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Objective: There is currently a lack of validated questionnaires designed specifically to assess mental health within patients with chronic gastroduodenal symptoms. This research describes the multi-phase process used to develop and validate a novel mental health scale for patients with chronic gastroduodenal symptoms, the Alimetry® Gut-Brain Wellbeing (AGBW) Survey. Methods: A patient-centered multi-phase process was implemented. In Phase 1, the most relevant concepts for this patient population were selected from existing mental health scales, using data from 79 patients. In Phase 2, an interdisciplinary panel of experts generated scale items. In Phase 3, the scale underwent pre-testing with gastroenterologists (n = 9), health psychologists (n = 3), and patients (n = 12), with feedback incorporated over multiple rounds. Lastly, the psychometric properties of the scale were assessed in a sample of 311 patients via an online survey. Results: The AGBW Survey comprises a patient preface, 10 close-ended questions, and an optional open-ended question. This multidimensional scale assesses general mental health, alongside specific subscales relating to depression, stress, and anxiety. The subscale and total scores demonstrated high internal consistency (α = 0.91 for the total scale; α = 0.72-0.86 for subscales) and good convergent, divergent, concurrent validity, and known groups validity, with large effect sizes. Conclusion: The AGBW Survey is a brief, valid, and reliable scale for assessing mental health in patients with chronic gastroduodenal symptoms. It can be used as a tool to complement physiological tests and has the potential to guide psychological referrals, inform multidisciplinary management, and evaluate treatment outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Fibromuscular dysplasia (FMD) is a type of unexplained nonatherosclerotic vascular disease that usually involves the renal and internal carotid arteries and rarely involves the mesenteric artery. Mesenteric artery FMD is difficult to distinguish from Crohn’s disease (CD) and Behcet’s disease (BD) solely based on symptoms. Patients with mesenteric artery FMD can present with an acute abdomen, but case reports of patients who have a long medical history and undergo multiple bowel resections are extremely rare. Case presentation The patient was a 45-year-old woman with an 11-year history of intermittent lower abdominal pain and fever. At the age of 34 years, she underwent right hemicolectomy and appendectomy due to an acute abdomen. She suffered from oral ulcers between 34 and 36 years old. A clinical diagnosis of presumed CD was made by the age of 41, and she was treated with mesalazine; however, the effect was poor. At the age of 42, she came to our centre, and based on her atypical symptoms and examination results, we thought she had CD. Hence, she was treated with glucocorticoids for 3 years. However, when she was 45, due to steroid dependence, thalidomide tablets were added. Unfortunately, she suffered from another episode of intestinal obstruction. Therefore, she underwent enterectomy. The postoperative histopathological diagnosis was mesenteric artery FMD. She no longer underwent pharmacotherapy after the surgery. Although she did not have any of her previous symptoms and postoperative colonoscopy showed no signs of recurrence, splenomegaly and abnormal routine blood results were still present. Conclusions Patients with mesenteric artery FMD can present with an acute abdomen. In addition, the symptoms and endoscopic manifestations of mesenteric artery FMD may appear similar to CD and BD. Hence, it is difficult to make a clear clinical diagnosis and proceed with treatment. Mesenteric artery FMD often requires surgical pathology to confirm its diagnosis. For patients who suffer from this disorder, surgery may be the best choice to improve the patient’s quality of life.

The continuous development of VANET has accelerated the development of V2X communication. In the DSRC communication mode of VANET, the location information of the vehicles is interfered by factors such as high-density broadcasting and electromagnetic radiation, which can lead to the loss of the original vehicle information data collected by GPS easily. To solve it, this paper proposed the Least Squared SVM based Beacon Data Complete Algorithm. Unlike previous studies that historical trends of vehicle operation were mainly used to predict vehicle location., this method attempts to find a function, which is used to establish the relationship between the lost value and the past value of the vehicle. On this basis, a nonlinear function approximation strategy is used to predict the position of the missing vehicle. Part of the original data was lost artificially to complete checking calculation and to verify the effectiveness of it. The results show that the average relative error between the complemented vehicle position data and the real data is 0.45% and the maximum absolute relative error is 8.25%. This method has the advantage of not needing to extract historical trend data and high calculation accuracy compared with the methods such as PWHOG algorithm, difference matrix, and moving average data preprocessing. It is suitable for real-time acquisition of vehicle position of VANET and can reduce the complexity of detection time.

Abstract Background Several studies on the relationship between morphological parameters and traumatic diseases of the knee have already been conducted. However, few studies focused on the association between knee morphology and posterior cruciate ligament (PCL) avulsion fracture in adults. The objective of this study was to evaluate the impact of knee morphology on PCL avulsion fracture. Methods 76 patients (comprised 40 men and 36 women) with PCL avulsion fracture and 76 age- and sex-matched controls without PCL avulsion fracture were studied from 2012 to 2020. MRI measurements of the knee were acquired in the sagittal, coronal, and axial planes. The assessed measurements including intercondylar notch width index, coronal tibial slope, and medial/lateral posterior tibial slopes were compared between men and women, and between case and control groups respectively using independent sample t-tests. In addition, binary logistic regression analyses were used to identify independent risk factors of PCL avulsion fracture. Results Except notch width index (coronal) (p = 0.003) in the case groups, there was no statistical difference in the assessed measurements including notch width index (axial), coronal tibial slope, medial posterior tibial slope, and lateral posterior tibial slope between men and women in the case and control groups (p > 0.05). When female patients were analyzed, the notch width index (coronal) was significantly smaller (p = 0.0004), the medial posterior tibial slope (p = 0.018) and the lateral posterior tibial slope (p = 0.033) were significantly higher in the case group. The binary logistic regression analysis showed that the notch width index (coronal) (B = -0.347, OR = 0.707, p = 0.003) was found to be an independent factor of PCL avulsion fracture. However, none of the assessed measurements was found to have a statistical difference between the case and control groups in men (p > 0.05). Conclusions Notch width index (coronal), medial posterior tibial slope, and lateral posterior tibial slope were found to affect PCL avulsion fracture in women, but no such measurements affected the PCL avulsion fracture in men. Furthermore, a smaller notch width index (coronal) in women was found to be a risk factor in PCL avulsion fracture.

Prostate cancer (PCa) is one of the most common malignancies in Western countries. Studies have shown that androgen contributes to the progression of PCa, but how androgen promotes PCa remains largely unknown. Here, we demonstrated that androgen suppressed the expression of miR-760 depending on the interaction between androgen and androgen receptor (AR). miR-760 was downregulated in prostate cancer tissues compared with normal tissues. Functional experiments showed that miR-760 downregulation promoted the proliferation and growth of LNCaP and 22rv1 cells. In contrast, miR-760 ectopic expression inhibited the proliferation of LNCaP and 22rv1 cells. DNA synthesis was suppressed by miR-760. Mechanistically, miR-760 bound to the 3'UTR of interleukin 6 (IL6 ). A mutation in the binding site disrupted their interaction. In addition, silencing ofIL 6 suppressed the proliferation of LNCaP and 22rv1 cells. IL6 was upregulated in PCa tissues. Our study reveals that androgen downregulates miR-760 to promote the growth of PCa cells by regulating IL6.

BackgroundThere has been a paucity of evidence examining whether preventable behavioral risk factors led to ethnic differences of gastric precancerous lesions (GPL). We aimed to investigate the ethnic disparity of associations between GPL and lifestyle factors in Mongolian and Han Chinese populations.MethodsThe study included participants aged 36-75 years enrolled in the Cancer Screening Program during 2016-2017 in Hohhot and Tongliao City, Inner Mongolia. GPL was defined as the gross cascading events (i.e., gastric ulcer, atrophic gastritis, intestinal metaplasia, and dysplasia) that preceded gastric cancer.ResultsA total of 61638 participants were included, of whom 6863(11·1%) were Mongolians. Alcohol consumption was positively associated with GPL risk in both ethnic groups, but the magnitude was greater in Mongolians (odds ratio (OR) 6·91, 95%CI 5·82-8·28) than in Han Chinese (OR 5·64, 95%CI 5·27-6·04), corresponding to a higher population attributable fraction (PAF) for Mongolians (53·18% vs 43·71%). Besides, the strength of the positive association between physical inactivity and GPL risk was greater among Mongolians (OR 2·02, 95%CI 1·70-2·41; OR 1·09, 95%CI 1·02-1·17 among Han Chinese) with a higher PAF. Smoking was strongly associated with GPL risk in both ethnic groups as well, but the association was more prominent among Han Chinese (OR 5·24 (1·70-2·41) for

The extracellular matrix is essential for the biofilm formation of food spoilers. Pseudomonas fluorescens PF07 is a previous isolate from spoiled marine fish; however, the genes involved in the extracellular matrix formation of PF07 biofilms remain poorly defined. In this study, PF07 formed a wrinkled macrocolony biofilm through the high production of extracellular matrix. The genes involved in biofilm matrix formation and regulation were screened and identified by RNA-seq-dependent transcriptomic analysis and gene knock-out analysis. The macrocolony biofilms of PF07 grown for 5 days (PF07_5d) were compared with those grown for 1 day (PF07_1d). A total of 1,403 genes were significantly differentially expressed during biofilm formation. These mainly include the genes related to biofilm matrix proteins, polysaccharides, rhamnolipids, secretion system, biofilm regulation, and metabolism. Among them, functional amyloid genes fapABCDE were highly upregulated in the mature biofilm, and the operon fapA-E had a –24/–12 promoter dependent on the sigma factor RpoN. Moreover, the RNA-seq analyses of the rpoN mutant, compared with PF07, revealed 159 genes were differentially expressed in the macrocolony biofilms, and fapA-E genes were positively regulated by RpoN. In addition, the deletion mutants of fapC, rpoN, and brfA (a novel gene coding for an RpoN-dependent transcriptional regulator) were defective in forming mature macrocolony biofilms, solid surface-associated (SSA) biofilms, and pellicles, and they showed significantly reduced biofilm matrices. The fap genes were significantly downregulated in ΔbrfA, as in ΔrpoN. These findings suggest that the functional amyloid Fap is the main component of PF07 biofilm matrices, and RpoN may directly regulate the transcription of fap genes, in conjunction with BrfA. These genes may serve as potential molecular targets for screening new anti-biofilm agents or for biofilm detection in food environments.

PurposeTo investigate the association between preoperative systemic immune-inflammation index (SII) and neutrophil–lymphocyte ratio (NLR) and oncological outcomes in localized prostate cancer (PCa) patients after radical prostatectomy (RP).MethodsBetween January 2014 and December 2019, 291 patients with pathologically confirmed localized PCa who underwent RP were included in this study. The threshold values of SII and NLR for biochemical recurrence (BCR) were calculated according to Youden’s index based on the receiver operating characteristic (ROC) curve, then the patients were divided into two groups by the threshold values of SII and NLR, and the clinicopathological outcomes were analyzed and compared between groups, respectively. The binary logistic regression model was used to evaluate the association between SII, NLR, and pathological outcomes including Gleason score (GS) and pathological T (pT) stage. Kaplan–Meier curves and univariable and multivariable Cox regression models were used to determine the association between high SII, high NLR, and BCR-free survival, respectively.ResultsThe median follow-up time was 48 months (IQR 36–62), and 114 (39.18%) patients developed BCR. The AUC of SII for BCR was 0.813 (P < 0.001), with a threshold value of 528.54, a sensitivity of 72.9%, and a specificity of 76.3%; the AUC of NLR for BCR was 0.824 (P < 0.001), with a threshold value of 2.62, a sensitivity of 71.2%, and a specificity of 81.6%. Patients were divided into two groups according to the threshold values of SII and NLR, respectively. Patients in the high SII group had higher tPSA, GS, pT stage, and BCR rate than patients in the low SII group (P = 0.004, 0.04, 0.007, and

A calculation method considering ventilation resistance was proposed for designing a cluster-based inductive ventilation system for a real passenger-dedicated railway tunnel. In the system, jet fans were installed only at the two portals, instead of being arranged along the tunnel. A 20 MW train fire was simulated in Fire Dynamics Simulator (FDS) 6.6 to reproduce the designed fire, and the tunnel ventilation was validated using full-scale ventilation experiments. The simulation results showed that the growth of the ventilation velocities was periodically fluctuating. At a height of 2 m above the rail surface, the temperatures always remained below 60 °C, and the visibilities upstream of the fire were not affected by the smoke. It can be concluded that the designed ventilation scheme can effectively inhibit smoke backflow, and both the cluster-based inductive ventilation system and calculation method are feasible.

Dormancy is a common survival strategy in plants to temporarily suspend visible growth under unsuitable conditions. The elaborate mechanism underlying bud break in perennial woody plants is gradually illustrated. Here, we identified a grape vine WRKY transcription factor, VvWRKY37, which was highly expressed in dormant buds. It was particularly induced by the application of exogenous abscisic acid, and depressed on exposure to gibberellin and low temperature (4°C) stress at the transcript level. The yeast one-hybrid assay confirmed that VvWRKY37 had a transcriptional activity. Ectopic over-expression of VvWRKY37 significantly delayed bud break of transgenic poplar plants. As an ABA-inducible gene, VvWRKY37 also depressed the expression of ABA catabolic gene CYP707As and enhanced the accumulation of endogenous ABA in transgenic poplar plants. The molecular pieces of evidence showed that VvWRKY37 preferentially recognized and bound W-box 5′-G/CATTGACT/C/G-3′ cis-element in vitro. Additionally, VvABI5 and VvABF2 acted as the upstream transcriptional activators of VvWRKY37 via protein-DNA interactions. Taken together, our findings provided valuable insights into a new regulatory mechanism of WRKY TF by which it modulates bud break through ABA-mediated signaling pathways.

Abstract The SARS‐CoV‐2 Omicron BA.1 variant of concern contains more than 30 mutations in the spike protein, with half of these mutations localized in the receptor‐binding domain (RBD). Emerging evidence suggests that these large number of mutations impact the neutralizing efficacy of vaccines and monoclonal antibodies. We investigated the relative contributions of spike protein and RBD mutations in Omicron BA.1 variants on infectivity, cell–cell fusion, and their sensitivity to neutralization by monoclonal antibodies or vaccinated sera from individuals who received homologous (CoronaVac, SinoPharm) or heterologous (CoronaVac—BNT162b2, BioNTech) and nonhuman primates that received a recombinant RBD protein vaccine. Our data overall reveal that the mutations in the spike protein reduced infectivity and cell–cell fusion compared to the D614G variant. The impaired infectivity and cell–cell fusion were dependent on non‐RBD mutations. We also find reduced sensitivity to neutralization by monoclonal antibodies and vaccinated sera. However, our results also show that nonhuman primates receiving a recombinant RBD protein vaccine show substantial neutralization activity. Our study sheds light on the molecular differences in neutralizing antibody escape by the Omicron BA.1 variant, and highlights the promise of recombinant RBD vaccines in neutralizing the threat posed by the Omicron BA.1 variant.

Glioma is the most common primary malignant brain tumor in adults. It accounts for about 75% of such tumors and occurs more commonly in men. The incidence rate has been increasing in the past 30 years. Moreover, the 5-year overall survival rate of glioma patients is < 35%. Different locations, grades, and molecular characteristics of gliomas can lead to different behavioral deficits and prognosis, which are closely related to patients' quality of life and associated with neuroplasticity. Some advanced magnetic resonance imaging (MRI) technologies can explore the neuroplasticity of structural, topological, biochemical metabolism, and related mechanisms, which may contribute to the improvement of prognosis and function in glioma patients. In this review, we summarized the studies conducted on structural and topological plasticity of glioma patients through different MRI technologies and discussed future research directions. Previous studies have found that glioma itself and related functional impairments can lead to structural and topological plasticity using multimodal MRI. However, neuroplasticity caused by highly heterogeneous gliomas is not fully understood, and should be further explored through multimodal MRI. In addition, the individualized prediction of functional prognosis of glioma patients from the functional level based on machine learning (ML) is promising. These approaches and the introduction of ML can further shed light on the neuroplasticity and related mechanism of the brain, which will be helpful for management of glioma patients.

BackgroundThe expression of homeobox A10 (HOXA10) in endometrial stromal cells is regulated by steroid hormones, especially by estrogen. As a precursor molecule of estrogen, abnormal cholesterol metabolism is significantly positively correlated with endometriosis. The purpose of this study was to explore the regulation of HOXA10 on cholesterol synthesis in endometrial stromal cells.MethodmRNA expression data of eutopic endometrial stromal cell (ESC) and ovarian endometriotic cysts stromal cell (OESC) were download from the Gene Expression Omnibus (GEO) databases. Overexpression and silence of HOXA10 were conducted in cultured ESC and subjected to mRNA sequencing. The differentially expressed genes (DEGs) were selected by analyzing the sequencing data. Weighted gene co-expression network analysis (WGCNA) was applied to identify the key genes associated with HOXA10. The methylation rate of HOXA10 CpGs and the correlation between HOXA10 expression and the methylation in eutopic endometrial tissue (EU) and ovarian cyst (OC) were analyzed.ResultsHOXA10 in ESC was significantly higher expressed than that in OESC. Six key genes (HMGCR, MSMO1, ACAT2, HMGCS1, EBP, and SQLE), which were regulated by HOXA10, were identified from the salmon4 module by WGCNA. All these key genes were enriched in cholesterol synthesis. Moreover, the expression of HOXA10 was negatively related to its CpGs methylation rate.ConclusionIn this study, six key genes that were regulated by HOXA10 were selected, and all of them were enriched in cholesterol synthesis. This finding provided a new insight into the metabolic mechanism of cholesterol in ESC. It also provided a potential treatment strategy for cholesterol metabolism maladjustment in patients with ovarian endometriosis.

Menaquinone-7 (MK-7) is an important vitamin K2, synthesized from the menaquinone parent ring and seven isoprene side chains. Presently, the synthesis of MK-7 stimulated by environmental stress primarily focuses on oxygen stress, while the effect of alkali stress is rarely studied. Therefore, this study researched the effects of alkali stress on the fermentation performance and gene expression of Bacillus subtilis natto. The organism’s growth characteristics, biomass, sporogenesis, MK-7 biosynthesis, and gene expression were analyzed. After a pH 8.5 stress adaptation treatment for 0.5 h and subsequent fermentation at pH 8.5, which promoted the growth of the strain and inhibited the spore formation rate. In addition, biomass was significantly increased (P < 0.05). The conversion rate of glycerol to MK-7 was 1.68 times higher than that of the control group, and the yield of MK-7 increased to 2.10 times. Transcriptomic analysis showed that the MK-7 high-yielding strain had enhanced carbon source utilization, increased glycerol and pyruvate metabolism, enhanced the Embden-Meyerhof pathway (EMP), tricarboxylic acid (TCA) circulation flux, and terpenoid biosynthesis pathway, and promoted the accumulation of acetyl-CoA, the side-chain precursor of isoprene. At the same time, the up-regulation of transketolase increased the metabolic flux of the pentose phosphate (HMP) pathway, which was conducive to the accumulation of D-erythrose 4-phosphate, the precursor of the menadione parent ring. This study’s results contribute to a better understanding of the effects of environmental stress on MK-7 fermentation by Bacillus subtilis natto and the molecular regulatory mechanism of MK-7 biosynthesis.

BackgroundThis study aims to explore the key targets and signaling pathways of the traditional Chinese medicine Phellodendron and Anemarrhena drug pair (PADP) for the treatment of liver cancer.MethodsFirstly, bioinformatics technology was used to analyze GSE62232 gene chip to obtain the differential genes of liver cancer. A network pharmacology technology was used to find the active components of PADP and their targets. Secondly, the differential genes were imported into STRING database to draw a PPI network, and network topology structure map combined with Cytoscape software. And the R language was used to identify differential gene targets and pathways through GO and KEGG pathway enrichment analysis. In addition, AutoDock Vina was used for molecular docking of core targets and core compounds. Moreover, GEPIA online analysis tool was used to perform survival analysis of the core target genes. Finally, RT-PCR was used to verify the changes of key target genes. CCK−8 assay was performed to detect cell proliferation. Flow cytometry was performed to detect the cell cycle and apoptotic. Transwell invasion assay was performed to detect cell invasion.ResultsFirstly, a total of 21,654 genes were obtained. After screening, 1019 differential genes were obtained, including 614 down-regulated genes and 405 up-regulated genes. Furthermore, after screening by ADME standards, 52 active ingredients were obtained, of which 37 were Phellodendron and 15 were Anemarrhena. And a total of 36 differential genes have been identified, including 13 up-regulated genes and 23 down-regulated genes. Moreover, through enrichment analysis, we found that PADP may treat liver cancer through multiple channels and multiple pathways including the p53 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway and so on. Secondly, the molecular docking results showed that there was certain affinity between the core compounds and core target genes. In addition, GEPIA online analysis showed that ESR1, AR, CCNB1, CDK1, AKR1C3 and CCNA2 might become potential target genes for the survival and prognosis of PADP for the treatment of liver cancer. Finally, it was found that PADP could up regulate genes ESR1 and AR, down regulate genes CCNB1, CDK1, AKR1C3, and CCNA2. PADP could promote the apoptosis of liver cancer cells, shorten the cell cycle, and inhibit the proliferation and invasion of liver cancer cells.ConclusionPADP may treat liver cancer through multiple targets, multiple channels, and multiple pathways, thereby suppressing cancer cells and improving the living quality of patients.

Abstract Background Invasion depth is an important index for staging and clinical treatment strategy of bladder cancer (BCa). The aim of this study was to investigate the feasibility of segmenting the BCa region from bladder wall region on MRI, and quantitatively measuring the invasion depth of the tumor mass in bladder lumen for further clinical decision-making. This retrospective study involved 20 eligible patients with postoperatively pathologically confirmed BCa. It was conducted in the following steps: (1) a total of 1159 features were extracted from each voxel of both the certain cancerous and wall tissues with the T2-weighted (T2W) MRI data; (2) the support vector machine (SVM)-based recursive feature elimination (RFE) method was implemented to first select an optimal feature subset, and then develop the classification model for the precise separation of the cancerous regions; (3) after excluding the cancerous region from the bladder wall, the three-dimensional bladder wall thickness (BWT) was calculated using Laplacian method, and the invasion depth of BCa was eventually defined by the subtraction of the mean BWT excluding the cancerous region and the minimum BWT of the cancerous region. Results The segmented results showed a promising accuracy, with the mean Dice similarity coefficient of 0.921. The “soft boundary” defined by the voxels with the probabilities between 0.1 and 0.9 could demonstrate the overlapped region of cancerous and wall tissues. The invasion depth calculated from proposed segmentation method was compared with that from manual segmentation, with a mean difference of 0.277 mm. Conclusion The proposed strategy could accurately segment the BCa region, and, as the first attempt, realize the quantitative measurement of BCa invasion depth.

Abstract This study aimed to determine the characteristics of CT changes in patients with severe coronavirus disease 2019 (COVID-19) based on prognosis. Serial CT scans in 47 patients with severe COVID-19 were reviewed. The patterns, distribution and CT score of lung abnormalities were assessed. Scans were classified according to duration in weeks after onset of symptoms. These CT abnormalities were compared between discharged and dead patients. Twenty-six patients were discharged, whereas 21 passed away. Discharged patients were characterized by a rapid rise in CT score in the first 2 weeks followed by a slow decline, presence of reticular and mixed patterns from the second week, and prevalence of subpleural distribution of opacities in all weeks. In contrast, dead patients were characterized by a progressive rise in CT score, persistence of ground-glass opacity and consolidation patterns in all weeks, and prevalence of diffuse distribution from the second week. CT scores of death group were significantly higher than those of discharge group (P

Abstract. Background. Recent studies have reported circular RNA (circRNA) expression profiles in various tissue types; however, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. This work aimed to compare circRNA expression patterns in EAT between the heart failure (HF) and non-HF groups. Methods. RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups. Quantitative real-time polymerase chain reaction was performed for validation. Comparisons of patient characteristics between the two groups were using t test, Mann-Whitney U test, and Chi-squared test. Results. A total of 141 circRNAs substantially different between the HF and non-HF groups (P 2) were detected, including 56 up-regulated and 85 down-regulated. Among them, hsa_circ_0005565 stood out, for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including GSE1, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B, and SPECC1. The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance, respectively. Conclusion. These data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.

Abstract Background Recent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients. Methods A total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization. Results Type 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037–5.051; P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377, P

The real-time reverse transcription-polymerase chain reaction (RT-PCR) detection of viral RNA from sputum or nasopharyngeal swab had a relatively low positive rate in the early stage of coronavirus disease 2019 (COVID-19). Meanwhile, the manifestations of COVID-19 as seen through computed tomography (CT) imaging show individual characteristics that differ from those of other types of viral pneumonia such as influenza-A viral pneumonia (IAVP). This study aimed to establish an early screening model to distinguish COVID-19 from IAVP and healthy cases through pulmonary CT images using deep learning techniques. A total of 618 CT samples were collected: 219 samples from 110 patients with COVID-19 (mean age 50 years; 63 (57.3%) male patients); 224 samples from 224 patients with IAVP (mean age 61 years; 156 (69.6%) male patients); and 175 samples from 175 healthy cases (mean age 39 years; 97 (55.4%) male patients). All CT samples were contributed from three COVID-19-designated hospitals in Zhejiang Province, China. First, the candidate infection regions were segmented out from the pulmonary CT image set using a 3D deep learning model. These separated images were then categorized into the COVID-19, IAVP, and irrelevant to infection (ITI) groups, together with the corresponding confidence scores, using a location-attention classification model. Finally, the infection type and overall confidence score for each CT case were calculated using the Noisy-OR Bayesian function. The experimental result of the benchmark dataset showed that the overall accuracy rate was 86.7% in terms of all the CT cases taken together. The deep learning models established in this study were effective for the early screening of COVID-19 patients and were demonstrated to be a promising supplementary diagnostic method for frontline clinical doctors.

Traditional research on lake eutrophication has failed to consider the effect of the South-to-North Water Transfer Project (SNWTP) policy; thus, the difference-in-differences (DID) model, which is usually applied to economic factors, was innovatively introduced to evaluate the effect of such policies on lake eutrophication. Nansi Lake and Dongping Lake in the Shandong Peninsula were selected as the experimental group, and Daming Lake and Mata Lake were selected as the control group. The eutrophication indices of the experimental group and the control group were calculated by the measured chlorophyll-a, total phosphorus, total nitrogen, water transparency and chemical oxygen demand data and used as the explanatory variables of the DID model. Nine environmental and socio-economic factors, such as dissolved oxygen and rural population, were selected as the control variables of the DID model to analyze the impact of the SNWTP policy on lake eutrophication. A joint consideration of environmental and socio-economic factors showed that the eutrophication degree of the experimental lakes deteriorated by 7.10% compared with the control under the influence of the implemented policy. Dissolved oxygen is the main factor affecting the eutrophication of the Shandong Peninsula. This study verifies that the DID model has the potential for use in quantitative analyses of the effect of the SNWTP policy on lake eutrophication. HIGHLIGHTS Using DID model to estimate the impact of policy on lake eutrophication is reasonable.; Eutrophication deteriorated by 7.10% under the effect of policy and control variables.; DO is the key control variables influencing the eutrophication of the Shandong Peninsula.;

Abstract Background Transforaminal percutaneous endoscopic lumbar surgeries (PELS) for lumbar disc herniation and spinal stenosis are growing in popularity. However, there are some problems in the establishment of the working channel and foraminoplasty such as nerve and blood vessel injuries, more radiation exposure, and steeper learning curve. Rapid technological advancements have allowed robotic technology to assist surgeons in improving the accuracy and safety of surgeries. Therefore, the purpose of this study is to develop a robot-assisted system for transforaminal PELS, which can provide navigation and foraminoplasty. Methods The robot-assisted system consists of three systems: preoperative planning system, navigation system, and foraminoplasty system. In the preoperative planning system, 3D visualization of the surgical segment and surrounding tissues are realized using the multimodal image fusion technique of computed tomography and magnetic resonance imaging, and the working channel planning is carried out to reduce the risk for injury to vital blood vessels and nerves. In the navigation system, the robot can obtain visual perception ability from a visual receptor and automatically adjust the robotic platform and robot arm to the appropriate positions according to the patient’s position and preoperative plan. In addition, the robot can automatically register the surgical levels through intraoperative fluoroscopy. After that, the robot will provide navigation using the 6 degree-of-freedom (DOF) robot arm according to the preoperative planning system and guide the surgeon to complete the establishment of the working channel. In the foraminoplasty system, according to the foraminoplasty planning in the preoperative planning system, the robot performs foraminoplasty automatically using the high speed burr at the end of the robot arm. The system can provide real-time feedback on the working status of the bur through multi-mode sensors such as multidimensional force, position, and acceleration. Finally, a prototype of the system is constructed and performance tests are conducted. Discussion Our study will develop a robot-assisted system to perform transforaminal PELS, and this robot-assisted system can also be used for other percutaneous endoscopic spinal surgeries such as interlaminar PELS and percutaneous endoscopic cervical and thoracic surgeries through further research. The development of this robot-assisted system can be of great significance. First, the robot can improve the accuracy and efficiency of endoscopic spinal surgeries. In addition, it can avoid multiple intraoperative fluoroscopies, minimize exposure to both patients and the surgical staff, shorten the operative time, and improve the learning curve of beginners, which is beneficial to the popularization of percutaneous endoscopic spinal surgeries.

Background/Aims: The risk factors of colorectal stricture associated with ulcerative colitis (UC) carcinogenesis in the long-term disease duration remain unclear. Methods: This study included all UC patients registered from a prospectively maintained database between June 1986 to July 2018. The demographic data, clinical features, and outcomes in patients with dysplasia and stricture were assessed using univariable analysis and multivariate logistic regression models. Results: A total of 246 eligible patients were included in the analysis. The median follow-up time was 13.0 years (interquartile range [IQR], 9.0 to 16.0). There were 35 cases (14.2%) of colorectal stricture. Patients with stricture had worse clinical outcomes. Stricture formation (odds ratio [OR], 9.350; 95% confidence interval [CI], 2.842 to 30.762), inflammatory polyps (OR, 5.464; 95% CI, 1.692 to 17.638), disease duration of more than 10 years (OR, 3.223; 95% CI, 1.040 to 9.985), and age >40 years at diagnosis (OR, 8.499; 95% CI, 1.903 to 37.956) were significantly associated with high-grade dysplasia or colorectal cancer. In addition, disease duration of more than 5 years (OR, 3.211; 95% CI, 1.168 to 8.881), moderated anemia (OR, 3.373; 95% CI, 1.472 to 7.731), and primary sclerosing cholangitis (OR, 5,842; 95% CI, 1.395 to 24.468) were contributing factors for the development of colorectal stricture. Conclusions: Colorectal stricture had the highest risk for malignant transformation. Earlier initiation of colonoscopic surveillance in UC patients with risk factors for stricture should be considered to prevent stricture formation and further malignant transformation.

Atherosclerosis (AS) is the leading cause of heart attacks, stroke, and peripheral vascular disease. Berberine (BBR), a botanical medicine, has diversified anti-atherosclerotic effects but with poor absorption. The aim of this study was to develop an effective BBR-entrapped nano-system for treating AS in high-fat diet (HFD)-fed Apoe(−/−) mice, and also explore the possible underlying mechanisms involved. Three d-α-tocopherol polyethylene glycol (PEG) succinate (TPGS) analogues with different PEG chain lengths were synthesized to formulate BBR-entrapped micelles. HFD-fed Apoe(−/−) mice were administered with optimized formula (BBR, 100 mg/kg/day) orally for 5 months. The artery plaque onset and related metabolic disorders were evaluated, and the underlying mechanisms were studied. Our data showed that, BT1500M increased BBR deposition in liver and adipose by 107.6% and 172.3%, respectively. In the Apoe(−/−) mice, BT1500M ameliorated HFD-induced hyperlipidemia and lipid accumulation in liver and adipose. BT1500M also suppressed HFD-induced chronic inflammation as evidenced by the reduced liver and adipose levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β); and decreased plasma level of TNF-α, IL-6, IL-1β, interferon-γ (IFN-γ), monocyte chemotactic protein (MCP), and macrophage inflammatory factor (MIP). The mechanism study showed that BT1500M changed Ampk and Nf-κb gene expression, and interrupted a crosstalk process between adipocytes and macrophages. Further investigation proved that BT1500M decreased endothelial lesion and subsequent macrophage activation, cytokines release, as well as cholesteryl ester gathering in the aortic arch, resulting in ameliorated artery plaque build-up. Our results provide a practical strategy for treating AS using a BBR-entrapped nano-system.

Abstract Background We propose a new classification system for chronic symptomatic osteoporotic thoracolumbar fracture (CSOTF) based on fracture morphology. Research on CSOTF has increased in recent years; however, the lack of a standard classification system has resulted in inconvenient communication, research, and treatment. Previous CSOTF classification studies exhibit different symptoms, with none being widely accepted. Methods Imaging data of 368 patients with CSOTF treated at our hospital from January 2010 to June 2017 were systematically analyzed to develop a classification system. Imaging examinations included dynamic radiography, computed tomography scans, and magnetic resonance imaging. Ten investigators methodically studied the classification system grading in 40 cases on two occasions, examined 1 month apart. Kappa coefficients (κ) were calculated to determine intraobserver and interobserver reliability. Based on the radiographic characteristics, the patients were divided into 5 types, and different treatments were suggested for each type. Clinical outcome evaluation included using the visual analog score (VAS), the Oswestry disability index (ODI), and the American Spinal Injury Association (ASIA) impairment scale. Results The new classification system for CSOTF was divided into types I–V according to whether the CSOTF exhibited dynamic instability, spinal stenosis or kyphosis deformity. Intra- and interobserver reliability were excellent for all types (κ = 0.83 and 0.85, respectively). The VAS score and ODI of each type were significantly improved at the final follow-up compared with those before surgery. In all patients with neurological impairment, the ASIA grading after surgery was significantly improved compared with that before surgery (P < 0.001). Conclusions The new classification system for CSOTF demonstrated excellent reliability in this initial assessment. The treatment algorithm based on the classification can result in satisfactory improvement of clinical efficacy for the patients of CSOFT.

Abstract Background At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application. Methods First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein–protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects. Results First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine–cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels. Conclusions DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.

Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders during childhood, which lasts until adulthood in most cases. In recent years, ADHD classification based on functional magnetic resonance imaging (fMRI) data has become a research hotspot. Most existing classification algorithms reported in the literature assume that samples are balanced; however, ADHD data sets are usually imbalanced. Imbalanced data sets can cause the performance degradation of a classifier by imbalanced learning, which tends to overfocus on the majority class. In this study, we considered an imbalanced neuroimaging classification problem: classification of ADHD using resting state fMRI. We used the functional connection matrix of fMRI as the classification feature and proposed a multi-objective data classification scheme based on a support vector machine (SVM) to aid the diagnosis of ADHD. In this scheme, the imbalanced data classification problem is formulated as an SVM model with three objectives: maximizing the margin, minimizing the sum of positive errors, and minimizing the sum of negative errors. Accordingly, the positive and negative sample empirical errors can be separately handled. Then, the model is solved by a multi-objective optimization method, i.e., normal boundary intersection method. A set of representative classifiers are computed for selection by decision makers. The proposed scheme was tested and evaluated on five data sets from the ADHD-200 consortium and compared with traditional classification methods. Experimental results show that the proposed three-objective SVM classification scheme is better than traditional classification methods reported in the literature. It can effectively address the data imbalance problem from the algorithm level. This scheme can be used in the diagnosis of ADHD as well as other diseases, such as Alzheimer’s and Autism.

Abstract Background Growing studies have focused on the role of microRNA-21 (miR-21) in glioma, thus our objective was to discuss the effect of M2 bone marrow-derived macrophage (BMDM)-derived exosomes (BMDM-Exos) shuffle miR-21 on biological functions of glioma cells by regulating paternally expressed gene 3 (PEG3). Methods Seventy-one cases of human glioma tissues and 30 cases of non-tumor normal brain tissues were collected and stored in liquid nitrogen. PEG3 and miR-21 expression in glioma tissues was tested. The fasting venous blood of glioma patients and healthy control was collected and centrifuged, and then the supernatant was stored at − 80 °C refrigerator. The contents of interferon (IFN)-γ and transforming growth factor-β1 (TGF-β1) in serum were tested by ELISA. Glioma cells and normal glial cells were cultured to screen the target cells for further in vitro experiments. BMDM-Exos was obtained by ultra-high speed centrifugation and then was identified. BMDM-Exos was co-cultured with U87 cells to detect the biological functions. The fasting venous blood of glioma patients was extracted and treated with ethylene diamine tetraacetic acid-K2 anti-freezing, and then CD8+T cells were isolated. CD8+T cells were co-cultured with U87 cells to detect the CD8+T proliferation, cell cytotoxic activity, U87 cell activity, as well as IFN-γ and TGF-β1 levels. Moreover, BALB/c-nu/nu mice was taken, and the human-nude mouse glioma orthotopic transplantation model was established with U87 cells, and then mice were grouped to test the trends in tumor growth. The brain of mice (fixed by 10% formaldehyde) was sliced to detect the expression of Ki67 and proliferating cell nuclear antigen (PCNA). The spleen of mice was taken to prepare single-cell suspension, and the percentage of T lymphocytes in spleen to CD8+T cells was detected. Results PEG3 expression was decreased and miR-21 expression was increased in glioma cells and tissues. Depleting miR-21 or restoring PEG3 suppressed growth, migration and invasion as well as accelerated apoptosis of glioma cells, also raised CD8+T proliferation, cell cytotoxic activity, and IFN-γ level as well as decreased U87 cell activity and TGF-β1 level. BMDM-Exos shuttle miR-21 promoted migration, proliferation and invasion as well as suppressed apoptosis of glioma cells by reducing PEG3. Exosomes enhanced the volume of tumor, Ki67 and PCNA expression, reduced the percentage of CD8+T cells in glioma mice. Conclusion BMDM-Exos shuffle miR-21 to facilitate invasion, proliferation and migration as well as inhibit apoptosis of glioma cells via inhibiting PEG3, furthermore, promoting immune escape of glioma cells.

Abstract Background Non-invasive discrimination between lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes of non-small-cell lung cancer (NSCLC) could be very beneficial to the patients unfit for the invasive diagnostic procedures. The aim of this study was to investigate the feasibility of utilizing the multimodal magnetic resonance imaging (MRI) radiomics and clinical features in classifying NSCLC. This retrospective study involved 148 eligible patients with postoperative pathologically confirmed NSCLC. The study was conducted in three steps: (1) feature extraction was performed using the online freely available package with the multimodal MRI data; (2) feature selection was performed using the Student’s t test and support vector machine (SVM)-based recursive feature elimination method with the training cohort (n = 100), and the performance of these selected features was evaluated using both the training and the validation cohorts (n = 48) with a non-linear SVM classifier; (3) a Radscore model was then generated using logistic regression algorithm; (4) Integrating the Radscore with the semantic clinical features, a radiomics–clinical nomogram was developed, and its overall performance was evaluated with both cohorts. Results Thirteen optimal features achieved favorable discrimination performance with both cohorts, with area under the curve (AUC) of 0.819 and 0.824, respectively. The radiomics–clinical nomogram integrating the Radscore with the independent clinical predictors exhibited more favorable discriminative power, with AUC improved to 0.901 and 0.872 in both cohorts, respectively. The Hosmer–Lemeshow test and decision curve analysis results furtherly showed good predictive precision and clinical usefulness of the nomogram. Conclusion Non-invasive histological subtype stratification of NSCLC can be done favorably using multimodal MRI radiomics features. Integrating the radiomics features with the clinical features could further improve the performance of the histological subtype stratification in patients with NSCLC.