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1.
J Cancer ; 15(11): 3284-3296, 2024.
Article in English | MEDLINE | ID: mdl-38817876

ABSTRACT

Background: To explore the hub gene closely related to the progression of gastric cancer (GC), so as to provide a theoretical basis for revealing the therapeutic mechanism of GC. Methods: The gene expression profile and clinical data of GSE15459 in Gene Expression Omnibus (GEO) database were downloaded. The weighted gene co-expression network analysis (WGCNA) was used to screen the key modules related to GC progression. Survival analysis was used to assess the influence of hub genes on patients' outcomes. CIBERSORT analysis was used to predict the tissue infiltrating immune cells in patients. Immunohistochemical staining was conducted to further verify the expression of hub genes. Results: Through WGCNA, a total of 26 co-expression modules were constructed, in which salmon module and royalblue module had strong correlation with GC progression. The results of enrichment analysis showed that genes in the two modules were mainly involved in toll-like receptor signaling pathway, cholesterol metabolism and neuroactive ligand-receptor interaction. Six hub genes (C1QA, C1QB, C1QC, FCER1G, FPR3 and TYROBP) related to GC progression were screened. Survival analysis showed overall survival in the high expression group was significantly lower than that in the low expression group. CIBERSORT analysis revealed that immune characteristics difference between patients in early stage and advanced stage. Immunohistochemical results confirmed that C1QB, FCER1G, FPR3 and TYROBP were significantly associated with disease progression in GC. Conclusion: Our study identified that C1QB, FCER1G, FPR3 and TYROBP played important roles in the progression of GC, and their specific mechanisms are worth further study.

2.
Mol Biol Rep ; 51(1): 120, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38227070

ABSTRACT

BACKGROUND: The isolation rate and drug resistance rate of Acinetobacter baumannii (A.baumannii) have increased over the years, which has become one of the main causes of infection and death in intensive care unit (ICU) patients. Analysis of the distribution characteristics, drug resistance and influencing factors of A.baumannii in ICU could provide basis and reference for the infection prevention and clinical treatment. METHODS AND RESULTS: In this study, patients diagnosed with A.baumannii infection in ICU from January 2020 to December 2021 were selected. Samples of patients were collected for bacterial culture, drug sensitivity test analysis and drug resistant gene detection of A.baumannii. A total of 197 strains of A.baumannii were cultured in 2021, which was 18 strains more than in 2020. The specimens were mainly from lower respiratory tract secretions, and the isolated strains were multi-drug resistant. The resistance of isolates to tobramycin, gentamicin, and trimethoprim-sulfamethoxazole in 2021 showed a significant increase compared to 2020, while there were no significant differences observed in other resistance changes. The prevalence of multi-drug resistant A.baumannii in ICU remains high. Among them, all imipenem-resistant A.baumannii strains carried OXA-23 gene. CONCLUSION: Clinical treatment should use antibiotics reasonably based on the characteristics of bacterial resistance, and strengthen the prevention and control of hospital infection, pay more attention to the disinfection and isolation to reduce the risk of cross infection.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Cross Infection , Humans , Acinetobacter baumannii/genetics , Intensive Care Units , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Cross Infection/drug therapy , Cross Infection/epidemiology , Drug Resistance
3.
World J Clin Cases ; 11(26): 6165-6169, 2023 Sep 16.
Article in English | MEDLINE | ID: mdl-37731554

ABSTRACT

BACKGROUND: Left atrial flutter without prior cardiac interventions is uncommon, especially dual-loop macro-reentry atrial flutter. The critical step to ablate dual-loop macro-reentry atrial flutter is to identify the dominant loop and key isthmus. Although entrainment mapping could help identify the dominant loop and key isthmus, it may alter or terminate tachycardia. High-density mapping allows the generation of electroanatomic maps without altering or terminating tachycardia. CASE SUMMARY: Here, we report a case of symptomatic left atrial flutter without prior intervention. In this case, high-density mapping revealed a dual-loop macro-reentry around the mitral annulus and central scar of the anterior wall. The propagation result showed that the dominant loop was around the mitral annulus, and the key isthmus was between the central scar and mitral annulus. The atrial flutter terminated successfully after ablation was performed. CONCLUSION: In this case, we demonstrate that high-density mapping technology may help identify the dominant loop of dual-loop atrial flutter without entrainment, which makes ablation easier.

4.
Int J Colorectal Dis ; 38(1): 13, 2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36645524

ABSTRACT

PURPOSE: Mechanical bowel preparation (MBP) has been widely used to reduce intestinal feces and bacteria and is considered necessary to prevent surgical infections. However, it is still controversial which intensity level of MBP is the most beneficial for patients before colorectal surgery. Our study aimed to determine the impact of different intensity levels of MBP on the progression-free survival (PFS) and overall survival (OS) for colorectal cancer (CRC) patients. METHODS: We evaluated 694 patients pathologically diagnosed with CRC and underwent MBP before surgery at 4 general hospitals from January 2011 to December 2015. The survival status of patients, the disease progression, and the time of death or progression were obtained through telephone follow-up at the deadline October 10, 2018. Hazard ratios were estimated by Cox proportional hazard models. Survival was assessed using the Kaplan-Meier method followed by the log-rank test. RESULTS: Of 694 patients included, 462 received low-intensity MBP and 232 received high-intensity MBP. A significantly higher PFS in low-intensity MBP was observed (p = 0.009). PFS at 2000 days was 69.331% in the low-intensity arm and 58.717% in the high-intensity arm. Patients who underwent low-intensity MBP also showed higher OS (p = 0.009). Nine patients in the low-intensity MBP group received secondary surgery, and two patients in the high-intensity MBP group received secondary surgery. CONCLUSIONS: In this retrospective cohort, low-intensity MBP was associated with better PFS and OS, which could provide a reference for doctors when choosing the intensity of MBP.


Subject(s)
Colorectal Neoplasms , Colorectal Surgery , Digestive System Surgical Procedures , Humans , Surgical Wound Infection/prevention & control , Colorectal Surgery/methods , Retrospective Studies , Prognosis , Preoperative Care/methods , Colorectal Neoplasms/surgery
5.
Front Oncol ; 11: 620945, 2021.
Article in English | MEDLINE | ID: mdl-33996544

ABSTRACT

Objectives: To evaluate whether incorporating the radiomics, genomics, and clinical features allows prediction of metastasis in colorectal cancer (CRC) and to develop a preoperative nomogram for predicting metastasis. Methods: We retrospectively analyzed radiomics features of computed tomography (CT) images in 134 patients (62 in the primary cohort, 28 in the validation cohort, and 44 in the independent-test cohort) clinicopathologically diagnosed with CRC at Dazhou Central Hospital from February 2018 to October 2019. Tumor tissues were collected from all patients for RNA sequencing, and clinical data were obtained from medical records. A total of 854 radiomics features were extracted from enhanced venous-phase CT of CRC. Least absolute shrinkage and selection operator regression analysis was utilized for data dimension reduction, feature screen, and radiomics signature development. Multivariable logistic regression analysis was performed to build a multiscale predicting model incorporating the radiomics, genomics, and clinical features. The receiver operating characteristic curve, calibration curve, and decision curve were conducted to evaluate the performance of the nomogram. Results: The radiomics signature based on 16 selected radiomics features showed good performance in metastasis assessment in both primary [area under the curve (AUC) = 0.945, 95% confidence interval (CI) 0.892-0.998] and validation cohorts (AUC = 0.754, 95% CI 0.570-0.938). The multiscale nomogram model contained radiomics features signatures, four-gene expression related to cell cycle pathway, and CA 19-9 level. The multiscale model showed good discrimination performance in the primary cohort (AUC = 0.981, 95% CI 0.953-1.000), the validation cohort (AUC = 0.822, 95% CI 0.635-1.000), and the independent-test cohort (AUC = 0.752, 95% CI 0.608-0.896) and good calibration. Decision curve analysis confirmed the clinical application value of the multiscale model. Conclusion: This study presented a multiscale model that incorporated the radiological eigenvalues, genomics features, and CA 19-9, which could be conveniently utilized to facilitate the individualized preoperatively assessing metastasis in CRC patients.

6.
Precis Clin Med ; 4(2): 109-118, 2021 Jun.
Article in English | MEDLINE | ID: mdl-35694157

ABSTRACT

Colonoscopy is an effective tool for early screening of colorectal diseases. However, the application of colonoscopy in distinguishing different intestinal diseases still faces great challenges of efficiency and accuracy. Here we constructed and evaluated a deep convolution neural network (CNN) model based on 117 055 images from 16 004 individuals, which achieved a high accuracy of 0.933 in the validation dataset in identifying patients with polyp, colitis, colorectal cancer (CRC) from normal. The proposed approach was further validated on multi-center real-time colonoscopy videos and images, which achieved accurate diagnostic performance on detecting colorectal diseases with high accuracy and precision to generalize across external validation datasets. The diagnostic performance of the model was further compared to the skilled endoscopists and the novices. In addition, our model has potential in diagnosis of adenomatous polyp and hyperplastic polyp with an area under the receiver operating characteristic curve of 0.975. Our proposed CNN models have potential in assisting clinicians in making clinical decisions with efficiency during application.

7.
Front Oncol ; 10: 578884, 2020.
Article in English | MEDLINE | ID: mdl-33282732

ABSTRACT

INTRODUCTION: Worldwide, the incidence and mortality of lung cancer are at the highest levels, and the most lesions are located in the lung periphery. Despite extensive screening and diagnosis, the pathologic types of peripheral pulmonary lesions (PPLs) are difficult to diagnose by noninvasive examination. This study aimed to identify a novel index-time difference of arrival (TDOA)-to discriminate between benign inflammation and malignant PPLs. METHODS: Using contrast-enhanced ultrasound (CEUS), we retrospectively analyzed 96 patients with PPLs who had undergone biopsy to confirm the pathologic types. All data were collected from Dazhou Central Hospital between December 2012 and July 2019. The parameters of CEUS were analyzed by two assistant chief physicians of ultrasound diagnosis. Area under the receiver operating characteristic curve analysis, sensitivity, specificity, positive predictive value, and negative predictive value were calculated to assess the diagnostic ability of different indices. RESULTS: We found that the TDOA significantly distinguished benign inflammation from malignant lesions. The TDOA was markedly increased in patients with malignant lesions than benign inflammation lesions (P < 0.001). Compared with conventional time-intensity curve (TIC) indices, TDOA showed high diagnostic accuracy (area under the curve = 0.894). Moreover, conventional diagnostic indices did not affect the diagnostic performance of TDOA by adjusting the receiver operating characteristic curve. CONCLUSION: TDOA is feasible for the diagnosis of benign inflammation and malignant PPLs.

8.
Front Oncol ; 10: 575422, 2020.
Article in English | MEDLINE | ID: mdl-33178604

ABSTRACT

Introduction: Prognosis prediction is essential to improve therapeutic strategies and to achieve better clinical outcomes in colorectal cancer (CRC) patients. Radiomics based on high-throughput mining of quantitative medical imaging is an emerging field in recent years. However, the relationship among prognosis, radiomics features, and gene expression remains unknown. Methods: We retrospectively analyzed 141 patients (from study 1) diagnosed with CRC from February 2018 to October 2019 and randomly divided them into training (N = 99) and testing (N = 42) cohorts. Radiomics features in venous phase image were extracted from preoperative computed tomography (CT) images. Gene expression was detected by RNA-sequencing on tumor tissues. The least absolute shrinkage and selection operator (LASSO) regression model was used for selecting imaging features and building the radiomics model. A total of 45 CRC patients (study 2) with immunohistochemical (IHC) staining of CXCL8 diagnosed with CRC from January 2014 to October 2018 were included in the independent testing cohort. A clinical model was validated for prognosis prediction in prognostic testing cohort (163 CRC patients from 2014 to 2018, study 3). We performed a combined radiomics model that was composed of radiomics score, tumor stage, and CXCL8-derived radiomics model to make comparison with the clinical model. Results: In our study, we identified the CXCL8 as a hub gene in affecting prognosis, which is mainly through regulating cytokine-cytokine receptor interaction and neutrophil migration pathway. The radiomics model incorporated 12 radiomics features screened by LASSO according to CXCL8 expression in the training cohort and showed good performance in testing and IHC testing cohorts. Finally, the CXCL8-derived radiomics model combined with tumor stage performed high ability in predicting the prognosis of CRC patients in the prognostic testing cohort, with an area under the curve (AUC) of 0.774 [95% confidence interval (CI): 0.674-0.874]. Kaplan-Meier analysis of the overall survival probability in CRC patients stratified by combined model revealed that high-risk patients have a poor prognosis compared with low-risk patients (Log-rank P < 0.0001). Conclusion: We demonstrated that the radiomics model reflected by CXCL8 combined with tumor stage information is a reliable approach to predict the prognosis in CRC patients and has a potential ability in assisting clinical decision-making.

9.
Front Med (Lausanne) ; 7: 312, 2020.
Article in English | MEDLINE | ID: mdl-32766259

ABSTRACT

Background: The aim of this study is to evaluate the clinical efficacy of vitamin D (VitD) supplementation in terms of response to treatment and improvement of disease activity in rheumatoid arthritis (RA). Methods: This study analyzed 1180 RA patients' records treated at Mianyang Central Hospital from February 2015 to July 2019. The patients were allocated into VitD group and control group based on their medical regimens. The outcome measures were primary efficacy, defined as treatment response-based EULAR response criteria in RA, and secondary efficacy, defined as improvement in disease activity indicators. Safety was evaluated according to the incidence of all-cause infections. Results: At month 6, the primary efficacy revealed that there were 22.8% good responders and 19.0% moderate responders in the VitD group, and 22.3% good responders and 22.3% moderate responders in the control group; there were no differences between the two groups (p = 0.754). The similar primary efficacy outcomes were observed at months 3, 12, and >12. The secondary efficacy indicated that there were no differences in most indexes between the two groups at months 1, 3, 6, 12, and >12. The subgroups (based on baseline DAS28 (CRP), glucocorticoids use and disease duration) analysis results suggested that VitD group didn't have the advantage for treating RA. The incidence of infections was similar in the two groups. Conclusion: VitD supplementation did not provide additional benefit for anti-rheumatic treatment. These data supported the need for prospective, randomized, controlled trials to evaluate the role of VitD supplementation in treating RA.

10.
J Cardiovasc Pharmacol ; 76(4): 437-444, 2020 10.
Article in English | MEDLINE | ID: mdl-32675747

ABSTRACT

Increased late sodium current (INa) induces long QT syndrome 3 with increased risk of atrial fibrillation (AF). The role of atrial late INa in the induction of AF and in the treatment of AF was determined in this study. AF parameters were measured in isolated rabbit hearts exposed to late INa enhancer and inhibitors. Late INa from isolated atrial and ventricular myocytes were measured using whole-cell patch-clamp techniques. We found that induced-AF by programmed S1S2 stimulation and spontaneous episodes of AF were recorded in hearts exposed to either low (0.1-3 nM) or high (3-10 nM) concentrations of ATX-II (n = 10). Prolongations in atrial monophasic action potential duration at 90% completion of repolarization and effective refractory period by ATX-II (0.1-15 nM) were greater in hearts paced at slow than at fast rates (n = 5-10, P < 0.05). Both endogenous and ATX-II-enhanced late INa density were greater in atrial than that in ventricular myocytes (n = 9 and 8, P < 0.05). Eleclazine and ranolazine reduced AF window and AF burden in association with the inhibition of both endogenous and enhanced atrial late INa with half maximal inhibitory concentrations (IC50) of 1.14 and 9.78, and 0.94 and 8.31 µM, respectively. The IC50s for eleclazine and ranolazine to inhibit peak INa were 20.67 and 101.79 µM, respectively, in atrial myocytes. In conclusion, enhanced late INa in atrial myocytes increases the susceptibility for AF. Inhibition of either endogenous or enhanced late INa, with increased atrial potency of drugs is feasible for the treatment of AF.


Subject(s)
Atrial Fibrillation/metabolism , Atrial Function , Heart Atria/metabolism , Heart Rate , Myocytes, Cardiac/metabolism , Sodium/metabolism , Action Potentials , Animals , Anti-Arrhythmia Agents/pharmacology , Atrial Fibrillation/chemically induced , Atrial Fibrillation/physiopathology , Atrial Fibrillation/prevention & control , Atrial Function/drug effects , Cardiac Pacing, Artificial , Cnidarian Venoms , Disease Models, Animal , Female , Heart Atria/drug effects , Heart Atria/physiopathology , Heart Rate/drug effects , Isolated Heart Preparation , Myocytes, Cardiac/drug effects , Rabbits , Refractory Period, Electrophysiological , Sodium Channel Blockers/pharmacology , Time Factors
11.
Cancer Med ; 9(15): 5436-5445, 2020 08.
Article in English | MEDLINE | ID: mdl-32536037

ABSTRACT

BACKGROUND: This study aimed to explore the possibility of serum tumor markers (TMs) combinations in assessing tumor metastasis in patients with lung cancer. METHODS: We performed a retrospective analysis of 541 patients diagnosed with lung cancer between January 2016 and December 2017 at the Pneumology Department of Dazhou Central Hospital. Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA153, CA199, CA724, cytokeratin 19 fragment (CYFRA), and neuron-specific enolase (NSE) levels were quantified in each patient at the time of lung cancer diagnosis. Metastasis was confirmed by computed tomography, and/or positron emission tomography, and/or surgery or other necessary methods. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the performance of the model. RESULTS: Of the 541 patients eligible for final analysis, 253 were detected with metastasis and 288 were detected without metastasis. Compared with those in nonmetastatic patients, the serum CEA, CA125, CA199, CA153, CYFRA, and NSE levels were notably higher in metastatic patients (P < .05). The ROC curve demonstrated that the CEA-CA125-CA199-CA153-CYFRA-NSE-CA724 combination based on the cut-off value had an optimal area under the curve and specificity in assessing tumor metastasis. The decision tree model is a convenient and valuable tool for guiding the appropriate application of our model to assess metastasis in lung cancer patients. CONCLUSIONS: Our study suggested that the nomogram of the regression model is valuable for assessing tumor metastasis in newly diagnosed lung cancer patients before traditional standard methods are used. These findings could aid in the evaluation of metastasis in the clinic.


Subject(s)
Biomarkers, Tumor/blood , Lung Neoplasms/complications , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Retrospective Studies
12.
PeerJ ; 7: e7433, 2019.
Article in English | MEDLINE | ID: mdl-31410309

ABSTRACT

BACKGROUND: Carcinoembryonic antigen (CEA) as a diagnostic or prognostic marker has been widely studied in patients with lung cancer. However, the relationship between serum CEA and tumor metastasis in lung cancer remains controversial. This study aimed to investigate the ability of serum CEA to assess tumor metastasis in lung cancer patients. METHODS: We performed a retrospective analysis of 238 patients diagnosed with lung cancer from January to December 2016 at pneumology department of Dazhou Central Hospital (Dazhou, China). Serum CEA levels were quantified in each patient at the time of diagnosis of lung cancer. Metastasis was confirmed by computed tomography (CT), and/or positron emission tomography (PET) and/or surgery or other necessary detecting methods. RESULTS: Of the 213 patients eligible for final analysis, 128 were diagnosed with metastasis and 85 were diagnosed without metastasis. Compared to non-metastatic patients, the serum CEA was markedly higher in patients with metastasis (p < 0.001), and the area under the curve (AUC) was 0.724 (95% CI [0.654-0.793]). Subsequent analyses regarding the number and location of tumor metastases showed that CEA also had clinical value for multiple metastases versus single metastasis (AUC = 0.780, 95% CI [0.699-0.862]) and distant metastasis versus non-distant metastasis (AUC = 0.815, 95% CI [0.733-0.897]). In addition, we found that tumor size, histology diagnosis, age and gender had no impact on the assessment performance of CEA. CONCLUSION: Our study suggested the serum CEA as a valuable marker for tumor metastases assessment in newly diagnosed lung cancer patients, which could have some implications in clinical application.

13.
Biochem Biophys Res Commun ; 517(1): 8-14, 2019 09 10.
Article in English | MEDLINE | ID: mdl-31307785

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is the most common progressive cardiac arrhythmia and is often associated with rapid contraction in both atria and ventricles. The role of atrial energy and metabolic homeostasis in AF progression is under-investigated. OBJECTIVES: To determine the remodeling of energy metabolism during persistent AF and the effect of eplerenone (EPL), an aldosterone inhibitor, on metabolic homeostasis. METHODS: A nonsustained atrial pacing sheep model was developed to simulate the progression of AF from paroxysmal to persistent. Metabolomic and proteomic analyses at termination of the experiment were used to analyze atrial tissues obtained from sheep in sham, sugar pill (SP) and EPL-treated groups. RESULTS: Proteomic analysis indicated that compared to the sham group, in SP group, fatty acid (FA) synthesis, FA oxidation, tricarboxylic acid (TCA) cycle processes and amino acids (AAs) transport and metabolism were reduced, while glycolytic processes were increased. In metabolomic analysis, the levels of intermediate metabolites of the glycolytic pathways, including 2-phosphoglyceric acid (2 PG), 1,3-bisphosphoglyceric acid (1,3 PG), and pyruvate, HBP (uridine diphosphate-N-acetylglucosamine, UDP-GlcNAc), TCA (citrate) and AAs were greater while the levels of the majority of lipid classes, including phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylglycerol (PG), glycerophosphoglycerophosphates (PGP), glycerophosphoinositols (PI) and glycerophosphoserines (PS), were decreased in the atria of SP group than in those of sham group. EPL-pretreatment decreased the expression of glut4 and increased the content of acylcarnitines and lipids, such as lyso phospholipids, phospholipids and neutral lipids. CONCLUSION: In the metabolic remodeling during AF, glucose and lipid metabolism were up- and down-regulated, respectively, to sustain TCA cycle anaplerosis. EPL partialy reversed the metabolic shifting.


Subject(s)
Atrial Fibrillation/metabolism , Energy Metabolism , Myocardium/metabolism , Animals , Atrial Fibrillation/drug therapy , Atrial Fibrillation/pathology , Citric Acid Cycle/drug effects , Disease Models, Animal , Energy Metabolism/drug effects , Eplerenone/therapeutic use , Glucose/metabolism , Homeostasis/drug effects , Lipid Metabolism/drug effects , Male , Metabolic Networks and Pathways/drug effects , Mineralocorticoid Receptor Antagonists/therapeutic use , Myocardium/pathology , Sheep
14.
Front Genet ; 10: 1360, 2019.
Article in English | MEDLINE | ID: mdl-32038715

ABSTRACT

C-X-C motif chemokine ligand 8 (CXCL8) is involved in tumor proliferation, migration, and invasion. However, the function of CXCL8 in colorectal cancer (CRC) is controversial. Here, we analyzed RNA-sequencing (RNA-seq) data to identify differentially expressed genes and pathways according to gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with CRC. The levels of the mRNA encoding CXCL8 were significantly increased in early and advanced stages of CRC, as well as in metastases and nonmetastasis cases using RNA-seq analysis (n = 91). These findings were consistent with immunohistochemical analysis of CXCL8 expression (n = 87). Protein-protein interaction (PPI) prediction combined with transcriptional profiling data revealed that CXCL8 levels positively correlated with cAMP responsive element binding protein 1 (CREB1)/ribosomal protein S6 kinase B1 (RPS6KB1) expression, which promotes cell proliferation and differentiation in high expression, while inversely correlated with the expression of Bcl2 associated agonist of cell death (BAD) protein to inhibit apoptosis during the progression of CRC. These findings provide compelling clinical and molecular evidence to support the conclusion that CXCL8 contributes to the genesis and progression of CRC.

15.
Oncotarget ; 9(63): 32149-32160, 2018 Aug 14.
Article in English | MEDLINE | ID: mdl-30181805

ABSTRACT

Breast cancer (BC) is one of the leading causes of death among women worldwide. The gene expression profile GSE22358 was downloaded from the Gene Expression Omnibus (GEO) database, which included 154 operable early-stage breast cancer samples treated with neoadjuvant capecitabine plus docetaxel, with (34) or without trastuzumab (120), to identify gene signatures during trastuzumab treatment and uncover their potential mechanisms. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed by Cytoscape software. There were 2284 DEGs, including 1231 up-regulated genes enriched in DNA replication, protein N-linked glycosylation via asparagine, and response to toxic substances, while 1053 down-regulated genes were enriched in axon guidance, protein localization to plasma membrane, protein stabilization, and protein glycosylation. Eight hub genes were identified from the PPI network, including GSK3B, RAC1, PXN, ERBB2, HSP90AA1, FGF2, PIK3R1 and RAC2. Our experimental results showed that GSK3B was also highly expressed in breast cancer tissues and was associated with poor survival, as was ß-catenin. In conclusion, the present study indicated that the identified DEGs and hub genes further our understanding of the molecular mechanisms underlying trastuzumab treatment in BC and highlighted GSK3B, which might be used as a molecular target for the treatment of BC.

16.
Sci Rep ; 7(1): 981, 2017 04 20.
Article in English | MEDLINE | ID: mdl-28428622

ABSTRACT

Cardiac arrhythmias associated with intracellular calcium inhomeostasis are refractory to antiarrhythmic therapy. We hypothesized that late sodium current (I Na) contributed to the calcium-related arrhythmias. Monophasic action potential duration at 90% completion of repolarization (MAPD90) was significantly increased and ventricular arrhythmias were observed in hearts with increased intracellular calcium concentration ([Ca2+]i) by using Bay K 8644, and the increase became greater in hearts treated with a combination of ATX-II and Bay K 8644 compared to Bay K 8644 alone. The prolongations caused by Bay K 8644 and frequent episodes of ventricular tachycardias, both in absence and presence of ATX-II, were significantly attenuated or abolished by late I Na inhibitors TTX and eleclazine. In rabbit ventricular myocytes, Bay K 8644 increased I CaL density, calcium transient and myocyte contraction. TTX and eleclazine decreased the amplitude of late I Na, the reverse use dependence of MAPD90 at slower heart rate, and attenuated the increase of intracellular calcium transient and myocyte contraction. TTX diminished the phosphorylation of CaMKII-δ and Nav 1.5 in hearts treated with Bay K 8644 and ATX-II. In conclusion, late I Na contributes to ventricular arrhythmias and its inhibition is plausible to treat arrhythmias in hearts with increased [Ca2+]i.


Subject(s)
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology , Arrhythmias, Cardiac/metabolism , Calcium Channel Agonists/pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Calcium/metabolism , Sodium Channels/metabolism , Animals , Arrhythmias, Cardiac/physiopathology , Disease Models, Animal , Male , Muscle Contraction/drug effects , Oxazepines/pharmacology , Phosphorylation , Rabbits , Tetrodotoxin/pharmacology
17.
J Am Heart Assoc ; 6(3)2017 Mar 20.
Article in English | MEDLINE | ID: mdl-28320745

ABSTRACT

BACKGROUND: Cataracts are the main cause of poor vision and blindness worldwide. The effects of statin administration on cataracts remain debated. Therefore, we conducted a systematic review and meta-analysis to determine whether statin use affects the risk of cataracts. METHODS AND RESULTS: We performed a systematic search of the electronic databases PubMed, EMBASE, and the Cochrane Library through January 2016. Weighted averages were reported as relative risk values with 95% CIs. Statistical heterogeneity scores were assessed with the standard Cochran's Q test and the I2 statistic. A total of 6 cohort studies, 6 case-control studies, and 5 randomized controlled trials, together involving more than 313 200 patients, were included in our study. The pooled estimates of cohort studies indicated that the use of statins moderately increases the risk of cataracts (relative risk, 1.13; 95% CI, 1.01-1.25). The pooled estimates of case-control studies (relative risk=1.10, 95% CI, 0.99-1.23) and randomized controlled trials (relative risk, 0.89; 95% CI, 0.72-1.10) indicated that the use of statins does not increase the risk of cataracts. The sensitivity analysis confirmed the stability of the results. Heterogeneity was found among the cohort and case-control studies. CONCLUSIONS: Based on the present meta-analysis of these studies, we could only conclude that there is no clear evidence showing that statin use increases the risk of cataracts. The most likely case is that there is no association between statin use and cataracts. Because of the considerable benefits of statins in cardiovascular patients, this issue should not deter their use.


Subject(s)
Cataract/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Humans , Risk Factors
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