UBXN11 Predicts as a Poor Index for Colorectal Cancer and Contributes to the Tumorigenesis by Activating NF-κB Signaling.

BACKGROUND: The complex mechanisms of colorectal cancer (CRC) pathogenesis and progression remain poorly understood. This study endeavors to unravel the role of UBXN11within the context of CRC. METHODS: UBXN11 expression level in CRC, stomach adenocarcinoma and esophageal carcinoma, and the overall survival in corresponding cancers were analyzed using UALCAN database. Human CRC cell lines and xenograft mouse model with UBXN11 overexpression were established to investigate the pathological role of UBXN11 in CRC progression. Luciferase assay, qPCR, and Western blot were performed to dissect the interaction between UBXN11 and NF-κB signaling. RESULTS: Heightened UBXN11 expression was observed in various digestive tract tumors, which was positively correlated with the reduced overall survival rates in CRC patients. Overexpression of UBXN11 significantly enhanced CRC cell proliferation in vitro and promoted tumor growth in vivo. Mechanistically, UBXN11 promoted CRC tumorigenesis through increasing the activation of NF-κB signaling pathway. CONCLUSIONS: This study underscores the pivotal role of UBXN11 in CRC progression and paves the way for novel therapeutic strategies for CRC treatment.

The coumarin component isofraxidin targets the G-protein-coupled receptor S1PR1 to modulate IL-17 signaling and alleviate ulcerative colitis.

OBJECTIVE: The increasing global prevalence of ulcerative colitis (UC) underscores the imperative to explore novel therapeutic approaches. Traditional Chinese medicine has historically shown potential in addressing this ailment. The current study aimed to elucidate the functional attributes and underlying mechanisms of isofraxidin, a coumarin derivative from Acanthopanax, in the context of UC. METHODS: A murine model of dextran sodium sulfate (DSS)-induced UC was established, and we conducted a comprehensive assessment of the influence of isofraxidin on UC symptomatology, colonic histopathological manifestations, the inflammatory response, and apoptosis. The potential receptor of isofraxidin was initially identified through the Target database and molecular docking analysis. Subsequent in vivo and in vitro experiments were conducted to determine the effects of isofraxidin on the identified receptor and associated signaling pathways. Transfection was used to examine the receptor's role in the regulatory mechanism of isofraxidin. RESULTS: Isofraxidin reduced UC symptoms and colonic histopathological impairments. Furthermore, isofraxidin ameliorated the DSS-induced inflammatory response and apoptosis in tissues. S1PR1 was identified as a target of isofraxidin and effectively suppressed activation of the IL-17 signaling pathway. Intriguingly, cellular experiments indicated that overexpression of S1PR1 counteracted the protective effect of isofraxidin. DISCUSSION: In summary, our investigation revealed that isofraxidin could modulate S1PR1 and regulate the IL-17 signaling pathway, thus ameliorating DSS-induced UC. These findings establish a robust foundation for considering isofraxidin as a prospective therapeutic intervention to treat UC.

Constructing models for Crohn's disease diagnosis and prediction of infliximab non-response based on angiogenesis-related genes.

Background: Angiogenesis response plays a crucial role in the occurrence and development of Crohn's disease (CD) and may involve the mechanism of infliximab non-response. However, the role of angiogenesis-related genes in Crohn's disease has not been comprehensively studied. This study aimed to explore the expression profiles of angiogenesis-related genes in CD patients and construct models for disease diagnosis and prediction of infliximab non-response. Methods: CD-related microarray datasets were collected from the GEO database. Unsupervised consensus clustering analysis was performed based on differentially expressed angiogenesis-related genes to divide CD samples into two distinct clusters. Weighted gene co-expression network analysis (WGCNA) was conducted on the clusters to identify angiogenesis-related module. Based on the differentially expressed genes in the module, machine learning algorithms were employed to further identify hub genes and construct a disease diagnostic model. Subsequently, treatment outcome-related genes were extracted from these hub genes, and a predictive model for infliximab non-response in CD patients was ultimately built. Results: Based on angiogenesis-related genes, we identified two distinct CD clusters (C1 and C2). Compared to C1, the metabolic pathways in C2 were significantly upregulated, and there was a higher abundance of cell clusters such as M1 macrophages and plasma cells. Additionally, C2 showed a poorer response to infliximab. Furthermore, a predictive model for infliximab non-response in CD patients was constructed based on the hub genes, and it was successfully validated using an external dataset. Conclusion: Comprehensive analysis of angiogenesis-related genes revealed different clusters of CD, which exhibited differential response rates to infliximab. The construction of models provides a reference for disease diagnosis and drug selection, aiding in clinical decision-making.

In Vivo Base Editing of Scn5a Rescues Type 3 Long QT Syndrome in Mice.

BACKGROUND: Pathogenic variants in SCN5A can result in long QT syndrome type 3, a life-threatening genetic disease. Adenine base editors can convert targeted A T base pairs to G C base pairs, offering a promising tool to correct pathogenic variants. METHODS: We generated a long QT syndrome type 3 mouse model by introducing the T1307M pathogenic variant into the Scn5a gene. The adenine base editor was split into 2 smaller parts and delivered into the heart by adeno-associated virus serotype 9 (AAV9-ABEmax) to correct the T1307M pathogenic variant. RESULTS: Both homozygous and heterozygous T1307M mice showed significant QT prolongation. Carbachol administration induced Torsades de Pointes or ventricular tachycardia for homozygous T1307M mice (20%) but not for heterozygous or wild-type mice. A single intraperitoneal injection of AAV9-ABEmax at postnatal day 14 resulted in up to 99.20% Scn5a transcripts corrected in T1307M mice. Scn5a mRNA correction rate >60% eliminated QT prolongation; Scn5a mRNA correction rate <60% alleviated QT prolongation. Partial Scn5a correction resulted in cardiomyocytes heterogeneity, which did not induce severe arrhythmias. We did not detect off-target DNA or RNA editing events in ABEmax-treated mouse hearts. CONCLUSIONS: These findings show that in vivo AAV9-ABEmax editing can correct the variant Scn5a allele, effectively ameliorating arrhythmia phenotypes. Our results offer a proof of concept for the treatment of hereditary arrhythmias.

Trends and projections of ovarian cancer incidence in Hong Kong: A population-based study.

INTRODUCTION: This study analyzed the incidence of ovarian cancer in Hong Kong and its association with age, calendar period and birth cohort, made projections through 2030, and attributed differences in new cancer cases to demographic and epidemiologic changes. MATERIAL AND METHODS: Incidence data for ovarian cancer were obtained from the Hong Kong Cancer Registry. We employed the age-period-cohort modeling approach to investigate the association between ovarian cancer incidence and age in Hong Kong women, with particular emphasis on examining the changing trends of period and cohort effects on incidence. We projected the incidence of ovarian cancer in Hong Kong between 2018 and 2030 and attributed the rise in new cancer cases to epidemiologic and demographic shifts. RESULTS: Between 1990 and 2017, a total of 11 182 women were diagnosed with ovarian cancer in Hong Kong. Crude and age-standardized rates increased from 8.2 and 7.8 per 100 000 person-years to 16.3 and 11.5 per 100 000 person-years, respectively. New cases of ovarian cancer rose from 225 in 1990 to 645 in 2017. We observed an increased risk of ovarian cancer throughout the study period and in the post-1940 birth cohort. The projected incidence rate and new cases of ovarian cancer are expected to continue growing due to demographic and epidemiologic changes such as fertility patterns and lifestyle factors, with an estimated 981 cases in 2030. CONCLUSIONS: The period risk and cohort risk of ovarian cancer among Hong Kong women is increasing. Demographic and epidemiologic changes may continue to increase ovarian cancer incidence and new cases in Hong Kong.

Metabolomics reveals the defense mechanism of histidine supplementation on high-salt exposure-induced hepatic oxidative stress.

AIMS: This study mainly evaluated the protective mechanism of histidine against the hepatic oxidative stress after high-salt exposure (HSE) through combined analysis of non-targeted metabolomics and biological metabolic networks. MATERIALS AND METHODS: Dahl salt-sensitive (SS) rats were fed with normal-salt diet or HSE ± histidine in addition to drinking water for 14 days. Gas chromatography-mass spectrometry was used to analyze the hepatic metabolites. The metabolic profile was analyzed by SIMCA-14.1, the metabolic correlation network was performed using Gephi-0.9.2, and pathway enrichment was analyzed using MetaboAnalyst 5.0 online website. KEY FINDINGS: Results indicated that HSE disturbed the hepatic metabolic profile, generated abnormal liver metabolism and exacerbated oxidative stress. Histidine supplementation significantly reversed the hepatic metabolic profile. Of note, 14 differential metabolic pathways were enriched after histidine supplementation, most of which played an important role in ameliorating redox and nitric oxide (NO) metabolism. Histidine administration decreased the levels of hydroperoxide and malondialdehyde, and increased the activities of antioxidant enzymes (Catalase, Superoxide Dismutase, Glutathione S-transferase and Glutathione reductases). Histidine effectively enhanced the endogenous synthesis of glutathione by increasing the levels of glutamate and cysteine, thereby enhancing the antioxidant capacity of the glutathione system. After histidine administration, lysine, glutamate, and hypotaurine owned a higher metabolic centrality in the correlation network. In addition, histidine could also effectively increase the endogenous synthesis of NO by enhancing the L-arginine/NO pathway. SIGNIFICANCE: This study offers new insights into the metabolic mechanisms underlying the antioxidant protective effect of histidine on the liver.

Supplementation of amino acids and organic acids prevents the increase in blood pressure induced by high salt in Dahl salt-sensitive rats.

A high-salt (HS) diet leads to metabolic disorders in Dahl salt-sensitive (SS) rats, and promotes the development of hypertension. According to the changes in the metabolites of SS rats, a set of combined dietary supplements containing amino acids and organic acids (AO) were designed. The purpose of the present study was to evaluate the effect of AO supplementation on the blood pressure of SS rats after the HS diet and clarify the mechanism of AO by metabolomics and biochemical analyses. The results showed that AO supplementation avoided the elevation of blood pressure induced by the HS diet in SS rats, increased the renal antioxidant enzyme activities (catalase, superoxide dismutase, glutathione reductase, and glutathione S-transferase), reduced the H2O2 and MDA levels, and restored the normal antioxidant status of the serum and kidneys. AO also reversed the decrease in the nitric oxide (NO) levels and NO synthase activity induced by the HS feed, which involved the L-arginine/NO pathway. Metabolomics analysis showed that AO administration increased the levels of amino acids such as cysteine, glycine, hypotaurine, and lysine in the renal medulla and the levels of leucine, isoleucine, and serine in the renal cortex. Of note, lysine, hypotaurine and glycine had higher metabolic centrality in the metabolic correlation network of the renal medulla after AO administration. In conclusion, AO intervention could prevent HS diet-induced hypertension in SS rats by restoring the metabolic homeostasis of the kidneys. Hence, AO has the potential to become a functional food additive to improve salt-sensitive hypertension.

ß-Aminoisobutyric acid supplementation attenuated salt-sensitive hypertension in Dahl salt-sensitive rats through prevention of insufficient fumarase.

The human Dietary Approaches to Stop Hypertension-Sodium Trial has shown that ß-aminoisobutyric acid (BAIBA) may prevent the development of salt-sensitive hypertension (SSHT). However, the specific antihypertensive mechanism remains unclear in the renal tissues of salt-sensitive (SS) rats. In this study, BAIBA (100 mg/kg/day) significantly attenuated SSHT via increased nitric oxide (NO) content in the renal medulla, and it induced a significant increase in NO synthesis substrates (L-arginine and malic acid) in the renal medulla. BAIBA enhanced the activity levels of total NO synthase (NOS), inducible NOS, and constitutive NOS. BAIBA resulted in increased fumarase activity and decreased fumaric acid content in the renal medulla. The high-salt diet (HSD) decreased fumarase expression in the renal cortex, and BAIBA increased fumarase expression in the renal medulla and renal cortex. Furthermore, in the renal medulla, BAIBA increased the levels of ATP, ADP, AMP, and ADP/ATP ratio, thus further activating AMPK phosphorylation. BAIBA prevented the decrease in renal medullary antioxidative defenses induced by the HSD. In conclusion, BAIBA's antihypertensive effect was underlined by the phosphorylation of AMPK, the prevention of fumarase's activity reduction caused by the HSD, and the enhancement of NO content, which in concert attenuated SSHT in SS rats.

Global burden attributable to high sodium intake from 1990 to 2019.

BACKGROUND AND AIMS: High sodium intake is associated with a higher risk of a wide range of diseases. We aimed to estimate the pattern and trend of the global disease burden associated with high sodium intake from 1990 to 2019. METHODS AND RESULTS: We obtained numbers and rates of death and disability-adjusted life year (DALY) attributable to high sodium intake by sex, socio-demographic index, and country from the Global Burden of Disease Study 2019. We calculated the estimated annual percentage change to evaluate the age-standardized rate (ASR) of the burden attributable to high sodium intake between 1990 and 2019. We further calculated the contribution of population growth, population aging, and age-specific rates of death and DALY to the net change in the total number of deaths and DALYs attributable to high sodium intake. From 1990 to 2019, global age-standardized rates of death and DALY attributable to high sodium intake substantially decreased for both sexes. However, there were significant increases in the total numbers of deaths and DALYs attributable to high sodium intake, which were driven by population growth and population aging. The attribution of population growth and population aging varied widely across countries, with a higher contribution of population growth in most developing countries and a higher contribution of population aging in countries with slow population growth. CONCLUSIONS: Although the global burden attributable to high sodium intake in terms of age-standardized rate declined from 1990 to 2019, the absolute burden increased significantly, which was driven by population growth and population aging.

Ginsenoside Rh7 Suppresses Proliferation, Migration and Invasion of NSCLC Cells Through Targeting ILF3-AS1 Mediated miR-212/SMAD1 Axis.

It is reported that ginsenosides have a significant anti-tumor effect on a variety of tumors. However, the role and mechanism of Rh7 in non-small cell lung cancer (NSCLC) are unclear. In this study, we aimed to study the anti-tumor effect of Rh7 on the proliferation and progression of NSCLC. Bioinformatics analysis showed that ILF3-AS1 was regulated by ginsenoside Rh7 in NSCLC. Down-regulation of ILF3-AS1 could significantly inhibit the proliferation, metastasis and invasion of NSCLC. In addition, ILF3-AS1 negatively controlled miR-212, which in turn targeted SMAD1 expression, thereby regulating NSCLC cell viability and apoptosis. Our results indicate that ILF3-AS1 can be used as a diagnostic and therapeutic target for non-small cell lung cancer. It is discovered for the first time that ginsenoside Rh7 inhibits the expression of ILF3-AS1 and exerts antitumor effects.

Protective effect of oral histidine on hypertension in Dahl salt-sensitive rats induced by high-salt diet.

AIMS: Salt-sensitive hypertension is a risk factor for cardiovascular disease. Previous studies have shown that insufficient arginine in the kidney caused by metabolic imbalance is an important factor in salt-sensitive hypertension. Whether the high nitrogen content of histidine can affect the balance of nitrogen metabolism in Dahl salt-sensitive (SS) rats. This article aimed to study the effects of oral histidine on salt-sensitive hypertension, kidney damage and metabolic patterns of high-salt diet in SS rats. MAIN METHODS: Adult rats were divided into four groups, and blood pressure was measured using a non-invasive tail-cuff system. Gas chromatography-mass spectrometry analyzed metabolites in serum and kidney tissues. KEY FINDINGS: High-salt diet significantly increased the blood pressure of rats and aggravated kidney damage. Of note, histidine can attenuate salt-sensitive hypertension and kidney damage by improving metabolic pattern, reducing Reactive Oxygen Species (ROS) and increasing nitric oxide levels in SS rats. SIGNIFICANCE: These results suggest that histidine could be a potential adjuvant to prevent and control salt-sensitive hypertension.

Endothelial transdifferentiation of human HGC-27 gastric cancer cells in vitro.

Malignant tumor cells are able to transdifferentiate into other cell types in various tissues or organs. Recent studies have demonstrated the ability of cancer cells to transdifferentiate into functional endothelial cells (ECs). However, whether human gastric cancer (GC) cells are able to transdifferentiate into other cell types has remained largely elusive. Furthermore, whether HGC-27 cells are able to participate in GC angiogenesis remains to be clarified. In the present study, the HGC-27 cell line grown under hypoxic conditions for 4 days exhibited the typical 'flagstone' appearance, which is typical for cultured ECs. HGC-27 cells cultured on Matrigel under hypoxic conditions gradually formed net-like structures. Furthermore, the cultured HGC-27 cells expressed CD31, CD34 and von Willebrand factor, the molecular markers for ECs, under hypoxic conditions. These results indicated that HGC-27 cells, cultured under hypoxic conditions, are able to transdifferentiate into EC-like cells in vitro.

Ginsenoside Rg3 enhances the anticancer effect of 5­FU in colon cancer cells via the PI3K/AKT pathway.

Chemotherapy is one of the most commonly used treatments for patients with advanced colon cancer, yet the toxicity of chemotherapy agents, such as 5­fluorouracil (5­FU), limits the effectiveness of chemotherapy. Ginsenoside Rg3 (Rg3) is an active ingredient isolated from ginseng. Rg3 has been shown to display anticancer effects on a variety of malignancies. Yet, whether Rg3 synergizes the effect of 5­FU to inhibit the growth of human colon cancer remains unknown. The present study was designed to ascertain whether Rg3 is able to enhance the anti­colon cancer effect of 5­FU. The results revealed that combined treatment of Rg3 and 5­FU significantly enhanced the inhibition of the proliferation, colony formation, invasion and migration of human colon cancer cells (SW620 and LOVO) in vitro. We also found that combined treatment of Rg3 and 5­FU significantly enhanced the apoptosis of colon cancer cells by activating the Apaf1/caspase 9/caspase 3 pathway and arrested the cell cycle of the colon cancer cells in G0/G1 by promoting the expression of Cyclin D1, CDK2 and CDK4. In addition, the PI3K/AKT signaling pathway in colon cancer cells was suppressed by Rg3 and 5­FU. In vivo, Rg3 synergized the effect of 5­FU to inhibit the growth of human colon cancer xenografts in nude mice. Similarly, combined treatment of Rg3 and 5­FU altered the expression of colon cancer protein in vivo and in vitro. Collectively, the present study demonstrated that ginsenoside Rg3 enhances the anticancer effect of 5­FU in colon cancer cells via the PI3K/AKT pathway.

Oriented Neural Spheroid Formation and Differentiation of Neural Stem Cells Guided by Anisotropic Inverse Opals.

Isotropic inverse opal structures have been extensively studied for the ability to manipulate cell behaviors such as attachment, migration, and spheroid formation. However, their use in regulate the behaviors of neural stem cells has not been fully explored, besides, the isotropic inverse opal structures usually lack the ability to induce the oriented cell growth which is fundamental in neural regeneration based on neural stem cell therapy. In this paper, the anisotropic inverse opal substrates were obtained by mechanically stretching the poly (vinylidene fluoride) (PVDF) inverse opal films. The anisotropic inverse opal substrates possessed good biocompatibility, optical properties and anisotropy, provided well guidance for the formation of neural spheroids, the alignment of neural stem cells, the differentiation of neural stem cells, the oriented growth of derived neurons and the dendritic complexity of the newborn neurons. Thus, we conclude that the anisotropic inverse opal substrates possess great potential in neural regeneration applications.

Epigallocatechin gallate reverses gastric cancer by regulating the long noncoding RNA LINC00511/miR-29b/KDM2A axis.

Epigallocatechin gallate (EGCG), as one of the main ingredients of green tea, has been reported to have potential prevention on a variety of solid tumors. However, the system-wide molecular mechanisms targeted to EGCG's anti-tumor effect have not been illustrated. Here, AGS and SGC7901 GC cells were used to investigate the EGCG-mediated change of gene expression. Our data showed that EGCG retarded cell growth and promoted cell death of GC in dose-dependent manner. Analyses based on transcription, translation as well as function were performed to explore the elusive anticancer role of EGCG. Of them, cell cycle was probably implicated key pathway of EGCG. Besides, our data revealed numerous LncRNAs activated after EGCG treatment. In this study, LINC00511 was discovered to be suppressed by EGCG and highly expressed in GC cells and tissues. Knockdown of LINC00511 inhibited cell growth and promoted cell death ratio in GC. Additionally, our data suggested LINC00511 could decrease the expression of miR-29b, followed by inducing GC development. Knockdown of miR-29b recovered the effects of LINC00511 silencing. In addition, we found overexpression of KDM2A, a target of miR-29b, would rescue the level of LINC00511. All the data showed that the LINC00511/miR-29b/KDM2A axis can be used as a diagnostic and therapeutic target for GC.

Green Tea Polyphenol EGCG Attenuates MDSCs-mediated Immunosuppression through Canonical and Non-Canonical Pathways in a 4T1 Murine Breast Cancer Model.

Several studies in the past decades have reported anti-tumor activity of the bioactive compounds extracted from tea leaves, with a focus on the compound epigallocatechin-3-gallate (EGCG). However, further investigations are required to unravel the underlying mechanisms behind the anti-tumor activity of EGCG. In this study, we demonstrate that EGCG significantly inhibits the growth of 4T1 breast cancer cells in vitro and in vivo. EGCG ameliorated immunosuppression by significantly decreasing the accumulation of myeloid-derived suppressor cells (MDSCs) and increasing the proportions of CD4+ and CD8+ T cells in spleen and tumor sites in 4T1 breast tumor-bearing mice. Surprisingly, a low dose of EGCG (0.5-5 µg/mL) effectively reduced the cell viability and increased the apoptosis rate of MDSCs in vitro. EGCG down-regulated the canonical pathways in MDSCs, mainly through the Arg-1/iNOS/Nox2/NF-κB/STAT3 signaling pathway. Moreover, transcriptomic analysis suggested that EGCG also affected the non-canonical pathways in MDSCs, such as ECM-receptor interaction and focal adhesion. qRT-PCR further validated that EGCG restored nine key genes in MDSCs, including Cxcl3, Vcan, Col4a1, Col8a1, Oasl2, Mmp12, Met, Itsnl and Acot1. Our results provide new insight into the mechanism of EGCG-associated key pathways/genes in MDSCs in the murine breast tumor model.

miR-25 Promotes Cardiomyocyte Proliferation by Targeting FBXW7.

Induction of endogenous cardiomyocyte (CM) proliferation is one of the key strategies for heart regeneration. Increasing evidence points to the potential role of microRNAs (miRNAs) in the regulation of CM proliferation. Here, we used human embryonic stem cell (hESC)-derived CMs (hESC-CMs) as a tool to identify miRNAs that promote CM proliferation. We profiled miRNA expression at an early stage of CM differentiation and identified a list of highly expressed miRNAs. Among these miRNAs, miR-25 was enriched in early-stage hESC-CMs, but its expression decreased over time. Overexpression of miR-25 promoted CM proliferation. RNA sequencing (RNA-seq) analysis revealed that genes related to cell-cycle signal were strongly influenced by miR-25 overexpression. We further showed that miR-25 promoted CM proliferation by targeting FBXW7. Finally, the function of miR-25 in the regulation of CM proliferation was demonstrated in zebrafish. Our study suggested that miR-25 is a promising molecule for heart regeneration.

Short-term outcomes of double versus single pyloromyotomy at peroral endoscopic pyloromyotomy in the treatment of gastroparesis (with video).

BACKGROUND AND AIMS: The prevalence of gastroparesis (Gp), a chronic debilitating disorder, and resulting hospitalizations are increasing. Gastric peroral endoscopic pyloromyotomy (POP or GPOEM) is a novel technique in the treatment of refractory Gp. Despite the initial promising results of GPOEM, one-third of patients do not exhibit any clinical response. Furthermore, loss of clinical response was reported in several studies. No response or loss of response after GPOEM may be related to inadequate myotomy. The aim of our study is to examine whether double pyloromyotomy at GPOEM is superior to single pyloromyotomy. METHOD: A retrospective case-controlled study of patients who underwent GPOEM for refractory Gp at our tertiary care institution between June 2015 and March 2018 was performed. Because the follow-up time for the single myotomy group was much longer than that of the double myotomy group, we matched the length of follow-up for the single myotomy group to that of the double myotomy group. The outcomes were measured by the changes in the Gastroparesis Cardinal Symptom Index (GCSI) before and 3 to 6 months after the procedure. Adverse events and other procedural and clinical parameters were also compared. RESULTS: Ninety patients underwent GPOEM (55 single and 35 double pyloromyotomy). The mean age was 47 ± 14 years, and the mean duration of symptoms was 5.3 ± 4.4 years. The average GCSI score was 3.8 before the GPOEM, and the average GCSI score 6 months after procedure was 1.8. Thirty-seven of 55 (67%) patients who underwent single pyloromyotomy achieved clinical response compared with 30 of 35 (86%) patients who underwent double pyloromyotomy. There were no significant differences for procedure time, postoperative pain, or length of hospital stay between the 2 groups. There was no difference in adverse events in the 2 pyloromyotomy groups. CONCLUSION: Double pyloromyotomy is a safe and feasible technique during GPOEM. Clinical success was higher in patients undergoing double pyloromyotomy compared with single pyloromyotomy in this nonrandomized, short-term follow-up study. Long-term studies are needed to further confirm our results.

Evaluation of Plasma Extracellular Vesicle MicroRNA Signatures for Lung Adenocarcinoma and Granuloma With Monte-Carlo Feature Selection Method.

Extracellular Vesicle (EV) is a compilation of secreted vesicles, including micro vesicles, large oncosomes, and exosomes. It can be used in non-invasive diagnosis. MicroRNAs (miRNAs) processed by exosomes can be detected by liquid biopsy. To objectively evaluate the discriminative ability of miRNAs from whole plasma, EV and EV-free plasma, we analyzed the miRNA expression profiles in whole plasma, EV and EV-free plasma of 10 lung adenocarcinoma and 9 granuloma patients. With Monte-Carlo feature selection method, the top discriminative miRNAs in whole plasma, EV and EV-free plasma were identified, and they were quite different. Using the Repeated Incremental Pruning to Produce Error Reduction (RIPPER) method, we learned the classification rules: in whole plasma, granuloma patients did not express hsa-miR-223-3p while the lung adenocarcinoma patients expressed hsa-miR-223-3p; in EV, the hsa-miR-23b-3p was highly expressed in granuloma patients but not lung adenocarcinoma patients; in EV-free plasma, hsa-miR-376a-3p was expressed in granuloma patients but barely expressed in lung adenocarcinoma patients. For prediction performance, whole plasma had the highest weighted accuracy and EV outperformed EV-free plasma. Our results suggested that EV can be used as lung cancer biomarker. However, since it is less stable and not easy to detect, there are still technological difficulties to overcome.

THBS4 predicts poor outcomes and promotes proliferation and metastasis in gastric cancer.

Gastric cancer (GC), a common and lethal cancer in the world, has a high risk of metastasis. Our study was to explore the effects of THBS4 on GC progress and metastasis and the underlying mechanisms. The proliferations of MGC-803 and BGC-823 cells were analyzed via cell count, MTT, and soft agar colony formation assay. The migration and invasion of transfected GC cells was investigated via transwell migration and invasion assay. The mRNA abundance of THBS4 and KLF9 was detected by quantitative real-time PCR (qPCR). The analysis of Gene Expression Omnibus (GEO) dataset (GSE26253) suggested that THBS4 was up-regulated in recurrent GC patients and was positively correlated with the increase in pathological stage and poor prognosis in GC. THBS4 stimulated the proliferations of GC cells. Moreover, THBS4 overexpression fostered the migration and invasion of GC cells. Further, the bioinformatics analysis of the cancer genome atlas dataset suggested that there may be a positive correlation between THBS4 and KLF9 expression. QPCR analysis proved that transfected with THBS4 overexpression plasmid enhanced KLF9 expression in GC cells. THBS4 mRNA and protein expression were up-regulated in MGC-803 and BGC-823 cells compared to those in non-tumoral gastric cells. KLF9 overexpression significantly stimulated the proliferation and metastasis of MGC-803 and BGC-823 cells. Besides, KLF9 siRNA inhibited the enhanced viability, migration, and invasion of MGC-803 cells caused by the transfection with THBS4 overexpression plasmid. In conclusion, THBS4 had positive effects on GC proliferation and metastasis via targeting KLF9.