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Dan Yu,1,&ast; Di-Xiao Yang,2,&ast; Yao Li,3 Bi Guan,2 Qian Ming,2 Yan Li,2 Yi-Ping Zhu,4 Li-Qing Chen,1 Wei-Xiang Luo5 1Department of Otolaryngology and Hepatobiliary, Chengdu Fifth People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China; 2Nursing Department, Chengdu Fifth People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China; 3Intensive Care Unit, Chengdu Fifth People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China; 4Department of Oncology, Chengdu Wenjiang District People’s Hospital, Chengdu, 611130, Sichuan, People’s Republic of China; 5Department of Nursing, Shenzhen People’s Hospital (2nd Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, 518020, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei-Xiang LuoDepartment of Nursing, Shenzhen People’s Hospital (2nd Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology), Shenzhen, 518020, Guangdong, People’s Republic of ChinaTel +86 755-25533018-2887Email luoweixiang688@hotmail.comBackground: Due to the poor healing of superficial malignant tumor ulcer wounds, patients suffer great pain and significantly reduced quality of life. Related research shows that oxygen therapy can reduce wound bleeding and promote wound healing.Objective: This study aims to explore the therapeutic effect of nano-silver antibacterial dressing combined with high-flow oxygen therapy on surface malignant tumor ulcers.Methods: In this retrospective analysis, 64 patients with superficial malignant tumors and ulcer infection were included and divided into the research group and the control group, with 32 cases in each group. After conventional debridement, the control group was treated with vaseline dressing, while the research group was treated with nano-silver medical antibacterial dressing combined with high-flow oxygen therapy. Both groups were treated for 7 days. The frequency of dressing change and the number of times of blood oozing between the two groups after treatment were recorded. The pain, clinical efficacy, and levels of procalcitonin (PCT) and C-reactive protein (CRP) were compared between the two groups before and after treatment.Results: The dressing changes and blood oozing were less frequent in the research group compared with the control group. The pain score and the levels of PCT and CRP in the research group were lower than those in the control group. The overall response rate was significantly higher in the research group as compared to the control group. All the above differences were statistically significant (P< 0.05).Conclusion: Nano-silver medical antibacterial dressing combined with high-flow oxygen therapy can reduce the frequency of dressing changes in patients, relieve pain, reduce inflammation, and accelerate the healing of superficial malignant tumor ulcer wounds.Keywords: nano-silver medical antibacterial dressing, high flow oxygen therapy, body surface malignant tumor, ulcer, wound

Stroke, a major neurological disorder and a leading cause of disability and death, often inflicts damage upon other organs, particularly the kidneys. While chronic kidney disease (CKD) has long been established as a significant risk factor for cerebrovascular disease, stroke can induce renal dysfunction, manifesting as acute kidney injury (AKI) or CKD. Mounting clinical and basic research evidence supports the existence of a bidirectional brain-kidney crosstalk following stroke, implicating specific mechanisms and pathways in stroke-related renal dysfunction. This review analyzes pertinent experimental studies, elucidating the underlying mechanisms of this cerebro-renal interaction following stroke. Additionally, we summarize the current landscape of clinical research investigating brain-kidney interplay and discuss potential challenges in the future. By enhancing our understanding of the scientific underpinnings of brain-kidney crosstalk, this review paves the way for improved treatment strategies and outcomes for stroke patients. Recognizing the intricate interplay between the brain and kidneys after stroke holds profound clinical implications., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Traumatic brain injury (TBI) is a global public-health problem. Astrocytes, and their mitochondria, are important factors in the pathogenesis of TBI-induced secondary injury. Mitochondria extracted from healthy tissues and then transplanted have shown promise in models of a variety of diseases. However, the effect on recipient astrocytes is unclear. Here, we isolated primary astrocytes from newborn C57BL/6 mice, one portion of which was used to isolate mitochondria, and another was subjected to stretch injury (SI) followed by transplantation of the isolated mitochondria. After incubation for 12 h, cell viability, mitochondrial dysfunction, calcium overload, redox stress, inflammatory response, and apoptosis were improved. Live-cell imaging showed that the transplanted mitochondria were incorporated into injured astrocytes and fused with their mitochondrial networks, which was in accordance with the changes in the expression levels of markers of mitochondrial dynamics. The astrocytic IKK/NF-κB pathway was decelerated whereas the AMPK/PGC-1α pathway was accelerated by transplantation. Together, these results indicate that exogenous mitochondria from untreated astrocytes can be incorporated into injured astrocytes and fuse with their mitochondrial networks, improving cell viability by ameliorating mitochondrial dysfunction, redox stress, calcium overload, and inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) has a high incidence and mortality. Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis, progression, and metastasis of CRC., Aim: To investigate the effect of indole-3-acetaldehyde (IAAD) on CRC., Methods: The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines (HCT116 and DLD-1). Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests. Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide. Invasiveness was investigated using the transwell assay. Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor (AhR) downstream genes. The PharmMapper, SEA, and SWISS databases were used to screen for potential target proteins of IAAD, and the core proteins were identified through the String database., Results: IAAD reduced tumorigenesis in a syngeneic mouse model. In CRC cell lines HCT116 and DLD1, IAAD exhibited cytotoxicity starting at 24 h of treatment, while it reduced Ki67 expression in the nucleus. The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells, which may be related to the activation of AhR. IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells. At low concentrations (< 12.5 μmol/L), IAAD only exhibited cytotoxic effects without promoting cell invasion. In addition, predictions based on online databases, protein-protein interaction analysis, and molecular docking showed that IAAD can bind to matrix metalloproteinase-9 (MMP9), angiotensin converting enzyme (ACE), poly(ADP-ribose) polymerase-1 (PARP1), matrix metalloproteinase-2 (MMP2), and myeloperoxidase (MPO)., Conclusion: Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC; however, at high concentrations (≥ 25 μmol/L), it can also promote epithelial-mesenchymal transition and invasion in CRC cells. IAAD activates AhR and directly binds MMP9, ACE, PARP1, MMP2, and MPO, which partly reveals why it has a bidirectional effect., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: We declare no competing interests.

Purpose: Hypofractionated radiation therapy (HFRT) is a common treatment for thoracic tumors, typically delivered as 60 Gy in 15 fractions. We aimed to identify dosimetric risk factors associated with radiation pneumonitis in patients receiving HFRT at 4 Gy per fraction, focusing on lung V20, mean lung dose (MLD), and lung V5 as potential predictors of grade ≥2 pneumonitis., Methods and Materials: All patients were treated with thoracic HFRT to 60 Gy in 15 fractions or 72 Gy in 18 fractions at a single health care system from 2013 to 2020. Tumors near critical structures (trachea, proximal tracheobronchial tree, esophagus, spinal cord, or heart) were considered central (within 2 cm), and those closer were classified as ultracentral (within 1 cm). The primary endpoint was grade ≥2 pneumonitis. Logistic regression analyses, adjusting for target size and dosimetric variables, were used to establish a dose threshold associated with <20% risk of grade ≥2 pneumonitis., Results: During a median 24.3-month follow-up, 18 patients (16.8%) developed grade ≥2 radiation pneumonitis, with no significant difference between the 2 dose regimens (17.3% vs 16.3%, P = .88). Four patients (3.7%) experienced grade ≥3 pneumonitis, including 2 grade 5 cases. Patients with grade ≥2 pneumonitis had significantly higher lung V20 (mean 23.4% vs 14.5%, P < .001), MLD (mean 13.0 Gy vs 9.5 Gy, P < .001), and lung V5 (mean 49.6% vs 40.6%, P = .01). Dose thresholds for a 20% risk of grade ≥2 pneumonitis were lung V20 <17.7%, MLD <10.6 Gy, and V5 <41.3%. Multivariable analysis revealed a significant association between lung V20 and grade ≥2 pneumonitis (adjusted odds ratio, 1.48, P = .03)., Conclusions: To minimize the risk of grade ≥2 radiation pneumonitis when delivering 4 Gy per fraction at either 60 Gy or 72 Gy, it is advisable to maintain lung V20<17.7%. MLD <10.6 Gy and V5<41.3% can also be considered as lower-priority constraints. However, additional validation is necessary before incorporating these constraints into clinical practice or trial planning guidelines., Competing Interests: Disclosures Dr Park discloses the following relationships: AstraZeneca (consulting, advisory board), Bristol Myers Squibb (speaking fees/honoraria), Curio Sciences (consulting), G1 Therapeutics (speaking fees/honoraria), Galera Medical (advisory board), Merck (research funding), and RefleXion Medical (research funding, consulting). All other authors have no relevant disclosures., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Assessing the glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS) may be helpful for mild traumatic brain injury (mTBI) management., Purpose: To assess glymphatic function using DTI-ALPS and its associations with global white matter damage and cognitive impairment in mTBI., Study Type: Prospective., Population: Thirty-four controls (44.1% female, mean age 49.2 years) and 58 mTBI subjects (43.1% female, mean age 48.7 years), including uncomplicated mTBI (N = 32) and complicated mTBI (N = 26)., Field Strength/sequence: 3-T, single-shot echo-planar imaging sequence., Assessment: Magnetic resonance imaging (MRI) was done within 1 month since injury. DTI-ALPS was performed to assess glymphatic function, and peak width of skeletonized mean diffusivity (PSMD) was used to assess global white matter damage. Cognitive tests included Auditory Verbal Learning Test and Digit Span Test (forward and backward)., Statistical Tests: Neuroimaging findings comparisons were done between mTBI and control groups. Partial correlation and multivariable linear regression assessed the associations between DTI-ALPS, PSMD, and cognitive impairment. Mediation effects of PSMD on the relationship between DTI-ALPS and cognitive impairment were explored. P-value <0.05 was considered statistically significant, except for cognitive correlational analyses with a Bonferroni-corrected P-value set at 0.05/3 ≈ 0.017., Results: mTBI showed lower DTI-ALPS and higher PSMD, especially in complicated mTBI. DTI-ALPS was significantly correlated with verbal memory (r = 0.566), attention abilities (r = 0.792), executive function (r = 0.618), and PSMD (r = -0.533). DTI-ALPS was associated with verbal memory (β = 8.77, 95% confidence interval [CI] 5.00, 12.54), attention abilities (β = 5.67, 95% CI 4.56, 6.97), executive function (β = 2.34, 95% CI 1.49, 3.20), and PSMD (β = -0.79, 95% CI -1.15, -0.43). PSMD mediated 46.29%, 20.46%, and 24.36% of the effects for the relationship between DTI-ALPS and verbal memory, attention abilities, and executive function., Data Conclusion: Glymphatic function may be impaired in mTBI reflected by DTI-ALPS. Glymphatic dysfunction may cause cognitive impairment related to global white matter damage after mTBI., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Sphingosine-1-phosphate (S1P) is biologically active lipid, leading to neuroinflammation and macrophage invasion in central nervous system, plays an important role in the development of multiple sclerosis (MS) model in experimental allergic encephalomyelitis (EAE) rats. Vitamin D is observed to be a key factor in regulating cell S1P levels. We detected vitamin D can alleviate the symptoms of EAE rats, but the exact mechanism is unclear. In PC12 cells, vitamin D can reverse S1P-induced cell death, but the signaling pathway unclear. This study was aimed to investigate S1P regulation mechanism or signaling pathway mediated by vitamin D in EAE and PC12 model. In our experiments, S1P and Sphingosine kinase type 1 (SphK1) mRNA and protein expression in EAE rats group, control group, vitamin D feeding group were detected by HPLC, ELISA, RT-PCR and western blot. PC12 cell death was detected by Propidium (PI) staining. VDR plasmid overexpression and RNA interference, immunofluorescence, real-time cell analysis, protein immunoblotting was used to detect SphK1 transcriptional regulation, cell-substrate attachment quality, the signaling pathway of cell apoptosis and inflammation related gene expression (Bax/Bcl-2, Casepase-3, Il-6, TGF-β, TNF-α). Our study showed vitamin D can reverse the elevation of S1P level in EAE rats, reduce the severity and shorten the course of EAE. 1,25-(OH) 2 D 3 coupled with vitamin D receptor (VDR) inhibited SphK1 transcription. 1,25-(OH) 2 D 3 significantly reduced PC12 cell death rate induced by S1P, in addition improved the cell substrate attachment quality. 1,25-(OH) 2 D 3 can block S1P-induced p-ERK activation and PI3K /Akt signaling pathway reduced Il-6, TGF-β, TNF-α cytokine release and Bax/Bcl-2, Casepase-3 apoptosis protein expression. On the other hand, immunofluorescence staining showed 1,25-(OH) 2 D 3 can increase the expression of neuronal perinuclear protein MAP2 in PC12 cells probably protect nerve cells further. In summary, the ameliorative effect of vitamin D was derived from its ability to reduce S1P levels, provides an idea for vitamin D as a combination therapy for disease., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Chronic liver disease (CLD) imposes a heavy burden on millions of people worldwide. Despite substantial research on the pathogenesis of CLD disorders, no optimal treatment is currently available for some diseases, such as liver cancer. Exosomes, which are extracellular vesicles, are composed of various cellular components. Exosomes have unique functions in maintaining cellular homeostasis and regulating cell communication, which are associated with the occurrence of disease. Furthermore, they have application potential in diagnosis and treatment by carrying diverse curative payloads. Hepatic macrophages, which are key innate immune cells, show extraordinary heterogeneity and polarization. Hence, macrophage-derived exosomes may play a pivotal role in the initiation and progression of various liver diseases. This review focuses on the effects of macrophage-derived exosomes on liver disease etiology and their therapeutic potential, which will provide new insights into alleviating the global pressure of CLD., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Stereotactic ablative radiotherapy (SAbR) is an emerging non-invasive definitive treatment option for primary renal cell carcinoma (RCC), particularly when surgery is not ideal. Employing ablative doses, SAbR delivered in one to five fractions to the primary tumor has been shown to achieve high local control rates with favorable toxicity profile in multiple retrospective and prospective series, and has dispelled previous notions of RCC radio-resistance. Moreover, emerging evidence suggests possible immunomodulatory effects, leading to clinical investigations of SAbR in combination with systemic and surgical management in patients with metastatic disease. In this review, we summarize key evidence supporting SAbR delivered to the primary tumor including preclinical rationale, dose escalation studies, recent prospective trials, and outcomes from ongoing multi-institutional registries. We also discuss areas of active clinical investigation including the use of primary SAbR in combination with systemic therapies in patients with metastatic disease. The accumulated body of evidence supports SAbR as promising indication being increasingly incorporated into the multi-disciplinary management of primary RCC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

The genus Ciliochorella is a group of pestalotioid fungi, which typically occurs in subtropical and tropical areas. Species from the Ciliochorella genus play important roles in the decomposition of litter. In this study, we introduce two new species ( Ciliochorellachinensis sp. nov. and C.savannica sp. nov. ) that were found on leaf litter collected from savanna-like vegetation in hot dry valleys of southwestern China. Phylogenetic analyses of combined LSU, ITS and tub2 sequence datasets indicated that C.chinensis and C.savannica respectively form a distinct clade within the Ciliochorella genus. The comparison of the morphological characteristics indicated that the two new species are well differentiated within this genus species. Analysis of the evolutionary history suggests that Ciliochorella originated from the Eurasian continent during the Paleogene (38 Mya). Further, we find that both new species can produce cellulase and laccase, playing a decomposer role., Competing Interests: The authors have declared that no competing interests exist., (Jia-Yu Song, Hai-Xia Wu, Jin-Chen Li, Wei-Feng Ding, Cui-Ling Gong, Xiang-Yu Zeng, Nalin N. Wijayawardene, Da-Xin Yang.)

Sarcopenia is a common skeletal muscle degenerative disease characterized by decreased skeletal muscle mass and mitochondrial dysfunction that involves microRNAs (miR) as regulatory factors in various pathways. Exercise reduces age-related oxidative damage and chronic inflammation and increases autophagy, among others. Moreover, whether aerobic exercise can regulate mitochondrial homeostasis by modulating the miR-128/insulin-like growth factor-1 (IGF-1) signaling pathway and can improve sarcopenia requires further investigation. Interestingly, zebrafish have been used as a model for aging research for over a decade due to their many outstanding advantages. Therefore, we established a model of zebrafish sarcopenia using d-galactose immersion and observed substantial changes, including reduced skeletal muscle cross-sectional area, increased tissue fibrosis, decreased motility, increased skeletal muscle reactive oxygen species, and notable alterations in mitochondrial morphology and function. We found that miR-128 expression was considerably upregulated, where as Igf1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were significantly downregulated; moreover, mitochondrial homeostasis was reduced. Four weeks of aerobic exercise delayed sarcopenia progression and prevented the disruption of mitochondrial function and homeostasis. The genes related to atrophy and miR-128 were downregulated, Igf1 expression was considerably upregulated, and the phosphorylation levels of Pi3k, Akt, and Foxo3a were upregulated. Furthermore, mitochondrial respiration and homeostasis were enhanced. In conclusion, aerobic exercise improved skeletal muscle quality and function via the miR-128/IGF-1 signaling pathway, consequently ameliorating mitochondrial homeostasis in aging skeletal muscle., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Studies have found that the phosphatase actin regulatory factor 1 expression can be related to stroke, but it remains unclear whether changes in phosphatase actin regulatory factor 1 expression also play a role in traumatic brain injury. In this study we found that, in a mouse model of traumatic brain injury induced by controlled cortical impact, phosphatase actin regulatory factor 1 expression is increased in endothelial cells, neurons, astrocytes, and microglia. When we overexpressed phosphatase actin regulatory factor 1 by injection an adeno-associated virus vector into the contused area in the traumatic brain injury mice, the water content of the brain tissue increased. However, when phosphatase actin regulatory factor 1 was knocked down, the water content decreased. We also found that inhibiting phosphatase actin regulatory factor 1 expression regulated the nuclear factor kappa B signaling pathway, decreased blood-brain barrier permeability, reduced aquaporin 4 and intercellular adhesion molecule 1 expression, inhibited neuroinflammation, and neuronal apoptosis, thereby improving neurological function. The findings from this study indicate that phosphatase actin regulatory factor 1 may be a potential therapeutic target for traumatic brain injury., Competing Interests: None

Nitrogen deposition has serious consequences to global change. Excessive nitrogen deposition leads to nitrogen saturation in forests, resulting in soil acidification, nitrate leaching, an increase in nitrous oxide emissions, and a decrease in plant species diversity and vegetation productivity. Under the reduction of atmospheric nitrogen deposition in Europe, North America, and China, summarizing the response of forests to decreasing nitrogen deposition can not only improve the knowledge framework of the impact of nitrogen deposition on forests, but also evaluate the effects of emission abatement actions, as well as provide scientific basis for future air pollution control. This study reviewed the response of soil, surface water, nitrogen cycle, and vegetation of temperate forests in Europe and North America and subtropical forests in southwest China to the reduction in atmospheric nitrogen pollution gases and thus nitrogen deposition. The soil water nitrogen concentration responded rapidly to the nitrogen deposition reduction, although the trend was inconsistent. The soil acidification and nitrogen cycles showed a delayed response of recovery from high nitrogen deposition. The nitrogen mineralization and immobilization, soil carbon retention, and net primary production might take decades to respond to the nitrogen deposition reduction. However, the soil inorganic nitrogen pool and nitrogen leaching decreased with the decline in nitrogen deposition, although a one-or two-year lag existed. The surface water nitrogen concentration was closely related to nitrogen status in forests. After the nitrogen deposition decreased, the nitrogen leaching and thus the surface water nitrogen concentration decreased in the areas with historically high nitrogen deposition. However, the low surface water nitrogen concentration in the nitrogen-limited forests was not significantly affected by the nitrogen deposition changes. The recovery of surface water acidification was affected by soil sulfur desorption/mineralization and nitrification/denitrification. The foliar nitrogen concentration decreased with the decline in nitrogen deposition. The nitrogen-saturated forests and regional surface water in southwest China showed a recovery trend from high nitrogen deposition, as a consequence of the implementation of the Total Emissions Control of Air Pollutants and later the Action Plan of Air Pollution Prevention and Control.

Background: Myxomas are the most common primary cardiac tumors. Intracardiac myxomas, although benign, could cause serious consequences such as tricuspid or mitral valve obstruction, hemodynamic collapse, and acute heart failure, which pose challenges during anesthetic management. The current study was designed to summarize the anesthetic management of patients undergoing cardiac myxoma resection., Methods: This study was performed retrospectively from the perioperative period of patients who underwent myxoma resection. Patients were divided into two groups according to whether the myxoma prolapsed into the ventricle (group O) or not (group N) to evaluate the impact of tricuspid or mitral valve with obstruction., Results: 110 patients, aged 17-78 years, undergoing cardiac myxoma resection between January 2019 and December 2021 were collected, and their perioperative characteristics were recorded. In the preoperative evaluation, common clinical symptoms included dyspnea and palpitation, whereas embolic events occurred in 8 patients, including 5 (4.5%) cerebral thromboembolic events, 2 (1.8%) femoral artery, and 1 (0.9%) obstructive coronary artery. According to the echocardiography, left atrial myxoma was detected in 104 (94.5%) patients, the average dimension of myxoma was 4.03 cm ± 1.52 cm in the largest diameter, and 48 patients were divided into group O. During intraoperative anesthetic management, hemodynamic instability occurred in 38 (34.5%) patients after anesthesia induction. More patients in group O had hemodynamic instability (47.9% vs. 24.2%, p  = 0.009) than in group N. The mean postoperative length of stay in the hospital was 10.64 ± 3.01 days, and most of the patients made an uneventful postoperative recovery., Conclusions: Anesthetic management for myxoma resection can be composed by assessing the myxoma, particularly the echocardiography evaluation and preventing cardiovascular instability. Typically, tricuspid or mitral valve with obstruction is a premier ingredient in anesthetic management., Competing Interests: 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., (© 2023 Qi, Yu, Yang, Hu, Chen, Yao and the Evidence in Cardiovascular Anesthesia (EICA) Group.)

Currently, porcine coronaviruses are prevalent in pigs, and due to the outbreak of COVID-19, porcine coronaviruses have become a research hotspot. porcine epidemic diarrhea virus (PEDV), Transmissible Gastroenteritis Virus (TGEV), and Porcine Deltacoronavirus (PDCoV) mentioned in this study mainly cause diarrhea in pigs. These viruses cause significant economic losses and pose a potential public health threat. In this study, specific primers and probes were designed according to the M gene of PEDV, the S gene of TGEV, and the M gene of PDCoV, respectively, and TaqMan probe-based multiplex real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was developed for the simultaneous detection of PEDV, TGEV, and PDCoV. This method has high sensitivity and specificity, and the detection limit of each virus can reach 2.95 × 10 0 copies/μl. An assay of 160 clinical samples from pigs with diarrhea showed that the positive rates of PEDV, TGEV, and PDCoV were 38.13, 1.88, and 5.00%; the coinfection rates of PEDV+TGEV, PEDV+PDCoV, TGEV+PDCoV, PEDV+TGEV+PDCoV were 1.25, 1.25, 0, 0.63%, respectively. The positive coincidence rates of the multiplex qRT-PCR and single-reaction qRT-PCR were 100%. This method is of great significance for clinical monitoring of the porcine enteric diarrhea virus and helps reduce the loss of the breeding industry and control the spread of the disease., Competing Interests: 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 © 2023 Li, Niu, Zhou, Chu, Zhang, Gou, Yang, Zhang, Li, Liao and Zhai.)

Deep learning (DL) models have demonstrated state-of-the-art performance in the classification of diagnostic imaging in oncology. However, DL models for medical images can be compromised by adversarial images, where pixel values of input images are manipulated to deceive the DL model. To address this limitation, our study investigates the detectability of adversarial images in oncology using multiple detection schemes. Experiments were conducted on thoracic computed tomography (CT) scans, mammography, and brain magnetic resonance imaging (MRI). For each dataset we trained a convolutional neural network to classify the presence or absence of malignancy. We trained five DL and machine learning (ML)-based detection models and tested their performance in detecting adversarial images. Adversarial images generated using projected gradient descent (PGD) with a perturbation size of 0.004 were detected by the ResNet detection model with an accuracy of 100% for CT, 100% for mammogram, and 90.0% for MRI. Overall, adversarial images were detected with high accuracy in settings where adversarial perturbation was above set thresholds. Adversarial detection should be considered alongside adversarial training as a defense technique to protect DL models for cancer imaging classification from the threat of adversarial images.

Background: According to the pathoanatomic classification system, progressive hemorrhagic injury (PHI) can be categorized into progressive intraparenchymal contusion or hematoma (pIPCH), epidural hematoma (pEDH), subdural hematoma (pSDH), and traumatic subarachnoid hemorrhage (ptSAH). The clinical features of each type differ greatly. The objective of this study was to determine the predictors, clinical management, and outcomes of PHI according to this classification., Methods: Multivariate logistic regression analysis was used to identify independent risk factors for PHI and each subgroup. Patients with IPCH or EDH were selected for subgroup propensity score matching (PSM) to exclude confounding factors before evaluating the association of hematoma progression with the outcomes by classification., Results: In the present cohort of 419 patients, 123 (29.4%) demonstrated PHI by serial CT scan. Of them, progressive ICPH (58.5%) was the most common type, followed by pEDH (28.5%), pSDH (9.8%), and ptSAH (3.2%). Old age (≥ 60 years), lower motor Glasgow Coma Scale score, larger primary lesion volume, and higher level of D-dimer were independent risk factors related to PHI. These factors were also independent predictors for pIPCH, but not for pEDH. The time to first CT scan and presence of skull linear fracture were robust risk factors for pEDH. After PSM, the 6-month mortality and unfavorable survival rates were significantly higher in the pIPCH group than the non-pIPCH group (24.2% vs. 1.8% and 12.1% vs. 7.3%, respectively, p < 0.001), but not significantly different between the pEDH group and the non-pEDH group., Conclusions: Understanding the specific patterns of PHI according to its classification can help early recognition and suggest targeted prevention or treatment strategies to improve patients' neurological outcomes., (© 2023. The Author(s).)

Sirtuin 2 (SIRT2) inhibition or Sirt2 knockout in animal models protects against the development of neurodegenerative diseases and cerebral ischemia. However, the role of SIRT2 in traumatic brain injury (TBI) remains unclear. In this study, we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema, attenuated disruption of the blood-brain barrier, decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, reduced the activity of the effector caspase-1, reduced neuroinflammation and neuronal pyroptosis, and improved neurological function. Knockout of Sirt2 in a mechanical stretch injury cell model in vitro also decreased expression of the NLRP3 inflammasome and pyroptosis. Our findings suggest that knockout of Sirt2 is neuroprotective against TBI; therefore, Sirt2 could be a novel target for TBI treatment., Competing Interests: None

Objective: The role of radiation therapy (RT) in melanoma has historically been limited to palliative care, with surgery as the primary treatment modality. However, adjuvant RT can be a powerful tool in certain cases and its application in melanoma has been increasingly explored in recent years. The aim of this study is to explore national patterns of care and associations surrounding the use of adjuvant RT for stage III melanoma., Methods: The National Cancer Data Base (NCDB) was used to identify patients who were diagnosed with stage III melanoma between 2004 and 2014. Exclusion criteria included those with distant metastatic disease, in-situ histology, no confirmed positive nodes, palliative intent therapy, and dosing regimens inconsistent with National Comprehensive Cancer Network (NCCN) guidelines for adjuvant RT in melanoma. Patients treated with and without adjuvant RT were compared and factors associated with use of adjuvant RT were identified using multivariable logistic regression analyses., Results: A total of 7,758 cases of stage III melanoma were analyzed, of which 11.7% received adjuvant RT. The mean age of the overall cohort was 58.5 years, and the majority of patients were male (64.7%), white (96.6%), on private insurance (51.3%), and presented to a non-high-volume facility (90.3%). Multivariable regression analyses revealed that patients who present to the hospital in 2009-2014 as compared to 2004-2008 (odds ratio [OR] 1.61, 95% confidence interval [CI] 1.36-1.92), had 4 or more positive nodes (OR 4.30, 95% CI 3.67-5.04), and had microscopic residual tumor (OR 2.11, 95% CI 1.46-3.04) were more likely to receive adjuvant RT. Factors that were negatively associated with receiving adjuvant RT included female gender (OR 0.72, 95% CI 0.61-0.85) and median income of at least $63,000 (OR 0.66, 95% CI 0.52-0.83)., Conclusions: This study demonstrates the rising use of RT for stage III melanoma in recent years and identifies demographic, social, clinical, and hospital-specific factors associated with patients receiving adjuvant RT. Further investigation is needed to explore disease benefits to improve guidance on the utilization of RT in melanoma., Competing Interests: JL serves on the La Roche Posay Advisory Board. The remaining 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 © 2023 King, Lee, Yu, Mirza, Zogg, Yang, Tran, Leventhal and An.)

Objective: To explore the effect of macrophage-derived exosomes on the activation of hepatic stellate cells and its possible mechanism. Methods: Differential ultracentrifugation was used to extract macrophage exosomes. The exosomes were co-cultured with the mouse hepatic stellate cell line JS1, and a control group was established with phosphate buffered saline (PBS). Cell immunofluorescence was used to observe the expressional conditions of F-actin. Cell counting kit-8 (CCK8) was used to detect the survival rate of JS1 cells in the two groups. The activation indices of JS1 cells [collagen type Ⅰ (Col Ⅰ) and α-smooth muscle actin (α-SMA)] and its key signal pathway activation index expression level [transforming growth factor (TGF)-β1/Smads, platelet-derived growth factor (PDGF)] in the two groups were determined using Western blot and RT-PCR. Data comparison between two groups was performed using an independent sample t-test. Results: The membrane structure of exosomes was clearly observed by transmission electron microscopy. The expression of exosome marker proteins CD63 and CD81 was positive, suggesting that exosomes were successfully extracted. Exosomes were co-cultured with JS1 cells. Compared with the PBS control group, there was no statistically significant difference in the proliferation rate of JS1 cells in the exosomes group ( P ＞0.05). The expression of F-actin was significantly increased in the exosome group. The mRNA and protein expression levels of α-SMA and ColⅠwere significantly increased in exosome group JS1 cells (all P ＜0.05). The mRNA relative expression levels of α-SMA in PBS and exosome group were 0.25±0.07 and 1.43±0.19, respectively, while that of ColⅠ was 1.03±0.04 and 1.57±0.06, respectively. The mRNA and protein expressions of PDGF were significantly increased in exosome group JS1 cells ( P ＜0.05). The mRNA relative expression levels of PDGF in the PBS group and exosome group were 0.27±0.04 and 1.65±0.12, respectively. There were no statistically significant differences in the mRNA and protein expressions of TGF-β1, Smad2 and Smad3 between the two groups ( P ＞0.05). Conclusion: Macrophage-derived exosomes significantly promote the activation of hepatic stellate cells. JS1 cells may be the underlying mechanism for the up-regulation of PDGF expression.

Edwardsiella tarda represents one of the most important pathogens that infects a variety of hosts including aquatic animals and humans. The outbreak of E. tarda infection is frequently reported in aquaculture that causes huge economic loss. Due to the widespread of antibiotic resistance, available antibiotics to treat bacterial infection are limited. Therefore, enhancing aquatic animals to survive upon E. tarda infection become an urgent issue. In this study, we profiled the metabolomic change of tilapia in-between the dying and survival fish upon E. tarda infection. The dying and survival fish mounts differential metabolic response, from which we identify a key metabolite, taurine, whose abundance is increased in both the survival group and the dying group but is more significant in the survival group. Exogenous taurine increases tilapia survival rate by 37.5% upon E. tarda infection. Further quantitative PCR analysis demonstrate taurine increases the expression of immune genes in liver, spleen and head kidney. Therefore, our study shows a new strategy to enhance fish immune response against bacterial infection., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Urolithin A (UA) is a natural metabolite produced from polyphenolics in foods such as pomegranates, berries, and nuts. UA is neuroprotective against Parkinson's disease, Alzheimer's disease, and cerebral hemorrhage. However, its effect against traumatic brain injury remains unknown. In this study, we established adult C57BL/6J mouse models of traumatic brain injury by controlled cortical impact and then intraperitoneally administered UA. We found that UA greatly reduced brain edema; increased the expression of tight junction proteins in injured cortex; increased the immunopositivity of two neuronal autophagy markers, microtubule-associated protein 1A/B light chain 3A/B (LC3) and p62; downregulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR), two regulators of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathway; decreased the phosphorylation levels of inhibitor of NFκB (IκB) kinase alpha (IKKα) and nuclear factor kappa B (NFκB), two regulators of the neuroinflammation-related Akt/IKK/NFκB signaling pathway; reduced blood-brain barrier permeability and neuronal apoptosis in injured cortex; and improved mouse neurological function. These findings suggest that UA may be a candidate drug for the treatment of traumatic brain injury, and its neuroprotective effects may be mediated by inhibition of the PI3K/Akt/mTOR and Akt/IKK/NFκB signaling pathways, thus reducing neuroinflammation and enhancing autophagy., Competing Interests: None

Background Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL). Although it often has an indolent course, it can progress to more aggressive CTCL forms. There is sparse data in current literature describing specific clinical factors associated with in-hospital mortality in mycosis fungoides patients. An understanding of patients at greatest risk for in-hospital mortality can aid in developing recommendations for prophylaxis and empirical management. Aim We aim to characterize factors associated with in-hospital mortality in MF patients. Materials and methods The Nationwide Emergency Department Sample (NEDS) was queried for MF cases from 2006 to 2015. Baseline demographic and hospital characteristics were stratified based on survival outcomes. Multivariable logistic regression was used to identify factors associated with in-hospital mortality. Results A total of 57,665 patients with MF presenting to the ED between 2006 and 2015 were identified. Sézary syndrome, sepsis, and advanced age were associated with MF in-hospital mortality, while female sex was inversely associated. There was a downtrend in in-hospital mortality among MF patients presenting to the ED from 2006 to 2015. Conclusions Our study highlights factors crucial for risk-stratification for hospitalized MF patients., Competing Interests: James B. Yu receives speaking and consulting fees from Boston Scientific and advisory board fees from Galera Pharmaceuticals. Michael Girardi is on the advisory board for Mallinckrodt and receives research funding support from AbbVie. None of these are relevant to the present work., (Copyright © 2022, King et al.)

The 2D self-assemblies and structural transitions of pentacene on a Cd(0001) surface have been investigated with low temperature scanning tunneling microscopy (STM). With increasing coverage, pentacene molecules show a structural evolution from the initial disordered gas-like phase through the porous network phase to the herringbone phase, and finally to the brickwall phase at the full monolayer. In particular, orientational frustration and cooperative rotation of pentacene molecules take place in the herringbone phase. Furthermore, successive STM scanning leads to structural interconversions between the porous network phase, herringbone phase, and brickwall phase, indicating the metastability of the 2D assembled structures of pentacene on Cd(0001). These structural transitions and interconversion can be attributed to the interplay between the repulsive electrostatic forces resulting from the charge transfer from the substrate to pentacene and the attractive effects originating from dipole-dipole interactions and intermolecular van der Waals forces.

Objective: To investigate the association of MRI-visible perivascular spaces (PVS) with cognitive impairment in military veterans with traumatic brain injury (TBI), and whether cerebrospinal fluid (CSF) p-tau and Aβ mediate this effect., Materials and Methods: We included 55 Vietnam War veterans with a history of TBI and 52 non-TBI Vietnam War veterans from the Department of Defense Alzheimer's Disease Neuroimaging Initiative (ADNI) database. All the subjects had brain MRI, CSF p-tau, Aβ, and neuropsychological examinations. MRI-visible PVS number and grade were rated on MRI in the centrum semiovale (CSO-PVS) and basal ganglia (BG-PVS). Multiple linear regression was performed to assess the association between MRI-visible PVS and cognitive impairment and the interaction effect of TBI. Additionally, mediation effect of CSF biomarkers on the relationship between MRI-visible PVS and cognitive impairment was explored in TBI group., Results: Compared with military control, TBI group had higher CSO-PVS number ( p = 0.001), CSF p-tau ( p = 0.022) and poorer performance in verbal memory ( p = 0.022). High CSO-PVS number was associated with poor verbal memory in TBI group (β = -0.039, 95% CI -0.062, -0.016), but not in military control group (β = 0.019, 95% CI -0.004, 0.043) ( p -interaction = 0.003). Further mediation analysis revealed that CSF p-tau had a significant indirect effect (β = -0.009, 95% CI: -0.022 -0.001, p = 0.001) and mediated 18.75% effect for the relationship between CSO-PVS and verbal memory in TBI group., Conclusion: MRI-visible CSO-PVS was more common in Vietnam War veterans with a history of TBI and was associated with poor verbal memory, mediated partially by CSF p-tau., Competing Interests: 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 © 2022 Wang, Yang, Sun, Li, Zou, Li, Wu and Li.)

The problem of fraud in China's health insurance has existed for a long time and is becoming more serious, which needs to be solved urgently. This article constructs a tripartite evolutionary game model to study the formation mechanism of the Health Insurance fraud, game participants including medical administrative organization (MAO, a government department responsible for health insurance supervision), medical institutions (MI, such as hospitals), and insured individuals (II, who participating in medical and healthcare insurance). By analyzing the equilibrium of the tripartite evolutionary game, this paper makes an in-depth study on the formation and resolution of health insurance fraud. The results show that: (1) How to prevent the fraud behavior of the medical institutions is the difficulty and core of the problem. It is necessary to achieve effective supervision of the MAO, improve the internal management of the MI and give play to the supervisory role of the II. (2) The regulatory behavior of the MAO needs to focus on protecting the interests of the II, not only to encourage them to actively play the role of supervision and reporting but also to prevent their collusion with MI. (3) On the one hand, the MAO needs to strengthen supervision and increase the punishment for fraud. On the other hand, they also need to take incentive measures to guide all subjects to form a sound internal management mechanism., Competing Interests: 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 © 2022 Fei, Fu, Yang and Hu.)

Immunotherapy has become the breakthrough strategies for treatment of cancer in recent years. The application of messenger RNA in cancer immunotherapy is gaining tremendous popularity as mRNA can function as an effective vector for the delivery of therapeutic antibodies on immune targets. The high efficacy, decreased toxicity, rapid manufacturing and safe administration of mRNA vaccines have great advantages over conventional vaccines. The unprecedent success of mRNA vaccines against infection has proved its effectiveness. However, the instability and inefficient delivery of mRNA has cast a shadow on the wide application of this approach. In the past decades, modifications on mRNA structure and delivery methods have been made to solve these questions. This review summarizes recent advancements of mRNA vaccines in cancer immunotherapy and the existing challenges for its clinical application, providing insights on the future optimization of mRNA vaccines for the successful treatment of cancer., Competing Interests: 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 © 2022 Duan, Wang, Zhang, Yang and Zhang.)

Chiral resolution is of fundamental importance to conglomerate or racemate crystallization. Here we demonstrate that the spontaneous chiral resolution of pentahelicene racemates occurred in the monolayer domains. When deposited on a Cd(0001) surface, pentahelicene molecules crystallize into a commensurate (6 × 6) R 0° structure built mainly from homochiral trimers. Spontaneous chirality separation takes place in the form of opposite mirror domains, where 2D enantiomorphism is not expressed by the oblique adlattice, but by the supramolecular chirality of the pentahelicene trimers. Furthermore, annealing the sample or extreme close-packing lead to the presence of lattice handedness through the formation of a porous network structure or an edge-on phase. These results provide valuable insight for 2D conglomerate crystallization and stereochemical recognition.

Purpose: Deep learning (DL) models have rapidly become a popular and cost-effective tool for image classification within oncology. A major limitation of DL models is their vulnerability to adversarial images, manipulated input images designed to cause misclassifications by DL models. The purpose of the study is to investigate the robustness of DL models trained on diagnostic images using adversarial images and explore the utility of an iterative adversarial training approach to improve the robustness of DL models against adversarial images., Methods: We examined the impact of adversarial images on the classification accuracies of DL models trained to classify cancerous lesions across three common oncologic imaging modalities. The computed tomography (CT) model was trained to classify malignant lung nodules. The mammogram model was trained to classify malignant breast lesions. The magnetic resonance imaging (MRI) model was trained to classify brain metastases., Results: Oncologic images showed instability to small pixel-level changes. A pixel-level perturbation of 0.004 (for pixels normalized to the range between 0 and 1) resulted in most oncologic images to be misclassified (CT 25.6%, mammogram 23.9%, and MRI 6.4% accuracy). Adversarial training improved the stability and robustness of DL models trained on oncologic images compared with naive models ([CT 67.7% v 26.9%], mammogram [63.4% vs 27.7%], and MRI [87.2% vs 24.3%])., Conclusion: DL models naively trained on oncologic images exhibited dramatic instability to small pixel-level changes resulting in substantial decreases in accuracy. Adversarial training techniques improved the stability and robustness of DL models to such pixel-level changes. Before clinical implementation, adversarial training should be considered to proposed DL models to improve overall performance and safety., Competing Interests: Enoch ChangResearch Funding: Radiological Society of North America James S. DuncanPatents, Royalties, Other Intellectual Property: Systems, Methods and Apparatuses for Generating Regions of Interest from Voxel Mode Based Thresholds, Publication No: US20190347788A1, application No. 15/978,904. Filed on May 14, 2018, Publication Date: November 14, 2019. Inventors: Van Breugel J, Abajian A, Treli- hard J, Smolka S, Chapiro J, Duncan JS and Lin M. Joint application from Philips, N.V. and Yale University. US Patent 10,832,403 (2020) Antonio OmuroConsulting or Advisory Role: Merck, KIYATEC, Ono Pharmaceutical, BTGResearch Funding: Arcus Biosciences (Inst) Roy HerbstLeadership: Jun Shi Pharmaceuticals, ImmunocoreConsulting or Advisory Role: AstraZeneca, Genentech/Roche, Merck, Pfizer, AbbVie, Biodesix, Bristol Myers Squibb, Lilly, EMD Serono, Heat Biologics, Jun Shi Pharmaceuticals, Loxo, Nektar, NextCure, Novartis, Sanofi, Seattle Genetics, Shire, Spectrum Pharmaceuticals, Symphogen, TESARO, Neon Therapeutics, Infinity Pharmaceuticals, ARMO Biosciences, Genmab, Halozyme, Tocagen, Bolt Biotherapeutics, IMAB Biopharma, Mirati Therapeutics, Takeda, Cybrexa Therapeutics, eFFECTOR Therapeutics, Inc, Candel Therapeutics, Inc, Oncternal Therapeutics, STCube Pharmaceuticals, Inc, WindMIL Therapeutics, Xencor, Inc, Bayer HealthCare Pharmaceuticals Inc, Checkpoint Therapeutics, DynamiCure Biotechnology, LLC, Foundation Medicine, Inc, Gilead/Forty Seven, HiberCell, Inc, Immune-Onc Therapeutics, Inc, Johnson and Johnson, Ocean Biomedical, Inc, Oncocyte Corp, Refactor Health, Inc, Ribbon Therapeutics, Ventana Medical Systems, IncResearch Funding: AstraZeneca, Merck, Lilly, Genentech/Roche Harlan M. KrumholzEmployment: Hugo Health (I), FPrimeStock and Other Ownership Interests: Element Science, Refactor Health, Hugo HealthConsulting or Advisory Role: UnitedHealthcare, AetnaResearch Funding: Johnson and JohnsonExpert Testimony: Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm Sanjay AnejaSanjay Aneja is an Associate Editor for JCO Clinical Cancer Informatics. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Prophet Consulting (I)Research Funding: The MedNet, Inc, American Cancer Society, National Science Foundation, Agency for Healthcare Research and Quality, National Cancer Institute, ASCOPatents, Royalties, Other Intellectual Property: Provisional patent of deep learning optimization algorithmTravel, Accommodations, Expenses: Prophet Consulting (I), Hope FoundationOther Relationship: NRG Oncology Digital Health Working Group, SWOG Digital Engagement Committee, ASCO mCODE Technical Review GroupNo other potential conflicts of interest were reported.

Our previous study showed that cell cycle exit and neuronal differentiation 1 (CEND1) may participate in neural stem cell cycle exit and oriented differentiation. However, whether CEND1-transfected neural stem cells can improve the prognosis of traumatic brain injury remained unclear. In this study, we performed quantitative proteomic analysis and found that after traumatic brain injury, CEND1 expression was downregulated in mouse brain tissue. Three days after traumatic brain injury, we transplanted CEND1-transfected neural stem cells into the area surrounding the injury site. We found that at 5 weeks after traumatic brain injury, transplantation of CEND1-transfected neural stem cells markedly alleviated brain atrophy and greatly improved neurological function. In vivo and in vitro results indicate that CEND1 overexpression inhibited the proliferation of neural stem cells, but significantly promoted their neuronal differentiation. Additionally, CEND1 overexpression reduced protein levels of Notch1 and cyclin D1, but increased levels of p21 in CEND1-transfected neural stem cells. Treatment with CEND1-transfected neural stem cells was superior to similar treatment without CEND1 transfection. These findings suggest that transplantation of CEND1-transfected neural stem cells is a promising cell therapy for traumatic brain injury. This study was approved by the Animal Ethics Committee of the School of Biomedical Engineering of Shanghai Jiao Tong University, China (approval No. 2016034) on November 25, 2016., Competing Interests: None

Objectives: This study aimed to determine the performance of Sonazoid-based contrast-enhanced ultrasound (CEUS) in the microwave ablation (MWA) of primary hyperparathyroidism (pHPT)., Methods: Forty patients with pHPT were enrolled and treated with percutaneous ultrasound (US)-guided MWA assisted by CEUS. All patients underwent immediate CEUS examinations following MWA. On post-ablation day 1, patients who did not display a decrease in intact parathyroid hormone (iPTH) levels to the norm were examined by CEUS to evaluate an incomplete ablation. We compared the serum iPTH and calcium levels and the nodule volumes before and after MWA. The complications were evaluated during and after treatment., Results: Immediately following MWA, CEUS demonstrated complete ablation with all 44 parathyroid nodules. On post-ablation day 1, five nodules in five patients displayed annular enhancement around the ablation zone on CEUS. The average maximum diameters of the nodules and the ablation zone were 1.09 ± 0.28 cm and 1.36 ± 0.23 cm, respectively. An ablation zone larger than the primary lesion ( p  < 0.05) generated a higher rate of complete ablation. Compared with pre-MWA, serum iPTH and calcium levels were significantly improved. Treatment success was achieved in 38 patients (95%). Hoarseness was a major complication in six patients (15%); however, it improved spontaneously within 1-4 months. We observed two recurrences (2/40, 5%) at 9 months and 11 months following MWA, respectively., Conclusion: US-guided percutaneous MWA assisted by CEUS for pHPT is an effective and safe therapy. CEUS can avoid operative failure and improve the cure rate.

Introduction: Several studies have investigated the efficacy of human urinary kallidinogenase (HUK) combined with edaravone (Eda) in acute ischemic stroke (AIS) patients. Our aim was to provide the best available evidence for clinical practice and further research programs for stroke treatment., Methods: We searched the online database for paper published between January 2015 and April 2021. We calculated weighted mean difference (WMD) or odds risk (OR) and their corresponding 95% confidence interval (95% CI) of reported outcomes between HUK plus Eda and Eda groups for each study. The random-effect models or fixed-effect models were used to pool the analysis., Results: Thirteen studies with 1242 patients were included. In the pooled analysis, the scores of NIHSS in the HUK plus Eda group were significantly lower than that in patients receiving Eda (WMD = -3.92, 95% CI (-4.82, -3.02), p < .0001). The ADL scores in the HUK plus Eda group were significantly greater than that in patients receiving Eda (WMD = 14.13, 95% CI (10.67, 17.60), p < .0001). Furthermore, HUK plus Eda was associated with a higher rate of total efficacy (OR = 3.97, 95% CI (2.81, 5.59), p < .0001)., Conclusions: HUK combined with Eda provides potential clinical benefits as a treatment for AIS. Further high-quality, large-scale randomized trials are needed to confirm these results., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Phytosterols oleogel-based flavor emulsions were successfully fabricated for the first time using natural tea saponin as emulsifier and one-pot ultrasonic technique. The effects of ultrasonic time and power, surfactant concentration, and type of flavor oils (e.g., orange, lemon and peppermint) on the emulsion droplet size were investigated. Submicron emulsions with a dispersed phase made by flavor oil (20 wt%) + phytosterol (4 wt%) were stabilized with 3 wt% saponin were obtained by applying an ultrasonic time of 5 min and ultrasonic power of 280 W. The natural tea saponin emulsions exhibited a superior stability and encapsulation efficiency of phytosterol, compared to traditional emulsifiers. Flavor oil-phytosterol enriched powders were prepared by spray-drying and characterized by SEM, XRD and repose angle. The natural saponin encapsulated oil + phytosterol powders had excellent fluidity, redispersion behavior and low phytosterol crystallinity. It was demonstrated that ultrasound is an effective and suitable technique for fabricating fortified flavor emulsions and microcapsules, which may be used for developing functional lipids-based applications in the food, beverage and cosmetic industries., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Overactive immune response is a critical factor triggering host death upon bacterial infection. However, the mechanism behind the regulation of excessive immune responses is still largely unknown, and the corresponding control and preventive measures are still to be explored. In this study, we find that Nile tilapia, Oreochromis niloticus , that died from Edwardsiella tarda infection had higher levels of immune responses than those that survived. Such immune responses are strongly associated with metabolism that was altered at 6 h postinfection. By gas chromatography-mass spectrometry-based metabolome profiling, we identify glycine, serine, and threonine metabolism as the top three of the most impacted pathways, which were not properly activated in the fish that died. Serine is one of the crucial biomarkers. Exogenous serine can promote O. niloticus survival both as a prophylactic and therapeutic upon E. tarda infection. Our further analysis revealed exogenous serine flux into the glycine, serine, and threonine metabolism and, more importantly, the glutathione metabolism via glycine. The increased glutathione synthesis could downregulate reactive oxygen species. Therefore, these data together suggest that metabolic modulation of immune responses is a potential preventive strategy to control overactive immune responses. IMPORTANCE Bacterial virulence factors are not the only factors responsible for host death. Overactive immune responses, such as cytokine storm, contribute to tissue injury that results in organ failure and ultimately the death of the host. Despite the recent development of anti-inflammation strategies, the way to tune immune responses to an appropriate level is still lacking. We propose that metabolic modulation is a promising approach in tuning immune responses. We find that the metabolomic shift at as early as 6 h postinfection can be predictive of the consequences of infection. Serine is a crucial biomarker whose administration can promote host survival upon bacterial infection either in a prophylactic or therapeutic way. Further analysis demonstrated that exogenous serine promotes the synthesis of glutathione, which downregulates reactive oxygen species to dampen immune responses. Our study exemplifies that the metabolite(s) is a potential therapeutic reagent for overactive immune response during bacterial infection.

Objective: To explore the clinical characteristics and risk factors of patients with Coronavirus Disease 2019 (COVID-19) when developing multiple organ dysfunction syndrome (MODS). Methods: Data from 458 inpatients of confirmed COVID-19 in Wuhan, Shanghai and Tongling from December 29, 2019 to March 24, 2020 were retrospectively collected. COVID-19 was confirmed by real-time RT-PCR of throat swab samples. Data of demographics, clinical presentation, laboratory tests, imaging findings, treatment and prognosis were obtained from medical record and compared between COVID-19 patients with and without MODS. Risk factors for the development of MODS were analyzed by univariate and multivariate logistic regression analysis. Results: Of the 458 COVID-19 patients (266 from Wuhan, 208 from Shanghai, and 24 from Tongling), 103 developed transient or persistent MODS in the course. More male patients were found in those with MODS (72.8% vs 54.6%, P= 0.001). And MODS patients were of older age (72.8% vs 54.6%, P= 0.001), more chronic comorbidities (68.0% vs 43.4%, P <0.001), and longer onset-to-admission interval (9.0 vs 7.0 d, P <0.001). In addition, patients with MODS had more expectoration (45.6% vs 29.9%, P= 0.003) and shortness of breath (52.4% vs 19.4%, P <0.001), dysfunction of various systems, decreased cellular immunity and elevated IL-6 (9.6 vs 7.6 g/L, P= 0.015) in laboratory tests, isolation of other pathogens (18.4% vs 5.6%, P <0.001), and infiltration of all five lobes (75.3% vs 57.6%, P= 0.003). During hospitalization, patients with MODS needed a higher proportion of comprehensive treatment and reached a mortality rate of 66.0%. Independents risk factors for development of MODS in COVID-19 patients were: onset-to-admission interval>7 days ( OR =2.17, 95% CI : 1.11-4.22, P= 0.023), shortness of breath ( OR =3.19, 95% CI : 1.60-6.37, P= 0.001), lymphocyte count<1×10 9 /L ( OR =2.67, 95% CI : 1.31-5.46, P= 0.007), blood urea nitrogen>7mol/L ( OR =6.27, 95% CI : 2.80-14.08, P <0.001), procalcitonin>0.1 ng/mL ( OR =2.48, 95% CI : 1.20-5.13, P= 0.014), and C-reactive protein>10 mg/L ( OR =3.92, 95% CI : 1.41-10.89, P= 0.009). Conclusions: COVID-19 patients with MODS were of higher severity and mortality. Early identification of high-risk groups with MODS according to risk factors may be helpful for early treatment.

The interfacial structures of C 60 molecules adsorbed on solid surfaces are essential for a wide range of scientific and technological processes in carbon-based nanodevices. Here, we report structural transitions of the C 60 monolayer on the Bi(111) surface studied via low-temperature scanning tunneling microscopy (STM). With an increase in temperature, the structure of the C 60 monolayer transforms from local-order structures to a (√93 × √93) R20° superstructure, and then to a (11 × 11) R0° superstructure. Moreover, the individual C 60 molecules in different superstructures have different orientations. C 60 molecules adopt the 6 : 6 C-C bond and 5 : 6 C-C bond facing-up, mixed orientations, and hexagon facing-up in the local-order structure, (√93 × √93) R20°, and (11 × 11) R0° superstructure, respectively. These results shed important light on the growth mechanism of C 60 molecules on solid surfaces., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Development of immunity-based strategy to manage bacterial infection is urgently needed in aquaculture due to the widespread of antibiotic-resistant bacteria. Phagocytosis serves as the first line defense in innate immunity that engulfs bacteria and restricts their proliferations and invasions. However, the mechanism underlying the regulation of phagocytosis is not fully elucidated and the way to boost phagocytosis is not yet explored. In this manuscript, we profiled the metabolomes of monocytes/macrophages isolated from Nile tilapia, prior and after phagocytosis on Vibrio alginolyticus . Monocytes/macrophages showed a metabolic shift following phagocytosis. Interestingly, succinate was accumulated after phagocytosis and was identified as a crucial biomarker to distinguish before and after phagocytosis. Exogenous succinate increased the phagocytotic rate of monocytes/macrophages in a dose-dependent manner. This effect was dependent on the TCA cycle as the inhibitor of malonate that targets succinate dehydrogenase abrogated the effect. Meanwhile, exogenous succinate regulated the expression of genes associated with innate immune and phagocytosis. In addition, succinate-potentiated phagocytosis was applicable to both gram-negative and -positive cells, including V. alginolyticus, Edwardsiella tarda, Streptococcus agalactiae , and Streptococcus iniae . Our study shed light on the understanding of how modulation on host's metabolism regulates immune response, and this can be a potent therapeutic approach to control bacterial infections in aquaculture., Competing Interests: 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 © 2021 Yang, Yang, Cao, Jiang, Zheng and Peng.)

Background: In the wake of the US opioid epidemic, there have been efforts to curb opioid prescribing. However, it is unknown whether these efforts have affected prescribing among oncologists, whose patients often require opioids for symptom management. We investigated temporal patterns in opioid prescribing for Medicare beneficiaries among oncologists and nononcologists., Methods: We queried the Centers for Medicare and Medicaid Services Part D prescriber dataset for all physicians between January 1, 2013, and December 31, 2017. We used population-averaged multivariable negative binomial regression to estimate the association between time and per-provider opioid and gabapentinoid prescribing rate, defined as the annual number of drug claims (original prescriptions and refills) per beneficiary, among oncologists and nononcologists on a national and state level., Results: From 2013 to 2017, the national opioid-prescribing rate declined by 20.7% (P < .001) among oncologists and 22.8% (P < .001) among non oncologists. During this time frame, prescribing of gabapentin increased by 5.9% (P < .001) and 23.1% (P < .001) among oncologists and nononcologists, respectively. Among palliative care providers, opioid prescribe increased by 15.3% (P < .001). During the 5-year period, 43 states experienced a decrease (P < .05) in opioid prescribing among oncologists, and in 5 states, opioid prescribing decreased more among oncologists than nononcologists (P < .05)., Conclusions: Between 2013 and 2017, the opioid-prescribing rate statistically significantly decreased nationwide among oncologists and nononcologists, respectively. Given similar declines in opioid prescribing among oncologists and nononcologists, there is concern that opioid-prescribing guidelines intended for the noncancer population are being applied inappropriately to patients with cancer and cancer survivors., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Cancer registries are important real-world data sources consisting of data abstraction from the medical record; however, patients with unknown or missing data are underrepresented in studies that use such data sources., Objective: To assess the prevalence of missing data and its association with overall survival among patients with cancer., Design, Setting, and Participants: In this retrospective cohort study, all variables within the National Cancer Database were reviewed for missing or unknown values for patients with the 3 most common cancers in the US who received diagnoses from January 1, 2006, to December 31, 2015. The prevalence of patient records with missing data and the association with overall survival were assessed. Data analysis was performed from February to August 2020., Exposures: Any missing data field within a patient record among 63 variables of interest from more than 130 total variables in the National Cancer Database., Main Outcomes and Measures: Prevalence of missing data in the medical records of patients with cancer and associated 2-year overall survival., Results: A total of 1 198 749 patients with non-small cell lung cancer (mean [SD] age, 68.5 [10.9] years; 628 811 men [52.5%]), 2 120 775 patients with breast cancer (mean [SD] age, 61.0 [13.3] years; 2 101 758 women [99.1%]), and 1 158 635 patients with prostate cancer (mean [SD] age, 65.2 [9.0] years; 100% men) were included in the analysis. Among those with non-small cell lung cancer, 851 295 patients (71.0%) were missing data for variables of interest; 2-year overall survival was 33.2% for patients with missing data and 51.6% for patients with complete data (P < .001). Among those with breast cancer, 1 161 096 patients (54.7%) were missing data for variables of interest; 2-year overall survival was 93.2% for patients with missing data and 93.9% for patients with complete data (P < .001). Among those with prostate cancer, 460 167 patients (39.7%) were missing data for variables of interest; 2-year overall survival was 91.0% for patients with missing data and 95.6% for patients with complete data (P < .001)., Conclusions and Relevance: This study found that within a large cancer registry-based real-world data source, there was a high prevalence of missing data that were unable to be ascertained from the medical record. The prevalence of missing data among patients with cancer was associated with heterogeneous differences in overall survival. Improvements in documentation and data quality are necessary to make optimal use of real-world data for clinical advancements.

Objective: This study aims to evaluate the changes in left ventricular diastolic function after coronary artery bypass grafting through tissue Doppler imaging (TDI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and the correlation between the two., Patients and Methods: A total of 133 patients who underwent coronary artery bypass grafting between January 2016 and December 2018 were included in this study. Echocardiography and NT-proBNP concentration were reviewed pre-operation, 1 month post-operation, and 3-6 months post-operation. The transmitral peak flow velocity (E) of the mitral valve was measured at each of the three-time points using spectral Doppler imaging. The mitral annulus displacement (Ea peak and Aa peak) was then measured at each of the time points using TDI, and the E/Ea ratio was calculated. Subsequently, the correlation of the E value, Ea value, and E/Ea ratio with NT-proBNP concentration was statistically analyzed., Results: The data obtained at the three-time points were compared with the respective concentrations of NT-proBNP. Multiple linear regression analysis revealed a correlation between NT-proBNP concentration and E value, Ea value, and E/Ea ratio., Conclusions: Left ventricular diastolic function gradually recovered at 1 month and 3-6 months after coronary artery bypass grafting. There was a correlation between TDI-related values and NT-proBNP concentration.

Development of low-cost and eco-friendly approaches to fight bacterial pathogens is especially needed in aquaculture. We previously showed that exogenous malate reprograms zebrafish's metabolome to potentiate zebrafish survival against Vibrio alginolyticus infection. However, the underlying mechanism is unknown. Here, we use GC-MS based metabolomics to identify the malate-triggered metabolic shift. An activated TCA cycle and elevated taurine are identified as the key metabolic pathways and the most crucial biomarker of the reprogrammed metabolome, respectively. Taurine elevation is attributed to the activated TCA cycle, which is further supported by the increased expression of genes in the metabolic pathway of taurine biosynthesis from the isocitrate of the TCA cycle to taurine. Exogenous taurine increases the survival of zebrafish against V. alginolyticus infection as malate did. Moreover, exogenous taurine and malate regulate the expression of innate immunity genes and promote the generation of reactive oxygen species and nitrogen oxide in a similar way. The two metabolites can alleviate the excessive immune response to bacterial challenge, which protects fish from bacterial infection. These results indicate that malate enhances the survival of zebrafish to V. alginolyticus infection via taurine. Thus, our study highlights a metabolic approach to enhance a host's ability to fight bacterial infection.

The aim of this study was to explore the dynamic changes in characteristic serum metabolic markers and pathways during early sepsis in rats. By using cecal ligation and puncture (CLP), we made rat models of sepsis, which were randomly divided into 5 groups with 10 rats in each group: group A, group B, group C, group D, and group E. We collected 2 mL of arterial blood at 0, 6, 12, 24, and 48 hours from rats in group A-E respectively and isolated serum via centrifugation. Next, adopting metabolomics analysis methods, we screened for metabolites from the animal serum with statistically and biologically significant abundance changes, and used the KEGG database to analyze the respective metabolic pathways. In all, our findings reveal that D-glucosamine 6-phosphate, D-glucosamine phosphate, α-D-glucosamine 1-phosphate, D-glucosamine 1-phosphate, and 5-hydroxy isocyanate decline continuously from 12 hours, while L-phenylalanine, (S) -α-amino-β-phenylpropionic acid, 5-methoxy indole acetic acid salt, 5-methoxy indole acetic acid, goose deoxyglycolic acid salt, goose deoxyglycolic acid, and Chen's deoxygenated sugar alcohol started to decrease from 6 hours. Additionally, 3.2,3-Bis-O-(geranyl geranyl)-sn-glycerol- 1-phosphoric acid-L-serine levels rose continuously from 12 hours. We found 13 differentially regulated ions, primarily ones involved in pathways responsible for the metabolism of sugar, amino acids, and lipids, which are related to the disorder of energy metabolism. Our findings mark serum-derived D-glucosamine and its phosphorous derivatives as characteristic metabolic markers of sepsis in rats., (Copyright 2020 Biolife Sas. www.biolifesas.org.)

Purpose: Management options for localized prostate cancer include definitive radiation therapy (RT) or radical prostatectomy, with a subset of surgical patients requiring adjuvant or salvage RT after prostatectomy. The use of a peri-rectal hydrogel spacer in patients receiving definitive RT has been shown to reduce rectal doses and toxicity. However, in the postprostatectomy setting, a hydrogel spacer cannot be routinely placed. Therefore, we sought to compare rectal dosimetry between definitive RT with a hydrogel spacer versus postoperative RT., Methods and Materials: We identified patients with prostate cancer who underwent conventionally fractionated RT. Rectal dosimetry was evaluated between 2 groups: definitive RT with a hydrogel spacer (79.2 Gy, group 1) and postoperative RT (70.2 Gy, group 2). Rectal dosimetry values were tabulated and compared using Mann-Whitney U test. We implemented a Bonferroni correction to account for multiple comparisons (threshold P < .005). Linear regression analysis evaluated predictors of candidate rectal dose-volume parameters., Results: We identified 51 patients treated during years 2017 to 2018; 16 (31%) and 35 (69%) patients were included in groups 1 and 2, respectively. The rectal volume receiving ≥65 Gy (V65) was significantly lower in group 1 (median, 2.1%; interquartile range, 0.9%-3.1%) than in group 2 (10.7%, 6.6%-14.5%) ( P < .001). Use of a hydrogel spacer in the definitive setting was independently associated with lower V65 ( P < .001). Similar results were found for V60, V55, V50, and V45 ( P < .005 for all)., Conclusions: Rectal dosimetry is more favorable for definitive RT (79.2 Gy) with a hydrogel spacer compared with postoperative RT (70.2 or 66.6 Gy). This may inform shared decision-making regarding primary management of prostate cancer, especially among patients at high risk of needing postoperative RT after prostatectomy., (© 2020 The Author(s).)

Background: Patients with cancer may be at risk of high opioid use due to physical and psychosocial factors, although little data exist to inform providers and policymakers. Our aim is to examine overdoses from opioids leading to emergency department (ED) visits among patients with cancer in the United States., Methods: The Healthcare Cost and Utilization Project Nationwide Emergency Department Sample was queried for all adult cancer-related patient visits with a primary diagnosis of opioid overdose between 2006 and 2015. Temporal trends and baseline differences between patients with and without opioid-related ED visits were evaluated. Multivariable logistic regression analysis was used to identify risk factors associated with opioid overdose. All statistical tests were two-sided., Results: Between 2006 and 2015, there were a weighted total of 35 339 opioid-related ED visits among patients with cancer. During this time frame, the incidence of opioid-related ED visits for overdose increased twofold (P < .001). On multivariable regression (P < .001), comorbid diagnoses of chronic pain (odds ratio [OR] 4.51, 95% confidence interval [CI] = 4.13 to 4.93), substance use disorder (OR = 3.54, 95% CI = 3.28 to 3.82), and mood disorder (OR = 3.40, 95% CI = 3.16 to 3.65) were strongly associated with an opioid-related visit. Patients with head and neck cancer (OR = 2.04, 95% CI = 1.82 to 2.28) and multiple myeloma (OR = 1.73, 95% CI = 1.32 to 2.26) were also at risk for overdose., Conclusions: Over the study period, the incidence of opioid-related ED visits in patients with cancer increased approximately twofold. Comorbid diagnoses and primary disease site may predict risk for opioid overdose., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Prescription opioids are frequently prescribed to treat cancer-related pain. However, limited information exists regarding rates of prescription opioid use and misuse in populations with cancer., Objectives: To estimate the prevalence and likelihood of prescription opioid use and misuse in adult cancer survivors compared with respondents without cancer and to identify characteristics associated with prescription opioid use and misuse in adult cancer survivors., Design, Setting, and Participants: This cross-sectional study is a retrospective, population-based study using data from 169 162 respondents to the National Survey on Drug Use and Health from January 2015 to December 2018. Survey data sets were queried for all respondents aged 18 years or older. Those with a reported history of cancer were termed cancer survivors and further divided into more recent (had cancer within 12 months of survey) and less recent (had cancer more than 12 months prior to survey) cohorts. Respondents with nonmelanoma skin cancer were excluded., Main Outcomes and Measures: Prescription opioid use and misuse within the past 12 months., Results: Among 169 162 respondents, 5139 (5.2%) were cancer survivors, with 1243 (1.2%) and 3896 (4.0%) reporting having more recent and less recent cancer histories, respectively. Higher rates of prescription opioid use were observed among more recent cancer survivors (54.3%; 95% CI, 50.2%-58.4%; odds ratio [OR], 1.86; 95% CI, 1.57-2.20; P < .001) and less recent cancer survivors (39.2%; 95% CI, 37.3%-41.2%; OR, 1.18; 95% CI, 1.08-1.28; P < .001) compared with respondents without cancer (30.5%, reference group). Rates of prescription opioid misuse were similar among more recent (3.5%; 95% CI, 2.4%-5.2%; OR, 1.27; 95% CI, 0.82-1.96; P = .36) and less recent (3.0%; 95% CI, 2.4%-3.6%; OR, 1.03; 95% CI, 0.83-1.28; P = .76) survivors compared with respondents without cancer (4.3%, reference group). Younger age (aged 18-34 years vs ≥65 years: OR, 7.06; 95% CI, 3.03-16.41; P < .001), alcohol use disorder (OR, 3.22; 95% CI, 1.45-7.14; P = .005), and nonopioid drug use disorder (OR, 14.76; 95% CI, 7.40-29.44; P < .001) were associated with prescription opioid misuse among cancer survivors., Conclusions and Relevance: In this study, prescription opioid use was higher among more and less recent cancer survivors compared with the population without a history of cancer. Rates of prescription opioid misuse were low and similar among all 3 cohorts. These findings suggest that higher prescription opioid use among cancer survivors may not correspond to increased short-term or long-term misuse.