Nomogram to predict recurrent chest pain in patients with myocardial bridging.

OBJECTIVE: Patients with myocardial bridging (MB) frequently experience recurrent chest pain, even in those without coronary heart disease. This study aims to predict the risk of recurrent chest pain in patients with MB by using a novel predictive nomogram. METHODS: This retrospective study enrolled 250 patients with acute chest pain who underwent coronary computed tomography angiography (CCTA) between January and December 2018, including 111 patients with MB and 139 control patients. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses were used to screen for significant parameters that were included to develop a novel predictive nomogram model. Receiver operating characteristic curve, calibration curve, and decision curve analyses were used to evaluate the performance and clinical utility of the nomogram. RESULTS: A predictive nomogram was constructed in 111 patients with MB, 34 of whom (30.9%) had recurrent chest pain. The significant predictors screened out by the LASSO regression included age, sex, branch type MB, and systolic compression index. The area under the curves (AUCs) for recurrent chest pain at 12, 24, and 36 months were 0.688, 0.742, and 0.729, respectively, indicating remarkable accuracy of the nomogram. The calibration curve and decision curve analyses indicated a good agreement with the observations and utility of the nomogram. CONCLUSIONS: This study presents a high-accuracy nomogram to predict recurrent chest pain in patients with MB. This model incorporates clinical risk factors and CT imaging features and can be conveniently used to facilitate the individualised prediction. KEY POINTS: • Symptomatic patients with myocardial bridging often present with recurrent chest pain. • The potential predictors of recurrent chest pain in patients with myocardial bridging were age, sex, branch type MB, and systolic compression index. • Nomogram based on clinical CT imaging features is valuable to predict recurrent chest pain in patients with myocardial bridging.

Host miRNAs-microbiota interactions in gastric cancer.

It is widely acknowledged that gastric cancer seriously affects the quality of life and survival of patients. The correlation between the microbiota and gastric cancer has attracted extensive attention in recent years, nonetheless the specific mechanism of its impact on gastric cancer remain largely unclear. Recent studies have shown that in addition to its role in the host's inflammatory and immune response, the microbiota can also affect the occurrence and development of gastric cancer by affecting the expression of miRNAs. This paper brings together all currently available data on miRNAs, microbiota and gastric cancer, and preliminarily describes the relationship among them.

Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization.

BACKGROUND: Polydatin, a glucoside of resveratrol, has been shown to have protective effects against various diseases. However, little is known about its effect on hepatic ischemia-reperfusion (I/R) injury. This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism. METHODS: After gavage feeding polydatin once daily for a week, mice underwent a partial hepatic I/R procedure. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hematoxylin-eosin (H&E) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response and reactive oxygen species (ROS) production was also investigated. Furthermore, immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages. RESULTS: Compared with the I/R group, polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis. The oxidative stress marker (dihydroethidium fluorescence, malondialdehyde, superoxide dismutase and glutathione peroxidase) and I/R related inflammatory cytokines (interleukin-1ß, interleukin-10 and tumor necrosis factor-α) were significantly suppressed after polydatin treatment. In addition, the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro. Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway. CONCLUSIONS: Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NF-κB signaling.

Reduced plasma level of basic fibroblast growth factor is associated with incomplete device endothelialization at six months following left atrial appendage closure.

OBJECTIVES: To investigate whether inflammatory and growth factors (IGFs) were associated with incomplete device endothelialization (IDE) at 6 months after successful left atrial appendage closure (LAAC). BACKGROUND: IDE after LAAC is correlated with device-related thrombus (DRT) formation and subsequent thromboembolic events. However, biomarkers for early detection of IDE remain lacking. METHODS: Plasma levels of IGFs including basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), stromal cell derived factor (SDF)-1a, transforming growth factor (TGF)-ß1, vascular growth factor receptor-1 (VEGF-R1) and von Willebrand factor (vWF) were determined using ELISA kits in 55 consecutive patients with atrial fibrillation (AF) at 6 months after LAAC with Watchman devices. The status of device endothelialization was assessed by transesophageal echocardiography and cardiac CT. RESULTS: IDE and complete device endothelialization(CDE)were detected in 38 and 17 patients, respectively. Among the six IGFs, only plasma level of bFGF was significantly lower in patients with IDE compared to those with CDE (303.49 ± 246.84 vs. 556.31 ± 197.84 pg/ml, p < 0.001). C-statistics of plasma bFGF for discriminating patients with IDE from those with CDE was 0.785 (95 % CI: 0.663-0.907, p < 0.001), with a cut-off value of 440.52pg/ml (sensitivity 0.765; specificity 0.789). Multivariate logistic regression model showed that lower bFGF was an independent factor for IDE (OR: 11.752, 95 % CI: 2.869-48.144, P = 0.001). bFGF improved the classification of patients (NRI: 0.677,95 % CI: 0.320-1.033, p = 0.004). CONCLUSIONS: Reduced plasma bFGF level confers an increased risk for IDE after LAAC. Further prospective studies are warranted to examine if bFGF could serve as a biomarker for IDE post LAAC.

Influence of malformation of right coronary artery originating from the left sinus in hemodynamic environment.

BACKGROUND: The anomalous origin of the right coronary artery (RCA) from the left coronary artery sinus (AORL) is one of the abnormal origins of the coronary arteries. Most of these issues rarely have any effects on human health, but some individuals may exhibit symptoms, such as myocardial ischemia or even sudden death. Recently, researchers have investigated the AORL through clinical cases, but studies based on computational fluid dynamics (CFD) have rarely been reported. In this study, the hemodynamic changes between the normal origin of the RCA and the AORL are compared based on numerical simulation results. METHODS: Realistic three-dimensional (3D) models of the 16 normal right coronary arteries and 26 abnormal origins of the RCAs were constructed, respectively. The blood flow was numerically simulated using the ANSYS software. This study used a one-way fluid-solid coupling finite element model, wherein the blood is assumed to be an incompressible Newtonian fluid, and the vessel is assumed to be made of an isotropic linear elastic material. RESULTS: The cross-sectional area differences between the inlet of the normal group and that of the abnormal group were significant (P < 0.0001). Moreover, there were significant differences in the volumetric flow (P = 0.0001) and pressure (P = 0.0002). Positive correlation exists for the ratio of the cross-sectional area of the RCA to the inlet area of the ascending aorta (AAO), and the ratio of the inlet volumetric flow of the RCA to the volumetric flow of the AAO, in the normal (P = 0.0001, r = 0.8178) and abnormal (P = 0.0033, r = 0.6107) groups. CONCLUSION: This study demonstrates that the cross-sectional area of the AORL inlet may cause ischemia symptoms. The results obtained by this study may contribute to the further understanding of the clinical symptoms of the AORL based on the hemodynamics.

A velocity-based impedance control system for a low impact docking mechanism (LIDM).

In this paper, an impedance control algorithm based on velocity for capturing two low impact docking mechanisms (LIDMs) is presented. The main idea of this algorithm is to track desired forces when the position errors of two LIDMs are random by designing the relationship between the velocity and contact forces measured by a load sensing ring to achieve low impact docking. In this paper, the governing equation of an impedance controller between the deviation of forces and velocity is derived, and simulations are designed to verify how impedance parameters affect the control characteristics. The performance of the presented control algorithm is validated by using the MATLAB and ADAMS software for capturing simulations. The results of capturing simulations demonstrate that the impedance control algorithm can respond fast and has excellent robustness when the environmental errors are random, and the contact forces and torques satisfy the low impact requirements.

Revolutionary multi-omics analysis revealing prognostic signature of thyroid cancer and subsequent in vitro validation of SNAI1 in mediating thyroid cancer progression through EMT.

Thyroid carcinoma (TC), the most commonly diagnosed malignancy of the endocrine system, has witnessed a significant rise in incidence over the past few decades. The integration of scRNA-seq with other sequencing approaches offers researchers a distinct perspective to explore mechanisms underlying TC progression. Therefore, it is crucial to develop a prognostic model for TC patients by utilizing a multi-omics approach. We acquired and processed transcriptomic data from the TCGA-THCA dataset, including mRNA expression profiles, lncRNA expression profiles, miRNA expression profiles, methylation chip data, gene mutation data, and clinical data. We constructed a tumor-related risk model using machine learning methods and developed a consensus machine learning-driven signature (CMLS) for accurate and stable prediction of TC patient outcomes. 2 strains of undifferentiated TC cell lines and 1 strain of PTC cell line were utilized for in vitro validation. mRNA, protein levels of hub genes, epithelial-mesenchymal transition (EMT)-associated phenotypes were detected by a series of in vitro experiments. We identified 3 molecular subtypes of TC based on integrated multi-omics clustering algorithms, which were associated with overall survival and displayed distinct molecular features. We developed a CMLS based on 28 hub genes to predict patient outcomes, and demonstrated that CMLS outperformed other prognostic models. TC patients of relatively lower CMLS score had significantly higher levels of T cells, B cells, and macrophages, indicating an immune-activated state. Fibroblasts were predominantly enriched in the high CMLS group, along with markers associated with immune suppression and evasion. We identified several drugs that could be suitable for patients with high CMLS, including Staurosporine_1034, Rapamycin_1084, gemcitabine, and topotecan. SNAI1 was elevated in both undifferentiated TC cell lines, comparing to PTC cells. Knockdown of SNAI1 reduced the cell proliferation and EMT phenotypes of undifferentiated TC cells. Our findings highlight the importance of multi-omics analysis in understanding the molecular subtypes and immune characteristics of TC, and provide a novel prognostic model and potential therapeutic targets for this disease. Moreover, we identified SNAI1 in mediating TC progression through EMT in vitro.

An Enhanced IDBO-CNN-BiLSTM Model for Sentiment Analysis of Natural Disaster Tweets.

The Internet's development has prompted social media to become an essential channel for disseminating disaster-related information. Increasing the accuracy of emotional polarity recognition in tweets is conducive to the government or rescue organizations understanding the public's demands and responding appropriately. Existing sentiment analysis models have some limitations of applicability. Therefore, this research proposes an IDBO-CNN-BiLSTM model combining the swarm intelligence optimization algorithm and deep learning methods. First, the Dung Beetle Optimization (DBO) algorithm is improved by adopting the Latin hypercube sampling, integrating the Osprey Optimization Algorithm (OOA), and introducing an adaptive Gaussian-Cauchy mixture mutation disturbance. The improved DBO (IDBO) algorithm is then utilized to optimize the Convolutional Neural Network-Bidirectional Long Short-Term Memory (CNN-BiLSTM) model's hyperparameters. Finally, the IDBO-CNN-BiLSTM model is constructed to classify the emotional tendencies of tweets associated with the Hurricane Harvey event. The empirical analysis indicates that the proposed model achieves an accuracy of 0.8033, outperforming other single and hybrid models. In contrast with the GWO, WOA, and DBO algorithms, the accuracy is enhanced by 2.89%, 2.82%, and 2.72%, respectively. This study proves that the IDBO-CNN-BiLSTM model can be applied to assist emergency decision-making in natural disasters.

Brain Network for Exploring the Change of Brain Neurotransmitter 5-Hydroxytryptamine of Autism Children by Resting-State EEG.

The study was aimed at understanding the brain network and the change rule of brain neurotransmitter 5-hydroxytryptamine (5-HT) in autism children through resting-state electroencephalogram (EEG). 20 autistic children in hospital were selected and defined as the observation group. Meanwhile, 20 healthy children were defined as the control group. EEG signals were collected for the two groups. Fuzzy C-means (FCM) algorithm was used to extract features of EEG signals, and DTF was applied for the causal association between multichannel EEG signals. The two groups were compared for the average function value and regional efficiency of the brain neurotransmitter 5-HT. The results showed that the classification accuracy of frontal F7 channel, left frontal FP1 channel, and temporal T6 channel was 95.2%, 95.3%, and 91.2%, respectively. The average of high beta frequency band, low beta frequency band, theta frequency band, and alpha frequency band in the control group was significantly higher than that in the observation group under the optimal threshold (P < 0.05). Compared with normal subjects (34.27), the average function of 5-HT in the brain was 20.13 in patients with low function and 45.74 in patients with hyperfunction. In conclusion, FCM algorithm can feature extraction of EEG signals, especially in the frontal F7 channel, the left frontal FP1 channel, and the TEMPORAL T6 channel, which has high classification accuracy and can well express the EEG signals of autistic children. The level of 5-HT in autistic children is lower than that in healthy people, and it is closely related to loneliness and depression.

Identification of Tumor Mutation Burden, Microsatellite Instability, and Somatic Copy Number Alteration Derived Nine Gene Signatures to Predict Clinical Outcomes in STAD.

Genomic features, including tumor mutation burden (TMB), microsatellite instability (MSI), and somatic copy number alteration (SCNA), had been demonstrated to be involved with the tumor microenvironment (TME) and outcome of gastric cancer (GC). We obtained profiles of TMB, MSI, and SCNA by processing 405 GC data from The Cancer Genome Atlas (TCGA) and then conducted a comprehensive analysis though "iClusterPlus." A total of two subgroups were generated, with distinguished prognosis, somatic mutation burden, copy number changes, and immune landscape. We revealed that Cluster1 was marked by a better prognosis, accompanied by higher TMB, MSIsensor score, TMEscore, and lower SCNA burden. Based on these clusters, we screened 196 differentially expressed genes (DEGs), which were subsequently projected into univariate Cox survival analysis. We constructed a 9-gene immune risk score (IRS) model using LASSO-penalized logistic regression. Moreover, the prognostic prediction of IRS was verified by receiver operating characteristic (ROC) curve analysis and nomogram plot. Another independent Gene Expression Omnibus (GEO) contained specimens from 109 GC patients was designed as an external validation. Our works suggested that the 9-gene-signature prediction model, which was derived from TMB, MSI, and SCNA, was a promising predictive tool for clinical outcomes in GC patients. This novel methodology may help clinicians uncover the underlying mechanisms and guide future treatment strategies.

Cisplatin plus anti-PD-1 antibody enhanced treatment efficacy in advanced esophageal squamous cell carcinoma.

Therapies for patients with advanced esophageal squamous cell carcinoma (ESCC) are limited and accompanied by dismal prognosis. Here we use ESCC cell line K30 and TE-1 to investigate the antitumor efficacy of cisplatin plus anti-PD-1 antibody. Enhanced antitumor effects and increased CD8+ tumor-infiltrating lymphocytes of combination therapy were observed in TE-1 cells bearing humanized mice model. Lower cell viability and more cell apoptosis were found in the combination therapy in vitro. We next analyzed clinical data from patients with advanced ESCC received cisplatin-based chemotherapy plus an anti-PD-1 antibody (Tislelizumab or Sintilimab) as first line therapy from two clinical trials (NCT03469557, NCT03748134). With the response rate of 81.8%, duration of response of 15.2 months, median progression-free survival of 15.5 months, median overall survival of 21.5 months and manageable toxicity in patients with advanced ESCC, we demonstrated that cisplatin-based chemotherapy plus anti-PD-1 antibody is an effective and safe option. We further confirmed sublethal cisplatin could induce PD-L1 expression in ESCC cells and cisplatin-treated ESCC cells suppressed the activation and function of immune cells while the addition of sintilimab prevented this process. These results highlight the effectiveness of cisplatin combining with anti-PD-1 antibody in patients with advanced ESCC, revealed its capability to promote the PD-L1 expression in ESCC cells and act synergistically with anti-PD-1 antibody to restore exhausted immune cells activities, thus providing a theoretical basis for further explorations in the mechanism of the combination treatment of cisplatin-based chemotherapy with immune checkpoint inhibitors in ESCC.

ASF1b is a novel prognostic predictor associated with cell cycle signaling pathway in gastric cancer.

Gastric cancer (GC) is one of the most common malignant tumors with poor outcomes. Identification of new therapeutic targets is urgently needed. Accumulating evidence has shown that anti-silencing function 1b (ASF1b) contributes to the progression in multiple cancer types. However, detailed mechanisms of ASF1b tumorigenesis in gastric cancer remain elusive. This study showed that ASF1b was upregulated in GC tissues and remarkably correlated with TNM stage, histological grade and poor prognosis of GC. We induced down and up-regulation of ASF1b in GC cell lines and monitored the changes in their biological behavior. Furthermore, loss of ASF1b was efficient to suppress subcutaneous xenograft tumor growth in vivo. We demonstrate that ASF1b is involved in regulation of cell cycle and PI3K/AKT/mTOR signaling through experiments and database analysis. Mechanistically, ASF1b promoted the proliferation, migration and invasion of GC cells. Taken together, this study highlights the role of ASF1b, which provided new insights into the underlying mechanism of progression and metastasis in GC for the first time.

EXOSC5 promotes proliferation of gastric cancer through regulating AKT/STAT3 signaling pathways.

Purpose: Exosome component 5 (EXOSC5) is a non-catalytic component of the RNA exosome complex, which is interacted with the Zinc-finger antiviral protein to degrade the target RNA and aberrantly expressed in various malignances. We explored the molecular mechanisms and biological roles by which EXOSC5 promotes the progression of GC. Methods: We used quantitative real-time PCR, Western blotting and immunohistochemistry to analyze EXOSC5 expression in GC samples. An GC organoid-based functional model was assessed, and cancer cell CCK-8 assay, colony formation assay and flow cytometry were performed to reveal the role of EXOSC5 in GC cell proliferation and tumorigenesis. In vivo, nude mice tumorigenesis assay were performed to explore the effects of EXOSC5 knockdown on growth of GC. The roles of EXOSC5 on AKT and STAT3 signaling pathways were measured by Western blot. Results: The expression of EXOSC5 was up-regulated in GC tissues and cell lines compared with normal group, and highly expressed EXOSC5 indicated a poorer clinical outcome for GC patients and was positively correlated with tumor size and TNM stage. EXOSC5 overexpression facilitated the growth of GC cells and organoids, while EXOSC5 downregulation inhibited proliferation and induced G1/S phase transition arrest. Moreover, mechanistic studies demonstrated that EXOSC5 increased cyclinD1 expression levels and decreasing the expression levels of p21 and p27 via regulation of the AKT and STAT3 pathway. Conclusion: The expression of EXOSC5 is upregulated and correlated with tumorigenesis and poor prognosis of GC. EXOSC5 increases GC proliferation partly through activating AKT and STAT3 pathways.

Application of discrete shape function in absolute nodal coordinate formulation.

To solve integrals in the absolute nodal coordinate method and address the difficulty in applying it to an arbitrary-section beam, this paper focuses on two methods involving single integrals:the invariant matrix method and the Gerstmayr method, with cross-section characteristics by applying the interpolation of a discrete function. Such single integrals demonstrate that the nodal coordinate method can be applied to an arbitrary-section beam. The Euler-Bernoulli beam used in engineering structures is characterised by a symmetrical cross-section, small section size, zero odd integrals and negligible high-order even integrals, which simplifies the single integrals of the two methods. Finally, the Gaussian integration is adopted to improve the solving efficiency of elastic force and force Jacobian.

Integrated Analysis of Copy Number Variation, Microsatellite Instability, and Tumor Mutation Burden Identifies an 11-Gene Signature Predicting Survival in Breast Cancer.

Genetic variants such as copy number variation (CNV), microsatellite instability (MSI), and tumor mutation burden (TMB) have been reported to associate with the immune microenvironment and prognosis of patients with breast cancer. In this study, we performed an integrated analysis of CNV, MSI, and TMB data obtained from The Cancer Genome Atlas, thereby generating two genetic variants-related subgroups. We characterized the differences between the two subgroups in terms of prognosis, MSI burden, TMB, CNV, mutation landscape, and immune landscape. We found that cluster 2 was marked by a worse prognosis and lower TMB. According to these groupings, we identified 130 differentially expressed genes, which were subjected to univariate and least absolute shrinkage and selection operator-penalized multivariate modeling. Consequently, we constructed an 11-gene signature risk model called the genomic variation-related prognostic risk model (GVRM). Using ROC analysis and a calibration plot, we estimated the prognostic prediction of this GVRM. We confirmed the predictive efficiency of this GVRM by validating it in another independent International Cancer Genome Consortium cohort. Our results conclude that an 11-gene signature developed by integrated analysis of CNV, MSI, and TMB has a high potential to predict breast cancer prognosis, which provided a strong rationale for further investigating molecular mechanisms and guiding clinical decision-making in breast cancer.

The Essential Factors of Establishing Patient-derived Tumor Model.

Establishing an applicable preclinical model is vital for translational cancer research. Patient-derived xenograft has been important preclinical model systems and widely used for cancer research. Patient-derived xenograft models that represent the tumors of the patients are necessary to better translate research discoveries and to test potential therapeutic approaches. However, research in this field is hampered by the limited engraftment rate. In this review, we go over a large number of researches on patient-derived xenograft transplantation and firstly systematically summarize the main factors in methodology to successfully establish models. These results will be applied to the development of patient-derived xenograft leading to better preclinical research.

Comprehensive Roles and Future Perspectives of Exosomes in Peritoneal Metastasis of Gastric Cancer.

Gastric cancer (GC) is one of the most prevalent digestive malignancies. A great number of patients at first visit or post curative resections are diagnosed with widespread metastasis within the peritoneal cavity. Overwhelming evidence has demonstrated that exosomes, a variety of biologically functional extracellular vesicles comprising active factors, mediate the progression and metastasis of GC. Although the regulatory mechanisms of exosomes remain fairly elusive, they are responsible for intercellular communication between tumor cells and normal stroma, cancer-related fibroblasts, immune cells within the primary tumor and metastatic niche. In this review, we provide new insight into the molecular signatures of GC-associated exosomes in reprogramming the tumor microenvironment and the subsequent promotion of peritoneal metastasis-including infiltration of the gastric wall, implantation of tumor cells onto the pre-metastatic peritoneum, and remodeling of the pre-metastatic niche. Based on this review, we hope to draw a more general conclusion for the functions of exosomes in the progression and peritoneal metastasis of GC and highlight the future perspective on strategies targeting exosomes in prognostic biomarkers and therapy for peritoneal metastasis.

Transient numerical simulation of the right coronary artery originating from the left sinus and the effect of its acute take-off angle on hemodynamics.

BACKGROUND: An anomalous origin of the right coronary artery from the left coronary artery sinus is usually characterized by an acute take-off angle. Most affected patients have no clinical symptoms; however, some patients have decreased blood flow into the right coronary artery during exercise, which can lead to symptoms such as myocardial ischemia. Most researchers who have studied an anomalous origin of the right coronary artery from the left coronary artery sinus have done so through clinical cases. In this study, we used numerical simulation to evaluate the hemodynamics of this condition and the effect of an acute take-off angle on hemodynamic parameters. We expect that the results of this study will help in further understanding the clinical symptoms of this anomaly and the hemodynamic impact of an acute take-off angle. METHODS: Three-dimensional models were reconstructed based on the computed tomography images from 16 patients with a normal right coronary artery and 26 patients with an anomalous origin of the right coronary artery from the left coronary artery sinus. A numerical simulation of a two-way fluid-structure interaction was executed with ANSYS Workbench software. The blood was assumed to be an incompressible Newtonian fluid, and the vessel was assumed to be an isotropic, linear elastic material. Hemodynamic parameters and the effect of an acute take-off angle were statistically analyzed. RESULTS: During the systolic period, the wall pressure in the right coronary artery was significantly reduced in patients with an anomalous origin of the right coronary artery (t =1.32 s, P=0.0001; t =1.34-1.46 s, P<0.0001). The wall shear stress in the abnormal group was higher at the beginning of the systolic period (t =1.24 s, P=0.0473; t =1.26 s, P=0.0193; t =1.28 s, P=0.0441). The acute take-off angle was smaller in patients with clinical symptoms (27.81°±4.406°) than in patients without clinical symptoms (31.86°±2.789°; P=0.017). In the symptomatic group, pressure was negatively correlated with the acute take-off angle (P=0.0185-0.0341, r=-0.459 to -0.4167). CONCLUSIONS: This study shows that an anomalous origin of the right coronary artery from the left coronary artery sinus causes changes in hemodynamic parameters, and that an acute take-off angle in patients with this anomaly is associated with terminal ischemia of the right coronary artery.

MiR-301a-5p/SCIN promotes gastric cancer progression via regulating STAT3 and NF-κB signaling.

Objective: Gastric cancer (GC) is a type of highly malignant cancer. Although the diagnostic and therapeutic methods are innovating, the outcome of GC patients is still poor. Therefore, our research was carried out to explore potential molecular mechanism in the diagnosis of GC. Materials and methods: Bioinformatics analyses were used to obtain microRNA and target mRNA of interest. The expression level of miR-301a-5p and Scinderin (SCIN) mRNA were detected by quantitative real-time PCR (qRT-PCR). Western blot assay was used to investigate SCIN protein level. Cell Counting Kit-8 assay (CCK-8) and colony formation assay were used to investigate cell proliferation ability. Transwell assay was employed to examine cell motility. The interaction between miR-301a-5p and SCIN mRNA was verified by dual-luciferase reporter assay. Results: The qRT-PCR analysis revealed that the expression of miR-301a-5p was higher in gastric cancer tissues than para-cancer tissues (P<0.05). Cox regression analysis showed upregulated miR-301a-5p was associated with larger tumor size (P=0.036) and more advanced TNM stage (P=0.048). The Kaplan-Meier analysis showed a correlation between increased miR-301a-5p expression and shorter overall survival (OS)(P=0.018). By using bioinformatic analysis, SCIN was predicted as one of the targets of miR-301a-5p. Overexpressing miR-301a-5p promoted proliferation and motility of GC cells while knockdown of SCIN exhibited the same performance. Further, we verified the alteration of miR-301a-5p and SCIN expression level could affect the epithelial-mesenchymal transition (EMT) progression on GC cells via STAT3 and NF-κB signaling. Conclusion: Highly expressed miR-301a-5p was associated with aggressiveness of GC. Upregulation of miR-301a-5p promoted malignant phenotype of GC by targeting SCIN. The present results indicated miR-301a-5p might be a promising molecule in the prognosis of GC.

Use of 99mTc-sestamibi SPECT/CT imaging in predicting the degree of pathological hyperplasia of the parathyroid gland: semi-quantitative analysis.

BACKGROUND: Previous studies have demonstrated that 99mTc-sestamibi (99mTc-MIBI) Single-Photon Emission Computed Tomography/ Computed Tomography (SPECT/CT) imaging is an effective isotopic technique for locating the parathyroid in secondary hyperparathyroidism (SHPT). This study aimed to explore further the correlation between 99mTc-MIBI SPECT/CT imaging and SHPT to demonstrate the value of 99mTc-MIBI SPECT/CT in evaluating the degree of pathological hyperplasia of the parathyroid gland (PG). METHODS: The demographics, surgical records, and follow-up information of 91 patients were recorded and analyzed. A total of 216 paraffin-embedded PGs of 54 patients were obtained and analyzed. RESULTS: Patients with 99mTc-MIBI negative PG(s) had significantly lower preoperative serum phosphorus and higher serum calcium levels at 6 months postoperatively compared to those with 99mTc-MIBI positive PG(s) (P<0.05). We also found a higher total uptake ratio of the region of interest (URRI) and higher URRI max in the hypocalcemia group than in the non-hypocalcemia group. Both URRI total (P=0.003) and URRI max (P=0.028) were independent risk factors for hypocalcemia 6 months postoperatively. The URRI values of the PGs were significantly positively correlated with glandular weight (R2=0.343, P<0.001), glandular volume (R2=0.240, P<0.001), and degree of pathological hyperplasia (P<0.001). However, the URRI value of the PGs exhibited a notably weak correlation with proliferating cell nuclear antigen (PCNA) (R2=0.035, P=0.006). The area under the receiver operating characteristic curve showed a URRI evaluative value of 0.771 for diffuse and nodular types in 216 PGs (P<0.001). We further evaluated 167 nodular-type PGs, distinguishing between nodular hyperplasia and a single nodule; the URRI evaluative value reached 0.819, which was higher than the volume or weight (P<0.001). CONCLUSIONS: The 99mTc-MIBI SPECT/CT scintigraphy results were related to serum calcium levels at 6 months after total parathyroidectomy with autotransplantation (TPTX+AT), suggesting the occurrence of hypocalcemia (6 months after TPTX+AT). More importantly, this technique effectively evaluated the pathological hyperplasia of PGs preoperatively, and therefore, could assist surgeons in selecting the PGs with the lowest degree of hyperplasia intraoperatively.