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Introduction and objectiveNutritional therapy is a crucial component of treatment for severely burned patients. Although overly aggressive enteral nutrition immediately after burn injury has potential risks, nutritional disruption after a severe burn can also increase infection risk and delay wound healing. For approximately six decades, the Ruijin Hospital Burn Center has used two distinct approaches for patients during the early period after burn injury: complete fasting or adaptive feeding. Notably, adaptive feeding more closely resembles enteral nutrition. In this retrospective study, we analyzed factors influencing the selection of either modality, as well as the benefits of adaptive feeding. We sought to promote adaptive feeding as a precursor to initiating enteral nutrition.Patients and methodsThis retrospective study analyzed medical data from adult patients with extensive burns between January 2009 and December 2020. All patients had been admitted to the burn department within 24 h after injury and had a burned area comprising >30% of total body surface area. Patients were divided into two groups: adaptive feeding and fasting. We examined the total burned area, full-thickness burned area, burn type, inhalation injury, start time of adaptive feeding, and start time of enteral nutrition. Outcome measures were 28-day mortality and hospital mortality.ResultsUnivariate analysis revealed significant differences in burn type, percent of total body surface area (TBSA), full-thickness burned area, and inhalation injury between the adaptive feeding and fasting groups (all p

ObjectiveTo explore the value of 18F-fluordeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph node metastasis (LNM) of cervical cancer (FIGO 2018 stage I-II).Materials and MethodsA total of 65 patients with stage I-II cervical cancer underwent 18F-FDG PET/CT were included in our study. Comparing the primary tumor 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of 18F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM.ResultsThere were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all p

IntroductionMorchella esculenta is a popular edible fungus with high economic and nutritional value. However, the rot disease caused by Lecanicillium aphanocladii, pose a serious threat to the quality and yield of M. esculenta. Biological control is one of the effective ways to control fungal diseases.Methods and resultsIn this study, an effective endophytic B. subtilis A9 for the control of M. esculenta rot disease was screened, and its biocontrol mechanism was studied by transcriptome analysis. In total, 122 strains of endophytic bacteria from M. esculenta, of which the antagonistic effect of Bacillus subtilis A9 on L. aphanocladii G1 reached 72.2% in vitro tests. Biological characteristics and genomic features of B. subtilis A9 were analyzed, and key antibiotic gene clusters were detected. Scanning electron microscope (SEM) observation showed that B. subtilis A9 affected the mycelium and spores of L. aphanocladii G1. In field experiments, the biological control effect of B. subtilis A9 reached to 62.5%. Furthermore, the transcritome profiling provides evidence of B. subtilis A9 bicontrol at the molecular level. A total of 1,246 differentially expressed genes (DEGs) were identified between the treatment and control group. Gene Ontology (GO) enrichment analysis showed that a large number of DEGs were related to antioxidant activity related. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the main pathways were Nitrogen metabolism, Pentose Phosphate Pathway (PPP) and Mitogen-Activated Protein Kinases (MAPK) signal pathway. Among them, some important genes such as carbonic anhydrase CA (H6S33_007248), catalase CAT (H6S33_001409), tRNA dihydrouridine synthase DusB (H6S33_001297) and NAD(P)-binding protein NAD(P) BP (H6S33_000823) were found. Furthermore, B. subtilis A9 considerably enhanced the M. esculenta activity of Polyphenol oxidase (POD), Superoxide dismutase (SOD), Phenylal anineammonia lyase (PAL) and Catalase (CAT).ConclusionThis study presents the innovative utilization of B. subtilis A9, for effectively controlling M. esculenta rot disease. This will lay a foundation for biological control in Morchella, which may lead to the improvement of new biocontrol agents for production.

IntroductionEarly and accurate diagnosis of urinary tract infection (UTI) can prevent serious sequelae including chronic kidney disease. Multiple individual studies have identified urine neutrophil gelatinase-associated lipocalin (uNGAL) as a promising biomarker for early diagnosis of UTI. We sought to understand the distribution and diagnostic accuracy of uNGAL values in patients presenting with UTI symptoms.MethodsOur systematic literature reviews in PubMed, Embase, and Cochrane Reviews up to March 2024, identified 25 studies reporting mean/median, standard deviation/quartiles, and detection limits of uNGAL in symptomatic patients with and without culture-confirmed UTI. Seventeen studies were in children. Meta-analyses were performed using the quantile estimation (QE) method estimating the distributions of uNGAL, which were then compared between the UTI and non-UTI groups for identifying the best cut-off points maximizing the Youden index. Sensitivity analyses were performed on all 25 studies including adult patients.ResultsWe found that uNGAL levels were significantly higher in samples with confirmed UTI compared to those without. In pediatric studies, median and 95% confidence interval (CI) of uNGAL values were 22.41 (95% CI of 9.94, 50.54) ng/mL in non-UTI group vs. 118.85 (95% CI of 43.07, 327.97) ng/mL in UTI group. We estimated the cut-off point of 48.43 ng/mL with highest sensitivity (96%) and specificity (97%) in children. Sensitivity analysis including both pediatric and adult studies yielded similar results.DiscussionThe level of uNGAL in symptomatic patients with confirmed UTI is much higher than that reported in patients without UTI. It may be used as a diagnostic tool to identify UTI early among symptomatic patients. The range of uNGAL concentrations and cut-off points reported in subjects with UTI is much lower than that reported in patients with acute intrinsic kidney injury.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42023370451).

ObjectiveTo explore the clinical effect of bladder cancer patients with Fear of Cancer Recurrence (FCR) after applying the gratitude extension construction theory nursing program.Methods168 patients with bladder cancer hospitalized in the Department of Urology from December 2021 to June 2023 in a hospital are study subjects. The experimental subjects are uniformly designed as an experimental group and a control group, with 52 participants in each group. The former receives routine nursing care, while the later receives nursing interventions based on gratitude extension construction theory. The baseline data, Quality of life Questionnaire-core 30, Quality of Life Questionnaire-non Invasive Bladder Cancer 24, Fear of Progression Questionnaire-Short Form, gratitude level questionnaire, Self-Rating Depression Scale, Self-rating Anxiety Scale, patient compliance behavior score, Overall Survival, and Progression-free Survival are evaluated.ResultsThe basic data revealed no statistical significance. The quality of life questionnaire-core 30 and quality of life questionnaire-noninvasive bladder cancer 24 was no significant difference before treatment and after treatment for 1 month. After 9 months, There was a significant difference in pre-treatment scores. The experimental group had no significant difference before and after treatment. For the overall survival rates, the two groups were 67.25% and 79.56%. The progression-free survival rates were 56.35% and 72.35%, respectively, with statistical difference. The compliance rates were 86.54% and 98.08%. The compliance rate of the experimental group exceeded the control group. After 3, 6, and 12 months, the gratitude level questionnaire score and the fear of progression questionnaire-short form in the experimental group were improved. After 3, 6, and 12 months, the control group had no statistically significant difference in the gratitude level questionnaire and the fear of progression questionnaire-short form scores. Compared with the control group, the scores on the gratitude level questionnaire and the fear of progression questionnaire-short form were significantly higher after 3, 6, and 12 months of intervention.ConclusionAfter applying the gratitude extension construction theory nursing program, the FCR of bladder cancer patients is significantly reduced. The quality of life and compliance rate are significantly improved, and anxiety and depression are relieved.

Introduction:Vitiligo, a common autoimmune acquired pigmentary skin disorder, poses challenges due to its unclear pathogenesis. Evidence suggests inflammation and metabolism’s pivotal roles in its onset and progression. This study aims to elucidate the causal relationships between vitiligo and inflammatory proteins, immune cells, and metabolites, exploring bidirectional associations and potential drug targets.Methods:Mendelian Randomization (MR) analysis encompassed 4,907 plasma proteins, 91 inflammatory proteins, 731 immune cell features, and 1400 metabolites. Bioinformatics analysis included Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Subnetwork discovery and hub protein identification utilized the Molecular Complex Detection (MCODE) plugin. Colocalization analysis and drug target exploration, including molecular docking validation, were performed.Results:MR analysis identified 49 proteins, 39 immune cell features, and 59 metabolites causally related to vitiligo. Bioinformatics analysis revealed significant involvement in PPI, GO enrichment, and KEGG pathways. Subnetwork analysis identified six central proteins, with Interferon Regulatory Factor 3 (IRF3) exhibiting strong colocalization evidence. Molecular docking validated Piceatannol’s binding to IRF3, indicating a stable interaction.Conclusion:This study comprehensively elucidates inflammation, immune response, and metabolism’s intricate involvement in vitiligo pathogenesis. Identified proteins and pathways offer potential therapeutic targets, with IRF3 emerging as a promising candidate. These findings deepen our understanding of vitiligo’s etiology, informing future research and drug development endeavors.

It of great importance in assessing built thermal environment level and evaluating corresponding indoor air conditioning demand for energy conservation in construction sectors. Nevertheless, because of the unique meteorological features in plateau area, classical building performance simulation approach contributes to thermal performance evaluation errors since most design codes or standards relies on low attitude regions. In this paper, a modified and improved dynamic thermal design model is put forward for built environment and energy consumption estimation for passive buildings for plateau buildings. Moreover, the simplified experiment is set up to monitor dynamic thermal responses for modelling building. The testing validation illustrate that the onsite measurement accuracy level is quite acceptable for engineering applications with less than 30% relative change range coefficient. Besides, the experiment data demonstrates that window-to-wall ratios, architectural orientation, thermal insulation coefficients, have substantial impacts for solar heat gains in plateau buildings. The study renders building design guidance for energy conservation in high altitude plateau areas.

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma–carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.

Safety is the primary guarantee for achieving coal mine production. The degree of water in the overlying rock of the coal seam has a significant impact on the mechanical strength of the rock, which can lead to subsidence, roof collapse, and rock burst in the mining area. Therefore, it is important to study the law of water-rich damage and deterioration of coal seam overlying rock, as well as the characteristics of bursting liability to prevent and control mining disasters. This paper aims to investigate the change in compressive strength, elastic modulus, and bursting liability of coal measure strata under different water content and their relationship with lithology, particle size, pore characteristics, and mineral characteristics. We carried out uniaxial compression tests on drilled and prepared samples of coal measure strata in the east of Ordos City. We also monitored the acoustic emission characteristics of the rock failure process under different water content. The results demonstrate that, in the dry state, the compressive strength of siltstone >fine sandstone >medium sandstone >coarse sandstone. As the water content increases, the rock transitions from brittle to plastic, and the compressive strength, elastic modulus, and bursting liability gradually decrease. The stress-strain curve changes from a single peak to bimodal and multimodal, and the active degree of acoustic emission events decreases, especially the low-value ringing count. Calcareous cementation, clay minerals, and chlorite exhibit strong softening properties when subjected to water, while the grain skeleton (comprising quartz, feldspar, mica) and siliceous cementation displays weak softening properties in such conditions. The most significant is the mechanical strength deterioration of siltstone containing a clay matrix. The research findings can provide reference and theoretical support for safe mining practices in coal mines.

Accidents occur frequently in underground chambers owing to the high-stress environment, poor stability of rocks, and unreasonable mining and construction layout. Significant damage to the deep surrounding rock mass by confined water can result in water inrush and flooding accidents. This study numerically investigated the mechanical properties and acoustic emission (AE) signal evolution mechanism of water-bearing sandstone in deep high-stress mining environments. The results showed that, the lower the confining pressure, the lower is the compressive strength of the specimen, resulting in evident failure. The confining pressure inhibited the radial strain and enhanced the strength of the specimen. Furthermore, under the same confining pressure and different water pressure, the higher the water pressure value, the more evident was the failure phenomenon, and the lower was the peak stress. The water pressure decreased the strength of the specimen and its ability to resist damage. Moreover, for the same water pressure, the smaller the confining pressure, the larger was the maximum AE number and the total cumulative amount of acoustic emissions. When the specimen reached the peak stress and produced macroscopic failure, the AE number reached the maximum value. Finally, the AE activity decreased as the water pressure increased, and the higher the water pressure, the smaller was the cumulative AE number. Owing to the existence of water pressure, the internal structure of the model specimen was affected by the softening effect, which decreased the model strength, thereby suppressing the AE activity of the specimen. Our findings can provide a basis for numerical simulation research on mechanical properties and AE evolution mechanism of water-bearing sandstone under three-way stress state.

Engineered cementitious composites (ECC) exhibits impressive tensile strength but has significant environmental drawbacks due to high cement consumption. Recently, engineered geopolymer composites (EGC) have gained attention as a potential ECC alternative. This comprehensive study reviews the latest EGC advancements, encompassing mix design, design theory, engineering properties, environmental benefits, and durability. It emphasizes how factors like activators, precursors, fibers, additives, and aggregates impact EGC properties, making it a cost-effective material for fire, chemical resistance, and dynamic loads. To address limitations in traditional literature reviews, innovative research methods, including scientometric analysis, were employed to provide a cohesive analysis. This review aims to facilitate knowledge dissemination and collaboration by summarizing EGC advances and highlighting remaining challenges in developing practical applications. It is revealed from the review that various manufacturing methods enhance geopolymers, especially in geopolymer concrete, where replacing 50% of ordinary Portland cement with fly ash boosts strength. Geopolymer concrete excels in pre-cast applications, offering durability and resistance to harsh conditions as an eco-friendly alternative to Portland cement. It suits highway pavement, walls, marine coatings, and tiles, reducing carbon emissions and promoting efficient waste management. EGCs find broad use in construction due to their strong, durable, and eco-friendly qualities, supporting sustainable infrastructure development.

Social equity is essential in the governance of protected areas (PAs), as ignoring such consideration can lead to resistance and jeopardize conservation objectives. However, more research is required to understand the spatial heterogeneity of perceived social equity and its underlying spatial factors. Using a survey of 361 respondents, we presented spatial distribution patterns of perceived equity by kernel density estimation (KDE) in Giant Panda National Park, China. The regression analysis showed that local residents who live closer to the PA boundary are more likely to develop negative responses and those who with easy access to tourism spots have more positive procedural and distributional perceptions. Notably, the proximity to the PA authority decreases locals’ perceptions of fairness in all aspects, which is potentially due to the opaque participative channels provided by the PA authority. We argue that those spatial differentials in fairness perceptions are driven by the intrinsic discrepancy of biodiversity protection requirements and the unevenly distributed consequences of management policies. Key steps to advance social equity considerations include multi-industry guidance, extending participative channels, and co-producing better compensation plans. Herein, this study appeals to a greater focus on the spatial aspect of social equity issues in PAs.

ObjectiveThe detection rates of adrenal masses (AMs) have recently increased. The present study aimed to examine the clinical characteristics of these adrenal masses for guiding the clinical diagnosis and treatment among hospitalized children.MethodsThe clinical data of AM cases admitted to our hospital from January 2014 to March 2023 were collected and analyzed retrospectively. The data included composition, sex, age, initial presentation, size and site of mass, functional tumor, intervention or surgery, pathological or clinical diagnosis, and imaging data.ResultsA total of 207 hospitalized children were included. Among them, adrenal hematoma was the most common finding (53.6%), followed by adrenal neuroblastoma (36.2%). Most masses were larger-sized (51.2%) and non-functional (94.7%). We found that adrenal hematoma commonly occurred in a neonate or child with abdominal trauma. Most adrenal hematoma cases were found in male patients (63.1%), on the right side (71.2%), and with sizes 0.05). However, CT showed a priority over ultrasound in the diagnosis of neuroblastoma (P

Forages fed to goats influence ruminal microbiota, and further contribute to affect growth performance, meat quality and its nutritional composition. Our objective for current study was to investigate the effects of different forages on growth performance, carcass traits, meat nutritional composition, rumen microflora, and the relationships between key bacteria and amino acids and fatty acids in the longissimus dorsi and semimembranosus muscles of goats. Boer crossbred goats were separately fed commercial concentrate diet supplemented with Hemarthria altissima (HA), Pennisetum sinese (PS), or forage maize (FG), and then slaughtered 90 days after the beginning of the experiment. Growth performances did not vary but carcass traits of dressing percentage, semi-eviscerated slaughter percentage, and eviscerated slaughter percentage displayed significant difference with the treatment studied. Meats from goats fed forage maize, especially semimembranosus muscles are rich in essential amino acids, as well as an increase in the amount of beneficial fatty acids. Our 16S rRNA gene sequencing results showed that the Firmicutes, Bacteroidetes, and Proteobacteria were the most dominant phyla in all groups but different in relative abundance. Further, the taxonomic analysis and linear discriminant analysis effect size (LEfSe) identified the specific taxa that were differentially represented among three forage treatments. The spearman’s correlation analysis showed that rumen microbiota was significantly associated with the goat meat nutritional composition, and more significant positive correlations were identified in semimembranosus muscles when compared with longissimus dorsi muscles. More specifically, the lipid metabolism-related bacteria Rikenellaceae_RC9_gut_group showed positively correlated with meat amino acid profile, while genera Oscillospiraceae_UCG-005 were positively correlated with fatty acid composition. These bacteria genera might have the potential to improve nutritional value and meat quality. Collectively, our results showed that different forages alter the carcass traits, meat nutritional composition, and rumen microflora in fattening goats, and forage maize induced an improvement in its nutritional value.

Tryptophan derivatives are various aromatic compounds produced in the tryptophan metabolic pathway, such as 5-hydroxytryptophan, 5-hydroxytryptamine, melatonin, 7-chloro-tryptophan, 7-bromo-tryptophan, indigo, indirubin, indole-3-acetic acid, violamycin, and dexoyviolacein. They have high added value, widely used in chemical, food, polymer and pharmaceutical industry and play an important role in treating diseases and improving life. At present, most tryptophan derivatives are synthesized by biosynthesis. The biosynthesis method is to combine metabolic engineering with synthetic biology and system biology, and use the tryptophan biosynthesis pathway of Escherichia coli, Corynebacterium glutamicum and other related microorganisms to reconstruct the artificial biosynthesis pathway, and then produce various tryptophan derivatives. In this paper, the characteristics, applications and specific biosynthetic pathways and methods of these derivatives were reviewed, and some strategies to increase the yield of derivatives and reduce the production cost on the basis of biosynthesis were introduced in order to make some contributions to the development of tryptophan derivatives biosynthesis industry.

PurposeTo investigate cerebrovascular hemodynamics, including critical closing pressure (CrCP) and pulsatility index (PI), and their independent relationship with cerebral small vessel disease (CSVD) burden in patients with small-vessel occlusion (SVO).MethodsWe recruited consecutive patients with SVO of acute cerebral infarction who underwent brain magnetic resonance imaging (MRI), transcranial Doppler (TCD) and CrCP during admission. Cerebrovascular hemodynamics were assessed using TCD. We used the CSVD score to rate the total MRI burden of CSVD. Multiple regression analysis was used to determine parameters related to CSVD burden or CrCP.ResultsNinety-seven of 120 patients (mean age, 64.51 ± 9.99 years; 76% male) completed the full evaluations in this study. We observed that CrCP was an independent determinant of CSVD burden in four models [odds ratio, 1.41; 95% confidence interval (CI), 1.17–1.71; P < 0.001] and correlated with CSVD burden [β (95% CI): 0.05 (0.04–0.06); P < 0.001]. In ROC analysis, CrCP was considered as a predictor of CSVD burden, and AUC was 86.2% (95% CI, 78.6–93.9%; P < 0.001). Multiple linear regression analysis showed that CrCP was significantly correlated with age [β (95% CI): 0.27 (0.06 to 0.47); P = 0.012], BMI [β (95% CI): 0.61 (0.00–1.22)] and systolic BP [β (95% CI): 0.16 (0.09–0.23); P < 0.001].ConclusionsCrCP representing cerebrovascular tension is an independent determinant and predictor of CSVD burden. It was significantly correlated with age, BMI and systolic blood pressure. These results provide new insights in the mechanism of CSVD development.

BackgroundThe microsatellite stability(MSS) subtype of Colorectal Cancer(CRC) represents approximately 95% of mCRC cases. Immunotherapy was not as encouraging as the data for MSS mCRC cancer. We report the treatment of a series of patients with extrahepatic metastasis of MSS colorectal cancer, which can provide reference and guidance for the treatment of non-hepatic metastasis of MSS colorectal.Case presentationThis report describes 8 typical cases of successful MSS treatment with lung metastases of CRC. We systematically reviewed the clinical data and detailed medical history of one of these patients with extrahepatic metastasis from MSS colorectal cancer, and reviewed the literature to analyze and discuss the related epidemiological features, mechanisms and recent research findings of the special subgroup of the population.ConclusionsAlthough MSS colon rectal cancer is still known as a cold tumor in the industry, immunotherapy combined with multi-targeted anti-vascular tyrosine kinase inhibitors had brought clinical benefits to patients with non-hepatic metastases from MSS colorectal cancer.

IntroductionThe primary factor for cardiovascular disease and upcoming cardiovascular events is atherosclerosis. Recently, carotid plaque texture, as observed on ultrasonography, is varied and difficult to classify with the human eye due to substantial inter-observer variability. High-resolution magnetic resonance (MR) plaque imaging offers naturally superior soft tissue contrasts to computed tomography (CT) and ultrasonography, and combining different contrast weightings may provide more useful information. Radiation freeness and operator independence are two additional benefits of M RI. However, other than preliminary research on MR texture analysis of basilar artery plaque, there is currently no information addressing MR radiomics on the carotid plaque.MethodsFor the automatic segmentation of MRI scans to detect carotid plaque for stroke risk assessment, there is a need for a computer-aided autonomous framework to classify MRI scans automatically. We used to detect carotid plaque from MRI scans for stroke risk assessment pre-trained models, fine-tuned them, and adjusted hyperparameters according to our problem.ResultsOur trained YOLO V3 model achieved 94.81% accuracy, RCNN achieved 92.53% accuracy, and MobileNet achieved 90.23% in identifying carotid plaque from MRI scans for stroke risk assessment. Our approach will prevent incorrect diagnoses brought on by poor image quality and personal experience.ConclusionThe evaluations in this work have demonstrated that this methodology produces acceptable results for classifying magnetic resonance imaging (MRI) data.

Background: Large bone defects resulting from trauma and diseases still a great challenge for the surgeons. Exosomes modified tissue engineering scaffolds are one of the promising cell-free approach for repairing the defects. Despite extensive knowledge of the variety kinds of exosomes promote tissue regeneration, little is known of the effect and mechanism for the adipose stem cells-derived exosomes (ADSCs-Exos) on bone defect repair. This study aimed to explore whether ADSCs-Exos and ADSCs-Exos modified tissue engineering scaffold promotes bone defects repair.Material/Methods: ADSCs-Exos were isolated and identified by transmission electron microscopy nanoparticle tracking analysis, and western blot. Rat bone marrow mesenchymal stem cells (BMSCs) were exposed to ADSCs-Exos. The CCK-8 assay, scratch wound assay, alkaline phosphatase activity assay, and alizarin red staining were used to evaluate the proliferation, migration, and osteogenic differentiation of BMSCs. Subsequently, a bio-scaffold, ADSCs-Exos modified gelatin sponge/polydopamine scaffold (GS-PDA-Exos), were prepared. After characterized by scanning electron microscopy and exosomes release assay, the repair effect of the GS-PDA-Exos scaffold on BMSCs and bone defects was evaluated in vitro and in vivo.Results: The diameter of ADSCs-exos is around 122.1 nm and high expressed exosome-specific markers CD9 and CD63. ADSCs-Exos promote the proliferation migration and osteogenic differentiation of BMSCs. ADSCs-Exos was combined with gelatin sponge by polydopamine (PDA)coating and released slowly. After exposed to the GS-PDA-Exos scaffold, BMSCs have more calcium nodules with osteoinductive medium and higher expression the mRNA of osteogenic related genes compared with other groups. The quantitative analysis of all micro-CT parameters showed that GS-PDA-Exos scaffold promote new bone formed in the femur defect model in vivo and confirmed by histological analysis.Conclusion: This study demonstrates the repair efficacy of ADSCs-Exos in bone defects, ADSCs-Exos modified scaffold showing a huge potential in the treatment of large bone defects.

BackgroundTesticular torsion (TT) is a common urological emergency posing serious health problem in children. Prompt diagnosis and treatment of TT are very important for children to protect the affected testis. The aim of this study was to evaluate the historical features, physical examination findings, laboratory tests, and ultrasound examinations in children with TT, as well as to identify the predictors of testicular salvage in children.Materials and methodsWe conducted a retrospective record of clinical findings, laboratory data, ultrasound findings, operating results, and the results of follow-up in hospitalized children with TT from November 2004 to December 2021. A multivariable logistic regression model was used to identify predictors of testicular salvage.ResultsA total 102 hospitalized children who presented with TT were included. Patients were aged from 1 month to 16 years, with a median age of 7.71 years. TT is significantly more common in the winter. Of these patients, 77 torsions were left-sided, 24 were on the right side, and only 1 was on bilateral sides. Meanwhile, we detected that 88 children suffering from TT had intravaginal torsion of the spermatic cord, and the rest were outside. Anticlockwise torsion was found in 65 cases (63.73%) and clockwise torsion in 37 (36.27%). As a result, 60 underwent orchidectomy, while 42 had a scrotal exploration with fixation of the testis. Multivariate analysis showed that cause of TT, time to intervention, white blood cell (WBC), and mean platelet volume (MPV) were correlated with the risk of a surgical outcome.ConclusionOnly a small proportion of TT children received timely surgical management. Testicular salvage can be predicted by cause of TT, time to intervention, WBC, and MPV. Early scrotal exploration based on careful physical examination decreases the risk of misdiagnosis of spermatic cord torsion. A certain percentage of children with TT presenting with scrotal trauma or epididymo-orchitis should have their testicles checked to make sure that they do not have torsion, especially those who visit in the cold season.

ObjectiveThe present study aimed to evaluate the value of Modified Nutrition Risk in Critically ill (mNUTRIC) and Nutrition Risk Screening 2002 (NRS2002) in the prognosis of severely burned patients.MethodsThe retrospective cohort study used medical data of severely burned patients admitted to the burn center of Shanghai Ruijin Hospital between January 2015 and September 2021. Demographics, clinical characteristics, laboratory nutritional indicators, mNUTRIC score and NRS2002 score were collected and analyzed in evaluation the value of two nutrition risk screening tools. Spearman correlation analysis was carried out to show the correlation between variables. The area under receiver operating characteristic (ROC) curve was used to assess the ability of mNUTRIC and NRS2002 to predict mortality. Kaplan–Meier survival curves and log-rank tests were conducted to compare the overall survival (OS). Multivariate Cox proportional hazard regression model was used to identify risk factors for 28-day mortality of severely burned patients.ResultsA total of 429 adult patients with burn area larger than 30% total body surface area (TBSA) were included in this study. Incidence of nutrition risk was detected in 52.21% by mNUTRIC and 20.51% by NRS2002. However, mNUTRIC was superior to NRS2002 in predicting 28-day mortality (area under ROC curve: 0.795 vs. 0.726). Multivariate Cox regression analysis showed that high mNUTRIC [hazard ratio (HR) = 4.265, 95% CI = 1.469–12.380, P = 0.008] and TBSA (HR = 1.056, 95% CI = 1.033–1.079, P < 0.001) were independent predictors for 28-day mortality. After adjusting for covariates, high NRS2002 was not associated with 28-day mortality (P = 0.367).ConclusionThe present study illustrated the effectiveness of mNUTRIC as nutrition risk screening tool among severely burned patients. Early identification of nutrition risk may help to maximize benefits of nutritional therapy by providing more aggressive nutritional therapy for patients at nutrition risk.

ObjectivesPrediction of the efficacy of continuous positive airway pressure (CPAP) on bronchiolitis is necessary for timely treatment. This study aims to establish a nomogram for efficacy of CPAP on bronchiolitis, and compares accuracy with Pediatric Risk of Mortality III (PRISM III), Brighton Pediatric Early Warning Score (Brighton PEWS) and Pediatric Critical Illness Score (PCIS).MethodsFrom February 2014 to December 2020, data on children diagnosed with bronchiolitis and treated with CPAP in Chongqing was collected. The nomogram was evaluated by using multivariate logistic regression analysis. We compared the predictive value of model with PRISM III, PEWS and PCIS.ResultsA total of 510 children were included. The nomogram prediction model including fever, APTT, white blood cells, serum potassium concentration, lactic acid, immunodeficiency, atelectasis, lung consolidation, congenital airway dysplasia and congenital heart disease was established. The AUC of the nomogram was 0.919 in the training set and 0.947 in the validating set. The model fitted well, as evidenced by the calibration curve and Hosmer-Lemeshow goodness-of-fit test. We discovered that the nomogram significantly performed better than PRISM III, PCIS and PEWS.ConclusionsA nomogram including ten factors for predicting the efficacy of CPAP on bronchiolitis was established. It had higher performance than the PRISM III, PCIS, and PEWS in terms of clinical benefits.

BackgroundQuantitative contrast-enhanced ultrasonography parameters are affected by various factors. We evaluated corrected quantitative contrast enhanced ultrasonography in differentiating benign adnexal tumors from malignant tumors.MethodsPatients with adnexal masses who underwent conventional and contrast-enhanced ultrasonography were included. Contrast-enhanced ultrasonography parameters such as base intensity, arrival time, peak intensity, time to peak intensity, ascending slope, and descending slope were measured. Corrected (time to peak intensity − arrival time) mass/(time to peak intensity − arrival time) uterus and (peak intensity − base intensity) mass/(peak intensity − base intensity) uterus were calculated. Lesions were confirmed by pathologic examination of surgical specimens.ResultsThis study included 31 patients with 35 adnexal lesions including 20 (57.10%) benign and 15 (42.90%) malignant lesions. The corrected contrast-enhanced ultrasonography quantitative parameters in lesions were statistically different between malignant and benign groups (P

Preterm birth is a worldwide problem that affects infants throughout their lives significantly. Therefore, differentiating brain disorders, and further identifying and characterizing the corresponding biomarkers are key issues to investigate the effects of preterm birth, which facilitates the interventions for neuroprotection and improves outcomes of prematurity. Until now, many efforts have been made to study the effects of preterm birth; however, most of the studies merely focus on either functional or structural perspective. In addition, an effective framework not only jointly studies the brain function and structure at a group-level, but also retains the individual differences among the subjects. In this study, a novel dense individualized and common connectivity-based cortical landmarks (DICCCOL)-based multi-modality graph neural networks (DM-GNN) framework is proposed to differentiate preterm and term infant brains and characterize the corresponding biomarkers. This framework adopts the DICCCOL system as the initialized graph node of GNN for each subject, utilizing both functional and structural profiles and effectively retaining the individual differences. To be specific, functional magnetic resonance imaging (fMRI) of the brain provides the features for the graph nodes, and brain fiber connectivity is utilized as the structural representation of the graph edges. Self-attention graph pooling (SAGPOOL)-based GNN is then applied to jointly study the function and structure of the brain and identify the biomarkers. Our results successfully demonstrate that the proposed framework can effectively differentiate the preterm and term infant brains. Furthermore, the self-attention-based mechanism can accurately calculate the attention score and recognize the most significant biomarkers. In this study, not only 87.6% classification accuracy is observed for the developing Human Connectome Project (dHCP) dataset, but also distinguishing features are explored and extracted. Our study provides a novel and uniform framework to differentiate brain disorders and characterize the corresponding biomarkers.

Drug combinations can increase the therapeutic effect by reducing the level of toxicity and the occurrence of drug resistance. Therefore, several drug combinations are often used in the management of complex diseases. However, due to the exponential growth in drug development, it would be impractical to evaluate all combinations through experiments. In view of this, we developed Pathway Interaction Network (PINet) biological model to estimate the optimal drug combinations for various diseases. The random walk with restart (RWR) algorithm was used to capture the “disease state” and “drug state,” while PINet was used to evaluate the optimal drug combinations and the high-order drug combination1. The model achieved a mean area under the curve of a receiver operating characteristic curve of 0.885. In addition, for some diseases, PINet predicted the optimal drug combination. For example, in the case of acute myeloid leukemia, PINet correctly predicted midostaurin and gemtuzumab as effective drug combinations, as demonstrated by the results of a Phase-I clinical trial. Moreover, PINet also correctly predicted the potential drug combinations for diseases that lacked a training dataset that could not be predicted using standard machine learning models.

We aimed to validate the performance of the ratio of the platelet count (PLT) to liver stiffness measurement (LSM) in excluding high-risk varices (HRVs) in patients with hepatitis B virus (HBV)-related compensated cirrhosis beyond Baveno VI criteria. A total of 310 patients were assessed. The performances of the PLT:LSM ratio (PLER), PLER adjusted for the international normalized ratio, etiology, age, and sex (PLEASE), and the sequential algorithm for HRV screening (VariScreen) in excluding HRVs were evaluated and compared with those of expanded Baveno VI criteria (LSM 110×109/L, EB6C); PLT >150×109/L and model for end-stage liver disease score = 6 (P150M6 criterion); PLT >120×109/L and albumin >36 g/L (P120A36 criterion); and albumin-bilirubin (ALBI) grade and PLT score (ALBI-PLT score). Among the enrolled patients, 43 (13.9%) had HRVs. The area under the receiver operating characteristic curve of PLER for predicting HRVs (0.771, 95% confidence interval, 0.720–0.817) was significantly higher than that for PLT and LSM (p < 0.01). PLER was an independent risk factor for HRVs. VariScreen, PLEASE, and PLER could spare 20 (6.5%), 91 (29.4%), and 60 (19.4%) endoscopies, with 0, 3 (3.3%), and 1 (1.7%) HRVs missed, respectively. The EB6C and P120A36 criteria could spare 45 (14.5%) and 36 (11.6%) endoscopies, with 1 (2.2%) and 1 (2.8%) HRVs missed, respectively. The P150M6 criterion and ALBI-PLT score missed 6.8% and 10.3% of HRVs, respectively. We found that PLER performed better than other non-invasive tests. VariScreen secured the screening of HRVs in patients with HBV-related cirrhosis beyond Baveno VI criteria.

PurposeIn this study, we aim to further evaluate the accuracy of ultrasound tracking for intra-fraction pancreatic tumor motion during radiotherapy by a phantom-based study.MethodsTwelve patients with pancreatic cancer who were treated with stereotactic body radiation therapy were enrolled in this study. The displacement points of the respiratory cycle were acquired from 4DCT and transferred to a motion platform to mimic realistic breathing movements in our phantom study. An ultrasound abdominal phantom was placed and fixed in the motion platform. The ground truth of phantom movement was recorded by tracking an optical tracker attached to this phantom. One tumor inside the phantom was the tracking target. In the evaluation of the results, the monitoring results from the ultrasound system were compared with the phantom motion results from the infrared camera. Differences between infrared monitoring motion and ultrasound tracking motion were analyzed by calculating the root-mean-square error.ResultsThe 82.2% ultrasound tracking motion was within a 0.5 mm difference value between ultrasound tracking displacement and infrared monitoring motion. 0.7% ultrasound tracking failed to track accurately (a difference value > 2.5 mm). These differences between ultrasound tracking motion and infrared monitored motion do not correlate with respiratory displacements, respiratory velocity, or respiratory acceleration by linear regression analysis.ConclusionsThe highly accurate monitoring results of this phantom study prove that the ultrasound tracking system may be a potential method for real-time monitoring targets, allowing more accurate delivery of radiation doses.

Established a model of lipopolysaccharide (LPS)-induced mastitis in mice, pathological sections and myeloperoxidase were used to detect the degree of tissue damage, enzyme-linked immunosorbent assay (ELISA) was performed to detect the expression of pro-inflammatory cytokines, meanwhile fluorescence quantitative PCR experiments were performed to detect the mRNA expression of CD14/TLR4/NF-κB/MAPK signalling pathway, and the faeces of mice were collected for 16S measurement of flora. The results showed that Abrus cantoniensis total flavonoids (ATF) could significantly reduce the damage of LPS on mammary tissue in mice and inhibit the secretion of inflammatory factors such as TNF-α, IL-1β and IL-6. At the mRNA level, ATF inhibited the expression of CD14/TLR4/NF-κB/MAPK pathway and enhanced the expression of tight junction proteins in the blood-milk barrier. In the results of the intestinal flora assay, ATF were found to be able to regulate the relative abundance of the dominant flora from the phylum level to the genus level, restoring LPS-induced gut microbial dysbiosis. In summary, ATF attenuated the inflammatory response of LPS on mouse mammary gland by inhibiting the expression of CD14/TLR4/NF-κB/MAPK pathway, enhancing the expression of tight junction proteins and restoring LPS-induced gut microbial dysbiosis. This suggests that ATF could be a potential herbal remedy for mastitis.

In the current social media environment, emotional branding communication has become a common marketing tool for brand owners, and therefore it has become particularly important and urgent to study it. Based on the perspective of brand equity theory, combined with the new characteristics of marketing communication in the social media environment, this paper constructed an emotional branding communication model in the social media environment. The system dynamics (SD) method was used to simulate and analyze the new product marketing system to assess whether it could stir the emotional needs of the consumers and resonate within their hearts. This paper discusses the asymmetric communication of different brands regarding the same commodity to determine the impact of this exchange mechanism, that is, only the weak brands in the market initially adopt marketing methods, while the strong brands do not participate in social marketing activities. It was found that the influence of marketing frequency and marketing intensity on symmetric and asymmetric communications was different. In the face of different types of competitors, the marketing strategy of weak brands needs emphasis. Through unit consistency test, structure verification test, effectiveness, and rationality test, it was proven that the emotional branding communication model and new product sales interaction simulation model established in this paper were reasonable and effective.

The δ-opioid receptor (δOR) has been considered as a therapeutic target in multiple neurological and neuropsychiatric disorders particularly as δOR agonists are deemed safer alternatives relative to the more abuse-liable µ-opioid receptor drugs. Clinical development of δOR agonists, however, has been challenging in part due to the seizure-inducing effects of certain δOR agonists. Especially agonists that resemble the δOR-selective agonist SNC80 have well-established convulsive activity. Close inspection suggests that many of those seizurogenic δOR agonists efficaciously recruit β-arrestin, yet surprisingly, SNC80 displays enhanced seizure activity in β-arrestin 1 knockout mice. This finding led us to hypothesize that perhaps β-arrestin 1 is protective against, whereas β-arrestin 2 is detrimental for δOR-agonist-induced seizures. To investigate our hypothesis, we characterized three different δOR agonists (SNC80, ADL5859, ARM390) in cellular assays and in vivo in wild-type and β-arrestin 1 and β-arrestin 2 knockout mice for seizure activity. We also investigated downstream kinases associated with β-arrestin-dependent signal transduction. We discovered that δOR agonist-induced seizure activity strongly and positively correlates with β-arrestin 2 efficacy for the agonist, but that indirect inhibition of ERK activation using the MEK inhibitor SL327 did not inhibit seizure potency and duration. Inhibition of the PI3K/AKT/mTOR signaling with honokiol but not PQR530, attenuated SNC80 seizure duration in β-arrestin 1 knockout, but honokiol did not reduce SNC80-induced seizures in wild-type mice. Ultimately, our results indicate that β-arrestin 2 is correlated with δOR agonist-induced seizure intensity, but that global β-arrestin 1 knockout mice are a poor model system to investigate their mechanism of action.

Under low confinement axial compression, the failure of brittle rock is mainly caused by tensile fracture. Many scholars adopt the sliding crack as an idealized model to present the intrinsic mechanism of the tensile failure but due to the complex configuration of sliding crack, its stress intensity factor (SIF) calculation has always been a difficult problem. In this study, an improved model of sliding crack is proposed; in the context of linear elastic fracture mechanics (LEFM) and weight function method, the expression of stress intensity factor (SIF) has been derived. The propagation manners of sliding crack under axial loading and lateral unloading conditions have been further analyzed. The extended finite element method (XFEM) is employed to verify the correctness of the theoretical SIF formulation and its inferences. The formula of SIF shows that a sliding crack is highly sensitive to the change of the lateral stress, which theoretically explains compressive failure characteristics of brittle rock as follows: 1) under the condition of axial compression, increasing the lateral stress has a very strong no-linear impact on the strength of brittle rock; 2) under the condition of lateral unloading, the destruction of rock is more abrupt and ferocious than that of the loading case. In order to confirm that micro-fractures in rocks are notably influenced by confining pressure, as the former theoretical fracture analysis predicted, the tri-axial compression test combined with the acoustic emission monitoring technique has been conducted on basalt samples. According to the acoustic waveform parameter method, it shows that increasing the confining pressure will greatly reduce the proportion of tension-type fractures, which indirectly proves the correctness of the sliding crack hypothesis and fracture analysis.

AimsTo explore the effects of age and sex on the outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients with the three-vessel disease (TVD).Methods and ResultsThe study is a subanalysis of data from a prospective cohort of 8,943 patients with angiographically confirmed TVD at Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China. The primary end point was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. In total, 2,819 patients with NSTE-ACS who received CABG (43.6%) or PCI (56.4%) were included, among whom 32.7% were of 65–74 years, 7.2% were ≥75 years, and 22.6% were women. The median follow-up duration was 6.8 years. The superiority of CABG relative to PCI in terms of MACCE was decreased with age (adjusted hazard ratio [HR] [95% confidence interval (CI)]:

The Achilles tendon (AT) is responsible for running, jumping, and standing. The AT injuries are very common in the population. In the adult population (21–60 years), the incidence of AT injuries is approximately 2.35 per 1,000 people. It negatively impacts people’s quality of life and increases the medical burden. Due to its low cellularity and vascular deficiency, AT has a poor healing ability. Therefore, AT injury healing has attracted a lot of attention from researchers. Current AT injury treatment options cannot effectively restore the mechanical structure and function of AT, which promotes the development of AT regenerative tissue engineering. Various nanofiber-based scaffolds are currently being explored due to their structural similarity to natural tendon and their ability to promote tissue regeneration. This review discusses current methods of AT regeneration, recent advances in the fabrication and enhancement of nanofiber-based scaffolds, and the development and use of multiscale nanofiber-based scaffolds for AT regeneration.

Aluminum grating has wide applications in laser systems and photoelectric equipment. Research on the laser damage characteristics of aluminum grating has guiding significance and application value for improving the laser damage resistance. The aim of this study is to investigate the characteristics of damage induced by nanosecond pulsed lasers on the aluminum grating. To better understand the laser damage characteristics of aluminum grating, herein, Maxwell’s equations were numerically solved according to the finite difference time-domain method, and the electric field model of 1,064 nm Gaussian laser damage aluminum grating was established. The simulation results showed that the light field is modulated by the grating; furthermore, the maximum value of the electric field occurred at the ridge of the grating when the laser is irradiated vertically. Analysis suggested that the electric field distribution is in accordance with the laser energy distribution, and the distribution region of the maximum electric field is a vulnerable location. To further verify the local electric field enhancement effect, based on the 1-on-1 laser damage measurement method, an experimental study of the nanosecond laser (@1,064 nm, 6.5 ns) damage to the aluminum grating was carried out. Moreover, the damage morphology was analyzed using a scanning electron microscope (SEM), and the simulation results showed good agreement with the experimental results.

This study aimed to evaluate the role of the clinical pharmacist in the rational use of proton pump inhibitors (PPIs) in a general surgery department. All enrolled patients had attended the general surgery department of a tertiary hospital. This single-center prospective study compared differences in the overall rate of rational PPI use, proportion of unindicated PPI use, utilization rate, average defined daily dose (DDD), drug costs, PPI costs, and cost-effectiveness of clinical pharmacist intervention between the intervention (538 cases) and control (536 cases) groups. In the intervention group, Pareto and fishbone diagram analyses were combined with the Plan-Do-Check-Act cycle; Statistical Package for the Social Sciences was used for analyzing all data. The overall rate of rational PPI use was significantly higher in the intervention group than in the control group (p < 0.01). The proportion of unindicated PPI use, utilization rate, average DDD, drug costs, and PPI costs were significantly lower in the intervention group than in the control group (p < 0.05). Cost-effectiveness analysis for the overall rate of rational PPI use indicated a positive impact of intervention, with economic benefits in the intervention group. Clinical pharmacist intervention for rational use of PPIs in general surgery departments could significantly increase the overall rate of rational PPI use; it could also reduce the proportion of unindicated PPI use, utilization rates, average DDDs, drug costs, and PPIs costs. Pharmacist intervention also offers economic benefits by improving the overall rate of rational PPI use.

PurposeTo evaluate the association between diabetes risk reduction diet (DRRD) score and the risk of lung cancer in a large population.MethodsData of participants in this study were collected from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in the Cox proportional hazards regression model for the association of DRRD score and lung cancer incidence in all included participants. Prespecified subgroup analyses were performed to evaluate whether the observed association was modified by age, sex, BMI, race/ethnicity, family history of lung cancer, smoking status and history of diabetes.ResultsA total of 98,159 participants were included in this study. The mean (SD) age of the study participants cohort at baseline was 65.5 (5.73) years old. The mean (SD) follow-up time was 8.83 (1.96) years. The mean (SD) score of DRRD was 26.82 (5.19), and ranged from 20.47 (2.3) to 33.65 (2.42) from the lowest quartile to the highest quartile of the DRRD score, inferring the possibility of highest through the lowest risk of type 2 diabetes. The calculated HRs showed there was a trend that higher quartile indicated lower risk of lung cancer after adjusted for covariates (HRQ4vsQ1: 0.85; 95% CI:0.73,0.98; p for trend =0.036). The inverse trend between higher DRRD score and the risk of squamous cell carcinoma was more evident (HRQ4vsQ1: 0.50; 95% CI:0.34,0.73; p for trend =0.002). The inverse association between DRRD score and the incidence of lung cancer was more pronounced in participants who had a clear family history of lung cancer (p for interaction=0.016).ConclusionA protective association between DRRD score and risk of lung cancer is obtained. People are encouraged to adhere to higher DRRD score in their daily diet. Further studies should be conducted to confirm the result and explore the mechanism.

Depression is one of the main diseases that lead to disability and loss of ability to work. As a traditional Chinese medicine, Zhi-zi-chi decoction is utilized to regulate and improve depression. However, the research on the antidepressant mechanism and efficacy material basis of Zhi-zi-chi decoction has not been reported yet. Our previous research has found that Zhi-Zi-chi decoction can reduce glutamate-induced oxidative stress damage to PC 12 cells, which can exert a neuroprotective effect, and the antidepressant effect of Zhi-Zi-chi decoction was verified in CUMS rat models. In this study, the animal model of depression was established by chronic unpredictable mild stimulation combined with feeding alone. The brain metabolic profile of depressed rats was analyzed by the method of metabolomics based on ultra-performance liquid chromatography-quadrupole/time-of-flight mass. 26 differential metabolites and six metabolic pathways related to the antidepressant of Zhi-zi-chi decoction were screened and analyzed. The targeted metabolism of the glutathione metabolic pathway was analyzed. At the same time, the levels of reactive oxygen species, superoxide dismutase, glutathione reductase, glutathione peroxidase in the brain of depressed rats were measured. Combined with our previous study, the antioxidant effect of the glutathione pathway in the antidepressant effect of Zhi-zi-chi decoction was verified from the cellular and animal levels respectively. These results indicated that Zhi-zi-chi decoction exerted a potential antidepressive effect associated with reversing the imbalance of glutathione and oxidative stress in the brain of depressed rats.

The invasiveness and high proliferation rate of growth hormone-secreting pituitary adenomas (GHPAs) are closely related to poor prognosis in patients. We previously reported that abnormal glycolysis participates in this process; however, the role of mitochondria in the invasion and proliferation of GHPAs remains unknown. In the current study, stereological methods were first used to quantitatively calculate the number and morphology of mitochondria. The results revealed that the numbers, volumes and membrane areas of mitochondria were decreased in invasive GHPAs (IGHPAs) samples compared to noninvasive GHPAs (NIGHPAs) samples. Furthermore, significantly downregulated mRNA and protein levels of dynamin-related protein 1 (Drp1) were detected in IGHPAs, but no notable changes in fusion related molecules (Mfn1, Mfn2 and OPA1) were detected, suggesting that the abnormal mitochondrial dynamics in IGHPAs are characterized by hypofission. Mitochondrial hypofission caused by Mdivi-1, a specific Drp1 inhibitor, enhanced the invasion and proliferation of GH3 cell lines and primary cells from patients with GHPAs in vitro and in vivo, while overexpression of Drp1 reversed these processes. Mechanistically, mitochondrial hypofission might activate signal transducer and activator of transcription 3 (STAT3). Specifically, elevated nuclear pSTAT3Y705 may promote GH3 cell invasion by upregulating the activity of matrix metalloproteinase 2/9, and elevated mitochondrial pSTAT3S727 may promote GH3 cell proliferation by inhibiting the mitochondria-dependent apoptotic pathway. Taken together, our findings suggest that mitochondrial hypofission induced by Drp1 might strengthen the invasion and proliferation of GHPA tumor cells by activating STAT3, providing us with a new perspective on how mitochondria regulate the development of IGHPAs.

Objective: To explore the value of 18F-fluordeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) semi-quantitative parameters of primary tumor combined with squamous cell carcinoma antigen (SCC-Ag) in predicting lymph nodemetastasis (LNM) of cervical cancer (FIGO2018 stage I-II). Materials and Methods: A total of 65 patients with stage I-II cervical cancer underwent 18F-FDG PET/CT were included in our study. Comparing the primary tumor 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag between the LNM group and the non-LNM group. Logistic regression and receiver operating characteristic (ROC) were used to analyze the value of 18F-FDG PET/CT metabolic parameters and SCC-Ag in predicting LNM. Results: There were 14 and 51 patients were classified as having LNM and NLNM. The semi-quantitative parameters, including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), the total lesion glycolysis (TLG), the metabolic tumor volume (MTV) of the tumor and SCC-Ag were all significantly higher in LNM than in NLNM (SUVmax, 16.07 ± 7.81 vs 11.19 ± 4.73, SUVmean, 9.16 ± 3.48 vs 6.29 ± 2.52, SUVpeak, 12.70 ± 5.26 vs 7.65 ± 3.26, MTV, 22.77 ± 12.36 vs 7.09 ± 5.21, TLG, 211.01 ± 154.25 vs 43.38 ± 36.17, SCC-Ag, 5.39 ± 4.56 vs 2.13 ± 2.50, all p<0.01). Logistic regression analysis showed that TLG was an independent predictor of LNM in stage I-II cervical cancer (OR 1.032, 95% CI 1.013-1.052, p<0.01). Moreover, the predictive value of TLG combined with SUVpeak and SCC-Ag increased and the area under the curve increased compared SUVpeak and SCC-Ag. Conclusion: 18F-FDG PET/CT semi-quantitative parameters and SCC-Ag have promise for assessing LNM in stage I-II cervical cancer. TLG of primary tumor provides independent and increasing values in predicting LNM in stage I-II cervical cancer. [ABSTRACT FROM AUTHOR]

BackgroundThe overall survival (OS) of pancreatic cancer (PC) patients with bone metastasis (BM) is extremely low, and it is pretty hard to treat bone metastasis. However, there are currently no effective nomograms to predict the diagnosis and prognosis of pancreatic cancer with bone metastasis (PCBM). Therefore, it is of great significance to establish effective predictive models to guide clinical practice.MethodsWe screened patients from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2016. The independent risk factors of PCBM were identified from univariable and multivariable logistic regression analyses, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors affecting the prognosis of PCBM. In addition, two nomograms were constructed to predict the risk and prognosis of PCBM. We used the area under the curve (AUC), C-index and calibration curve to determine the predictive accuracy and discriminability of nomograms. The decision curve analysis (DCA) and Kaplan-Meier(K-M) survival curves were employed to further confirm the clinical effectiveness of the nomogram.ResultsMultivariable logistic regression analyses revealed that risk factors of PCBM included age, primary site, histological subtype, N stage, radiotherapy, surgery, brain metastasis, lung metastasis, and liver metastasis. Using Cox regression analyses, we found that independent prognostic factors of PCBM were age, race, grade, histological subtype, surgery, chemotherapy, and lung metastasis. We utilized nomograms to visually express data analysis results. The C-index of training cohort was 0.795 (95%CI: 0.758-0.832), whereas that of internal validation cohort was 0.800 (95%CI: 0.739-0.862), and the external validation cohort was 0.787 (95%CI: 0.746-0.828). Based on AUC of receiver operating characteristic (ROC) analysis, calibration plots, and decision curve analysis (DCA), we concluded that the risk and prognosis model of PCBM exhibits excellent performance.ConclusionNomogram is sufficiently accurate to predict the risk and prognostic factors of PCBM, allowing for individualized clinical decisions for future clinical work.

Since the emergence of deep neural network (DNN), it has achieved excellent performance in various research areas. As the combination of DNN and reinforcement learning, deep reinforcement learning (DRL) becomes a new paradigm for solving differential game problems. In this study, we build up a reinforcement learning environment and apply relevant DRL methods to a specific bio-inspired differential game problem: the dog sheep game. The dog sheep game environment is set on a circle where the dog chases down the sheep attempting to escape. According to some presuppositions, we are able to acquire the kinematic pursuit and evasion strategy. Next, this study implements the value-based deep Q network (DQN) model and the deep deterministic policy gradient (DDPG) model to the dog sheep game, attempting to endow the sheep the ability to escape successfully. To enhance the performance of the DQN model, this study brought up the reward mechanism with a time-out strategy and the game environment with an attenuation mechanism of the steering angle of sheep. These modifications effectively increase the probability of escape for the sheep. Furthermore, the DDPG model is adopted due to its continuous action space. Results show the modifications of the DQN model effectively increase the escape probabilities to the same level as the DDPG model. When it comes to the learning ability under various environment difficulties, the refined DQN and the DDPG models have bigger performance enhancement over the naive evasion model in harsh environments than in loose environments.

Patients with severe chronic graft-versus-host disease (cGVHD) always experience debilitating tissue injury and have poorer quality of life and shorter survival time. The early stage of cGVHD is characterized by inflammation, which eventually leads to extensive tissue fibrosis in various organs, such as skin and lung, eventually inducing scleroderma-like changes and bronchiolitis obliterans syndrome. Here we review the functions of serum/glucocorticoid regulated kinase 1 (SGK1), a hub molecule in multiple signal transduction pathways and cell phosphorylation cascades, which has important roles in cell proliferation and ion channel regulation, and its relevance in cGVHD. SGK1 phosphorylates the ubiquitin ligase, NEDD4, and induces Th cells to differentiate into Th17 and Th2 phenotypes, hinders Treg development, and promotes inflammatory fibrosis. Phosphorylation of NEDD4 by SGK1 also leads to up-regulation of the transcription factor SMAD2/3, thereby amplifying the fibrosis-promoting effect of TGF-β. SGK1 also up-regulates the inflammatory transcription factor, nuclear factor-κB (NF-κB), which in turn stimulates the expression of multiple inflammatory mediators, including connective tissue growth factor. Overexpression of SGK1 has been observed in various fibrotic diseases, including pulmonary fibrosis, diabetic renal fibrosis, liver cirrhosis, hypertensive cardiac fibrosis, peritoneal fibrosis, and Crohn’s disease. In addition, SGK1 inhibitors can attenuate, or even reverse, the effect of fibrosis, and may be used to treat inflammatory conditions and/or fibrotic diseases, such as cGVHD, in the future.

ObjectivesThe purpose of this study is to independently compare the performance of the inverse planning algorithm utilized in Gamma Knife (GK) Lightning Treatment Planning System (TPS) to manual forward planning, between experienced and inexperienced users, for different types of targets.Materials and MethodsForty patients treated with GK stereotactic radiosurgery (SRS) for pituitary adenoma (PA), vestibular schwannoma (VS), post-operative brain metastases (pBM), and intact brain metastases (iBM) were randomly selected, ten for each site. Three inversely optimized plans were generated for each case by two experienced planners (OptExp1 and OptExp2) and a novice planner (OptNov) using GK Lightning TPS. For each treatment site, the Gradient Index (GI), the Paddick Conformity Index (PCI), the prescription percentage, the scaled beam-on time (sBOT), the number of shots used, and dosimetric metrics to OARs were compared first between the inversely optimized plans and the manually generated clinical plans, and then among the inversely optimized plans. Statistical analyses were performed using the Student’s t-test and the ANOVA followed by the post-hoc Tukey tests.ResultsThe GI for the inversely optimized plans significantly outperformed the clinical plans for all sites. PCIs were similar between the inversely optimized and clinical plans for PA and VS, but were significantly improved in the inversely optimized plans for iBM and pBM. There were no significant differences in the sBOT between the inversely optimized and clinical plans, except for the PA cases. No significant differences were observed in dosimetric metrics, except for lower brain V12Gy and PTV D98% in the inversely optimized plans for iBM. There were no noticeable differences in plan qualities among the inversely optimized plans created by the novice and experienced planners.ConclusionInverse planning in GK Lightning TPS produces GK SRS plans at least equivalent in plan quality and similar in sBOT compared to manual forward planning in this independent validation study. The automatic workflow of inversed planning ensures a consistent plan quality regardless of a planner’s experience.

PurposeIn radiotherapy, high radiation exposure to optic nerve (ON) can cause optic neuropathy or vision loss. In this study, we evaluated the pattern and extent of the ON movement using MRI, and investigated the potential dosimetric effect of this movement on radiotherapy.MethodsMRI was performed in multiple planes in 5 human subjects without optic pathway abnormalities to determine optic nerve motion in different scenarios. The subjects were requested to gaze toward five directions during MRI acquisitions, including neutral (straight forward), left/right (horizontal movement), and up/down (vertical movement). Subsequently, the measured displacement was applied to patients with peri-optic tumors to evaluate the potential dosimetric effect of this motion.ResultsThe motion of ON followed a nearly conical shape. By average, the anterior end of ONs moved with 10.8 ± 2.2 mm horizontally and 9.3 ± 0.8 mm vertically, while posterior end has negligible displacement. For patients who underwent stereotactic radiotherapy to a peri-optic tumors, the movement of ON in this measured range introduced non-negligible dosimetric effect.ConclusionThe range of motion of the anterior portions of the optic nerves is on the order of centimeters, which may need to be considered with extra attention during radiation therapy in treating peri-optic lesions.

With the increasing control of air pollution, the levels of atmospheric particulates in the Pearl River Delta (PRD) region are gradually decreasing. However, ozone pollution has become more and more serious, and the problem of secondary aerosol pollution caused by photochemical reactions cannot be ignored. Based on the observation data of environmental and meteorological stations in the nine cities of the PRD during 2019, we investigated the variations of secondary PM2.5 (PM2.5-sec) in the PRD under different photochemical reactivity backgrounds. It was shown that the photochemical reactivities appeared more significant in the central and western areas than those in the eastern areas of the PRD and appeared more significant in inland areas than those in coastal areas. The days of moderate and high photochemical reactivities mainly appeared from August to November. PM2.5-sec concentrations were the highest in autumn, during which the regional discrepancies appeared most significantly with the highest levels in the southern areas. With the enhancement of the photochemical reactivity background, the PM2.5-sec level at each station increased significantly, which appeared significantly higher in coastal areas than in inland areas. Both PM2.5-sec and ozone concentrations showed single-peak variations, which appeared higher in the daytime than at night with the peak occurring at about 15:00. For each pollutant, the average maximum concentration appeared higher for polluted stations than for clean ones, indicating that the atmospheric oxidation background was conducive to the formation of PM2.5-sec.

ObjectivesThe beam output of a double scattering proton system varies for each combination of beam option, range, and modulation and therefore is difficult to be accurately modeled by the treatment planning system (TPS). This study aims to design an empirical method using the analytical and machine learning (ML) models to estimate proton output in a double scattering proton system.Materials and MethodsThree analytical models using polynomial, linear, and logarithm–polynomial equations were generated on a training dataset consisting of 1,544 clinical measurements to estimate proton output for each option. Meanwhile, three ML models using Gaussian process regression (GPR) with exponential kernel, squared exponential kernel, and rational quadratic kernel were also created for all options combined. The accuracy of each model was validated against 241 additional clinical measurements as the testing dataset. Two most robust models were selected, and the minimum number of samples needed for either model to achieve sufficient accuracy ( ± 3%) was determined by evaluating the mean average percentage error (MAPE) with increasing sample number. The differences between the estimated outputs using the two models were also compared for 1,000 proton beams with a randomly generated range, and modulation for each option.ResultsThe polynomial model and the ML GPR model with exponential kernel yielded the most accurate estimations with less than 3% deviation from the measured outputs. At least 20 samples of each option were needed to build the polynomial model with less than 1% MAPE, whereas at least a total of 400 samples were needed for all beam options to build the ML GPR model with exponential kernel to achieve comparable accuracy. The two independent models agreed with less than 2% deviation using the testing dataset.ConclusionThe polynomial model and the ML GPR model with exponential kernel were built for proton output estimation with less than 3% deviations from the measurements. They can be used as an independent output prediction tool for a double scattering proton beam and a secondary output check tool for a cross check between themselves.

Background: Both Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) play a key role on dyslipidaemia. We aim to evaluate whether NPC1L1 and HMGCR genetic variants are associated with susceptibility of premature triple-vessel disease (PTVD).Methods: Four single-nucleotide polymorphisms (SNPs) (rs11763759, rs4720470, rs2072183, and rs2073547) of NPC1L1; and three SNPs (rs12916, rs2303151, and rs4629571) of HMGCR were genotyped in 872 PTVD patients (males ≤ 50 years old and females ≤ 60 years old), and 401 healthy controls.Results: After adjusting for age and sex, rs12916 of HMGCR was associated with the risk of PTVD in dominance model [odds ratio (OR) = 1.68, 95% confidence intervals (CI): 1.29–2.18, P < 0.001], recessive model (OR = 1.43, 95% CI: 1.08–1.90, P = 0.013) and codominant model (OR = 1.38, 95% CI: 1.17–1.63, P < 0.001); meanwhile, rs4720470 of NPC1L1 was related to increased risk of PTVD in recessive model (OR = 1.74, 95% CI: 1.14–2.74, P = 0.013). Patients who carried both variant rs4720470 and rs12916 also had the risk of PTVD (P < 0.001); however, there were no correlation between these SNPs and the SNYTAX score (all P > 0.05).Conclusions: This is the first report that rs4720470 is a novel polymorphism of the NPC1L1 gene associated with PTVD, and rs12916 of HMGCR gene appears to be a strong genetic marker of PTVD. Our study may improve the early warning, therapeutic strategies and drug development of PTVD.

PurposeThis study was conducted in order to determine the reproducibility and repeatability of cone-beam computed tomography (CBCT) radiomics features.MethodsThe first-, second-, and fifth-day CBCT images from 10 head and neck (H&N) cancer patients and 10 pelvic cancer patients were retrospectively collected for this study. Eighteen common radiomics features were extracted from the longitudinal CBCT images using two radiomics packages. The reproducibility of CBCT-derived radiomics features was assessed using the first-day image as input and compared across the two software packages. The site-specific intraclass correlation coefficient (ICC) was used to quantitatively assess the agreement between packages. The repeatability of CBCT-based radiomics features was evaluated by comparing the following days of CBCT to the first-day image and quantified using site-specific concordance correlation coefficient (CCC). Furthermore, the correlation with volume for all the features was assessed with linear regression and R2 as correlation parameters.ResultsThe first-order histogram-based features such as skewness and entropy showed good agreement computed in either software package (ICCs ≥ 0.80), while the kurtosis measurements were consistent in H&N patients between the two software tools but not in pelvic cases. The ICCs for GLCM-based features showed good agreement (ICCs ≥ 0.80) between packages in both H&N and pelvic groups except for the GLCM-correction. The GLRLM-based texture features were overall less consistent as calculated by the two different software packages compared with the GLCM-based features. The CCC values of all first-order and second-order GLCM features (except GLCM-energy) were all above 0.80 from the 2-day part test–retest set, while the CCC values all dropped below the cutoff after 5-day treatment scans. All first-order histogram-based and GLCM-texture-based features were not highly correlated with volume, while two GLRLM features, in both H&N and pelvic cohorts, showed R2 ≥0.8, meaning a high correlation with volume.ConclusionThe reproducibility and repeatability of CBCT-based radiomics features were assessed and compared for the first time on both H&N and pelvic sites. There were overlaps of stable features in both disease sites, yet the overall stability of radiomics features may be disease-/protocol-specific and a function of time between scans.

Staphylococcus aureus (S. aureus) is now regarded as a zoonotic agent. Methicillin-susceptible S. aureus (MSSA) ST398 is a livestock-associated bacterium that is most prevalent in China, but there are currently no data available for Shandong. Therefore, the aim of this study was to investigate the epidemiology and characterization of MSSA ST398 from retail pork and bulk tank milk (BTM) in Shandong. A total of 67 S. aureus isolates were collected from retail pork between November 2017 and June 2018. Among the isolates, high antimicrobial resistance rates were observed for penicillin (97.0%), and 92.5% of the isolates were multi-drug resistant (MDR). Eight sequence types (STs) were identified in the retail pork isolates, and the predominant type was ST15 (n=26), which was followed by ST398 (n=14). Staphylococcal protein A gene (spa) typing identified spa types t034 and t1255 in MSSA ST398 from retail pork. Using whole-genome sequencing analysis, we described the phylogeny of 29 MSSA ST398 isolates that were obtained from retail pork (n=14) and BTM (n=15). The phylogenetic tree showed that the MSSA ST398 isolates from different sources had the same lineage. Among the 29 MSSA ST398 isolates, five resistance genes were detected, and all isolates carried DHA-1. Fifteen toxin genes were detected, and all isolates carried eta, hla, and hlb. In conclusion, this study found that a high risk for MSSA ST398 was present in retail pork and BTM. These findings have major implications for how investigations of MSSA ST398 outbreaks should be conducted in the One-Health context.