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Severe trauma can lead to numerous serious complications, threating the well-being and vitality of the afflicted. The quantity and functionality of PMNs undergo rapid transformations in response to severe trauma, playing a pivotal role in the trauma response. The absence of CCAAT/enhancer-binding protein ε (C/EBPε) profoundly impairs the functionality of polymorphonuclear neutrophils (PMNs), a function of paramount importance in trauma. In this study, by generating mice with C/EBPε knocked out or overexpressed, we substantiate that C/EBPε ensures the restoration of PMN function, enhancing the expression of antimicrobial proteins and thereby promoting trauma recovery. Furthermore, diminished expression of C/EBPε is observed in trauma patients, with levels displaying a negative correlation with ISS and APACHE II scores, suggesting its potential as a prognostic indicator for clinical treatment. Mechanistically, we uncover the upregulation of SIRT1 and the inhibition of P300 participating in the suppression of C/EBPε acetylation, consequently reducing the resilience of mice to trauma. As therapeutic interventions, whether through the sole administration of PMN, NAM treatment, or their combination, all result in an increased survival rate in traumatic mice. In conclusion, our study elucidates the role of C/EBPε in enhancing the resilience to trauma and identifies C/EBPε acetylation as a critical regulatory mechanism, offering potential therapeutic approaches involving PMN transfusion and NAM treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: In recent years, hypervirulent Klebsiella pneumoniae (hvKp) has attracted increasing attention. It usually causes liver abscesses, which spread through the bloodstream to other parts such as the eyes, brain, lungs. 5.5% of all paroxysmal sympathetic hyperactivity syndrome are associated with infection, hydrocephalus, brain tumors, and some unknown causes. Younger patients with focal lesions of the brain parenchyma are at higher risk of paroxysmal sympathetic hyperactivity (PSH)., Case Presentation: This case report details the clinical features of Klebsiella pneumoniae diagnosed in a healthy individual. In addition to liver abscesses, bacteremia, and hyperglycemia, there are also brain abscesses, hernias, and postoperative paroxysmal sympathetic hyperactivity, an unexpected association between diseases or symptoms. The patient stabilized after comprehensive treatment, including early drainage of abscesses, rapid pathogen diagnosis, and timely and appropriate antibiotics. At a two-month follow-up, no signs of infection recurrence were noted, and the patient regained neurological function and could participate in regular physical activity., Discussion: Symptoms of Klebsiella pneumoniae infection usually appear gradually, and misdiagnosis is common. When young patients suddenly develop high fever and abscess at a particular site, Klebsiella pneumoniae infection should be considered routine. Paroxysmal sympathetic hyperactivity syndrome caused by infection is rare, but a clinical score (PSH assessment measure, PSH-AM score) should be performed when clinical features appear. Early diagnosis and treatment can improve the prognosis., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Xuefang Liu, Ning Yu, Huaihai Lu, Yinlong Zhao, Junyu Zhu, Ya Liu.)

Infection is a common medical problem at present. Different pathogens can lead to different infections. Severe infections can ultimately lead to sepsis, resulting in multiple organ dysfunction and the high mortality of patients. Therefore, studying the occurrence and development of severe infections is essential to improve the survival rate of patients. More and more studies have revealed the important role of connection between intestine and liver in infectious diseases. The maintenance of intestinal mechanical barrier and biological barrier function and the regulation of intestinal flora metabolites can reduce infectious liver injury. Bile acids are important metabolites in the liver, which can inhibit the progression of certain infectious intestinal injuries and promote intestinal damage caused by certain pathogens. In this article, the mechanism of action of the intestinal-liver axis in infection was reviewed to find a new target for the treatment of clinical infection.

Acidification of aroma-enhanced black tea during storage was studied. UPLC-Q-TOF/MS (Ultra Performance Liquid Chromatography and Quadrupole-Time of Flight Mass Spectrometer) and HPLC (High-Performance Liquid Chromatography) analysis of non-volatile substances and organic acids revealed a decrease of soluble sugars and amino acids in aroma-enhanced black tea, while an increase in organic acids such as oxalic acid, malic acid and quinic acid. Further in vitro experiments indicated that the acidification of aroma-enhanced tea during storage can be attributed to decomposition of sugars and amino acids by heating, oxidation of aromatic aldehydes. Meanwhile, the amino acids, catechins, soluble sugars and flavonoids that constitute the taste of black tea are further reduced, changing the taste composition of tea infusion and further increasing its acidity. This study revealed the reasons for black tea acidification during aroma enhancement and storage and provided a theoretical basis for improving black tea quality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The interaction of gut microbiota and its metabolites with the host not only plays an important role in maintaining gut homeostasis and host health, but also is a key link in responding to pathogen infections. A thorough understanding of the changes in gut microbiota and its metabolites during infection, as well as their role and mechanism in host defense against infection, is helpful to guide anti-infection treatment. This review focuses on the role of gut microbiota and their metabolites in host defense against bacterial, fungal, and viral infections, and reveals that they can exert anti-infection effects through resistance mechanisms (inducing antimicrobial substances, training immunity, inhibiting pathogen respiration, directly neutralizing pathogens, immune regulation) and tolerance mechanisms (altering energy metabolism patterns of microbiota, cell proliferation and tissue damage repair, maintaining physiological signal transduction in extraintestinal organs, inflammation regulation, maintaining the integrity of the intestinal barrier), and also summarizes measures to regulate gut microbiota against pathogen infections, in order to provide more ideas for novel anti-infection prevention and treatment strategies targeting gut microbiota and its metabolites.

Objective: The objective was to explore the possible relationship between the serum vitamin D level and olfactory impairment in a population of multiple sclerosis (MS) patients in Guizhou, China., Methods: We included 25 patients with MS and 18 healthy controls (HCs) who were recruited from the Affiliated Hospital of Guizhou Medical University from February 2021 to September 2021. The University of Pennsylvania Smell Identification Test (UPSIT) was used to test the patients' sense of smell, and the level of serum 25-hydroxyethylene polyprotein D was measured., Results: Serum vitamin D levels and UPSIT scores were significantly different between the MS group and the control group (both p  < 0.001). Moreover, a significant positive correlation emerged between vitamin D levels and UPSIT scores in MS patients ( r  = 0.537, p  = 0.021)., Conclusions: The serum vitamin D level may be involved in the regulation of olfactory dysfunction in MS patients in Guizhou, China.

Here, we present the complete genome sequence of Kineothrix sp. MB12-C1 (= BCRC 81406), isolated from the feces of black soldier fly ( Hermetia illucens ) larvae. The genome of strain MB12-C1 was chosen for further species classification and comparative genomic analysis., Competing Interests: The authors declare no conflict of interest.

Semantic scene completion (SSC) aims to predict the semantic occupancy of each voxel in the entire 3D scene from limited observations, which is an emerging and critical task for autonomous driving. Recently, many studies have turned to camera-based SSC solutions due to the richer visual cues and cost-effectiveness of cameras. However, existing methods usually rely on sophisticated and heavy 3D models to process the lifted 3D features directly, which are not discriminative enough for clear segmentation boundaries. In this paper, we adopt the dense-sparse-dense design and propose a one-stage camera-based SSC framework, termed SGN, to propagate semantics from the semantic-aware seed voxels to the whole scene based on spatial geometry cues. Firstly, to exploit depth-aware context and dynamically select sparse seed voxels, we redesign the sparse voxel proposal network to process points generated by depth prediction directly with the coarse-to-fine paradigm. Furthermore, by designing hybrid guidance (sparse semantic and geometry guidance) and effective voxel aggregation for spatial geometry cues, we enhance the feature separation between different categories and expedite the convergence of semantic propagation. Finally, we devise the multi-scale semantic propagation module for flexible receptive fields while reducing the computation resources. Extensive experimental results on the SemanticKITTI and SSCBench-KITTI-360 datasets demonstrate the superiority of our SGN over existing state-of-the-art methods. And even our lightweight version SGN-L achieves notable scores of 14.80% mIoU and 45.45% IoU on SeamnticKITTI validation with only 12.5 M parameters and 7.16 G training memory. Code is available at https://github.com/Jieqianyu/SGN.

Introduction: In recent years, researchers have been exploring the plastic-degrading abilities of bacteria residing in the guts of Styrofoam-eating Tenebrio molitor larvae. However, none of the reported strains have displayed highly efficient plastic degradation capabilities, and it's noteworthy that none of the existing studies have focused on strictly anaerobic microbes., Methods: In this study, we exclusively fed Styrofoam to T. molitor larvae and examined how this dietary change influence the gut's bacterial community composition, as observed through fecal bacteria using bacterial 16S rRNA gene amplicon sequencing and the small-scale culturomics method with 20 types of anaerobic media under four different conditions., Results: The results revealed a significant shift in the dominant phylogroup from Lactococcus (37.8%) to Escherichia-Shigella (54.7%) when comparing the feces of larvae fed with bran and Styrofoam, as analyzing through the bacterial 16S rRNA gene amplicon sequencing. For small-scale culturomics method, a total of 226 strains of anaerobic bacteria were isolated and purified using the rolling-tube/strictly anaerobic technique. Among them, 226 strains were classified into 3 phyla, 7 classes, 9 orders, 17 families, 29 genera, 42 known species and 34 potential novel species., Discussion: Interestingly, 24 genera in total, identified through the culturomics method, were not found in the results obtained from amplicon sequencing. Here, we present a collection of culturable anaerobic bacteria from the feces of T. molitor larvae, which might be a promising avenue for investigating the biodegradability of plastics by combining specific strains, either randomly or intentionally, while considering the abundance ratio of the microbial community composition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Chen, Chen, Qiu, Yu, Guo and Wang.)

Here, we report the complete genome sequence of Proteiniborus sp. MB09-C3 (= BCRC 81405), isolated from the feces of black soldier fly ( Hermetia illucens ) larvae. The genome of strain MB09-C3 was selected for further species delineation and comparative genomic analysis., Competing Interests: The authors declare no conflict of interest.

Microplastics (MPs) are small plastic pieces less than 5 mm in size. Previous studies have focused on the sources, transports, and fates of MPs in marine or sediment environments. However, limited attention has been given to the role of land as the primary source of MPs, and how plastic polymers are transformed into MPs through biological or abiotic effects during the transport process remains unclear. Here, we focus on the exploration of the main sources of MPs in the soil, highlighting that MP generation is not solely a byproduct of plastic production but can also result from the impact of biological and abiotic factors during the process of MPs transport. This review presents a new perspective on understanding the degradation of MPs in soil, considering soil as a distinct fluid and suggesting that the main transformation and change mediated by abiotic factors occur on the soil surface, while the main biodegradation occurs in the soil interior. This viewpoint is suggested because the role of some abiotic factors becomes less obvious in the soil interior, and MPs, whose surface is expected to colonize microorganisms, are gradually considered a carbon source independent of photosynthesis and net primary production. This review emphasizes the need to understand basic MPs information in soil for a rational evaluation of its environmental toxicity. Such understanding enables better control of MPs pollution in affected areas and prevents contamination in unaffected regions. Finally, knowledge gaps and future research directions necessary for advancements in this field are provided., Competing Interests: Declaration of competing interest All the authors declared that they have no conflicts of interest to this work. And we declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Although many CTC isolation and detection methods can provide information on cancer cell counts, downstream gene and protein analysis remain incomplete. Therefore, it is crucial to develop a technology that can provide comprehensive information on both the number and profile of CTC., Methods: In this study, we developed a novel microfluidics-based CTC separation and enrichment platform that provided detailed information about CTC., Results: This platform exhibits exceptional functionality, achieving high rates of CTC recovery (87.1%) and purification (∼4 log depletion of WBCs), as well as accurate detection (95.10%), providing intact and viable CTCs for downstream analysis. This platform enables successful separation and enrichment of CTCs from a 4 mL whole-blood sample within 15 minutes. Additionally, CTC subtypes, selected protein expression levels on the CTC surface, and target mutations in selected genes can be directly analyzed for clinical utility using immunofluorescence and real-time polymerase chain reaction, and the detected PD-L1 expression in CTCs is consistent with immunohistochemical assay results., Conclusion: The microfluidic-based CTC enrichment platform and downstream molecular analysis together provide a possible alternative to tissue biopsy for precision cancer management, especially for patients whose tissue biopsies are unavailable., Competing Interests: Authors XZ, HZ, WZ, YH, ZL, TQ, and TX were employed by the company Cellomics ShenZhen Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cai, Deng, Wang, Zhu, Huang, Du, Wang, Yu, Liu, Yang, Wang, Wang, Ma, Huang, Zhou, Zou, Zhang, Huang, Li, Qin, Xu, Guo and Yu.)

Objective: To investigate the utility of fluorescence in situ hybridization (FISH) in secondary electroresection of bladder cancer., Methods: From January 2016 to April 2022, bladder cancer patients who had undergone secondary electroresection in Tongji Hospital and had preoperative urine FISH were recruited, and the positive rate, accuracy, sensitivity, specificity, genetic material changes and predictive power on malignancy degree of FISH in the secondary electroresection of bladder cancer were examined., Results: Twenty-six patients with bladder cancer were included in this study, and 8 were confirmed by secondary electroresection, including 6 cases positive for FISH positive and 2 negative for FISH. Besides, among the subjects, 18 were without tumor recurrence, including 1 case with positive FISH results and 17 with negative FISH results. Tumor recurrence was diagnosed in 85.71% (6/7) of FISH-positive patients in secondary electroresection while only 10.53% (2/19) of FISH-negative patients were found to develop tumor recurrence in the secondary electroresection. The sensitivity of FISH for the detection of bladder cancer before secondary electroresection was 75%, with a specificity of 94.44%, and an accuracy of 88.46%. A 6-month follow-up revealed that 2 of the 8 recurrent patients underwent radical resection of bladder cancer, and the remaining 6 patients had no recurrence, as confirmed by regular bladder perfusion and microscopy. In the 18 non-recurrent patients during secondary electroresection, no recurrence developed., Conclusions: Urine FISH can achieve a high detection rate and specificity for secondary electroresection of bladder cancer. If a bladder cancer patient who are indicated for secondary electroresection is negative for urine FISH, the recurrence rate after secondary electroresection will be low, and the cystoscopy can be performed before deciding whether to perform secondary electroresection., (© 2013-2023 Bladder, All rights reserved.)

This study delved into the aroma characteristics of "Qingxiang" oolong tea, analyzing six different cultivars and their processing modes. The findings showed that both cultivars and processing modes have a significant impact on the oolong tea aroma system. The study identified 18 terpenoid volatiles (VTs), 11 amino-acid-derived volatiles (AADVs), 15 fatty-acid-derived volatiles (FADVs), 3 carotenoid-derived volatiles (CDVs), and 10 other compounds in oolong tea that differentiate it from green and black tea. The turn-over stage was found to be the primary processing stage for oolong tea aroma formation. Molecular sensory analysis revealed that the "fresh" odor attribute is the basis for its aroma, while "floral and fruity" fragrances are its aroma characteristics. The perception of oolong tea as "fresh" and "floral and fruity" is influenced by the interactions of its aroma components. These findings provide a new basis for breed improvement and process enhancement in oolong tea production., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Calreticulin (CRT) on the cell surface that acts as an "eat me" signal is vital for macrophage-mediated programmed cell removal. The polyhydroxylated fullerenol nanoparticle (FNP) has appeared as an effective inducer to cause CRT exposure on cancer cell surface, but it failed in treating some cancer cells such as MCF-7 cells based on previous findings. Here, we carried out the 3D culture of MCF-7 cells, and interestingly found that the FNP induced CRT exposure on cells in 3D spheres via re-distributing CRT from endoplasmic reticulum (ER) to cell surface. Phagocytosis experiments in vitro and in vivo illustrated the combination of FNP and anti-CD47 monoclonal antibody (mAb) further enhanced macrophage-mediated phagocytosis to cancer cells. The maximal phagocytic index in vivo was about three times higher than that of the control group. Moreover, in vivo tumorigenesis experiments in mice proved that FNP could regulate the progress of MCF-7 cancer stem-like cells (CSCs). These findings expand the application of FNP in tumor therapy of anti-CD47 mAb and 3D culture can be used as a screening tool for nanomedicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Xianglian Pill (XLP) is a classical Chinese medicine prescription applied for controlling ulcerative colitis (UC). Whereas, the underlying mechanism remains unclear., Aim of the Study: The present work was aimed to investigate the mechanism of XLP in dextran sulfate sodium (DSS)-induced UC via the Toll Like Receptor 4 (TLR4)/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-B (NF-κB) signaling in mice., Materials and Methods: The major components of XLP were detected by high-performance liquid chromatography-diode array detection (HPLC-DAD). The ulcerative colitis model was induced by DSS in mice. 5-Amino Salicylic Acid (5-ASA) group and XLP group were intragastrically treated. Disease activity index (DAI) and colon length were monitored and hematoxylin-eosin (HE) staining was conducted. Gasdermin D (GSDMD)-N and TLR4 expressions in colon tissues were visualized by immunofluorescence. TLR4 mRNA was measured by Real Time Quantitative PCR (RT-qPCR). The expressions of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), active-caspase-1, GSDMD-N, TLR4, MYD88, NF-κB, p-NF-κB, and the ubiquitination of TLR4 in colon tissues were detected by Western blot. Myeloperoxidase (MPO) enzyme activity was examined and serum inflammatory factors Interleukin (IL)-1β, IL-6, Tumor Necrosis Factor-α (TNF-α), and IL-18 were determined by Enzyme-linked Immunosorbent Assay (ELISA). TLR4 -/- mice were applied for verifying the mechanism of XLP attenuated DSS symptoms., Results: The XLP treatment extended colon length, reduced DAI, and attenuated histopathological alteration in DSS-induced mice. XLP administration suppressed MPO activity and reduced the content of IL-1β, IL-6, TNF-α and IL-18 in serum. XLP also inhibited the expression levels of GSDMD-N, TLR4, NLRP3, active-caspase-1, MyD88, p-NF-κB/NF-κB in colon tissues of DSS-induced mice. TLR4 -/- mice proved that TLR4 was involved in XLP-mediated beneficial effect on DSS-induced ulcerative colitis., Conclusions: XLP might treat ulcerative colitis by regulating the TLR4/MyD88/NF-κB signaling pathway., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recently, the need for antibacterial dressings has amplified because of the increase of traumatic injuries. However, there is still a lack of ideal, natural antibacterial dressings that show an efficient antibacterial property with no toxicity. Polyimide (PI) used as an implantable and flexible material has been recently reported as a mixture of particles showing more desirable antibacterial properties. However, we have identified a novel type of natural polyimide (PI) fiber that revealed antibacterial properties by itself for the first time. The PI fiber material is mainly composed of C, N, and O, and contains a small amount of Ca and Cl; the characteristic peaks of polyimide appear at 1774 cm -1 , 1713 cm -1 , 1370 cm -1 , 1087 cm -1 , and 722 cm -1 . PI fibers displayed significant antibacterial activities against Escherichia coli (as a Gram-negative bacteria model) and methicillin-resistant Staphylococcus aureus (MRSA, as a Gram-positive bacteria model) according to the time-kill kinetics in vitro , and PI fibers damaged both bacterial cell walls directly. PI fibers efficiently ameliorated a local infection in vivo , inhibited the bacterial burden, decreased infiltrating macrophages, and accelerated wound healing in an E. coli - or MRSA-infected wound model. In conclusion, PI fibers used in the present study may act as potent antibacterial dressings protecting from MRSA or E. coli infections and as promising candidates for antimicrobial materials for trauma and surgical applications., Competing Interests: The authors declare that they have no competing interests., (This journal is © The Royal Society of Chemistry.)

The cellulose content in vegetable waste (VW) is high and cannot be directly digested by black soldier fly larvae (BSFL). In this study, in order to treat VW using BSFL composting, kitchen waste (KW) is used as the only nutritional supplement for VW to analyze the effects of the different contents of crude protein (CP), crude fat (EE), carbohydrate (3C), compost thickness (CT), and treatment time on the larval weight (LW), survival rate (SR), dry matter reduction rate (DMR), bioconversion rate (BCR), physical and chemical properties of BSFL sand and changes in the microbial community. Our results showed that when the average 3C content increased by 40%, the average LW increased by 47.6%, and the SR, DMR, BCR, and organic matter (OM) content increased by 16.82%, 8.5%, 4.77%, and 3.86%, respectively. In contrast, when the average compost thickness increased by 5 cm, the average weight of BSFL decreased by 22.64%, while the SR of larvae, DMR, BCR, OM, and total nutrients (TN + P 2 O 5  + K 2 O) decreased by 5%, 5.2%, 4.42%, 9.6%, and 0.78%, respectively. Germination test showed that BSFL sand alone could not be used as soilless culture substrate. After BSFL treatment, we found that the dominant phyla in BSFL sand were Firmicutes (95.77%), Proteobacteria (2.54%), Actinobacteria (0.74%), and Chloroflexi (0.6%). Our results indicate that BSFL composting is an effective method of treating VW, and 3C content and CT have a significant effect on BSFL composting., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To determine the association of post-traumatic acute respiratory distress syndrome (ARDS) on poor prognosis, and provide a theoretical basis for the treatment of patients with post-traumatic ARDS in clinical practice., Methods: This was a retrospective study including trauma victims in the intensive care unit (ICU) of Daping Hospital. The patients were classified as having ARDS or non-ARDS, according to the Berlin definition. Subsequently, these patients were divided into subgroups, according to age, gender and injury site. The relationship between ARDS and prognosis was analyzed, including mechanical ventilation days, length of ICU stay, length of hospital stay, infection, sepsis, multiple organ dysfunction syndrome (MODS) and death., Results: There were 507 trauma patients, out of which 287 (56.61%) cases were with ARDS. The duration of mechanical ventilation, ICU stay and hospital stay in the ARDS group was significantly longer than that in the non-ARDS group (5 days vs 3 days, 10 days vs 4 days, 30 days vs 27 days, respectively). In addition, ARDS was associated with an increased risk of nfection (p<0.05; OR=4.17; 95%CI=2.72-6.41), sepsis (p<0.05; OR=3.45; 95%CI=2.28-5.22), and MODS (p<0.05; OR=2.82; 95% CI=1.67-4.72), but had no significant association with mortality (p>0.05). Similar results were found in the subgroup analyses., Conclusion: In conclusion, the prognosis of the patients with post-traumatic ARDS was worse; however, ARDS had little effect on death.

Aberrant epigenetic regulation is critically involved in the pathogenesis of nasopharyngeal carcinoma (NPC), where abnormal histone methylation can be found in polycomb repressive complex-2 (PRC2) related cancer gene loci. This study investigated some novel combinational strategies against NPC in vitro using PRC2-targeting agents as a backbone. PRC2 subunit proteins were overexpressed in over 70% of NPC tumors and enhancer of zeste homolog-2 (EZH2) expression correlated with more advanced T-stage. Basal expression of EZH2 and embryonic ectoderm development (EED) was higher in Epstein-Bar virus (EBV) + NPC cells than EBV - cells. Treatment with an EED inhibitor (EED226) led to reduced levels of H3K27me3 with minimal inhibitory effect on NPC cell growth. The combination of an EZH2 inhibitor (EPZ-6438) and trichostatin-A (TSA) yielded the highest synergy score (12.64) in NPC cells in vitro than combinations using EED226 and agents like chemotherapy and azacitadine. Global gene expression analysis showed that EED226 predominantly affects the expression of major histocompatibility complex (MHC) class I genes and cell cycle-related genes in NPC cells. Furthermore, treatment with EED226 resulted in increased MHC-I proteins in vitro . Based on the prediction of an artificial neural network, a synergistic inhibitory effect on growth was found by combining EED226 with cyclin dependent kinase (CDK) 4/6 inhibitor (LEE011) in NPC cells. In summary, this study found that PRC2-targeting agents could exert synergistic effect on growth inhibition when combined with TSA or LEE011 in NPC cells. Since MHC-I genes alterations are found in a third of NPC tumors, the effect of EED226 on MHC-I genes expression on response to immunotherapy in NPC warrants further investigations., Competing Interests: None., (AJCR Copyright © 2020.)

Ethnopharmacological Relevance: Jiao Mei Gu (JMG), Cayratia albifolia C.L.Li, is a type of Dong plant widely growing in Dong autonomous counties, Hunan province, China. As a type of traditional herbal medicine, the root of JMG plant has been used to treat inflammatory-related diseases such as arthritis because of its prominent anti-inflammatory effects in Dong medicine., Aim of the Study: This work investigated the anti-inflammatory effects and mechanisms of the water extract from the root of JMG on lipopolysaccharide (LPS)-induced inflammatory models., Methods: Endotoxemia was induced in C57BL/6 mice by intraperitoneal injection of LPS (20 mg/kg), meanwhile intraperitoneal administration of safe doses of JMG. The survival curve of mice was determined. Serum inflammatory cytokines were detected by the Bio-Plex Mouse Cytokine 23-Plex Panel Kit and enzyme-linked immunosorbent assay (ELISA) at 6 h after drug treatment. Hematoxylin-eosin (HE) staining of important organs was completed at 24 h after treatment. The mechanism of inflammatory action was investigated in vitro on LPS-stimulated macrophages. Macrophage inflammation was then induced using 10 μg/mL LPS. The anti-inflammatory effect of JMG was investigated by the quantitative polymerase chain reaction (qPCR) and ELISA. The anti-inflammatory mechanism was determined using western blotting, the electrophoretic mobility shift assay, and immunocytochemistry. Finally, the antimicrobial activity of JMG was verified by survival experiments in vivo and by bacterial culture experiments in vitro., Results: A 200 mg/kg water extract of JMG was safe for mice and had a significant protective effect on LPS-induced sepsis. Organ damage of heart, liver, lung and kidney was also significantly reduced at 24 h in the JMG group, when compared with the LPS group. The serum MIP-1α (CCL-3), MIP-1β (CCL-4), IL-1β, and TNFα cytokines were significantly decreased at 6 h in the JMG group, when compared with the LPS group. In a similar manner, 0.2μg/ml JMG significantly reduced mRNA and protein levels of MIP-1α (CCL-3), MIP-1β (CCL-4), IL-1β, and TNFα in LPS-stimulated macrophage. JMG treatment inhibited the phosphorylation of NF-κB p65 and reduced nuclear transduction, thus reducing transcriptional activity. At the same time, we showed that JMG had no protective effect on Escherichia coli-induced sepsis, as well as no antimicrobial activity., Conclusions: Our results showed that a water-soluble extract of JMG inhibited LPS-induced inflammation via attenuating the NF-κB signaling pathway, which provides an important rationale for the treatment of inflammation-related diseases., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the impact of additional gastrectomy after endoscopic submucosal dissection(ESD) on the prognosis of early gastric cancer., Methods: Clinical data of 107 early gastric cancer patients undergoing additional gastrectomy after ESD (research group, n=44) or radical surgery (control group, n=63) from January 2008 to December 2014 in Zhongshan Hospital were retrospectively analyzed. The reasons for additional gastrectomy after ESD included positive resection margin (n=10), lymphovascular invasion (n=5), well-differentiated mucosal tumor with a diameter >3 cm (n=10), poor-differentiated mucosal tumor with a diameter >2 cm (n=4), submucosal tumor(sm1) with a diameter >3 cm (n=10), and submucosal tumor(sm2) (n=9). Operation time, length of stay, lymph node metastasis, tumor recurrence and disease-free survival rate were compared between two groups., Results: Baseline data of two groups were not significantly different (all P>0.05). After evaluation, absolute and relative indications were identified in 19 cases (43.2%) and 25 cases (56.8%) of research group, and in 28 cases (44.4%) and 35 cases(55.6%) of control group without significant difference (P=0.897). Lymph node metastasis occurred in 6 patients (4.5%) after surgery in research group and 6.3% in control group (P=0.690). Operation time was (218.5±74.3) minutes in research group and (219.8±81.8) minutes in control group (P=0.932). Length of stay was (10.0±12.3) days in research group and (10.8±9.9) days in control group (P=0.687). Follow-up time was (35.5±15.0) months in research group and (29.5±18.1) months in control group (P=0.072). Tumor recurrence rate was 4.5% in research group and 9.5% in control group (χ(2)=0.928, P=0.229). Mortality was 4.5% in research group and 7.9% in control group (χ(2)=0.487, P=0.485). Besides, no significant differences of operation mode (P=0.164), lymphatic clearance mode (P=0.330), number of harvested lymph node (P=0.467), morbidity of postoperative infection or fever (P=0.923) were found. Three-year tumor-free survival rate was 95.5% and 89.2% in research and control group respectively without significant differences (P=0.571)., Conclusion: Additional gastrectomy after endoscopic submucosal dissection has no negative influence on the prognosis of patients with early gastric cancer, whose efficacy is similar to simple radical gastrectomy.

Objective: To study the anti-inflammatory effects of idazoxan (IDA) on endotoxin lipopolysaccharide (LPS) challenged mice in vivo and activated macrophages in vitro, and explore its potential molecular mechanisms., Methods: To do the experiments in vivo,30 adult male C57BL/6 mice were randomly divided into control group, model group, and low,medium and high doses IDA groups (IDA-L,IDA-M, and IDA-H groups),n =6 in each group. The inflammatory model was reproduced by intraperitoneal injection of LPS 10 mg/kg, and the control group was injected with the same amount of normal saline. The IDA groups received LPS (10 mg/kg) and IDA 0.3,1.0 and 3.0 mg/kg, respectively. The blood samples of mice in each group were collected at 6 hours after the reproduction of the model .For the in vitro experiments, primary peritoneal macrophages were collected from 20 adult male C57BL/6 mouse cells and they were divided into control group, LPS group (10 mg/L) and LPS+IDA-L,IDA-M,IDA-H groups (10 mg/L LPS + 5,25,100 μmol/L IDA, respectively).Cell culture supernatants were collected at 24 hours after the reproduction of the model. Detection methods: enzyme linked immunosorbent assay (ELISA) was used to determine the levels of serum tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),monocyte chemotactic protein-1 (MCP-1) and nitric oxide (NO).Western Blot was used to determine the effect of IDA on the expression levels of nuclear factor-κB (NF-κB) in macrophages., Results: ① For the in vivo experiment, the serum levels of TNF-α and IL-6 were significantly elevated in the model group as compared with those in the control group [TNF-o (ng/L):403.96 ± 40.98 vs.17.50 ± 8.68;IL-6 (ng/L):61 400.31 ± 7 826.61 vs.2 436.30 ± 448.89;both P ＜ 0.01].IDA treatment could inhibit the elevation of inflammatory cytokines in a dose-dependent manner, with the most significant decrease in LPS+IDA-H group [TNF-α (ng/L):170.09 ± 28.53 vs.403.96 ± 40.98,IL-6 (ng/L):16 570.81 ± 1 083.65 vs.61 400.31± 7 826.61;both P ＜ 0.01].② For the in vitro experiment, the levels of TNF-α,IL-6,MCP-1,and NO secreted by LPS-stimulated macrophages were distinctly higher in the LPS group than those in the control group [TNF-α (ng/L):7 259.14 ± 320.70 vs.28.50±27.08,IL-6 (ng/L):14809.60±5852.73 vs.1 113.47±465.53,MCP-1 (ng/L):20847.37± 1 788.33 vs.447.37± 395.69,NO (μmol/L):1 900.00 ± 144.31 vs.603.03 ± 102.18;all P ＜ 0.01]. However, IDA intervention could lower the secretion of TNF-α,IL-6,MCP-1 and NO in a dose-dependent manner, with the most notable decrease in the LPS+IDA-H group [TNF-α (ng/L):784.40±281.90 vs.7259.14±320.70,IL-6 (ng/L):1 802.96± 1 534.18 vs.14 809.60± 5 852.73,MCP-1 (ng/L):2005.26± 1 534.28 vs.20847.37 ± 1 788.33,NO (μ mol/L):654.54± 150.21 vs.1 900.00 ± 144.31;all P ＜ 0.05].In addition, IDA at the concentration of 100 μmol/L could promote the translocation of NF-κBp65 in macrophages into the nucleus 15 minutes early and lead to increased NF-κBp65 expression (gray value:18.70 ± 2.29 vs.1.09 ± 0.36,P ＜ 0.05),hut significantly reduce the expression levels of NF-κBp50 in the nucleus at 45 minutes after treatment (gray value:1.99 ± 0.14 vs.2.94 ± 0.54,P ＜ 0.05)., Conclusions: IDA could significantly reduce inflammation of mice challenged with LPS and inhibit inflammatory cytokines and mediators secreted by macrophage in a dose-dependent manner. High concentration of IDA (100 μmol/L) exhibited the greatest anti-inflammatory effects. The anti-inflammatory effect of IDA may be worked through NF-κB signaling pathway.

Objective: To determine the feasibility and efficacy of endoscopic submucosal dissection(ESD) in treating early gastric cancer(EGC) and precancerous lesions in the remnant stomach of patients after gastrectomy., Methods: Clinical data of 36 patients with EGC and precancerous lesions in remnant stomach undergoing ESD in Endoscopy Center of Zhongshan Hospital from January 2008 to December 2013 were retrospectively analyzed. Operative, postoperative conditions and long-term follow-up of these patients were evaluated., Results: Both the success rate and the complete resection rate were 100%. The average maximum diameter of the tumor was 1.5(range 0.6-4.5) cm. During the ESD process, two bleeding cases were treated successfully by endoscopic hemostasis. The average operation time was 40(10-80) min. The delayed hemorrhage developed in 2 cases within 1-3 days after operation, and were also treated successfully by endoscopic hemostasis. There was no perforation or delayed perforation. No emergency surgery was required for the complication. Twelve cases were diagnosed as mild-moderate dysplasia, 7 cases as high grade intraepithelial neoplasia, 16 cases as hyperplastic polyps, and 1 case as signet ring cell carcinoma with T1 stage, who underwent operation for resecting gastric stump and lymph node dissection 7 days after ESD without subsequent follow-up. The curative resection rate was 92.7%(35/36). The median follow-up of the remaining 35 patients was 36(6-78) months without discomfort and recurrence under gastroscopy., Conclusion: ESD is safe and effective for EGC and precancerous lesions in the remnant stomach.