tumor necrosis factor (TNF)-α, and interleukin 6 (IL-6) were determined by enzyme-linked immunosorbent assay. Cell proliferation, migration, and tube-formation assays were performed in vitro. RESULTS: Triptolide at doses of 0.035 mg/kg BW (66,562 ± 39,253 µm2, n = 5, Pï¼0.05) and 0.07 mg/kg BW (37,271 ± 25,182 µm2, n = 5, Pï¼0.001) significantly reduced CNV areas by 54.9 and 74.8 %, respectively, compared with PBS control (147,699 ± 112,900 µm2, n = 5) in a dose-dependent manner. Protein levels of VEGF, ICAM-1, TNF-α, and IL-6 in the RPE-choroid-sclera complex were significantly downregulated by triptolide treatment on day 3, which was in accordance with the reduced number of infiltrated F4/80+ macrophages and the reduced ratio of M2/F4/80+ macrophages. However, no toxic effects of triptolide on the retina or other systemic organs were observed. In addition, triptolide treatment exerted inhibitory effects on cell proliferation, migration, and tube formation in vitro in a concentration-dependent manner. CONCLUSIONS: Triptolide has therapeutic potential in CNV owing to its anti-angiogenic effect.
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Inibidores da Angiogênese/farmacologia , Corioide/irrigação sanguínea , Neovascularização de Coroide/prevenção & controle , Diterpenos/farmacologia , Fotocoagulação a Laser , Macrófagos/efeitos dos fármacos , Fenantrenos/farmacologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Células Cultivadas , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Compostos de Epóxi/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos Endogâmicos C57BL , Fenótipo , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To investigate the effectiveness and safety of intravitreal injection of conbercept (IVC) as the initial treatment for exudative circumscribed choroidal hemangioma (CCH). METHODS: Forty-two eyes of 42 patients received 3 monthly IVC (0.5 mg/0.05 mL) as the initial treatment. Three months later, the patients were assessed for further treatment including observation, reinjection of conbercept, laser photocoagulation (if the lesion was 3,000 µm away from the macular fovea), or photodynamic therapy (PDT; if the lesion was under the macular fovea). Anatomical and functional responses including best corrected visual acuity (BCVA), central foveal thickness (CFT), and tumor size were analyzed. RESULTS: Twenty-three patients (54.76%) were sensitive to the monotherapy of IVC. Fourteen patients (33.33%) were insensitive to IVC and underwent rescue laser photocoagulation, and 5 patients (11.90%) underwent rescue PDT due to insensitivity to IVC treatment at 3 months. For subgroup analysis, although no statistical difference was found for BCVA at any follow-up time point compared to baseline, an increasing tendency of BCVA was found in the IVC group (p> 0.05). The mean CFT decreased significantly from 427.13 ± 214.74 µm at baseline to 259.83 ± 61.68 µm at 6 months in the IVC group (p< 0.05). No influence on tumor size was found in the IVC group. CONCLUSION: IVC as the initial treatment might be an option for exudative CCH.
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Neoplasias da Coroide , Hemangioma , Proteínas Recombinantes de Fusão , Neoplasias da Coroide/tratamento farmacológico , Hemangioma/tratamento farmacológico , Humanos , Injeções Intravítreas , Proteínas Recombinantes de Fusão/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento , Acuidade VisualRESUMO
Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA), improve glucose metabolism in diabetic subjects, although the underlying mechanisms remain unclear. In this study, we observed dysregulated expression of cyclooxygenase-2, prostacyclin biosynthesis, and the I prostanoid receptor (IP) in the liver's response to diabetic stresses. High doses of ASA reduced hepatic prostaglandin generation and suppressed hepatic gluconeogenesis in mice during fasting, and the hypoglycemic effect of ASA could be restored by IP agonist treatment. IP deficiency inhibited starvation-induced hepatic gluconeogenesis, thus inhibiting the progression of diabetes, whereas hepatic overexpression of IP increased gluconeogenesis. IP deletion depressed cAMP-dependent CREB phosphorylation and elevated AKT phosphorylation by suppressing PI3K-γ/PKC-ζ-mediated TRB3 expression, which subsequently downregulated the gluconeogenic genes for glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 in hepatocytes. We therefore conclude that suppression of IP modulation of hepatic gluconeogenesis through the PKA/CREB and PI3K-γ/PKC-ζ/TRB3/AKT pathways contributes to the effects of NSAIDs in diabetes.
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Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Gluconeogênese/efeitos dos fármacos , Fígado/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Receptores de Prostaglandina/fisiologia , Animais , Aspirina/farmacologia , Proteínas de Ciclo Celular/fisiologia , Diabetes Mellitus Experimental/prevenção & controle , Dieta Hiperlipídica , Epoprostenol/fisiologia , Jejum , Glucose-6-Fosfatase/metabolismo , Camundongos , Camundongos Knockout , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Epoprostenol , Receptores de Prostaglandina/deficiênciaRESUMO
New-onset diabetes might help to yield biomarkers for the early diagnosis of pancreatic cancer (PaC). In this study, we computationally predicted and experimentally validated osteoprotegerin (OPG) being associated with pancreatic cancer related new-onset diabetes. We first performed a meta-analysis on microarray datasets to search for genes specifically highly expressed in PaC, and then filtered for cytokines involved in islet dysfunction. The expression of OPG in PaC and normal pancreas were validated by immunohistochemistry. Serum OPG levels in healthy controls, non-cancerous diabetes and PaC patients with or without diabetes were detected by enzyme-linked immunosorbent assay (ELISA). In silico assay found that OPG up-regulated in PaC tissues in comparison to normal pancreas. Immunohistochemical data further confirmed that OPG was overexpressed in PaC samples. Furthermore, increased expression of OPG in PaC tissues correlated to the occurrence of new-onset diabetes, and adversely affected the patients' overall survival in both univariate and multivariate analysis. In addition, the serum levels of OPG were significantly higher in pancreatic cancer patients with new-onset diabetes than other groups including pancreatic patients without diabetes, new-onset type 2 diabetes and healthy controls. In conclusion, there is a close association between OPG and pancreatic cancer related new-onset diabetes, and OPG might serve as a potential biomarker for the early diagnosis of pancreatic cancer from populations with new-onset diabetes.
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Biomarcadores Tumorais/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Osteoprotegerina/sangue , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/fisiopatologia , Mineração de Dados , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Pancreáticas/sangue , Análise Serial de ProteínasRESUMO
PURPOSE: To investigate the effects of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of choroidal neovascularization (CNV), together with its underlying mechanisms. METHODS: C57BL/6J mice were used to induce CNV by laser photocoagulation. (99)Tc-MDP at the doses of 0.5 × 10(-1), 1 × 10(-1), and 2 × 10(-1) µg/kg or the same volume of PBS was intraperitoneally injected daily after photocoagulation until the end of the experiment. Seven days after laser injury, mice were perfused with fluorescein-labeled dextran, and areas of CNV were measured. Numbers of infiltrating macrophages, protein levels of VEGF, and inflammation-related molecules including intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, and matrix metalloproteinases (MMPs) in the RPE-choroid complex were detected 3 days after laser photocoagulation. Effects of (99)Tc-MDP on VEGF-induced endothelial cell migration and tube formation were also studied. Toxicity of (99)Tc-MDP was evaluated in vivo and in vitro. RESULTS: Areas of CNV were significantly suppressed by (99)Tc-MDP treatment without toxicity to the retina compared with PBS treatment in a dose-dependent manner: (99)Tc-MDP treatment of 0.5 × 10(-1) µg/kg (5698.60 ± 1037.70 µm(2)), 1 × 10(-1) µg/kg (3678.34 ± 1328.18 µm(2)), and 2 × 10(-1) µg/kg (2365.78 ± 923.80 µm(2)) suppressed the development of CNV by 36.12%, 58.76%, and 73.48%, respectively, compared with that in the PBS treatment group (8920.36 ± 1097.29 µm(2); P < 0.001). (99)Tc-MDP treatment led to significant inhibition of macrophages infiltrating to CNV together with downregulated protein expressions of VEGF, ICAM-1, TNF-α, and MMP-2. (99)Tc-MDP also showed an inhibitive effect on cell proliferation and VEGF-induced migration and capillary-like tube formation of endothelial cells. CONCLUSIONS: Anti-inflammatory treatment with (99)Tc-MDP has therapeutic potential for CNV-related diseases.
Assuntos
Anti-Inflamatórios , Movimento Celular/fisiologia , Neovascularização de Coroide , Medronato de Tecnécio Tc 99m , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Corioide/citologia , Corioide/efeitos dos fármacos , Corioide/fisiologia , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/patologia , Modelos Animais de Doenças , Eletrorretinografia , Células Endoteliais/citologia , Expressão Gênica/efeitos dos fármacos , Técnicas In Vitro , Fotocoagulação , Macaca mulatta , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Camundongos , Camundongos Endogâmicos C57BL , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Retina/citologia , Retina/efeitos dos fármacos , Retina/fisiologia , Medronato de Tecnécio Tc 99m/síntese química , Medronato de Tecnécio Tc 99m/farmacologia , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
OBJECTIVE: To investigate the ocular blood-aqueous barrier (BAB) alteration after laser peripheral iridotomy (LPI) or surgery peripheral iridectomy (SPI) in patients with primary chronic angle-closure glaucoma (PCACG). METHODS: This was a clinical randomized controlled trial. Sixty eyes of 60 subjects with early stage of PCACG were randomly received either LPI or SPI and followed up postoperatively at day 3, week 1, 2, 3, and 4. Aqueous flare in anterior chamber was measured by FC-2000 flare-cell photometry, intraocular pressure (IOP) measured by tonometer, central corneal endothelium cell counted by endothelioscopy, peripheral anterior synechiae (PAS) detected by gonioscopy. Data were analyzed by using two-way ANOVA for repeated measures, independent samples t-test, paired t-test, nonparametric test, and Spearman rank correlation test. RESULTS: On follow-ups of pre-operative and post-operative 3 days, 1 week (w), 2w, 3w and 4w respectively, the mean aqueous flare values for LPI group were (5.47 ± 1.09), (11.96 ± 3.07), (8.08 ± 2.18), (5.68 ± 0.83), (5.80 ± 1.00), (5.69 ± 1.12) PC/ms, and for SPI group were (5.43 ± 1.13), (8.44 ± 3.22), (6.42 ± 1.77), (5.35 ± 0.71), (5.53 ± 1.26), (5.45 ± 1.23) PC/ms. During post-operative 1w the flare values in both LPI and SPI groups were significantly higher than that on pre-operation (t = -12.753, -8.101, P < 0.05; t = -5.971, -3.870;P < 0.05) and LPI group had a significantly higher mean flare value than SPI group (t = 4.329, 3.231;P < 0.05). The IOP spike in LPI group was significantly (χ(2) = 5.079, 4.022, P < 0.05) higher than that in SPI group at week 1 of post-operation. Increased IOP was positively correlated with BAB damage (r = 0.899, 0.833; P < 0.05). The numbers of medications required to maintain IOP ≤ 21 mm Hg (1 mm Hg = 0.133 kPa) at week 4 of post-operation in LPI was significantly (Z = -1.984, P < 0.05) more than that in SPI group. There were no significant differences in central corneal endothelium cell count at week 1 (t = -0.696, 0.008) and in extension of PAS at week 4 (Z = -1.270, -1.490) of post-operation when compared to pre-operation (P > 0.05). No obvious complications occurred in both groups. CONCLUSIONS: Our results demonstrated that IOP spike in both of LPI and SPI is due, at least in part, to BAB damage, which appears to be more severe in LPI group and can recover within two weeks. PAS progression and central corneal endothelium cell loss are not aggravated in 1 month after operation.
Assuntos
Barreira Hematoaquosa/fisiopatologia , Glaucoma de Ângulo Fechado/fisiopatologia , Glaucoma de Ângulo Fechado/cirurgia , Iridectomia/métodos , Idoso , Feminino , Glaucoma de Ângulo Fechado/metabolismo , Humanos , Pressão Intraocular , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Tonometria OcularRESUMO
PURPOSE: To compare the influence of krypton laser with different power densities combined with Nd:YAG laser peripheral iridotomy (LPI) on the intraocular pressure, blood-aqueous barrier and inflammatory of anterior chamber as well as the therapeutic effect. METHODS: Using a laser flare cell meter and Goldmann tonometer, the level of aqueous protein, the number of cells in the anterior chamber and intraocular pressure of 31 patients (62 eyes) who underwent krypton laser with different power densities combined with Nd:YAG laser peripheral iridotomy were examined and recorded preoperatively and postoperatively. RESULTS: The mean preoperative and 1-hour, 3-day, 7-day, 1-month postoperative intraocular pressure (IOP) of the high power-density group were (15.68 +/- 2.41), (27.13 +/- 3.48), (20.97 +/- 5.27), (16.35 +/- 1.14) and (15.06 +/- 2.02) mmHg, while those of the low were (15.35 +/- 1.78), (22.77 +/- 3.26), (16.26 +/- 2.41), (15.68 +/- 2.06) and (15.06 +/- 1.36) mmHg. The mean preoperative and 3-day, 7-day, 1-month postoperative flare intensity of the high power-density group were (4.65 +/- 1.50), (10.41 +/- 2.47), (7.31 +/- 2.31) and (6.15 +/- 2.16) pc/ms, while those of the low were (4.45 +/- 1.19), (6.47 +/- 1.11), (4.81 +/- 0.55) and (4.98 +/- 1.48) pc/ms. The number of aqueous cells of the high was (0.47 +/- 0.42), (36.22 +/- 9.16), (18.54 +/- 3.60) and (6.29 +/- 0.98), while that of the low was (0.58 +/- 0.52), (24.73 +/- 6.09), (10.61 +/- 1.70) and (2.96 +/- 1.35). The mean 1-hour and 3-day postoperative IOP of the high was higher than that of the low. Both the mean flare intensity and the mean number of aqueous cells of the high power-density group were higher than those of the low. The differences were of statistical significance (P < 0.05). The mean flare intensity of the high power-density group in the 1-month postoperative follow-up was still higher than the baseline. The mean number of aqueous cells of both the high and the low power-density groups in the 1-month postoperative follow-up was still higher than the baseline. During 1-month follow-up, no obvious visual damage, diffuse corneal endothelial burns or corneal decompensation, lens injury and closure of the peripheral iris incision were observed. CONCLUSION: When krypton laser combined with Nd:YAG laser peripheral iridotomy is under consideration, relatively low power-density krypton laser is recommended because it can achieve the similar therapeutic effects as high power-density krypton laser but leads to less complications and a briefer recovery. More follow-ups are needed after LPI, because the number of aqueous cells in 1-month follow-up was still abnormal.
Assuntos
Câmara Anterior , Iris/cirurgia , Criptônio/uso terapêutico , Terapia a Laser/métodos , Adulto , Câmara Anterior/citologia , Câmara Anterior/metabolismo , Câmara Anterior/cirurgia , Barreira Hematoaquosa , Feminino , Seguimentos , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Período Pós-OperatórioRESUMO
OBJECTIVE: To study the clinical effect of photodynamic therapy (PDT) with Visudyne for polypoidal choroidal vasculopathy (PCV). METHODS: Ten patients (10 eyes) with PCV who were diagnosed by fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), optic coherence tomography (OCT) were treated by PDT with Visudyne. Eight cases (8 eyes) were male, the other two cases (2 eyes) were female. Their ages ranged from 50 to 77 years, mean (59.5 +/- 9.70) years. The best corrected visual activity (BCVA) before PDT was 0.1 - 0.5. The changes of BCVA, fundus photography, FFA and ICGA before and after PDT were compared. Follow-up time varied from 6 months to 36 months, mean 24 months. RESULTS: 1 month after PDT the BCVA was found to be unchanged in 4 eyes, increased in 1 line in 3 eyes, increased in 2 lines in 2 eyes, decreased in 3 lines in 1 eye. FFA and/or ICGA showed no leakage in 4 eyes, leakage reduced in 3 eyes, slight leakage in 2 eyes. At the last follow-up, the BCVA was found to be unchanged in 4 eyes, increased in 1 line in 2 eyes, increased in 2 lines in 2 eyes, increased in 3 lines in 1 eye which received 3 times PDT, decreased in 2 lines in 1 eye. FFA/ICGA showed no leakage in 7 eyes, slight leakage in 2 eyes. No systemic or local adverse effect was found during or after PDT, except 1 eye with extensive subretinal hemorrhage suffered vitreous hemorrhage one month after PDT. CONCLUSIONS: Photodynamic therapy with Visudyne may stop or reduce the macular leakage, facilitate the absorption of hemorrhage, exudates and edema, stabilize or increase the patients' visual activities. It could be a choice for the treatment of PCV. Certainly these tendencies need to be confirmed in a multi-center randomized controlled investigation with longer follow-up time.