Identification of Potential Crucial Biomarkers in STEMI Through Integrated Bioinformatic Analysis. / Identificação de Potenciais Biomarcadores Cruciais em IAMCSST por Meio de Análise Bioinformática Integrada.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. OBJECTIVES: In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. METHODS: We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of |log2fold change| > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. RESULTS: 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. CONCLUSIONS: This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI.

FUNDAMENTO: O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. OBJETIVOS: Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. MÉTODOS: Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de |log2fold change| > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. RESULTADOS: 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. CONCLUSÕES: Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.

Identificação de Potenciais Biomarcadores Cruciais em IAMCSST por Meio de Análise Bioinformática Integrada / Identification of Potential Crucial Biomarkers in STEMI Through Integrated Bioinformatic Analysis

Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de -log2fold change- > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST.

Abstract Background ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. Objectives In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. Methods We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of -log2fold change- > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. Results 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. Conclusions This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI.

Global, regional, and national burden of disease study of atrial fibrillation/flutter, 1990-2019: results from a global burden of disease study, 2019.

BACKGROUND: Data from the Global Burden of Disease, Injury, and Risk Factor Study 2019 (GBD 2019) was used to assess the burden and change in prevalence, incidence, deaths, disability-adjusted life years, and risk factors for atrial fibrillation/flutter in 204 countries and territories between 1990 and 2019. METHODS: Incidence, prevalence, deaths, disability-adjusted life years (DALYs), and their age-standardized rates of AF/AFL were analyzed by age, sex, socio-demographic index (SDI), and human development index (HDI) using the Global Burden of Disease study 2019 (GBD2019) results，and risk factors for AF/AFL (mainly high systolic blood pressure, high body-mass index, alcohol use, smoking and diet high in sodium) were differentially analyzed. RESULTS: There are 59.70 million (95% uncertainty interval (UI) 45.73-75.29 million) AF/AFL patients worldwide in 2019, with 4.72 million (95% uncertainty interval (UI) 3.64-5.96 million) new cases and 0.315 million deaths (95% uncertainty interval (UI) 0.268-0.361 million) and 8.39 million disability-adjusted years (95% uncertainty interval (UI) 6.69-10.54 million). The highest risk factor for deaths, DALYs attributable to AF/AFL in 2019 was high systolic blood pressure, high body-mass index, alcohol use, smoking, and diet high in sodium. It is estimated that between 2030 and 2034, the total incidence of male AF/ AFL will be 16.08 million, and the total number of deaths will be 1.01 million. For females, the total number of incidence is 16.85 million, and the total number of deaths is 1.49 million. CONCLUSIONS: AF/AFL remains a major global public health problem, although the ASR of prevalence, incidence, and DALY at the worldwide level showed a decreasing trend from 1990 to 2019(the ASR of deaths increased slightly). However, the unfavorable trend observed in this study in countries with lower SDI suggests that current prevention and treatment strategies should be reoriented. Some countries should develop more targeted and specific strategies to prevent the increase of AF/AFL.

Bracket-like suture method: a novel, circular marked, simplest sided purse-string suture technique for intracorporeal circular-stapled oesophagojejunostomy during laparoscopic total gastrectomy.

PURPOSE: Total laparoscopic total gastrectomy (TLTG) has been limited in application because of the difficulty of intracorporeal oesophagojejunostomy. Theoretically, an intracorporeal single-stapling oesophagojejunostomy using a circular stapler could be commonly used and provide favourable outcomes for TLTG, as in open total gastrectomy(OTG), in which the use of circular staplers in oesophagojejunostomy is common and the standard procedure. This could be possible if use of a laparoscopic purse-string suture along the distal oesophagus were made easy and simple. However, the simple and optimal use of this procedure remains to be developed. METHODS: Between October 2018 and March 2020, 21 consecutive patients with gastric cancer underwent TLTG using the bracket-like suture method (BLSM) for intracorporeal circular-stapled oesophagojejunostomy in our institution. The surgical details and postoperative outcomes were analysed to evaluate this method. RESULTS: The mean operation time was 227.6 ± 13.6 min. The median time for the two-sided purse-string suture was 4 min (range, 3-5 min). It took an average of 11.5 min for the completion of purse-string suture and anvil placement. Tumour-free margins were achieved in 21 patients with a median length of 2.5 cm (range, 2-6 cm) proximal margin. Three patients developed postoperative complications. There was no mortality. During the median follow-up period of 12 months, no anastomosis-related complications were observed. CONCLUSION: The results suggest that the method cannot only facilitate safe and easy purse-string creation, using the simplest two-sided suture in a short amount of time by circular marking of the intended transection level for intracorporeal circular-stapled oesophagojejunostomy, but can also be completed by laparoscopic surgeons with basic laparoscopic suturing skills.

Rivaroxaban for cancer-associated venous thromboembolism.

All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from cancer-associated VTE. However, there is still a debate about whether the new oral anticoagulant, rivaroxaban, can bring better efficacy and safety outcomes globally. Thus, this systematic review and meta-analysis was conducted to evaluate the efficacy and safety of rivaroxaban. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure for relevant published papers before 1 September 2019, with no language restrictions. The primary outcomes are defined as the recurrence of VTE. The secondary outcomes are defined as clinically relevant non-major bleeding, adverse major bleeding events, and all-cause of death. The data were analyzed by Stata with risk ratio (RR) and 95% confidence interval (CI). Four trials encompassing 1996 patients were included. Rivaroxaban reduced recurrent VTE with no significant difference (RR = 0.68, 95% CI = 0.43-1.07). Similarly, there were no significant differences in adverse major bleeding events (RR = 0.86, 95% CI = 0.37-2.00), clinically relevant non-major bleeding (RR = 1.24, 95% CI = 0.73-2.12) and all-cause mortality (RR = 0.76, 95% CI = 0.40-1.44). In a selected study population of cancer patients with VTE, rivaroxaban is as good as other anticoagulants. Further, carefully designed randomized controlled trials should be performed to confirm these results.

Association between body mass index and clinical characteristics, as well as with management, in Chinese patients with breast cancer.

OBJECTIVE: Body mass index (BMI) is a risk factor associated with breast cancer in postmenopausal women. This study aimed to identify the associations of BMI with clinical characteristics and management of breast cancer in female Chinese patients. METHODS: Clinicopathological information on 1296 women who were diagnosed with breast cancer was collected at our hospital. We recorded the clinicopathological characteristics, molecular phenotypes, manner of diagnosis, implementation rate of preoperative examinations, and surgical method used. RESULTS: Significant differences were found in the tumor size, disease stage, manner of diagnosis, implementation rate of preoperative examinations, and the surgical method among different BMI groups. In premenopausal patients, significant differences were found in the distribution of molecular phenotypes and surgical approach among different BMI groups. In postmenopausal patients, different BMI groups showed significant differences in the tumor size, disease stage, distribution of molecular phenotypes, manner of diagnosis, rate of implementation of preoperative mammography, and surgical method. CONCLUSION: Higher BMI is associated with a larger tumor size, more advanced disease stage, diagnosis by physical examination, higher implementation rate of preoperative examinations, and lower radical surgery rate in Chinese women with breast cancer. However, the relationship between BMI and molecular phenotypes differs between pre- and postmenopausal women.

Predominant classic circular-stapled double-tract reconstruction after totally laparoscopic proximal gastrectomy: safe, feasible, time-saving anastomoses by technical tie-up.

BACKGROUND: The double-tract reconstruction (DTR) could be a preferable option in avoiding the postoperative esophageal reflux and anastomotic stenosis during totally laparoscopic proximal gastrectomy (TLPG). An optimal procedure to achieve the DTR in TLPG remains to be established. METHODS: During March 2018 to April 2019, 15 consecutive patients with gastric cancer in the upper third of the stomach underwent intracorporeal DTR after TLPG at our hospital. The intracorporeal esophagojejunostomy (E-J), gastrojejunostomy (G-J) and jejunojejunostomy (J-J) were, respectively, performed using circular staplers by the Self-Pulling and Holding Purse-String Suture Technique, Intraluminal Poke Technique and U-shaped Parallel Purse-string Suture Technique (Technical Tie-Up). Demographic and clinicopathologic characteristics, perioperative details and postoperative outcomes were analyzed. RESULTS: The mean operating time was 216.1 ± 18.2 min. Total time for three anastomoses was 49.8 ± 6.1 min, and the time for E-J, G-J, J-J was 22.4 ± 5.0 min, 13 (range 11-16) min, 14.2 ± 2.8 min, respectively. The median proximal and distal resection margins were 2.5 (range 2-4) cm and 6 (range 5-7) cm, respectively, which were all tumor-free in 15 patients. No major complications and mortality occurred. During the median follow-up period of 14 months (range 7 to 20.5 months), there were no postoperative anastomosis-related complications observed, such as anastomotic bleeding, leakage or stenosis. No patients complained the symptoms indicating esophageal reflux and remnant gastritis. CONCLUSIONS: Predominant classic circular-stapled double-tract reconstruction is safe, feasible and time-saving in TLPG by the technical tie-up.

A porphyrin-based optical sensor membrane prepared by electrostatic self-assembled technique for online detection of cadmium(II).

An optical sensor membrane was prepared by electrostatic self-assembled technique for online detection of cadmium ion (II) (Cd(II)). The optical indicator 5,10,15,20-tetrakis(4-N-methylpyridyl) porphyrin p-toluenesulfonate (TMPyP) was adsorbed on a hydrolyzed polyacrylonitrile (PAN) membrane by electrostatic attraction and further immobilized through layer-by-layer deposition of poly(allylamine hydrochloride) (PAH) and poly(sodium 4-styrenesulfonate) (PSS) on the membrane surface. The electrostatic self-assembly of polyelectrolytes on the membrane is influenced by pH and salt concentration of polyelectrolytes. The optical sensor membrane shows distinct color and spectral response to Cd(II) under static and flow-through conditions based on the coordination of TMPyP with Cd(II). A faster detection of Cd(II) is achieved at higher feed concentration of Cd(II) or appropriate lower immobilization capacity of TMPyP on the membrane. The flow-through detection is also influenced by the flow rate; higher flow rate led to faster response to Cd(II) during filtration. Compared with the static process, the flow-through conditions are more conducive to faster analysis of ppb level concentration of Cd(II) (10-3 mg L-1) due to a promoted mass transfer and filtration enrichment. Hence, the development of the optical sensor membrane in this study demonstrated the prospect to make membranes multifunctional with advantages for online chromatic warning in addition to adsorption/rejection of heavy metal ions in the solutions that are treated.

Rivaroxaban for cancer-associated venous thromboembolism: A systematic review and meta-analysis protocol.

BACKGROUND: All cancers increase developing venous thromboembolism risk, and VTE is the second-leading cause of death among cancer patients. The anticoagulant drugs are considered to be the optimal treatment for patients with cancer-associated VTE. However, there is still controversy whether rivaroxaban, a new oral anticoagulant, can lead to better outcomes globally. METHODS: We will search PubMed, Web of Science, Cochrane Central Register of Controlled Trials and China National Knowledge Infrastructure for relevant published studies before 1 September, 2019, without any language restrictions. Only published randomized controlled trials that meet the inclusion criteria will be included. Subgroup analysis of the type of cancer, the type of VTE, cancer stage, age, sex, ethnicity, history of smoking and drinking as well as the mean, dose and duration of anticoagulants will be performed. DISCUSSION: Our study aims to estimate the efficacy and safety of rivaroxaban for patients with cancer-associated VTE and to provide recommendations to key stakeholders. TRIAL REGISTRATION: PROSPERO, October 23, 2019, CRD42019143265, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=143265.

Manipulation of Grafting Location via Photografting To Fabricate High-Performance Ethylene Vinyl Alcohol Copolymer Membrane for Protein Separation.

Ethylene vinyl alcohol copolymer (EVAL) membrane has great potential for applications in protein separation and purification, but the uncontrollable distribution of grafting location when membranes are modified by the grafting method limits the membrane performance. Herein, an effective strategy for controlling the distribution of grafting location was designed to fabricate a high-performance EVAL membrane via photografting. The UV intensity through the membranes was weakened when the local concentration of the photoinitiator benzophenone (BP) on the topside of the membrane increased; thus, the grafting location inside the EVAL membrane changed from homogenous to asymmetric distribution based on the UV absorbability of BP. The grafting inside the membrane pores can be promoted when the loose and porous surface of the EVAL membrane was used as the UV-facing side. More importantly, the varied distribution of grafting location played different roles on improving the membrane performance. For protein binding, the limited convection in the membrane bed was avoided, and the desorption efficiency could be improved when the grafting location enriched inside the membrane pores. For protein filtration, the antifouling properties of the EVAL membrane were enhanced when the grafting location enriched on the topside. This research offers a novel approach to achieve controllable grafting location distribution of membranes and provides a perspective to design the high-performance EVAL membranes for protein separation.

Intracorporeal circular-stapled anastomosis after totally laparoscopic gastrectomy: A novel, simplest u-shaped parallel purse-string suture technique.

BACKGROUND: Intracorporeal anastomoses in totally laparoscopic gastrectomy (TLG) remain technical challenges to many surgeons, although the intracorporeal jejunojejunal or gastrojejunal anastomosis is an essential procedure during TLG. Standardized, reproducible and simple circular-stapled anastomosis in open gastrectomy is limited in TLG due to the difficulties of intracorporeal purse-string suture or anvil placement. An optimal procedure for intracorporeal anastomosis in TLG remains to be established. METHODS: Between February 2018 and January 2019, 31 consecutive patients with gastric cancer underwent totally laparoscopic total gastrectomy (TLTG) or totally laparoscopic distal gastrectomy (TLDG) using the novel u-shaped parallel purse-string suture technique along the jejunum for anvil placement. The intracorporeal circular-stapled jejunojejunostomy of Roux-en-Y reconstruction in TLTG and gastrojejunostomy of Billroth II in TLDG were, respectively, performed. RESULTS: The total mean ± SD operative time was 214.7 ± 48.6 minutes. The time required for purse-string suture and anvil placement was 2.3 ± 0.5 and 4.4 ± 1.1 minutes, respectively. There were no instances of postoperative jejunojejunal or gastrojejunal anastomosis-related complications observed during the median follow-up period of 5.5 months. CONCLUSIONS: The novel procedure conceptionally and technically changes the conventional circular-shaped purse-string suture into a much simpler way, u-shaped parallel purse-string suture. This could be the simplest published intracorporeal pure-string suture technique.

Intracorporeal classic circular-stapled gastrojejunostomy and jejunojejunostomy during laparoscopic distal gastrectomy: A simple, safe "intraluminal poke technique" for anvil placement.

BACKGROUND: Totally laparoscopic distal gastrectomy is being increasingly performed. However, an optimal procedure to achieve intracorporeal gastrojejunostomy and jejunojejunostomy for Roux-en-Y reconstruction after laparoscopic distal gastrectomy remains to be established. Compared with the simple and preferable circular-stapled Roux-en-Y reconstruction in open gastrectomy, application of intracorporeal circular-stapled gastrojejunostomy and jejunojejunostomy of Roux-en-Y reconstruction during laparoscopic distal gastrectomy have been limited (no report of intracorporeal circular-stapled jejunojejunostomy) because of the difficulties of intracorporeal purse-string suture and anvil placement. To address these problems, a simple and safe intraluminal poke technique of universal surgical concept and procedure was introduced and evaluated. METHODS: Between March 2018 and August 2018, 24 consecutive patients with gastric cancer underwent totally laparoscopic distal gastrectomy in our hospital. Roux-en-Y reconstruction of intracorporeal circular-stapled gastrojejunostomy and jejunojejunostomy with the intraluminal poke technique was performed in all patients. Demographic and clinicopathologic characteristics, perioperative details and postoperative outcomes were analyzed. RESULTS: The mean operative time was 203.6±26.2min, both proximal and distal tumor-free margins were achieved in all patients. The time for anvil placement at stomach and intestine was 5.9±1.3min and 3.9±0.7min, respectively. Intracorporeal gastrojejunostomy and jejunojejunostomy were successively completed following anvil placement with no any anastomosis-related sutures. There were 5 postoperative complications. Morbidities included pancreas fistula (n=1), stasis (n=2), atelectasis (n=1), pneumonia (n=1). These all patients recovered after conservative treatment. No postoperative anastomosis-related complications, such as anastomotic bleeding and leakage, or stenosis occurred during the median follow-up of 6.5 months. CONCLUSION: The initial results suggest that the technique allowing easy and common anvil placement at stomach and intestine may be a simple, safe, preferable and time-saving procedure to accomplish intracorporeal circular-stapled gastrojejunostomy and jejunojejunostomy of Roux-en-Y reconstruction in totally laparoscopic distal gastrectomy as open surgery.

Protein changes in gastric epithelial cells RGM-1 in response to Helicobacter pylori infection.

Helicobacter pylori-induced inflammation significantly increases the risk of gastric cancer. To investigate the role of H. pylori infection in gastric epithelial cell carcinogenesis, flow cytometry was used to analyze the apoptosis of gastric epithelial cells infected by H. pylori. Next, LTQ MS mass spectrometry (MS) was applied to identify protein changes in gastric epithelial cells infected with H. pylori, and then bioinformatics was adopted to analyze the cellular localization and biological function of differential proteins. LTQ MS/MS successfully identified identified 22 differential proteins successfully, including 20 host-cell proteins and two H. pylori bacterial proteins. Also, human proteins were located in all areas of cells and involved in various cell biological functions. The oncogene proteins p53, p16, and C-erbB-2 proteins in H. pylori-infected RGM-1 cells were remarkably increased from the analysis by Western blot analysis. H. pylori infection of gastric epithelial cells leads to changes in various protein components in the cell, and enhances the expression of oncogene proteins, thereby increasing the possibility of possibility of carcinogenesis of H. pylori infection.

Itraconazole inhibits invasion and migration of pancreatic cancer cells by suppressing TGF-ß/SMAD2/3 signaling.

Pancreatic cancer is the fourth leading cause of cancer-associated mortality worldwide, with an overall 5-year survival rate <8%. We studied the therapeutic effect of itraconazole (ITZ), a commonly used broad-spectrum anti-fungal agent, in the treatment of pancreatic cancer, and to reveal the underlying anticancer mechanisms. Effects of ITZ on cell proliferation, apoptosis, invasion and migration were observed by MTT assays and colony formation assays, flow cytometry, wound scratch assays and transwell assays, respectively. Western blotting and immunofluorescence were performed to investigate the effect of ITZ on the epithelial to mesenchymal transition (EMT) of pancreatic cancer cells. Recombinant transforming growth factor-ß (TGF-ß) and TGF-ß neutralizing antibody were used to study the effect of ITZ on the TGF-ß/SMAD2/3 signaling. Transgenic engineered mice which harboring the spontaneous pancreatic cancer was applied to investigate the therapeutic role of ITZ in vivo. We report that ITZ inhibited the viability and induced apoptosis of pancreatic cancer cells. Furthermore, ITZ suppressed the invasion and migration of pancreatic cancer cells. We found that ITZ treatment was efficient in suppressing EMT and that the effect of ITZ was partially mediated by impaired TGF-ß/SMAD2/3 signaling. The role of TGF-ß/SMAD2/3 signaling in mediating the effect of ITZ was confirmed based on the results that recombinant TGF-ß induced, but the TGF-ß neutralizing antibody inhibited EMT as well as the invasion and migration of pancreatic cancer cells. Also, the anticancer effect of ITZ could be partially reversed by recombinant TGF-ß. Furthermore, treatment with ITZ suppressed growth of tumor in vivo. Taken together, we suggest that ITZ may potentially serve as a new chemotherapeutic agent for the treatment of pancreatic cancer.

LncRNATCF7 promotes the growth and self-renewal of glioma cells via suppressing the miR-200c-EpCAM axis.

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in tumor initiation and development. Recent studies illustrated that lncRNATCF7 was highly expressed in lung cancer and liver cancer, however, the expression pattern and function of lncRNATCF7 in glioma remains to be elucidated. Here, we found that lncTCF7 was highly expressed in glioma tissues and cell lines. Overexpression of lncTCF7 promoted the proliferation and migration of glioma cells. Down-regulation of lncTCF7 significantly suppressed the tumorigenesis of glioma. Mechanistically, lncTCF7 enhanced the self-renewal of glioma cells via up-regulating the expression of epithelial cell adhesion molecule (EpCAM). The detailed molecular mechanism uncovered that lncTCF7 bound to miR-200c and decreased the abundance of miR-200c, which consequently attenuated the negative regulation of miR-200c on EpCAM. Collectively, these data provide evidence to demonstrate the critical role of lncTCF7 in the tumorigeneis of glioma, which suggested that lncTCF7 might be a promising target in the treatment of glioma.

Prognosis genes in gastric adenocarcinoma identified by cross talk genes in disease­related pathways.

The aim of the present study was to investigate the prognostic value of genes that participate in the development of gastric adenocarcinoma, via exploring gene cross talk in disease­related pathways. Differentially expressed genes (DEGs) in the gastric samples were identified by analyzing the expression data downloaded from the GEO database. The DEGs were subjected to the human protein­protein interaction (PPI) network to construct the PPI network of DEGs, which was then used for the identification of key genes in cancer samples via the expression deviation score and degree in the network. A total of 635 DEGs, including 432 downregulated and 203 upregulated ones were screened in the gastric adenocarcinomas samples. The PPI network of DEGs comprised 590 DEGs and 4,299 interaction pairs. A total of 200 key genes were obtained, which were significantly enriched in six downregulated and six upregulated pathways. Cross talk genes in the connected pathways were analyzed, and the Kyoto Encyclopedia of Genes and Genomes pathways hsa00980 (Metabolism of xenobiotics by cytochrome P450) and hsa00982 (Drug metabolism) were reported to share 8 cross talk genes: ADH7, ALDH3A1, GSTA1, GSTA2, UGT2B17, UGT2B10, ADH1B and CYP2C18. Among all cross talk genes, ADH7, ALDH3A1 and CLDN3 were the most specific genes. The high­ and low­risk samples identified by the prognosis model presented a remarkable difference in total survival time, indicating its robustness and sensitivity as the prognosis genes for gastric adenocarcinoma. ADH7, ALDH3A1, GSTA1, GSTA2, UGT2B17, UGT2B10, ADH1B, CYP2C18ADH7, ALDH3A1 and CLDN3 may be used as the prognosis markers and target biomarkers for chemotherapies in gastric adenocarcinoma.

Key Genes in Stomach Adenocarcinoma Identified via Network Analysis of RNA-Seq Data.

RNA-seq data of stomach adenocarcinoma (STAD) were analyzed to identify critical genes in STAD. Meanwhile, relevant small molecule drugs, transcription factors (TFs) and microRNAs (miRNAs) were also investigated. Gene expression data of STAD were downloaded from The Cancer Genome Atlas (TCGA). Differential analysis was performed with package edgeR. Relationships with correlation coefficient > 0.6 were retained in the gene co-expression network. Functional enrichment analysis was performed for the genes in the network with DAVID and KOBASS 2.0. Modules were identified using Cytoscape. Relevant small molecules drugs, transcription factors (TFs) and microRNAs (miRNAs) were revealed by using CMAP and WebGestalt databases. A total of 520 DEGs were identified between 285 STAD samples and 33 normal controls, including 244 up-regulated and 276 down-regulated genes. A gene co-expression network containing 53 DEGs and 338 edges was constructed, the genes of which were significantly enriched in focal adhesion, ECM-receptor interaction and vascular smooth muscle contraction pathways. Three modules were identified from the gene co-expression network and they were associated with skeletal system development, inflammatory response and positive regulation of cellular process, respectively. A total of 20 drugs, 9 TFs and 6 miRNAs were acquired that may regulate the DEGs. NFAT-COL1A1/ANXA1, HSF2-FOS, SREBP-IL1RN and miR-26-COL5A2 regulation axes may be important mechanisms for STAD.

Porphyrin-functionalized porous polysulfone membrane towards an optical sensor membrane for sorption and detection of cadmium(II).

In this study, an optical sensor membrane was prepared for sorption and detection of cadmium(II) (Cd(II)) in aqueous solution. A polyanion, poly(sodium 4-styrenesulfonate) (PNaSS), was grafted onto the chloromethylated polysulfone (CMPSF) microporous membrane via surface-initiated ATRP. 5,10,15,20-tetrakis(4-N-methylpyridyl) porphyrin p-toluenesulfonate (TMPyP) was immobilized onto the PNaSS-grafted polysulfone (PSF-PNaSS) membrane through electrostatic interaction. The TMPyP-functionalized membrane exhibited an enhanced sorption for, and distinct color and spectral response to cadmium(II) (Cd(II)) in aqueous solution. Larger immobilization capacity of TMPyP on the membrane led to stronger sorption for Cd(II), and smaller one made the optical sensor have a faster (in minutes) and more sensitive response to the ion. The detection limit study indicated that the functional membrane with proper amount of TMPyP (<0.5 mg/g) could still have color and spectral response to Cd(II) solutions at an extreme low concentration (10(-4) mg/L). The optical sensor membrane exhibited good stability and reusability which made it efficient for various sorptive removal and detection applications.

Design of isolated iron species for Fenton reactions: lyophilization beats calcination treatment.

Lyophilization is used to prepare a Fenton catalyst containing a predominant amount of isolated Fe(3+) species with an 8.90% iron content. This catalyst shows a higher catalytic rate and H2O2 utilization efficiency but lower iron leaching in phenol degradation, compared with the calcination sample.