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BACKGROUND: The therapeutic strategy for patients with spontaneous rupture of the esophagus includes surgical repair, endoscopic therapy, supportive care, and others. However, no evidence exists to direct clinical decision-making regarding the choice of operative and nonoperative management. The aim of this study was to determine the clinical efficacy of different therapeutic strategies in both general and stratified patients. METHODS: This study retrospectively analyzed a consecutive cohort of 101 patients at nine tertiary referral hospital centers in China. Patients were divided into operative and nonoperative groups based on the initial treatment. Short-term outcomes, including 90-day mortality, length of hospital stay, and postoperative leakage were compared. Subgroup analysis was performed based on treatment timing and Pittsburgh perforation severity score (PSS). RESULTS: Of 101 patients, 60 (58.4%) underwent operative management. A significant difference of 90-day mortality between operative and nonoperative groups was observed (15.0% vs. 34.1%, P=0.031). Operative management tend to yield similar therapeutic benefits in timely (OR, 0.250; 95% CI, 0.05-1.14, P=0.073) and delayed (OR, 0.42; 95% CI, 0.12-1.47, P=0.175) treatment groups. Based on PSS stratification, operative management significantly decreased the risk of 90-day mortality (OR, 0.211; 95% CI, 0.064-0.701; P=0.011) for patients in low- and moderate-risk groups but may be detrimental for patients in high-risk group (OR, 1.333; 95% CI, 0.233-7.626; P=0.746). CONCLUSIONS: Operative management might be superior to nonoperative management for low- and moderate-risk patients with spontaneous rupture of the esophagus. However, for patients at high risks, operative management might not provide additional benefits compared with nonoperative management. Further research involving larger sample sizes is required for accurate patient stratification and conclusive evidence-based guideline.
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Spinal cord injury (SCI) is a complex problem in modern medicine. Fibroblast activation and fibroscarring after SCI impede nerve recovery. Non-coding RNA plays an important role in the progression of many diseases, but the study of its role in the progression of spinal fibrosis is still emerging. Here, we investigated the function of circular RNAs, specifically antisense to the cerebellar degeneration-related protein 1 (CDR1as), in spinal fibrosis and characterized its molecular mechanism and pathophysiology. The presence of CDR1as in the spinal cord was verified by sequencing and RNA expression assays. The effects of inhibition of CDR1as on scar formation, inflammation and nerve regeneration after spinal cord injury were investigated in vivo and in vitro. Further, gene expression of miR-7a-5p and protein expression of transforming Growth Factor Beta Receptor II (TGF-ßR2) were measured to evaluate their predicted interactions with CDR1as. The regulatory effects and activation pathways were subsequently verified by miR-7a-5p inhibitor and siCDR1as. These results indicate that CDR1as/miR-7a-5p/TGF-ßR2 interactions may exert scars and nerves functions and suggest potential therapeutic targets for treating spinal fibrotic diseases.
Subject(s)
Fibrosis , MicroRNAs , RNA, Circular , RNA, Long Noncoding , Signal Transduction , Spinal Cord Injuries , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/genetics , Spinal Cord Injuries/physiopathology , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Spinal Cord/metabolism , Spinal Cord/pathology , Smad Proteins/metabolism , Smad Proteins/genetics , Nerve Regeneration , Female , Male , Receptor, Transforming Growth Factor-beta Type II/genetics , Receptor, Transforming Growth Factor-beta Type II/metabolism , Mice, Inbred C57BL , Mice , Recovery of FunctionABSTRACT
Background: Prevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and delivery in clinical translation. Methods: In this study, optimal dosages of gelatin and pentamidine were validated by gelatin concentration test. Following cell viability, cell migration, live and dead cell, and cell adhesion assay of the Turkey tenocytes, a model of Turkey tendon repair was established to evaluate the effectiveness of the Pentamidine-Gelatin sheet. Results: Pentamidine carried with gelatin, a Food and drug administration (FDA) approved material for drug delivery, showed good dynamic release, biocompatibility, and degradation. The optimal dose of pentamidine (25ug) was determined in the in vivo study using tenocyte viability, migration, and cell adhesion assays. Further biochemical analyses demonstrated that this positive effect may be due to pentamidine downregulating the Wnt signaling pathway without affecting collagen expression. Conclusions: We tested a FDA-approved antibiotic, pentamidine, for reducing adhesion formation after flexor tendon repair in both in vitro and in vivo using a novel turkey animal model. Compared with the non-pentamidine treatment group, pentamidine treated turkeys had significantly reduced adhesions and improved digit function after six weeks of tendon healing. The translational potential of this article: This study for the first time showed that a common clinical drug, pentamidine, has a potential for clinical application to reduce tendon adhesions and improve tendon gliding function without interfering with tendon healing.
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BACKGROUND: Whether T2 esophageal squamous cell carcinoma should be subclassified remains controversial. We aimed to investigate the impact of the depth of muscularis propria invasion on nodal status and survival outcomes. METHODS: We identified patients with pT2 esophageal squamous cell carcinoma who underwent primary surgery from January 2009 to June 2017. Clinical data were extracted from prospectively maintained databases. Tumor muscularis propria invasion was stratified into superficial or deep. Binary logistic regression was used to determine risk factors for lymph node metastases. The impact of the depth of muscularis propria invasion on survival was investigated using KaplanâMeier analysis and a Cox proportional hazard regression model. RESULTS: A total of 750 patients from three institutes were investigated. The depth of muscularis propria invasion (odds ratio [OR]: 3.95, 95% confidence interval [CI]: 2.46-6.35; p < 0.001) was correlated with lymph node metastases using logistic regression. T substage (hazard ratio [HR]: 1.37, 95% CI: 1.05-1.79; p < 0.001) and N status (HR: 1.51, 95% CI: 1.05-2.17; p < 0.001) were independent risk factors in multivariate Cox regression analysis. The deep muscle invasion was associated with worse overall survival (HR: 1.52, 95% CI: 1.19-1.94; p = 0.001) than superficial, specifically in T2N0 patients (HR: 1.38, 95% CI: 1.08-1.94; p = 0.035). CONCLUSIONS: We found that deep muscle invasion was associated with significantly worse outcomes and recommended the substaging of pT2 esophageal squamous cell carcinoma in routine pathological examination.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Lymphatic Metastasis , Neoplasm Invasiveness , Humans , Male , Female , Esophageal Neoplasms/pathology , Esophageal Neoplasms/mortality , Esophageal Neoplasms/surgery , Middle Aged , Esophageal Squamous Cell Carcinoma/pathology , Esophageal Squamous Cell Carcinoma/surgery , Esophageal Squamous Cell Carcinoma/mortality , Aged , Survival Rate , Retrospective Studies , Esophagectomy , Neoplasm Staging , Follow-Up Studies , Prognosis , Lymph Nodes/pathology , Lymph Nodes/surgery , Prospective StudiesABSTRACT
Two novel vanadoborate compounds, [Cu(en)2]3[Li(H2O)]4[Li(H2O)3]2[V12B18O50(OH)10(H2O)]2·33.5H2O (1) and (H2en)4[Li(H2O)]4[V12B18O55(OH)5(H2O)]·14H2O (2), were synthesized via hydrothermal synthesis under identical conditions except for temperature. Structural analysis revealed that although both contain [V12B18O60]n- cluster anion, the different countercations potentially lead to variations in the [V12B18O60]n- cluster anion skeletons. In compound 1, the V4+/V5+ ratio was 10:2; while in compound 2 the ratio was 11:1. It is speculated that different countercations may influence the valence states of cluster anions. In this study, quantum chemical calculations revealed that the aromaticity and activity of the two compounds were different, and two-dimensional correlation infrared spectroscopy (2D-COS-IR) under magnetic perturbation confirmed that distinct response peaks of functional group vibrations to the magnetic field due to the different V4+/V5+ ratios and aromaticity of the two compounds. An electrochemical analysis revealed that compound 2 exhibits higher electrocatalytic activity. The results of quantum chemical calculations are aligned not only with the changes in the 2D-COS-IR spectra but also with the conclusions obtained from experiments on electrochemical properties. Overall, this work proposes a novel strategy for interpreting the alteration of vanadoborate anionic skeleton due to the introduction of different countercations by combining 2D-COS-IR with quantum chemical calculations.
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BACKGROUND: Nerve injuries can result in detrimental functional outcomes. Currently, autologous nerve graft offers the best outcome for segmental peripheral nerve injury. Allografts are alternatives, but do not have comparable results. This study evaluated whether plasma-derived exosome can improve nerve regeneration and functional recovery when combined with decellularized nerve allografts. METHODS: The effect of exosomes on Schwann cell proliferation and migration were evaluated. A rat model of sciatic nerve repair was used to evaluate the effect on nerve regeneration and functional recovery. A fibrin sealant was used as the scaffold for exosome. Eighty-four Lewis rats were divided into autograft, allograft, and allograft with exosome groups. Gene expression of nerve regeneration factors was analyzed on postoperative day 7. At 12 and 16 weeks, rats were subjected to maximum isometric tetanic force and compound muscle action potential. Nerve specimens were then analyzed by means of histology and immunohistochemistry. RESULTS: Exosomes were readily taken up by Schwann cells that resulted in improved Schwann cell viability and migration. The treated allograft group had functional recovery (compound muscle action potential, isometric tetanic force) comparable to that of the autograft group. Similar results were observed in gene expression analysis of nerve regenerating factors. Histologic analysis showed no statistically significant differences between treated allograft and autograft groups in terms of axonal density, fascicular area, and myelin sheath thickness. CONCLUSIONS: Plasma-derived exosome treatment of decellularized nerve allograft may provide comparable clinical outcomes to that of an autograft. This can be a promising strategy in the future as an alternative for segmental peripheral nerve repair. CLINICAL RELEVANCE STATEMENT: Off-the-shelf exosomes may improve recovery in nerve allografts.
Subject(s)
Exosomes , Peripheral Nerve Injuries , Rats , Animals , Rats, Sprague-Dawley , Rats, Inbred Lew , Transplantation, Homologous/methods , Sciatic Nerve/injuries , Nerve Regeneration/physiology , Schwann Cells/transplantation , Peripheral Nerve Injuries/surgery , Allografts/transplantationABSTRACT
Although esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers, there are major bottlenecks in its therapeutic approaches, primarily the identification of clinically relevant targets and the lack of effective targeted therapeutics. Herein, we identified the hallmarks of ESCC, namely, high T-lymphokine-activated killer cell-originated protein kinase (TOPK) expression in human ESCC tumors and its correlation with poor patient prognosis and hypoxia in the tumor microenvironment. We developed hypoxia-sensitive nanoparticles encapsulating TOPK inhibitor OTS964 and photosensitizer chlorin e6 for the imaging-directed precision therapy of ESCC tumors. The sub-100 nm monodisperse nanoparticles efficiently delivered drugs into the human ESCC KYSE 150 cancer cells to kill the cells. The nanoparticles were selectively accumulated in the ESCC tumors after intravenous (i.v.) injection, thereby enabling the diagnosis and photoacoustic imaging-guided local laser irradiation of tumors. The combination of chemotherapy and photodynamic therapy effectively eradicated human ESCC KYSE 150 tumors and inhibited liver metastasis and recurrence by suppressing TOPK and inducing ESCC cell apoptosis. The nanoparticle-based therapies further stimulated high rates of natural killer cells in ESCC tumors, thereby exhibiting the potential of immunotherapy. This study identified important therapeutic targets of ESCC tumors and delineated an effective nanocarrier-based approach for tumor microenvironment and molecular targeted therapy.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Liver Neoplasms , Humans , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/drug therapy , Cell Line, Tumor , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Immunotherapy , Tumor MicroenvironmentABSTRACT
Aim: This study was to detect the effects of purified exosome product (PEP) on C28/I2 cells and chondrocytes derived from osteoarthritis patients. Materials & methods: Cell viability and apoptosis assays were used to detect the effect of PEP on cells. qRT-PCR and cell fluorescence assays were used to investigate the potential mechanism of PEP on cell chondrogenesis. Results: PEP was internalized by cells at a fast rate and enhanced cellular proliferation and migration while attenuating apoptosis. These findings reflect the fact that PEP can increase the expression of PCNA and reduce the expression of CASP3/7/9 and BAX. Conclusion: This study suggests an innovative strategy for chondrogenesis that could be applied to osteoarthritis repair in the future.
Subject(s)
Chondrocytes , Osteoarthritis , Humans , Research DesignABSTRACT
BACKGROUND: This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors. METHODS: We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were identified using univariate and multivariate analyses. RESULTS: A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR]: 4.10, 95% confidence interval [CI]: 1.57-10.75, p = 0.004) and adjuvant therapy (HR: 0.28, 95% CI: 0.16-0.51, p < 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). The SRD group had significantly improved survival compared to the SNRD group (HR: 0.33, 95% CI: 0.19-0.58, p < 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p < 0.001) but not in the SRD group (p = 0.061). CONCLUSIONS: Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.
Subject(s)
Carcinoma, Small Cell , Esophageal Neoplasms , Humans , Esophagectomy/methods , Carcinoma, Small Cell/surgery , Carcinoma, Small Cell/pathology , Retrospective Studies , Neoplasm Staging , Esophageal Neoplasms/surgery , Prognosis , Treatment OutcomeABSTRACT
Early diagnosis of esophageal squamous cell carcinoma (ESCC), a common malignant tumor with a low overall survival rate due to metastasis and recurrence, is critical for effective treatment and improved prognosis. Raman spectroscopy, an advanced detection technology for esophageal cancer, was developed to improve diagnosis sensitivity, specificity, and accuracy. This study proposed a novel, effective, and noninvasive Raman spectroscopy technique to differentiate and classify ESCC cell lines. Seven ESCC cell lines and tissues of an ESCC patient with staging of T3N1M0 and T3N2M0 at low and high differentiation levels were investigated through Raman spectroscopy. Raman spectral data analysis was performed with four machine learning algorithms, namely principal components analysis (PCA)- linear discriminant analysis (LDA), PCA-eXtreme gradient boosting (XGB), PCA- support vector machine (SVM), and PCA- (LDA, XGB, SVM)-stacked Gradient Boosting Machine (GBM). Four machine learning algorithms were able to classifiy ESCC cell subtypes from normal esophageal cells. The PCA-XGB model achieved an overall predictive accuracy of 85% for classifying ESCC and adjacent tissues. Moreover, an overall predictive accuracy of 90.3% was achieved in distinguishing low differentiation and high differentiation ESCC tissues with the same stage when PCA-LDA, XGM, and SVM models were combined. This study illustrated the Raman spectral traits of ESCC cell lines and esophageal tissues related to clinical pathological diagnosis. Future studies should investigate the role of Raman spectral features in ESCC pathogenesis.
Subject(s)
Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Biomarkers, Tumor , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/metabolism , Esophageal Squamous Cell Carcinoma/diagnosis , Humans , Machine Learning , Spectrum Analysis, Raman/methods , Support Vector MachineABSTRACT
A refractory cervical anastomotic fistula with sinus formation will seriously impede a patient's return to normal life. It is necessary to find ways to shorten the recovery time for such patients. We used a multilayered, pursestring inverted suture-embedding method for 7 patients, 6 of whom recovered; 1 patient with severe anastomotic stricture and failed. A multilayered, pursestring inverted suture-embedding method can be used to treat persistent neck anastomotic fistula with sinus formation, but it is not suitable for patients who still have a fistula to the mediastinum, thoracic cavity, or severely narrowed anastomoses.
Subject(s)
Esophageal Neoplasms , Fistula , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Anastomotic Leak/surgery , Esophageal Neoplasms/surgery , Esophagectomy/methods , Fistula/surgery , Humans , Retrospective StudiesABSTRACT
BACKGROUND: Clearance of myelin debris and remyelination of myelin are necessary steps for peripheral nerve remodeling and regeneration. It has yet to be clarified which genes or proteins are involved in endocytosis or exocytosis in the removal of myelin debris during peripheral nerve repair. METHODS: For this project, a rat model of subacute stage of sciatic nerve injury was established first. Subsequently, normal Schwann cells (NSCs) and activated Schwann cells (ASCs) were harvest before and after peripheral nerve injury (PNI). Following methylated DNA immunoprecipitation sequencing (MeDIP-seq) and tandem mass tags (TMT) labeling analysis of NSCs and ASCs, what common biomarkers changes in peripheral nervous systems remain to be elucidated. RESULTS: A total of 14,770 different expression genes (DEGs) and 3249 different expression proteins (DEPs) were screened between ASCs and NSCs. For the exosomes, the diameter and particles concentration of exosomes were 141.7 ânm and 2.97 â× â107 particles/mL, respectively. The size distribution of exosomes was 50-200 ânm. ASCs showed higher cellular uptake ability than the NSCs by cellular uptake test. Moreover, RAB7A, ARF6, ARF1, VPS45, RAB11A, DNM3, and NEDD4 were the core markers and may control the molecular mechanism of the Endocytosis pathway. CONCLUSION: These biomarkers may play significant roles in the initiation phase of demyelination and axon regeneration. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: This study explores that the endocytosis-associated patterns of Schwann cells may be new therapeutic strategy for nerve tissue engineering and nerve regeneration.
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The challenge for surgical management of a pancreatic pseudocyst during esophagectomy is not only to preserve the gastric wall, but also to avoid forming a pancreatic fistula. We report a case of a 54-year-old man with an esophageal squamous cell carcinoma who had a synchronous pancreatic pseudocyst. Roux-en-Y cystojejunostomy was performed during a McKeown esophagectomy to enable drainage of the pancreatic pseudocyst through the jejunum. The patient recovered after the operation, and the formation of a pancreatic fistula was avoided successfully.
Subject(s)
Drainage/methods , Esophageal Neoplasms/surgery , Esophageal Squamous Cell Carcinoma/surgery , Pancreatic Pseudocyst/surgery , Anastomosis, Roux-en-Y/methods , Esophageal Neoplasms/complications , Esophageal Neoplasms/diagnosis , Esophageal Squamous Cell Carcinoma/complications , Esophageal Squamous Cell Carcinoma/diagnosis , Humans , Jejunum/surgery , Male , Middle Aged , Pancreatic Pseudocyst/diagnosis , Tomography, X-Ray ComputedABSTRACT
Schwann cells are unique glial cells in the peripheral nervous system. These cells provide a range of cytokines and nutritional factors to maintain axons and support axonal regeneration. However, little is known concerning adhesion-associated epigenetic changes that occur in Schwann cells after peripheral nerve injury (PNI). In the present study, adhesion-associated DNA methylation biomarkers were assessed between normal and injury peripheral nerve. Specifically, normal Schwann cells (NSCs) and activated Schwann cells (ASCs) were obtained from adult Wistar rats. After the Schwann cells were identified, proliferation and adhesion assays were used to assess differences between NSCs and ASCs. Methylated DNA immunoprecipitation-sequencing and bioinformatics analysis were used to identify and analyze the differentially methylated genes. Reverse transcription-quantitative PCR was performed to assess the expression levels of adhesion-associated genes. In the present study, the proliferation and adhesion assays demonstrated that ASCs had a more robust proliferative activity and adhesion compared with NSCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify methylation-associated biological processes and signaling pathways. Protein-protein interaction network analysis revealed that Fyn, Efna1, Jak2, Vav3, Flt4, Epha7, Crk, Kitlg, Ctnnb1 and Ptpn11 were potential markers for Schwann cell adhesion. The expression levels of several adhesion-associated genes, such as vinculin, BCAR1 scaffold protein, collagen type XVIII α1 chain and integrin subunit ß6, in ASCs were altered compared with those in NSCs. The current study analyzed adhesion-associated DNA methylation patterns of Schwann cells and identified candidate genes that may potentially regulate Schwann cell adhesion in Wistar rats before and after PNI.
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Reducing tendon failure after repair remains a challenge due to its poor intrinsic healing ability. The purpose of this study is to investigate the effect of a novel tissue-engineered purified exosome product (PEP) patch on tendon healing in a canine ex vivo model. Lacerated flexor digitorum profundus (FDP) tendons from three canines' paws underwent simulated repair with Tisseel patch alone or biopotentiated with PEP. For the ex vivo model, FDP tendons were randomly divided into three groups: FDP tendon repair alone group (Control), Tisseel patch alone group, and the Tisseel plus PEP (TEPEP) patch group. Following 4 weeks of tissue culture, the failure load, stiffness, histology, and gene expression of the healing tendon were evaluated. Transmission electron microscopy revealed that in exosomes of PEP the diameters ranged from 93.70 to 124.65 nm, and the patch release test showed this TEPEP patch could stably release the extracellular vesicle over 2 weeks. The failure strength of the tendon in the TEPEP patch group was significantly higher than that of the Control group and Tisseel alone group. The results of histology showed that the TEPEP patch group had the smallest healing gap and the largest number of fibroblasts on the surface of the injured tendon. Quantitative reverse transcription polymerase chain reaction showed that TEPEP patch increased the expression of collagen type III, matrix metallopeptidase 2 (MMP2), MMP3, MMP14, and reduced the expression of transforming growth factor ß1, interleukin 6. This study shows that the TEPEP patch could promote tendon repair by reducing gap formation and inflammatory response, increasing the activity of endogenous cells, and formation of type III collagen.
Subject(s)
Exosomes , Tendon Injuries , Animals , Dogs , Fibrin Tissue Adhesive , Fibroblasts , Tendon Injuries/pathology , Tendon Injuries/surgery , Tendons/pathologyABSTRACT
Nerve damage can lead to movement and sensory dysfunction, with high morbidity and disability rates causing severe burdens on patients, families, and society. DNA methylation is a kind of epigenetics, and a great number of previous studies have demonstrated that DNA methylation plays an important role in the process of nerve regeneration and remodeling. However, compared with the central nervous system, the peripheral nervous system shows stronger recovery after injury, which is related to the complex microenvironment and epigenetic changes occurring at the site of injury. Therefore, what common epigenetic changes between the central and peripheral nervous systems remain to be elucidated. We first screened differential methylation genes after spinal cord injury and sciatic nerve injury using whole-genome bisulfite sequencing and methylated DNA immunoprecipitation sequencing, respectively. Subsequently, a total of 16 genes had the same epigenetic changes after spinal cord injury and sciatic nerve injury. The Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to identify the critical biological processes and pathways. Furthermore, a protein-protein interaction network analysis indicated that Dnm3, Ntrk3, Smurf1, Dpysl2, Kalrn, Shank1, Dlg2, Arsb, Reln, Bmp5, Numbl, Prickle2, Map6, and Htr7 were the core genes. These outcomes may provide novel insights into the molecular mechanism of the subacute phase of nerve injury. These verified genes can offer potential diagnostic and therapeutic targets for nerve injury.
Subject(s)
DNA Methylation/genetics , Peripheral Nerve Injuries/genetics , Sciatic Neuropathy/genetics , Spinal Cord Injuries/genetics , Animals , Cellular Microenvironment/genetics , Epigenesis, Genetic/genetics , Gene Expression Regulation/genetics , Genome/genetics , Humans , Male , Peripheral Nerve Injuries/pathology , Protein Interaction Maps/genetics , Rats , Reelin Protein , Sciatic Nerve/injuries , Sciatic Nerve/metabolism , Sciatic Nerve/pathology , Sciatic Neuropathy/pathology , Sequence Analysis, DNA , Spinal Cord Injuries/pathologyABSTRACT
@#Objective To compare the quality of life (QOL) of advanced Siewert type Ⅱ adenocarcinoma esophagogastric junction (AEG) patients treated by the total gastrectomy, traditional proximal gastrectomy or proximal gastrectomy with gastric tube reconstruction opertations, and to provide some clinical basis for the choice of surgical methods for AEG. Methods A total of 90 patients with Siewert type Ⅱ AEG were retrospectively collected from the Affiliated Hospital of North Sichuan Medical College. Patients were divided into 3 groups according to different surgical methods (n=30 in each group), a total gastrectomy group (23 males, 7 females, aged 47-79 years), a traditional proximal gastrectomy group (treated with the traditional proximal gastrectomy procedure, 19 males, 11 females, aged 44-80 years), and a narrow gastric tube group (treated with the proximal gastrectomy with gastric tube reconstruction procedure, 25 males, 5 females, aged 47-83 years). The Chinese version of Quality of Life Questionnaire Core-30 (QLQ-C30) and Quality of Life Questionnaire Oesophagogastric-25 (QLQ-OG25) designed by European Organization for Research and Treatment of Cancer (EORTC) were used to collect the patients’ information in the three groups about their QOL during the first six months and one year after the three procedures. Results There was no statistical difference in the clinical data among the three groups (all P>0.05). QOL during the first six months after the operations assessed by the QLQ-C30 questionnaire table showed that the narrow gastric tube group was significantly best in total QOL, physical function, fatigue, and emotional function among the three groups (all P<0.05). The total gastrectomy group was the worst in role function, dyspnea, fatigue and diarrhea among the three groups (all P<0.05). The traditional proximal gastrectomy group had a worse evaluation in lose of appetite than the other two groups (P<0.05). QOL during the first six months after the operations assessed by the QLQ-OG25 questionnaire table showed that the traditional proximal gastrectomy group had a significantly worse evaluation in palirrhea than the other two groups (both P<0.05). The total gastrectomy group had a significantly worse evaluation in anxiety than the other two groups (both P<0.05). QOL during the first year after the operations assessed by the QLQ-C30 questionnaire table showed that the narrow gastric tube group had a significantly highest evaluation in total QOL physical function and emotional function among the three groups (all P<0.05). The total gastrectomy group had a significantly worst evaluation in diarrhea among the three groups (P<0.05). QOL during the first year after operations assessed by QLQ-OG25 questionnaire table showed that the traditional proximal gastrectomy group had a significantly worse evaluation in palirrhea than the other two groups (all P<0.05). Conclusion The narrow tubular esophagogastric anastomosis is better than the total gastrectomy and the traditional proximal gastrectomy for the treatment of the advanced Siewert type Ⅱ adenocarcinoma of esophagogastric junction, so this operation is worth being recommended.
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BACKGROUND Spinal cord injury (SCI) is a serious disease with high disability and mortality rates, with no effective therapeutic strategies available. In SCI, abnormal DNA methylation is considered to be associated with axonal regeneration and cell proliferation. However, the roles of key genes in potential molecular mechanisms of SCI are not clear. MATERIAL AND METHODS Subacute spinal cord injury models were established in Wistar rats. Histological observations and motor function assessments were performed separately. Whole-genome bisulfite sequencing (WGBS) was used to detect the methylation of genes. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID database. Protein-protein interaction (PPI) networks were analyzed by Cytoscape software. RESULTS After SCI, many cavities, areas of necrotic tissue, and many inflammatory cells were observed, and motor function scores were low. After the whole-genome bisulfite sequencing, approximately 96 DMGs were screened, of which 50 were hypermethylated genes and 46 were hypomethylated genes. KEGG pathway analysis highlighted the Axon Guidance pathway, Endocytosis pathway, T cell receptor signaling pathway, and Hippo signaling pathway. Expression patterns of hypermethylated genes and hypomethylated genes detected by qRT-PCR were the opposite of WGBS data, and the difference was significant. CONCLUSIONS Abnormal methylated genes and key signaling pathways involved in spinal cord injury were identified through histological observation, behavioral assessment, and bioinformatics analysis. This research can serve as a source of additional information to expand understanding of spinal cord-induced epigenetic changes.
Subject(s)
DNA Methylation , Spinal Cord Injuries/genetics , Animals , Computational Biology/methods , Disease Models, Animal , Epigenesis, Genetic , Female , Gene Expression Profiling/methods , Gene Ontology , Gene Regulatory Networks , Protein Interaction Maps , Rats , Rats, Wistar , Signal Transduction , Spinal Cord/pathology , Spinal Cord Injuries/pathologyABSTRACT
BACKGROUND: Spinal cord injury (SCI) is a traumatic disease of the central nervous system, accompanied with high incidence and high disability rate. Tissue engineering scaffold can be used as therapeutic systems to provide effective repair for SCI. PURPOSE: In this study, a novel tissue engineering scaffold has been synthesized in order to explore the effect of nerve repair on SCI. PATIENTS AND METHODS: Polycaprolactone (PCL) scaffolds loaded with actived Schwann cells (ASCs) and induced pluripotent stem cells -derived neural stem cells (iPSC-NSCs), a combined cell transplantation strategy, were prepared and characterized. The cell-loaded PCL scaffolds were further utilized for the treatment of SCI in vivo. Histological observation, behavioral evaluation, Western-blot and qRT-PCR were used to investigate the nerve repair of Wistar rats after scaffold transplantation. RESULTS: The iPSCs displayed similar characteristics to embryonic stem cells and were efficiently differentiated into neural stem cells in vitro. The obtained PCL scaffolds werê0.5 mm in thickness with biocompatibility and biodegradability. SEM results indicated that the ASCs and (or) iPS-NSCs grew well on PCL scaffolds. Moreover, transplantation reduced the volume of lesion cavity and improved locomotor recovery of rats. In addition, the degree of spinal cord recovery and remodeling maybe closely related to nerve growth factor and glial cell-derived neurotrophic factor. In summary, our results demonstrated that tissue engineering scaffold treatment could increase tissue remodeling and could promote motor function recovery in a transection SCI model. CONCLUSION: This study provides preliminary evidence for using tissue engineering scaffold as a clinically viable treatment for SCI in the future.
Subject(s)
Induced Pluripotent Stem Cells/cytology , Neural Stem Cells/cytology , Polyesters/chemistry , Schwann Cells/cytology , Spinal Cord Injuries/therapy , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Axons/pathology , Behavior, Animal , Cell Separation , Coculture Techniques , Fetal Blood/cytology , Induced Pluripotent Stem Cells/ultrastructure , Leukocytes, Mononuclear/cytology , Mice , Nerve Growth Factors/metabolism , Neural Stem Cells/metabolism , Neural Stem Cells/ultrastructure , Rats, Wistar , Schwann Cells/ultrastructure , Spinal Cord/pathologyABSTRACT
OBJECTIVES: Schwann cells (SCs) have a wide range of applications as seed cells in the treatment of nerve injury during transplantation. However, there has been no report yet on kinds of proteomics changes that occur in Schwann cells before and after peripheral nerve injury. MATERIALS AND METHODS: Activated Schwann cells (ASCs) and normal Schwann cells (NSCs) were obtained from adult Wistar rat sciatic nerves. After immunofluorescence identification, we identified differentially expressed proteins in the ASCs and NSCs using isobaric tags for relative and absolute quantitation (iTRAQ) combined with high-resolution Orbitrap liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). In addition, all the differentially expressed proteins were analyzed by Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Finally, several differentially expressed proteins were selected for Western blot verification. RESULTS: A total of 122 differentially expressed proteins in ASCs and NSCs were screened. GO analysis suggested that these different proteins are likely to accumulate in the cytoplasm and are associated with single-multicellular organism processes. The KEGG pathway analysis suggested that proteins related to purine metabolism were significantly enriched. The expression of Transmembrane glycoprotein NMB (GPNMB), Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3), and other proteins were consistent with the proteomics data obtained by Western blot analysis. CONCLUSION: GPNMB, ENPP3, GFPT2, and other proteins may play an important role in the repair of peripheral nerve injury. This study may provide new insights into changes in SCs after peripheral nerve injury.