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Clinical islet transplantation has the potential to cure type 1 diabetes. Despite recent therapeutic success, it is still uncommon because transplanted islets are damaged by multiple challenges, including instant blood mediated inflammatory reaction (IBMIR), inflammatory cytokines, hypoxia/reperfusion injury, and immune rejection. The transplantation microenvironment plays a vital role especially in intraportal islet transplantation. The identification and targeting of pathways that function as "master regulators" during deleterious inflammatory events after transplantation, and the induction of immune tolerance, are necessary to improve the survival of transplanted islets. In this article, we attempt to provide an overview of the influence of microenvironment on the survival of transplanted islets, as well as possible therapeutic targets., 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 © 2022 Yan, Ye, Chen, He, Zhang, Mao and Li.)

Background: Gastric cancer (GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori ( H. pylori ) and Epstein-Barr virus (EBV), and genetic components., Aim: To investigate microbiomes and host genome instability by cost-effective, low-coverage whole-genome sequencing, as biomarkers for GC subtyping., Methods: Samples from 40 GC patients were collected from Taizhou Hospital, Zhejiang Province, affiliated with Wenzhou Medical University. DNA from the samples was subjected to low-coverage whole-genome sequencing with a median genome coverage of 1.86 × (range: 1.03 × to 3.17 ×) by Illumina × 10, followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector., Results: Of the 40 GC samples, 20 (50%) were found to be enriched with microbiomes. EBV DNA was detected in 5 GC patients (12.5%). H. pylori DNA was found in 15 (37.5%) patients. The other 20 (50%) patients were found to have relatively higher genomic instability. Copy number amplifications of the oncogenes, ERBB2 and KRAS, were found in 9 (22.5%) and 7 (17.5%) of the GC samples, respectively. EBV enrichment was found to be associated with tumors in the gastric cardia and fundus. H. pylori enrichment was found to be associated with tumors in the pylorus and antrum. Tumors with elevated genomic instability showed no localization and could be observed in any location. Additionally, H. pylori- enriched GC was found to be associated with the Borrmann type II/III and gastritis history. EBV-enriched GC was not associated with gastritis. No statistically significant correlation was observed between genomic instability and gastritis. Furthermore, these three different molecular subtypes showed distinct survival outcomes ( P = 0.019). EBV-positive tumors had the best prognosis, whereas patients with high genomic instability (CIN+) showed the worst survival. Patients with H. pylori infection showed intermediate prognosis compared with the other two subtypes., Conclusion: Thus, using low-coverage whole-genome sequencing, GC can be classified into three categories based on disease etiology; this classification may prove useful for GC diagnosis and precision medicine., Competing Interests: Conflict-of-interest statement: Author Qian ZL was employed by the company Suzhou Hongyuan Biotech Inc., and Zhang XG and Zhai LJ were employed by the company Catcher Bio Inc. 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., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

The PTEN/AKT/mTOR signaling pathway is frequently dysregulated in non-small cell lung cancer (NSCLC), but the mechanisms are not well-understood. The present study found that the ubiquitin ligase TRIM25 is highly expressed in NSCLC tissues and promotes NSCLC cell survival and tumor growth. Mechanistic studies revealed that TRIM25 binds to PTEN and mediates its K63-linked ubiquitination at K266. This modification prevents the plasma membrane translocation of PTEN and reduces its phosphatase activity therefore accumulating PI(3,4,5)P3. TRIM25 thus activates the AKT/mTOR signaling. Moreover, we found that the antibacterial nitroxoline can activate PTEN by reducing its K63-linked polyubiquitination and sensitizes NSCLC to cisplatin-induced apoptosis. This study thus identified a novel modulation on the PTEN signaling pathway by TRIM25 and provides a potential target for NSCLC treatment., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

N 6-Threonylcarbamoyladenosine (t6A) is a universal and pivotal tRNA modification. KEOPS in eukaryotes participates in its biogenesis, whose mutations are connected with Galloway-Mowat syndrome. However, the tRNA substrate selection mechanism by KEOPS and t6A modification function in mammalian cells remain unclear. Here, we confirmed that all ANN-decoding human cytoplasmic tRNAs harbor a t6A moiety. Using t6A modification systems from various eukaryotes, we proposed the possible coevolution of position 33 of initiator tRNAMet and modification enzymes. The role of the universal CCA end in t6A biogenesis varied among species. However, all KEOPSs critically depended on C32 and two base pairs in the D-stem. Knockdown of the catalytic subunit OSGEP in HEK293T cells had no effect on the steady-state abundance of cytoplasmic tRNAs but selectively inhibited tRNAIle aminoacylation. Combined with in vitro aminoacylation assays, we revealed that t6A functions as a tRNAIle isoacceptor-specific positive determinant for human cytoplasmic isoleucyl-tRNA synthetase (IARS1). t6A deficiency had divergent effects on decoding efficiency at ANN codons and promoted +1 frameshifting. Altogether, our results shed light on the tRNA recognition mechanism, revealing both commonality and diversity in substrate recognition by eukaryotic KEOPSs, and elucidated the critical role of t6A in tRNAIle aminoacylation and codon decoding in human cells., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Hepatic ischemia reperfusion injury (IRI), a fascinating topic that has drawn a lot of interest in the last few years, is a major complication caused by a variety of clinical situations, such as liver transplantation, severe trauma, vascular surgery, and hemorrhagic shock. The IRI process involves a series of complex events, including mitochondrial deenergization, metabolic acidosis, adenosine-5'-triphosphate depletion, Kupffer cell activation, calcium overload, oxidative stress, and the upregulation of pro-inflammatory cytokine signal transduction. A number of protective strategies have been reported to ameliorate IRI, including pharmacological therapy, ischemic pre-conditioning, ischemic post-conditioning, and machine reperfusion. However, most of these strategies are only at the stage of animal model research at present, and the potential mechanisms and exact therapeutic targets have yet to be clarified. IRI remains a main cause of postoperative liver dysfunction, often leading to postoperative morbidity or even mortality. Very recently, it was reported that the activation of peroxisome proliferator-activated receptor γ (PPARγ), a member of a superfamily of nuclear transcription factors activated by agonists, can attenuate IRI in the liver, and FAM3A has been confirmed to mediate the protective effect of PPARγ in hepatic IRI. In addition, non-coding RNAs, like LncRNAs and miRNAs, have also been reported to play a pivotal role in the liver IRI process. In this review, we presented an overview of the latest advances of treatment strategies and proposed potential mechanisms behind liver IRI. We also highlighted the role of several important molecules (PPARγ, FAM3A, and non-coding RNAs) in protecting against hepatic IRI. Only after achieving a comprehensive understanding of potential mechanisms and targets behind IRI can we effectively ameliorate IRI in the liver and achieve better therapeutic effects., 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 © 2022 Mao, Cai, Chen, Wang, Jiang, Ye and Li.)

Introduction: Currently, there still are no selection criteria for endoscopic resection (ER) versus laparoscopic resection (LR) of gastric gastrointestinal stromal tumours (GIST) (2 to 4 cm) originating from the muscularis propria layer (MP-GISTs)., Aim: To investigate and compare the long-term prognosis of ER and LR for resecting gastric MP-GISTs, with at least 5 years of follow-up., Material and Methods: Between January 2010 and December 2015, 134 patients with gastric MP-GISTs were consecutively enrolled in this study. The main comparison measurements included the short-term and long-term outcomes between the ER group ( n = 89) and the LR group ( n = 45)., Results: In this study, there were no significant differences in the rates of complete resection ( p = 0.220) and short-term complications ( p = 0.663) between the ER group and the LR group. The ER group had a shorter operation time (50.1 ±18.2 min vs. 120.6 ±32.5 min, p < 0.001), shorter hospital stays (5.1 ±1.9 days vs. 6.4 ±3.7 days, p = 0.026), and lower hospitalization costs (16639.5 ±5091.3 CNY vs. 24030.4 ±6803.1 CNY, p < 0.001) than the LR group. The ER group had a lower rate of long-term complications than the LR group ( p = 0.001) during the follow-up period (84.2 ±17.9 months vs. 89.0 ±16.8 months, p = 0.207)., Conclusions: Our results showed that ER was a more feasible treatment approach than LR when the gastric MP-GIST was located in or near the cardia/pylorus. ER also had several other advantages over LR, such as a shorter procedure time, shorter hospital stay, and lower hospitalization costs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

In tRNA, the epigenetic m 3 C modification at position 32 in the anticodon loop is highly conserved in eukaryotes, which maintains the folding and basepairing functions of the anticodon. However, the responsible enzymes METTL2 and METTL6 were identified only in recent years. The loss of human METTL6 (hMETTL6) affects the translational process and proteostasis in cells, while in mESCs cells, it leads to defective pluripotency potential. Despite its important functions, the catalytic mechanism of the C32 methylation by this enzyme is poorly understood. Here we present the 1.9 Å high-resolution crystal structure of hMETTL6 bound by SAH. The key residues interacting with the ligand were identified and their roles were confirmed by ITC. We generated a docking model for the hMETTL6-SAH-CMP ternary complex. Interestingly, the CMP molecule binds into a cavity in a positive patch with the base ring pointing to the inside, suggesting a flipped-base mechanism for methylation. We further generated a model for the quaternary complex with tRNA Ser as a component, which reasonably explained the biochemical behaviors of hMETTL6. Taken together, our crystallographic and biochemical studies provide important insight into the molecular recognition mechanism by METTL6 and may aid in the METTL-based rational drug design in the future., (© 2021. The Author(s).)

Liver disease is a severe health problem that endangers human health worldwide. Mesenchymal stem cell (MSC) therapy is a novel treatment for patients with different liver diseases due to its vast expansion potential and distinctive immunomodulatory properties. Despite several preclinical trials having confirmed the considerable efficacy of MSC therapy in liver diseases, the questionable safety and efficacy still limit its application. As a precursor cell, MSCs can adjust their characteristics in response to the surrounding microenvironment. The microenvironment provides physical and chemical factors essential for stem cell survival, proliferation, and differentiation. However, the mechanisms are still not completely understood. We, therefore, summarized the mechanisms underlying the MSC immune response, especially the interaction between MSCs and the liver microenvironment, discussing how to achieve better therapeutic effects., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Shan-jing Xu et al.)

Background: Diffuse large B-cell lymphoma (DLBCL) is a common aggressive B-cell non-Hodgkin lymphoma (B-NHL). While combined chemotherapy has improved the outcomes of DLBCL, it remains a highly detrimental disease. Pyroptosis, an inflammatory programmed cell death, is considered to have both tumor-promoting and tumor-suppressing effects. The role of pyroptosis in DLBCL has been gradually appreciated, but its value needs further investigation. Methods: We analyzed mutations and copy number variation (CNV) alterations of pyroptosis-related genes (PRGs) from The Cancer Genome Atlas (TCGA) cohort and evaluated the differences in expression in normal B cells and DLBCL patients in two Gene Expression Omnibus (GEO) datasets (GSE12195 and GSE56315). Based on the expression of 52 PRGs, we divided 421 DLBCL patients from the GSE31312 dataset into distinct clusters using consensus clustering. The Kaplan-Meier method was used to prognosis among the three clusters, and GSVA was used to explore differences in the biological functions. ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) were used to analyze the tumor immune microenvironment (TME) in different clusters. A risk score signature was developed using a univariate survival analysis and multivariate regression analysis, and the reliability and validity of the signature were verified. By combining the signature with clinical factors, a nomogram was established to predict the prognosis of DLBCL patients. The alluvial diagram and correlation matrix were used to explore the relationship between pyroptosis risk score, clinical features and TME. Results: A large proportion of PRGs are dysregulated in DLBCL and associated with the prognosis. We found three distinct pyroptosis-related clusters (cluster A, B, and C) that differed significantly with regard to the prognosis, biological process, clinical characteristics, chemotherapeutic drug sensitivity, and TME. Furthermore, we developed a risk score signature that effectively differentiates high and low-risk patients. The nomogram combining this signature with several clinical indicators showed an excellent ability to predict the prognosis of DCBCL patients. Conclusions: This work demonstrates that pyroptosis plays an important role in the diversity and complexity of the TME in DLBCL. The risk signature of pyroptosis is a promising predictive tool. A correct and comprehensive assessment of the mode of action of pyroptosis in individuals will help guide more effective treatment., 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 © 2021 Wang, Xu, Teng, Zhu, Guo, Wang, Mao, Li and Luo.)

Backgroud and Study Aims: Esophageal stricture is a serious adverse event occurring after circular endoscopic submucosal dissection (ESD) involving the whole esophagus. However, there is still a lack of effectively preventive methods. The main purpose of this study is to evaluate the efficacy of application of acellularized dermis matrix (ADM) for the prevention of post-ESD esophageal stricture. The main objective of this study was to evaluate the use of decellularized dermal matrix (ADM) in the prevention of post-esophageal ESD strictures., Patients and Methods: A pilot, single-center, prospective study was conducted. The study enrolled seven patients who had high-risks with extended resection of developing post-ESD esophageal stricture. After undergoing ESD, we attached different size of ADM patches to the mucosal defects using titanium clips then fixed with a metal mesh stent. The stent covered with metal mesh was removed at the median time of 27 days after the endoscopic procedure. Follow-up and repeated outpatient endoscopic screening were performed at appropriate scheduled times., Results: The average longitudinal diameter of the resected specimens was 58.3 mm (range 38-90 mm). There were three patients developing strictures postoperatively at a mean time of 87 days (range 42-140). The median number of postoperative endoscopic balloon dilatation (EBD) in patients with stenosis was 2 (range 2-9). There were no deaths during a median follow-up period of 6 moths (range 1-12)., Conclusions: This study was performed to assess the efficacy and safe method of relieving the severity of esophageal stricture after ESD through transplantation of ADM., Competing Interests: The authors declare that they have no conflict interests., (© 2021 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Background: Endoscopic resection of duodenal subepithelial lesions (SELs) is a difficult procedure with a high risk of perforation. At present, dealing with perforation after endoscopic resection of duodenal SELs is still considered a great challenge., Aim: To evaluate the effectiveness and safety of an over-the-scope clip (OTSC) in the treatment of perforation post-endoscopic resection of duodenal SELs., Methods: From May 2015 to November 2019, 18 patients with perforation following endoscopic resection of duodenal SELs were treated with OTSCs. Data comprising the rate of complete resection, closure of intraprocedural perforation, delayed bleeding, delayed perforation, and postoperative infection were extracted., Results: The rate of complete removal of duodenal SELs and successful closure of the perforation was 100%. The median perforation size was 1 cm in diameter. Seventeen patients had minor intraoperative bleeding, while the remaining 1 patient had considerable amount of bleeding during the procedure. Seven patients had postoperative abdominal infections, of which 1 patient developed an abscess in the right iliac fossa and another patient developed septic shock. All 18 patients recovered and were discharged. No delayed bleeding or perforation was reported. The mean time taken to resume normal diet after the procedure was 6.5 d. The mean postoperative hospital stay was 9.5 d. No residual or recurrent lesions were detected during the follow-up period (15-66 mo)., Conclusion: Closing a perforation after endoscopic resection of duodenal SELs with OTSCs seems to be an effective and reasonably safe therapeutic method., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Although liver transplantation is considered to be the best choice for patients with end-stage liver diseases, postoperative immune rejection still cannot be overlooked. Patients with liver transplantation have to take immunosuppressive drugs for a long time or even their entire lives, in which heavy economic burden and side effects caused by the drugs have become the major impediment for liver transplantation. There is a growing body of evidences indicating that mesenchymal stem cell (MSC) transplantation, a promising tool in regenerative medicine, can be used as an effective way to induce immune tolerance after liver transplantation based on their huge expansion potential and unique immunomodulatory properties. MSCs have been reported to inhibit innate immunity and adaptive immunity to induce a tolerogenic microenvironment. In in vitro studies, transplanted MSCs show plasticity in immune regulation by altering their viability, migration, differentiation, and secretion in the interactions with the surrounding host microenvironment. In this review, we aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and ultimately to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. Only after exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Shao-wei Li et al.)

tRNAs harbor the most diverse posttranscriptional modifications. The 3-methylcytidine (m3C) is widely distributed at position C32 (m3C32) of eukaryotic tRNAThr and tRNASer species. m3C32 is decorated by the single methyltransferase Trm140 in budding yeasts; however, two (Trm140 and Trm141 in fission yeasts) or three enzymes (METTL2A, METTL2B and METTL6 in mammals) are involved in its biogenesis. The rationale for the existence of multiple m3C32 methyltransferases and their substrate discrimination mechanism is hitherto unknown. Here, we revealed that both METTL2A and METTL2B are expressed in vivo. We purified human METTL2A, METTL2B, and METTL6 to high homogeneity. We successfully reconstituted m3C32 modification activity for tRNAThr by METT2A and for tRNASer(GCU) by METTL6, assisted by seryl-tRNA synthetase (SerRS) in vitro. Compared with METTL2A, METTL2B exhibited dramatically lower activity in vitro. Both G35 and t6A at position 37 (t6A37) are necessary but insufficient prerequisites for tRNAThr m3C32 formation, while the anticodon loop and the long variable arm, but not t6A37, are key determinants for tRNASer(GCU) m3C32 biogenesis, likely being recognized synergistically by METTL6 and SerRS, respectively. Finally, we proposed a mutually exclusive substrate selection model to ensure correct discrimination among multiple tRNAs by multiple m3C32 methyltransferases., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Recent studies show that the expression of CCND1, a key factor in cell cycle control, is increased following the progress and deteriotation of glioma and predicts poor outcomes. On the other hand, dysregulated deubiquitinase USP10 also predicts poor prognosis for patients with glioblastoma (GBM). In the present study, we investigated the interplay between CCND1 protein and USP10 in GBM cells. We showed that the expression of CCND1 was significantly higher in both GBM tissues and GBM-derived stem cells. USP10 interacted with CCND1 and prevented its K48- but not K63-linked polyubiquitination in GBM U251 and HS683 cells, which led to increased CCND1 stability. Consistent with the action of USP10 on CCND1, knockdown of USP10 by single-guided RNA downregulated CCND1 and caused GBM cell cycle arrest at the G1 phase and induced GBM cell apoptosis. To implement this finding in the treatment of GBMs, we screened a natural product library and found that acevaltrate (AVT), an active component derived from the herbal plant Valeriana jatamansi Jones was strikingly potent to induce GBM cell apoptosis, which was confirmed by the Annexin V staining and activation of the apoptotic signals. Furthermore, we revealed that AVT concentration-dependently suppressed USP10-mediated deubiquitination on CCND1 therefore inducing CCND1 protein degradation. Collectively, the present study demonstrates that the USP10/CCND1 axis could be a promising therapeutic target for patients with GBMs., (© 2020. CPS and SIMM.)

With the rapid development of science and technology, artificial intelligence (AI) systems are becoming ubiquitous, and their utility in gastroenteroscopy is beginning to be recognized. Digestive endoscopy is a conventional and reliable method of examining and diagnosing digestive tract diseases. However, with the increase in the number and types of endoscopy, problems such as a lack of skilled endoscopists and difference in the professional skill of doctors with different degrees of experience have become increasingly apparent. Most studies thus far have focused on using computers to detect and diagnose lesions, but improving the quality of endoscopic examination process itself is the basis for improving the detection rate and correctly diagnosing diseases. In the present study, we mainly reviewed the role of AI in monitoring systems, mainly through the endoscopic examination time, reducing the blind spot rate, improving the success rate for detecting high-risk lesions, evaluating intestinal preparation, increasing the detection rate of polyps, automatically collecting maps and writing reports. AI can even perform quality control evaluations for endoscopists, improve the detection rate of endoscopic lesions and reduce the burden on endoscopists., 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 © 2021 Song, Mao, Zhou, He, Chen, Zhang, Xu, Yan, Tang, Ye and Li.)

In the early December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, China, followed by an outbreak that spread around the world. Numerous studies have shown that liver injury is common in patients with coronavirus disease 2019 (COVID-19), and may aggravate the severity of the disease. However, the exact cause and specific mechanism of COVID-associated liver injury needs to be elucidated further. In this review, we present an analysis of the clinical features, potential mechanisms, and treatment strategies for liver injury associated with COVID-19. We hope that this review would benefit clinicians in devising better strategies for management of such patients., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest related to this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Liver fibrosis refers to the process underlying the development of chronic liver diseases, wherein liver cells are repeatedly destroyed and regenerated, which leads to an excessive deposition and abnormal distribution of the extracellular matrix such as collagen, glycoprotein and proteoglycan in the liver. Liver fibrosis thus constitutes the pathological repair response of the liver to chronic injury. Hepatic fibrosis is a key step in the progression of chronic liver disease to cirrhosis and an important factor affecting the prognosis of chronic liver disease. Further development of liver fibrosis may lead to structural disorders of the liver, nodular regeneration of hepatocytes and the formation of cirrhosis. Hepatic fibrosis is histologically reversible if treated aggressively during this period, but when fibrosis progresses to the stage of cirrhosis, reversal is very difficult, resulting in a poor prognosis. There are many causes of liver fibrosis, including liver injury caused by drugs, viral hepatitis, alcoholic liver, fatty liver and autoimmune disease. The mechanism underlying hepatic fibrosis differs among etiologies. The establishment of an appropriate animal model of liver fibrosis is not only an important basis for the in-depth study of the pathogenesis of liver fibrosis but also an important means for clinical experts to select drugs for the prevention and treatment of liver fibrosis. The present study focused on the modeling methods and fibrosis characteristics of different animal models of liver fibrosis, such as a chemical-induced liver fibrosis model, autoimmune liver fibrosis model, cholestatic liver fibrosis model, alcoholic liver fibrosis model and non-alcoholic liver fibrosis model. In addition, we also summarize the research and application prospects concerning new organoids in liver fibrosis models proposed in recent years. A suitable animal model of liver fibrosis and organoid fibrosis model that closely resemble the physiological state of the human body will provide bases for the in-depth study of the pathogenesis of liver fibrosis and the development of therapeutic drugs., 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 © 2021 Bao, Wang, Pan, Zhang, Chen, Xu, Mao and Li.)

Background: Multiple myeloma (MM) is a malignant hematopoietic disease that is usually incurable. RNA-binding proteins (RBPs) are involved in the development of many tumors, but their prognostic significance has not been systematically described in MM. Here, we developed a prognostic signature based on eight RBP-related genes to distinguish MM cohorts with different prognoses., Method: After screening the differentially expressed RBPs, univariate Cox regression was performed to evaluate the prognostic relevance of each gene using The Cancer Genome Atlas (TCGA)-Multiple Myeloma Research Foundation (MMRF) dataset. Lasso and stepwise Cox regressions were used to establish a risk prediction model through the training set, and they were validated in three Gene Expression Omnibus (GEO) datasets. We developed a signature based on eight RBP-related genes, which could classify MM patients into high- and low-score groups. The predictive ability was evaluated using bioinformatics methods. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and gene set enrichment analyses were performed to identify potentially significant biological processes (BPs) in MM., Result: The prognostic signature performed well in the TCGA-MMRF dataset. The signature includes eight hub genes: HNRNPC , RPLP2 , SNRPB , EXOSC8 , RARS2 , MRPS31 , ZC3H6 , and DROSHA . Kaplan-Meier survival curves showed that the prognosis of the risk status showed significant differences. A nomogram was constructed with age; B2M , LDH , and ALB levels; and risk status as prognostic parameters. Receiver operating characteristic (ROC) curve, C-index, calibration analysis, and decision curve analysis (DCA) showed that the risk module and nomogram performed well in 1, 3, 5, and 7-year overall survival (OS). Functional analysis suggested that the spliceosome pathway may be a major pathway by which RBPs are involved in myeloma development. Moreover, our signature can improve on the R-International Staging System (ISS)/ISS scoring system (especially for stage II), which may have guiding significance for the future., Conclusion: We constructed and verified the 8-RBP signature, which can effectively predict the prognosis of myeloma patients, and suggested that RBPs are promising biomarkers for MM., 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 © 2021 Wang, Xu, Zhu, Guo, Zhu, Mao, Chen, Li and Luo.)

Abstract: The aim of this study was to evaluate the ability of the red blood cell distribution width (RDW) to predict prognosis and treatment response in chronic myeloid leukemia (CML)-chronic phase (CP) patients treated with tyrosine kinase inhibitor (TKIs).We retrospectively enrolled 93 newly diagnosed CML-CP patients treated with TKIs from 2009 to 2018 at the First Hospital of Lanzhou University. Patients were divided into 2 groups using an RDW of 18.65% determined by receiver operating characteristic curve analysis. We analyzed the correlation of treatment responses and the RDW compared to common scoring systems, as well as the correlation of the RDW with disease outcome, including overall survival (OS) and progression-free survival (PFS), and demographic and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used.The median age of patients was 40 years, and 51 patients (54.8%) were men. A high RDW could predict treatment response at 3 months (P = .03) and 6 months (P = .02). The RDW was significantly lower in patients who achieved molecular response by 3 months (P < .001) and complete cytogenetic response by 6 months (P = .001) than in those who did not respond. Patients with a high RDW (>18.65%, n = 35) had significantly worse 5-year OS (77.1% vs 96.6%; P = .008) and PFS (80.0% vs 98.3%; P = .002) than those with a low RDW (≤18.65%, n = 58). Multivariate analysis demonstrated that a high RDW was an adverse predictor of OS (P = .005, HR (hazard ratio) = 9.741) and PFS (P = .009, HR = 16.735).The RDW is a readily available prognostic marker of outcome in patients with CML-CP and can predict treatment response to TKIs. Further larger and prospective studies are required., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Although endoscopic resection (ER) is already established as a minimally invasive technique for small (< 4.0 cm) upper gastrointestinal subepithelial tumors originating from the muscularis propria layer (MP-SETs), published data of ER for large (≥ 4.0 cm) upper gastrointestinal MP-SETs are extremely rare and limited to case reports. This retrospective study aimed to evaluate the feasibility and safety of ER for large (≥ 4.0 cm) upper gastrointestinal MP-SETs in a large case series., Methods: Between June 2012 and December 2018, 101 patients with large (≥ 4 cm) upper gastrointestinal MP-SETs were enrolled in this study. The main outcome measures included complete resection, total complications, and local residual or recurrent tumor., Results: The rate of complete resection was 86.1%. Thirteen patients (12.9%) experienced complications including gas-related complications (6/101, 5.9%), localized peritonitis (4/101, 4.0%), esophageal/cardiac mucosal laceration (2/101, 2.0%), and delayed bleeding (1/101, 1.0%). These 13 patients recovered after endoscopic and conservative treatment. The independent risk factor for incomplete resection was tumor size (P = 0.005), and the independent risk factors for total complications were tumor size (P = 0.011) and tumor extraluminal growth (P = 0.037). During the median follow-up of 36 months, local residual tumor was detected in 1 patient. No local recurrence occurred in any patient., Conclusions: Despite being associated with a relatively low complete resection rate, ER is an alternative therapeutic method for large (≥ 4.0 cm) upper gastrointestinal MP-SETs when performed by an experienced endoscopist. This method is especially valuable for patients who are unwilling to undergo surgery.

Backgrounds: Colorectal cancer (CRC) with high incidence, has the third highest mortality of tumors. DNA damage and repair influence a variety of tumors. However, the role of these genes in colon cancer prognosis has been less systematically investigated. Here, we aim to establish a corresponding prognostic signature providing new therapeutic opportunities for CRC. Method: After related genes were collected from GSEA, univariate Cox regression was performed to evaluate each gene's prognostic relevance through the TCGA-COAD dataset. Stepwise COX regression was used to establish a risk prediction model through the training sets randomly separated from the TCGA cohort and validated in the remaining testing sets and two GEO datasets (GSE17538 and GSE38832). A 12-DNA-damage-and-repair-related gene-based signature able to classify COAD patients into high and low-risk groups was developed. The predictive ability of the risk model or nomogram were evaluated by different bioinformatics- methods. Gene functional enrichment analysis was performed to analyze the co-expressed genes of the risk-based genes. Result: A 12-gene based prognostic signature established within 160 significant survival-related genes from DNA damage and repair related gene sets performed well with an AUC of ROC 0.80 for 5 years in the TCGA-CODA dataset. The signature includes CCNB3, ISY1, CDC25C, SMC1B, MC1R, LSP1P4, RIN2, TPM1, ELL3, POLG, CD36, and NEK4. Kaplan-Meier survival curves showed that the prognosis of the risk status owns more significant differences than T, M, N, and stage prognostic parameters. A nomogram was constructed by LASSO regression analysis with T, M, N, age, and risk as prognostic parameters. ROC curve, C-index, Calibration analysis, and Decision Curve Analysis showed the risk module and nomogram performed best in years 1, 3, and 5. KEGG, GO, and GSEA enrichment analyses suggest the risk involved in a variety of important biological processes and well-known cancer-related pathways. These differences may be the key factors affecting the final prognosis. Conclusion: The established gene signature for CRC prognosis provides a new molecular tool for clinical evaluation of prognosis, individualized diagnosis, and treatment. Therapies based on targeted DNA damage and repair mechanisms may formulate more sensitive and potential chemotherapy regimens, thereby expanding treatment options and potentially improving the clinical outcome of CRC patients., 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 © 2021 Wang, Xu, Wang, Piao, Mao, Zhou, Wang, Wu, Ye and Li.)

Endoscopic submucosal dissection (ESD) has been widely accepted as an effective treatment for early esophageal cancer. However, post-ESD esophageal stricture remains a thorny issue. We herein review many strategies for preventing post-ESD esophageal stricture, as well as discuss their strengths and weaknesses. These strategies include pharmacological prophylaxis, esophageal stent and tissue engineering and regenerative medicine treatment. In this review, we summarize these studies and discuss the underlying progress and future directions of tissue engineering and regenerative medicine treatment., Competing Interests: The authors declare no conflict of interest., (© 2021 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Development and the dynamics of stable aggregates in many soils are known to be closely related to the cycling as well as accumulation of soil organic carbon (SOC). This study explored the aggregation processes and distributions of soil organic carbon in soils developed from limestone (L), quaternary red earth (Q), granite (G), basalt (B), and tertiary red sandstone (T) subtropical China related to the addition of maize residues during 7 days and 184 days of incubation. The soils were sieved to<0.25 mm before incubation. We aimed to clarify the mechanisms underlying SOC mineralization across soils from the perspective of soil aggregate protection. Fractionation of the water stable aggregates showed that addition of maize straw promoted the formation of>2 mm and 2-1 mm aggregates, while only 1.0-0.5, 0.5-0.25 and <0.25 mm aggregates were detected in the absence maize straw. The proportion of macroaggregates as well as their stability was always higher in L, Q, and B developed soils than those in G and T developed soils. In amended soils, the accumulation of total SOC was much obvious in L, Q, and B developed soils than those in G and T developed soils, and these increases were mainly contributed by the >0.25 mm macroaggregate-associated SOC. This result indicated that>0.25 mm macroaggregates were important spots for SOC sequestration. Furthermore, the proportions of>0.25 mm macroaggregate-associated SOC were also significantly ( P <0.05) higher in L, Q, and B developed soils than those in G and T developed soils, and the free light organic carbon (fLOC) followed an inverse parent material pattern as>0.25 mm macroaggregate-associated SOC. Results also demonstrated that ratios of accumulative mineralized CO 2 -C to total soil organic carbon in L, Q, and B soils were significantly ( P <0.05) lower than those in G and T soils. The correlation analysis further suggested that ratios of cumulative respired CO 2 -C to total soil organic carbon were significantly and positively correlated ( P <0.01) with the proportion of fLOC, but inversely correlated ( P <0.01) with the proportion of>0.25 mm macroaggregate-associated SOC. By applying 13 C-NMR to characterize the inherent chemical composition of soil organic carbon fractions, we noted that fLOC was more deeply decomposed than intra-aggregate light organic carbon (intra-aggregate LOC), and both the fractions were advanced decomposed in G and T developed soils, verifying enhanced protection of added maize residues inside soil aggregates. The findings of the research suggested that the parent material exerts a significant influence on SOC mineralization by controlling the formation of aggregates and location of SOC in the hierarchical structure of the soil aggregate system. We demonstrated that enhanced physical protection of SOC by forming more stable macroaggregates contributes to carbon accumulation in limestone, quaternary red earth, and basalt developed soils treated with organic amendments.

RNF6, a RING-type ubiquitin ligase, has been identified as an oncogene in various cancers but its role in multiple myeloma (MM) remains elusive. In the present study we first showed that the expression levels of RNF6 in MM were significantly elevated compared with the bone marrow cells of healthy donors. Overexpression of RNF6 in LP1 and PRMI-8266 MM cell lines promoted cell proliferation, whereas knockdown of RNF6 led to apoptosis of MM cells. Furthermore, we revealed that RNF6, as a ubiquitin ligase, interacted with glucocorticoid receptor (GR) and induced its K63-linked polyubiquitination. Different from current knowledge, RNF6 increased GR stability at both endogenous and exogenous contexts. Such an action greatly promoted GR transcriptional activity, which was confirmed by luciferase assays and by the increased expression levels of prosurvival genes including Bcl-xL and Mcl-1, two typical downstream genes of the GR pathway. Consistent with these findings, ectopic expression of RNF6 in MM cells conferred resistance to dexamethasone, a typical anti-myeloma agent. In conclusion, we demonstrate that RNF6 promotes MM cell proliferation and survival by inducing atypical polyubiquitination to GR, and RNF6 could be a promising therapeutic target for the treatment of MM.

c-Maf is a critical oncogenic transcription factor that contributes to myelomagenesis. Our previous studies demonstrated that the deubiquitinase USP5 stabilizes c-Maf and promotes myeloma cell proliferation and survival; therefore, the USP5/c-Maf axis could be a potential target for myeloma therapy. As a concept of principle, the present study established a USP5/c-Maf-based luciferase system that was used to screen an FDA-approved drug library. It was found that mebendazole, a typical anthelmintic drug, preferentially induced apoptosis in c-Maf-expressing myeloma cells. Moreover, oral administration of mebendazole delayed the growth of human myeloma xenografts in nude mice but did not show overt toxicity. Further studies showed that the selective antimyeloma activity of mebendazole was associated with the inhibition of the USP5/c-Maf axis. Mebendazole downregulated USP5 expression and disrupted the interaction between USP5 and c-Maf, thus leading to increased levels of c-Maf ubiquitination and subsequent c-Maf degradation. Mebendazole inhibited c-Maf transcriptional activity, as confirmed by both luciferase assays and expression measurements of c-Maf downstream genes. In summary, this study identified mebendazole as a USP5/c-Maf inhibitor that could be developed as a novel antimyeloma agent.

Dendritic cells (DCs) are key components of the immune system, serving as antigen-presenting cells to activate adaptive immunity. Whereas mature DCs promote immune responses, immature DCs induce or maintain immunological tolerance by downregulating T-cell responses. Therefore, DCs are potent antigen (Ag)-presenting cells in the immune system. MicroRNAs are noncoding RNAs that posttranscriptionally regulate mRNA by binding the 3'-untranslated region (UTR) of these molecules, modulating their expression. Many recent studies have suggested a potential role of miRNAs in DCs maturation and differentiation, but the exact mechanisms governing this process are unclear. How and whether miR-199a-3p affects DC maturation has not been investigated. Here, we found that MiR-199a-3p levels are correlated with DC maturation, inflammatory cytokine secretion, and PI3K/AKT/NF-κB signaling pathway activity. In addition, we analyzed the stimulation of regulatory T-cells by DCs. Through this work, we determined CD86 to be targeted by miR-199a-3p, thereby linking it to DC maturation. miR-199a-3p therefore directly inhibits CD86 expression via 3'-UTR targeting, subsequently prolonging allograft survival in a mouse heart transplantation model. miR-199a-3p over-expression may therefore be a potential therapeutic strategy for use in organ transplantation or patients with autoimmune diseases., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

There has been an increasing number of studies about microRNAs as key regulators in the development of hepatic fibrosis. Here, we demonstrate that miR-542-3p can promote hepatic fibrosis by downregulating the expression of bone morphogenetic protein 7 (BMP-7), which is known to antagonize transforming growth factor β1 (TGFβ1)-mediated fibrogenesis effect. The expression of miR-542-3p is increased in activated hepatic stellate cells (HSCs). Downregulation of MiR-542-3p by antisense inhibitors can inhibit HSCs activation markers, including α-smooth muscle actin (α-SMA) and collagen as well as TGFβ signaling pathways. MiR-542-3p was significantly upregulated in carbon tetrachloride (CCl 4 )-induced hepatic fibrosis in mice, and downregulation of miR-542-3p by lentivirus could prevent the development of hepatic fibrosis. In addition, miR-542-3p can directly bind to the 3'-untranslated region of BMP-7 mRNA, indicating that its profibrotic effect appears to be caused by its inhibition of BMP-7. Our results suggest that downregulation of miR-542-3p prevents liver fibrosis both in vitro and in vivo, highlighting its potential as a novel biomarker or therapeutic target for hepatic fibrosis., (© 2018 Wiley Periodicals, Inc.)

Objective: To investigate the mechanism of Paris forrestii (Takht.) H. Li (PCT3)-suppressing the proliferation of HL-60, K562, KG-1 and HT-93 cells., Methods: cute myeloid leukemia cell lines such as HL-60, K562, KG-1 and HT-93 were treated with Paris forrestii (Takht.) H. Li (PCT3) for 24, 48, and 72 h, and MTT assay was employed to determine the cells proliferation. Meanwhile, the apoptosis of K562, HL-60, KG-1 and HT-93 cells were detected by flow cytometry after PCT3 (Control, 4 μg/ml, 8 μg/ml) treated for 24 h and the Western blot was performed to detect the expression of PARP,Caspase-3, MCL-1, BAX, BCL-2, P53, and P27. GAPDH was used as an internal loading control., Results: MTT assay showed that Paris forrestii (Takht.) H. Li (PCT3) significantly inhibited the proliferation of HL-60, K562, KG-1 and HT-93 cells in concentration and time-dependent manners. Compared with the control group, the leukemia cell viabilities were significantly suppressed (r =0.9436; r =0.8623; r =0.9922; r =0.8918). Paris forrestii (Takht.) H. Li (PCT3) induced apoptosis of leukemia cells in a concentration dependent manner, compared with the control group (P＜0.05 or P＜0.01). Western blot revealed that PARP, a major enzyme in DNA damage repair, and Caspase-3 another one of the major executive apoptotic enzymes were cleaved in cell lines examined, and this cleavage was concentration dependent. Anti-apoptotic proteins such as MCL-1 and BCL-2 were down regulated by Paris forrestii (Takht.) H. Li (PCT3), and Pro-apoptotic protein BAX was upregulated. And the protein of tumor suppressor gene P53 and its downstream signaling protein P27 increased., Conclusion: Paris forrestii (Takht.) H. Li (PCT3) can inhibit the proliferation of leukemia cells by activating endogenous apoptosis pathway, and provide a potential new drug selection for clinical treatment of AML leukemia.

Objective: To investigate the serum calcium level in 86 patients with newly diagnosed multiple myeloma (MM) and its correlation with clinical features., Methods: The clinical data of 86 patients with newly diagnosed multiple myeloma in our hospital from 2009 to 2016 were retrospectively analyed. Clinical data of sex, age, hemoglobin, albumin, globulin, creatinine, uric acid, serum phosphorus, β2-microglobulin, immunophenotyping and disease staging were collected. After the serum calcium level was corrected, the patients were grouped into low serum calcium (<2.20 mmol/L), normal serum calcium (2.20-2.60 mmol/L) and high serum calcium (>2.60 mmol/L). The correlation between the clinical characteristics and the serum calcium level was analysed, the clinical characteristics between the low and non-low calcium group were compared., Results: The number of cases in low, normal and high serum cnlcium groups before correction was 58 (67.4%), 18 (20.9%) and 10 (11.6%) respactively, while the number of cases in 3 group after correction was 34 (39.5%), 36 (41.9%) and 16 (18.6%) respectively. The age, globulin, creatinine, uric acid and serum phosphorus levels were positively correlated with serum calcium level in patients with multiple myeloma, while the sex, hemoglobin,albumin and β2-microglobulin levels did not correlated with serum calcium level. There was significant difference in the age, globulin, creatinine and serum phosphorus between low calcium and non-low calcium group (P<0.05). However the differences of sex, hemoglobin, albumin, uric acid, β2-microglobulin, immunophenotyping and clinical stage were not statistically significant (P>0.05)., Conclusion: Multiple myeloma patients suffered from both hypercalcemia and hypocalcemia, and the incidence of hypocalcemia is not low. The levels of serum calcium in patients with multiple myeloma correlate with age, globulin, creatinine, uric acid, serum phosphorus level and other factors, thus it is necessary to correct the level of ionized calcium with physiological activity.

Interferon-α (IFN-α) inhibits tumor growth and mimics graft-versus-leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the current case-control study, we compared treatment responses in acute leukemia patients with relapse tendency post-allo-HSCT receiving preemptive IFN-α after withdrawal of immunosuppressants (n = 31) vs. receiving no IFN-α (n = 67). In the IFN-α group, 25 patients responded to the treatment without progressing to hematological relapse. In the non-IFN-α group, only 22 patients responded to the treatment. The response rate differed significantly (80.6 vs. 32.8%, P < 0.001). The 2-year cumulative incidence of relapse was 31.6 and 61.2% in the IFN-α and the non-IFN groups, respectively (P = 0.006). The 2-year leukemia-free survival and overall survival rate was 57.4 vs. 28.4% (P < 0.001) and 67.6 vs. 32.9% (P = 0.001), respectively. Among the 31 patients in the IFN-α group, 18 patients (58.1%) developed graft-versus-host disease (GVHD): 6 acute and 12 limited chronic GVHD. Patients who developed GVHD had higher treatment response rate than patients without GVHD (88.9 vs. 53.8%, P = 0.022). In conclusion, preemptive IFN-α therapy is a safe and effective treatment to prevent disease progression in high-risk patients with relapse tendency post-allo-HSCT.

Objective: The purpose of this study was to demonstrate the feasibility of endoscopic retrograde appendicitis therapy (ERAT) in treating patients with acute appendicitis., Materials and Methods: Between January 2014 and December 2014, 22 patients with acute appendicitis underwent ERAT. Patient demographics, colonoscopy findings, endoscopic retrograde appendiceal radiography (ERAR) findings, and treatment outcomes of the ERAT and adverse events associated with ERAT were analyzed., Results: In this study, 22 patients with acute appendicitis underwent ERAT. The median age of the patients was 39.5 years. Colonoscopy findings included mucosal hyperemia and swelling of the appendiceal orifice and/or its surrounding mucosa (86.4 %, 19/22) and pus at the appendiceal orifice (40.9 %, 9/22). ERAR findings included irregular contour (76.2 %, 16/21), appendiceal lumen dilation (28.6 %, 6/21), appendiceal lumen stenosis (42.9 %, 9/21), and filling defect of the appendiceal lumen (23.8 %, 5/21). Deep intubation was successfully performed in 21 of the 22 patients (95.5 %). Sixteen patients underwent endoscopic appendiceal stent placement after endoscopic appendiceal irrigation (EAI) due to lumen stenosis of the appendiceal, excessive pus, or appendiceal fecalith, and the remaining 6 patients only underwent EAI. Among the 22 patients who underwent ERAT, their abdominal pain was noticeably relieved following the procedure. The main adverse events associated with ERAT were spontaneous discharge of the stent, recurrent abdominal pain, and recurrent appendicitis. During the follow-up (median 33 months), 2 patients underwent laparoscopic appendectomy., Conclusions: ERAT provide a new alternative therapeutic method for patients with acute appendicitis, particularly for certain patients who are unwilling to undergo an appendectomy., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim: To evaluate the long-term efficacy of endoscopic resection (ER) for small (≤ 4.0 cm) gastric gastrointestinal stromal tumors (GISTs) originating from the muscularis propria layer., Methods: Between June 2005 and February 2015, we retrospectively analyzed 229 consecutive patients with gastric MP-GISTs who underwent ER with a follow-up at least 36 mo. The main outcome measurements included complete resection rate, complications, and long-term follow-up outcomes., Results: ER included endoscopic muscularis excavation in 179 cases, endoscopic full-thickness resection in 32 cases, and submucosal tunneling endoscopic resection in 18 cases. The median size of GISTs was 1.90 cm. Of the 229 GISTs, 147 were very low risk, 72 were low risk, 8 were intermediate risk, and 2 were high risk. Short-term outcomes showed the complete resection rate was 96.5%, and 8 patients (3.5%) had complications. Of the 8 patients with complications, only one patient required surgical intervention. Long-term outcomes showed 225 patients were actively followed-up until composition of this manuscript. The remaining 4 patients were lost because of unrelated death. During the follow-up period (median, 57 mo), no residual, recurrent lesions, or distant metastasis were detected in any patients. Binary logistic regression analysis showed tumor size was a risk factor associated with a high mitotic index (≥ 5/50 HPF) of GISTs ( P = 0.002)., Conclusion: ER seems to be an effective and safe method for gastric MP-GISTs ≤ 4.0 cm, and, for some intermediate or high risk GISTs, adjuvant therapy and/or additional surgery might be required to reduce the risk of recurrence or metastasis., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report.

Abnormal phosphorylation of tau, one of the most common symptoms of dementia, has become increasingly important in the study of the etiology and development of Alzheimer's disease. Paeoniflorin, the main bioactive component of herbaceous peony, is a monoterpene glycoside, which has been reported to exert beneficial effects on neurodegenerative disease. However, the effect of paeoniflorin on tauopathies remains ambiguous. SH-SY5Y cells were treated with okadaic acid (OA) for 8 h to induce tau phosphorylation and no cell death was observed. Optical microscopy results showed that paeoniflorin ameliorated okadaic acid induced morphological changes, including cell swelling and synapsis shortening. Western blotting data illustrated that paeoniflorin reversed okadaic acid induced tau hyperphosphorylation, which was enhanced by inhibiting the activities of calpain, Akt and GSK-3β. Transmission electron microscopy results showed that paeoniflorin alone can reduce the number of autophagosomes and stabilize the microtubule structure. In addition, calpastain and paeoniflorin enhance the effect of paeoniflorin on stabilizing microtubules. In addition, calpastain markedly enhanced the effect of paeoniflorin on reversing okadaic acid-lowered fluorescence intensity of both MAP-2 and β III-tubulin, two microtubule-associated proteins. This study shows that paeoniflorin protected SH-SY5Y cells against okadaic acid assault by interfering with the calpain/Akt/GSK-3β-related pathways, in which autophagy might be involved. Besides, paeoniflorin is found to relieve the stress response of the microtubule structure system caused by okadaic acid treatment. The results presented in this study suggest that paeoniflorin potentially plays an important role in tauopathies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Fragility fracture is one of the common complications of osteoporosis. Elevated oxidative stress-induced apoptosis is thought to be one of the unfavorable factors to osteoblastic dysfunction, which increased the risk of bone fracture. However, the molecular mechanisms for oxidative stress-induced osteoblast cells apoptosis still need to be elucidated. This study aims to investigate the protective function of miR-214 in H2O2-induced apoptosis of MC3T3-E1 osteoblasts., Materials and Methods: MC3T3-E1 cells were treated with 400 μM H2O2. Flow cytometry was adopted to detect the apoptosis rate; malondialdehyde (MDA) and glutathione peroxidase (Gpx) levels were used to determine the reactive oxygen species (ROS) level. Reverse transcription-polymerase chain reaction (RT-PCR) was employed to test the expression level of miR-214 and ATF4. After transfected MC3T3-E1 cells with miR-214 mimics and inhibitor, RT-PCR was used to detect activating transcription factor 4 (ATF4) expression level., Results: H2O2 treatment increased ROS induced intracellular oxidative injury. Flow cytometry showed that 400 μM H2O2 induced the apoptosis of MC3T3-E1 cells. Moreover, RT-PCR showed decreased expression level of MiR-214. Furthermore, the apoptosis induced by high ROS level was reversed by increased miR-214 expression level. The regulatory ability of MiR-214 to apoptosis is by regulating ATF4 expression., Conclusions: miR-214 plays a protective role in H2O2 induced MC3T3 osteoblasts apoptosis and its protective effect is proceeded by regulating ROS level and ATF4 expression level.

The signal transducer and activator of transcription 3 (STAT3) plays a critical role in platelet functions. This study sought to understand the effects of the STAT3 inhibitor SC99 on platelet activation and aggregation. Immunoblotting assays were applied to measure the effects of SC99 on the STAT3 signaling pathway. A ChronoLog aggregometer was used to evaluate platelet aggregation. A flow cytometer was used to evaluate P-selectin expression in the presence of SC99. AlamarBlue and Annexin-V staining were used to evaluate platelet viability and apoptosis, respectively. A fluorescence microscope was applied to analyze platelet spreading. SC99 inhibited the phosphorylation of JAK2 and STAT3 in human platelets but had no effects on the phosphorylation of AKT, p65 or Src, all of which are involved in platelet activation. Further studies revealed that SC99 inhibited human platelet aggregation induced by collagen and thrombin in a dose-dependent manner. SC99 inhibited thrombin-induced P-selectin expression and fibrinogen binding to single platelets. Moreover, SC99 inhibited platelet spreading on fibrinogen and clot retraction mediated by outside-in signaling. SC99 inhibited platelet aggregation in mice but it did not significantly prolong the bleeding time. Taken together, the present study revealed that SC99 inhibited platelet activation and aggregation as a STAT3 inhibitor. This agent can be developed as a promising treatment for thrombotic disorders.

Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study is to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia., (Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Endoscopic removal of a duodenal lesion is still considered to be a challenging procedure that can be fraught with potentially serious complications, specifically perforation or delayed bleeding. This study was to assess the safety of endoscopic resection for duodenal subepithelial lesions (SELs) with wound closure using clips and an endoloop., Methods: From October 2010 to July 2015, a total of 68 consecutive patients with duodenal SELs were treated with endoscopic resection with wound closure using clips and an endoloop. The main outcome measures considered were the incidence of complete resection, perioperative perforation, delayed perforation, delayed bleeding, residual lesions, and lesion recurrence., Results: Complete resection was successfully achieved for all 68 patients. The median lesion size was 1.7 cm. The median procedure time was 62 min. The mean hospital stay was 5.5 days. During the procedure, five patients developed perioperative perforations (7.4 %) and no patients developed delayed bleeding, delayed perforation, or other serious complications. The five patients with perioperative perforations recovered after conservative treatment. The perioperative perforation rate was significantly higher for lesions originating in the muscularis propria layer (18.2 %) than in the submucosal layer (2.2 %; p < 0.05). No residual or recurrent lesions were detected during the follow-up period (median: 27 months)., Conclusions: Endoscopic resection with wound closure using clips and an endoloop is an effective and reasonably safe therapeutic method for treating/removing duodenal SELs when managed by an experienced endoscopic team, and it can provide an alternative treatment option for patients with duodenal SELs.

Background: Genetic variations in the genes of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of ischemic stroke (IS). Here we investigate the association between MMP-1 -1607 1G/2G and MMP-3 -1171 5A/6A genetic polymorphisms and etiological subtypes of IS in the Han Chinese population., Methods: A total of 640 eligible patients with IS and 637 age- and gender-matched apparently healthy volunteers were enrolled. Subtypes of IS were classified by Trial of Org 10172 in Acute Stroke Treatment criteria. MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism., Results: The frequencies of the 5A/6A + 5A/5A genotypes and 5A allele were significantly higher in patients with IS than in controls (P <.001, P <.001, respectively). No association was found between MMP-1 1G/2G polymorphism and overall IS. In subgroup analyses, MMP-1 1G/2G and 2G/2G genotypes increased the risk of small-artery occlusion (SAO) subtype (multivariate-adjusted, P <.001, P = .002, respectively), and MMP-3 5A/6A + 5A/5A genotypes were related with large-artery atherosclerosis (LAA) subtype (multivariate-adjusted, P <.001). Haplotype analyses indicated that 2G-6A and 1G-5A increased the risk of SAO (multivariate-adjusted, P = .029) and LAA (multivariate-adjusted, P <.001), respectively., Conclusions: MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms may contribute to different subtypes of IS susceptibility., (Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The apoptosis of mono-hepatocellular induced by the active ingredients of the Zanthoxyli Radix was investigated using laser Raman spectroscopy. Hepatoma cells (BEL-7404) were treated with 10 mg•L⁻¹ nitidine chloride and 3 g•L⁻¹ the extracts of Zanthoxyli Radix, respectively, then were divided into two parts, one for fluorescence staining, the other for determination of Raman spectroscopy. The acquired spectra were then processed by background elimination, smoothing, and normalization. Fluorescence staining results showed that the nucleuses from untreated group were uniformly stained, while those from the group treated for 48 hours were densely stained and broken. The spectra results revealed that the intensity of peaks associated with nucleic acid and protein decreased after the cells were incubated with the extracts of Zanthoxyli Radix for 12, 24, 36 and 48 hours. The intensity of peaks at 785,1 002,1 175,1 660 cm⁻¹ was decreased with the time of the cells were incubated by the extracts of Zanthoxyli Radix. The results indicated that the extracts of Zanthoxyli Radix could induce the apoptosis of hepatoma cells and reduce the amount of nucleic acid and protein in the cells. There is a certain relevance between the drug treatment time and the efficacy. The above results suggest that Raman spectra can provide abundant information about the changes in biological macromolecules within the cells after incubated by the extracts of Zanthoxyli Radix and serve as an effective method for the real time measurement of apoptosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

The human leukocyte antigen class II (HLA II) molecules are implicated in the immunopathogenesis of allergic rhinitis (AR). The HLA II contains three allelic isotypes HLA-DR, -DQ, and -QP that exhibit considerably different susceptibility to AR. Here, we investigated the structural basis and energetic landscape of the susceptibility difference between the three HLA II isotypes to AR by combining computational analysis and experimental assay. Multiple sequence alignment revealed a low conservation among the three subtypes with sequence identity of ∼10% between them, suggesting that the peptide repertoires presented by HLA-DR, -DP and -DQ are not overlapped to each other, and they may be involved in different immune functions and dysfunctions. Structural analysis imparted that the antigenic peptides are rooted on the peptide-binding groove of HLA molecules and hold in a PPII-like helical conformation. Subsequently, the interaction behavior of 17 AR allergen-derived peptides with HLA-DR, -DP and -DQ was investigated using a statistics-based quantitative structure-activity relationship (QSAR) predictor. It was found a significant difference between the binding capabilities of these antigenic peptides to HLA-DR and to HLA-DP/-DQ; the former showed a generally higher affinity than the latter with p-value of 0.02 obtained from 2-tailed Student's t-test. The computational findings were then confirmed by HLA II-peptide stability assay, which demonstrated that the AR allergen-derived peptides have a high in vitro selectivity for HLA-DR over HLA-DP/-DQ. Thus, the HLA-DR isotype, rather than HLA-DP and -DQ, is expected to associate with the pathological process of AR., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Little is known about the impact of the 5A/6A polymorphism of matrix metalloproteinase-3 (MMP-3) on recurrence of atherosclerotic ischemic stroke in Chinese. The aim of this study was to investigate the association of MMP-3 serum level and 5A/6A genetic polymorphism with the recurrence of atherosclerotic ischemic stroke in the Chinese Han population. We analyzed 106 large artery atherosclerosis (LAA) recurrent ischemic stroke patients and 545 LAA first onset ischemic stroke patients from January 2009 to June 2014. Serum MMP-3 concentrations were measured with an enzyme-linked immunosorbent assay. The genotypes of MMP-3 promoter polymorphism (-1171 5A/6A) were determined using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of MMP-3 5A/6A+5A/5A (32.08% vs. 21.47%, p = 0.02) genotype and 5A (16.98% vs. 11.01%, p = 0.01) allele in the recurrent group was significantly higher than those in the first onset group. After adjustment for vascular risk factors, multivariate logistic regression analysis suggested that the MMP-3 5A/6A+5A/5A genotype was an independent risk factor for LAA recurrent ischemic stroke (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.09-2.79, p = 0.021). No significant difference was observed for the MMP-3 serum concentrations between the recurrent group and the first onset group (22.23 ± 8.31 vs. 21.49 ± 7.89 ng/ul, t = 0.88, p = 0.38). The MMP-3 (-1171 5A/6A) polymorphism may contribute to LAA recurrent ischemic stroke susceptibility. Analysis of 5A/6A polymorphism in MMP-3 may identify patients at higher risk for LAA ischemic stroke recurrence, who may be selected for intensive preventive therapy.

Polo-like kinase 1 (PLK1) is an important regulator in diverse aspects of the cell cycle and proliferation. The protein has a highly conserved polo-box domain (PBD) present in C-terminal noncatalytic region, which exhibits a relatively broad sequence specificity in recognizing and binding phosphorylated substrates to control substrate phosphorylation by the kinase. In order to elucidate the structural basis, thermodynamic property, and biological implication underlying PBD-substrate recognition and association, a systematic amino acid preference profile of phosphopeptide interaction with PLK1 PBD domain was established via virtual mutagenesis analysis and mutation energy calculation, from which the contribution of different amino acids at each residue position of two reference phosphopeptides to domain-peptide binding was characterized comprehensively and quantitatively. With the profile, we are able to determine the favorable, neutral, and unfavorable amino acid types for each position of PBD-binding phosphopeptides, and we also explored the molecular origin of the broad sequence specificity in PBD-substrate recognition. To practice computational findings, the profile was further employed to guide rational design of potent PBD binders; three 6-mer phosphopeptides (i.e., IQSpSPC, LQSpTPF, and LNSpTPT) were successfully developed, which can efficiently target PBD domain with high affinity (Kd = 5.7 ± 1.1, 0.75 ± 0.18, and 7.2 ± 2.6 μm, resp.) as measured by a fluorescence anisotropy assay. The complex structure of PLK1 PBD domain with a newly designed, potent phosphopeptide LQSpTPF as well as diverse noncovalent chemical forces, such as H-bonds and hydrophobic interactions at the complex interface, were examined in detail to reveal the molecular mechanism of high affinity and stability of the complex system., (© 2016 Wiley-VHCA AG, Zürich.)

Objectives: Although endoscopic resection is an accepted technique for upper gastrointestinal subepithelial tumors (SETs) originating from the muscularis propria (MP) layer, published data regarding its complications are highly variable and limited to small data series. This study aimed to analyze the safety of endoscopic resection in a large case series., Methods: A total of 726 consecutive patients with 733 upper gastrointestinal SETs originating from the MP layer underwent endoscopic resection from June 2005 to December 2014. The complete resection rate, perioperative perforation rate, and perioperative bleeding rate were the main outcome measurements., Results: The complete resection rate was 97.1%. Ninety-four patients had complications (12.9%), including 88 with perioperative perforations (12.1%), 13 with perioperative bleeding (1.8%), 5 with localized peritonitis (0.7%), and one with delayed bleeding (0.1%). Eleven patients required surgery; the others were treated endoscopically. Risk factors for incomplete resection were extensive connection of the tumor to the MP layer (P=0.007) and extraluminal growth (P=0.048). Risk factors for perioperative perforation were larger tumor size (≤2.0 cm vs. 2.1-3.0 cm vs. >3.0 cm, P=0.021), extraluminal growth (P=0.046), and extensive connection (P<0.001). A risk factor for perioperative bleeding was larger tumor size (P=0.045). No residual or recurrent lesions were detected during the follow-up period (median: 28 months)., Conclusions: Endoscopic resection is an effective and reasonably safe therapeutic method for treating/removing upper gastrointestinal SETs originating from the MP layer when managed by an experienced endoscopic team.

Background and Aims: At present, removing a circumferential superficial esophageal lesion (SEL) via en bloc resection is still a great challenge. Based on the previous success of submucosal tunneling endoscopic resection, this study aimed to evaluate the safety and effectiveness of complete circular endoscopic resection (CER) using a submucosal tunnel technique combined with esophageal stent placement for patients with circumferential SELs., Methods: From August 2012 to June 2014, 23 patients with circumferential SELs were treated by CER using a submucosal tunnel technique combined with esophageal stent placement. The following steps were performed: (1) circular mucosa incisions were made at the anal and oral side of the lesion after marking the margin, (2) two submucosal tunnels were created from the oral to anal side using a hybrid knife, which was followed by submucosal dissection, and (3) following the completion of CER, a retrievable esophageal stent was placed to prevent postoperative stricture., Results: CER using the submucosal tunnel technique combined with esophageal stent placement was successfully performed for all 23 cases. The complete resection and success rate were 100%, while the mean longitudinal diameter of the lesions was 65 mm. Mediastinal emphysema, pneumothorax, and postoperative stenosis were detected in 8.7% (2/23), 4.3% (1/23), and 17.4% (4/23) of the cases, respectively. Pathological diagnoses of the lesions included carcinomas (13/23) and high-grade intraepithelial neoplasias (10/23). No residual or recurrent tumors were detected in any patient during the follow-up period., Conclusions: CER using the submucosal tunnel technique combined with esophageal stent placement seems to be a safe and effective procedure for treating patients with SELs that result in a higher en bloc resection rate with fewer or minor complications.

In order to investigate the resistance development law and biochemical resistance mechanism of Laodelphax striatellus to buprofezin, spraying rice seedlings was used to continuously screen resistant strains of L. striatellus and dipping rice seedlings was applied to determine the toxicity and cross-resistance of L. striatellus to insecticides. After 32-generation screening with buprofezin, L. striatellus developed 168.49 folds resistance and its reality heritability (h2) was 0.11. If the killing rate was 80%-90%, L. striatellus was expected to develop 10-fold resistance to buprofezin only after 5 to 6 generations breeding. Because the actual reality heritability of field populations was usually lower than that of the resistant strains, the production of field populations increasing with 10-fold resistance would need much longer time. The results of cross-resistance showed that resistant strain had high level cross-resistance with thiamethoxam and imidacloprid, low level cross-resistance with acetamiprid, and no cross-resistance with pymetrozine and chlorpyrifos. The activity of detoxification enzymes of different strains and the syergism of synergist were measured. The results showed that cytochrome P450 monooxygenase played a major role in the resistance of L. striatellus to buprofezin, the esterase played a minor role and the GSH-S-transferase had no effect. Therefore, L. striatellus would have high risk to develop resistance to buprofezin when used in the field and might be delayed by using pymetrozine and chlorpyrifos.

Minimally invasive endoscopic resection has become an increasingly popular method for patients with small (less than 3.5 cm in diameter) gastric subepithelial tumors (SETs) originating from the muscularis propria (MP) layer. Currently, the main endoscopic therapies for patients with such tumors are endoscopic muscularis excavation, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection. Although these endoscopic techniques can be used for complete resection of the tumor and provide an accurate pathological diagnosis, these techniques have been associated with several negative events, such as incomplete resection, perforation, and bleeding. This review provides detailed information on the technical details, likely treatment outcomes, and complications associated with each endoscopic method for treating/removing small gastric SETs that originate from the MP layer.

The aim of the present study was to investigate the expression of microRNA-218 (miRNA-218) in the serum and cervical tissue and its association with the clinicopathological features of cervical cancer (CC). The expression of miRNA-218 was detected in the serum and cervical tissue of 112 patients with CC and 50 age-matched hysteromyoma patients via the reverse transcription-quantitative polymerase chain reaction. The clinical data were collected and the association between the expression of miRNA-218 and the clinicopathological characteristics of the patients was analyzed. The expression of miRNA-218 in the cancer group was significantly decreased in the cervical tissue and serum compared with that in the control group (P<0.001). The decreased expression of miRNA-218 was associated with a later International Federation of Gynecology and Obstetrics stage, a more invasive pathological type and lymphatic node metastasis but not with age, age at menarche, menopausal status, number of pregnancies and deliveries, family history of cancer or tumor size. In conclusion, miRNA-218 was found to be downregulated in the cancer tissue and serum of the patients with CC. The decreased expression of miRNA-218 in CC was associated with the invasiveness of the tumor.

Effects of chemical fertilizers and organic manure on the soil organic carbon (SOC) content in particle size fractions of paddy soil were investigated in a 17-year long-term fertilization field experiment in Zhejiang Province, China. The inherent chemical composition of silt- and clay-associated SOC was evaluated with solid-state 13C-NMR spectroscopy. Compared to CK (no fertilizer treatment), NPKRS (NPK fertilizers plus rice straw) , NPKOM (NPK fertilizers plus organic manure) , NPK (NPK fertilizers) and OM (organic manure alone) treatments significantly (P <0. 05) increased the SOC content of sand- (2-0.02 mm), silt- (0.02-0.002 mm) and clay-sized (< 0.002 mm) fractions. However, no significant difference was observed in the accumulation of silt- and clay-associated SOC between CK and rice straw (RS) treatments. Besides, in comparison with plots applied with NPK fertilizers alone, combined application of organic amendments and NPK fertilizers facilitated the storage of newly sequestered SOC in silt- and clay-sized fractions, which could be more conducive to the stability of SOC. Based on 13C-NMR spectra, both silt and clay fractions were composed of Alkyl-C, O-alkyl-C, Aromatic-C and carbonyl-C. Changes in the relative proportion of different C species were observed between silt and clay fractions: the clay fraction had relatively more Alkyl-C, carbonyl-C and less O-alkyl-C, Aromatic-C than those in the silt fraction. This might be ascribed to the fact that the organic matter complexed with clay was dominated by microbial products, whereas the silt appeared to be rich in aromatic residues derived from plants. The spectra also showed that the relative proportion of different C species was modified by fertilization practices. In comparison with organic amendments alone, the relative proportion of Alkyl-C was decreased by 9.1%-11.9% and 13.7%-19.9% under combined application of organic amendments and chemical fertilizers, for silt and clay, respectively, and that of O-alkyl-C was increased by 2.9%-6.3% and 13.4%-22.1%, respectively. These results indicated that NPKOM and NPKRS treatments reduced the decomposition rate of SOC. The aromaticity, hydrophobicity and, hence, chemical recalcitrance of silt- and clay-associated SOC in the NPK fertilizer treatments were lower than those of the organically amended plots and unfertilized treatments, indicating decreased recalcitrance of SOC against decomposition. We concluded that long-term application of organic manure combined with chemical fertilizers, either through increased accumulation of both recalcitrant compounds and carbohydrates or reduced decomposition of organic matter, was a sustainable strategy for facilitating carbon accumulation of the paddy soil investigated in this study.

Background/aims: This study was designed to evaluate the safety and efficacy of endoscopic excavation for esophageal subepithelial tumors originating from the muscularis propria., Methodology: Forty-five patients with esophageal subepithelial tumors originating from the muscularis propria were treated with endoscopic excavation between January 2010 and June 2012. The key steps were: (1) making several dots around the tumor; (2) incising the mucosa along with the marker dots, and then seperating the tumor from the muscularis propria by using a hook knife or an insulated-tip knife; (3) closing the artificial ulcer with clips after the tumor was removed., Results: The mean tumor diameter was 1.1 ± 0.6 cm. Endoscopic excavation was successfully performed in 43 out of 45 cases (95.6%), the other 2 cases were ligated with nylon rope. During the procedure perforation occurred in 4 (8.9%) patients, who recovered after conservative treatment. No massive bleeding or delayed bleeding occurred. Histologic diagnosis was obtained from 43 (95.6%) patients. Pathological diagnoses of these tumors were leiomyomas (38/43) and gastrointestinal stromal tumors (5/43)., Conclusions: Endoscopic excavation is a safe and effective method for the treatment of small esophageal subepithelial tumors originating from the muscularis propria.

Background: Because of the difficulty associated with making an accurate diagnosis of gastric heterotopic pancreas (HP) before surgery, surgical resection is usually performed in suspected cases. However, this is an invasive procedure and prone to certain surgical complications., Aims: This study was designed to evaluate the feasibility of endoscopic excavation for gastric HP, as well as the value of endoscopic ultrasonography (EUS) in diagnosing gastric HP., Methods: Between January 2007 and January 2013, 42 consecutive patients with gastric HP were enrolled in this retrospective study. Key steps: (1) Injection of a solution (100 ml saline + 2 ml indigo carmine + 1 ml epinephrine) into the submucosal layer after making several dots around the lesion; (2) Incision of the mucosa outside the marker dots with a needle-knife, and then circumferential excavation until complete resection of the lesion; (3) Closure of the artificial ulcer with several clips after tumor removal., Results: In this study, 18 cases (42.9%) were suspected as gastric HP (assessed by two experienced endoscopists before endoscopic excavation), 8 (19.0%) were suspected as gastrointestinal stromal tumors, 7 (16.7%) as gastric polyp, and the remaining 9 cases (21.4%) were still unknown. The mean procedure duration was 28.6 min. En bloc resection by endoscopic excavation was achieved in 40 cases (95.2%), and no massive bleeding, delayed bleeding, perforation, or other severe complication occurred in these patients. Among the 42 lesions, a tube echo could be detected in 11 cases by EUS. Those 11 cases were diagnosed as gastric HP by histopathology., Conclusions: Endoscopic excavation appears to be a safe and feasible procedure for accurate histopathologic evaluation and curative treatment in gastric HP. Use of EUS has some value in the diagnosis of gastric HP before the procedure