Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

Serum bile acid profiles are associated with heart failure with preserved ejection fraction in patients with metabolic dysfunction-associated fatty liver disease: An exploratory study.

AIM: To analyse the association between serum bile acid (BA) profile and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: We enrolled 163 individuals with biopsy-proven MAFLD undergoing transthoracic echocardiography for any indication. HFpEF was defined as left ventricular ejection fraction >50% with at least one echocardiographic feature of HF (left ventricular diastolic dysfunction, abnormal left atrial size) and at least one HF sign or symptom. Serum levels of 38 BAs were analysed using ultra-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: Among the 163 patients enrolled (mean age 47.0 ± 12.8 years, 39.3% female), 52 (31.9%) and 43 (26.4%) met the HFpEF and pre-HFpEF criteria, and 38 serum BAs were detected. Serum ursodeoxycholic acid (UDCA) and hyocholic acid (HCA) species were lower in patients with HFpEF and achieved statistical significance after correction for multiple comparisons. Furthermore, decreases in glycoursodeoxycholic acid and tauroursodeoxycholic acid were associated with HF status. CONCLUSIONS: In this exploratory study, specific UDCA and HCA species were associated with HFpEF status in adults with biopsy-confirmed MAFLD.

Organic-Inorganic Hybrid Crystal-Assisted Etching of Nickel Foam for the Collectively Exhaustive Electrochemical Performance of Oxygen Evolution Reaction.

In this work, an organic-inorganic hybrid crystal, violet-crystal (VC), was used to etch the nickel foam (NF) to fabricate a self-standing electrode for the water oxidation reaction. The efficacy of VC-assisted etching manifests the promising electrochemical performance towards the oxygen evolution reaction (OER), requiring only ~356 and ~376 mV overpotentials to reach 50 and 100 mA cm-2 , respectively. The OER activity improvement is attributed to the collectively exhaustive effects arising from the incorporation of various elements in the NF, and the enhancement of active site density. Furthermore, the self-standing electrode is robust, exhibiting a stable OER activity after 4,000 cyclic voltammetry cycles, and ~50 h. The anodic transfer coefficients (αa ) show that the first electron transfer step is the rate-determining step on the surface of NF-VCs-1.0 (NF etched by 1 g of VCs) electrode, while the chemical step involving dissociation following the first electron transfer step is identified as the rate-limiting step in other electrodes. The lowest Tafel slope value observed in the NF-VCs-1.0 electrode indicates the high surface coverage of oxygen intermediates and more favorable OER reaction kinetics, as confirmed by high interfacial chemical capacitance and low charge transport/interfacial resistance. This work demonstrates the importance of VCs-assisted etching of NF to activate the OER, and the ability to predict reaction kinetics and rate-limiting step based on αa values, which will open new avenues to identify advanced electrocatalysts for the water oxidation reaction.

A Secondary Al-CO2 Battery Enabled by Aluminum Iodide as a Homogeneous Redox Mediator.

As an emerging energy storage concept, Al-CO2 batteries have not yet been demonstrated as a rechargeable system that can deliver a high discharge voltage and a high capacity. In this work, we present a homogeneous redox mediator to access a rechargeable Al-CO2 battery with an ultralow overpotential of 0.05 V. In addition, the resulting rechargeable Al-CO2 cell can maintain a high discharge voltage of 1.12 V and delivers a high capacity of 9394 mAh/gcarbon. Nuclear magnetic resonance (NMR) analysis indicates that the discharge product is aluminum oxalate which can facilitate the reversible operation of Al-CO2 batteries. The rechargeable Al-CO2 battery system demonstrated here holds great promise as a low-cost and high-energy alternative for future grid energy storage applications. Meanwhile, the Al-CO2 battery system could facilitate capture and concentration of atmospheric CO2, ultimately benefiting both the energy and environmental sectors of society.

Environmental evaluation of radioactivity levels and associated radiation hazards in groundwater around the WIPP site.

Groundwater may contain radioactive substances which can be dangerous to human health. Concentrations of natural radionuclides polonium (Po), thorium (Th), uranium (U), and radium (Ra) isotopes were measured in groundwater samples collected from different locations in the vicinity of the Waste Isolation Pilot Plant (WIPP) site in Carlsbad, New Mexico. The average values of gross activity concentrations of 210Po, 228Th, 238U, 234U, 226Ra and 228 Ra isotopes were determined to be 1.62 Bq L-1 in shallow groundwater and 5.88 Bq L-1 in deep groundwater, respectively. The total radioactivity in deep groundwater was higher than that in shallow groundwater, and most of the radioactivity in the water is from 226Ra. Furthermore, the effective doses for ingestion of natural radionuclides were about 0.333 mSv y-1 for shallow groundwater and about 1.338 mSv y-1 for deep groundwater samples, which are higher than the World Health Organization (WHO, 2017) guideline level (0.1 mSv y-1) for drinking water. Ra dominated the total ingestion dose, contributing 93.06 % and 75.40 % of the total effective doses to the deep and shallow groundwater, respectively. The ingrowth and decay of natural radionuclides suggested that 228Ra/226Ra ratio can be a useful indicator of the source of radioactive contamination. The radioactivity data obtained from the investigated groundwater samples can be used to establish a baseline for radioactivity levels in groundwater around the WIPP site.

Role of contrast-enhanced ultrasonography in MR-guided focused ultrasound ablation on uterus fibroids: lesion selection and assessment of ablative effects.

OBJECTIVES: To determine whether contrast-enhanced ultrasonography (CEUS) can be used for selecting lesions and assessing the ablative effects of MRgFUS ablation on uterus fibroids, compared with MR imaging. METHODS: This retrospective study was approved by the institutional review board of our hospital. From April 2018 to November 2019, a total of 44 symptomatic fibroids in 38 patients who underwent MRgFUS ablation were included. The association between pre-ablation characteristics on CEUS/MR imaging and the non-perfusion volume (NPV) after ablation was analyzed using multivariable linear regression analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve values was compared between the CEUS and MR imaging regression models. NPV after ablation was compared between CEUS and enhanced MR imaging. RESULTS: On CEUS, entangled branch vessels, fast-in, and fast-out patterns were significantly associated with NPV, with an AUC of 0.95 (95% CI; 0.88, 1.00). On MR imaging, hyper-intensity on T2-weighted images (T2WI), hyper-intense ring-like signal on T2WI images, and hyper-enhancement on contrast-enhanced T1WI images were correlated with NPV, with an AUC of 0.86 (95% CI; 0.70, 1.00). After ablation, no differences in NPV were noted between contrast-enhanced T1WI (84.13 ± 75.42 cm3) and CEUS (80.22 ± 76.49 cm3). CONCLUSIONS: Some pre-ablation characteristics of uterine fibroids on CEUS were associated with NPV after MRgFUS. CEUS may contribute to the evaluation of ablative outcomes and patient selection, similar to MR imaging. KEY POINTS: • Contrast-enhanced ultrasonography (CEUS) is effective for selecting the appropriate uterine fibroids before MR-guided focused ultrasound (MRgFUS) ablation and evaluating non-perfusion volumes (NPV) after ablation, as a potential alternative to MR imaging. • Before ablation, entangled branch vessels, fast-in, and fast-out patterns on CEUS were significantly associated with NPV after MRgFUS. • No significant differences in NPV were detected between contrast-enhanced T1WI and CEUS after ablation.

A functional peptide-mediated colorimetric assay for mercury ion based on dual-modified gold nanoparticles.

In the work, a rapid and accurate biosensor for mercury ions (Hg2+) was constructed, with which aggregation of dual-modified (DGPFHR- and CALNN-) gold nanoparticles (D/C-AuNPs) could be triggered by the high specificity of peptides to Hg2+. The given peptide DGPFHR possesses great capability of capturing Hg2+, accompanied by the conformational folding. Under the circumstances, D/C-AuNPs were employed as the detection probes to accomplish the quantitative analysis of Hg2+. This is primarily because the specific Hg2+-induced folding of peptides reduces the electrostatic repulsion and steric hindrance, thus accelerating the AuNPs aggregation. The principle and application potential of this proposal was proved by evidence. And the results demonstrated that Hg2+ ions could be selectively detected as low as 28 nM with a linear range of 100-800 nM. In consideration of superior simplicity, selectivity, accuracy and stability, the protocol was advantageous over other projects in practical measurement of various water samples.

Helicobacter pylori infection with atrophic gastritis: An independent risk factor for colorectal adenomas.

BACKGROUND: The significance of Helicobacter pylori (H. pylori) infection and atrophic gastritis (AG) in the prevalence of colorectal adenomas has been examined in a limited number of studies. However, these studies reported disputed conclusions. AIM: To investigate whether H. pylori infection, AG, and H. pylori-related AG increase the risk of colorectal adenomas. METHODS: This retrospective cross-sectional study included 6018 health-check individuals. The relevant data for physical examination, laboratory testing, 13C-urea breath testing, gastroscopy, colonoscopy and histopathological examination of gastric and colorectal biopsies were recorded. Univariate and multivariate logistic regression analyses were performed to determine the association between H. pylori-related AG and colorectal adenomas. RESULTS: Overall, 1012 subjects (16.8%) were diagnosed with colorectal adenomas, of whom 143 (2.4%) had advanced adenomas. Among the enrolled patients, the prevalence of H. pylori infection and AG was observed as 49.5% (2981/6018) and 10.0% (602/6018), respectively. Subjects with H. pylori infection had an elevated risk of colorectal adenomas (adjusted odds ratio [OR] of 1.220, 95% confidence interval (CI): 1.053-1.413, P = 0.008) but no increased risk of advance adenomas (adjusted OR = 1.303, 95%CI: 0.922-1.842, P = 0.134). AG was significantly correlated to an increased risk of colorectal adenomas (unadjusted OR = 1.668, 95%CI: 1.352-2.059, P < 0.001; adjusted OR = 1.237, 95%CI: 0.988-1.549, P = 0.064). H. pylori infection accompanied by AG was significantly associated with an increased risk of adenomas (adjusted OR = 1.491, 95%CI: 1.103-2.015, P = 0.009) and advanced adenomas (adjusted OR = 1.910, 95%CI: 1.022-3.572, P = 0.043). CONCLUSION: H. pylori-related AG was associated with a high risk of colorectal adenomas and advanced adenomas in Chinese individuals.

[A comparative study of technique of humeral ending insertion of rotator cuff under arthroscopy and traditional techniques in the treatment of giant rotator cuff tear].

OBJECTIVE: To explore the feasibility of arthroscopic humeral ending insertion of rotator cuff, and to provide a scheme for the treatment of giant rotator cuff tears. METHODS: From February 2014 to April 2018, 40 patients with giant rotator cuff tears were operated on and divided into two groups. The study group consisted of 20 patients, including 8 males and 12 females, aged 42 to 82(57.55±8.90) years, with a course of 1 h to 2 years;the treatment of giant rotator cuff tears was carried out by using the technique of rotator cuff moving inward at the humeral head stop and reconstructing complete rotator cuff. The control group consisted of 20 patients, including 10 males and 10 females, aged 45 to 75 (57.75±9.10) years, with a course of 1 h to 5 years;after traditional cleaning, part of the rotator cuff was sutured or in situ high tension suture was used to treat the huge rotator cuff tear. The clinical effect of the two groups was evaluated by VAS, constant and UCLA. RESULTS: All patients were followed up for 12 to 14 months. The VAS, Constant score, UCLA score before operation of two groups were significantly improved compared with those before operation (P<0.05);the VAS, Constant score, UCLA score and excellent effect of the study group were significantly better than those of the control group (P<0.05). CONCLUSION: Arthroscopic transposition of rotator cuff and humerus ending insertion is a feasible method for the treatment of giant rotator cuff tears, which relieves shoulder pain and improves function satisfactorily.

Risk scores for predicting dysphagia in critically ill patients after cardiac surgery.

BACKGROUND: This study aimed at developing and validating a scoring model to stratify critically ill patients after cardiac surgery based on risk for dysphagia, a common but often neglected complication. METHODS: Data were prospectively collected and analyzed from January 2016 to June 2017 from 395 consecutive post cardiac surgery patients at the cardiac care unit (CCU) at a single center; 103 (26.1%) developed dysphagia. Univariate and multivariate logistic analyses were used to identify independent predictors for dysphagia. The survival nomogram was developed on the basis of a multivariable Cox model, which allowed us to obtain survival probability estimations. The predictive performance of the nomogram was verified for discrimination and calibration. Areas under receiver operating characteristic curve analysis were used to illustrate and evaluate the diagnostic performance of the novel model. RESULTS: The final novel scoring model, named SSG-OD, consists of three independent factors: gastric intubation (OR = 1.024, 95% CI 1.015-1.033), sedative drug use duration (OR = 1.031, 95% CI 1.001-1.063) and stroke or not (OR = 6.182, 95% CI 3.028-12.617). SSG-OD identified patients at risk for dysphagia with sensitivity of 68.5% and specificity of 89.0% (OR = 0.833, 95% CI: 0.782-0.884). The positive and negative likelihood ratios were 6.22 and 0.35. CONCLUSIONS: The novel SSG-OD scoring system to risk stratify CCU patients for dysphagia is an easy-to-use bedside prognostication aid with good predictive performance and the potential to reduce aspiration incidence and accelerate recovery.

Rational design of an anchoring peptide for high-efficiency and quantitative modification of peptides and DNA strands on gold nanoparticles.

The pentapeptide Cys-Ala-Leu-Asn-Asn (CALNN) could stabilize gold nanoparticles (AuNPs), most of which serve as anchoring blocks for various bioanalyses by introducing recognition blocks. However, the typical conjugation strategy greatly suffers from excessive use of peptides, overnight incubation and consequently low efficiency. In this study, new design criteria for the efficacious anchor were established. In addition, a stable, instantaneous and effective modification of the anchoring peptide RRFPDD or its derivatives on AuNPs is first proposed for the first time. With low consumption of peptides (50 µM), the loading process could be realized in 100 seconds. The anchor RRFPDD also allowed for the quantitative adsorption of appended recognition blocks (e.g., peptides or DNAs), thus adjusting their proportions for better performance. In particular, the biological characteristics of those recognition blocks were fully retained. Furthermore, the anchor RRFPDD contributed to a time-saving and high-efficiency (85%) hydrolysis of peptide-capped AuNPs. Considering these advantages of the new anchor, a reliable assay for cardiac troponin I (cTnI) was developed with a detection limit as low as 0.45 ng mL-1, and also successfully applied in human serum samples.

Effects of silibinin-loaded thermosensitive liposome-microbubble complex on inhibiting rabbit liver VX2 tumors in sub-hyperthermia fields.

In the present study, the effects of silibinin-loaded thermosensitive liposome-microbubble complex (STLMC) on rabbit liver VX2 tumors in sub-hyperthermia fields were investigated using two-dimensional ultrasonography (2D US), contrast-enhanced US (CEUS), hematoxylin and eosin (H&E) staining, immunohistochemistry and ultrastructure observation. 50 rabbits with VX2 liver tumors were divided into five groups: Sub-hyperthermia microwave ablation group (SHM), STLMC injection group (STLMC), SHM ablation plus STLMC injection group (SHM + STLMC), microbubble injection group and blank control group without any treatment. Rabbits in each group were examined using 2D US and CEUS in order to evaluate the tumor volume and diameter before treatment and at day 7 and 21 after treatment. Morphology, expression of CD163 and CD206, and ultrastructure of the tumors were assessed. The average post-treatment volume of tumors in group SHM + STLMC was 1.17±0.88 cm3 at day 7 and 2.15±0.96 cm3 at day 21, which was significantly decreased compared with all other groups (P<0.05). H&E staining indicated that the number of disordered macrophages in the SHM + STLMC group significantly increased compared with the other groups (P<0.05). Immunohistochemical results demonstrated that in the SHM + STLMC, the expression of CD163 and CD206 significantly decreased compared with all other groups (P<0.05). These results suggested that STLMC has a potential function in preventing tumor growth, which may be due to its inhibitory effect on tumor-associated macrophages in the tumor microenvironment.

Percutaneous Radiofrequency Ablation of Obstructive Right Ventricular Giant Myxoma.

Surgical resection is the conventional therapeutic action for patients with an obstructive cardiac tumor. However, for patients in poor clinical condition, cardiac operation can be risky. We report on the successful percutaneous radiofrequency (RF) ablation treatment of a right ventricular giant myxoma in a 70-year-old woman with right ventricular outflow tract (RVOT) and pulmonary artery stenosis, who was unable to tolerate operation. The treatment was effective in relieving RVOT stenosis and improving symptoms. We believe the RF ablation may also be used as a supplementary technique for the treatment of obstructive cardiac tumors, when only partial resection is possible.

Impact of non-alcoholic fatty liver disease and smoking on colorectal polyps.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) and smoking have similar mechanisms of promoting colorectal polyps. The potential link between NAFLD and smoking in men and colorectal polyps has not been adequately evaluated. The aim is to investigate this association. METHODS: A retrospective cross-sectional study was conducted on 2409 individuals undergoing a health check. Univariate and multivariate logistic regression were performed for analyzing the association between risk factors and colorectal polyps. Individuals were divided into four groups: Q1: NAFLD (-)/smoking (-); Q2: NAFLD (+)/smoking (-); Q3: NAFLD (-)/smoking (+); Q4: NAFLD (+)/smoking (+). Logistic analyses were used to explore associations for the whole study population and stratified groups. RESULTS: The prevalence of colorectal polyps was 38.8% in males, and that of colorectal polyps in smokers and individuals with NAFLD were 47.0% (428/911) and 42.9% (267/622), respectively. With Q1 as reference, subjects with NAFLD (+) and smoking habits (+) had the highest ORs for colorectal polyps (OR = 2.64, 95% CI: 1.91 - 3.64, P < 0.001), adenomatous polyps (OR = 2.06, 95% CI: 1.38 - 3.05, P < 0.05), non-adenomatous polyps (OR = 1.97, 95% CI: 1.39 - 2.80, P < 0.05), ≥ 3 polyps (OR = 2.05, 95% CI: 1.31 - 3.22, P < 0.05) and proximal polyps (OR = 1.58, 95% CI: 1.02 - 2.45, P < 0.05) after adjusting for confounding variables. CONCLUSIONS: Men with NAFLD and smoking habits have an increasing risk of colorectal polyps.

Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking.

Background: Low-intensity ultrasound (LIUS) was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies. Determination of the molecular mechanisms underlying the anti-inflammatory effects of LIUS allows to optimize this technique as a therapy for the treatment of malignancies and aseptic inflammatory disorders. Methods: We conducted cutting-edge database mining approaches to determine the anti-inflammatory mechanisms exerted by LIUS. Results: Our data revealed following interesting findings: (1) LIUS anti-inflammatory effects are mediated by upregulating anti-inflammatory gene expression; (2) LIUS induces the upregulation of the markers and master regulators of immunosuppressor cells including MDSCs (myeloid-derived suppressor cells), MSCs (mesenchymal stem cells), B1-B cells and Treg (regulatory T cells); (3) LIUS not only can be used as a therapeutic approach to deliver drugs packed in various structures such as nanobeads, nanospheres, polymer microspheres, and lipidosomes, but also can make use of natural membrane vesicles as small as exosomes derived from immunosuppressor cells as a novel mechanism to fulfill its anti-inflammatory effects; (4) LIUS upregulates the expression of extracellular vesicle/exosome biogenesis mediators and docking mediators; (5) Exosome-carried anti-inflammatory cytokines and anti-inflammatory microRNAs inhibit inflammation of target cells via multiple shared and specific pathways, suggesting exosome-mediated anti-inflammatory effect of LIUS feasible; and (6) LIUS-mediated physical effects on tissues may activate specific cellular sensors that activate downstream transcription factors and signaling pathways. Conclusions: Our results have provided novel insights into the mechanisms underlying anti-inflammatory effects of LIUS, and have provided guidance for the development of future novel therapeutic LIUS for cancers, inflammatory disorders, tissue regeneration and tissue repair.

High stability of gold nanoparticles towards DNA modification and efficient hybridization via a surfactant-free peptide route.

With the assistance of peptides, a stable and highly efficient approach for the quick loading of thiol-DNA onto AuNPs is proposed with a high DNA utilization, which is generally applicable to specific DNA detection and diverse AuNP sizes. The maximum efficiency of hybridization reached 93% while the reaction time was shortened to 30 min.

Sex-influenced association of non-alcoholic fatty liver disease with colorectal adenomatous and hyperplastic polyps.

AIM: To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and colorectal adenomatous and hyperplastic polyps. METHODS: A retrospective cross-sectional study was conducted on 3686 individuals undergoing health checkups (2430 males and 1256 females). All subjects underwent laboratory testing, abdominal ultrasonography, colonoscopy, and an interview to ascertain the baseline characteristics and general state of health. Multinomial logistic regression analysis was performed to examine the association between NAFLD and the prevalence of colorectal adenomatous and hyperplastic polyps. Furthermore, the relationship was analyzed in different sex groups. Subgroup analysis was performed based on number, size, and location of colorectal polyps. RESULTS: The prevalence of colorectal polyps was 38.8% in males (16.2% for adenomatous polyps and 9.8% for hyperplastic polyps) and 19.3% in females (8.4% for adenomatous polyps and 3.9% for hyperplastic polyps). When adjusting for confounding variables, NAFLD was significantly associated with the prevalence of adenomatous polyps (OR = 1.28, 95%CI: 1.05-1.51, P < 0.05) and hyperplastic polyps (OR = 1.35, 95%CI: 1.01-1.82, P < 0.05). However, upon analyzing adenomatous and hyperplastic polyps in different sex groups, the significant association remained in males (OR = 1.53, 95%CI: 1.18-2.00, P < 0.05; OR = 1.42, 95%CI: 1.04-1.95, P < 0.05) but not in females (OR = 0.44, 95%CI: 0.18-1.04, P > 0.05; OR = 1.18, 95%CI: 0.50-2.78, P > 0.05). CONCLUSION: NAFLD is specifically associated with an increased risk of colorectal adenomatous and hyperplastic polyps in men. However, NAFLD may not be a significant factor in the prevalence of colorectal polyps in women.

Establishment and Characterization of a Nude Mouse Model of Subcutaneously Implanted Tumors and Abdominal Metastasis in Gastric Cancer.

A mouse gastric cancer model is an important tool for studying the mechanisms of gastric cancer. To establish subcutaneously implanted tumors, MKN-45 cell suspensions and tumor tissues were implanted into the middle of the right armpit of nude mice. To generate an abdominal metastasis model, MKN-45 cell suspensions and tumor tissue homogenates were implanted into the middle of the lower abdomen. We measured the weights of the nude mice and the longest dimension, shortest dimension, thickness, and volume of the tumor. We also analyzed the rate of tumor formation, the time required for tumor formation, and the number and size of abdominal tumors in the mice. The rates of formation of the subcutaneously implanted tumors were 100%, 0%, and 100% in the nude mice inoculated with 2 × 107 cells/mL or 1 × 107 cells/mL of the MKN-45 cell suspension or the tumor tissue homogenate (2 × 107 cells/mL), respectively. The rates of metastatic abdominal tumor formation were 100%, 50%, and 75% in mice inoculated with 5 × 107 cells/mL or 1 × 107 cells/mL of the tumor tissue homogenate or the MKN-45 cell suspension (5 × 107 cells/mL), respectively. We derived tumor tissues and tumor tissue homogenates from nude mice prior to establishing the subcutaneous model of implanted tumors and the abdominal metastasis model of gastric cancer, respectively.

MicroRNA-29b Inhibits Angiogenesis by Targeting VEGFA through the MAPK/ERK and PI3K/Akt Signaling Pathways in Endometrial Carcinoma.

OBJECTIVE: The purpose of this study is to explore the effects of microRNA-29b (miR-29b) regulating MAPK/ERK and PI3K/Akt signaling pathways on angiogenesis in endometrial carcinoma (EC) by targeting VEGFA. METHODS: Between February 2013 and April 2015, 126 EC patients admitted to the Second Affiliated Hospital of Nanchang University were randomly selected, with 126 EC tissues and the corresponding adjacent normal tissues collected after surgery. The human EC cell lines RL-95-2 and HEC-1-B and human endometrial cells were assigned to the normal group (human endometrial cells), the blank group (untransfected RL-95-2 or HEC-1-B cells), the pMIR-control group (RL-95-2 or HEC-1-B cells transfected with an empty vector), the pMIR-miR-29b group (RL-95-2 or HEC-1-B cells transfected with the miR-29b plasmid), LNA-control group (RL-95-2 or HEC-1-B cells transfected with an oligonucleotide inhibitors control), the LNA-miR-29b inhibitors group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors), the LNA-miR-29b inhibitors + PD98059 group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and PD98059, an inhibitor of the MAPK/ERK signaling pathway) and the LNA-miR-29b inhibitors + wortmannin group (RL-95-2 or HEC-1-B cells transfected with miRCURY LNATM miR-29b inhibitors and wortmannin, an inhibitor of the PI3K/Akt signaling pathway). qRT-PCR and Western blotting were conducted to detect the miR-29b expression and the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2. Immunohistochemistry (IHC) was performed to determine the microvessel density (MVD) expression in the EC tissues, adjacent normal tissues and nude-mice. RESULTS: Compared with the adjacent normal tissues, miR-29b expression was down-regulated, the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were up-regulated, and MVD expression was increased in the EC tissues. Compared with the normal group, miR-29b expression was down-regulated, while the mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were up-regulated in the other groups. Compared with the blank, pMIR-control and LNA-control groups, miR-29b expression was increased, while mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 were decreased in the pMIR-miR-29b group. The LNA-miR-29b inhibitors group exhibited elevated miR-29b expression and decreased mRNA and protein expressions of VEGFA, ERK, Akt, mTOR and Bcl-2 (All P < 0.05). Additionally, miR-29b expression was reduced in the LNA-miR-29b inhibitors + PD98059 and LNA-miR-29b inhibitors + wortmannin groups. In comparison to the normal group, MVD expression was elevated in the other groups. Compared with the blank, pMIR-control, LNA-control, LNA-miR-29b inhibitors + PD98059 and LNA-miR-29b inhibitors + wortmannin groups, MVD expression was decreased in the pMIR-miR-29b group but increased in the LNA-miR-29b inhibitors group. CONCLUSION: Our results indicate that miR-29b negatively modulates the MAPK/ERK and PI3K/Akt signaling pathways to inhibit angiogenesis in EC by targeting VEGFA.

Granulocytic sarcoma of the breast: A case report.

Granulocytic sarcoma (GS) is an unusual type of tumor composed of immature cells outside the bone marrow. The disease exhibits a correlation with acute myeloid leukemia and other myeloproliferative disorders. Although it can invade a number of areas of the body, the involvement of the breast is uncommon. The present study reports the case of a 58-year-old female with a mildly tender lump in the left breast that had been apparent for one year. Available diagnostic techniques, including ultrasound, magnetic resonance imaging and mammography, were systematically used to determine a diagnosis of GS, and lumpectomy and systemic chemotherapy were performed. The patient was satisfied with the result of no local recurrence at the one year follow-up examination. The present study discusses the clinical and pathological characteristics of the present case of GC.