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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.

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.

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.

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.

Background and Objectives: Although the pathogenesis and treatment of coronavirus disease 2019 (COVID-19) have been gradually revealed, the risk for re-emergence of coronavirus nucleic acids in recovered patients remains poorly understood. Hence, this study evaluated the risk predictors associated with re-positivity for virus nucleic acid.Methods: Between February 1 and March 20, 2020, we retrospectively reviewed the clinical epidemiological data of 129 COVID-19 patients who were treated at Zhongxiang People's Hospital of Hubei Province in China. Subsequently, a risk prediction model for the re-positivity of virus nucleic acid was developed, and a receiver operating characteristic (ROC) curve was drawn for further validation.Results: In this study, the rate of re-positivity for virus nucleic acid was 17.8% (23/129) where all re-positivity cases were asymptomatic. The median time interval from discharge to nucleic acid re-positivity to discharge after being cured again was 11.5 days (range: 7–23 days). Multivariate logistic regression analysis showed that leukocytopenia [odds ratio (OR) 7.316, 95% confidence interval (CI) 2.319–23.080, p = 0.001], prealbumin < 150 mg/L (OR 4.199, 95% CI 1.461–12.071, p = 0.008), and hyperpyrexia (body temperature >39°C, OR 4.643, 95% CI 1.426–15.117, p = 0.011) were independent risk factors associated with re-positivity. The area under the ROC curve was 0.815 (95% CI, 0.729–0.902).Conclusion: COVID-19 patients with leukocytopenia, low prealbumin level, and hyperpyrexia are more likely to test positive for virus nucleic acid after discharge. Timely and effective treatment and appropriate extension of hospital stays and quarantine periods may be feasible strategies for managing such patients.

BackgroundMultiple 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.MethodAfter 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.ResultThe 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.ConclusionWe 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.

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.

Hydrogen sulfide (H2S), a common air pollutant and toxic gas, is detrimental to organisms and the environment. Exposure to highly concentrated H2S can induce oxidative stress and autophagy. However, the mechanism underlying the liver damage caused by H2S has not been identified. Lipopolysaccharide (LPS), the key component of endotoxin, can induce oxidative stress and autophagy. For this experiment, we used one-day-old chickens as model organisms to evaluate the effects of H2S combined with LPS on oxidative stress and autophagy. The four groups (control group, LPS group, H2S group and H2S-LPS group) were observed by electron microscopy, detected by oxidative stress kit, analyzed by quantitative real-time quantitative PCR, and analyzed by Western blot. We found that the activities of antioxidant enzymes (superoxide dismutase, antioxidant glutathione, catalase, and glutathione peroxidase) decreased in the H2S group compared to those in the control group; however, malondialdehyde levels in the H2S group increased. Molecular-level studies showed that the expression of genes associated with the PI3K/ AKT/ TOR pathways in the H2S group decreased, whereas the expression of other autophagy-related genes (Beclin1, ATG5 and the ratio of LC3-II/ LC3-I) increased compared to that in the control group. These findings suggest that H2S caused oxidative stress and induced autophagy through the PI3K/ AKT/ TOR pathway in chicken liver cells. Additionally, exposure to H2S aggravated LPS-induced oxidative stress and autophagy injury. Capsule: Aerial exposure to H2S can cause oxidative stress in chicken livers and induce autophagy through the PI3K/AKT/TOR pathway, and can aggravate LPS-induced oxidative stress and autophagy.

Cadmium (Cd) is a heavy metal that poses a hazard to animal health due to its toxicity. Selenium (Se) is an important nutritional trace element. However, the potential protective effects of Se against Cd-induced toxicity remain to be elucidated. To investigate the cytotoxicity of Cd on bird immunocytes in vitro and the protective effects of Se against exposure to Cd, chicken splenic lymphocytes received Cd (10−6 mol/L), Se (10−7 mol/L), and the mixture of 10−7 mol/L Se and 10−6 mol/L Cd and were incubated for 12 h, 24 h, 36 h, 48 h, respectively. The transcription of heat shock protein (HSP) 27, HSP40, HSP60, HSP70 and HSP90 mRNA was tested by fluorescence quantitative PCR. The results showed that the mRNA expression of HSPs exposed to 10−6 mol/L Cd showed a sustained decrease at 12–48 h exposure. A statistically significant increase in the mRNA expression of HSPs in the case of Se group was observed, as compared to the control group of chicken splenic lymphocytes. Concomitantly, treatment of chicken splenic lymphocytes with Se in combination with Cd enhanced the mRNA expression of HSPs which were reduced by Cd treatment. This indicated that the protective effect of Se against the toxicity of Cd might, at least partially, be attributed to stimulation of the level of HSPs.

O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) is critical for the biosynthesis and transformation of selenocysteine (Sec) and plays an important role in the biological function of Se through the regulation of selenoprotein synthesis. Selenium (Se) and Selenoprotein play a pivotal role in brain function. However, how intake of the micronutrient Se affects gene expression and how genetic factors influence Se metabolism in the brain is unknown. To investigate the regulation of SepSecS transcription induced by Se in the chicken brain, we determined the Se content of brain tissue, SepSecS gene expression levels and mRNA stability in the chicken brain and primary cultured chicken embryos neurons receiving Se supplements. These results showed that Se content in the brain remains remarkably stable during Se supplementation. A significant increase in SepSecS mRNA levels was observed in all of the brain tissues of chickens fed diets containing 1-5 mg/kg sodium selenite. Most strikingly, significant changes in SepSecS mRNA levels were not observed in neurons treated with Se. However, Se altered the SepSecS mRNA half-life in cells. These data suggest that Se could regulate SepSecS mRNA stability in the avian brain and that SepSecS plays an important role in Se homeostasis regulation.

BackgroundStem cell transplantation is a promising potential therapy for muscular dystrophies, but for this purpose, the cells need to be systemically-deliverable, give rise to many muscle fibres and functionally reconstitute the satellite cell niche in the majority of the patient's skeletal muscles. Human skeletal muscle-derived pericytes have been shown to form muscle fibres after intra-arterial transplantation in dystrophin-deficient host mice. Our aim was to replicate and extend these promising findings.Methodology/principal findingsIsolation and maintenance of human muscle derived cells (mdcs) was performed as published for human pericytes. Mdscs were characterized by immunostaining, flow cytometry and RT-PCR; also, their ability to differentiate into myotubes in vitro and into muscle fibres in vivo was assayed. Despite minor differences between human mdcs and pericytes, mdscs contributed to muscle regeneration after intra-muscular injection in mdx nu/nu mice, the CD56+ sub-population being especially myogenic. However, in contrast to human pericytes delivered intra-arterially in mdx SCID hosts, mdscs did not contribute to muscle regeneration after systemic delivery in mdx nu/nu hosts.Conclusions/significanceOur data complement and extend previous findings on human skeletal muscle-derived stem cells, and clearly indicate that further work is necessary to prepare pure cell populations from skeletal muscle that maintain their phenotype in culture and make a robust contribution to skeletal muscle regeneration after systemic delivery in dystrophic mouse models. Small differences in protocols, animal models or outcome measurements may be the reason for differences between our findings and previous data, but nonetheless underline the need for more detailed studies on muscle-derived stem cells and independent replication of results before use of such cells in clinical trials.

BACKGROUND:Fibrosis, the excessive deposition of scar tissue by fibroblasts, is one of the largest groups of diseases for which there is no therapy. Fibroblasts from lesional areas of scleroderma patients possess elevated abilities to contract matrix and produce alpha-smooth muscle actin (alpha-SMA), type I collagen and CCN2 (connective tissue growth factor, CTGF). The basis for this phenomenon is poorly understood, and is a necessary prerequisite for developing novel, rational anti-fibrotic strategies. METHODS AND FINDINGS:Compared to healthy skin fibroblasts, dermal fibroblasts cultured from lesional areas of scleroderma (SSc) patients possess elevated Rac activity. NSC23766, a Rac inhibitor, suppressed the persistent fibrotic phenotype of lesional SSc fibroblasts. NSC23766 caused a decrease in migration on and contraction of matrix, and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. SSc fibroblasts possessed elevated Akt phosphorylation, which was also blocked by NSC23766. Overexpression of rac1 in normal fibroblasts induced matrix contraction and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. Rac1 activity was blocked by PI3kinase/Akt inhibition. Basal fibroblast activity was not affected by NSC23766. CONCLUSION:Rac inhibition may be considered as a novel treatment for the fibrosis observed in SSc.

Abstract Background Transforming growth factor beta (TGFβ), a multifunctional cytokine, plays a crucial role in the accumulation of extracellular matrix components in lung fibrosis, where lung fibroblasts are considered to play a major role. Even though the effects of TGFβ on the gene expression of several proteins have been investigated in several lung fibroblast cell lines, the global pattern of response to this cytokine in adult lung fibroblasts is still unknown. Methods We used Affymetrix oligonucleotide microarrays U95v2, containing approximately 12,000 human genes, to study the transcriptional profile in response to a four hour treatment with TGFβ in control lung fibroblasts and in fibroblasts from patients with idiopathic and scleroderma-associated pulmonary fibrosis. A combination of the Affymetrix change algorithm (Microarray Suite 5) and of analysis of variance models was used to identify TGFβ-regulated genes. Additional criteria were an average up- or down- regulation of at least two fold. Results Exposure of fibroblasts to TGFβ had a profound impact on gene expression, resulting in regulation of 129 transcripts. We focused on genes not previously found to be regulated by TGFβ in lung fibroblasts or other cell types, including nuclear co-repressor 2, SMAD specific E3 ubiquitin protein ligase 2 (SMURF2), bone morphogenetic protein 4, and angiotensin II receptor type 1 (AGTR1), and confirmed the microarray results by real time-PCR. Western Blotting confirmed induction at the protein level of AGTR1, the most highly induced gene in both control and fibrotic lung fibroblasts among genes encoding for signal transduction molecules. Upregulation of AGTR1 occurred through the MKK1/MKK2 signalling pathway. Immunohistochemical staining showed AGTR1 expression by lung fibroblasts in fibroblastic foci within biopsies of idiopathic pulmonary fibrosis. Conclusions This study identifies several novel TGFβ targets in lung fibroblasts, and confirms with independent methods the induction of angiotensin II receptor type 1, underlining a potential role for angiotensin II receptor 1 antagonism in the treatment of lung fibrosis.