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Objective: To investigate the clinical features of acute macular neuroretinopathy (AMN) following coronavirus disease 2019 (COVID-19). Methods: This retrospective case series study included 15 patients (28 eyes) diagnosed with AMN at the Department of Ophthalmology, Peking University Third Hospital, from November 2022 to January 2023. The AMN group comprised 4 males and 11 females, with a mean age of (31.36±8.08) years. A control group of 15 individuals [5 males, 10 females; mean age (33.20±5.10) years] who had COVID-19 but did not develop AMN was also included. Data collected for all patients included best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fluorescein fundus angiography (FFA), and optical coherence tomography (OCT) results. Serum cytokine levels, including interleukins (ILs), interferons (IFNs), and tumor necrosis factor-alpha (TNF-α), were measured for both groups. Results: Among the 28 eyes, severe vision loss (BCVA≤0.3) was observed in 3 eyes (10.7%), moderate vision loss (BCVA>0.3 and≤0.5) in 2 eyes (13.3%), and mild vision loss (BCVA>0.5 and≤1.0) in 23 eyes (82.1%). OCT findings in all 28 eyes revealed hyperreflectivity of the outer nuclear layer and disruption of outer retinal structure. Additionally, 3 eyes (10.7%) exhibited cotton wool spots in the posterior pole, 2 eyes (7.1%) showed mild cystoid macular edema with intraretinal hyperreflective dots, and 1 eye (3.6%) presented with paracentral acute middle maculopathy. FFA indicated retinal vasculitis in 2 cases (4 eyes, 14.3%). Serum levels of IL-4, IL-5, IFN-α, and IFN-γ were significantly higher in the AMN group compared to the control group: IL-4 [4.49 (3.66, 6.08) vs. 1.40 (0.62, 1.68) pg/ml], IL-5 [7.34 (5.04, 14.06) vs. 0.17 (0.11, 1.86) pg/ml], IFN-α [8.42 (6.31, 14.89) vs. 0.50 (0.30, 0.83) pg/ml], and IFN-γ [17.93 (12.75, 32.44) vs. 7.43 (0.00, 14.74) pg/ml], with all differences being statistically significant (all P<0.05). Conclusion: AMN following COVID-19 can present with wedge-shaped dark red lesions in the macular area, often accompanied by cotton wool spots and retinal vasculitis. Additionally, there is a significant elevation in various inflammatory cytokines in the serum.
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COVID-19 , Doenças Retinianas , SARS-CoV-2 , Tomografia de Coerência Óptica , Humanos , COVID-19/epidemiologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , China/epidemiologia , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Angiofluoresceinografia/métodos , Macula Lutea/patologia , Macula Lutea/diagnóstico por imagem , Doença Aguda , Citocinas/sangueRESUMO
With the extensive application of targeted drugs, the survival rate of cancer patients has been significantly improved. However, adverse reactions to the drugs have also become apparent, especially those affecting the ocular surface, which can severely impact patients' vision and quality of life. The article systematically analyzes a variety of targeted drugs, including epidermal growth factor receptor inhibitors, human epidermal growth factor receptor 2 inhibitors, fibroblast growth factor receptor inhibitors, selective estrogen receptor modulators, vascular endothelial growth factor receptor inhibitors, aromatase inhibitors, proteasome inhibitors, antibody-drug conjugates, Bruton's tyrosine kinase inhibitors, FMS-like tyrosine kinase 3 inhibitors, and cyclin-dependent kinase inhibitors, and discusses their adverse reactions on the ocular surface. The review emphasizes the role of clinicians in monitoring and managing patients' ocular surface health and the importance of early diagnosis and intervention to ensure that patients receive optimal visual protection while undergoing antitumor treatment.
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Antineoplásicos , Humanos , Antineoplásicos/efeitos adversos , Neoplasias/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a MedicamentosRESUMO
OBJECTIVE: To evaluate the implications of the prognostic nutrition index (PNI) in non-metastatic renal cell carcinoma (RCC) patients treated with surgery and to compare it with other hematological biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII). METHODS: A cohort of 328 non-metastatic RCC patients who received surgical treatment between 2010 and 2012 at Peking University First Hospital was analyzed retrospectively. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff values of the hematological biomarkers. The Youden index was maximum for PNI was value of 47.3. So we divided the patients into two groups (PNI≤ 47. 3 and >47. 3) for further analysis. Categorical variables [age, gender, body mass index (BMI), surgery type, histological subtype, necrosis, pathological T stage and tumor grade] were compared using the Chi-square test and Student' s t test. The association of the biomarkers with overall survival (OS) and disease-free survival (DFS) was analyzed using Kaplan-Meier methods with log-rank test, followed by multivariate Cox proportional hazards model. RESULTS: According to the maximum Youden index of ROC curve, the best cut-off value of PNI is 47. 3. Low level of PNI was significantly associated with older age, lower BMI and higher tumor pathological T stage (P < 0.05). Kaplan-Meier univariate analysis showed that lower PNI was significantly correlated with poor OS and DFS (P < 0.05). In addition, older age, lower BMI, tumor necrosis, higher tumor pathological T stage and Fuhrman grade were significantly correlated with poor OS (P < 0.05). Cox multivariate analysis showed that among the four hematological indexes, only PNI was an independent factor significantly associated with OS, whether as a continuous variable (HR=0.9, 95%CI=0.828-0.978, P=0.013) or a classified variable (HR=2.397, 95%CI=1.061-5.418, P=0.036). CONCLUSION: Low PNI was a significant predictor for advanced pathological T stage, decreased OS, or DFS in non-metastatic RCC patients treated with surgery. In addition, PNI was superior to the other hematological biomar-kers as a useful tool for predicting prognosis of RCC in our study. It should be externally validated in future research before the PNI can be used widely as a predictor of RCC patients undergoing nephrectomy.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Prognóstico , Avaliação Nutricional , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Biomarcadores , Neoplasias Renais/cirurgia , Neoplasias Renais/patologiaRESUMO
Pain is the fifth major vital sign, and chronic pain is a large category of diseases that affects health seriously. At present, the incidence of chronic pain is high, but the overall treatment satisfaction is low. It is necessary to continuously optimize pain diagnosis and treatment strategies and improve the connotation of pain management. Based on the clinical practice of our pain center, combined with relevant literature, the article proposes a diagnosis and treatment strategy of "whole field pain management" should be carried out from the four dimensions of feeling, emotion, cognition, and behavior. Innovative digital pain diagnosis and treatment technologies such as VR/MR and brain-computer interface are used to regulate emotional, cognitive, and behavioral regulation, and combined with lifestyle changes, rehabilitation physiotherapy, drugs, and minimally invasive interventional therapy to constitute a " whole field pain management strategy" to explore the new development direction of further improving the management of chronic pain.
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Dor Crônica , Manejo da Dor , Humanos , Manejo da Dor/métodos , Dor Crônica/diagnóstico , Dor Crônica/terapia , Modalidades de Fisioterapia , Emoções , CogniçãoRESUMO
Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.
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Tumor Glômico , Paraganglioma Extrassuprarrenal , Masculino , Feminino , Humanos , Criança , Tumor Glômico/cirurgia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Paraganglioma Extrassuprarrenal/metabolismo , Paraganglioma Extrassuprarrenal/patologia , Imuno-HistoquímicaRESUMO
BACKGROUND: Quantitative measurement of plasma Epstein-Barr virus (EBV) DNA by real-time PCR at the end of primary treatment is a robust prognostic marker for nasopharyngeal carcinoma (NPC) patients. However, up to 40% of patients who would later develop disease recurrence had undetectable post-treatment plasma EBV DNA. Targeted sequencing for the entire EBV genome potentially allows a more comprehensive and unbiased detection of plasma EBV DNA and enables the use of other parameters such as fragment size as biomarkers. Hence, we explored if plasma EBV DNA sequencing might allow more accurate prognostication of NPC patients. PATIENTS AND METHODS: Plasma samples collected from 769 patients with stage IIB-IVB NPC at 6-8 weeks after radiotherapy were analysed using targeted sequencing for EBV DNA. RESULTS: The sensitivities of the PCR-based analysis, at a cut-off of any detectable levels of plasma EBV DNA, for prediction of local and distant recurrences were 42.3% and 85.3%, respectively. The sequencing-based analysis (involving quantitation and size profiling) achieved better performance for both local and distant recurrences than PCR. Using a cut-off of the proportion of plasma EBV DNA deduced by sequencing at 0.01%, the sensitivities of the sequencing-based analysis for local and distant recurrences were 88.5% and 97.1%, with the resultant negative predictive values of 99.1% and 99.4%, respectively. Among patients with undetectable EBV DNA on quantitative PCR, sequencing could further define a subgroup that enjoyed superior survival outcomes based on the proportion of plasma EBV DNA, with a 5-year progression-free survival (PFS) approaching 90%. On multivariate analysis, sequencing-based quantitative level of plasma EBV DNA was the independent prognostic factor with the highest hazard ratio for prediction of overall survival and PFS. CONCLUSION: NPC prognostication using post-treatment plasma EBV DNA could be enhanced through sequencing.
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Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , DNA Viral/genética , Herpesvirus Humano 4/genética , Humanos , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/terapia , Recidiva Local de Neoplasia/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Medição de RiscoRESUMO
The epidemic of tuberculosis has posed a serious burden in Qinghai province, it is necessary to clarify the epidemiological characteristics and spatial-temporal distribution of TB for future prevention and control measures. We used descriptive epidemiological methods and spatial statistical analysis including spatial correlation and spatial-temporal analysis in this study. Furthermore, we applied an exponential smoothing model for TB epidemiological trend forecasting. Of 43 859 TB cases, the sex ratio was 1.27:1 (M:F), and the average annual TB registered incidence was 70.00/100 000 of 2009-2019. More cases were reported in March and April, and the worst TB stricken regions were the prefectures of Golog and Yushu. High TB registered incidences were seen in males, farmers and herdsmen, Tibetans, or elderly people. 7132 cases were intractable, which were recurrent, drug resistant, or co-infected with other infections. Three likely cases clusters with significant high risk were found by spatial-temporal scan on data of 2009-2019. The exponential smoothing winters' additive model was selected as the best-fitting model to forecast monthly TB cases in the future. This research indicated that TB in Qinghai is still a serious threaten to the local residents' health. Multi-departmental collaboration and funds special for TB treatments and control are still needed, and the exponential smoothing model is promising which could be applied for forecasting of TB epidemic trend in this high-altitude province.
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Modelos Estatísticos , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China/epidemiologia , Análise por Conglomerados , Feminino , Previsões , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Análise Espaço-Temporal , Tuberculose/prevenção & controle , Adulto JovemRESUMO
BACKGROUND: Neoadjuvant chemoradiotherapy is a standard treatment for locally advanced rectal cancer, for which pathological complete response is typically used as a surrogate survival endpoint. Neoadjuvant rectal score is a new biomarker that has been shown to correlate with survival. The main objectives of this study were to investigate factors contributing to pathological complete response, to validate the prognostic significance of neoadjuvant rectal score, and to investigate factors associated with a lower neoadjuvant rectal score in a cohort of Hong Kong Chinese. METHODS: Data of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy from August 2006 to October 2018 were retrieved from hospital records and retrospectively analysed. RESULTS: Of 193 patients who had optimal response to neoadjuvant chemoradiotherapy and surgery, tumour down-staging was the only independent prognostic factor that predicted pathological complete response (P<0.0001). Neoadjuvant rectal score was associated with overall survival (hazard ratio [HR]=1.042, 95% confidence interval [CI]=1.021-1.064; P<0.0001), disease-free survival (HR=1.042, 95% CI=1.022-1.062; P<0.0001), locoregional recurrence-free survival (HR=1.070, 95% CI=1.039-1.102; P<0.0001) and distant recurrence-free survival (HR=1.034, 95% CI=1.012-1.056; P=0.002). Patients who had pathological complete response were associated with a lower neoadjuvant rectal score (P<0.0001), but pathological complete response was not associated with survival. For patients with intermediate neoadjuvant rectal scores, late recurrences beyond 72 months from diagnosis were observed. CONCLUSION: Neoadjuvant rectal score is an independent prognostic marker of survival and disease recurrence in a cohort of Hong Kong Chinese patients who received neoadjuvant chemoradiotherapy for locally advanced rectal cancer.
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Terapia Neoadjuvante , Neoplasias Retais , Biomarcadores , Quimiorradioterapia , Intervalo Livre de Doença , Hong Kong , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Phosphatidylserine (PS) is an important apoptotic-cell surface signal that exists in bacterial and cancer cells. The mechanism by which melittin interacts with the PS membrane remains unclear. Here, we revealed this mechanism by using a dual-channel fluorescence microscope to observe the concentration-dependent process of pore formation in giant unilamellar vesicles (GUVs) that were exposed to melittin solution. We found that unsaturated PS membranes differed significantly from saturated PS membranes in different phases. This study provides a reference for research and development of anticancer drugs.
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Meliteno , FosfatidilserinasRESUMO
Objective: To address the limitations of existing methods and tools for evaluating clinical practice guidelines, we aimed to develop a comprehensive instrument focusing on the three main dimensions of guideline development: scientificity, transparency, applicability. We will use it to rank the guidelines according to the scores. We abbreviated it as STAR, and its reliability, validity and usability were also tested. Methods: A multidisciplinary expert working group was set up, including methodologists, statisticians, journal editors, medical professionals, and others. Scoping review, Delphi methods and hierarchical analysis were used to determine the final checklist of STAR. Results: The new instrument contained 11 domains and 39 items. Intrinsic reliability of each domain was indicated by Cronbach's α coefficient, with a average value of 0.646. The Cohen's kappa coefficients for methodological evaluators and clinical evaluators were 0.783 and 0.618. The overall content validity index was 0.905. The R2 for the criterion validity analysis was 0.76. The average score for usability of the items was 4.6, and the mean time spent to evaluate each guideline was 20 minutes. Conclusion: The instrument has good reliability, validity and evaluating efficiency, and can be used for evaluating and ranking guidelines more comprehensively.
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Objective: To compare and analyze the predictive value of different inflammatory factors and tumor markers in intrahepatic cholangiocarcinoma and to develop a new and effective preoperative prognostic scoring system. Methods: 102 and 72 cases with intrahepatic cholangiocarcinoma who underwent radical surgery in Tianjin Medical University Cancer Institute and Hospital and the Affiliated Hospital of Weifang Medical University were selected as the experimental group and the validation group, respectively. Clinicopathological and follow-up data were collected. Cox proportional-hazards model was used to analyze the predictive value of different prognostic markers. The relationship between prognostic markers and clinicopathological data was analyzed by rank sum test, χ2 or Fisher's exact test. Results: Among the direct inflammatory factors, tumor markers and combined inflammatory factors, prognostic inflammatory index (PII), carbohydrate antigen (CA) 19-9 and systemic inflammation score (SIS) were the most significant predictive factors for postoperative survival outcomes in patients with intrahepatic cholangiocarcinoma. The prognostic inflammatory and tumor score (PITS) was proposed as a new prognostic scoring system for intrahepatic cholangiocarcinoma. PII and CA19-9 were included into the scoring criteria for prognostic stratification of patients. PITS was an independent predictor of tumor-free survival and overall survival in patients with intrahepatic cholangiocarcinoma. Patients with high-grade PITS had later tumor grade and higher frequency of vascular invasion. Conclusion: PITS is highly effective prognostic scoring system for patients with intrahepatic cholangiocarcinoma. In addition, PITS is recommended for preoperative prognostic stratification in patients with intrahepatic cholangiocarcinoma.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Biomarcadores Tumorais , Antígeno CA-19-9 , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patologia , Humanos , Prognóstico , Estudos RetrospectivosRESUMO
Dry eye is the most common disease in ophthalmic clinics besides refractive error, which seriously affects the life quality of patients and has become an important public health problem in China. Dry eye as a kind of multifactorial disease can be induced or accelerated by contact lens wear, which is considered as one of the risk factors of dry eye. Studies have shown that the incidence of dry eye is higher in contact lens wearers than in normal people. In 2017, the Tear Film and Ocular Surface Society included contact lens-associated dry eye (CLADE) in the iatrogenic dry eye for the first time, and its importance is evident. However, ophthalmologists mostly used to focus on serious complications such as keratitis caused by contact lens wear, and CLADE has not been well valued and understood. This article reviews the latest studies on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of CLADE.
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Lentes de Contato , Síndromes do Olho Seco , Erros de Refração , Lentes de Contato/efeitos adversos , Síndromes do Olho Seco/epidemiologia , Síndromes do Olho Seco/etiologia , Humanos , Fatores de Risco , LágrimasRESUMO
The cornea is a transparent tissue with significant refractive and barrier functions. Corneal epithelium constitutes the first line of defense against foreign pathogens. Corneal epithelial cells interact to form a functionally selective permeability barrier. Dysfunction of this barrier leads to corneal impairment followed by a series of ocular surface diseases and even blindness. Tight junctions (TJ), located at the top of the intercellular space of corneal epithelial superficial cells, play a critical role in establishing and maintaining the barrier function. Previous studies have shown that destruction of the TJ acts as a crucial step of the occurrence and progression of multiple ocular surface diseases. Understanding the fundamental features and functions of the TJ, noticing the risk factors of TJ disruption, and clarifying the key role of TJ in the pathogenesis of various ocular surface diseases will help to better understand and treat ocular surface diseases.
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Doenças da Córnea , Epitélio Corneano , Córnea , Epitélio Corneano/patologia , Humanos , Permeabilidade , Junções Íntimas/patologiaRESUMO
Earth-abundant Fe, Ni, and Co aza macrocyclic and polypyridine complexes have been thoroughly investigated for CO2 electrochemical and visible-light-driven reduction. Since the first reports in the 1970s, an enormous body of work has been accumulated regarding the two-electron two-proton reduction of the gas, along with mechanistic and spectroscopic efforts to rationalize the reactivity and establish guidelines for structure-reactivity relationships. The ability to fine tune the ligand structure and the almost unlimited possibilities of designing new complexes have led to highly selective and efficient catalysts. Recent efforts toward developing hybrid systems upon combining molecular catalysts with conductive or semi-conductive materials have converged to high catalytic performances in water solutions, to the inclusion of these catalysts into CO2 electrolyzers and photo-electrochemical devices, and to the discovery of catalytic pathways beyond two electrons. Combined with the continuous mechanistic efforts and new developments for in situ and in operando spectroscopic studies, molecular catalysis of CO2 reduction remains a highly creative approach.
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Liver is rich in blood supply, with soft and crisp texture, therefore its resection requires accurate and safe bleeding control techniques. The hemostatic effect of complete hepatic inflow occlusion is complete, but the side effects are comparatively serious and the blocking time is limited. The side effects of anatomical hepatic inflow occlusion are light, but there is more bleeding in the process of practice, especially the bleeding of the preserved side of the liver. Based on the dynamic watershed theory, there is traffic flow between hepatic segments and lobes, which is the reason for the poor effect of anatomic hepatic blood flow occlusion. We propose cross interface blood control maneuver. In this strategy, we use a variety of blood control methods alone or in combination, to control the borderline blood flow between segments/lobes. Therefore, compared with anatomic hepatic blood flow occlusion, this strategy can control bleeding well and reduce various side effects of total hepatic blood inflow occlusion.
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Neoplasias Hepáticas , Fígado , Perda Sanguínea Cirúrgica , Hepatectomia , Humanos , Neoplasias Hepáticas/cirurgiaRESUMO
In the past,treatment of acute ilio-femoral deep vein thrombosis (IFDVT) was mainly based on anticoagulation alone,but 30%-50% of patients will develop post-thrombotic syndrome,causing a serious medical burden.Thrombus removal technology such as catheter-directed thrombolysis and percutaneous mechanical thrombectomy can effectively remove blood clots and compensate for the deficiencies of simple anticoagulation,which is expected to improve the prognosis of such disease,but the current evidence is insufficient,and other treatments such as filter implantation and compression therapy are also controversial.This article summarizes the treatment strategies and the latest progress of acute IFDVT,hoping to help the treatment of this type of disease.
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Choroidal thinning is an important feature of high myopia and has a negative correlation with the degree of myopia. However, due to the limitations of choroidal imaging, specific changes in choroidal thickness and vasculature are unclear. In recent years, the development of optical coherence tomography technology and optical coherence tomography angiography technology has made it possible to solve the problem. Emergence of biomarkers that objectively quantify choroidal thickness and vascular changes will help us understand the pathogenesis of high myopia and provide new ideas for the prognosis and treatment of myopia. In this review, in order to provide reference for clinical work, we summarize recent advances in the application of the two technologies in observing morphological changes of the choroid in high myopia and discuss the problems and prospects when they are combined with artificial intelligence for choroidal imaging. (Chin J Ophthalmol, 2021, 57: 459-464).
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Inteligência Artificial , Miopia , Angiografia , Corioide/diagnóstico por imagem , Humanos , Tomografia de Coerência ÓpticaRESUMO
The feline endogenous RD114 glycoprotein has proved to be an attractive envelope to pseudotype both retroviral and lentiviral vectors. As a surface protein, its detection on packaging cells as well as viral particles would be useful in different fields of its use. To address this, we generated a monoclonal antibody against RD114 by immunization of rats, termed 22F10. Once seroconversion was confirmed, purified 22F10 was cloned into murine Fc and characterized with a binding affinity of 10nM. The antibody was used to detect RD114 and its variant envelopes on different stable viral packaging cell lines (FLYRD18 and WinPac-RD). 22F10 was also shown to prevent the infections of different strains of RD-pseudotyped vectors but not related envelope glycoproteins by blocking cell surface receptor binding. We are the first to report the neutralization of viral particles by a monoclonal αRD114 antibody.
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Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Vetores Genéticos , Proteínas dos Retroviridae/imunologia , Proteínas do Envelope Viral/imunologia , Sistema ASC de Transporte de Aminoácidos/metabolismo , Animais , Anticorpos Neutralizantes/biossíntese , Especificidade de Anticorpos , Gatos , Retrovirus Endógenos , Humanos , Lentivirus/genética , Camundongos , Antígenos de Histocompatibilidade Menor/metabolismo , Ratos , Receptores Virais/metabolismo , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Retroviridae/genética , Proteínas dos Retroviridae/metabolismo , Proteínas do Envelope Viral/metabolismoRESUMO
BACKGROUND: After curative radiotherapy (RT) or chemoradiation (CRT), there is no validated tool to accurately identify patients for adjuvant therapy in nasopharyngeal carcinoma (NPC). Post-RT circulating plasma Epstein-Barr virus (EBV) DNA can detect minimal residual disease and is associated with recurrence and survival independent of TNM (tumor-lymph node-metastasis) stage. We aimed to develop and validate a risk model for stratification of NPC patients after completion of RT/CRT to observation or adjuvant therapy. PATIENTS AND METHODS: The prospective multicenter 0502 EBV DNA screening cohort (Hong Kong NPC Study Group 0502 trial) enrolled from 2006 to 2015 (n = 745) was used for model development. For internal validation, we pooled independent patient cohorts from prospective clinical studies enrolled from 1997 to 2006 (n = 340). For external validation, we used retrospective cohort of NPC patients treated at Sun Yat-sen University Cancer Center from 2009 to 2012 (n = 837). Eligible patients had histologically confirmed NPC of Union for International Cancer Control (UICC) 7th Edition stage II-IVB who completed curative RT/CRT with or without neoadjuvant chemotherapy, had post-RT EBV DNA tested within 120 days after RT and received no adjuvant therapy. The primary end point was overall survival (OS). We used recursive-partitioning analysis (RPA) to classify patients into groups of low, intermediate, and high risk of death. RESULTS: Combining post-RT EBV DNA level (0, 1-49, 50-499, and ≥500 copies/ml) and TNM stage (II, III, IVAB), RPA model classified patients into low-, intermediate-, and high-risk groups with 5-year OS of 89.4%, 78.5% and 37.2%, respectively. The RPA low-risk group had comparable OS to TNM stage II (5-year OS 88.5%) but identified more patients (64.8% versus stage II 28.1%) that could potentially be spared adjuvant therapy toxicity. The RPA model (c-index 0.712) showed better risk discrimination than either the TNM stage (0.604) or post-RT EBV DNA alone (0.675) with improved calibration and consistence. These results were validated in both internal and external cohorts. CONCLUSION: Combining post-RT EBV DNA and TNM stage improved risk stratification in NPC.
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Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , DNA Viral/genética , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4/genética , Humanos , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Plasma , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Medição de RiscoRESUMO
Dysregulation of the adipo-osteogenic differentiation balance of mesenchymal stem cells (MSCs), which are common progenitor cells of adipocytes and osteoblasts, has been associated with many pathophysiologic diseases, such as obesity, osteopenia, and several neurodegenerative disorders. Growing evidence suggests that lipid metabolism is crucial for maintaining stem cell homeostasis and cell differentiation, however, the detailed underlying mechanisms are largely unknown. In this study, we demonstrate that CYP46A1 genes are key determinants of MSC increasing lipid droplet formation. Brain cholesterol is synthesized in situ and cannot cross the blood-brain barrier: to be exported from the central nervous system into the blood circuit, excess cholesterol must be converted to 24S-hydroxycholesterol by the cholesterol 24-hydroxylase encoded by the CYP46A1 gene. To address this issue, we used an adenoassociated virus (AAV) gene transfer strategy to increase CYP46A1 expression in order to investigate the consequences on the human mesenchymal stem cell (hU-MSCs). CYP46A1 expression was assessed with Western blotting and quantitative reverse transcription PCR. We found that CYP46A1 expression was increased during adipogenesis, and treatment with exogenous CYP46A1 increased adipogenesis. Thus, we hypothesize that CYP46A1 overexpression in hU-MSCs would significantly enhance cholesterol turnover in the brain of hypoxic-ischemic encephalopathy (HIE). CYP46A1 can potentially serve as a specific target to modify the therapeutic and biological effects of hU-MSCs on HIE patients.