Publications by authors named "Pan Gao"

215 Publications

Prediction of the Growth Rate of Early-Stage Lung Adenocarcinoma by Radiomics.

Front Oncol 2021 15;11:658138. Epub 2021 Apr 15.

Department of Radiology, Huadong Hospital Affiliated With Fudan University, Shanghai, China.

Objectives: To investigate the value of imaging in predicting the growth rate of early lung adenocarcinoma.

Methods: From January 2012 to June 2018, 402 patients with pathology-confirmed lung adenocarcinoma who had two or more thin-layer CT follow-up images were retrospectively analyzed, involving 407 nodules. Two complete preoperative CT images and complete clinical data were evaluated. Training and validation sets were randomly assigned according to an 8:2 ratio. All cases were divided into fast-growing and slow-growing groups. Researchers extracted 1218 radiomics features from each volumetric region of interest (VOI). Then, radiomics features were selected by repeatability analysis and Analysis of Variance (ANOVA); Based on the Univariate and multivariate analyses, the significant radiographic features is selected in training set. A decision tree algorithm was conducted to establish the radiographic model, radiomics model and the combined radiographic-radiomics model. Model performance was assessed by the area under the curve (AUC) obtained by receiver operating characteristic (ROC) analysis.

Results: Sixty-two radiomics features and one radiographic features were selected for predicting the growth rate of pulmonary nodules. The combined radiographic-radiomics model (AUC 0.78) performed better than the radiographic model (0.727) and the radiomics model (0.710) in the validation set.

Conclusions: The model has good clinical application value and development prospects to predict the growth rate of early lung adenocarcinoma through the combined radiographic-radiomics model.
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http://dx.doi.org/10.3389/fonc.2021.658138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082461PMC
April 2021

Mechanism of the inhibition and detoxification effects of the interaction between nanoplastics and microalgae Chlorella pyrenoidosa.

Sci Total Environ 2021 Apr 6;783:146919. Epub 2021 Apr 6.

School of Resource and Environmental Sciences, Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan, Hubei 430079, China. Electronic address:

Most previous studies have focused on the toxicity of microplastics on aquatic organisms. However, research on nanoplastics is still limited and poses significant threat to aquatic organisms than microplastics. Therefore, this study investigated the effects of nanoplastics (80 nm) on the microalgae Chlorella pyrenoidosa. One unanticipated finding was that inhibition and detoxification effects existed in the interaction between nanoplastics and C. pyrenoidosa. Nanoplastics contributed the maximum inhibition rates of 27.73%, 29.64%, and 11.76% on algal growth, chlorophyll a, and Fv/Fm, respectively, which were much higher than those of microplastics. However, the inhibitory effect of nanoplastics gradually decreased with prolonged exposure time after reaching a maximum. The transcriptomic analysis explained that the inhibition effect of nanoplastics was due to the blockage of the gene expression of aminoacyl tRNA synthetase and the synthesis of related enzymes and proteins at low concentrations (10 mg·L). Moreover, it affected DNA damage repair and hindered photosynthesis at high concentrations (50 mg·L). The detoxification phenomenon is attributed to the promotion of cell proliferation, the acceleration of the degradation of damaged proteins and organs, and the regulation of intracellular osmotic pressure in algae. The results of this study provide an understanding of the mechanism underlying the interaction between nanoplastics and microalgae.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146919DOI Listing
April 2021

Preconditioning increases brain resistance against acute brain injury via neuroinflammation modulation.

Exp Neurol 2021 Apr 2;341:113712. Epub 2021 Apr 2.

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China. Electronic address:

Acute brain injury (ABI) is a broad concept mainly comprised of sudden parenchymal brain injury. Acute brain injury outcomes are dependent not only on the severity of the primary injury, but the delayed secondary injury that subsequently follows as well. These are both taken into consideration when determining the patient's prognosis. Growing clinical and experimental evidence demonstrates that "preconditioning," a prophylactic approach in which the brain is exposed to various pre-injury stressors, can induce varying degrees of "tolerance" against the impact of the ABI by modulating neuroinflammation. In this review, we will summarize the pathophysiology of ABI, and discuss the involved mechanisms of neuroinflammation in ABI, as well as existing experimental and clinical studies demonstrating the efficacy of preconditioning methods in various types of ABI by modulating neuroinflammation.
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http://dx.doi.org/10.1016/j.expneurol.2021.113712DOI Listing
April 2021

A Clinical Nomogram for Predicting Lymph Node Metastasis in Penile Cancer: A SEER-Based Study.

Front Oncol 2021 9;11:640036. Epub 2021 Mar 9.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

We developed a nomogram to predict the possibility of lymph node metastasis in patients with squamous cell carcinoma of the penis. Identifying patients with squamous cell carcinoma of the penis diagnosed between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate analyses were carried out by logistic regression to assess significant predictors associated with lymph node metastasis. A nomogram was established and validated by a calibration plot and receptor operating characteristic curve (ROC) analysis. A total of 1,016 patients with penile squamous cell carcinoma (SCCP) were enrolled in this study. One hundred and ninety-five patients (19%) had lymph node involvement (N1-3). Multivariate analysis showed that age, primary tumor site, grade, tumor size, and T stage were identified as being significantly ( < 0.05) associated with lymph node involvement. All the above factors that showed a statistically significant predictive capability were selected for building the nomogram. This model had a calibration slope of 0.9 and a c-index of 0.776, indicating the good discrimination and effectiveness of the nomogram in predicting lymph node status. Although the prediction model has some limitations, the nomogram revealed the relationship between the clinicopathological characteristics of SCCP patients and the risk of lymph node metastasis. This tool will assist patients in counseling and guide treatment decisions for SCCP patients.
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http://dx.doi.org/10.3389/fonc.2021.640036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985344PMC
March 2021

Prime editing in mice reveals the essentiality of a single base in driving tissue-specific gene expression.

Genome Biol 2021 Mar 16;22(1):83. Epub 2021 Mar 16.

Department of Medicine, Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, 30912, USA.

Background: Most single nucleotide variants (SNVs) occur in noncoding sequence where millions of transcription factor binding sites (TFBS) reside. Here, a comparative analysis of CRISPR-mediated homology-directed repair (HDR) versus the recently reported prime editing 2 (PE2) system was carried out in mice over a TFBS called a CArG box in the Tspan2 promoter.

Results: Quantitative RT-PCR showed loss of Tspan2 mRNA in aorta and bladder, but not heart or brain, of mice homozygous for an HDR-mediated three base pair substitution in the Tspan2 CArG box. Using the same protospacer, mice homozygous for a PE2-mediated single-base substitution in the Tspan2 CArG box displayed similar cell-specific loss of Tspan2 mRNA; expression of an overlapping long noncoding RNA was also nearly abolished in aorta and bladder. Immuno-RNA fluorescence in situ hybridization validated loss of Tspan2 in vascular smooth muscle cells of HDR and PE2 CArG box mutant mice. Targeted sequencing demonstrated variable frequencies of on-target editing in all PE2 and HDR founders. However, whereas no on-target indels were detected in any of the PE2 founders, all HDR founders showed varying levels of on-target indels. Off-target analysis by targeted sequencing revealed mutations in many HDR founders, but none in PE2 founders.

Conclusions: PE2 directs high-fidelity editing of a single base in a TFBS leading to cell-specific loss in expression of an mRNA/long noncoding RNA gene pair. The PE2 platform expands the genome editing toolbox for modeling and correcting relevant noncoding SNVs in the mouse.
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http://dx.doi.org/10.1186/s13059-021-02304-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962346PMC
March 2021

Anxiety-like behavior and intestinal microbiota changes as strain-and sex-dependent sequelae of mild food allergy in mouse models of cow's milk allergy.

Brain Behav Immun 2021 Mar 9. Epub 2021 Mar 9.

Department of Biomedical Sciences, University of North Dakota School of Medicine & Health Sciences, Grand Forks, ND, USA. Electronic address:

A number of studies have reported comorbidity of food allergies with various neuropsychiatric disorders, such as anxiety, depression, attention-deficit hyperactivity disorder, and autism. However, inconsistent results across clinical studies have left the association between food allergy and behavioral disorders inconclusive. We postulated that the heterogeneities in genetic background among allergic cohorts affect symptom presentation and severity of food allergy, introducing bias in patient selection criteria toward individuals with overt physical reactions. To understand the influence of genetic background on food allergy symptoms and behavioral changes beyond anaphylaxis, we generated mouse models with mild cow's milk allergy by sensitizing male and female C57BL/6J and BALB/cJ mice to a bovine whey protein, β-lactoglobulin (BLG; Bos d 5). We compared strain- and sex-dependent differences in their immediate physical reactions to BLG challenge as well as anxiety-like behavior one day after the challenge. While reactions to the allergen challenge were either absent or mild for all groups, a greater number of BLG-sensitized BALB/cJ mice presented visible symptoms and hypothermia compared to C57BL/6J mice. Interestingly, male mice of both strains displayed anxiety-like behavior on an elevated zero maze without exhibiting cognitive impairment with the cross maze test. Further characterization of plasma cytokines/chemokines and fecal microbiota also differentiated strain- and sex-dependent effects of BLG sensitization on immune-mediator levels and bacterial populations, respectively. These results demonstrated that the genetic variables in mouse models of milk allergy influenced immediate physical reactions to the allergen, manifestation of anxiety-like behavior, levels of immune responses, and population shift in gut microbiota. Thus, stratification of allergic cohorts by their symptom presentations and severity may strengthen the link between food allergy and behavioral disorders and identify a population(s) with specific genetic background that have increased susceptibility to allergy-associated behavioral disorders.
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http://dx.doi.org/10.1016/j.bbi.2021.03.002DOI Listing
March 2021

"Self-doping" defect engineering in SnP@gamma-irradiated hard carbon anode for rechargeable sodium storage.

J Colloid Interface Sci 2021 Jun 24;592:279-290. Epub 2021 Feb 24.

Tianjin Municipal Key Laboratory of Advanced Fiber and Energy Storage Technology, School of Textile Science and Engineering, Tiangong University, Tianjin 300387, China.

Reasonable design of defect engineering in the electrode materials for sodium-ion batteries (SIBs) can significantly optimize battery performance. Here, compared with the traditional "foreign-doping" defects method, we report an innovative gamma-irradiation technique to introduce the "self-doping" defects in the popcorn hard carbon (HC). Considering the advantages of adsorption-intercalation-alloying sodium storage mechanism, the defect-rich HC-coated alloy structure (SnP@HC-γ) was integrated. Due to the high energy and strong penetrability of γ-rays, the constructed "self-doping" defect engineering effectively expands the interlayer structure of HC and forms the irregular ring structure. Simultaneously, the exposed large number of coordination unsaturated sites can accelerate the reaction kinetics on the surface. Based on the synergistic effect of the SnP@HC-γ, the composites exhibit an excellent reversible capacity of 668 mAh g at 0.1 A g in SIBs. Even, after 400 cycles at 1.0 A g, an exceptional cyclability with 88% capacity retention (430 mAh g) can be maintained. We envision that the γ-irradiation technology used in this research not only overturns the general perception that "self-doping" defects will reduce performance, but also provides reliable technical support for large-scale construction of high-defect, high-capacity and stable sodium-ion anode materials.
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http://dx.doi.org/10.1016/j.jcis.2021.02.060DOI Listing
June 2021

MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm.

Redox Biol 2021 May 20;41:101903. Epub 2021 Feb 20.

Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA. Electronic address:

Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy. Myocardin related transcription factor A (MRTFA, MKL1) is a multifaceted transcription factor, regulating diverse biological processes. However, a detailed understanding of the mechanistic role of MKL1 in AAA has yet to be elucidated. In this study, we showed induced MKL1 expression in thoracic and abdominal aneurysmal tissues, respectively in both mice and humans. MKL1 global knockout mice displayed reduced AAA formation and aortic rupture compared with wild-type mice. Both gene deletion and pharmacological inhibition of MKL1 markedly protected mice from aortic dissection, an early event in Angiotensin II (Ang II)-induced AAA formation. Loss of MKL1 was accompanied by reduced senescence/proinflammation in the vessel wall and cultured vascular smooth muscle cells (VSMCs). Mechanistically, a deficiency in MKL1 abolished AAA-induced p38 mitogen activated protein kinase (p38MAPK) activity. Similar to MKL1, loss of MAPK14 (p38α), the dominant isoform of p38MAPK family in VSMCs suppressed Ang II-induced AAA formation, vascular inflammation, and senescence marker expression. These results reveal a molecular pathway of AAA formation involving MKL1/p38MAPK stimulation and a VSMC senescent/proinflammatory phenotype. These data support targeting MKL1/p38MAPK pathway as a potential effective treatment for AAA.
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http://dx.doi.org/10.1016/j.redox.2021.101903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937568PMC
May 2021

Combining Multi-Dimensional Convolutional Neural Network (CNN) With Visualization Method for Detection of Glover Infection in Cotton Leaves Using Hyperspectral Imaging.

Front Plant Sci 2021 15;12:604510. Epub 2021 Feb 15.

Key Laboratory of Oasis Ecology Agriculture, Shihezi University, Shihezi, China.

Cotton is a significant economic crop. It is vulnerable to aphids ( Glovers) during the growth period. Rapid and early detection has become an important means to deal with aphids in cotton. In this study, the visible/near-infrared (Vis/NIR) hyperspectral imaging system (376-1044 nm) and machine learning methods were used to identify aphid infection in cotton leaves. Both tall and short cotton plants (Lumianyan 24) were inoculated with aphids, and the corresponding plants without aphids were used as control. The hyperspectral images (HSIs) were acquired five times at an interval of 5 days. The healthy and infected leaves were used to establish the datasets, with each leaf as a sample. The spectra and RGB images of each cotton leaf were extracted from the hyperspectral images for one-dimensional (1D) and two-dimensional (2D) analysis. The hyperspectral images of each leaf were used for three-dimensional (3D) analysis. Convolutional Neural Networks (CNNs) were used for identification and compared with conventional machine learning methods. For the extracted spectra, 1D CNN had a fine classification performance, and the classification accuracy could reach 98%. For RGB images, 2D CNN had a better classification performance. For HSIs, 3D CNN performed moderately and performed better than 2D CNN. On the whole, CNN performed relatively better than conventional machine learning methods. In the process of 1D, 2D, and 3D CNN visualization, the important wavelength ranges were analyzed in 1D and 3D CNN visualization, and the importance of wavelength ranges and spatial regions were analyzed in 2D and 3D CNN visualization. The overall results in this study illustrated the feasibility of using hyperspectral imaging combined with multi-dimensional CNN to detect aphid infection in cotton leaves, providing a new alternative for pest infection detection in plants.
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http://dx.doi.org/10.3389/fpls.2021.604510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917247PMC
February 2021

Risk factors of premature ejaculation and its influence on sexual function of spouse.

Basic Clin Androl 2021 Feb 18;31(1). Epub 2021 Feb 18.

The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.

Background: Premature ejaculation (PE) is a multifactorial problem with a complicated aetiology that has detrimental effects on female partners' sexual function. However, there is a lack of studies on the relationship between the factors related to PE and female sexual dysfunction (FSD) in China. We aimed to identify and explore the relationship between the factors associated with PE and FSD.

Results: Ultimately, information was collected from 761 couples: 445 couples with PE complaints and 316 couples without PE complaints. The mean ages of the men with and without PE complaints were 36.29 ± 9.87 years and 31.48 ± 10.77 years, respectively. Female partners in the group with PE complaints reported lower total and subdomain female sexual function index (FSFI) scores, and approximately 65% of them were diagnosed with FSD (vs.

Control Group: 31.96%). A PE duration of more than 14 months, a self-estimated intravaginal ejaculation latency time (self-estimated IELT) less than 2 min, a negative attitude towards PE problems, men's introversion, and men's depression were risk factors for FSD in the PE group.

Conclusions: PE affects not only the patient himself but also the spouse. Comprehensive analysis reveals a clear relationship and interaction between female sexual function and PE. Moreover, in PE treatment, we should not ignore the occurrence of FSD and its impact and should emphasize the treatment of couples together.
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http://dx.doi.org/10.1186/s12610-020-00120-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890845PMC
February 2021

Development of a Novel Highly Spontaneous Metastatic Model of Esophageal Squamous Cell Carcinoma Using Renal Capsule Technology.

Onco Targets Ther 2021 4;14:785-793. Epub 2021 Feb 4.

Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People's Republic of China.

Purpose: Increasing evidence has demonstrated that animal models are imperative to investigate the potential molecular mechanism of metastasis and discover anti-metastasis drugs; however, efficient animal models to unveil the underlying mechanisms of metastasis in esophageal squamous cell carcinoma (ESCC) are limited.

Methods: ESCC cell EC9706 with high invasiveness was screened by repeated Transwell assays. Its biological characteristics were identified by flow cytometry as well as by the wound healing and CCK-8 assays. Besides, the levels of epithelial-mesenchymal transition-related markers were examined using Western blotting. Parental (EC9706-I) and subpopulation (EC9706-I) cells were employed to establish the renal capsule model. Next, the tumor growth was detected by a live animal imaging system, and hematoxylin and eosin staining was applied to evaluate the metastatic status in ESCC.

Results: EC9706-I cells showed rapid proliferation ability, S phase abundance, and high invasive ability; obvious upregulation in N-cadherin, Snail, Vimentin, and Bit1; and downregulation in E-cadherin. EC9706-I cells were less sensitive to the chemotherapy drug 5-fluorouracil than EC9706-I cells; however, both cell lines reached a tumorigenesis rate of 100% in the renal capsule model. The live animal imaging system revealed that the tumors derived from EC9706-I cells grew more slowly than those from EC9706-I cells at weeks 3-14. The EC9706-I xenograft model displayed a spontaneous metastatic site, including kidney, heart, liver, lung, pancreas, and spleen, with a distant metastatic rate of 80%.

Conclusion: Our data suggested that the metastatic model was successfully established, providing a novel platform for further exploring the molecular mechanisms of metastasis in ESCC patients.
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http://dx.doi.org/10.2147/OTT.S290564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872218PMC
February 2021

Coordination-Driven Enhancement of Radiosensitization by Black Phosphorus Regulating Tumor Metabolism.

ACS Nano 2021 02 28;15(2):3047-3060. Epub 2021 Jan 28.

Department of Oncology, The First Affiliated Hospital, and Department of Chemistry, Jinan University, Guangzhou 510632, P. R. China.

Coordination-driven surface modification is an effective strategy to achieve nanosystem functionalization and improved physicochemical performance. Black phosphorus (BP)-based nanomaterials demonstrate great potential in cancer therapy, but their poor stability, low X-ray mass attenuation coefficient, and nonselectivity limit the application in radiotherapy. Herein, we used unsaturated iridium complex to coordinate with BP nanosheets to synthesize a two-dimensional layered nanosystem (RGD-Ir@BP) with higher biostability. Ir complex improves the photoelectric properties and photoinduced charge carrier dynamics of BP, hence Ir@BP generated more singlet oxygen after X-ray irradiation. In experiments, with X-ray irradiation, RGD-Ir@BP effectively inhibited nasopharyngeal carcinoma tumor growth but with minor side effects. Additionally, based on untargeted metabolomics analysis, the combined treatment specifically down-regulated the tumor proliferative mark of prostaglandin E2 in cancer cells. In general, this study provides a design strategy of high-performance coordination-driven BP-based nanosensitizer in cancer radiotherapy.
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http://dx.doi.org/10.1021/acsnano.0c09454DOI Listing
February 2021

Prpf31 is essential for the survival and differentiation of retinal progenitor cells by modulating alternative splicing.

Nucleic Acids Res 2021 02;49(4):2027-2043

Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, PR China.

Dysfunction of splicing factors often result in abnormal cell differentiation and apoptosis, especially in neural tissues. Mutations in pre-mRNAs processing factor 31 (PRPF31) cause autosomal dominant retinitis pigmentosa, a progressive retinal degeneration disease. The transcriptome-wide splicing events specifically regulated by PRPF31 and their biological roles in the development and maintenance of retina are still unclear. Here, we showed that the differentiation and viability of retinal progenitor cells (RPCs) are severely perturbed in prpf31 knockout zebrafish when compared with other tissues at an early embryonic stage. At the cellular level, significant mitotic arrest and DNA damage were observed. These defects could be rescued by the wild-type human PRPF31 rather than the disease-associated mutants. Further bioinformatic analysis and experimental verification uncovered that Prpf31 deletion predominantly causes the skipping of exons with a weak 5' splicing site. Moreover, genes necessary for DNA repair and mitotic progression are most enriched among the differentially spliced events, which may explain the cellular and tissular defects in prpf31 mutant retinas. This is the first time that Prpf31 is demonstrated to be essential for the survival and differentiation of RPCs during retinal neurogenesis by specifically modulating the alternative splicing of genes involved in DNA repair and mitosis.
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http://dx.doi.org/10.1093/nar/gkab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913766PMC
February 2021

The Creation of an Experimental Data Set Containing Coronal Section Images of a Human Head.

Ear Nose Throat J 2021 Jan 21:145561321989432. Epub 2021 Jan 21.

Department of Otolaryngology, Head and Neck Surgery, Affiliated General Hospital of Shenzhen University, Shenzhen, China.

Objectives: The aim of the research is to create an experimental data set of coronal section images of a human head.

Methods: The head of a 49-year-old male cadaver was scanned by computed tomography (CT), then perfused with a green filling material via the bilateral common carotid artery, before being frozen and embedded. The head was sectioned along the coronal plane by a computer-controlled 5520 engraving and milling machine, capable of either 0.03-mm or 0.06-mm interspacing. All images were captured with a Canon 5D-Mk III digital camera.

Results: A total of 3854 section images were obtained, each with a resolution of 5760 × 3840 pixels. The number of section images at 0.03- and 0.06-mm interspacing were 1437 and 2417, respectively. All the images were stored in JPG and RAW formats. The image size of each RAW format was about 24.5 MB, whereas for JPG format, the equivalent size was about 5.9 MB. All the RAW and JPG images together occupied 117.35 GB of disk space.

Conclusions: The interspacing of this data set section was thinner than those of any comparable studies, and the image resolution was higher, too. This data set was also the first to take coronal sections of the human head. The data set contains image information from the smallest structures within the human head and can satisfy the needs of future developments and applications, such as the virtual operation training systems for otolaryngology, ophthalmology, stomatology, and neurosurgery, and help develop medical teaching software and maps.
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http://dx.doi.org/10.1177/0145561321989432DOI Listing
January 2021

Novel Lytic Phages Protect Cells and Mice against Infection.

J Virol 2021 Jan 20. Epub 2021 Jan 20.

Respiratory Department, Allergy and Immunity Institute, Affiliated Hospital, Southwest Medical University, 646000, Luzhou, China.;

With the fast emergence of serious antibiotic resistance and the lagged discovery of novel antibacterial drugs, phage therapy for pathogenic bacterial infections has acquired great attention in the clinics. However, development of therapeutic phages also faces tough challenges, such as laborious screening and time to generate effective phage drugs since each phage may only lyse a narrow scope of bacterial strains. Identifying highly effective phages with broad host ranges is crucial for improving phage therapy. Here, we isolated and characterized several lytic phages from various environments specific for by testing their growth, invasion, host ranges, and potential for killing targeted bacteria. Importantly, we identified several therapeutic phages (HX1, PPY9, and TH15) with broad host ranges to lyse laboratory strains and clinical isolates of with multi-drug resistance (MDR) both and in mouse models. In addition, we analyzed critical genetic traits related to the high-level broad host coverages by genome sequencing and subsequent computational analysis against known phages. Collectively, our findings establish that these novel phages may have potential for further development as therapeutic options for patients who fail to respond to conventional treatments. Novel lytic phages isolated from various environmental settings were systematically characterized for their critical genetic traits, morphology structures, host ranges against laboratory strains and clinical multi-drug resistant (MDR) , and antibacterial capacity both and in mouse models. First, we characterized the genetic traits and compared with other existing phages. Furthermore, we utilized acute pneumonia induced by laboratorial strain PAO1, and W19, an MDR clinical isolate and chronic pneumonia by agar beads laden with FDR1, a mucoid phenotype strain isolated from the sputum of a cystic fibrosis (CF) patient. Consequently, we found that these phages not only suppress bacteria but also significantly reduce the infection symptom and disease progression , including lowered bug burdens, inflammatory responses and lung injury in mice, suggesting that they may be further developed as therapeutic agents against MDR
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http://dx.doi.org/10.1128/JVI.01832-20DOI Listing
January 2021

Temperament-Character Traits and Attitudes Toward Premature Ejaculation in 4 Types of Premature Ejaculation.

J Sex Med 2021 01 15;18(1):72-82. Epub 2020 Dec 15.

Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. Electronic address:

Background: Although temperament-character traits and attitudes toward premature ejaculation (PE) are known to be associated with PE, it is of great significance to study them in PE. Moreover, few studies have evaluated these traits and attitudes in the new classification of 4 subtypes of PE.

Aim: We investigated the temperament-character traits and attitudes toward PE in 4 types of PE and their associations with PE.

Methods: Between December 2018 and December 2019, we conducted a survey in our hospital, and enrolled 350 men who complained of PE and 252 men without any complaint of PE. Temperament-character traits and attitudes toward PE were independently assessed by the Temperament and Character Inventory-Revised and several targeted questions, respectively. The Index of Premature Ejaculation (IPE) was used to evaluate ejaculation control, sexual life satisfaction, and distress caused by PE.

Outcomes: The outcomes included differences of temperament-character traits and attitudes toward PE among 2 groups and their associations with PE.

Results: Of the 2 groups, men with PE complaints had lower novelty seeking/self-transcendence (NS/ST) scores and higher harm avoidance (HA) scores vs men without any complaints of PE. Among the 4 types of PE, men with variable PE had the highest score of HA and lowest score of NS; the lowest score of ST was recorded in men with lifelong PE. Additionally, the total and subdomain scores of IPE in men with subjective PE were higher than the other subtypes of PE. After adjusting for age, positive correlations were observed in HA score and total and subdomain scores of IPE, whereas the inverse was true corresponding to NS and ST.

Clinical Implications: The current study has provided a new perspective for understanding the impact of psychological factors on PE.

Strengths & Limitations: This is the first study to systematically assess the effects of personality traits and attitudes on PE, especially among the 4 types of PE. The main drawback is that the generalizability of this study may be limited by the fact that it was conducted in a single cultural/societal background.

Conclusion: Men who complained of PE tended to react with indifference or rejection to novelty, tended to feel unsatisfied, cannot effectively adapt to changes in the surrounding environment, and tended to avoid situations involving risk. These characteristics could lead to their becoming disheartened when faced with PE. Furthermore, the attitude of men with PE reflects the needs of the patient during treatment from one aspect. Gao P, Gao J Wang Y, et al. Temperament-Character Traits and Attitudes Toward Premature Ejaculation in 4 Types of Premature Ejaculation. J Sex Med 2021;18:72-82.
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http://dx.doi.org/10.1016/j.jsxm.2020.11.001DOI Listing
January 2021

Mep1a contributes to Ang II-induced cardiac remodeling by promoting cardiac hypertrophy, fibrosis and inflammation.

J Mol Cell Cardiol 2021 03 8;152:52-68. Epub 2020 Dec 8.

State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Institute of Basic Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing, China. Electronic address:

Pathological cardiac remodeling, characterized by excessive deposition of extracellular matrix proteins and cardiac hypertrophy, leads to the development of heart failure. Meprin α (Mep1a), a zinc metalloprotease, previously reported to participate in the regulation of inflammatory response and fibrosis, may also contribute to cardiac remodeling, although whether and how it participates in this process remains unknown. Here, in this work, we investigated the role of Mep1a in pathological cardiac remodeling, as well as the effects of the Mep1a inhibitor actinonin on cardiac remodeling-associated phenotypes. We found that Mep1a deficiency or chemical inhibition both significantly alleviated TAC- and Ang II-induced cardiac remodeling and dysfunction. Mep1a deletion and blocking both attenuated TAC- and Ang II-induced heart enlargement and increases in the thickness of the left ventricle anterior and posterior walls, and reduced expression of pro-hypertrophic markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and myosin heavy chain beta (β-MHC). In addition, Mep1a deletion and blocking significantly inhibited TAC- and Ang II-induced cardiac fibroblast activation and production of extracellular matrix (ECM). Moreover, in Mep1a mice and treatment with actinonin significantly reduced Ang II-induced infiltration of macrophages and proinflammatory cytokines. Notably, we found that in vitro, Mep1a is expressed in cardiac myocytes and fibroblasts and that Mep1a deletion or chemical inhibition both markedly suppressed Ang II-induced hypertrophy of rat or mouse cardiac myocytes and activation of rat or mouse cardiac fibroblasts. In addition, blocking Mep1a in macrophages reduced Ang II-induced expression of interleukin (IL)-6 and IL-1β, strongly suggesting that Mep1a participates in cardiac remodeling processes through regulation of inflammatory cytokine expression. Mechanism studies revealed that Mep1a mediated ERK1/2 activation in cardiac myocytes, fibroblasts and macrophages and contributed to cardiac remodeling. In light of our findings that blocking Mep1a can ameliorate cardiac remodeling via inhibition of cardiac hypertrophy, fibrosis, and inflammation, Mep1a may therefore serve as a strong potential candidate for therapeutic targeting to prevent cardiac remodeling.
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http://dx.doi.org/10.1016/j.yjmcc.2020.11.015DOI Listing
March 2021

Identification of Repurposable Drugs and Adverse Drug Reactions for Various Courses of COVID-19 Based on Single-Cell RNA Sequencing Data.

ArXiv 2020 May 16. Epub 2020 May 16.

Coronavirus disease 2019 (COVID-19) has impacted almost every part of human life worldwide, posing a massive threat to human health. There is no specific drug for COVID-19, highlighting the urgent need for the development of effective therapeutics. To identify potentially repurposable drugs, we employed a systematic approach to mine candidates from U.S. FDA-approved drugs and preclinical small-molecule compounds by integrating the gene expression perturbation data for chemicals from the Library of Integrated Network-Based Cellular Signatures project with a publicly available single-cell RNA sequencing dataset from mild and severe COVID-19 patients. We identified 281 FDA-approved drugs that have the potential to be effective against SARS-CoV-2 infection, 16 of which are currently undergoing clinical trials to evaluate their efficacy against COVID-19. We experimentally tested the inhibitory effects of tyrphostin-AG-1478 and brefeldin-a on the replication of the single-stranded ribonucleic acid (ssRNA) virus influenza A virus. In conclusion, we have identified a list of repurposable anti-SARS-CoV-2 drugs using a systems biology approach.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724679PMC
May 2020

Highly efficient adsorption behavior and mechanism of Urea-FeO@LDH for triphenyl phosphate.

Environ Pollut 2020 Dec 14;267:114142. Epub 2020 Feb 14.

National Engineering Laboratory for Biomass Power Generation Equipment, School of Renewable Energy, North China Electric Power University, Beijing, 102206, China. Electronic address:

The emergence of organophosphorus flame retardants and the efficient removal from aquatic environments have aroused increasing concerns. The Urea functionalized FeO@LDH (Urea-FeO@LDH) was prepared and used to adsorb triphenyl phosphate (tphp) for the first time. The tphp adsorption capacity was up to 589 mg g, and the adsorption rate reached 49.9 mg g min. Moreover, the influences of various environmental factors (pH, ionic strength and organic matter) on the tphp adsorption on the Urea-FeO@LDH were investigated. The initial pH of the solution significantly affected the tphp adsorption, whereas the ionic strength and HA slightly affected the adsorption. The main adsorption mechanism was attributed to electrostatic interaction and π-π interaction. We believe that urea is one of excellent functional groups for the tphp adsorption removal and the materials with urea groups as the adsorbents exhibit good prospects in the future.
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http://dx.doi.org/10.1016/j.envpol.2020.114142DOI Listing
December 2020

Deep-learning-assisted detection and segmentation of rib fractures from CT scans: Development and validation of FracNet.

EBioMedicine 2020 Dec 10;62:103106. Epub 2020 Nov 10.

Radiology Department, Huadong Hospital, affiliated to Fudan University, Shanghai, China; Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai, China. Electronic address:

Background: Diagnosis of rib fractures plays an important role in identifying trauma severity. However, quickly and precisely identifying the rib fractures in a large number of CT images with increasing number of patients is a tough task, which is also subject to the qualification of radiologist. We aim at a clinically applicable automatic system for rib fracture detection and segmentation from CT scans.

Methods: A total of 7,473 annotated traumatic rib fractures from 900 patients in a single center were enrolled into our dataset, named RibFrac Dataset, which were annotated with a human-in-the-loop labeling procedure. We developed a deep learning model, named FracNet, to detect and segment rib fractures. 720, 60 and 120 patients were randomly split as training cohort, tuning cohort and test cohort, respectively. Free-Response ROC (FROC) analysis was used to evaluate the sensitivity and false positives of the detection performance, and Intersection-over-Union (IoU) and Dice Coefficient (Dice) were used to evaluate the segmentation performance of predicted rib fractures. Observer studies, including independent human-only study and human-collaboration study, were used to benchmark the FracNet with human performance and evaluate its clinical applicability. A annotated subset of RibFrac Dataset, including 420 for training, 60 for tuning and 120 for test, as well as our code for model training and evaluation, was open to research community to facilitate both clinical and engineering research.

Findings: Our method achieved a detection sensitivity of 92.9% with 5.27 false positives per scan and a segmentation Dice of 71.5%on the test cohort. Human experts achieved much lower false positives per scan, while underperforming the deep neural networks in terms of detection sensitivities with longer time in diagnosis. With human-computer collobration, human experts achieved higher detection sensitivities than human-only or computer-only diagnosis.

Interpretation: The proposed FracNet provided increasing detection sensitivity of rib fractures with significantly decreased clinical time consumed, which established a clinically applicable method to assist the radiologist in clinical practice.

Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. The funding sources played no role in the study design; collection, analysis, and interpretation of data; writing of the report; or decision to submit the article for publication .
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http://dx.doi.org/10.1016/j.ebiom.2020.103106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670192PMC
December 2020

Evaluation of Chemical Properties of Commercial Extra Virgin Olive Oil in China.

J Oleo Sci 2020 Dec 12;69(12):1541-1549. Epub 2020 Nov 12.

Key Laboratory for Deep Processing of Major Grain and Oil (Wuhan Polytechnic University) of Ministry of Education in China, College of Food Science and Engineering, Wuhan Polytechnic University.

The aim of the study was to investigate the chemical properties of the most popular commercial extra virgin olive oils (EVOOs) in China. A total of 14 EVOO samples were collected and evaluated, and significant differences were observed with respect to physicochemical properties, fatty acid composition, minor components, and the oxidation stability index (OSI). The results showed that the chemical properties of EVOOs were significantly affected by different producing areas. The oleic acid (C18:1) content (average value: 77.80%), squalene content (average value: 6052.28 mg/kg), and OSI (average value: 9.90 h) of the Spanish olive oil were higher than those of the other oils investigated, while the total phenolic content (average value: 308.34 mg/kg) was the lowest. Greek EVOOs had the lowest total sterol content (average value: 1023.48 mg/kg) and OSI (average value: 4.22 h). The C18:1 content (66.42%) and squalene content (3173.42 mg/kg) of the EVOO from China were lower than those of the other oils, while the palmitic acid (C16:0, 16.82%), linoleic acid (C18:2, 12.18%), total phenolic (553.17 mg/kg), and total sterol content (1904.77 mg/kg) were higher than those of the other olive oils. The EVOOs of the various countries could be distinguished by hierarchical cluster analysis (HCA). In addition, multiple linear regression (MLR) analyses between the OSI and chemical properties revealed that squalene (R = 0.729) and the unsaturation determined by the specific UV adsorption at 232 nm (K, R = -0.300) were the main factors to affecting the EVOO oxidation stability.
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http://dx.doi.org/10.5650/jos.ess20218DOI Listing
December 2020

Comparative Analysis of Rapeseed Oils Prepared by Three Different Methods.

J Oleo Sci 2020 Dec 12;69(12):1641-1648. Epub 2020 Nov 12.

Key Laboratory for Deep Processing of Major Grain and Oil (Wuhan Polytechnic University) of Ministry of Education in China, College of Food Science and Engineering, Wuhan Polytechnic University.

Flavoured rapeseed oils prepared using traditional technologies (oils A and B) and a fragrant rapeseed oil obtained using an enzymatic Maillard reaction (oil C) were analysed to show that oil C featured basic indicators and a fatty acid composition similar to those of traditional oils while exhibiting a higher comprehensive sensory evaluation score. Volatile component, odour activity value (OAV), and relative odour activity value (ROAV) analyses revealed that oil C had an elevated content of pyrazines (20.83%) and aldehydes (38.15%), which resulted in stronger charred and caramel flavours. The aroma of oil C was directly impacted by 3-methylbutyraldehyde (OAV > 1) and was modified by 3-methylthiopropionaldehyde and nonanal (RAOV > 1 in both cases). Thus, the developed technology was found to be well suited for the production of novel and safe fragrant rapeseed oil.
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http://dx.doi.org/10.5650/jos.ess20188DOI Listing
December 2020

MicroRNA-302/367 Cluster Impacts Host Antimicrobial Defense via Regulation of Mitophagic Response Against Infection.

Front Immunol 2020 7;11:569173. Epub 2020 Oct 7.

Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, United States.

Mitophagy has recently been implicated in bacterial infection but the underlying mechanism remains largely unknown. Here, we uncover a role of microRNA-302/367 cluster in regulating mitophagy and its associated host response against bacterial infection. We demonstrate that miR-302/367 cluster expression was significantly increased after infection. Enhanced expression of miR-302/367 cluster accelerated the mitophagic response in macrophages, thus increasing clearance of invading by regulating production of reactive oxygen species (ROS), while application of miR-302/367 cluster inhibitors decreased bacterial clearance. Blocking mitophagy with siRNA against mitophagy receptor prohibitin 2 (PHB2) reduced the effect of miR-302/367 cluster on induction of mitophagy and its-associated elimination. In addition, we found that miR-302/367 cluster also increased bacterial clearance in mouse model. Mechanistically, we illustrate that miR-302/367 cluster binds to the 3'-untranslated region of nuclear factor kappa B (NF-κB), a negative regulator of mitophagy, accelerated the process of mitophagy by inhibiting NF-κB. Furthermore, inhibition of NF-κB in macrophages attenuated the ROS or cytokines production and may reduce cell injury by infection to maintain cellular homeostasis. Collectively, our findings elucidate that miR-302/367 cluster functions as potent regulators in mitophagy-mediated elimination and pinpoint an unexpected functional link between miRNAs and mitophagy.
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http://dx.doi.org/10.3389/fimmu.2020.569173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576609PMC
October 2020

The Role of Iron, Its Metabolism and Ferroptosis in Traumatic Brain Injury.

Front Cell Neurosci 2020 25;14:590789. Epub 2020 Sep 25.

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Traumatic brain injury (TBI) is a structural and physiological disruption of brain function caused by external forces. It is a major cause of death and disability for patients worldwide. TBI includes both primary and secondary impairments. Iron overload and ferroptosis highly involved in the pathophysiological process of secondary brain injury. Ferroptosis is a form of regulatory cell death, as increased iron accumulation in the brain leads to lipid peroxidation, reactive oxygen species (ROS) production, mitochondrial dysfunction and neuroinflammatory responses, resulting in cellular and neuronal damage. For this reason, eliminating factors like iron deposition and inhibiting lipid peroxidation may be a promising therapy. Iron chelators can be used to eliminate excess iron and to alleviate some of the clinical manifestations of TBI. In this review we will focus on the mechanisms of iron and ferroptosis involving the manifestations of TBI, broaden our understanding of the use of iron chelators for TBI. Through this review, we were able to better find novel clinical therapeutic directions for further TBI study.
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http://dx.doi.org/10.3389/fncel.2020.590789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545318PMC
September 2020

Laparoscopic Pancreaticoduodenectomy with Superior Mesenteric Vein Resection and Artificial Vascular Graft Reconstruction for Borderline Resectable Pancreatic Cancer.

J Gastrointest Surg 2020 12 9;24(12):2906-2907. Epub 2020 Oct 9.

Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan Province, China.

Background: Laparoscopic pancreaticoduodenectomy (LPD) technique with artificial vascular graft reconstruction for patients with borderline resectable pancreatic cancer has been rarely reported since it is a very challenging technique. However, preliminary experience for the technique has been reported at the Department of Pancreatic Surgery, West China Hospital, Sichuan University.1,2 The rising popularity of neoadjuvant chemotherapy for pancreatic cancer patients may result in the increase of operative difficulty due to tissue edema and many other factors caused by the chemotherapy. The main aim of this study was to demonstrate the feasibility, safety, and key surgical procedure for LPD using video evidence.

Methods: A three-dimensional upper abdominal computed tomography angiography (CTA) scan done to a 51-year-old man brought to the center with upper abdominal pain showed a mass in the uncinate process of the pancreas, with over 180-degree involvement of the superior mesenteric vein. Percutaneous transhepatic cholangial drainage (PTCD) was performed to reduce jaundice while endoscopic ultrasound and fine-needle aspiration (EUS-FNA) were done to confirm the diagnosis of adenocarcinoma. The patient underwent two cycles of neoadjuvant chemotherapy using albumin-bound paclitaxel gemcitabine + program. The chemotherapy helped in significantly relieving the symptoms where CA 199 reduced from 586.7 IU/ml to 36.73 IU/ml, and the tumor maximum diameter was reduced from 4.3 cm to 2.2 cm. The violated superior mesenteric vein (SMV) and the tumor were en bloc resected, and a 4.0-cm artificial vascular graft was placed for reconstruction. Bing's anastomosis was performed using pancreaticojejunostomy3 while cholangiojejunostomy was performed using continuous stitching. The gastroduodenal artery (GDA) stump was wrapped with ligamentum teres hepatis after the completion of gastrointestinal anastomosis. The specimen was then removed through the extended umbilical incision (4 cm) and the operation was completed after the drainage tube was placed.

Results: The length of intraoperative excisional SMV, duration of artificial vascular graft reconstruction, operation time, and volume of intraoperative blood loss were 4.0 cm, 30 min, 520 min, and 800 mL, respectively. Histopathological examination of ypT2N1 indicated that 1 of the 27 lymph nodes was positive. Pathological results showed a moderately differentiated adenocarcinoma with all margins being negative.

Conclusions: This study demonstrated the feasibility of total laparoscopic pancreaticoduodenectomy combined with vascular resection and artificial vascular graft reconstruction in properly selected cases of pancreatic cancer with vein involvement after neoadjuvant chemotherapy. It is worth noting that skilled laparoscopic technicians and effective teamwork are necessities for safe completion of the procedure.
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http://dx.doi.org/10.1007/s11605-020-04808-yDOI Listing
December 2020

Contrast medium administration with a body surface area protocol in step-and-shoot coronary computed tomography angiography with dual-source scanners.

Sci Rep 2020 10 7;10(1):16690. Epub 2020 Oct 7.

Radiology Department, Huadong Hospital, Affiliated to Fudan University, Shanghai, China.

We evaluated the feasibility and image quality of prospective electrocardiography (ECG)-triggered coronary computed tomography angiography (CCTA) using a body surface area (BSA) protocol for contrast-medium (CM) administration on both second- and third-generation scanners (Flash and Force CT), without using heart rate control. One-hundred-and-eighty patients with suspected coronary heart disease undergoing CCTA were divided into groups A (BSA protocol for CM on Flash CT), B (body mass index (BMI)-matched patients; BMI protocol for CM on Flash CT), and C (BMI-matched patients; BSA protocol for CM on Force CT). Patient characteristics, quantitative and qualitative measures, and radiation dose were compared between groups A and B, and A and C. Of the 180 patients, 99 were male (median age, 62 years). Average BSA in groups A, B, and C was 1.80 ± 0.17 m, 1.74 ± 0.16 m, and 1.64 ± 0.17 m, respectively, with groups A and C differing significantly (P < 0.001). Contrast volume (50.50 ± 8.57 mL vs. 45.00 ± 6.18 mL) and injection rate (3.90 ± 0.44 mL/s vs. 3.63 ± 0.22 mL/s) differed significantly between groups A and C (P < 0.001). Groups A and C (both: all CT values > 250 HU, average scores > 4) achieved slightly lower diagnostic image quality than group B. The BSA protocol for CM administration was feasible in both Flash and Force CT, and therefore may be valuable in clinical practice.
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http://dx.doi.org/10.1038/s41598-020-73915-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541528PMC
October 2020

A comparison of the efficacy, safety, and duration of frame-based and Remebot robot-assisted frameless stereotactic biopsy.

Br J Neurosurg 2021 Jun 17;35(3):319-323. Epub 2020 Sep 17.

Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: The aim of this study was to compare the efficacy, safety, and duration of Remebot robot-assisted frameless brain biopsy with those of standard frame-based stereotactic biopsy.

Patients And Methods: A retrospective analysis of 66 patients undergoing stereotactic brain biopsy in our department from January 2015 to January 2019 was performed. We divided the patients into two groups: the frame-based group ( = 35) and the Remebot robot group ( = 31). Data on clinical characteristics, total procedure length, overall discomfort, diagnostic yield, complications, and postoperative length of hospital stay were retrospectively reviewed and compared between these two groups.

Results: No significant difference in diagnostic yield was detected in the two groups, with frame-based biopsy having a diagnostic yield of 91.4% and Remebot robot-assisted frameless brain biopsy having a diagnostic yield of 93.5%. The duration of the total procedure was 116.5 min for the frame-based biopsy and 80.1 min for the Remebot robot-assisted frameless brain biopsy ( < 0.001). There were no statistically significant differences in complication rate or postoperative duration of hospitalization between the two groups. The overall patient discomfort in the frame-based group was significantly greater than that in the Remebot robot group (visual analog scale score 2.7 ± 1.2 versus 1.5 ± 0.7,  = 0.001).

Conclusions: Remebot robot-assisted frameless brain biopsy was as efficacious and safe as standard stereotactic frame-based biopsy. However, frameless biopsy can alleviate the suffering of the patient and reduce the total duration of the procedure. Remebot robot-assisted frameless brain biopsy is easy to use and better accepted by patients than frame-based biopsy.
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http://dx.doi.org/10.1080/02688697.2020.1812519DOI Listing
June 2021

Assessment of the Contrast-Enhanced Ultrasound in Percutaneous Nephrolithotomy for the Treatment of Patients with Nondilated Collecting System.

J Endourol 2021 Apr 30;35(4):436-443. Epub 2020 Oct 30.

Department of Urology, The Second People's Hospital of China Three Gorges University, The Second People's Hospital of Yichang, Yichang, China.

To investigate the clinical value of contrast-enhanced ultrasound (CEUS) in percutaneous nephrolithotomy (PCNL) for kidney stone patients without hydronephrosis. Patients with nondilated collecting system kidney stones who underwent PCNL between October 2018 and December 2019 at our hospital were enrolled in this study. Patients who met the inclusion criteria were randomized into two groups: a CEUS-guided PCNL group and a conventional ultrasound (US)-guided PCNL group. The operation results of the two groups were compared, including the number of attempts for effective puncture, duration to effective puncture, stone clearance rate, blood loss, postoperative complications, and hospital stay. Fifty-six patients with a nondilated collecting system who underwent PCNL for 60 kidneys were included in this study, including 4 patients who underwent bilateral PCNL due to bilateral renal stones. There were 30 kidneys in each group. All patients successfully underwent PCNL. The CEUS-guided PCNL group had more accurate punctures, with a higher effective rate of one puncture and shorter puncture time. There was no statistically significant difference in stone clearance rate between the two groups. Four cases of double channels were established in the conventional US-guided PCNL group, while there was only one case in the CEUS-guided PCNL group. In the CEUS-guided PCNL group, most cases (96.7%, 29/30) had no or only mild complications, which were significantly better than the conventional US-guided PCNL group (76.7%, 23/30). The mean postoperative hemoglobin loss in the CEUS-guided PCNL group was 9.5 (range 1-25) g/L, which was significantly lower than 15.5 (range 5-52) g/L in the conventional US-guided PCNL group. The CEUS technique can improve visibility of the nondilated renal collecting system, facilitate selection of suitable calix, and identify renal calix fornix. It also benefits needle placement in patients with a nondilated collecting system.
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http://dx.doi.org/10.1089/end.2020.0564DOI Listing
April 2021

Small-Molecule Inhibitor of 8-Oxoguanine DNA Glycosylase 1 Regulates Inflammatory Responses during Infection.

J Immunol 2020 10 14;205(8):2231-2242. Epub 2020 Sep 14.

Department of Biomedical Sciences, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203;

The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises 8-oxo-7,8-dihydroguanine lesions induced in DNA by reactive oxygen species, has been linked to the pathogenesis of lung diseases associated with bacterial infections. A recently developed small molecule, SU0268, has demonstrated selective inhibition of OGG1 activity; however, its role in attenuating inflammatory responses has not been tested. In this study, we report that SU0268 has a favorable effect on bacterial infection both in mouse alveolar macrophages (MH-S cells) and in C57BL/6 wild-type mice by suppressing inflammatory responses, particularly promoting type I IFN responses. SU0268 inhibited proinflammatory responses during (PA14) infection, which is mediated by the KRAS-ERK1-NF-κB signaling pathway. Furthermore, SU0268 induces the release of type I IFN by the mitochondrial DNA-cGAS-STING-IRF3-IFN-β axis, which decreases bacterial loads and halts disease progression. Collectively, our results demonstrate that the small-molecule inhibitor of OGG1 (SU0268) can attenuate excessive inflammation and improve mouse survival rates during PA14 infection. This strong anti-inflammatory feature may render the inhibitor as an alternative treatment for controlling severe inflammatory responses to bacterial infection.
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http://dx.doi.org/10.4049/jimmunol.1901533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541742PMC
October 2020

Untargeted lipidomics reveals specific lipid abnormalities in Sjögren's syndrome.

Rheumatology (Oxford) 2021 Mar;60(3):1252-1259

Department of pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Objective: The relationship between serum lipid variations in SS and healthy controls was investigated to identify potential predictive lipid biomarkers.

Methods: Serum samples from 230 SS patients and 240 healthy controls were collected. The samples were analysed by ultrahigh-performance liquid chromatography coupled with Q Exactive™ spectrometry. Potential lipid biomarkers were screened through orthogonal projection to latent structures discriminant analysis and further evaluated by receiver operating characteristic analysis.

Results: A panel of three metabolites [phosphatidylcholine (18:0/22:5), triglyceride (16:0/18:0/18:1) and acylcarnitine (12:0)] was identified as a specific biomarker of SS. The receiver operating characteristic analysis showed that the panel had a sensitivity of 84.3% with a specificity of 74.8% in discriminating patients with SS from healthy controls.

Conclusion: Our approach successfully identified serum biomarkers associated with SS patients. The potential lipid biomarkers indicated that SS metabolic disturbance might be associated with oxidized lipids, fatty acid oxidation and energy metabolism.
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http://dx.doi.org/10.1093/rheumatology/keaa456DOI Listing
March 2021