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关键词： Epstein-Barr virus   BRLF1   Primary infection   Transcriptome   Pre-mRNA splicing  

摘要： The immediate-early protein BRLF1 plays important roles in lytic infection of Epstein-Barr virus (EBV), in which it activates lytic viral transcription and replication. However, knowledge of the influence of BRLF1 on cellular gene expression and transcriptional reprogramming during the early lytic cycle remains limited. In the present study, deep RNA-sequencing analysis identified all differentially expressed genes (DEGs) and alternative splicing in B lymphoma cells subjected to wild-type and BRLF1-deficient EBV primary infection. The BRLF1-dependent cellular DEGs were annotated, and major differentially enriched pathways were related to DNA replication and transcription, immune and inflammatory responses, cytokine-receptor interactions and chemokine signaling and metabolic processes. Furthermore, analysis of BRLF1-binding proteins by mass spectrometry shows that BRLF1 binds to and cooperates with several transcription factors and components of the spliceosome and then influences both RNA polymerase II-dependent transcription and pre-mRNA splicing. The RTA-binding RRE motifs or specific motifs of unique cooperative transcription factors in viral and cellular DEG promoter regions indicate that BRLF1 employs different strategies for regulating viral and cellular transcription. Thus, our study characterized BRLF1-dependent cellular and viral transcriptional profile during primary infection and then revealed the comprehensive virus-cell interaction and alterations of transcription during EBV primary infection and lytic replication.

关键词： Anterior chamber   PACD   Low-add-power IOL   Cataract surgery   Hydrophilic  

摘要： Purpose To evaluate the temporary changes in visual outcomes and anterior segment parameters after cataract surgery plus low-add bifocal intraocular lens (IOL) implantation for primary angle closure disease (PACD). Methods This retrospective comparative case-control study included two groups: low-add-power segmented IOL and monofocal IOL. Postoperative examination involved evaluation of uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), uncorrected intermediate visual acuity (UIVA), and spherical equivalent (SE). Anterior segment examination was performed using anterior segment optical coherence tomography. Results This study included 19 eyes of 11 consecutive patients who underwent cataract surgery. The low-add group had better UDVA than the monofocal group at 3 months postoperatively, better UIVA at 1 month postoperatively, better UNVA at 1 week postoperatively. In the low-add group, SE increased at 1 and 3 months postoperatively compared with 1 week postoperatively. In the monofocal group, objective SE decreased at 1 and 3 months postoperatively compared with 1 week postoperatively. In the low-add group, the anterior chamber depth (ACD) became significantly deep gradually at 1 and 3 months compared with at 1 week postoperatively. In the monofocal group, the ACD became significantly shallow gradually at 1 and 3 months than at 1 week postoperatively. Conclusion The low-add-power segmented IOL achieved better far and intermediate distance visual acuity after cataract surgery in PACD patients than did the monofocal IOL. The ACD became deeper and SE showed a hyperopic shift with the low-add-power segmented IOL at 1 and 3 months after cataract surgery compared with at 1 week after cataract surgery.

关键词： A-type granite   Sr-Nd-Pb-Hf isotopes   Petrogenesis   LYRB   Crust-mantle interaction  

摘要： Many late Mesozoic granites within the Lower Yangtze River Belt (LYRB), eastern China, are defined as A-types based on their geochemical characteristics, although their petrogenesis is unclear. We present an integrated study combining geochronology, whole-rock geochemistry, Sr, Nd, Pb and zircon Hf isotopes andmineral chemistry for a lithologically-diverse suite of A-type granitoids at Bashan. The Bashan complex in the Chizhou area is composed of quartz monzonite, quartz syenite, syenogranite and alkali-feldspar granite. Zircon U\\Pb geochronology indicates that these intrusive rocks formed at 126-123 Ma. The quartz monzonites have intermediate SiO2 (60.5-63.1 wt%) and high Na2O + K2O (8.66-9.83 wt%) contents, arc-like trace element compositions, enriched whole-rock Sr, Nd and zircon Hf isotopes ((87Sr/86Sr) i = 0.7082-0.7091;eNd(t) = -6.9 to -7.1;eHf (t) = -5.3 to -8.2) and high radiogenic Pb isotopes (Pb-206/Pb-204(t) = 18.581-18.792). They are inferred to have been derived from partial melting of an enriched lithospheric mantle source, followed by fractional crystallisation and limited crustal contamination. The quartz syenites show high SiO2 (65.9-69.8 wt%) and Na2O+ K2O (11.3-12.3 wt%) contents, low MgO (0.14-0.23 wt%) contents, high 104 * Ga/Al (2.34-3.61) values, arc-like trace element compositions, and whole-rock Nd and Pb and zircon Hf isotopic compositions (epsilon(Nd)(t) = -6.8 to -7.0;epsilon(Hf)(t) = -7.3 to -12.3;Pb-206/Pb-204(t) = 18.559-18.970) similar to the quartz monzonite, suggesting that they were derived through fractional crystallisation of the quartz monzonite, with some crustal assimilation. The quartzmonzonite has higher Ti-in-zircon temperatures (TTi- in-Zrn= 696-832 degrees C) and lower zircon saturation temperatures (TZr= 772-818 degrees C) and oxygen fugacities (.FMQ=+1.8 to +2.8) than the quartz syenite (TTi- in-Zrn= 623-805 degrees C;TZr= 856-909 degrees C;.FMQ = +3.5 to +4.8), indicating that the zircons from the quartz syenite cryst

关键词： Cellular senescence   Ovarian cancer   Transcriptome  

摘要： Various types of human endothelial cells, including human umbilical vein endothelial cells (HUVECs) and the established hybrid EAhy926 cells, are used in experimental research. Here, we compared the biological properties of HUVECs and EAhy926 cells under normal (5 mM) and high glucose (30 mM;HG) conditions. The results showed that HG induced cellular senescence and a stronger DNA damage response in HUVECs than in EAhy926 cells. The magnitude of oxidative stress elicited in HUVECs by HG was also greater than that elicited in their established counterparts. Both endothelial cell types promoted the progression of breast (MCF7), ovarian (OVCAR-3), and lung (A549) cancer cells;however, the effects elicited by HG-treated HUVECs on adhesion (MCF7, OVCAR-3), proliferation (OVCAR-3), and migration (OVCAR-3) were more pronounced. Finally, HG stimulated the production of a higher number of proangiogenic agents in HUVECs than in EAhy926 cells. Collectively, our study shows that the functional properties of primary and established endothelial cells exposed to HG differ substantially, which seems to result from the higher sensitivity of the former to this stressor. The interchangeability of both types of endothelial cells in biomedical research should be considered with great care to avoid losing some biological effects due to the choice of cells with higher stress tolerance.

关键词： epithelial‐   to‐   mesenchymal transition   gene expression   genomic alteration   melanoma subtypes   phenotypic switching  

摘要： Melanoma represents the deadliest skin cancer. Recent therapeutic developments, including targeted and immune therapies have revolutionized clinical management and improved patient outcome. This progress was achieved by rigorous molecular and functional studies followed by robust clinical trials. The identification of key genomic alterations and gene expression profiles have propelled the understanding of distinct characteristics within melanoma subtypes. The aim of this review is to summarize and highlight the main genetic and epigenetic findings of melanomas and highlight their pathological and therapeutic importance.

关键词： Primary cutaneous acral CD8(+) T-cell lymphoma   Gold sodium thiosulfate   Lymphomatoid contact allergic dermatitis  

摘要： Primary cutaneous CD8(+) T-cell lymphoma has been included as a provisional entity within the new revised classification of lymphoid neoplasms of the World Health Organization in 2016(1). It was initially described as indolent CD8(+). lymphoid proliferation of the ear(2) and a total of 29 cases of such neoplasm have been published in the literature so far. None of them have been linked to delayed contact hypersensitivity reactions. We present a case of acral type primary cutaneous lymphoma T CD8(+). involving both earlobes clearly related with the prolonged use of gold earrings, confirmed with epicutaneous tests, histopathology, immunohistochemical and molecular studies. Auricular skin lesions were induced again with a provocation test with identical histopathologycal and the same clonality, confirming both the diagnosis of lymphoma and its induction by the antigenic stimulus of gold. (C) 2021 AEDV. Published by Elsevier Espana, S.L.U.

关键词： cutaneous lymphomas   dermatopathology   hematopathology   in situ hybridization  

摘要： Primary cutaneous follicle center lymphoma (PCFCL) is the most common cutaneous B-cell lymphoma. The typical immunophenotype includes expression of both CD20 and BCL6, with the majority of cases lacking expression of CD10, BCL2, and the characteristic t(14;18)/IGH-BCL2 rearrangement seen in systemic follicular lymphoma (FL). Plasmacytic differentiation (PD) is an uncommon finding in both systemic and cutaneous FLs and presents a diagnostic challenge when present, leading to the potential for misdiagnosis as marginal zone lymphoma (MZL). Limited reports have described light chain restriction in the plasma cell component of FLs with PD, and rare cases of PCFCL with PD have been described. While the IGH-BCL2 translocation has been identified in a subset of FLs with PD, the presence of the BCL2 translocation in monotypic plasma cells of PCFCL has not been previously described to our knowledge. Here, we report a case of PCFCL with extensive PD in a 77-year-old woman that was favored to represent primary cutaneous MZL on an initial punch biopsy. Excisional biopsy, however, revealed that the atypical lymphocytes expressed CD10, BCL6, and BCL2, while the plasma cell component demonstrated light-chain lambda restriction. FISH studies showed the presence of an IGH-BCL2 translocation in both the lymphocytic and plasmacytic components.

关键词： head and neck squamous cell carcinoma   human epidermal growth factor receptor 2 human papilloma virus immunotherapy oropharynx  

摘要： Background The purpose of this study is to describe human epidermal growth factor 2 (HER2) overexpression in head and neck squamous cell carcinoma (HNSCC) and re-evaluate its potential as a target for HER2-directed immunotherapies. Methods A retrospective cohort of patients with HNSCC receiving curative treatment was identified, and HER2 expression evaluated in archival tissue by immunohistochemistry and correlated with clinicopathological characteristics. HER2 expression data were also determined for HNSCC patients in The Cancer Genome Atlas. Results Nineteen percent of HNSCC and 39% of oropharyngeal HNSCC (OPSCC) were HER2 positive. HER2 expression positively correlated with nodal metastasis (p = 0.035). Patients with HER2-positive tumors had decreased overall survival (p = 0.012), including within the human papilloma virus-positive OPSCC subgroup (p = 0.007). Conclusions A substantial fraction of HNSCC overexpresses HER2 protein, suggesting it may be a suitable target for antigen-directed immunotherapy. HER2 expression and its correlation with survival vary across HNSCC subsites, making it unsuitable as a prognostic marker.

关键词： stereotactic body radiotherapy   renal cell carcinoma   frail patients   oncological outcomes  

摘要： Simple Summary Surgical therapy is currently the standard of care for the treatment of primary renal cell carcinoma (RCC). Alternative strategies such as stereotactic body radiotherapy (SBRT) have emerged as potentially curative treatment approaches. In this study, we show a promising short-term local control effect of SBRT in the management of primary RCC. The treatment was well tolerated with no high-grade side effects. The main advantages are the outpatient management without anesthesia and the non-invasive approach. Thus, SBRT appears to be a promising alternative to surgery, or ablative therapy, to treat primary RCC in patients with poor physical health. Future studies are needed to definitively assess the place of SBRT in the RCC treatment portfolio. Introduction: The aim of this study was to report the oncological outcomes and toxicity of stereotactic body radiotherapy (SBRT) to treat primary renal cell carcinoma (RCC) in frail patients unfit for surgery or standard alternative ablative therapies. Methods: We retrospectively enrolled 23 patients who had SBRT for primary, biopsy-proven RCC at our tertiary center between October 2016 and March 2020. Treatment-related toxicities were defined using CTCAE, version 4.0. The primary outcome was local control which was defined using the Response Evaluation Criteria in Solid Tumors. Results: The median age, Charlson score and tumor size were 81 (IQR 79-85) years, 7 (IQR 5-8) and 40 (IQR 28-48) mm, respectively. The most used dose fractionation schedule was 35 Gy (78.3%) in five or seven fractions. The median duration of follow-up for all living patients was 22 (IQR 10-39) months. Local recurrence-free survival, event-free survival, cancer-specific survival and overall survival were 96 (22/23), 74 (18/23), 96 (22/23) and 83% (19/23), respectively. There were no grade 3-4 side effects. No patients required dialysis during the study period. No treatment-related deaths or late complications were reported. Conclusion: SBRT

关键词： DM   liver   hepatocytes   insulin-positive cells   Pdx1   MafA   Ngn3  

摘要： Due to a high occurrence of diabetes mellitus (DM) and its complications, insulin-positive cells detected in different organs are of great interest as they can probably partially compensate for insulin deficiency in DM. The development of pancreatic beta-cells is regulated by the consecutive expression of transcription factors, among which Pdx1, MafA and Ngn3 are most extensively explored. Specifically, these factors have been reported to be able to transdifferentiate a broad variety of cell types into insulin-positive cells. The goal of this study was to characterize insulin-positive (insulin(+)) cells in the liver and to evaluate the expression of transcription factors Pdx1, MafA and Ngn3 involved in their differentiation in an alloxan-induced rat model of type 1 DM (T1DM) and streptozotocin-nicotinamide-induced rat model of type 2 DM (T2DM). Experiments were carried out on male Wistar rats. In experimental animals, plasma levels of glucose, glycosylated hemoglobin and insulin were determined. The oral glucose tolerance test was performed and the insulin resistance index (HOMA-IR) was calculated. The expression of Pdx1(+), MafA(+) and Ngn3(+) was investigated immunohistochemically. Insulin(+), Pdx1(+), MafA(+) and Ngn3(+) cells were detected in the liver both of healthy animals and those with experimental models of T1DM and T2DM. The largest number of insulin(+) cells was found in animals with streptozotocin-nicotinamide-induced T2DM, wherein cells were localized throughout the hepatic lobule. In an alloxan-induced model of T1DM, these cells were detected mainly at the periphery of the hepatic lobule. The number of Pdx1(+), Mafa(+) and Ngn3(+) hepatic cells was different in intact animals vs. those with experimental DM. A correlation was established between the number of Ngn3(+) cells and insulin(+) cells in alloxan-induced DM, as well as between the number of MafA(+) cells and insulin(+) cells in both types of experimental DM. Thus, in rats with both experimental