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PurposeTo investigate the feasibility and safety of non-intubated general anesthesia with spontaneous breathing combined with paravertebral nerve blocks (PVNB) in young children undergoing video-assisted thoracic surgery (VATS) and to determine its significance for rapid recovery after pediatric thoracic surgery.MethodsThe data of 46 children aged 6–36 months with an American Society of Anesthesiologists status of I–II who underwent elective VATS under general anesthesia were retrospectively analyzed. Of these patients, 25 underwent non-intubated general anesthesia with spontaneous breathing combined with PVNB (non-intubation group), and 21 received conventional intubated general anesthesia combined with local infiltration anesthesia (intubation group). The following perioperative parameters were compared between the two groups: heart rate (HR), mean arterial pressure, saturation of pulse oximetry (SpO2), partial pressure end-tidal carbon dioxide, time from the completion of the operation to extubation or removing laryngeal masks, time to first feeding after the operation, length of postoperative in-hospital stay, incidence of postoperative complications, and hospitalization expenses.ResultsThe operations were completed successfully in both groups. When the non-intubation group was compared with the intubation group, the minimal SpO2 level during the surgery was higher (93% vs. 88%, P

BackgroundWhite matter hyperintensities (WMHs) are a subtype of cerebral small vessel disease and can be divided into periventricular WMHs (pvWMHs) and deep WMHs (dWMHs). pvWMHs and dWMHs were proved to be determined by different etiologies. This study aimed to develop a 2D Cascade U-net (Cascade U) for the segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images.MethodsA total of 253 subjects were recruited in the present study. All subjects underwent 2D T2-FLAIR scan on a 3.0 Tesla MR scanner. Both contours of pvWMHs and dWMHs were manually delineated by the observers and considered as the gold standard. Fazekas scale was used to evaluate the burdens of pvWMHs and dWMHs, respectively. Cascade U consisted of a segmentation U-net and a differentiation U-net and was trained with a combined loss function. The performance of Cascade U was compared with two other U-net models (Pipeline U and Separate U). Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), precision, and recall were used to evaluate the performances of all models. The linear correlations between WMHs volume (WMHV) measured by all models and the gold standard were also conducted.ResultsCompared with other models, Cascade U exhibited a better performance on WMHs segmentation and pvWMHs identification. Cascade U achieved DSC values of 0.605 ± 0.135, 0.517 ± 0.263, and 0.510 ± 0.241 and MCC values of 0.617 ± 0.122, 0.526 ± 0.263, and 0.522 ± 0.243 on the segmentation of total WMHs, pvWMHs, and dWMHs, respectively. Cascade U exhibited strong correlations with the gold standard on measuring WMHV (R2 = 0.954, p < 0.001), pvWMHV (R2 = 0.933, p < 0.001), and dWMHV (R2 = 0.918, p < 0.001). A significant correlation was found on lesion volume between Cascade U and gold standard (r > 0.510, p < 0.001).ConclusionCascade U showed competitive results in segmentation and differentiation of pvWMHs and dWMHs on 2D T2-FLAIR images, indicating potential feasibility in precisely evaluating the burdens of WMHs.

Tellurite [Te(IV)] is a high-toxicity metalloid. In this study, a fungus with high Te(IV) resistance was isolated. Strain AB1 could efficiently reduce highly toxic Te(IV) to less toxic Te(0). The reduced products formed rod-shaped biogenetic Te(0) nanoparticles (Bio-TeNPs) intracellularly. Further TEM-element mapping, FTIR, and XPS analysis showed that the extracted Bio-TeNPs ranged from 100 to 500 nm and consisted of Te(0), proteins, lipids, aromatic compounds, and carbohydrates. Moreover, Bio-TeNPs exhibited excellent antibacterial ability against Shigella dysenteriae, Escherichia coli, Enterobacter sakazakii, and Salmonella typhimurium according to inhibition zone tests. Further growth and live/dead staining experiments showed that E. coli and S. typhimurium were significantly inhibited by Bio-TeNPs, and cells were broken or shriveled after treatment with Bio-TeNPs based on SEM observation. Additionally, the antioxidant and cytotoxicity tests showed that the Bio-TeNPs exhibited excellent antioxidant capacity with no cytotoxicity. All these results suggested that strain AB1 showed great potential in bioremediation and Bio-TeNPs were excellent antibacterial nanomaterials with no cytotoxicity.

AimsThe cost of drug regimens prescribed to Chinese patients has not been evaluated. This study aims to evaluate the medical costs and hypoglycemic agents for diabetes mellitus patients with or without chronic respiratory disease in Beijing, and to investigate the changes in the costs and number of antidiabetic medications used for diabetes patients with chronic respiratory disease from 2016 to 2018.MethodsThis observational, retrospective study included diabetes patients with outpatient medication records from Beijing Medical Insurance between 2016 and 2018. The medications, including hypoglycemic and nonhypoglycemic drugs, insulin dosage, comorbidities, diabetes-related complications, treatment strategies, and annual medical costs, were recorded.ResultsThis study included 2,853,036 diabetes patients from 2016 to 2018. About 18.95%–20.53% of patients with chronic respiratory disease were predominantly distributed among those aged 45–84 years (88.7%–89.1%). Diabetes patients with chronic respiratory disease used more medications (4.48 ± 2.41 vs. 3.76 ± 2.33) and had higher total annual drug costs (¥12,286 ± 10,385 vs. ¥9700 ± 9202) to treat more comorbidities (2.52 ± 1.53 vs. 2.05 ± 1.85) than those without chronic respiratory disease (p

Offline perceptions are self-generated sensations that do not involve physical stimulus. These perceptions can be induced by external hallucinated objects or internal imagined objects. However, how the brain dissociates these visual sensations remains unclear. We aimed to map the brain areas involved in internal and external visual sensations induced by intracranial electrical stimulation and further investigate their neural differences. In this study, we collected subjective reports of internal and external visual sensations elicited by electrical stimulation in 40 drug-refractory epilepsy during presurgical evaluation. The response rate was calculated and compared to quantify the dissociated distribution of visual responses. We found that internal and external visual sensations could be elicited when different brain areas were stimulated, although there were more overlapping brain areas. Specifically, stimulation of the hippocampus and inferior temporal cortex primarily induces internal visual sensations. In contrast, stimulation of the occipital visual cortex mainly triggers external visual sensations. Furthermore, compared to that of the dorsal visual areas, the ventral visual areas show more overlap between the two visual sensations. Our findings show that internal and external visual sensations may rely on distinct neural representations of the visual pathway. This study indicated that implantation of electrodes in ventral visual areas should be considered during the evaluation of visual sensation aura epileptic seizures.

As transcriptional co-activator of AP-1/Jun, estrogen receptors and NF-κB, nuclear protein RBM39 also involves precursor mRNA (pre-mRNA) splicing. Porcine reproductive and respiratory syndrome virus (PRRSV) causes sow reproductive disorders and piglet respiratory diseases, which resulted in serious economic losses worldwide. In this study, the up-regulated expression of RBM39 and down-regulated of inflammatory cytokines (IFN-β, TNFα, NF-κB, IL-1β, IL-6) were determined in PRRSV-infected 3D4/21 cells, and accompanied with the PRRSV proliferation. The roles of RBM39 altering phosphorylation of c-Jun to inhibit the AP-1 pathway to promote PRRSV proliferation were further verified. In addition, the nucleocytoplasmic translocation of RBM39 and c-Jun from the nucleus to cytoplasm was enhanced in PRRSV-infected cells. The three RRM domain of RBM39 are crucial to support the proliferation of PRRSV. Several PRRSV RNA (nsp4, nsp5, nsp7, nsp10-12, M and N) binding with RBM39 were determined, which may also contribute to the PRRSV proliferation. Our results revealed a complex mechanism of RBM39 by altering c-Jun phosphorylation and nucleocytoplasmic translocation, and regulating binding of RBM39 with viral RNA to prompt PRRSV proliferation. The results provide new viewpoints to understand the immune escape mechanism of PRRSV infection.

High mobility group box 1 protein (HMGB1) is known to be a trigger of inflammation in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, it may play a different role in some way. Here we investigated the effect of HMGB1 on promoting sonic hedgehog (shh) release from astrocytes as well as the possible signal pathway involved in it. Firstly, shh increased in astrocytes after administration of recombinant HMGB1 or decreased after HMGB1 was blocked when stimulated by homogenate of the onset stage of EAE. Moreover, the expression of HMGB1 receptors, toll-like receptor (TLR) 2 and receptor for advanced glycation end products (RAGE) increased after HMGB1 administration in primary astrocytes. However, the enhancing effect of HMGB1 on shh release from astrocytes was suppressed only after RAGE was knocked out or blocked. Mechanistically, HMGB1 functioned by activating RAGE-mediated JNK, p38, stat3 phosphorylation. Moreover, HMGB1 could induce shh release in EAE. Additionally, intracerebroventricular injection of recombinant shh protein on the onset stage of EAE alleviated the progress of disease and decreased demylination, compared to the mice with normal saline treatment. Overall, HMGB1 promoted the release of shh from astrocytes through signal pathway JNK, p38 and stat3 mediated by receptor RAGE, which may provide new insights of HMGB1 function in EAE.

Evidences have suggested that Sjogren's syndrome (SS) is associated with viral infection. The aim of this study was to investigate the involvement of respiratory viral poly(I:C) in the pathogenesis of SS and potential mechanisms using a SS-like NOD/ShiLtJ (NOD) mouse model. 5-week female NOD mice were intratracheally administered poly(I:C) every other day for 5 times to mimic viral infection. Pilocarpine induced saliva secretion was determined every 8 days. Submandibular glands (SMG) and lungs were harvested for the detection of pathological changes. We found that intratracheal administration of poly(I:C) significantly advanced and enhanced the reduction of saliva flow rate in NOD mice. Furthermore, poly(I:C) treatment aggravated the histopathological lesions and inflammatory cells infiltration in SMG. Accompanied by elevated expression of IFN cytokines and IL-33, Th1 activation was enhanced in SMG of poly(I:C)-treated NOD mice, but Th17 cells activation was unchanged among the groups. In addition, intratracheal poly(I:C) exposure promoted the expression of IL-33 and increased T cells proportion in the lung, which were consistent with the change in SMG. Therefore, intratracheal poly(I:C) exposure aggravated the immunological and function disorder of SMG in NOD mice.

Cardiac allograft vasculopathy (CAV) charactered with aberrant remodeling and fibrosis usually leads to the loss of graft after heart transplantation. Our previous work has reported that extracellular high-mobility group box 1 (HMGB1) participated in the CAV progression via promoting inflammatory cells infiltration and immune damage. The aim of this study was to investigate the involvement of HMGB1 in the pathogenesis of CAV/fibrosis and potential mechanisms using a chronic cardiac rejection model in mice. We found high levels of transforming growth factor (TGF)-β1 in cardiac allografts after transplantation. Treatment with HMGB1 neutralizing antibody markedly prolonged the allograft survival accompanied by attenuated fibrosis of cardiac allograft, decreased fibroblasts-to-myofibroblasts conversion, and reduced synthesis and release of TGF-β1. In addition, recombinant HMGB1 stimulation promoted release of active TGF-β1 from cardiac fibroblasts and macrophages in vitro, and subsequent phosphorylation of Smad2 and Smad3 which were downstream of TGF-β1 signaling. These data indicate that HMGB1 contributes to the CAV/fibrosis via promoting the activation of TGF-β1/Smad signaling. Targeting HMGB1 might become a new therapeutic strategy for inhibiting cardiac allograft fibrosis and dysfunction.

The role of IL-33/ST2 signaling in cardiac allograft vasculopathy (CAV) is not fully addressed. Here, we investigated the role of IL-33/ST2 signaling in allograft or recipient in CAV respectively using MHC-mismatch murine chronic cardiac allograft rejection model. We found that recipients ST2 deficiency significantly exacerbated allograft vascular occlusion and fibrosis, accompanied by increased F4/80+ macrophages and CD3+ T cells infiltration in allografts. In contrast, allografts ST2 deficiency resulted in decreased infiltration of F4/80+ macrophages, CD3+ T cells and CD20+ B cells and thus alleviated vascular occlusion and fibrosis of allografts. These findings indicated that allografts or recipients ST2 deficiency oppositely affected cardiac allograft vasculopathy/fibrosis via differentially altering immune cells infiltration, which suggest that interrupting IL-33/ST2 signaling locally or systematically after heart transplantation leads different outcome.

Background: Dystonia and Huntington's disease (HD) are both hyperkinetic movement disorders but exhibit distinct clinical characteristics. Aberrant output from the globus pallidus internus (GPi) is involved in the pathophysiology of both HD and dystonia, and deep brain stimulation (DBS) of the GPi shows good clinical efficacy in both disorders. The electrode externalized period provides an opportunity to record local field potentials (LFPs) from the GPi to examine if activity patterns differ between hyperkinetic disorders and are associated with specific clinical characteristics.Methods: LFPs were recorded from 7 chorea-dominant HD and nine cervical dystonia patients. Differences in oscillatory activities were compared by power spectrum and Lempel-Ziv complexity (LZC). The discrepancy band power ratio was used to control for the influence of absolute power differences between groups. We further identified discrepant frequency bands and frequency band ratios for each subject and examined the correlations with clinical scores.Results: Dystonia patients exhibited greater low frequency power (6–14 Hz) while HD patients demonstrated greater high-beta and low-gamma power (26–43 Hz) (p < 0.0298, corrected). United Huntington Disease Rating Scale chorea sub-score was positively correlated with 26–43 Hz frequency band power and negatively correlated with the 6–14 Hz/26–43 Hz band power ratio.Conclusion: Dystonia and HD are characterized by distinct oscillatory activity patterns, which may relate to distinct clinical characteristics. Specifically, chorea may be related to elevated high-beta and low-gamma band power, while dystonia may be related to elevated low frequency band power. These LFPs may be useful biomarkers for adaptive DBS to treat hyperkinetic diseases.

Visuospatial working memory (WM) is a fundamental but severely limited ability to temporarily remember selected stimuli. Several studies have investigated the underlying neural mechanisms of maintaining various visuospatial stimuli simultaneously (i.e., WM load, the number of representations that need to be maintained in WM). However, two confounding factors, namely verbal representation and encoding load (the number of items that need to be encoded into WM), have not been well controlled in previous studies. In this study, we developed a novel delayed-match-to-sample task (DMST) controlling for these two confounding factors and recorded scalp EEG signals during the task. We found that behavioral performance deteriorated severely as memory load increased. Neural activity was modulated by WM load in a dynamic manner. Specifically, higher memory load induced stronger amplitude in occipital and central channel-clusters during the early delay period, while the inverse trend was observed in central and frontal channel-clusters during late delay. In addition, the same inverse memory load effect, that was lower memory load induced stronger amplitude, was observed in occipital channel-cluster alpha power during late delay. Finally, significant correlations between neural activity and individual reaction time showed a role of late-delay central and frontal channel-cluster amplitude in predicting behavioral performance. Because the occipital cortex is important for visual information maintenance, the decrease in alpha oscillation was consistent with the cognitive role that is “gating by inhibition.” Together, our results from a well-controlled DMST suggest that WM load not exerted constant but dynamic effect on neural activity during maintenance of visuospatial objects.

ObjectiveThis review aims to provide a quantitative and qualitative bibliometric analysis of literature from 2013 to 2023 on the role of exosomes in PC, with the goal of identifying current trends and predicting future hotspots.MethodsWe retrieved relevant publications concerning exosomes in PC, published between 2013 and 2023, from the Web of Science Core Collection. Bibliometric analyses were conducted using VOSviewer(1.6.19), CiteSpace(6.2.R4), and Microsoft Excel (2019).ResultsA total of 624 papers were analyzed, authored by 4017 researchers from 55 countries/regions and 855 institutions, published in 258 academic journals. China (n=285, 34.42%) and the United States (n=183, 24.87%) were the most frequent contributors and collaborated closely. However, publications from China had a relatively low average number of citations (41.45 times per paper). The output of Shanghai Jiao Tong University ranked first, with 28 papers (accounting for 4.5% of the total publications). Cancers (n=31, 4.9%); published the most papers in this field. Researcher Margot Zoeller published the most papers (n=12) on this topic. Research hotspots mainly focused on the mechanisms of exosomes in PC onset and progression, the role of exosomes in PC early diagnosis and prognosis, exosomes promote the development of PC chemoresistance, and potential applications of exosomes as drug carriers for PC therapies. We observed a shift in research trends, from mechanistic studies toward clinical trials, suggesting that clinical applications will be the focus of future attention. Emerging topics were pancreatic stellate cells, diagnostic biomarkers, mesenchymal stem cells, extracellular vesicles.ConclusionOur scientometric and visual analysis provides a comprehensive overview of the literature on the role of exosomes in PC published during 2013–2023. This review identifies the frontiers and future directions in this area over the past decade, and is expected to provide a useful reference for researchers in this field.

Orientation detection is an essential function of the visual system. In our previous works, we have proposed a new orientation detection mechanism based on local orientation-selective neurons. We assume that there are neurons solely responsible for orientation detection, with each neuron dedicated to detecting a specific local orientation. The global orientation is inferred from the local orientation information. Based on this mechanism, we propose an artificial visual system (AVS) by utilizing a single-layer of McCulloch-Pitts neurons to realize these local orientation-sensitive neurons and a layer of sum pooling to realize global orientation detection neurons. We demonstrate that such a single-layer perceptron artificial visual system (AVS) is capable of detecting global orientation by identifying the orientation with the largest number of activated orientation-selective neurons as the global orientation. To evaluate the effectiveness of this single-layer perceptron AVS, we perform computer simulations. The results show that the AVS works perfectly for global orientation detection, aligning with the majority of physiological experiments and models. Moreover, we compare the performance of the single-layer perceptron AVS with that of a traditional convolutional neural network (CNN) on orientation detection tasks. We find that the single-layer perceptron AVS outperforms CNN in various aspects, including identification accuracy, noise resistance, computational and learning cost, hardware implementation feasibility, and biological plausibility.

BackgroundVarious immune cell types in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) have been identified as important parameters associated with prognosis and responsiveness to immunotherapy. However, how various factors influence immune cell infiltration remains incompletely understood. Hence, we investigated the single cell multi-omics landscape of immune infiltration in HCC, particularly key gene and cell subsets that influence immune infiltration, thus potentially linking the immunotherapy response and immune cell infiltration.MethodsWe grouped patients with HCC according to immune cell infiltration scores calculated by single sample gene set enrichment analysis (ssGSEA). Differential expression analysis, functional enrichment, clinical trait association, gene mutation analysis, tumor immune dysfunction and exclusion (TIDE) and prognostic model construction were used to investigate the immune infiltration landscape through multi-omics. Stepwise regression was further used to identify key genes regulating immune infiltration. Single cell analysis was performed to explore expression patterns of candidate genes and investigate associated cellular populations. Correlation analysis, ROC analysis, Immunotherapy cohorts were used to explore and confirm the role of key gene and cellular population in predicting immune infiltration state and immunotherapy response. Immunohistochemistry and multiplexed fluorescence staining were used to further validated our results.ResultsPatients with HCC were clustered into high and low immune infiltration groups. Mutations of CTNNB1 and TTN were significantly associated with immune infiltration and altered enrichment of cell populations in the TME. TIDE analysis demonstrated that T cell dysfunction and the T cell exclusion score were elevated in the high and low infiltration groups, respectively. Six risk genes and five risk immune cell types were identified and used to construct risk scores and a nomogram model. CXCR6 and LTA, identified by stepwise regression, were highly associated with immune infiltration. Single cell analysis revealed that LTA was expressed primarily in tumor infiltrating T lymphocytes and partial B lymphocytes, whereas CXCR6 was enriched predominantly in T and NK cells. Notably, CXCR6+ CD8 T cells were characterized as tumor enriched cells that may be potential predictors of high immune infiltration and the immune-checkpoint blockade response, and may serve as therapeutic targets.ConclusionWe constructed a comprehensive single cell and multi-omics landscape of immune infiltration in HCC, and delineated key genes and cellular populations regulating immune infiltration and immunotherapy response, thus providing insights into the mechanisms of immune infiltration and future therapeutic control.

Obesity has become one of the major public health problems in both the developing and developed countries. Recent studies have suggested that the purinergic signalling is involved in obesity-associated end-organ damage through purine P1 and P2 receptors. In the search for new components for the treatments of obesity, we and other researchers have found much evidence that natural plant extracts may be promising novel therapeutic approaches by modulating purinergic signalling. In this review, we summarize a critical role of purinergic signalling in modulating obesity-associated end-organ damage, such as overhigh appetite, myocardial ischemia, inflammation, atherosclerosis, non-alcoholic fatty liver disease (NAFLD), hepatic steatosis and renal inflammation. Moreover, we focus on the potential roles of several natural plant extracts, including quercetin, resveratrol/trans-resveratrol, caffeine, evodiamine and puerarin, in alleviating obesity-associated end-organ damage via purinergic signalling. We hope that the current knowledge of the potential roles of natural plant extracts in regulating purinergic signalling would provide new ideas for the treatment of obesity and obesity-associated end-organ damage.

BackgroundAlthough the increase of perioperative complications in the elderly undergoing pancreaticoduodenectomy (PD) surgery has been recognized, the definition of the “old patient” of PD in the studies is different and there is no accepted cut-off value at present.Methods279 consecutive patients who have undergone PD in our center between January 2012 and May 2020 were analyzed. Demographic features, clinical-pathological data and short-term outcomes were collected. The patients were divided into two groups, and the cut-off value (62.5 years) is picked based on the highest Youden Index. Primary endpoints were perioperative morbidity and mortality, and complications were classified according to the Clavien-Dindo Score.ResultsA total of 260 patients with PD were included in this study. Postoperative pathology confirmed pancreatic tumors in 62 patients, bile duct tumor in 105, duodenal tumor in 90, and others in 3. Age (OR = 1.09, P

Coastal pollution, global warming, ocean acidification, and other reasons lead to the imbalance of the coral reef ecosystem, resulting in the increasingly serious problem of coral degradation. Coral bleaching is often accompanied by structural abnormalities of coral symbiotic microbiota, among which Vibrio is highly concerned. In this study, Vibrio fortis S10-1 (MCCC 1H00104), isolated from sea cucumber, was used for the bacterial infection on coral Seriatopora guttatus and Pocillopora damicornis. The infection of S10-1 led to coral bleaching and a significant reduction of photosynthetic function in coral holobiont, and the pathogenicity of V. fortis was regulated by quorum sensing. Meanwhile, Vibrio infection also caused a shift of coral symbiotic microbial community, with significantly increased abundant Proteobacteria and Actinobacteria and significantly reduced abundant Firmicutes; on genus level, the abundance of Bacillus decreased significantly and the abundance of Rhodococcus, Ralstonia, and Burkholderia–Caballeronia–Paraburkholderia increased significantly; S10-1 infection also significantly impacted the water quality in the micro-ecosystem. In contrast, S10-1 infection showed less effect on the microbial community of the live stone, which reflected that the microbes in the epiphytic environment of the live stone might have a stronger ability of self-regulation; the algal symbionts mainly consisted of Cladocopium sp. and showed no significant effect by the Vibrio infection. This study verified that V. fortis is the primary pathogenic bacterium causing coral bleaching, revealed changes in the microbial community caused by its infection, provided strong evidence for the “bacterial bleaching” hypothesis, and provided an experimental experience for the exploration of the interaction mechanism among microbial communities, especially coral-associated Vibrio in the coral ecosystem, and potential probiotic strategy or QS regulation on further coral disease control.

Among the existing gas storage facilities, salt cavern gas storage has the advantages of high injection production efficiency, low gas cushion volume, safety, flexibility, etc. It is of great significance to speed up the construction of underground gas storage by transforming abandoned salt caverns of salt industry into underground gas storage. However, old salt cavern wells cannot be directly converted into gas storage injection and production wells, so the old wellbore must be plugged to ensure the effectiveness of plugging. Therefore, a set of plugging optimization technology for salt cavern gas storage wells is urgently needed. In this paper, a 3D finite element model of the cement plug-formation system based on cohesive element method is established for the milling and plugging of the old well in the salt cavern gas storage section. The results show that under the condition of constant gas storage pressure, a certain degree of small deformation will occur at the bottom of the cement plug after compression, resulting in the shear direction deformation of the cement plug formation cementation interface, and peeling will occur after accumulation to a certain extent. With the increase of simulation time, the length of stripping section gradually increases and tends to be stable, and reaches the limit of stripping failure length. In the process of research, the factors and laws affecting the stripping failure length were also analyzed. It was found that the stripping failure length of cement plug formation cementation interface was related to the maximum operating pressure of gas storage, cement plug length, cement plug diameter, elastic modulus, Poisson’s ratio and other factors. The research results are helpful to judge whether the milling and plugging length of the old well section is sufficient, and provide theoretical guidance for ensuring the long-term safe operation of the gas storage.

BackgroundPostoperative recurrence impedes the curability of early-stage hepatocellular carcinoma (E-HCC). We aimed to establish a novel recurrence-related pathological prognosticator with artificial intelligence, and investigate the relationship between pathological features and the local immunological microenvironment.MethodsA total of 576 whole-slide images (WSIs) were collected from 547 patients with E-HCC in the Zhongshan cohort, which was randomly divided into a training cohort and a validation cohort. The external validation cohort comprised 147 Tumor Node Metastasis (TNM) stage I patients from The Cancer Genome Atlas (TCGA) database. Six types of HCC tissues were identified by a weakly supervised convolutional neural network. A recurrence-related histological score (HS) was constructed and validated. The correlation between immune microenvironment and HS was evaluated through extensive immunohistochemical data.ResultsThe overall classification accuracy of HCC tissues was 94.17%. The C-indexes of HS in the training, validation and TCGA cohorts were 0.804, 0.739 and 0.708, respectively. Multivariate analysis showed that the HS (HR= 4.05, 95% CI: 3.40-4.84) was an independent predictor for recurrence-free survival. Patients in HS high-risk group had elevated preoperative alpha-fetoprotein levels, poorer tumor differentiation and a higher proportion of microvascular invasion. The immunohistochemistry data linked the HS to local immune cell infiltration. HS was positively correlated with the expression level of peritumoral CD14+ cells (p= 0.013), and negatively with the intratumoral CD8+ cells (p< 0.001).ConclusionsThe study established a novel histological score that predicted short-term and long-term recurrence for E-HCCs using deep learning, which could facilitate clinical decision making in recurrence prediction and management.

Previous studies have reported that general or photo-specific social media use was associated with women’s body dissatisfaction and body image disturbance. The current study replicated and expanded upon these findings by identifying the positive association between social media influencer viewing and intentions to change appearance. This study surveyed a sample of 7,015 adult female TikTok users in China regarding their social media influencer viewing frequency, self-objectification, social comparison tendencies when watching short videos, intentions to change appearance, and demographics. The results showed that female TikTok users’ self-objectification mediated the association between their influencer viewing frequency and their intentions to change appearance. Furthermore, social comparison tendencies moderated the association between influencer viewing and intentions to change appearance in that the proposed association was stronger for female TikTok users who had lower social comparison tendencies when watching short videos, compared to female TikTok users who had higher social comparison tendencies. The counter-intuitive finding on social comparison tendencies indicated that women who have higher social comparison tendencies may be more aware of the negative influences and adjust their expectations. The observed association between social media influencer viewing and intentions to change appearance was statistically significant but trivial in terms of effect size. Although the result could warn policymakers and practitioners to design media and health literacy campaigns to cultivate body positivity, caution should be exercised when evaluating the practical implications.

Glucocorticoids are commonly used to treat anti-GBM crescentic glomerulonephritis, however, the mechanism underlying its therapeutic effectiveness is not completely understood. Since podocyte EGFR/STAT3 signaling is known to mediate the development of anti-GBM glomerulonephritis, we investigated the effect of glucocorticoids on EGFR/STAT3 signaling in podocytes. We found that the levels of phosphorylated (activated) EGFR and STAT3 in podocytes were markedly elevated in anti-GBM patients without glucocorticoids treatment, but were normalized in patients with glucocorticoids treatment. In a rat model of anti-GBM glomerulonephritis, glucocorticoids treatment significantly attenuated the proteinuria, crescent formation, parietal epithelial cell (PEC) activation and proliferation, accompanied by elimination of podocyte EGFR/STAT3 signaling activation. In cultured podocytes, glucocorticoids were found to inhibit HB-EGF-induced EGFR and STAT3 activation. The conditioned medium from podocytes treated with HB-EGF in the absence but not presence of glucocorticoids was capable of activating Notch signaling (which is known to be involved in PEC proliferation and crescent formation) and enhancing proliferative activity in primary PECs, suggesting that glucocorticoids prevent podocytes from producing secreted factors that cause PEC proliferation and crescent formation. Furthermore, we found that glucocorticoids can downregulate the expression of EGFR ligands, EGF and HB-EGF, while upregulate the expression of EGFR inhibitor, Gene 33, explaining how glucocorticoids suppress EGFR signaling. Taken together, glucocorticoids exert therapeutic effect on anti-GBM crescentic glomerulonephritis through inhibiting podocyte EGFR/STAT3 signaling and the downstream pathway that leads to PEC proliferation and crescent formation.

Object: Subdural or deep intracerebral electrodes are essential in order to precisely localize epileptic zone in patients with medically intractable epilepsy. Precise localization of the implanted electrodes is critical to clinical diagnosing and treatment as well as for scientific studies. In this study, we sought to automatically and precisely extract intracranial electrodes using pre-operative MRI and post-operative CT images. Method: The subdural and depth intracranial electrodes were readily detected using clustering-based segmentation. Depth electrodes were tracked by fitting a quadratic curve to account for potential bending during the neurosurgery. The identified electrodes can be manipulated using a graphic interface and labeled to cortical areas in individual native space based on anatomical parcellation and displayed in the volume and surface space. Results: The electrodes' localizations were validated with high precision. The electrode coordinates were normalized to a standard space. Moreover, the probabilistic value being to a specific area or a functional network was provided. Conclusions: We developed an integrative toolbox to reconstruct and label the intracranial electrodes implanted in the patients with medically intractable epilepsy. This toolbox provided a convenient way to allow inter-subject comparisons and relation of intracranial EEG findings to the larger body of neuroimaging literature. [ABSTRACT FROM AUTHOR]

Background: It remains unclear whether the short-term benefits of laparoscopic repeat hepatectomy (LRH) accrue to patients with recurrent liver tumors. The present study aimed to report our own center's experience and perform a meta-analysis to evaluate the safety and feasibility of LRH in comparison with open repeat hepatectomy (ORH) for treating recurrent liver tumors.Patients and Methods: A propensity score–matched study was performed including 426 patients receiving LRH or ORH for recurrent hepatocellular carcinoma between January 2017 and December 2018. Surgical outcomes and perioperative inflammation-based markers, including monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and systemic immune–inflammation index were collected from medical records and analyzed. Additionally, a systematic literature review was performed to identify relevant studies in PubMed, EMBASE, Web of Science, and Cochrane library databases up to October 1, 2020. Information including patient demographics, pathologic characteristics, and short-term outcomes was extracted and analyzed using random- or fixed-effects models.Results: Of 68 LRHs, 57 were matched with an ORH finally. Our study demonstrated that LRH was significantly associated with less intraoperative blood loss (50 vs. 100 mL; P < 0.001), lower rate of hepatic inflow occlusion (10.52 vs. 33.3%; P = 0.003), and shorter postoperative hospital stay (5 vs. 6 days; P = 0.001) after 1:1 propensity score matching. The operation time, rate of blood transfusion, and postoperative complications were similar between the two groups. Moreover, all four inflammation-based markers were significantly lower in LRH group on postoperative day 1. In the meta-analysis, a total of 12 studies comprising 1,315 patients receiving repeat hepatectomy met the selection criteria. Similar to our own study, the meta-analysis showed shorter hospital stay [standard mean difference (SMD) = −0.51, 95% confidence interval (CI) = −0.79 to −0.22, P < 0.001], less intraoperative blood loss (SMD = −0.79, 95% CI = −1.11 to −0.47, P < 0.001), and lower rate of major postoperative complications [odds ratio (OR) = 0.35, 95% CI = 0.19–0.66, P = 0.001] in the LRH group. There was no difference in the field of overall postoperative complication and operation time between LRH and ORH groups.Conclusion: Compared with ORH, LRH results in relatively better surgical outcomes and faster postoperative recovery. It could be considered a feasible and effective option for the treatment of recurrent liver tumors.

Background: Currently, most studies indicate that there is a potential link between maternal psychologic stress and the risk of atopic dermatitis (AD) in offspring. However, it is unknown which trimester of pregnancy is most sensitive to maternal stress in terms of risk of infant AD and whether the changes of maternal stress level in different trimesters of pregnancy may be associated with infant AD. In this study, we aimed to investigate the association between maternal perceived stress across three trimesters of pregnancy and AD in infants at 6 months.Methods: A total of 1,638 pregnant women participated in the population-based birth cohort study. Maternal prenatal stress was assessed by self-report questionnaires during each trimester. Infant AD was diagnosed at age 6 months, according to the UK Working Party diagnostic criteria. Univariate and multivariate logistic regression models were used to analyze the association between maternal prenatal stress in each trimester of pregnancy and infant AD.Results: Maternal perceived stress in the 2nd trimester was associated with AD in infants at 6 months (aOR 1.56; 95% CI 1.08–2.25, P = 0.019). Furthermore, increased level of perceived stress from the 1st to the 2nd trimester (aOR 2.05, 95% CI 1.33–3.15, P = 0.001) and from the 1st to the 3rd trimester (aOR 1.92, 95% CI 1.22–3.00, P = 0.004) were also associated with the risk of infant AD at 6 months.Conclusion: A high level of maternal perceived stress in the 2nd trimester and increased level of perceived stress from the 1st to the 2nd and 3rd trimesters of pregnancy may increase the risk of offspring developing AD at 6 months.

Drawing on spiritual leadership theory and intrinsic motivation theory, we proposed a homologous multilevel model to explore the effectiveness of spiritual leadership on employees’ task performance, knowledge sharing behaviors and innovation behaviors at the individual level. With questionnaires rated by 306 pairs of employees and their supervisors in 26 teams from the energy industry in mainland China, we conduct multilevel analysis to examine our hypotheses. The results show that spiritual leadership was positively related to employee task performance, knowledge sharing behaviors and innovation behavior, when we controlled for possible confounding effects of moral leadership and benevolent leadership, and ruled out alternative explanation of ethical leadership. The theoretical and practical implications are discussed.

Optimizing the utilization of applied nitrogen (N) in fruit trees requires N supply that is temporally matched to tree demand. We investigated how the timing of N application affected uptake, allocation, and remobilization within 14-year-old “Gala”/M26 apple trees (Malus domestica Borkh) over two seasons. In the 2017–2018 season, 30 g N tree−1 of 5.5 atom% 15N–calcium nitrate was applied by weekly fertigation in four equal doses, commencing either 4 weeks after full bloom (WAFB) (pre-harvest) or 1-week post-harvest, or fortnightly, divided between pre- and post-harvest (50:50 split). Nitrogen uptake derived from fertilizer (NDF) was monitored by leaf sampling before whole trees were destructively harvested at dormancy of the first season to quantify N uptake and allocation and at fruit harvest of the second season to quantify the remobilization of NDF. The uptake efficiency of applied N fertilizer (NUpE) was significantly higher from pre-harvest (32.0%) than from the other treatments (~17%). The leaf NDF concentration, an indicator of N uptake, increased concomitantly only when pre-harvest N was applied. Pre-harvest treated trees allocated more than half of the NDF into fruit and leaves and stored the same amount of NDF into perennial organs as the post-harvest treatment. Subsequent spring remobilization of NDF was not affected by the timing of N fertigation from the previous season. A seasonal effect of remobilization was observed with a decrease in root N status and a reciprocal increase in branch N status at fruit harvest of season two. These findings represent a shift in the understanding of dynamics of N use in mature deciduous trees and indicate that current fertilizer strategies need to be adjusted from post-harvest to primarily pre-harvest N application to optimize N use efficiency. This approach can provide adequate storage N to support early spring growth the following season with no detriment to fruit quality.

Background: Anthracyclines are widely used to treat childhood cancers; however, they cause cardiotoxicity. To address the paucity of clinical data from Asian populations, this study investigated the epidemiology of pediatric anthracycline-induced cardiotoxicity, during and after chemotherapy, in a multiethnic Asian population.Procedure: This was a single-center, retrospective analysis of 458 anthracycline-treated pediatric oncology patients at KK Women's and Children's Hospital, a tertiary children's hospital in Singapore from 2005 through 2015. We investigated cardiotoxicity (defined as left ventricular fractional shortening