Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice / 神经科学通报·英文版

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca2+ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca2+ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca2+ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-BarrVirus Associated Chronic Lymphocytic Leukemia / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to investigate the prognostic impact of Epstein-Barr virus(EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as wellas role of EBV-miR-BHRF1-1 in p53 gene. @*Materials and Methods@#Quantitative reverse transcription–polymerase chain reaction and western blotting wereused to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL. @*Results@#p53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p <0.001) which was also an independent prognostic marker for overall survival (p=0.028;hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLLpatients after adjusted with International Prognostic Index for patients with CLL. We identifiedEBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressedluciferase reporter activity by specific interaction with the seed region within the p53 3-untranslated region. Discordance of p53 messenger RNA and protein expression wasassociated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1-1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosisand decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferationin cell lines. @*Conclusion@#This study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our resultssupport the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLLwith p53 gene aberration.

Clinical efficacy of Matrine and Sodium Chloride Injection in treatment of 40 cases of COVID-19 / 中国中药杂志

In this paper, we analyzed medical records of 40 patients with coronavirus disease 2019(COVID-19), in order to explore the clinical efficacy of Matrine and Sodium Chloride Injection in the treatment of COVID-19. The investigation was based on the results of a previous animal test, which was aimed to investigate and confirme the clinical efficacy of Matrine and Sodium Chloride Injection in the treatment of COVID-19. The animal test demonstrated that Matrine and Sodium Chloride Injection has a significant therapeutic effect on the human coronavirus pneumonia for the model mice. The lung inhibition index reached up to 86.86%. The evaluation was conducted on 40 confirmed cases of COVID-19 treated at Jingzhou Hospital of Infectious Disease(Chest Hospital) of Hubei Pro-vince from January 30~(th) to March 21~(th), 2020. In these cases, patients were treated with other integrated Chinese and Western medicines regimens in the recommended Matrine and Sodium Chloride Injection diagnosis and treatment regimen. The clinical manifestations, laboratory data, nucleic acid clearance time, and imaging data were compared and analyzed before and after treatment. After administration with Matrine and Sodium Chloride Injection, the clinical symptoms of 40 cases were alleviated markedly, and their blood analysis and biochemical indexes returned to normal. The lung CT showed more than 50% of lesion absorption rate, and the viral nucleic acid test showed the average clearance time of patients was 16.6 days, and the average length of hospital stay was 25.9 days. After administration with Matrine and Sodium Chloride Injection, the symptoms of cough and fatigue were alleviated significantly, and the appetite was significantly improved compared with before, especially for patients with gastrointestinal symptoms. Additionally, laboratory indicators, especially absolute value and ratio of lymphocytes and CRP were significantly alleviated. According to the chest CT for short-term review, the absorption of lung lesions was faster than before, especially for grid-like and fibrotic lesions. Compared with antiviral drugs, such as Abidol and Kriging, the nucleic acid clearance time was significantly shorter than the cases treated with Matrine and Sodium Chloride Injection. The clinical effective rate of 40 cases was 100.0%. We believed that Matrine and Sodium Chloride Injection have a good clinical effect in the treatment of COVID-19, and suggested increasing the clinical application and further conducting large-sample-size cli-nical verification.

Albumin-to-Fibrinogen Ratio as an Independent Prognostic Parameter in Untreated Chronic Lymphocytic Leukemia: A Retrospective Study of 191 Cases / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Chronic lymphocytic leukemia (CLL) is one of the most frequent type of B-cell chronic lymphoproliferative disorders and chronic inflammation takes part in the development of CLL. However, there has been no valid immune biomarker to predict the prognosis of untreated CLL patients. MATERIALS AND METHODS: In this retrospective study, we analyzed the clinical correlations and prognostic value of albumin-to-fibrinogen ratio (AFR) detected at diagnosis in 191 CLL patients. RESULTS: The cut-off value of AFR was 9.7 calculated by X-tile. Patients who were more than 65 years old were often accompanied by low level of AFR (p < 0.001). Survival analysis showed that patients with low level of AFR had shorter overall survival (OS) than patients with high level of AFR (p < 0.001). Multivariate analysis illustrated that AFR had a negative impact on OS (p=0.003) and was independent of parameters involved in CLL international prognostic index and other prognostic markers such as CD38 and ZAP-70. CONCLUSION: These data provide a comprehensive view of AFR and shows that AFR at diagnosis is an adverse prognostic factor in untreated CLL patients.

Evaluation of the clinical efficacy of implant-supported overdenture with edentulous mandible in elderly patients / 华西口腔医学杂志

The aging society of the global population has led to an increase in the number of patients with edentulous jaw, a common multiple disease. Given the developments in implant techniques, the method of implant denture has received a positive and good response in terms of the quality of life and psychological well-being of patients. Implant-supported overdenture in mandible has two main advantages. 1) It has better retention and chewing efficiency than those of mandibular conventional denture. The required implant site of implant-supported overdenture is less than that of fixed implant-supported denture and can repair more defect tissues to help restore beauty and pronunciation. The price of the former is more acceptable than that of the latter. Therefore, this article aimed to systemically analyze and further discuss the clinical effect of implant-supported overdenture in elderly patients; combine existing related studies on the selection of number, site, and upper restoration of implants; and illustrate the advantages of removable implant-supported protheses in the repair of toothless mandible.

Presence of serum antinuclear antibodies correlating unfavorable overall survival in patients with chronic lymphocytic leukemia / 中华医学杂志(英文版)

BACKGROUND@#Serum antinuclear antibodies (ANAs) are positive in some patients with chronic lymphocytic leukemia (CLL), but the prognostic value of ANAs remains unknown. The aim of this study was to evaluate the role of ANAs as a prognostic factor in CLL.@*METHODS@#This study retrospectively analyzed clinical data from 216 newly diagnosed CLL subjects with ANAs test from 2007 to 2017. Multivariate Cox regression analyses were used to screen the independent prognostic factors related to time to first treatment (TTFT), progression free survival (PFS) and overall survival (OS). Receiver operator characteristic curves and area under the curve (AUC) were utilized to assess the predictive accuracy of ANAs together with other independent factors for OS.@*RESULTS@#The incidence of ANAs abnormality at diagnosis was 13.9%. ANAs positivity and TP53 disruption were independent prognostic indicators for OS. The AUC of positive ANAs together with TP53 disruption was 0.766 (95% confidence interval [CI]: 0.697-0.826), which was significantly larger than that of either TP53 disruption (AUC: 0.706, 95% CI: 0.634-0.772, P = 0.034) or positive ANAs (AUC: 0.595, 95% CI: 0.520-0.668, P < 0.001) in OS prediction. Besides, serum positive ANAs as one additional parameter to CLL-international prognostic index (IPI) obtained superior AUCs in predicting CLL OS than CLL-IPI alone.@*CONCLUSION@#This study identified ANAs as an independent prognostic factor for CLL, and further investigations are needed to validate this finding.

Advance in Photosensitizers and Light Delivery for Photodynamic Therapy

The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo.

Comparison of preliminary results of involved-field with extended field radiotherapy combined with chemotherapy for early stage Hodgkin's disease / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate whether involved-field (IF) radiotherapy is equally effective and less toxic in comparison with extended-field (EF) radiotherapy for patients with early-stage Hodgkin's disease (HD) who received combined modality therapy.</p><p><b>METHODS</b>The data of 88 early-stage HD patients treated with combined modality therapy were retrospectively reviewed. According to Ann Arbor classification, 12 patients (13.7%) had stage IA disease, 56 stage IIA (63.6%), and 20 IIB (22.7%). Forty-two (47.7%) patients underwent involved field radiotherapy (IF group), whereas the other 46 (52.3%) received extended field radiotherapy (EF group).</p><p><b>RESULTS</b>Of 6 patients who developed recurrence, 3 (7.1%) were in IF group and the other 3 (6.5%) in EF group. Only one patient's recurrence developed inside the radiation field in EF group. Three patients (7.2%) in IF group and 9 (19.5%) in EF group had WHO grade 1 and 2 leukopenia (P = 0.089). Overall survival rate at 1-, 2- and 3-year was 100.0%, 97.1%, and 97.1% in IF group versus 100.0%, 100%, and 95.8% in EF group (P = 0.86), respectively. Freedom from progression survival rate at 1-, 2- and 3-year was 97.6%, 94.8%, and 91.7% in IF group versus 97.8%, 93.2%, and 93.2% in EF group (P = 0.65), respectively.</p><p><b>CONCLUSION</b>Compared with extended-field radiotherapy, involved-field radiotherapy is equally effective and less toxic for patient with early-stage Hodgkin's disease treated with combined modality therapy.</p>