Identification of potential biomarkers in Barrett's esophagus derived esophageal adenocarcinoma.

Almost 50% of esophageal adenocarcinoma (EAC) patients progressed from Barrett's esophagus (BE). EAC is often diagnosed at late stages and is related to dismal prognosis. However, there are still no effective methods for stratification and therapy in BE and EAC. Two public datasets (GSE26886 and GSE37200) were analyzed to identify differentially expressed genes (DEGs) between BE and EAC. Then, a series of bioinformatics analyses were performed to explore potential biomarkers associated with BE-EAC. 27 up- and 104 down-regulated genes were observed between GSE26886 and GSE37200. The GO and KEGG enrichment analysis indicated that the DEGs were highly involved in tumorigenesis. Subsequently, Weighted Gene Co-Expression Network Analysis (WGCNA) were performed to explore the potential genes related to BE-EAC, which were validated in The Cancer Genome Atlas (TCGA) database, and 5 up-regulated genes (MYO1A, ACE2, COL1A1, LGALS4, and ADRA2A) and 3 down-regulated genes (AADAC, RAB27A, and P2RY14) were found in EAC. Meanwhile, ADRA2A and AADAC could contribute to EAC pathogenesis and progression. MYO1A, ACE2, COL1A1, LGALS4, ADRA2A, AADAC, RAB27A, and P2RY14 could be potential novel diagnostic and prognostic biomarkers in BE-EAC.

A new pyroptosis-related signature for predicting the immune status and injury of liver ischemia-reperfusion.

OBJECTIVE: Pyroptosis is a type of programmed cell death. This study aimed to explore the roles of key pyroptosis-related genes in liver ischemia-reperfusion injury. METHODS: After collection and standardization of the transcriptome data from GSE12720 database, differentially expressed pyroptosis-related genes were identified. The risk genes screened by a random forest model were used to establish the line graph model. Consensus clustering was used to classify all samples according to the differentially expressed pyroptosis-related genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was performed to investigate the immune cell infiltration after hepatic ischemia-reperfusion. Cytoscape was used to visualize the regulatory network of transcription factor (TF)-microRNA (miRNA)-target genes. RESULTS: We identified 18 significantly and differentially expressed pyroptosis-related genes between the disease and normal samples. Among these 18 genes, IL1ß was positively correlated with CXCL8 (r = 0.791) and BIRC3 (r = 0.78), while ADORA3 was negatively correlated with GZMB (r = -0.567) and CXCL8 (r = -0.566). Furthermore, the random forest model constructed using the top 10 pyroptosis-related genes could predict the risk of hepatic ischemia-reperfusion. Importantly, the decision curve analysis showed that patients could benefit from the risk prediction model. Moreover, we found that the expression of TXNIP, IRF1, and GJA1 was the mostly regulated by miRNAs, while the expression of BIRC3, NFκB1, and TXNIP was regulated by the TF RELA. RELA had the most hub genes involved in the regulation. CONCLUSION: Our study provides an overview of the expression landscape and the functional significance of pyroptosis-related genes in liver ischemia-reperfusion. Our findings also shed light on the clinical application of pyroptosis-related genes in the treatment of hepatic ischemia-reperfusion injury.

Recombinant Human Bone Morphogenic Protein-2 Immobilized Fabrication of Magnesium Functionalized Injectable Hydrogels for Controlled-Delivery and Osteogenic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells in Femoral Head Necrosis Repair.

Femoral head necrosis (FHN) is a clinically progressive disease that leads to overwhelming complications without an effective therapeutic approach. In recent decades, transplantation of mesenchymal stem cells (MSCs) has played a promising role in the treatment of FHN in the initial stage; however, the success rate is still low because of unsuitable cell carriers and abridged osteogenic differentiation of the transplanted MSCs. Biopolymeric-derived hydrogels have been extensively applied as effective cell carriers and drug vesicles; they provide the most promising contributions in the fields of tissue engineering and regenerative medicine. However, the clinical potential of hydrogels may be limited because of inappropriate gelation, swelling, mechanical characteristics, toxicity in the cross-linking process, and self-healing ability. Naturally, gelated commercial hydrogels are not suitable for cell injection and infiltration because of their static network structure. In this study, we designed a novel thermogelling injectable hydrogel using natural silk fibroin-blended chitosan (CS) incorporated with magnesium (Mg) substitutes to improve physical cross-linking, stability, and cell osteogenic compatibility. The presented observations demonstrate that the developed injectable hydrogels can facilitate the controlled delivery of immobilized recombinant human bone morphogenic protein-2 (rhBMP-2) and rat bone marrow-derived MSCs (rBMSCs) with greater cell encapsulation efficiency, compatibility, and osteogenic differentiation. In addition, outcomes of in vivo animal studies established promising osteoinductive, bone mineral density, and bone formation rate after implantation of the injectable hydrogel scaffolds. Therefore, the developed hydrogels have great potential for clinical applications of FHN therapy.

Key immune-related gene ITGB2 as a prognostic signature for acute myeloid leukemia.

BACKGROUND: The tumor microenvironment (TME) has an essential role in tumorigenesis, progression, and therapeutic response in many cancers. Currently, the role of TME in acute myeloid leukemia (AML) is unclear. This study investigated the correlation between immune-related genes and prognosis in AML patients. METHODS: Transcriptome RNA-Seq data for 151 AML samples were downloaded from TCGA database (https://portal.gdc.cancer.gov/), and the immune related genes (irgs) were selected from Immport database. Bioinformatics screening was used to identify irgs for AML, and genes with a critical role in the prognosis of AML were selected for further analysis. To confirm the prognostic role of irgs in AML, we undertook protein-protein interaction (PPI) network analysis of the top 30 interacting genes. We then investigated associations between immune cell infiltration and prognosis in AML patients. Immunohistochemistry was used to validate protein expression levels between AML and normal bone marrow samples. Analysis of the drug sensitivity of the selected gene was then performed. RESULTS: The integrin lymphocyte function-associated antigen 1 (CD11A/CD18; ITGAL/ITGB2) was identified as the key immune-related gene that significantly influenced prognosis in AML patients. Overexpression of ITGB2 indicated poor prognosis in AML patients (P=0.007). Risk modeling indicated that a high-risk score led to poor outcomes (P=3.076e-08) in AML patients. The risk model showed accuracy for predicting prognosis in AML patients, with area under curve (AUC) at 1 year, 0.816; AUC at 3 years, 0.82; and AUC at 5 years, 0.875. In addition, we found that ITGB2 had a powerful influence on immune cell infiltration into AML TME. The results of immunohistochemistry showed that AML patients had significantly higher ITGB2 protein expression than normal samples. The AML patients were divided into 2 groups based on ITGB2 risk scores. Drug sensitivity test results indicated that the high-risk group was sensitive to cytarabine, axitinib, bosutinib, and docetaxel, but resistant to cisplatin and bortezomib. CONCLUSIONS: In the present study, we found that ITGB2 may be able to serve as a biomarker for assessing prognosis and drug sensitivity in AML patients.

CircFAM120B knockdown inhibits osteosarcoma tumorigenesis via the miR-1205/PTBP1 axis.

BACKGROUND: Osteosarcoma (OS) is a highly prevalent bone malignancy with poor clinical outcomes. Expression of the circular RNA, hsa_circ_0078767 (circFAM120B) is elevated in OS, however, its mechanisms in OS are unclear. METHODS: CircFAM120B levels were detected in OS tissue and cell lines. Silenced circFAM120B experiments were performed to assess its effects on OS in vitro cancer phenotypes and in vivo tumor growth. Then, bioinformatics analyses were used to predict circFAM120B target microRNAs (miRNAs) and associated genes. RESULTS: CircFAM120B and the transcription factor, PTBP1 were elevated in OS tissue and cell lines, while miR-1205 was poorly expressed. Silenced circFAM120B significantly suppressed in vitro OS cell proliferation and invasion, and inhibited in vivo tumor growth. CircFAM120B also appeared to function as an miR-1205 sponge, as miR-1205 bound to PTBP1. Interestingly, overexpressed PTBP1 (or miR-1205 inhibition) reversed the inhibitory effects mediated by circFAM120B downregulation in OS cells. CONCLUSION: We hypothesize circFAM120B functions as a miR-1205 sponge to elevate PTBP1 levels, enhancing OS progression and associated malignant phenotypes. Thus, circFAM120B may function as a crucial mediator during OS progression.

Gypenoside XVII protects against spinal cord injury in mice by regulating the microRNA­21­mediated PTEN/AKT/mTOR pathway.

Gypenoside XVII (GP­17), one of the dominant active components of Gynostemma pentaphyllum, has been studied extensively and found to have a variety of pharmacological effects, including neuroprotective properties. However, the neuroprotective effects of GP­17 against spinal cord injury (SCI), as well as its underlying mechanisms of action remain unknown. The present study aimed to investigate the effects of GP­17 on motor recovery and histopathological changes following SCI and to elucidate the mechanisms underlying its neuroprotective effects in a mouse model of SCI. Motor recovery was evaluated using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. Spinal cord edema was detected by the wet/dry weight method. H&E staining was performed to examine the effect of GP­17 on spinal cord damage. Inflammatory response production was assessed by ELISA. Candidate miRNAs were identified following the integrated analysis of the Gene Expression Omnibus (GEO) dataset GSE67515. Western blot analysis was also performed to detect the expression levels of associated proteins. The results revealed that GP­17 treatment improved functional recovery, and suppressed neuronal apoptosis and the inflammatory response in the mouse model of SCI. Moreover, it was observed that miR­21 expression was downregulated following SCI, whereas it was upregulated following the administration of GP­17. The inhibition of miR­21 eliminated the protective effects of GP­17 on SCI­induced neuronal apoptosis and the inflammatory response. In addition, phosphatase and tensin homologue (PTEN), a key molecule in the activation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, was identified as a target of miR­21, and PTEN expression was downregulated by GP­17 through miR­21. Furthermore, the PTEN/AKT/mTOR pathway was inactivated by SCI, whereas it was re­activated by GP­17 through the regulation of miR­21 in mice with SCI. On the whole, the findings of the present study suggest that GP­17 plays a protective role in SCI via regulating the miR­21/PTEN/AKT/mTOR pathway.

[Effect of Quantitative indicators of ilium height on approach of percutaneous endoscopic lumbar discectomy treatment in patients with L 5, S 1 lumbar disc herniation].

OBJECTIVE: To identify effect of quantitative indicators of ilium height on approach of percutaneous endoscopic lumbar discectomy (PELD) treatment in patients with L 5, S 1 lumbar disc herniation. METHODS: A retrospective study between May 2014 and March 2016 was conducted, including 100 patients with disc herniation at L 5, S 1, who were initially enrolled for the PELD treatment. Among them, 66 patients were successfully treated with PELD (group A), and the other 34 patients failed to perform puncture, catheterization, or microscopical operation due to the influence of iliac bone and other peripheral bone structures and treated with alternative surgical plans. By analyzing the X-ray films of lumbar vertebrae (including bilateral ilium) of the two groups before operation, the concept of ilium height rate and ilium angle rate was put forward innovatively. The ilium height rate and ilium angle rate of the two groups were measured and compared, and the diagnostic critical points of ilium height rate and ilium angle rate were determined by ROC curve analysis. RESULTS: The ilium height rate was 0.61±0.09, 0.74±0.05 and the ilium angle rate was 0.66±0.08, 0.80±0.08 in groups A and B, respectively, showing significant differences between the two groups ( F=69.729, P=0.000; F=65.165, P=0.000). ROC curve analysis showed that the critical point of ilium height rate was 0.71 (area under ROC curve was 0.927, P=0.000), and the critical point of ilium angle rate was 0.75 (area under ROC curve was 0.965, P=0.000). CONCLUSION: PELD is not recommended for patients with L 5, S 1 intervertebral disc herniation, when the ilium height rate is greater than 0.71 and/or the ilium angle rate is greater than 0.75. Other surgical plans such as transpedicular approach, transpedicular approach, or open surgery, should be recommended to reduce the risk of surgery and the pain of patients.

Reliability issues of lead-free solder joints in electronic devices.

Electronic products are evolving towards miniaturization, high integration, and multi-function, which undoubtedly puts forward higher requirements for the reliability of solder joints in electronic packaging. Approximately 70% of failure in electronic devices originates during the packaging process, mostly due to the failure of solder joints. With the improvement of environmental protection awareness, lead-free solder joints have become a hot issue in recent years. This paper reviews the research progress on the reliability of lead-free solder joints and discusses the influence of temperature, vibration, tin whisker and electromigration on the reliability of solder joints. In addition, the measures to improve the reliability of solder joints are analyzed according to the problems of solder joints themselves, which provides a further theoretical basis for the study of the reliability of solder joints of electronic products in service.

Structure and properties of Sn-Cu lead-free solders in electronics packaging.

With the development of lead-free solders in electronic packaging, Sn-Cu lead-free solder has attracted wide attention due to its excellent comprehensive performance and low cost. In this article, we present recent developments in Sn-Cu lead-free solder alloys. From the microstructure and interfacial structure, the evolution law of the internal structure of solder alloy/solder joint was analysed, and the model and theory describing the formation/growth mechanism of interfacial IMC were introduced. In addition, the effects of alloying, particle strengthening and process methods on the properties of Sn-Cu lead-free solders, including wettability, melting and mechanical properties, were described. Finally, we outline the issues that need to be resolved in the future research.

Aquaporin 1 contributes to chondrocyte apoptosis in a rat model of osteoarthritis.

Aquaporins (AQPs) have been found to be associated with a number of diseases. However, the role of AQP­1 in the pathogenesis of osteoarthritis remains unclear. We previously found that AQP­1 expression was upregulated in osteoarthritic cartilage and strongly correlated with caspase­3 expression and activity. The aim of this study was to further investigate the association of AQP­1 expression with chondrocyte apoptosis in a rat model of osteoarthritis, using RNA interference to knock down AQP­1. For this purspose, 72 male Sprague­Dawley rats were randomly assigned to 3 groups as follows: the control group not treated surgically (n=24), the sham­operated group (n=24), and the osteoarthritis group (n=24). Osteoarthritis was induced by amputating the anterior cruciate ligament and medial collateral ligament and partially excising the medial meniscus. Chondrocytes from the rats with osteoarthritis were isolated and cultured. shRNAs were used to knock down AQP­1 expression in the cultured chondrocytes. The expression of AQP­1 and caspase­3 was determined by reverse transcription-quantitative polymerase chain reaction. Caspase­3 activity was measured using a caspase­3 colorimetric assay. The rats in our model of osteoarthritis exhibited severe cartilage damage. The knockdown of AQP­1 decreased caspase­3 expression and activity in the cultured chondrocytes. In addition, the expression of AQP­1 positively correlated with caspase­3 expression and activity. Thus, the findings of our study, suggest that AQP­1 promotes caspase­3 activation and thereby contributes to chondrocyte apoptosis and to the development of osteoarthritis.

Effects of osteoprotegerin, RANK and RANKL on bone destruction and collapse in avascular necrosis femoral head.

Avascular necrosis of femoral head (AVFH) is a clinically recalcitrant disease of hip that leads to joint destruction. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B (RANK) and RANK ligand (RANKL) regulates the balance, maturation and function of osteoclast and bone remodeling. This study aims to investigate molecular pathways which leads to AVN by studying expression profile of OPG, RANK and RANKL genes. Quantitative Real Time-PCR is used to evaluate mRNA expression of OPG, RANK and RANKL. mRNA and protein level in normal and necrotic tissue from 42 samples of ANFH specimens were analyzed. OPG and RANKL protein levels are estimated by western blotting. The results indicated that OPG mRNA levels are higher but not significantly different in necrotic tissue than that in normal tissue (P>0.05). Although expression of RANK and RANKL is significantly lower than that of OPG, RANK and RANKL mRNA levels are higher in necrotic tissue than normal tissue (P<0.05). Protein levels of OPG and RANKL show no significant difference. In conclusion, OPG, RANK and RANKL play important role in progress of bone remodeling in necrotic area and in disturbance of bone homeostasis, which might have an effect on bone destruction and subsequent collapse of hip joint.

Inhibitory effect of zinc on the advanced glycation end product-induced apoptosis of mouse osteoblastic cells.

Osteoporosis and diabetes have become serious health problems worldwide. Previous studies have suggested that diabetes is associated with osteoporosis and increased fracture risk. However, the mechanism underlying diabetes­induced osteoporosis remains to be elucidated. Therefore, the present study aimed to examine the mechanism underlying diabetes­induced osteoporosis, and determine the protective effects of zinc, which is known to be closely associated with osteoporosis and diabetes. The results of the present study demonstrated that zinc inhibited advanced glycation end product (AGE)­induced MC3T3­E1 cell apoptosis by attenuating the production of reactive oxygen species, inhibiting caspase­3 and caspase­9 activation, and inhibiting the release of cytochrome c from between the mitochondria and the cytosol. Furthermore, zinc was found to protect cells against AGE­induced apoptosis via the mitogen­activated protein kinase/extracellular signal­regulated kinase and phosphoinositide 3­kinase/AKT signaling pathways. In conclusion, these findings enable a better understanding of the mechanism underlying diabetes­induced osteoporosis, and may indicate a novel target for its prevention and treatment.

[Treatment of medial malleolus fractures with closed reduction and percutaneous internal fixation].

OBJECTIVE: To study clinical effects of minimally invasive, effective and economic operational method for the treatment of medial malleolus fractures. METHODS: From March 2008 to August 2010, 19 patients (12 males and 7 females, ranging in age from 17 to 42 years, averaged 31.7 years) with medial malleolus fractures were reviewed. Closed reduction and percutaneous internal fixation were applied, with a hollow compression screw inserted at the centre and perpendicularly to the fracture surface. A Kirschner wire was inserted through the cortical bone of opposite side and in accordance with the axis of inner malleolus. Postoperative therapeutic effect was evaluated by Kaikkonen sprained ankle scoring system and imageology examination. RESULTS: All the patients got primary healing of incisions and were followed up, the duration ranged from 6 to 30 months, with an average of 18.7 months. All the patients obtained bone union. Clinical healing time ranged from 2.6 to 3.8 months, averaged 3.2 months. According to Kaikkonen scoring system, the results were rated as excellent in 5 cases, good in 10 cases, moderate in 3 cases, and poor in 1 case. CONCLUSION: It is a minimally invasive, effective and economic method to treat medial malleolus fractures by closed reduction and percutaneous internal fixation with hollow compression screw and Kirschner wire.

[An experimental study on osteocyte apoptosis in steroid-induced early osteonecrosis of femoral head].

OBJECTIVE: To explore the significance of osteocyte apoptosis in steroid-induced osteonecrosis of the femoral head. METHODS: Sixty New Zealand rabbits were divided into experimental group and control group (n=30). The experimental group was given 10 ml/kg of horse serum intravenously 2 times at 2 weeks intervals and an intraperitoneal injection of 45 ml/kg x d of methylprednisolone acetate for 3 days; the control group was given equal isotonic Na chloride. Osteocyte apoptosis was observe by means of TUNEL. RESULTS: The number of apoptosis in the experimental group (112.33% per hundred +/- 26.12% per hundred) was significantly higher than that in the control (47.01% per hundred +/- 22.95% per hundred) (P < 0.01) in the 4th week. With time, osteocytes apoptosis progressively increased. In the 6th and 8th weeks, the percentage of empty osteocyte lacunae in the experimental group (17.23% +/- 3.44%, 28.56% +/- 3.45%) was significantly higher than that in the control group (11.29% +/- 2.89%, 11.26% +/- 2.75%, P < 0.05). The transmission electron microscope showed that the characteristics of osteocyte apoptosis included intact nuclear membrane,c omdensed chromatin and increased electron dense. CONCLUSION: Osteocytes apoptosis may play a key role in the process of steroid-induced early osteonecrosis of the femoral head.