Genome-wide enhancer RNA profiling adds molecular links between genetic variation and human cancers.

BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

Subclinical paraganglioma of the retroperitoneum: A case report.

BACKGROUND: Paraganglioma (PGL) located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location, lack of specific symptoms in the early stages, and absence of distinctive manifestations on imaging. CASE SUMMARY: A 56-year-old woman presented with a left upper abdominal mass discovered 1 wk ago during a physical examination. She did not have a history of smoking, alcohol consumption, or other harmful habits, no surgical procedures or infectious diseases, and had a 4-year history of hypertension. Upon admission, she did not exhibit fever, vomiting, or abdominal distension. Physical examination indicated mild percussion pain in the left upper abdomen, with no palpable enlargement of the liver or spleen. Laboratory tests and tumor markers showed no significant abnormalities. Enhanced computed tomography and magnetic resonance imaging of the upper abdomen revealed a cystic solid mass in the left epigastrium measuring approximately 6.5 cm × 4.5 cm, with inhomogeneous enhancement in the arterial phase, closely associated with the lesser curvature of the stomach and the pancreas. The patient underwent laparoscopic resection of the retroperitoneal mass, which was successfully removed without tumor rupture. A 12-month postoperative follow-up period showed good recovery. CONCLUSION: This case report details the successful laparoscopic resection of a retroperitoneal subclinical PGL, resulting in a good recovery observed at the 12-month follow-up. Interestingly, the patient also experienced unexpected cure of hypertensive disease.

Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells.

BACKGROUND: Bioinformatics analysis showed that the expression of the poly(A)-specific ribonuclease (PARN) gene in gastric cancer, head and neck squamous cell carcinoma, melanoma, cervical cancer and lung squamous cell carcinoma tissues was significantly higher than that in normal tissues and was associated with high stage and poor prognosis. The expression of the PARN gene in esophageal cancer (EC) tissue is also significantly higher than that in normal tissues, but the effect of PARN on the proliferation, migration and invasion of EC cells remains unclear. AIM: To investigate the relationship between PARN and the proliferation, migration and invasion of EC cells. METHODS: The EC tissues of 91 patients after EC surgery and 63 paired precancerous healthy tissues were collected. PARN mRNA levels were measured using a tissue microarray, and the PARN expression level was evaluated using immunohistochemistry to analyze the relationship between PARN expression and clinicopathologic features as well as the survival and prognosis of patients. In addition, the effects of PARN gene knockout on tumor cell proliferation, invasion and migration were studied by using shRNA during the in vitro culture of EC cell lines Eca-109 and TE-1, and the effects of the PARN gene on tumor growth in vivo were verified by a xenotransplantation nude mice model. RESULTS: The expression of PARN in EC tissues was higher than that in adjacent normal tissues, and the level of PARN expression was significantly positively correlated with lymphatic metastasis. Patients with high PARN levels had poor overall survival. BIM, IGFBP-5 and p21 levels were significantly increased in the PARN knockout group, while the expression levels of the antiapoptotic proteins Survivin and sTNF-R1 were significantly decreased in the apoptotic antibody array data. In addition, the expression levels of Akt, p-Akt, PIK3CA and CCND1 in the downstream signaling pathway regulating EC progression were significantly decreased. The culture of EC cell lines confirmed that the apoptosis rate of EC cells was significantly increased, the growth and proliferation of tumor cells were significantly inhibited, and the invasion and migration ability of tumor cells were significantly decreased after PARN gene knockout. In vivo experiments of BALB/c nude mice transfected with Eca-109 cells expressing control shRNA (sh-NC) and PARN shRNA (sh-PARN) showed that the tumor volume and weight of nude mice treated with sh-PARN were significantly decreased compared with those of nude mice treated with sh-NC, indicating that PARN knockdown significantly inhibited tumor growth in vivo. CONCLUSION: PARN has antiapoptotic effects on EC cells and promotes their proliferation, invasion and migration, which is associated with the development of EC and poor patient prognosis. PARN may become a potential target for the diagnosis, prognosis prediction and treatment of EC.

Value of acoustic cardiography in the clinical diagnosis of coronary heart disease.

BACKGROUND: To investigate the clinical value of acoustic cardiography in the diagnosis of coronary artery disease (CAD) and post-percutaneous coronary intervention (PCI) early asymptomatic left ventricular systolic dysfunction. METHODS: Inpatients in the department of cardiology were included in the research (n = 315); including 180 patients with angina pectoris and 135 patients with acute anterior wall myocardial infarction after emergency PCI did not present with signs and symptoms of heart failure. Color Doppler echocardiography, brain natriuretic peptide, acoustic cardiography examination were performed. The patients were divided into four groups: non-CAD group (n = 60), CAD group (n = 120), MIREF group (EF% < 50%, n = 75), and MINEF group (EF% ≥ 50%, n = 60). RESULTS: Acoustic cardiography parameters EMATc, systolic dysfunction index, S3 strength and S4 strength in the MIREF group were higher than those in MINEF group (p < .05), and the MINEF group was higher than CAD group (p < .05). S3 strength (area under the curve [AUC] 0.67, 95% CI 0.585-0.755, p < .001) and S4 strength (AUC 0.617, 95% CI 0.536-0.698, p = .011) are useful in the diagnosis of CAD. S3 strength (AUC 0.942, 95% CI 0.807-0.978, p < .001) was superior to other indicators in the diagnosis of early left ventricular systolic dysfunction after myocardial infarction. CONCLUSION: S4 combined with STT standard change can improve the diagnosis of CAD. Acoustic cardiography can be used as a non-invasive, rapid, effective, and simple method for the diagnosis of asymptomatic left ventricular systolic dysfunction in the early stage after myocardial infarction.

MiR-191-5p inhibits lung adenocarcinoma by repressing SATB1 to inhibit Wnt pathway.

BACKGROUND: To investigate the function of miR-191-5p in lung adenocarcinoma and its possible mechanism. METHODS: QRT-PCR was adopted for the detection of the expression levels of miR-191-5p and SATB1 (HGNC: 10541). The effects of miR-191-5p and SATB1 on cell proliferation and migration were examined through the CCK-8 and Transwell assays. Subsequently, the binding relationships between miR-191-5p and SATB1 were confirmed by dual-luciferase reporter gene assay. Finally, the potential mechanisms of action of miR-191-5p were explored through a serious of in vivo and in vitro experiments. RESULTS: Lung adenocarcinoma patients had a notably lower expression level of miR-191-5p than controls, patients with metastasis had a lower level than those without metastasis, and the level in patients with lung adenocarcinoma in stage III-IV was lower than that in patients with lung adenocarcinoma in stage I-II. Overexpression of miR-191-5p repressed the migration and proliferation of lung cancer A549/H1650 cells. According to the reporter gene assay, miR-191-5p could bind to SATB1. Besides, SATB1 was significantly overexpressed in cancer tissues of patients with lung adenocarcinoma, and SATB1 overexpression accelerated the migration and proliferation of A549/H1650 cells and reversed inhibition on cell migration and proliferation by miR-191-5p. CONCLUSION: Overexpression of miR-191-5p is capable of blocking the migration and proliferation of lung cancer cells, and its mechanism may be through targeting SATB1 thus downregulating Wnt signaling.

ω-3 Polyunsaturated Fatty Acid Postconditioning Protects the Isolated Perfused Rat Heart from Ischemia-Reperfusion Injury.

AIMS: This study aimed to evaluate the cardioprotective effects of ω-3 polyunsaturated fatty acids (PUFAs) postconditioning against ischemia-reperfusion (I/R) injury. METHODS: Sixty Sprague-Dawley rats were randomly divided into 4 groups (n = 15 for each) and used to generate the Langendorff isolated perfused rat heart model. The sham group received a continuous perfusion of 150 min. The remaining three I/R-treated groups sequentially received a 30-min perfusion, a 30-min cardioplegia, and a 90-min reperfusion. The I/R-ischemic preconditioning (IP) group additionally received three cycles of 20-s reperfusion and 20-s coronary reocclusion preceded the 90 min of reperfusion. The I/R-ω group were perfused with ω-3 PUFAs for 15 min before the 90 min of reperfusion. The myocardial infarct size, the degree of mitochondrial damage, the antioxidant capacity of the myocardium, and the cardiac functions during reperfusion were compared among groups. RESULTS: Compared with the I/R group, the I/R-ω group had significantly reduced myocardial infarct size, reduced levels of lactate dehydrogenase and malondialdehyde, elevated superoxide dismutase level, and elevated rising (+dp/dtmax) and descending (-dp/dtmax) rate of left ventricular pressure. The I/R-ω group had a significantly lower rate of mitochondrial damage in myocardial tissue compared with the I/R and I/R-IP groups. CONCLUSION: ω-3 PUFA postconditioning possesses good cardioprotective effects and may be developed into a therapeutic strategy for myocardial I/R injury.

[Establishment of a rabbit model of small diameter vascular graft replacement].

OBJECTIVE: To establish an rabbit model that mimics the hemodynamics of the bypass graft after coronary artery bypass surgery. METHODS: Sixteen New Zealand rabbits were randomly divided into two groups for abdominal aortic artery replacement using a 3-cm-long ePTFE graft with an inner diameter 4 mm through an incision at 1/3 from the middle to the lower part of the abdomen (group A) or in the lower abdomen (group B). The general conditions of the rabbits, operative time, number of collateral vessels that needed to be ligated, rate of massive intraoperative bleeding, fluctuation of vascular anastomosis after surgery, patency rate of the graft on day 7 after the operation were compared between the two groups. RESULTS: The two groups of rabbits had similar body weight, diameter of the abdominal aortic artery, intraoperative bleeding rate and occlusion rate of the vascular graft at 7 days after the procedure. The operative time was longer in group A, but the difference was not statistically significant. In group A, the number of the vascular branches that needed to be ligated was smaller and the rate normal femoral artery pulsation was higher than those in group B. CONCLUSION: It is feasible to establish models of small diameter vascular graft replacement in rabbits, and the patency rate of the graft can be monitored by observation of the general condition and ultrasound examination of the rabbits.

Endovascular stent-graft exclusion of adult giant patent ductus arteriosus through a hybrid transabdominal approach.

Endovascular stent-graft exclusion has proven to be a safe and effective alternative for adult patients with patent ductus arteriosus. We present a case of a 38-year-old woman with a large, symptomatic ductus. However, her small femoral and iliac arteries limited the access options. The patient underwent laparotomy and end-to-side anastomosis of a Dacron graft to the abdominal aorta. Then, the laparotomy was temporarily closed with the graft externalized, and the patient was transported to the radiology suite for successful stent-graft deployment. This hybrid transabdominal approach may be preferred in patients without suitable peripheral arteries to accommodate the device.

[Relationship between early spontaneous cardioversion of atrial fibrillation and thyroid hormone metabolism after mitral replacement in patients with rheumatic heart disease].

OBJECTIVE: To analyze the relationship between early spontaneous cardioversion of atrial fibrillation (AF) and thyroid hormone metabolism after mitral replacement in patients with rheumatic heart disease, and explore the treatment strategy of early spontaneous cardioversion after mitral valve replacement. METHODS: According to the occurrence of cardioversion, 138 patients with mitral valve replacement were divided into conversion group and non-conversion group, and based on the duration of sinus rhythm, the patients in conversion group were divided into < 3 days group and > 3 days group. Triiodothyronine (T3) was detected by radioimmunoassay in all the patients. RESULTS: T3 metabolism decreased significantly after the operation in all the patients. Early spontaneous cardioversion of AF occurred 2 h after the operation in 52 cases (37.7%), and 28 (20.3%) of the cases had a duration of sinus rhythm longer than 3 days. T3 was significantly decreased in conversion group and non-conversion group by 44.5% and 58.7% at 2 h, by 40.0% and 52.4% at 24 h and by 28.6% and 37.7% at 72 h after the operation, respectively. The levels of T3 in conversion group was significantly higher than the levels in non-conversion group, and showed no significant variation with the duration of sinus rhythm. CONCLUSION: Enhancement of T3 levels after mitral valve replacement may increase the probability of early spontaneous cardioversion of AF, but can not affect the duration of sinus rhythm. This finding supports the supplementation of T3 perioperatively in patients undergoing cardiac surgeries.

[Hemocompatibility evaluation in vitro of small-caliber expanded polytetrafluoroethylene vessel with silk fibroin coating sulfonated by low temperature plasma].

OBJECTIVE: To evaluate the hemocompatibility of a small-caliber expanded polytetrafluoroethylene vessel with silk fibroin coating sulfonated by low temperature plasma treatment. METHODS: The composite blood vessel was prepared by first coating the small-caliber expanded polytetrafluoroethylene vessel with silk fibroin followed by sulfonation by low temperature plasma treatment. After hemolysis test in vitro, dynamic coagulation time test, blood platelet adhesion test, and recalcification time test were performed to evaluate the hemocompatibility of the composite blood vessel. RESULTS: Scanning electronic microscopy revealed obvious platelets adhesion on the conventional artificial (control) vessel, which seldom occurred on the composite vessel. The curve of absorbance-clotting time of the composite vessel declined more slowly than that of the control vessel. The recalcification time of the composite blood vessel averaged 603 s, significantly longer than that of the control vessel (480 s, P = 0.000). CONCLUSION: The composite blood vessel has good antithrombotic activity and hemocompatibility as a promising vascular prosthesis.

[Expression of special AT-rich sequence-binding protein mRNA and its clinicopathological significance in non-small cell lung cancer].

OBJECTIVE: To detect the expression of AT-rich sequence-binding protein (SATB1) mRNA in non-small cell lung cancer (NSCLC) and explore the role of SATB1 in the development of NSCLC. METHODS: The total RNA was extracted from NSCLC tissues and normal lung tissues and reverse transcribed into cDNA. Real-time fluorescence quantitative RT-PCR was performed for detecting the expression of SATB1 mRNA these tissues. RESULTS: The expression of SATB1 mRNA was 13-fold higher in NSCLC tissues than in normal lung tissues (P<0.001), and in metastatic and nonmetastatic NSCLC, the expression was 23.63 and 5.57 folds that in normal lung tissues, respectively. CONCLUSION: SATB1 mRNA expression might be associated with the development and lymph node metastasis of NSCLC and may potentially used as an indicator for predicting the prognosis of NSCLC.