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Lung nodule localization using conventional image-guided video-assisted thoracoscopic surgery involves lung puncture, which increases the risk of needle-related complications. We aimed to evaluate the feasibility and safety of a single-stage non-invasive laser-guided stamping localization technique followed by resection under general anesthesia in a hybrid operating room. We retrospectively reviewed consecutive patients who underwent thoracoscopic surgery for small pulmonary nodules using laser-guided dye-stamping localization methods in a hybrid operating room between June 2023 and October 2023. During the study period, 18 patients with 20 lesions underwent single-stage intraoperative image-guided stamping video-assisted thoracoscopic surgery in the hybrid operating room. The median size of the nodules was 7.4 mm (interquartile range [IQR] 5.7-9.8 mm), and median distance from the pleural surface was 9.8 mm (IQR 7.7-14.6 mm). The median localization time was 26 min (IQR 23-34 min), whereas median operation time was 69 min (IQR 62-87 min). The total median operating room time was 146 min (IQR 136-157 min). Twelve patients underwent less than two cone-beam computed tomography scans, while 6 underwent more than two scans. The total median dose area product, including cone-beam computed tomography scans, was 5731.4 uGym 2 . No localization-related complications were observed, and the postoperative length of stay was 1 day (IQR 1-2 days). The single-stage image-guided pleural stamping technique for localizing small pulmonary nodules in a hybrid operating room is feasible and safe. Future research with larger cohorts is required to further explore the benefits of this workflow., Competing Interests: Declarations. Conflict of interest: Shwetambara Malwade works for Siemens Company as a research scientist. The other authors have no conflicts of interest or financial ties to disclose. Ethical statement: This study was approved by the Research Ethics Committee of the National Taiwan University Hospital (approval number: 202304131RINC). Informed consent: The requirement for individual consent was waived due to the retrospective nature of the study., (© 2024. Italian Society of Surgery (SIC).)

Purpose: We developed a novel augmented fluoroscopy-guided intrathoracic stamping technique for localizing small pulmonary nodules in the hybrid operating room. We conducted an observational study to investigate the feasibility of this technique and retrospectively compared two augmented fluoroscopy-guided approaches: intrathoracic and transbronchial., Methods: From August 2020 to March 2023, consecutive patients underwent single-stage augmented fluoroscopy-guided localization under general anaesthesia. This included intrathoracic stamping and bronchoscopic lung marking, followed by thoracoscopic resection in a hybrid operating room. Comparative analyses were performed between the two groups., Results: The data of 50 patients in the intrathoracic stamping and 67 patients in the bronchoscopic lung marking groups were analysed. No significant difference was noted in demographic data between the groups, except a larger lesion depth in the bronchoscopic lung marking group (14.7 ± 11.7 vs 11.0 ± 5.8 mm, p = 0.029). Dye localization was successfully performed in 49 intrathoracic stamping group patients (98.0%) and 67 bronchoscopic lung marking group patients (100%). No major procedure-related complications occurred in either group; however, the time flow (total anaesthesia time/global operating room time) was longer, and the radiation exposure (fluoroscopy duration/total dose area product) was larger in the bronchoscopic lung marking group., Conclusions: Augmented fluoroscopic stamping localization under intubated general anaesthesia is feasible and safe, providing an alternative with less global operating room time and lower radiation exposure for image-guided thoracoscopic surgery in the hybrid operating room., (© 2024. CARS.)

Rationale and Objectives: Percutaneous lung tumor ablations are mostly performed in computed tomography (CT) rooms under local anesthesia with conscious sedation. However, maintaining the breath-hold phase during this can be challenging, affecting image quality and increasing complications. With the advent of hybrid operating rooms (HORs), this procedure can be performed with endotracheal tube (ETGA) intubation under general anesthesia with lung separation, ensuring precise imaging in a single-stage setting. Lung separation provides surgical exposure of one lung while ensuring ample gas exchange with the other. This study evaluated tumor ablations performed in an HOR equipped with cone beam CT and laser guidance., Materials and Methods: This retrospective study included patients who underwent lung tumor ablation under general anesthesia with an ETGA in an HOR between July 2020 and May 2023. Anesthesia considerations, perioperative management, and postoperative follow-ups were evaluated., Results: 65 patients (78 tumors) underwent ablation using two types of lung ventilation methods including a single-lumen tube with a blocker (SLT/BL) (n = 15) and double-lumen tube (DLT) (n = 50). Most patients experienced desaturation during the apnea phase of dynamic CT and needling. The average SpO 2 value was significantly lower in the DLT group than in the SLT/BL group during the procedure (81.1% versus 88.7%, P = 0.033). Five, three, and two patients developed pneumothorax, subcutaneous emphysema, and pleural effusion, respectively., Conclusion: Percutaneous ablation under general anesthesia with endotracheal intubation and lung separation performed in HORs was feasible and safe. The setup minimized complication risks and maintained a balance between patient safety and successful procedures., Competing Interests: Declaration of Competing Interests Shwetambara Malwade works for Siemens Company as a research scientist. All other authors have no conflicts of interest or financial ties to disclose., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Different approaches are required in treating patients with multiple pulmonary lesions. A multistage procedure may increase the risk of complications and patient discomfort. This study reports an initial experience with single-stage management of multiple lung lesions using percutaneous ablation with thoracoscopic resection in a hybrid operating room (HOR)., Methods: We retrospectively evaluated patients who underwent combined ablation and resection in an HOR between May 2022 and July 2024. All patients received a single anesthesia via endotracheal tube intubation. The clinical data, operative findings, and pathological characteristics of the lung nodules were recorded., Results: A total of 22 patients were enrolled in this study. Twenty patients underwent unilateral procedures, while the other two patients underwent bilateral procedures. Ablations were performed before lung resection in 21 patients; only 1 patient underwent surgery first. The median global operating room time was 227.0 min. The median total radiation dose (dose area product) was 14,076 μGym 2 . The median hospital postoperative length of stay was 2 days., Conclusions: The single-stage procedure of percutaneous ablation with thoracoscopic resection under general anesthesia in an HOR is feasible and safe. This procedure is an alternative method for managing multiple pulmonary lesions.

In this article, the multidisciplinary team of the Taiwan Academy of Tumor Ablation, who have expertise in treating lung cancer, present their perspectives on percutaneous image-guided thermal ablation (IGTA) of lung tumors. The modified Delphi technique was applied to reach a consensus on clinical practice guidelines concerning ablation procedures, including a comprehensive literature review, selection of panelists, creation of a rating form and survey, and arrangement of an in-person meeting where panelists agreed or disagreed on various points. The conclusion was a final rating and written summary of the agreement. The multidisciplinary expert team agreed on 10 recommendations for the use of IGTA in the lungs. These recommendations include terms and definitions, line of treatment planning, modality, facility rooms, patient anesthesia settings, indications, margin determination, post-ablation image surveillance, qualified centers, and complication ranges. In summary, IGTA is a safe and feasible approach for treating primary and metastatic lung tumors, with a relatively low complication rate. However, decisions regarding the ablation technique should consider each patient's specific tumor characteristics., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

In this study, a marine medicinal brown alga Sargassum cristaefolium-derived fungal strain Xylaria acuta SC1019 was isolated and identified. Column chromatography of the extracts from liquid- and solid-fermented products of the fungal strain was carried out, and led to the isolation of twenty-one compounds. Their structures were characterized by spectroscopic analysis, and the absolute configurations were further established by single X-ray diffraction analysis or modified Mosher's method as nine previously undescribed compounds, namely xylarilactones A-C (1-3), ent-gedebic acid 8-O-α-D-glucopyranoside (4), 5R-hydroxylmethylmellein 11-O-α-D-glucopyranoside (5), ent-hymatoxin E 16-O-α-D-mannopyranoside (6), 19,20-epoxycytochalasin S (7), 19,20-epoxycytochalasin T (8), and (2R)-butylitaconic acid (9), along with twelve known compounds 10-21. All the isolates were subjected to anti-inflammatory and anti-angiogenic assays. Compounds 1, 5, 7, 10, and 17 showed moderate nitric oxide production inhibitory activities in lipopolysaccharide-activated BV-2 microglial cells with IC 50 values of 19.55 ± 0.35, 16.10 ± 0.57, 15.20 ± 0.87, 11.76 ± 0.49, and 11.30 ± 0.32 μM, respectively, as compared to curcumin (IC 50 = 2.69 ± 0.34 μM) without any significant cytotoxicity. Compounds 7, 8, and 21 displayed potent anti-angiogenic activities by suppressing the growth of human endothelial progenitor cells with IC 50 values of 0.44 ± 0.01, 0.47 ± 0.03, and 0.53 ± 0.01 μM, respectively, as compared to sorafenib (IC 50 = 5.50 ± 1.50 μM).

The influenza A virus (IAV) consists of 8 single-stranded, negative-sense viral RNA (vRNA) segments. After infection, vRNA is transcribed, replicated, and wrapped by viral nucleoprotein (NP) to form viral ribonucleoprotein (vRNP). The transcription, replication, and nuclear export of the viral genome are regulated by the IAV protein, NS2, which is translated from spliced mRNA transcribed from viral NS vRNA. This splicing is inefficient, explaining why NS2 is present in low abundance after IAV infection. The levels of NS2 and its subsequent accumulation are thought to influence viral RNA replication and vRNP nuclear export. Here we show that NS2 is ubiquitinated at the K64 and K88 residues by K48-linked and K63-linked polyubiquitin (polyUb) chains, leading to the degradation of NS2 by the proteasome. Additionally, we show that a host deubiquitinase, OTUB1, can remove polyUb chains conjugated to NS2, thereby stabilizing NS2. Accordingly, knock down of OTUB1 by siRNA reduces the nuclear export of vRNP, and reduces the overall production of IAV. These results collectively demonstrate that the levels of NS2 in IAV-infected cells are regulated by a ubiquitination-deubiquitination system involving OTUB1 that is necessary for optimal IAV replication., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The experience of thermal ablation of lung lesions is limited, especially performing the procedure under localisation by cone-beam CT in the hybrid operation room (HOR). Here, we present the experience of microwave ablation (MWA) of lung nodules in the HOR., Methods: We reviewed patients who underwent image-guide percutaneous MWA for lung nodules in the HOR under general anaesthesia between July 2020 and July 2022. The workflow in the HOR including the pre-procedure preparation, anaesthesia consideration, operation methods, and postoperative care was clearly described., Results: Forty lesions in 33 patients who underwent MWA under general anaesthesia (GA) in the HOR were analysed. Twenty-seven patients had a single pulmonary nodule, and the remaining six patients had multiple nodules. The median procedure time was 41.0 min, and the median ablation time per lesion was 6.75 min. The median global operation room time was 115.0 min. The median total dose area product was 14881 μGym 2 . The median ablation volume was 111.6 cm 3 . All patients were discharged from the hospital with a median postoperative stay of 1 day. Four patients had pneumothorax, two patients had pleural effusion during the first month of outpatient follow-up, and one patient reported intercostal neuralgia during the 3-month follow-up., Conclusions: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if we follow the workflow provided. The procedure provides an alternative to managing pulmonary nodules in patients., Clinical Relevance Statement: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if the provided workflow is followed., Key Points: • We tested the feasibility of microwave ablation of lung lesions performed in a hybrid operating room. • To this end, we provide a description of microwave ablation of the lung under cone-beam CT localisation. • We describe a workflow by which ablation of the pulmonary nodule can be performed safely under general anaesthesia., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

To optimize the extraction process of crude polysaccharides from Atractylodes and elaborate the mechanism of Atractylodes polysaccharides in treating diarrhea owing to spleen deficiency, so as to lay a foundation for further development and utilization of Atractylodes lancea, we used an orthogonal test to optimize the extraction process and established a model of spleen deficiency. It was further combined with histopathology and intestinal flora to elaborate the mechanism of Atractylodes polysaccharides in the treatment of spleen-deficiency diarrhea. The optimized extraction conditions were as follows: the ratio of material to liquid was 1:25; the rotational speed was 150 rpm; the extraction temperature was 60°C; the extraction time was 2 h; and the extraction rate was about 23%. The therapeutic effect of Atractylodes polysaccharides on a spleen-deficiency diarrhea model in mice showed that the water content of stools and diarrhea grade in the treatment group were alleviated, and the levels of gastrin, motilin and d-xylose were improved. The analysis results based on gut microbiota showed that the model group had a higher diversity of gut microbiota than the normal group and treatment group, and the treatment group could correct the diversity of gut microbiota in model mice. Analysis based on the level of phylum and genus showed that the treatment group could inhibit the abundance of Helicobacter pylori genus and increase beneficial bacteria genera. The conclusion was that the optimized extraction process of Atractylodes polysaccharides was reasonable and feasible, and had a good therapeutic effect on spleen deficiency diarrhea., (© 2024 John Wiley & Sons Ltd.)

Objectives: Persistent growth of Mycobacterium abscessus complex (MABC) in the respiratory system is not uncommon and may indicate continuous infection of MABC lung disease (MABC-LD), but its prevalence, risk factors, and clinical impact have not been investigated., Methods: The present study was conducted in two medical centers in northern Taiwan. We enrolled patients with MABC-LD and investigated the prevalence and predictors of persistent culture positivity (MABC-PP). Furthermore, we analyzed the association between MABC-PP and radiographic or clinical progression., Results: Among 189 patients with MABC-LD, 58 were in the MABC-PP group. Independent predictors for MABC-PP included an increasing radiographic score and highest acid-fast stain (AFS) of strong positivity (3-4+) at initial diagnosis (compared with negative AFS). MABC-PP and highest AFS were independently associated with MABC-LD progression by the multivariable analysis model. The adjusted hazard ratio increased to 3.56 when the two independent factors existed., Conclusions: MABC-PP accounted for 30.7% and was predicted by initial AFS grade and radiographic score. Patients with MABC-PP, and highest AFS grade might have disease progression., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lung cancer is the most lethal cancer type in Taiwan and worldwide. Early detection and treatment advancements have improved survival. However, small peripheral pulmonary nodules (PPN) biopsy is often challenging, relying solely on bronchoscopy with radial endobronchial ultrasound (EBUS). Augmented fluoroscopy overlays the intra-procedural cone-beam computed tomography (CBCT) images with fluoroscopy enabling real-time three-dimensional localization during bronchoscopic transbronchial biopsy. The hybrid operating room (HOR), equipped with various types of C-arm CBCT, is a perfect suite for PPN diagnosis and other interventional pulmonology. This study shares the single institute experience of EBUS transbronchial biopsy of PPN with the aid of augmented fluoroscopic bronchoscopy (AFB) and CBCT in an HOR. We retrospectively enrolled patients who underwent robotic CBCT, augmented fluoroscopy-guided, radial endobronchial ultrasound-confirmed transbronchial biopsy and cryobiopsy in a hybrid operating room. Patient demographic characteristics, computed tomography images, rapid on-site evaluation cytology, and final pathology reports were collected. Forty-one patients underwent transbronchial biopsy and 6 received additional percutaneous transthoracic core-needle biopsy during the same procedure. The overall diagnostic yield was 88%. The complications included three patients with pneumothorax after receiving subsequent CT-guided percutaneous transthoracic needle biopsy, and two patients with hemothorax who underwent transbronchial cryobiopsy. Overall, the bronchoscopic biopsy of PPN using AFB and CBCT as precise guidance in the hybrid operating room is feasible and can be performed safely with a high diagnostic yield.

TRIM5α is a host anti-retroviral restriction factor that destroys human immunodeficiency virus (HIV) virions and triggers innate immune signaling. TRIM5α also mediates the autophagic degradation of target proteins via TRIMosome formation. We previously showed that TRIM5α promotes Epstein-Barr virus (EBV) Rta ubiquitination and attenuates EBV lytic progression. In this study, we sought to elucidate whether TRIM5α can interact with and induce the degradation of EBV capsid proteins. Glutathione S-transferase (GST) pulldown and immunoprecipitation assays were conducted to identify interacting proteins, and mutants were generated to investigate key binding domains and ubiquitination sites. Results showed that TRIM5α binds directly with BORF1, an EBV capsid protein with a nuclear localization signal (NLS) that enables the transport of EBV capsid proteins into the host nucleus to facilitate capsid assembly. TRIM5α promotes BORF1 ubiquitination, which requires the surface patch region in the TRIM5α PRY/SPRY domain. TRIM5α expression also decreases the stability of BORF1(6KR), a mutant with all lysine residues mutated to arginine. However, chloroquine treatment restores the stability of BORF1(6KR), suggesting that TRIM5α destabilizes BORF1 via direct recognition of its substrate for autophagic degradation. These results reveal novel insights into the antiviral impact of TRIM5α beyond retroviruses., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Objectives: Hybrid operating rooms (HOR) have been increasingly used for image-guided lung surgery, and most surgical teams have used percutaneous localization for small pulmonary nodules. We evaluated the feasibility and safety of augmented fluoroscopic bronchoscopy localization under endotracheal tube intubation general anaesthesia followed by thoracoscopic surgery as a single-stage procedure in ab HOR., Methods: We retrospectively reviewed clinical records of patients who underwent single-stage augmented fluoroscopic bronchoscopy localization under general anaesthesia followed by thoracoscopic surgery in an HOR between August 2020 and March 2022., Results: Single-stage localization and resection were performed for 85 nodules in 74 patients. The median nodule size was 8 mm [interquartile range (IQR), 6-9 mm], and the median distance from the pleural space was 10.9 mm (IQR, 8-20 mm). All nodules were identifiable on cone-beam computed tomography images and marked transbronchially with indigo carmine dye (median markers per lesion: 3); microcoils were placed for deep margins in 16 patients. The median localization time was 30 min (IQR 23-42 min), and the median fluoroscopy duration was 3.3 min (IQR 2.2-5.3 min). The median radiation exposure (expressed as the dose area product) was 4303.6 μGym2 (IQR 2879.5-6268.7 μGym2). All nodules were successfully marked and resected, and the median global operating room time was 178.5 min (IQR 153.5-204 min). There were no localization-related complications, and the median length of postoperative stay was 1 day (IQR, 1-2 days)., Conclusions: Single-stage augmented fluoroscopic bronchoscopy localization under general anaesthesia followed by thoracoscopic surgery was feasible and safe., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Chromatographic separation on the liquid-state fermented products produced by the fungal strain Alternaria alstroemeriae Km2286 isolated from the littoral medicinal herb Atriplex maximowicziana Makino resulted in the isolation of compounds 1 - 9 . Structures were determined by spectroscopic analysis as four undescribed perylenequinones, altertromins A-D ( 1 - 4 ), along with altertoxin IV ( 5 ), altertoxin VIII ( 6 ), stemphyperylenol ( 7 ), tenuazonic acid ( 8 ), and allo -tenuazonic acid ( 9 ). Compounds 1 - 6 exhibited antiviral activities against Epstein-Barr virus (EBV) with EC 50 values ranging from 0.17 ± 0.07 to 3.13 ± 0.31 μM and selectivity indices higher than 10. In an anti-neuroinflammatory assay, compounds 1 - 4 , 6 , and 7 showed inhibitory activity of nitric oxide production in lipopolysaccharide-induced microglial BV-2 cells, with IC 50 values ranging from 0.33 ± 0.04 to 4.08 ± 0.53 μM without significant cytotoxicity. This is the first report to describe perylenequinone-type compounds with potent anti-EBV and anti-neuroinflammatory activities.

This study compared the transcriptome of Atractylodes lancea rhizome at different development stages and explored genes encoding the key enzymes of the sesquiterpenoid biosynthesis pathway. Specifically, Illumina NovaSeq 6000 was employed for sequencing the cDNA libraries of A. lancea rhizome samples at the growth stage(SZ), flowering stage(KH), and harvesting stage(CS), respectively. Finally, a total of 388 201 748 clean reads were obtained, and 16 925, 8 616, and 13 702 differentially expressed genes(DEGs) were identified between SZ and KH, KH and CS, and SZ and CS, separately. Among them, 53 genes were involved in the sesquiterpenoid biosynthesis pathways: 9 encoding 6 enzymes of the mevalonic acid(MVA) pathway, 15 encoding 7 enzymes of the 2-C-methyl-D-erythritol-4-phosphate(MEP) pathway, and 29 of sesquiterpenoid and triterpenoid biosynthesis pathway. Weighted gene co-expression network analysis(WGCNA) yielded 12 genes related to sesquiterpenoid biosynthesis for the SZ, 1 gene for the KH, and 1 gene for CS, and several candidate genes for sesquiterpenoid biosynthesis were discovered based on the co-expression network. This study laid a solid foundation for further research on the sesquiterpenoid biosynthesis pathway, analysis of the regulation mechanism, and mechanism for the accumulation of sesquiterpenoids in A. lancea.

Due to its advantages of high customization and rapid production, metal laser melting manufacturing (MAM) has been widely applied in the medical industry, manufacturing, aerospace and boutique industries in recent years. However, defects during the selective laser melting (SLM) manufacturing process can result from thermal stress or hardware failure during the selective laser melting (SLM) manufacturing process. To improve the product's quality, the use of defect detection during manufacturing is necessary. This study uses the process images recorded by powder bed fusion equipment to develop a detection method, which is based on the convolutional neural network. This uses three powder-spreading defect types: powder uneven, powder uncovered and recoater scratches. This study uses a two-stage convolutional neural network (CNN) model to finish the detection and segmentation of defects. The first stage uses the EfficientNet B7 to classify the images with/without defects, and then to locate the defects by evaluating three different instance segmentation networks in second stage. Experimental results show that the accuracy and Dice measurement of Mask-R-CNN network with ResNet 152 backbone can reach 0.9272 and 0.9438. The computational time of an image only takes approximately 0.2197 sec. The used CNN model meets the requirements of the early detected defects, regarding the SLM manufacturing process.

Purpose: Venous thromboembolic complications have been reported in association with coronavirus disease 2019 (COVID-19) infection. We raised awareness regarding a potential temporal association between COVID-19 infection and retinal vein occlusion (RVO)., Design: Multicenter, retrospective, nonconsecutive case series., Subjects: Patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection, were included. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization., Methods: This was a multicenter, retrospective, nonconsecutive case series including patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection. The exclusion criteria were as follows: age >50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization., Main Outcome Measures: Ophthalmic findings, including presenting and final visual acuity (VA), imaging findings, and clinical course., Results: Twelve eyes of 12 patients with CRVO (9 of 12) or HRVO (3 of 12) after COVID-19 infection were included. The median age was 32 years (range, 18-50 years). Three patients were hospitalized, but none were intubated. The median time from COVID-19 diagnosis to ophthalmic symptoms was 6.9 weeks. The presenting VA ranged from 20/20 to counting fingers, with over half (7 of 12) having a VA of ≥20/40. OCT revealed macular edema in 42% of the eyes; of these, 80% (4 of 5) were treated with anti-VEGF injections. Ninety-two percent (11 of 12) had partial or complete resolution of ocular findings at final follow-up. Four eyes (33%) had retinal thinning, as determined using OCT, by the end of the study interval. The final VA ranged from 20/20 to 20/60, with 11 of the 12 (92%) eyes achieving a VA of ≥20/40 at a median final follow-up period of 13 weeks (range, 4-52 weeks)., Conclusions: Although we acknowledge the high seroprevalence of COVID-19 and that a causal relationship cannot be established, we reported this series to raise awareness regarding the potential risk of retinal vascular events due to a heightened thromboinflammatory state associated with COVID-19 infection., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether prophylactic ranibizumab prevents the development of neovascular age-related macular degeneration (nAMD) in eyes with intermediate age-related macular degeneration (AMD) for patients with preexisting nAMD in their contralateral eye., Design: Multicenter randomized clinical trial., Participants: Adults aged 50 years and older with intermediate AMD (multiple intermediate drusen [≥63 μm and <125 μm] or ≥1 large drusen [≥125 μm] and pigmentary changes) in the study eye and nAMD in the contralateral eye., Intervention: Intravitreal ranibizumab injection (0.5 mg) or sham injection every 3 months for 24 months., Main Outcome Measures: Conversion to nAMD over 24 months (primary). Change in best-corrected visual acuity from baseline to 24 months (secondary)., Results: Among 108 enrolled participants (54 [50%] in each group), all except 2 were non-Hispanic Whites, 61 participants (56%) were female, and the mean age was 78 years. The mean baseline visual acuity was 77.7 letters (Snellen equivalent 20/32). Conversion to nAMD over 24 months occurred among 7 of 54 eyes (13%) in both groups (ranibizumab vs. sham hazard ratio = 0.91 [95% confidence interval (CI), 0.32-2.59]; P = 0.86). At 24 months, the cumulative incidence of nAMD adjusted for loss to follow-up was 14% (95% CI, 4%-23%) in the ranibizumab group and 15% (95% CI, 4%-25%) in the sham group. At 24 months, the mean change in visual acuity from baseline was -2.1 letters (standard deviation, 5.4 letters) with ranibizumab and -1.4 letters (standard deviation, 7.7 letters) with sham (adjusted difference = -0.8 letters [95% CI, -3.7 to 2.2 letters]; P = 0.62). The proportion of eyes that lost at least 10 letters of visual acuity from baseline at 24 months was 2 of 39 (5%) with ranibizumab and 4 of 40 (10%) with sham. There were no serious ocular adverse events in either group., Conclusions: Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD compared with sham injections; however, the study was likely underpowered given the 95% CI, and a clinically meaningful effect cannot be excluded. There also was no effect on visual acuity at 24 months. Other strategies to reduce neovascular conversion in these vulnerable eyes are needed., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Lung cancer with related pericardial effusion is not rare. Intervention is a crucial step for symptomatic effusion. It is unknown, however, whether the different invasive interventions for pericardial effusion result in different survival outcomes. This study analyzed the clinical characteristics and prognostic factors for patients with non-small-cell lung cancer (NSCLC) who have undergone different procedures., Methods: From January 2006 to June 2018, we collected data from patients with NSCLC who have received invasive intervention for pericardial effusions. The patients were divided into three categories: simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy. Kaplan-Meier curve and log-rank test were used to analyze the pericardial effusion recurrence-free survival (RFS) and overall survival (OS)., Results: A total of 244 patients were enrolled. Adenocarcinoma (83.6%) was the major NSCLC subtype. Invasive intervention, including simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy, had been carried out on 52, 170, and 22 patients, respectively. The 1-year RFS rates in simple pericardiocentesis, balloon pericardiotomy, and surgical pericardiectomy were 19.2%, 31.2%, and 31.8%, respectively (P = 0.128), and the median RFS was 1.67, 5.03, and 8.32 months, respectively (P = 0.008). There was no significant difference in OS, however, with the median OS at 1.67, 6.43, and 8.32 months, respectively (P = 0.064). According to the multivariable analysis, the gravity in pericardial fluid analysis, receiving systemic therapy after pericardial effusion, and the time period from stage IV lung cancer to the presence of pericardial effusion were independent prognostic factors for pericardial effusion RFS and OS., Conclusions: Patients who have undergone simple pericardiocentesis alone for the management of NSCLC-related pericardial effusion have lower 1-year RFS rates than those who have undergone balloon pericardiotomy and surgical pericardiectomy. Therefore, balloon pericardiotomy and surgical pericardiectomy should be carried out for patients with NSCLC-related pericardial effusion if tolerable., Competing Interests: Disclosure JYS has served as an advisory board member from AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai Pharma, Ono Pharmaceutical, Takeda, CStone Pharmaceuticals, Janssen, and Bristol Myers Squibb and received speaking honoraria from AstraZeneca, Roche, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai Pharma, Ono Pharmaceutical, and Bristol Myers Squibb, as well as grant from Roche. SGW has received speaking honoraria from AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Chugai, and Roche. All remaining authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The effective material basis of Chinese medicine is the key and difficult point in the quality control and modernization research of Chinese medicine. With the increasing application of pharmacophore-based virtual screening in computer-aided drug design, it is possible to employ this technology in the modernization of Chinese medicine. Based on the systematic research method of the pharmacophore model, the present study systematically reviewed the pharmacophore-based technologies and strategies in the identification of active components in Chinese medicine.

Atractylodis Rhizoma(AR) is a traditional Chinese medicinal material for food and medicine, with the functions of eli-minating dampness, strengthening the spleen, expelling wind evil and dispersing cold. AR contains a variety of compounds, including sesquiterpenoids, alkynes, triterpenoids, aromatic glycosides, polysaccharides and so on. At present, the researches on AR mainly focus on volatile components, with relatively fewer researches on non-volatile components. Polysaccharide from Atractylodis Rhizoma(ARP) is an important material basis among non-volatile components for the efficacy. Due to its many biological activities such as immunomodulatory activity, anti-tumors, anti-virus and anti-oxidation, ARP has certain research value and potential. The diversity of the polysaccharide structure is the basis for biological functions, but it also increases the difficulty of carbohydrate research. The research on the extraction, separation, purification, structure and activity of ARP is in the preliminary exploration stage, still with many shortcomings. Herein, recent advancements in the extraction, purification, structural characteristics and biological activities of ARP were summarized in this article to provide scientific reference for the in-depth systematic research of ARP and the development of AR resources.

An Escherichia coli ATP-dependent two-component protease, ClpYQ(HslUV), targets the SulA molecule, an SOS induced protein. ClpY recognizes, unfolds and translocates the substrates into the proteolytic site of ClpQ for degradation. ClpY is divided into three domains N, I and C. The N domain is an ATPase; the C domain allows for oligomerization, while the I domain coordinates substrate binding. In the ClpYQ complex, two layer pore sites, pore I and II, are in the center of its hexameric rings. However, the actual roles of two outer-loop (130~159 aa, L1 and 175~209 aa, L2) of the ClpY-I domain for the degradation of SulA are unclear. In this study, with ATP, the MBP-SulA molecule was bound to ClpY oligomer(s). ClpYΔL1 (ClpY deleted of loop 1) oligomers revealed an excessive SulA-binding activity. With ClpQ, it showed increased proteolytic activity for SulA degradation. Yet, ClpYΔL2 formed fewer oligomers that retained less proteolytic activity, but still had increased SulA-binding activity. In contrast, ClpYΔpore I had a lower SulA-binding activity. ClpYΔ pore I ΔL2 showed the lowest SulA-binding activity. In addition, ClpY (Q198L, Q200L), with a double point mutation in loop 2, formed stable oligomers. It also had a subtle increase in SulA-binding activity, but displayed less proteolytic activity. As a result, loop 2 has an effect on ClpY oligomerization, substrate binding and delivery. Loop 1 has a role as a gate, to prevent excessive substrate binding. Thus, accordingly, ClpY permits the formation of SulA-ClpY (6x) , with ATP(s), and this complex then docks through ClpQ (6x) for ultimate proteolytic degradation.

Ethnopharmacological Relevance: Atractylodis Rhizoma (AR), mainly includes Atractylodes lancea (Thunb.) DC. (A. lancea) and Atractylodes chinensis (DC.) Koidz. (A. chinensis) is widely used in East Asia as a diuretic and stomachic drug, for the treatment of rheumatic diseases, digestive disorders, night blindness, and influenza as it contains a variety of sesquiterpenoids and other components of medicinal importance., Aim of the Review: A systematic summary on the botany, traditional uses, phytochemistry, pharmacology, toxicology, and quality control of AR was presented to explore the future therapeutic potential and scientific potential of this plant., Materials and Methods: A review of the literature was performed by consulting scientific databases including Google Scholar, Web of Science, Baidu Scholar, Springer, PubMed, ScienceDirect, CNKI, etc. Plant taxonomy was confirmed to the database "The Plant List"., Results: Over 200 chemical compounds have been isolated from AR, notably sesquiterpenoids and alkynes. Various pharmacological activities have been demonstrated, especially improving gastrointestinal function and thus allowed to assert most of the traditional uses of AR., Conclusions: The researches on AR are extensive, but gaps still remain. The molecular mechanism, structure-activity relationship, potential synergistic and antagonistic effects of these components need to be further elucidated. It is suggested that further studies should be carried out in the aspects of comprehensive evaluation of the quality of medicinal materials, understanding of the "effective forms" and "additive effects" of the pharmacodynamic substances based on the same pharmacophore of TCM, and its long-term toxicity in vivo and clinical efficacy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To recognise clinical features of COVID-19 pneumonia and its differences from influenza pneumonia., Methods: 246 patients were enrolled into COVID-19 cohort and 120 patients into influenza cohort. All data were collected and analysed retrospectively. The variables under focus included demographic, epidemiological, clinical, laboratory and imaging characteristics of COVID-19 pneumonia and comparison were made with influenza pneumonia., Results: The COVID-19 cohort included 53.25% female and 46.75% male. Their main symptom was fever; while 28.05% of patients had only initially fever; 21.54% of them remained feverless. After excluding prior kidney diseases, some patients showed abnormal urinalysis (32.11%), elevated blood creatinine (15.04%) and blood urea nitrogen (19.11%). Typical CT features included ground glass opacity, consolidation and band opacity, which could present as characteristic 'bat wing sign'. Our data showed that male, aged 65 or above, smoking, with comorbidities including diabetes, cardiovascular and kidney diseases, would experience more severe COVID-19 pneumonia. In comparison, COVID-19 cohort showed significantly higher incidence of clustering; the influenza cohort showed higher rate of fever. Both cohorts showed reduced lymphocyte numbers; however, 6 influenza patients showed lymphocytes increased, which was statistical significant compared with COVID-19 cohort. Also, influenza cohort displayed higher white blood cell counts and PCT values., Conclusion: There is no significant gender difference in the incidence of COVID-19 pneumonia. It predominantly affects the lung as well as the kidney. Age, smoking and comorbidities could contribute to disease severity. Although COVID-19 is more infectious, the rate of secondary bacterial infection is lower than influenza.

Rta of Epstein-Barr virus (EBV) is thought to be expressed only during the lytic cycle to promote the transcription of lytic genes. However, we found that Rta is expressed in EBV-infected B cells during viral latency, at levels detectable by immunoblot analysis. Latent Rta expression cannot be attributed to spontaneous lytic activation, as we observed that more than 90% of Akata, P3HR1, and 721 cells latently infected by EBV express Rta. We further found that Rta is sequestered in the nucleolus during EBV latency through its interaction with MCRS2, a nucleolar protein. When Rta is sequestered in the nucleolus, it no longer activates RNA polymerase II-driven transcription, thus explaining why Rta expression during latency does not transactivate EBV lytic genes. Additional experiments showed that Rta can bind to 18S rRNA and become incorporated into ribosomes, and a transient transfection experiment showed that Rta promotes translation from an mRNA reporter. These findings reveal that Rta has novel functions beyond transcriptional activation during EBV latency and may have interesting implications for the concept of EBV latency., Competing Interests: Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Lindernia crustacea (L.) F.Muell. (Scrophulariaceae) was selected for phytochemical investigation owing to its traditional use against human herpes virus infection and its anti-Epstein-Barr virus (EBV) effect., Aims of the Study: The present study focused on the phytochemical investigation of L. crustacea including the isolation and structure determination of its biologically active compounds. Compounds with anti-EBV effects were also investigated., Materials and Methods: The EtOH extract of L. crustacea was subsequently partitioned using different solvents. The EtOAc fraction was subjected to several chromatographic methods to obtain pure compounds. The structures of all isolates were established by spectroscopic analysis and compared with previously reported physical data. The anti-EBV effect was evaluated in an EBV-containing Burkitt's lymphoma cell line (P3HR1) to study the expression of EBV lytic proteins., Results: Thirty-three compounds, including one diterpene (1), four anthraquinones (2-5), two ionones (6 and 7), fourteen phenylpropanoid glycosides (8-21), five flavonoids (22-26), one lignan glycoside (27), one phenethyl alcohol glycoside (28), one phenylpropene glycoside (29), one glucosyl glycerol derivative (30), one furanone (31), and two cinnamic acid derivatives (32 and 33), were isolated from the ethanolic extract of the plant. All isolated compounds were obtained for the first time from Lindernia sp. The evaluation of the anti-EBV activity of L. crustacea crude extract, partitioned fractions, and constituents was performed for the first time. Phytol (1), aloe-emodin (2), byzantionoside B (7), a mixture of trans-martynoside (8) and cis-martynoside (9), a mixture of trans-isomartynoside (10) and cis-isomartynoside (11), luteolin-7-O-β-D-glucopyranoside (24), and apigenin-7-O-[β-D-apiofuranosyl (1→6)-β-D-glucopyranoside] (25) exhibited significant inhibitory effects on the EBV lytic cycle at 20 μg/mL in the immunoblot analysis. On the other hand, (6R,7E,9R)-3-oxo-α-ionol-β-D-glucopyranoside (6) and a mixture of trans-dolichandroside A (12) and cis-dolichandroside A (13) showed moderate anti-EBV activity at 20 μg/mL., Conclusions: L. crustacea and its active isolates could be developed as potential candidates against EBV. Our findings provide scientific evidence for the traditional use of L. crustacea for its antiviral effects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Rta, a key transcription factor expressed by Epstein-Barr virus (EBV), primarily acts to induce activation of the EBV lytic cycle. Interestingly, we observed from an immunogold assay that Rta is also present on the EBV capsid in the host cell nucleus, and a centrifugation study further revealed that Rta cofractionates with EBV virions. Importantly, cofractionated Rta showed similar properties as the EBV tegument protein, BGLF4. Glutathione S-transferase (GST)-pulldown and coimmunoprecipitation assays subsequently demonstrated that Rta directly interacts with the EBV capsid protein, BORF1. Rta was observed to colocalize with BORF1 in the nucleus during EBV lytic induction, and this interaction appears to influence BORF1 stability. Moreover, we found that BORF1 is modified by ubiquitin, and Rta reduces this ubiquitination. These results indicate that Rta may act as an inner tegument protein to improve EBV capsid stability and critical to viral infection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To evaluate disease activity-free intervals of patients with neovascular age-related macular degeneration (nAMD) in the pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) to determine whether duration of response to previous treatment with ranibizumab informs future disease activity and need for subsequent injections., Design: Retrospective subgroup analysis of the phase 3 HARBOR study (clinicaltrials.gov identifier, NCT00891735)., Participants: Patients from the ranibizumab 0.5 mg pro re nata arm of the phase 3 HARBOR clinical trial who received all 3 loading injections and missed no more than 1 study visit (N = 217)., Methods: A disease activity-free interval was defined as a consecutive period in months when treatment was not required because the patient did not meet protocol retreatment criteria. Percentage of disease activity-free eyes at the next 1 and 2 months after a first disease activity-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was evaluated. Additionally, duration that eyes remained untreated after disease activity-free intervals was evaluated by Kaplan-Meier estimates., Main Outcome Measures: Key outcome measures included duration of the first treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months achieved by each patient; mean number of additional months patients remained treatment free after a treatment-free interval; and percentage of eyes requiring treatment within 2 months after each treatment-free interval., Results: Percentage of eyes requiring retreatment the month after a treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was 60% (90/151), 33% (33/100), 26% (20/77), 36% (24/66), and 19% (9/48), respectively. Percentage of eyes requiring retreatment within 2 months after a treatment-free interval of ≥2, ≥3, ≥4, ≥5, and ≥6 months was 73% (109/149), 53% (53/100), 53% (40/75), 47% (30/64), and 43% (20/46), respectively. After treatment-free intervals of ≥2, ≥3, ≥4, ≥5, and ≥6 months, mean (standard error of the mean) additional time treatment free was 1.3 months (0.17 month), 2.4 months (0.33 month), 2.9 months (0.44 month), 3.2 months (0.50 month), and 4.0 months (0.60 month), respectively., Conclusions: Longer treatment-free intervals may indicate longer future disease-free intervals; however, this association varies. Thus, although longer intervals suggest greater likelihood of not needing retreatment within 1 to 2 months, regular assessment is warranted owing to the unpredictability of nAMD disease activity., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Protoflavones, a rare group of natural flavonoids with a non-aromatic B-ring, are best known for their antitumor properties. The protoflavone B-ring is a versatile moiety that might be explored for various pharmacological purposes, but the common cytotoxicity of these compounds is a limitation to such efforts. Protoapigenone was previously found to be active against the lytic cycle of Epstein-Barr virus (EBV). Further, the 5-hydroxyflavone moiety is a known pharmacophore against HIV-integrase. The aim of this work was to prepare a series of less cytotoxic protoflavone analogs and study their antiviral activity against HIV and EBV. Twenty-seven compounds, including 18 new derivatives, were prepared from apigenin through oxidative de-aromatization and subsequent continuous-flow hydrogenation, deuteration, and/or 4'-oxime formation. One compound was active against HIV at the micromolar range, and three compounds showed significant activity against the EBV lytic cycle at the medium-low nanomolar range. Among these derivatives, protoapigenone 1'- O -isopropyl ether ( 6 ) was identified as a promising lead that had a 73-times selectivity of antiviral over cytotoxic activity, which exceeds the selectivity of protoapigenone by 2.4-times. Our results open new opportunities for designing novel potent and safe anti-EBV agents that are based on the natural protoflavone moiety.

Background: To determine whether aflibercept (Eylea; Regeneron Pharmaceuticals, Inc., Tarrytown, NY) could continue to extend the macular edema free interval in patients on a treat and extend (TAE) with non-ischemic central retinal vein occlusions (CRVOs) previously treated with ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA) or bevacizumab (Avastin; Genentech, Inc., South San Francisco, CA) in the second year., Methods: Twenty patients with macular edema secondary to non-ischemic CRVOs previously treated with ranibizumab or bevacizumab were prospectively treated with intravitreal aflibercept injection (IAI) using a TAE dosing regimen. Injection frequencies were extended 2 weeks if there were no signs of disease activity on OCT or change in visual acuity. In the second year of the study, patients who have recurrences of macular edema could be re-challenged with a longer treatment interval under the following criterion: absence of any macular edema on three consecutive visits with the same treatment interval., Results: Twenty patients had an average duration of a CRVO for 22 months (range 7-90) and averaged an anti-VEGF treatment every 42 days (range 28-60 days). The macular edema free interval increased from 38 to 75 days when switched to aflibercept (p = 0.000003) at month 24. There was an average increase of 37 days (median 34 days; range 0-91 days) in the macular edema free interval with aflibercept. At the month 24 visit, 50% (8/16) went > 12 weeks with a macular edema free interval between IAI. There was an improvement in vision (+ 8 ETDRS letters, p = 0.006) and decreased retinal thickness (158 µm, p = 0.00003) with aflibercept treatment at month 24., Conclusions: The 2-year results of the NEWTON study demonstrated the sustained benefits of a TAE dosing regimen with aflibercept in patients with chronic CRVOs. The visual acuity gains and anatomic improvements observed at year one were maintained through month 24 with less visits and treatments. This may help minimize the treatment burden in patients with recurrent macular edema secondary to non-ischemic CRVO. Trial Registration ClinicalTrials.gov, NCT01870427, Registered June 6, 2013, https://clinicaltrials.gov/ct2/show/NCT01870427?cond=NEWTON&rank=1.Presented at the RETICON 2017: The Retina Congress with Live Surgery, Chennai, India-April 2017., Competing Interests: The following authors have no financial disclosures: Alok S. Bansal, Louis K. Chang, James D. Palmer, and Chengqing Wu.

Purpose: To determine whether aflibercept (Eylea; Regeneron Pharmaceuticals, Tarrytown, NY) can extend the macular edema-free interval in patients with nonischemic central retinal vein occlusions (CRVOs) previously treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech, South San Francisco, CA)., Design: Prospective, single-arm, interventional study., Participants: Twenty patients with chronic nonischemic CRVOs., Methods: Patients with nonischemic CRVOs previously treated with ranibizumab or bevacizumab were switched to aflibercept. The inclusion criteria included treatment for ≥6 months with ≥3 initial loading doses and evidence of recurrence of edema when treatment with either ranibizumab or bevacizumab extended beyond 4 weeks. Intravitreal aflibercept was administered with a treat-and-extend dosing regimen. Injection frequencies were extended 2 weeks if there were no signs of disease activity on OCT or change in visual acuity., Main Outcome Measures: Macular edema-free interval at week 52., Results: Twenty patients had an average duration of a CRVO for 22 months (range, 7-90 months) and averaged an anti-vascular endothelial growth factor (anti-VEGF) treatment every 42 days (range, 28-60 days). These patients received a mean of 15 treatments (range, 5-47 treatments) of ranibizumab or bevacizumab for macular edema secondary to nonischemic CRVO. Among the 17 patients who completed 1 year of follow-up, 94% had a greater macular edema-free interval with aflibercept treatment. The macular edema-free interval increased from 5.4 weeks to 9.1 weeks when treatment was switched to aflibercept (P = 0.000003). There was an average increase of 26 days (range, 0-63 days) in the macular edema free interval with aflibercept. There was an improvement in vision (+6 Early Treatment Diabetic Retinopathy Study letters, P = 0.02) and decreased retinal thickness (152 μm, P = 0.0002) with aflibercept treatment., Conclusions: In patients previously treated with ranibizumab or bevacizumab for macular edema due to nonischemic CRVO, aflibercept increased the macular edema free interval. This may help minimize the treatment burden in patients with recurrent macular edema secondary to nonischemic CRVO., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Members of the microRNA miR-10 family are highly conserved and play many important roles in diverse biological mechanisms, including immune-related responses and cancer-related processes in certain types of cancer. In this study, we found the most highly upregulated shrimp microRNA from Penaeus vannamei during white spot syndrome virus (WSSV) infection was miR-10a. After confirming the expression level of miR-10a by northern blot and quantitative RT-PCR, an in vivo experiment showed that the viral copy number was decreased in miR-10a-inhibited shrimp. We found that miR-10a targeted the 5' untranslated region (UTR) of at least three viral genes ( vp26, vp28 , and wssv102 ), and plasmids that were controlled by the 5' UTR of these genes produced enhanced luciferase signals in transfected SF9 cells. These results suggest a previously unreported role for shrimp miR-10a and even a new type of host-virus interaction, whereby a co-opts the key cellular regulator miR-10a to globally enhance the translation of viral proteins.

Purpose: To investigate dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc) in the treatment of uveitic cystoid macular edema that had persisted in the absence of intraocular inflammation., Methods: In this prospective interventional case series, 10 patients with uveitic cystoid macular edema and quiescent uveitis were treated with dexamethasone intravitreal implant at baseline and evaluated monthly for one year. Patients were retreated whenever cystoid macular edema recurred. The primary outcome measure was best-corrected visual acuity (BCVA) at day 90., Results: At day 90, mean improvement from baseline BCVA was 14.4 letters (P = 0.0003), 70% of patients had a ≥10 letter BCVA improvement, 50% of patients had a ≥15 letter BCVA improvement, and the mean decrease from baseline central subfield retinal thickness was 140 μm (P = 0.008). Improvements were maintained through day 360 with retreatment as needed. At day 360, mean improvement in BCVA was 16.5 letters (P = 0.006) and the mean decrease in central subfield retinal thickness was 158 μm (P = 0.002). One patient experienced intraocular pressure >25 mmHg (managed with topical medication). Two phakic patients (2/8; 25%) had worsening of lens opacity requiring cataract extraction., Conclusion: Dexamethasone intravitreal implant may be an effective treatment for patients with persistent cystoid macular edema in quiescent uveitis.

Papillary thyroid carcinoma is the most common thyroid cancer and the incidence is increasing. Aberrant activation of the WNT/β‑catenin pathway plays an important role in carcinogenesis. In the present study, microarray analysis was employed to compare tissues from papillary thyroid cancer and adjacent normal tissues to determine candidate genes facilitating tumor invasion. The result demonstrated that genes involved in WNT/β‑catenin signaling pathway were activated in papillary thyroid cancer, WNT10A expression was found to be upregulated >4-fold. The variations in gene expression were verified in tissues obtained from other papillary thyroid cancer patients. Molecular mechanism exploration in thyroid cells showed that enhanced WNT10A/β‑catenin signaling pathway activation promoted cell proliferation and migration. The promotion was validated by RNA interference of WNT10A and LEF1 expression. Moreover, results from flow cytometry demonstrated that WNT/β‑catenin signaling pathway activation reduced the percentage of late apoptotic thyroid cells. Conclusively, the results suggest for the first time that WNT10A/β‑catenin signaling pathway plays a crucial role in human papillary thyroid cancer.

Importance: Intravitreal bevacizumab is a frequently used antivascular endothelial growth factor medication in the United States, but its off-label use is associated with risks associated with the compounding preparation., Objective: To determine the incidence of presumed silicone oil droplets after intravitreal bevacizumab was prepared in insulin syringes by a compounding pharmacy., Design, Setting, and Participants: A retrospective review was conducted of 60 patients who experienced intravitreal silicone oil droplets in the eye after intravitreal bevacizumab injections from a single specialist practice from October 1, 2015, to November 30, 2016. Bevacizumab, 1.25 mg/0.05 mL, was delivered in insulin syringes with a 31-gauge needle., Main Outcomes and Measures: Small, round clear spheres in vitreous on dilated biomicroscopic retinal examination., Results: Over a 14-month period involving 6632 intravitreal bevacizumab injections, 60 cases (35 [58%] women) of intravitreal silicone droplets were identified. Mean [SD] age of the patients was 80 [12] years; the population comprised 48 white, 9 Asian, and 3 Hispanic patients. The incidence of silicone oil droplet injections was 0.03% (1 of 3230) from October 2015 to April 2016 and 1.7% (59 of 3402) from May to November 2016 (Fisher exact test, P < .001; odds ratio [OR], 57; 95% CI, 9.8-2260). From May to November 2016, nonpriming the syringe before the intravitreal injection had a higher risk of intravitreal silicone oil droplets compared with priming the syringe (6.4% [47 of 739] vs 0.5% [12 of 2627]; Fisher exact test, P < .001; OR, 15.1; 95% CI, 7.9-33.4). Among the 60 cases, 41 patients (68%) were symptomatic, and the main symptom was floaters with spots of light. Among the patients with floaters, 36 (88%) improved over time (range, 2-8 months) despite the silicone droplets still being present on ophthalmoscopic examination., Conclusions and Relevance: An increase in intravitreal silicone oil associated with bevacizumab prepared with insulin syringes was documented. Priming the syringe before injection was associated with a lower frequency of this complication. These findings suggest that physicians should counsel their patients on the risk of floaters with intravitreal bevacizumab preloaded in insulin syringes.

Purpose: To describe the clinical and optical coherence tomography findings associated with the development of full-thickness macular holes after rhegmatogenous retinal detachment (RRD) repair., Methods: Retrospective, interventional case series. All patients who developed full-thickness macular holes after successful RRD repair from 3 clinical practices were reviewed. All cases of combined/simultaneous full-thickness macular hole and RRD were excluded. The main outcome measure was the presence of an epiretinal membrane at time of diagnosis of macular hole., Results: Twenty-five full-thickness macular holes were diagnosed after successful retinal detachment repair. Surgical approach to RRD repair included pneumatic retinopexy (6, 24%), scleral buckle alone (5, 20%), pars plana vitrectomy only (8, 32%), and combined scleral buckle and pars plana vitrectomy (6, 24%). The preceding RRD involved the macula in 19 patients (76%) before the formation of the macular hole. The median time to full-thickness macular hole diagnosis after RRD repair was 63 days (range, 4-4,080 days). An epiretinal membrane was present in all 25 (100%) macular holes. Two macular holes (8%) spontaneously closed, whereas the other 23 (92%) were successfully closed with a single surgical procedure. Mean visual acuity improved by approximately 5 lines to 20/72 (range, 20/20 to counting fingers at 1 foot) from 20/240 (range, 20/30 to hand motions) after macular hole repair (P < 0.0001)., Conclusion: Full-thickness macular hole formation can occur after all types of RRD repair and is associated with an epiretinal membrane. The epiretinal membrane may play a role in the pathogenesis of secondary macular hole formation after RRD repair.

Atrophic gastritis is considered to be an antecedent to intestinal metaplasia and gastric cancer. A previous study identified that Helicobacter pylori was absent at the severe atrophic gastritis stage, and alterations in the gastric microbial composition resembled those in gastric cancer. To explore the role of the bacteria absence of H. pylori in gastric carcinogenesis, in the current study, we compared the microbiota of clinically collected H. pylori -free gastric fluids from 30 patients with non-atrophic gastritis (N) and 22 patients with severe atrophic gastritis (S). We estimated the bacterial loads in the N and S groups by colony counting in culture agar as well as by measuring the concentration of the extracted DNA. The results showed a significant increase in bacterial load in patients with atrophic gastritis in comparison to non-atrophic gastritis. Then, we analyzed the microbial communities of the gastric fluids from all 52 patients using high-throughput sequencing of 16S rRNA amplicons. The Chao 1, Shannon and Simpson diversity indexes demonstrated that the bacterial richness and diversity were not significantly different between the N and S groups. Moreover, principal component analysis illustrated that the microbiomes from the S group were more scattered. Microbiota composition analysis showed that the entire dataset was clustered into 27 phyla, 61 classes, 106 orders, 177 families, 292 genera and 121 species. At the genus level, only the abundance of Prevotella was significantly different between the N and S groups. Further analysis showed that all the higher taxonomic categories were significantly different between the N and S groups. To assess the effects of the metabolic products of Prevotella spp. on gastric cell physiology, we treated the human gastric epithelial cell line AGS with acetic acid and monitored nitric oxide (NO) production. The results showed that acetic acid at low concentrations (0.5 and 5 µM) significantly inhibited AGS cells to secrete NO compared to phosphate buffer saline-treated control cells. These results suggest that the microbiota in non-atrophic gastritis may influence gastric epithelial cell physiology.

The association of perfluorodecanoicacid (PFDA) with tumor promotion and associated effects is not clear. Given that PDFA is mostly consumed with food and drinking water, we evaluated the effects of PFDA on a gastric cell line. When added to cell cultures, PFDA significantly increased growth rate and colony forming ability compared with control treatment. We found that suppression of cell senescence, but not apoptosis or autophagy was associated with PFDA-induced promotion of cell amount. To determine the molecular mechanism that was involved, DNA microarray assays was used to analyze changes in gene expression in response to PFDA treatment. Data analysis demonstrated that the vascular endothelial growth factor signaling pathway had the lowest p -value, with sPLA2-IIA ( pla2g2a ) exhibits the most altered expression pattern within the pathway. Moreover, sPLA2-IIA and its transcription factor TCF4, known as a direct target and a binding partner of Wnt/β-catenin signaling in gastric cells respectively, were the third and second most varied genes globally. Cells transfected with expression plasmids pENTER- tcf4 and pENTER- pla2g2a show reduced cell proliferation by more than 60% and 30% respectively. Knockdown with sPLA2-IIA siRNA provided additional evidence that sPLA2-IIA was a mediator of PFDA-induced cell senescence suppression. The results suggest for the first time that PFDA induced suppression of cell senescence through inhibition of sPLA2-IIA protein expression and might increased the proliferative capacity of an existing tumor., Competing Interests: CONFLICTS OF INTEREST None.

Yin Yang 1 (YY1) is a multifunctional zinc finger transcription factor that regulates many key cellular processes. In this study, we report the cloning of YY1 from Litopenaeus vannamei shrimp (LvYY1). This study shows that LvYY1 is ubiquitously expressed in shrimp tissues, and knockdown of LvYY1 expression by double-stranded RNA (dsRNA) injection in white spot syndrome virus (WSSV)-infected shrimp reduced both mRNA levels of the WSSV immediate early gene ie1 as well as overall copy numbers of the WSSV genome. The cumulative mortality rate of infected shrimp also declined with LvYY1 dsRNA injection. Using an insect cell model, we observed that LvYY1 activates ie1 expression, and a mutation introduced into the ie1 promoter subsequently repressed this capability. Moreover, reporter assay results suggested that LvYY1 is involved in basal transcriptional regulation via an interaction with L. vannamei TATA-binding protein (LvTBP). Electrophoretic mobility shift assay (EMSA) results further indicated that LvYY1 binds to a YY1-binding site in the region between positions -119 and -126 in the ie1 promoter. Chromatin immunoprecipitation analysis also confirmed that LvYY1 binds to the ie1 promoter in WSSV-infected shrimp. Taken together, these results indicate that WSSV uses host LvYY1 to enhance ie1 expression via a YY1-binding site and the TATA box in the ie1 promoter, thereby facilitating lytic activation and viral replication. IMPORTANCE WSSV has long been a scourge of the shrimp industry and remains a serious global threat. Thus, there is a pressing need to understand how the interactions between WSSV and its host drive infection, lytic development, pathogenesis, and mortality. Our successful cloning of L. vannamei YY1 (LvYY1) led to the elucidation of a critical virus-host interaction between LvYY1 and the WSSV immediate early gene ie1 We observed that LvYY1 regulates ie1 expression via a consensus YY1-binding site and TATA box. LvYY1 was also found to interact with L. vannamei TATA-binding protein (LvTBP), which may have an effect on basal transcription. Knockdown of LvYY1 expression inhibited ie1 transcription and subsequently reduced viral DNA replication and decreased cumulative mortality rates of WSSV-infected shrimp. These findings are expected to contribute to future studies involving WSSV-host interactions., (Copyright © 2017 American Society for Microbiology.)