Esophageal foreign body removal under holmium laser-assisted gastroscope: A case report

As a common clinical emergence, esophageal foreign body can lead to esophageal perforation followed by severe complications including aortic injury, mediastinal abscess and airway obstruction, leading to a high rate of mortality. Therefore, fast and effective diagnosis and treatment are of great necessity. In this case, holmium laser-assisted gastroscopy was adopted to remove the foreign body incarcerated in the esophagus, allowing patients to avoid traumatic and costly surgeries. It is a supplement to traditional methods of foreign body removal. The new combination tried in this report can bring development and innovation inspiration to the development of endoscopic technology

Alterations in intra- and inter-network connectivity associated with cognition impairment in insulinoma patients

ObjectiveCognitive dysfunction is common in insulinoma patients, but the underlying neural mechanisms are less well understood. This study aimed to explore the alterations of intra- and inter-network connectivity patterns associated with patients with insulinoma.MethodsResting-state fMRI were acquired from 13 insulinoma patients and 13 matched healthy controls (HCs). Group Independent component analysis (ICA) was employed to capture the resting-state networks (RSNs), then the intra- and inter-network connectivity patterns, were calculated and compared. Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function. The relationship between connectivity patterns and MoCA scores was also examined.ResultsInsulinoma patients performed significantly worse on MoCA compared to HCs. The intra-network connectivity analysis revealed that patients with insulinoma showed decreased connectivity in the left medial superior frontal gyrus within anterior default mode network (aDMN), and decreased connectivity in right lingual gyrus within the visual network (VN). The intra-network connectivity analysis showed that patients with insulinoma had an increased connectivity between the inferior-posterior default mode network (ipDMN) and right frontoparietal network (rFPN) and decreased connectivity between the ipDMN and auditory network (AUN). There was a significant negative correlation between the ipDMN-rFPN connectivity and MoCA score.ConclusionThis study demonstrated significant abnormalities in the intra- and inter-network connectivity in patients with insulinoma, which may represent the neural mechanisms underlying the cognitive impairment in insulinoma patients

Identification of common signature genes and pathways underlying the pathogenesis association between nonalcoholic fatty liver disease and atherosclerosis

BackgroundAtherosclerosis (AS) is one of the leading causes of the cardio-cerebral vascular incident. The constantly emerging evidence indicates a close association between nonalcoholic fatty liver disease (NAFLD) and AS. However, the exact molecular mechanisms underlying the correlation between these two diseases remain unclear. This study proposed exploring the common signature genes, pathways, and immune cells among AS and NAFLD.MethodsThe common differentially expressed genes (co-DEGs) with a consistent trend were identified via bioinformatic analyses of the Gene Expression Omnibus (GEO) datasets GSE28829 and GSE49541, respectively. Further, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. We utilized machine learning algorithms of lasso and random forest (RF) to identify the common signature genes. Then the diagnostic nomogram models and receiver operator characteristic curve (ROC) analyses were constructed and validated with external verification datasets. The gene interaction network was established via the GeneMANIA database. Additionally, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analysis were performed to explore the co-regulated pathways and immune cells.ResultsA total of 11 co-DEGs were identified. GO and KEGG analyses revealed that co-DEGs were mainly enriched in lipid catabolic process, calcium ion transport, and regulation of cytokine. Moreover, three common signature genes (PLCXD3, CCL19, and PKD2) were defined. Based on these genes, we constructed the efficiently predictable diagnostic models for advanced AS and NAFLD with the nomograms, evaluated with the ROC curves (AUC = 0.995 for advanced AS, 95% CI 0.971–1.0; AUC = 0.973 for advanced NAFLD, 95% CI 0.938–0.998). In addition, the AUC of the verification datasets had a similar trend. The NOD-like receptors (NLRs) signaling pathway might be the most crucial co-regulated pathway, and activated CD4 T cells and central memory CD4 T cells were significantly excessive infiltration in advanced NAFLD and AS.ConclusionWe identified three common signature genes (PLCXD3, CCL19, and PKD2), co-regulated pathways, and shared immune features of NAFLD and AS, which might provide novel insights into the molecular mechanism of NAFLD complicated with AS

Protective effects of γ-aminobutyric acid against H2O2-induced oxidative stress in RIN-m5F pancreatic cells

BACKGROUND: γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system and reported to maintain the redox homeostasis and insulin secretion function of pancreatic β cells. This study tested the hypothesis that GABA maintains cellular redox status, and modulates glycogen synthase kinase (GSK)-3β and antioxidant-related nuclear factor erythroid 2-related factor 2 (NRF2) nuclear mass ratio in the H2O2-injured RINm5F cells. METHODS: RINm5F cells were treated with/without GABA (50, 100 and 200 μmol/L) for 48 h and then exposed to 100 μmol/L H2O2 for 30 min. Viable cells were harvested, and dichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to detect reactive oxygen species (ROS) level; cellular redox status and insulin secretion were measured; cell viability was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; mitochondrial membrane potential (MMP) was detected by flow cytometry; relative genes levels were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR); western blotting was used to determine protein expression of GSK-3β and p-GSK-3β (Ser9), and nuclear and cytoplasmic NRF2. RESULTS: H2O2 increased ROS production, and induced adverse affects in relation to antioxidant defense systems and insulin secretion. These changes were restored by treatment with 100 and 200 μmol/L GABA. In addition, 100 or 200 μmol/L GABA induced membrane depolarization and increased cell viability. These effects were mediated by Caspase-3, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) expression. Western blotting indicated that GABA inhibited GSK-3β by increasing p-GSK-3β (Ser9) level, and directed the transcription factor NRF2 to the nucleus. CONCLUSION: In rat insulin-producing RINm5F cells, GABA exerts its protective effect by regulating GSK-3β and NRF2, which governs redox homeostasis by inhibiting apoptosis and abnormal insulin secretion by exposure to H2O2

Dosimetric superiority of IMRT with jaw tracking technique for whole esophagus and T-shaped field radiotherapy in advanced esophageal cancer.

PURPOSE:For whole esophagus and T-shaped field radiotherapy using intensity modulated radiotherapy (IMRT) technique in advanced esophageal cancer, lower absorbed doses to lung and heart remains a challenge. The aim of this study was to investigate the dosimetric superiority in IMRT plans with jaw tracking technique for whole esophagus radiotherapy. METHODS AND MATERIALS:Thirty-two patients with esophageal cancer were subjected to IMRT treatment plans using Eclipse treatment planning system. For every patient, four different plans were generated with six gantry angles: six large fields IMRT plans with fixed jaw (6F-IMRT), six large fields IMRT plans with jaw tracking technique (6F-IMRT-T), twelve small fields IMRT plans with fixed jaw (12F-IMRT), and twelve small fields IMRT plans with jaw tracking technique (12F-IMRT-T). Dosimetric evaluation was assessed for all plans. RESULTS:For every technique, there were no differences in planning target volume (PTV) coverage and conformity. 6F-IMRT-T plans could significantly reduce lung irradiation with 7.9% (P<0.001) reduction in V5lung and 2.5% (P<0.001) reduction in V20 lung respectively compared to 6F-IMRT plans. 12F-IMRT-T plans resulted in superior plans compared to 12-IMRT plans with a reduction of 2.9% (P<0.001) in V5lung and 0.9% (P<0.001) in V20 lung, respectively. For heart irradiation, 6F-IMRT-T and 12F-IMRT-T plans were slightly superior to 6F-IMRT and 12-IMRT plans respectively with a reduction of 1.1 Gy and 0.5 Gy in the respective mean doses. CONCLUSIONS:By the use of jaw tracking technique, the IMRT plans resulted in further lung and heart sparing compared to fixed jaw plans for radiotherapy in esophageal cancer

Biological Response of Nasopharyngeal Carcinoma to Radiation Therapy: A Pilot Study Using Serial F-18-FDG PET/CT Scans

We used serial F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) to evaluate tumors' maximum standardized uptake value (SUVmax) before, during, and after radiotherapy to explore the biological behavior of and response to radiation therapy in various subtypes of nasopharyngeal carcinoma (NPC). Sixty-one patients with pathologically diagnosed NPC were prospectively enrolled into the study. WHO type IIB disease had a higher initial SUVmax and more significant biological response at the primary site as compared with type IIA subtype. The two subtypes of WHO type II NPC may significantly differ in their biological behavior and response to radiotherapy.Major Projects of Fujian Natural Science Foundation [2008-59-11]; Youth Projects of Fujian Provincial Health Bureau [2008-1-51

Association of osteopontin polymorphisms with nasopharyngeal carcinoma risk

No previous study has reported the association of osteopontin polymorphisms with nasopharyngeal carcinoma (NPC) risk. We aimed to investigate the association in a Chinese population. Four variants of osteopontin, rs11730582, rs1126772, rs9138, and rs4754 polymorphisms, were assessed in a case-control study which consists of 108 NPC patients and 210 health controls, by using polymerase chain reaction – restriction fragment length polymorphism method. Serum osteopontin levels were measured by enzyme-linked immunosorbent assay. The serum osteopontin levels were significantly higher in NPC patients than those in controls (P 0.05). The variant rs11730582 of osteopontin is associated with NPC risk. It potentially serves as a genetic marker of NPC predisposition

Th22 cells are associated with hepatocellular carcinoma development and progression

Objective: IL-22-producing CD4+ T helper cells (Th22 cells) have been identified as major inducers of tissue inflammation and immune responses. Currently, no previous study explored the role of Th22 cells in the pathogenesis of hepatocellular carcinoma (HCC). The study aimed to determine the biological function of Th22 cells and its effector IL-22 in HCC patients. Methods: Forty-five HCC patients and 19 healthy controls were recruited and their peripheral blood was collected. The fresh HCC tissues, adjacent HCC tissues and ten normal liver tissues were also collected. Flow cytometry analysis was used to determine the frequencies of circulating Th22 cells and Th17 cells. Serum IL-22 levels were tested by enzyme-linked immunosorbent assay (ELISA). Immunohistochemical staining and real-time polymerase chain reaction (PCR) were used to detect IL-22 protein and mRNA in tissues specimens, respectively. Results: Circulating Th22 cells, Th17 cells and serum IL-22 levels were significantly elevated in HCC patients compared with those of healthy controls (P<0.001). Th22 cells were showed to be positively correlated with IL-22 in HCC patients (P<0.05), but not in healthy controls. No significant differences were found in HCC patients with HBeAg positivity or negativity in term of Th22 cells and serum IL-22 levels. The expression of IL-22 protein and mRNA was highest in HCC tissues, followed by adjacent HCC tissues and normal liver tissues. Furthermore, Th22 cells, serum IL-22 levels and IL-22 mRNA were elevated at stage III-IV compared with stage I-II of HCC (P<0.05). Conclusions: Elevation of circulating Th22 cells and IL-22 may be implicated in the pathogenesis of HCC, and potentially be cellular targets for therapeutic intervention

EGR1 mediates MDR1 transcriptional activity regulating gemcitabine resistance in pancreatic cancer

Abstract Background Gemcitabine is a cornerstone drug for the treatment of all stages of pancreatic cancer and can prolong the survival of patients with pancreatic cancer, but resistance to gemcitabine in pancreatic cancer patients hinders its efficacy. The overexpression of Early growth response 1(EGR1) in pancreatic ductal adenocarcinoma as a mechanism of gemcitabine chemoresistance in pancreatic cancer has not been explored. The major mechanisms of gemcitabine chemoresistance are related to drug uptake, metabolism, and action. One of the common causes of tumor multidrug resistance (MDR) to chemotherapy in cancer cells is that transporter proteins increase intracellular drug efflux and decrease drug concentrations by inducing anti-apoptotic mechanisms. It has been reported that gemcitabine binds to MDR1 with high affinity. The purpose of this research was to investigate the potential mechanisms by which EGR1 associates with MDR1 to regulate gemcitabine resistance in pancreatic cancer cells. Methods The following in vitro and in vivo techniques were used in this research to explore the potential mechanisms by which EGR1 binds to MDR1 to regulate gemcitabine resistance in pancreatic cancer cells. Cell culture; in vitro and in vivo study of EGR1 function by loss of function analysis. Binding of EGR1 to the MDR1 promoter was detected using the ChIP assay. qRT-PCR, Western blot assays to detect protein and mRNA expression; use of Annexin V apoptosis detection assay to test apoptosis; CCK8, Edu assay to test cell proliferation viability. The animal model of pancreatic cancer subcutaneous allograft was constructed and the tumours were stained with hematoxylin eosin and Ki-67 expression was detected using immunohistochemistry. Findings We revealed that EGR1 expression was increased in different pancreatic cancer cell lines compared to normal pancreatic ductal epithelial cells. Moreover, gemcitabine treatment induced upregulation of EGR1 expression in a dose- and time-dependent manner. EGR1 is significantly enriched in the MDR1 promoter sequence.Upon knockdown of EGR1, cell proliferation was impaired in CFPAC-1 and PANC-1 cell lines, apoptosis was enhanced and MDR1 expression was decreased, thereby partially reversing gemcitabine chemoresistance. In animal experiments, knockdown of EGR1 enhanced the inhibitory effect of gemcitabine on tumor growth compared with the sh-NC group. Conclusions Our study suggests that EGR1 may be involved in the regulation of MDR1 to enhance gemcitabine resistance in pancreatic cancer cells. EGR1 could be a novel therapeutic target to overcome gemcitabine resistance in pancreatic cancer

Association of interleukin-12 polymorphisms and serum IL-12p40 levels with osteosarcoma risk

No previous studies reported the association of IL-12 polymorphisms with osteosarcoma. We aimed to investigate the association in a Chinese population. IL-12A rs568408, rs2243115, and IL-12B rs3212227 polymorphisms were evaluated in a case–control study of 106 osteosarcoma patients and 210 health controls by using polymerase chain reaction–restriction fragment length polymorphism. Serum IL-12p40 levels were measured by enzyme-linked immunosorbent assay. The serum IL-12p40 levels were significantly higher in controls than those in osteosarcoma patients (p<0.01). Genotypes of rs568408 GA and GA/AA, and rs3212227 CC and AC/CC were associated with the risk of osteosarcoma (rs568408 GA: odds ratios [OR]=1.86, 95% confidence intervals [CI]=1.11–3.12; GA/AA: OR=1.75, 95% CI=1.06–2.89, and rs3212227 CC: OR=2.70, 95% CI=1.38–5.28; CC/AC: OR=1.73, 95% CI=1.03–2.90). Moreover, rs3212227 CC/AC genotypes were significantly associated with decreased serum IL-12p40 levels in osteosarcoma patients compared to AA genotypes (p=0.035). Stratification analysis showed no associations between rs3212227 variant and the patients' gender, tumor location, and metastasis. Our data suggest that the serum IL-12p40 levels associate with the risk of osteosarcoma and are regulated by IL-12B rs3212227 polymorphism. The IL-12A rs568408 and IL-12B rs3212227 may confer the susceptibility to osteosarcoma risk