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AIM: To investigate the research trend on refractive cataract surgery, compare the contributions of different countries, institutions, journals, and authors in the past 20y, and explore its potential research hotspots. METHODS: All publications were extracted relating to refractive cataract surgery from 2003 to 2022 from Web of Science. Document types were limited to original articles and reviews, and the language was limited to English. Quantitatively and qualitatively of the publications were analyzed through Microsoft Excel and GraphPad Prism. VOSviewer and CiteSpace were used for bibliometric and visualized analysis. RESULTS: A total of 2090 publications were enrolled. The United States contributed the most publications (434, 20.8%), followed by China (345, 16.5%) and England (163, 7.80%). Publications from the United States were cited more frequently (9552 citations) with the highest H-index of 48. China ranked second in the total number of publications, the papers were not cited that frequently (3237 citations), and the H-index ranked sixth (H-index=29). Journal of Cataract and Refractive Surgery published the most papers (333, 15.9%), and the University of London had the highest number of publications (75, 3.59%). Dick HB from Germany published the most papers. Corneal astigmatism-related research, cataract surgery method-related research, postoperative visual-quality relate to research, and postoperative complications-relate research are the hotspots in this field. The most significant limitation was that the database was updated frequently and the latest publications were not included. CONCLUSION: The bibliometric analysis shows a brief summarization of the contribution of the authors, institutions, countries, and journals. Corneal astigmatism, cataract surgery method, postoperative visual-quality and postoperative complications related researches have become the emerging hotspots, which can give a direction in the future researches.
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Tumefactive demyelinating lesion (TDL) is an immune-mediated disease which can be misdiagnosed as glioma. At present, there is no study comparing difference between the two disorders at the cellular level. Here, we perform integrative and comparative single-cell RNA sequencing (ScRNA-seq) transcriptomic analysis on TDL and glioma lesions. At single-cell resolution, TDL is comprised primarily of immune cells, which is completely different from glioma. The integrated analysis reveals a TDL-specific microglial subset involving in B cell activation and proliferation. Comparative analysis highlights remyelination function of glial cells and demyelination function of T cells in TDL. Subclustering and pseudotime trajectory analysis of T cells in TDL reveal their heterogeneity and diverse functions involving in TDL pathogenesis and recovery process. Our study identifies substantial differences between TDL and glioma at single-cell resolution. The observed heterogeneity and potentially diverse functions of cells in TDL may be critical in disease progression.
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Glioma , Análise de Célula Única , Perfilação da Expressão Gênica , Glioma/diagnóstico , Glioma/genética , Humanos , Neuroglia , TranscriptomaRESUMO
We find that tilt and decentration of intraocular lens (IOL) commonly cause visual quality deterioration after cataract surgery. Multiple factors affect IOL tilt and decentration in the pre-, mid-, and post-operation phases. Moreover, the tilt and decentration of 1-piece IOL are less correlated with internal ocular HOAs than those of 3-piece IOL. Aspherical IOLs are more sensitive to decentration or tilt than spherical IOLs. Furthermore, the optical performance of toric IOLs with an accurate axis remains stable irrespective of tilt and decentration. The optical quality of asymmetric multifocal IOLs varies significantly after decentration and tilt in different directions. The image quality enhances or deteriorates in the direction of the decentered IOL. An extended depth of focus IOL can achieve good visual acuity in the distant, intermediate, and near range. Additionally, its tilt and decentration have less impact on the vision than bifocal and trifocal IOL. This is the first review that compares the effect of IOL tilt and decentration on image quality for various IOL designs. The result indicates that a deeper understanding of tilt and decentration of various IOLs can help achieve a better visual effect to visually improve refractive cataract surgery.
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Objective To explore the clinical significance of the combined application of palpebral margin cleaning and antibiotic eye drops in inhibiting bacterial growth in the palpebral margin and conjunctival sacs before cataract extraction. Methods In this study, 61 patients (97 eyes) with age-related cataract who underwent phacoemulsification and intraocular lens implantation were selected, and randomly grouped. In the experimental group, the combined application of palpebral margin cleaning with cotton pads and levofloxacin eye drops was given for three days before the surgery. In the control group, levofloxacin eye drops alone were applied for three consecutive days. Bacteria samples from the conjunctival sac and eyelid margins were cultivated and identified before and three days after taking antimicrobial measures, respectively. Results In the experimental group, the positive rates of the two bacteria samples were 100% (50/50) and 40% (20/50) before and 10% (5/50) and 0% (0/50) after the treatment. In the control group, the positive rates of the two bacteria samples were 97.9% (46/47) and 29.8% (14/47) before and 40.4% (19/47) and 10.6% (5/47) after the treatment. The positive rates between the two groups were not significantly different before taking antimicrobial measures (P= 0.485 and 0.395), while they were significantly different after taking antimicrobial measures (P = 0.001 and 0.024). Conclusion Combined application of eyelid and palpebral margin cleaning with cotton pads and antibiotic eye drops before cataract extraction imparted excellent antibacterial effects.
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Extração de Catarata , Catarata , Antibacterianos/farmacologia , Bactérias , Túnica Conjuntiva/microbiologia , Pálpebras/microbiologia , Humanos , Levofloxacino/farmacologia , Levofloxacino/uso terapêutico , Soluções Oftálmicas/farmacologiaRESUMO
BACKGROUND: This study aims to establish an integrated model based on clinical, laboratory, radiological, and pathological factors to predict the postoperative recurrence of atypical meningioma (AM). MATERIALS AND METHODS: A retrospective study of 183 patients with AM was conducted. Patients were randomly divided into a training cohort (n = 128) and an external validation cohort (n = 55). Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, time-dependent receiver operating characteristic (ROC) curve analysis, and evaluation of clinical usage were used to select variables for the final nomogram model. RESULTS: After multivariable Cox analysis, serum fibrinogen >2.95 g/L (hazard ratio (HR), 2.43; 95% confidence interval (CI), 1.05-5.63; p = 0.039), tumor located in skull base (HR, 6.59; 95% CI, 2.46-17.68; p < 0.001), Simpson grades III-IV (HR, 2.73; 95% CI, 1.01-7.34; p = 0.047), tumor diameter >4.91 cm (HR, 7.10; 95% CI, 2.52-19.95; p < 0.001), and mitotic level ≥4/high power field (HR, 2.80; 95% CI, 1.16-6.74; p = 0.021) were independently associated with AM recurrence. Mitotic level was excluded after LASSO analysis, and it did not improve the predictive performance and clinical usage of the model. Therefore, the other four factors were integrated into the nomogram model, which showed good discrimination abilities in training cohort (C-index, 0.822; 95% CI, 0.759-0.885) and validation cohort (C-index, 0.817; 95% CI, 0.716-0.918) and good match between the predicted and observed probability of recurrence-free survival. CONCLUSION: Our study established an integrated model to predict the postoperative recurrence of AM.
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BACKGROUND: To evaluate the value of serum Lactate Dehydrogenase (LDH) level in predicting recurrence and the overall survival (OS) of glioma patients. MATERIALS AND METHODS: A total number of 216 patients with glioma in our institution were retrospectively recruited to analyze the relationship between preoperative serum LDH level and prognosis. RESULTS: Overall, the median age of patients was 46.0 (31.0-57.0) years old; 53.7% (116 of 216) of the enrolled patients were male. Multivariate analysis revealed that serum LDH level (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.96-0.98, P < 0.001) and World Health Organization (WHO) grade (grade II: OR = 19.64, 95%CI = 5.56-69.35, P < 0.001; grade III: OR =1 9.50, 95%CI = 7.08-53.73, P < 0.001; grade IV: OR = 15.23, 95%CI = 4.94-46.97, P < 0.001) were significant and independent of 1-year Progression-free survival (PFS) after adjusting for confounders. The predictive performance of serum LDH level was represented with area under curve (AUC) = 0.741, 95%CI = 0.677-0.798. Multivariate Cox analysis revealed that LDH level (hazard ratio [HR] = 2.56, 95%CI = 1.59-4.15, P < 0.001) and WHO grade (grade II: HR = 4.58, 95%CI = 0.56-37.23, P = 0.155; grade III: HR = 16.35, 95%CI = 2.16-123.80, P = 0.007; grade IV: HR = 42.13, 95%CI = 5.83-304.47, P < 0.001) remained associated with survival at 2-year follow-up. At 3-year follow-up, lymphocyte count (HR = 0.68, 95%CI = 0.51-0.91, P = 0.008), LDH level (HR = 2.21, 95%CI = 1.40-3.49, P = 0.001), and WHO grade (grade II: HR = 1.44, 95%CI = 0.44-4.68, P = 0.543; grade III: HR = 4.99, 95%CI = 1.68-14.87, P = 0.004; grade IV: HR = 16.96, 95%CI = 6.13-46.93, P < 0.001) remained associated with survival in multivariate Cox analysis. CONCLUSION: Our study demonstrated that preoperative serum LDH level could serve as a reliable indicator for predicting prognosis of glioma patients. Further multicenter studies are still required to verify our findings.
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Neoplasias Encefálicas/sangue , Glioma/sangue , L-Lactato Desidrogenase/sangue , Adulto , Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Progressão da Doença , Feminino , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Objective: This study aimed to explore the potential mechanism of peritumoral brain edema (PTBE) formation in vestibular schwannoma (VS) by detecting intra-tumoral vascular endothelial growth factor (VEGF) expression. Methods: Between January 2018 and May 2021, 15 patients with PTBE and 25 patients without PTBE were included in the analysis. All patients enrolled in our study underwent surgery in our institution. Expression level of VEGF and microvessel density (MVD) between the two groups were analyzed. Edema index (EI) of each patient with PTBE was calculated. Results: In the PTBE group, the average of EI was 1.53 ± 0.22. VEGF expression levels were significantly enhanced in the PTBE group compared with the non-PTBE group (p < 0.001). The expression level of VEGF in the PTBE group and non-PTBE group was 1.14 ± 0.21 and 0.52 ± 0.09, respectively. Similarly, there were significantly different amounts of MVD in the two groups (p < 0.001). The amount of MVD in the PTBE group and non-PTBE group was 11.33 ± 1.59 and 6.28 ± 1.77, respectively. Correlation analysis showed a highly significant positive correlation between VEGF and MVD (r = 0.883, p < 0.001) and VEGF and EI (r = 0.876, p < 0.001). Conclusion: Our study confirmed the close relationship among VEGF expression, tumor angiogenesis, and formation of PTBE in VS patients. It may be possible to develop new effective therapies to attenuate PTBE in VS for alleviation of symptoms and reduction of postoperative complication.
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RATIONALE: Glioblastoma is the most lethal and common malignant brain tumor but rare in patients with neurofibromatosis type 1. The clinical findings and pathological findings with gene signatures in female patients have not been well clarified. PATIENT CONCERNS: A 51-year-old female patient complained of headache and left limb weakness lasting for 20âdays. The patient underwent a cesarean section 20âyears ago and hysterectomy 1âyear ago because of uterine leiomyomas. Multiple café-au-lait spots and neurofibromas were found over patient's chest, neck, back, and arms. The myodynamia of left distant and proximate epipodite were grade 0 and grade 1 respectively. The myodynamia of lower left limb was grade 3. DIAGNOSES: Magnetic resonance imaging revealed a malignant lesion which was most likely a glioblastoma in the right temporo-parietal lobe, approximately 5.6 × 5.9 × 6.9 cm in size with a rounded boundary. INTERVENTIONS: A right temporo-parietal craniotomy was performed to resect the space-occupying lesion for gross total removal. Then, the patient received concurrent chemoradiotherapy. Histological examination confirmed a glioblastoma without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. OUTCOMES: After surgery, the headache was relieved and the muscular strength of left limbs did improve. After receiving the standard treatment regimen, the patient was alive at 13âmonths follow-up. LESSONS: This is the first reported glioblastoma in female neurofibromatosis type 1 patient without v-RAF murine sarcoma viral oncogene homolog B1 gene, isocitrate dehydrogenase 1 gene, and telomerase reverse transcriptase gene promoter mutations. Tumors in adult patients with these signatures were less aggressive with well-circumscribed border and had long-term survivals which strengthened the evidence that these patients may comprise a unique subset in glioblastoma.
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Biomarcadores Tumorais/genética , Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Neurofibromatose 1/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Craniotomia , Feminino , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/cirurgia , Humanos , Isocitrato Desidrogenase/genética , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mutação , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , Lobo Parietal/cirurgia , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Telomerase/genética , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologia , Lobo Temporal/cirurgia , Transcriptoma/genéticaRESUMO
BACKGROUND: To evaluate the prognostic value of serum inflammatory biomarkers and develop a risk stratification model for high-grade glioma (HGG) patients based on clinical, laboratory, radiological, and pathological factors. MATERIALS AND METHODS: A retrospective study of 199 patients with HGG was conducted. Patients were divided into a training cohort (n = 120) and a validation cohort (n = 79). The effects of potential associated factors on the overall survival (OS) time were investigated and the benefits of serum inflammatory biomarkers in improving predictive performance was assessed. Univariable and multivariable Cox regression analyses, the least absolute shrinkage and selection operator (LASSO) regression analysis, and support vector machines (SVM) were used to select variables for the final nomogram model. RESULTS: After multivariable Cox, LASSO, and SVM analysis, in addition to 3 other clinico-pathologic factors, platelet-to-lymphocyte ratio (PLR) >144.4 (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.25-3.38; P = 0.005) were left for constructing the predictive model. The model with PLR exhibited a better predictive performance than that without them in both cohorts. The nomogram based on the model showed an excellent ability of discrimination in the entire cohort (C-index, 0.747; 95%CI, 0.706-0.788). The calibration curves showed good consistency between the predicted and observed survival probability. CONCLUSION: Our study confirmed the prognostic value of serum inflammatory biomarkers including PLR and established a comprehensive scoring system for the OS prediction in HGG patients.
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Magnetic hyperthermia (MH) mediated by magnetic nanoparticles is one of the most promising antitumor modalities. The past several decades have witnessed great progress for MH antitumor therapy in scientific trials and clinic applications since it was initially advanced by Gilchrist et al. The ultimate object of MH in vivo is to efficiently kill cancer cells, and hence, it is of great importance to develop an optimized cellular MH method to evaluate the therapeutic efficiency in vitro. In this study, we systematically studied the considerable affecting factors of cancer cell-killing efficiency during the cellular MH process, including the region of cell vessel positioned inside the alternating magnetic field copper coil, the magnetic field amplitude, the types of cancer cells, etc. Taking all these into account, we introduced a method for standardizing the cellular MH process to evaluate the cell-killing efficiency.
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Hipertermia Induzida , Nanoestruturas , Linhagem Celular Tumoral , Compostos Férricos , Humanos , HipertermiaRESUMO
BACKGROUND Controversies exist in imaging modalities for predicting adenoma consistency. In this study, we proposed a method of predicting consistency by magnetic resonance T2-sequence imaging based on adenoma to cerebellar peduncle signal (TCTI) ratio. MATERIAL AND METHODS Between January 2013 and May 2017, 191 consecutive patients with pituitary adenoma diagnosed at our institution were retrospectively studied. The consistency grade for each lesion was assigned. And the TCTI ratio based on preoperative and postoperative T2-weighted imaging was calculated. RESULTS The median TCTI ratio was 1.55, 1.28, and 1.25 for soft, fibrous, and hard adenomas, respectively. The differences were significant for all groups (p<0.001). A cutoff value of 1.38 for soft adenomas was found to be 80.2% sensitive and 88.7% specific. The median ratio of the outermost layer of residual tumor was 1.25 (SD±0.408, 95% CI 1.27-1.42). It was less than that ratio of the upper, lower quarter, and middle region of adenoma, respectively, and the inter-group differences were all statistically significant with p≤0.001. The extent of resection for the soft group was significantly greater than that of the hard group (85.3% vs. 70.6%, p=0.011). Analysis of Variance (ANOVA) revealed that the consistency grade was the influencing factor of degree of resection. p=0.003. CONCLUSIONS The TCTI ratio showed a good correlation with pituitary adenoma consistency. We also determined the optimal ratio of the residual adenoma.
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Imageamento por Ressonância Magnética/métodos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/patologia , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adulto , Idoso , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pedúnculo Cerebelar Médio/diagnóstico por imagem , Pedúnculo Cerebelar Médio/metabolismo , Neoplasias Hipofisárias/metabolismo , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
Postoperative infection is an important factor contributing to poor prognosis after surgical treatment of cerebral cavernous malformations (CCM). However, the predictive factors of postoperative infection-related complications in adult patients with CCM have still not been well established. To identify possible predictive factors of postoperative infection after CCM surgery, we retrospectively evaluated the data of CCM patients who were enrolled into our prospective registry database. The relationship between preoperative characteristics of patients and postoperative infection-related complications was analyzed. A total of 167 CCM patients were included in this study. The average age was 39.69 ± 15.27 years old, and 21 of them had postoperative infection. For patients with postoperative infection, the Glasgow Coma Scale (GCS), Modified Rankin Scale (mRS), white blood cell (WBC) count, and neutrophil (NEU) count were all significantly higher than those of the group without infection. Our preliminary results showed that NEU count might have significant predictive value of intracranial infection, and GCS, mRS and CCM presenting with hemorrhage were all factors significantly related to postoperative pneumonia. Preoperative GCS, mRS and CCM presenting with hemorrhage might be used as predictive factors for postoperative pneumonia after CCM surgery, while preoperative NEU count can be used as an important predictive factor for postoperative intracranial infection after CCM surgery. Further large-scale studies are still needed to confirm this finding.
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Hemangioma Cavernoso do Sistema Nervoso Central/cirurgia , Infecções/epidemiologia , Infecções/etiologia , Contagem de Leucócitos , Neutrófilos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Bases de Dados Factuais , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV-related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV-related ACLF were enrolled in this open-label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow-derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%-84.8%) versus 55.6% (95% confidence interval 42.3%-68.9%) for the SMT group (P = 0.03). There were no infusion-related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5-24 of follow-up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow-derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End-Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). CONCLUSION: Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209-219).
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Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/terapia , Vírus da Hepatite B/isolamento & purificação , Hepatite B/complicações , Transplante de Células-Tronco Mesenquimais/métodos , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/fisiopatologia , Adulto , Causas de Morte , China , Feminino , Hepatite B/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
AIM: To assess quantitative changes of the macula in diabetic eyes after cataract surgery using optical coherence tomography (OCT) and to estimate the incidence of development or worsening of macular edema (ME) in diabetic eyes with or without pre-existing ME. METHODS: In this prospective, observational study, 92 eyes of 60 diabetic patients who underwent cataract surgery were evaluated before surgery and 1, 3mo after surgery using OCT. Macular thickness was measured with OCT at nine macular subfields defined by the 9 zones early treatment of diabetic retinopathy study (ETDRS), as well as total macular volume obtained by OCT at 1, 3mo after surgery were compared with baseline features obtained before surgery. In addition, the incidence of development or worsening of ME was analyzed in diabetic eyes with or without pre-existing ME. RESULTS: The central subfield mean thickness increased 21.0 µm and 25.5 µm at 1, 3mo follow-up, respectively (P<0.01). The average thickness of inner ring and outer ring increased 14.2 µm and 9.5 µm at 1mo, 18.2 µm and 12.9 µm at 3mo. Central-involved ME developed in 12 eyes at 3mo, including 4 eyes with pre-existing central-involved and 8 eyes with pre-existing non-central involved ME. Pre-existing diabetic macular edema (DME) was significantly associated with central-involved ME development (P<0.001). CONCLUSION: A statistically significant increase could be detected in the central subfield as well as perifoveal and parafoveal sectors though the increase was mild. And eyes with pre-operative DME prior to cataract surgery are at higher risk for developing central-involved ME.
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Calcineurin inhibitors, including tacrolimus, are largely responsible for advances in allotransplantation. However, the nephrotoxicity associated with these immunosuppressants impairs patients' long-term survival after renal allograft. Therefore, novel regimens that minimize or even eliminate calcineurin inhibitors could improve transplantation outcomes. In this pilot study, we investigated the use of low-dose tacrolimus in combination with mesenchymal stem cells (MSCs), which are immunosuppressive and prolong allograft survival in experimental organ transplant models. Donor-derived, bone marrow MSCs combined with a sparing dose of tacrolimus (0.04-0.05 mg/kg/day) were administered to 16 de novo living-related kidney transplant recipients; 16 other patients received a standard dose of tacrolimus (0.07-0.08 mg/kg/day). The safety of MSC infusion, acute rejection, graft function, graft survival, and patient survival were evaluated over ≥24 months following kidney transplantation. All patients survived and had stable renal function at the 24 month follow-up. The combination of low-dose tacrolimus and MSCs was as effective as standard dose tacrolimus in maintaining graft survival at least 2 years after transplantation. In addition, both groups had similar urea, urine protein, urinary RBC, urinary WBC, 24-h urine protein, and creatinine clearance rates from 7 days to 24 months after transplantation. Furthermore, no differences in the proportion of lymphocytes, CD19, CD3, CD34, CD38, and natural killer cells were detected between the control and experimental groups. None of the MSC recipients experienced immediate or long-term toxicity from the treatment. This preliminary data suggests that the addition of MSCs permits the use of lower dosages of nephrotoxic calcineurin inhibitors following renal transplantation.
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Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Tacrolimo/administração & dosagem , Adulto , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Projetos Piloto , Estudos ProspectivosRESUMO
Nuclear receptors (NRs) are major pharmacological targets that allow an access to the mechanisms controlling gene regulation. As such, some NRs were identified as biological targets of active compounds contained in herbal remedies found in traditional medicines. We aim here to review this expanding literature by focusing on the informative articles regarding the mechanisms of action of traditional Chinese medicines (TCMs). We exemplified well-characterized TCM action mediated by NR such as steroid receptors (ER, GR, AR), metabolic receptors (PPAR, LXR, FXR, PXR, CAR) and RXR. We also provided, when possible, examples from other traditional medicines. From these, we draw a parallel between TCMs and phytoestrogens or endocrine disrupting chemicals also acting via NR. We define common principle of action and highlight the potential and limits of those compounds. TCMs, by finely tuning physiological reactions in positive and negative manners, could act, in a subtle but efficient way, on NR sensors and their transcriptional network.
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Medicamentos de Ervas Chinesas/farmacologia , Fitoestrógenos/farmacologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Medicina Tradicional Chinesa , Receptores de Esteroides/metabolismoRESUMO
In the past decades increasing lines of evidence have demonstrated that adipose tissue, as an endocrine organ plays a central role in metabolic homeostasis and its related maladies. CCAAT/enhancer-binding protein (C/EBP) family members and the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) were known to be the vital transcription factors in the regulation of adipogenesis. However, the exact mechanism for increased marrow fat in patients with bone metabolic diseases, such as osteoporosis, is still poorly understood. Herein, we studied the expression pattern of PPARγ and C/EBPs in human bone marrow mesenchymal stem cell (hBMSC) adipogenesis and evaluated the effects of individual components of an adipogenic cocktail on the differentiation and transcription factor expression. We furthermore examined whether the ERK signaling pathway was involved in mediating these effects. These findings showed that C/EBPß and C/EBPδ were detected in undifferentiated hBMSC and maintained during the whole process of adipogenesis, and could initiate the expression of PPARγ1 under the treatment of dexamethasone and IBMX. Subsequently, the activation of PPARγ1 by indomethacin, its exogenous ligand, activated C/EBPα, which, together with IBMX, up-regulated PPARγ2 expression and therefore the fullest adipogenesis. Insulin and its downstream signal pathway extracellular signal-regulated kinases (ERK), however, were found not necessary for hBMSC adipogenesis. Our results revealed some unique characteristics of human adipocyte formation, which may help to understand the molecular mechanisms of bone marrow adipogenesis and give insights into the treatment of osteoporosis.
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Células da Medula Óssea/citologia , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Células-Tronco Mesenquimais/metabolismo , PPAR gama/metabolismo , 1-Metil-3-Isobutilxantina/farmacologia , Células 3T3-L1 , Adipogenia/efeitos dos fármacos , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Proteína delta de Ligação ao Facilitador CCAAT/genética , Proteína delta de Ligação ao Facilitador CCAAT/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/genética , Células Cultivadas , Dexametasona/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , PPAR gama/genética , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
Engraftment failure (EF) after autologous hematopoietic stem cell transplantation is a serious complication. We prospectively evaluated the effects and safeties of mesenchymal stem cells (MSCs) alone and MSCs combined with cord blood (CB) for EF. Twenty-two patients were randomized to receive MSCs (MSC group; n = 11) or MSCs plus CB (CB group; n = 11). Patients with no response (NR) to MSCs received the therapeutic schedule in the CB group, and those patients with partial response (PR) in the MSC group and patients without complete remission (CR) in the CB group received another cycle of MSC treatment. Patients who did not achieve CR after 2 cycles of treatments received other treatments, including allogeneic HSCT. After the first treatment cycle, response was seen in 7 of 11 patients in the MSC group and in 9 of 11 in the CB group (P = .635), with a significant difference in neutrophil reconstruction between the 2 groups (P = .030). After 2 treatment cycles, 16 patients achieved CR, 3 achieved PR, and 3 had NR. No patient experienced graft-versus-host disease (GVHD). With a median follow-up of 345 d (range, 129 to 784 d) post-transplantation, 18 patients remained alive and 4 had died (3 from primary disease relapse and 1 from cytomegalovirus pneumonia). The 2-year overall survival, disease-free survival, and cumulative incidence of tumor relapse post-transplantation were 75.2% ± 12.0%, 79.5% ± 9.4%, and 20.5% ± 9.4%, respectively. Our data indicate that the 2 strategies are effective for EF and do not result in GVHD or increase the risk of tumor relapse, but the MSC plus CB regimen has a superior effect on neutrophil reconstruction.
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Rejeição de Enxerto/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante Autólogo/efeitos adversos , Adolescente , Adulto , Quimerismo , Feminino , Sangue Fetal/citologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Masculino , Células-Tronco Mesenquimais , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
In this study, we investigated the nutritive composition in the muscle of Sinocyclocheilus grahami and S. tingi. The contents of crude protein in the fresh muscle of S. grahami and S. tingi can be described as being 21.7% and 20.6%, crude fat were 3.43% and 2.66%, and total amino acid were 19.23% and 17.67%, respectively. Essential amino acids accounted for 44.08% and 43.69% of total amino acids of S. grahami and S. tingi, respectively. The values of essential amino acid index (EAAI) of the two species were 70.00% and 65.99%, respectively, with S. grahami being better than S. tingi. Ultimately, the amino acid composition of S. grahami and S. tingi muscle tissue met the standards of the Food and Agriculture Organization of the United Nations as well as those of the World Health Organization (FAO/WHO). According to the nutritive evaluation in amino acid score (AAS), the first limited amino acids of both fish were cystine+methionine. Compared with other commercial fish, the nutrition value of the muscle of Sinocyclocheilus fish can generally be considered as being better.
Assuntos
Carne/análise , Músculo Esquelético/química , Aminoácidos/análise , Animais , China , Cyprinidae , Gorduras/análise , Proteínas de Peixes/análise , Valor NutritivoRESUMO
Mesenchymal stem cells (MSCs) are the common progenitors of osteoblasts and adipocytes. A reciprocal relationship exists between osteogenesis and adipogenesis in the bone marrow, and the identification of signaling pathways that stimulate MSC osteogenesis at the expense of adipogenesis is of great importance from the viewpoint of developing new therapeutic treatments for bone loss. The adipogenic transcription factor peroxisome proliferator-activated receptor γ (PPARγ) has been reported to play a vital role in modulating mesenchymal lineage allocation within the bone marrow compartment, stimulating adipocyte development at the expense of osteoblast differentiation. Hence, PPARγ may be a valuable target for drugs intended to enhance bone mass. However, little direct evidence is available for the role played by PPARγ in human mesenchymal lineage allocation. In this study, using human MSCs as an in vitro model, we showed that the two isoforms of PPARγ, PPARγ1 and PPARγ2, were differentially induced during hMSC adipogenesis, whereas only PPARγ1 was detected during osteogenesis. BADGE and GW9662, two potential antagonists of PPARγ, as well as lentivirus-mediated knockdown of PPARγ, inhibited hMSC adipogenesis but did not significantly affect osteogenesis. PPARγ knockdown did not significantly influence the expression level of the osteogenic transcription factor Runx2. Together, these results suggest that PPARγ is not the master factor regulating mesenchymal lineage determination in human bone marrow.