Knockdown of ACOT4 alleviates gluconeogenesis and lipid accumulation in hepatocytes.

Acyl-CoA thioesterase 4 (ACOT4) has been reported to be related to acetyl-CoA carboxylase activity regulation; However, its exact functions in liver lipid and glucose metabolism are still unclear. Here, we discovered explored the regulatory roles of ACOT4 in hepatic lipid and glucose metabolism in vitro. We found that the expression level of ACOT4 was significantly increased in the hepatic of db/db and ob/ob mice as well as obese mice fed a high fat diet. Adenovirus-mediated overexpression of ACOT4 promoted gluconeogenesis and high-glucose/high-insulin-induced lipid accumulation and impaired insulin sensitivity in primary mouse hepatocytes, whereas ACOT4 knockdown notably suppressed gluconeogenesis and decreased the triglycerides accumulation in hepatocytes. Furthermore, ACOT4 knockdown increased insulin-induced phosphorylation of AKT and GSK-3ß in primary mouse hepatocytes. Mechanistically, we found that upregulation of ACOT4 expression inhibited AMP-activated protein kinase (AMPK) activity, and its knockdown had the opposite effect. However, activator A769662 and inhibitor compound C of AMPK suppressed the impact of the change in ACOT4 expression on AMPK activity. Our data indicated that ACOT4 is related to hepatic glucose and lipid metabolism, primarily via the regulation of AMPK activity. In conclusion, ACOT4 is a potential target for the therapy of non-alcoholic fatty liver (NAFLD) and type 2 diabetes.

Impact of Metabolic Syndrome on Post-Operative Infection in Patients Undergoing Flexible Ureteroscopy Lithotripsy.

Background: To investigate retrospectively whether metabolic syndrome (MetS) of flexible ureteroscopy (fURS) lithotripsy can be used to predict post-operative infection. Patients and Methods: After screening, 1,110 patients who received fURS lithotripsy for upper urinary tract stones in our center between January 2015 and December 2022 were analyzed retrospectively. Patients were divided into MetS-positive group and MetS-negative group. Post-operative infection was divided into fever, urosepsis, and septic shock. Relevant data during the peri-operative period were collected. Univariable and multivariable logistic regression analyses were adopted to estimate the impact of metabolic syndrome on post-operative infection in patients undergoing fURS lithotripsy. Results: Among the 1,110 patients, 427 tested positive for MetS, whereas 683 tested negative. Eighty-eight patients suffered from fever (67 patients in the MetS-positive group and 21 in the MetS-negative group). Forty-nine patients had urosepsis (29 patients in the MetS-positive group and 20 in the MetS-negative group), of whom seven patients developed septic shock. No patient developed multiple organ failure or died because of infection. The prevalence of post-operative infections in the MetS-positive group was higher than that in the MetS-negative group (p < 0.001). Multivariable logistic regression analyses showed that diabetes mellitus, MetS-positive, positive urine culture, and longer operation time were positively correlated with post-operative fever. Positive MetS, positive urine culture, and longer operation time were strongly correlated with post-operative urosepsis. Conclusions: Metabolic syndrome was found to be associated with post-operative infection in patients undergoing fURS lithotripsy, suggesting it can serve as a predictive factor.

Study of prevalence and risk factors of chemotherapy-induced mucositis in gastrointestinal cancer using machine learning models.

Objective: Chemotherapy-induced mucositis (CIM) significantly impacts clinical outcomes and diminishes the quality of life in patients with gastrointestinal cancer. This study aims to prospectively determine the incidence, severity, and underlying risk factors associated with CIM in this patient population. Methods: To achieve this objective, we introduce a novel Machine Learning-based Toxicity Prediction Model (ML-TPM) designed to analyze the risk factors contributing to CIM development in gastrointestinal cancer patients. Within the winter season spanning from December 15th, 2018 to January 14th, 2019, we conducted in-person interviews with patients undergoing chemotherapy for gastrointestinal cancer. These interviews encompassed comprehensive questionnaires pertaining to patient demographics, CIM incidence, severity, and any supplementary prophylactic measures employed. Results: The study encompassed a cohort of 447 participating patients who provided complete questionnaire responses (100%). Of these, 328 patients (73.4%) reported experiencing CIM during the course of their treatment. Notably, CIM-induced complications led to treatment discontinuation in 14 patients (3%). The most frequently encountered CIM symptoms were diarrhea (41.6%), followed by nausea (37.8%), vomiting (25.1%), abdominal pain (21%), gastritis (10.5%), and oral pain (10.3%). Supplementary prophylaxis was administered to approximately 62% of the patients. The analysis revealed significant correlations between the overall incidence of CIM and gender (p=0.015), number of chemotherapy cycles exceeding one (p=0.039), utilization of platinum-based regimens (p=0.039), and administration of irinotecan (p=0.003). Specifically, the incidence of diarrhea exhibited positive correlations with prior surgical history (p=0.037), irinotecan treatment (p=0.021), and probiotics usage (p=0.035). Conversely, diarrhea incidence demonstrated an adverse correlation with platinum-based treatment (p=0.026). Conclusion: In conclusion, this study demonstrates the successful implementation of the ML-TPM model for automating toxicity prediction with accuracy comparable to conventional physical analyses. Our findings provide valuable insights into the identification of CIM risk factors among gastrointestinal cancer patients undergoing chemotherapy. Furthermore, the results underscore the potential of machine learning in enhancing our understanding of chemotherapy-induced mucositis and advancing personalized patient care strategies.

Proteogenomics in Cancer: Then and Now.

For years, the paths of sequencing technologies and mass spectrometry have occurred in isolation, with each developing its own unique culture and expertise. These two technologies are crucial for inspecting complementary aspects of the molecular phenotype across the central dogma. Integrative multiomics strives to bridge the analysis gap among different fields to complete more comprehensive mechanisms of life events and diseases. Proteogenomics is one integrated multiomics field. Here in this review, we mainly summarize and discuss three aspects: workflow of proteogenomics, proteogenomics applications in cancer research, and the SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis of proteogenomics in cancer research. In conclusion, proteogenomics has a promising future as it clarifies the functional consequences of many unannotated genomic abnormalities or noncanonical variants and identifies driver genes and novel therapeutic targets across cancers, which would substantially accelerate the development of precision oncology.

FGF9 Recruits ß-Catenin to Increase Hepatic ECM Synthesis and Promote NASH-Driven HCC.

Most nonalcoholic steatohepatitis (NASH) patients develop severe fibrosis through extracellular matrix (ECM) accumulation, which can lead to hepatocellular carcinoma (HCC). Fibroblast growth factor 9 (FGF9) is involved in serial types of cancer; however, the specific role of FGF9 in NASH-driven HCC is not fully understood. This study finds that FGF9 is increased in patients with NASH-associated HCC. Furthermore, NASH-driven HCC mice models by feeding wildtype mice with high-fat/high-cholesterol (HFHC) diet and low dose carbon tetrachloride (CCl4 ) treatment is established; and identified that hepatic FGF9 is increased; with severe fibrosis. Additionally, AAV-mediated knockdown of FGF9 reduced the hepatic tumor burden of NASH-driven HCC mice models. Hepatocyte-specific FGF9 transgenic mice (FGF9Alb ) fed with a HFHC diet without CCl4 treatment exhibited an increased hepatic ECM and tumor burden. However, XAV-939 treatment blocked ECM accumulation and NASH-driven HCC in FGF9Alb mice fed with HFHC diet. Molecular mechanism studies show that FGF9 stimulated the expression of ECM related genes in a ß-catenin dependent manner; and FGF9 exerts its effect on ß-catenin stability via the ERK1/2-GSK-3ß signaling pathway. In summary, the data provides evidence for the critical role of FGF9 in NASH-driven HCC pathogenesis; wherein it promotes the tumors formation through the ECM pathway.

Clinical Features and Prognosis of Young and Middle-Aged Adults With Skin Sebaceous Adenocarcinoma.

BACKGROUND: Sebaceous adenocarcinoma (SAC) mostly occurs in the elderly, and SAC in young and middle-aged population is inadequately investigated. OBJECTIVE: To explore the clinical features and prognosis of young and middle-aged adults with SAC. MATERIALS AND METHODS: Patients with skin SAC between ages 18 and 59 years from the Surveillance, Epidemiology, and End Results database (1975-2016) were eligible for this study. RESULTS: Seven hundred thirty-nine cases were identified. The proportion of extraocular SAC in the nonelderly increased from 1975-2005 to 2006-2016 ( p = .001), male predominance was observed in overall patients whereas female predominance in Asian population, and young patients had more head and neck SAC than middle-aged patients ( p = .014). The prognosis of young patients was better than middle-aged patients ( p = .004). Other independent prognostic factors included sex, marital status, tumor size, surgery, chemotherapy, and multiple primary cancer history. CONCLUSION: An increasing proportion of extraocular SAC was observed in young and middle-aged patients, and the young developed more head and neck SAC than the middle-aged. Female predominance was found in Asian population, and female patients had better prognosis. Younger age and married status indicated better prognosis, and around 20% of young and middle-aged patients might have poorer survival because of Muir-Torre syndrome.

Simvastatin Inhibits Tumor Growth and Migration by Mediating Caspase-1-Dependent Pyroptosis in Glioblastoma Multiforme.

OBJECTIVES: Glioblastoma multiforme (GBM) is the most common and lethal central nervous system cancer and is associated with a poor prognosis. Simvastatin, a kind of widely used hypolipidemic agent, has been investigated for its beneficial effects on various types of cancers. The main purpose of this paper is to investigate the potential inhibitory effects of simvastatin on GBM and the underlying mechanism. METHODS: Cell viability and cell cycle of simvastatin-treated U87 and U251 cells were determined by CCK8 assay and flow cytometry, respectively. Additionally, we assessed cell migration and invasion abilities using a wound-healing assay and transwell assay. mRNA and protein expression patterns of caspase-1 and its markers nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) and IL-1ß in different conditions were detected by real-time polymerase chain reaction, immunofluorescence staining, and Western blot. RESULTS: Simvastatin decreased the viability of GBM cells and inhibited cell migration and invasion in a dose-dependent manner. Moreover, suppression of pyroptosis, as characterized by decreased expression of caspase-1, NLRP3, and IL-1ß, was observed. However, use of an miR-214 inhibitor reversed the simvastatin suppressive effect on GBM cells. CONCLUSIONS: Simvastatin inhibits GBM progression by suppressing caspase-1-dependent pyroptosis, regulated by miR-214.

Immediate air exposure vs dressings following primary closure of clean and clean-contaminated surgical wounds: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: It is unknown whether dressings reduce the risk of SSI after clean and clean-contaminated surgery. OBJECTIVE: This meta-analysis was conducted to assess the outcomes of immediate air exposure of surgical sites after primary closure. MATERIALS AND METHODS: A systematic search of Embase, PubMed, and Web of Science from the time of database establishment through October 2021 was performed. The SSI incidence and other surgical wound-associated events were extracted and their effect sizes calculated. RESULTS: Six RCTs with a total of 1243 surgery cases (1228 non-contaminated, 15 contaminated) were included. SSI incidence of 11% and 11.1% was observed for immediate air exposure and dressings, respectively, when pooled irrespective of surgery type (RR, 0.95; 95% CI, 0.68-1.33 [P = .76]). Subgroup analysis showed similar SSI incidence between air exposure and dressings following clean (P = .39) and clean-contaminated surgery (P = .64). Neither gauze dressings (P = .65), film dressings (P = .07), nor tissue glue-as-a-dressing (P = .94) use resulted in significantly lower SSI incidence than air exposure. CONCLUSIONS: This meta-analysis shows that dressings (gauze dressings, film dressings, and tissue glue-as-a-dressing) do not outperform immediate air exposure in terms of SSI occurrence following primary closure of clean and clean-contaminated surgical wounds.

The Impact of ZIP8 Disease-Associated Variants G38R, C113S, G204C, and S335T on Selenium and Cadmium Accumulations: The First Characterization.

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

LINC00942 Promotes Tumor Proliferation and Metastasis in Lung Adenocarcinoma via FZD1 Upregulation.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to play important roles in the progression of human cancers. Herein, bioinformatic analysis identified that LINC00942 was a highly overexpressed lncRNA in lung adenocarcinoma (LUAD). The present study aimed to explore the roles and possible molecular mechanisms of LINC00942 in LUAD. METHODS: First, on the basis of TCGA database, the expression and prognosis of LINC00942 were analyzed in LUAD tissues. Then, si-LINC00942 was transfected into A549 and H1299 cells to knockdown the expression of LINC00942. Cell viability was detected by MTT assay. Flow cytometry was used to analyze cell apoptosis. The expressions of PCNA, Bax, Bcl-2, and wnt/ß-catenin pathway proteins were detected by western blotting. Dual-luciferase reporter assay was used to evaluate the regulatory relationship between LINC00942 and miR-5006-5p, or miR-5006-5p and FZD1. RESULTS: We discovered that LINC00942 was up-regulated in LUAD tissues compared with adjacent tissues. Besides, we found the increased LINC00942 expression was associated with poor survival. In addition, silencing of LINC00942 suppressed the proliferation, migration, invasion and facilitated the apoptosis of A549 and H1299 cells. Moreover, silencing of LINC00942 repressed the expression of PCNA, Bcl-2, and enhanced Bax expression in A549 and H1299 cells. Mechanically, LINC00942 exerted its effects via enhancing Wnt signaling. LINC00942 functioned as competing endogenous RNA (ceRNA) by binding to miR-5006-5p, upregulating the expression of FZD1, which was a direct target of miR-5006-5p. CONCLUSION: Our findings indicated that LINC00942/miR-5006-5p/FZD1 axis played important roles in LUAD growth through enhancing Wnt signaling. LINC00942/miR-5006-5p/FZD1 axis might serve as a potential biomarker and therapeutic target for LUAD treatment.

Polydopamine with Tailorable Photoelectrochemical Activities for the Highly Sensitive Immunoassay of Tumor Markers.

A simple and highly sensitive photoelectrochemical (PEC) immunoassay sensor was fabricated by using the two forms of polydopamine (PDA), the thin film and nanosphere, to serve as the photoelectrode-modified material and signal reporting label, respectively. The two forms of PDA show similar light absorption behavior but totally different PEC activities. The PDA film can extend the light absorption from the ultraviolet to near infrared light range, transfer a photoelectron to TiO2 nanoparticles and the underlying photoelectrode, and largely amplify the photocurrent response. However, the PDA nanospheres have insignificant photoelectron transport ability. When they are brought close to the PDA film and TiO2 nanocomposite-modified electrode via the sandwich immunoreaction, they function like a black hole to compete with the PDA film for light absorption, resist the access of the electron donor to regenerate the photoactive material, and capture the photoelectron generated from the PDA film. Besides, the heat generated from the PDA nanospheres also contributes to the photocurrent decrease. The PDA nanospheres with multiple quenching effects on the PDA film greatly decrease the photocurrent signal and lead to a highly sensitive PEC immunosensing strategy. Under optimal conditions, a wide linear range from 0.1 to 106 pg·mL-1 is obtained toward carcinoembryonic antigen, with a low limit of detection of 40 fg·mL-1. Besides, the PDA with excellent biosafety can be readily assembled with proteins, which thus simplifies the preparation procedures and decreases the costs. All these features indicate that the whole PDA-based PEC sensing strategy may have great application prospects for the point-of-care assay of various kinds of tumor markers.

Long non­coding RNA OIP5­AS1 facilitates the progression of ovarian cancer via the miR­128­3p/CCNG1 axis.

Long non­coding RNA (LncRNA) o­phthalaldehyde-interacting protein 5 antisense transcript 1 (OIP5­AS1) serves major roles in the progression of various types of cancer. The present study investigated its biological function in ovarian cancer (OC) and its mechanisms. The levels of OIP5­AS1, microRNA­128­3p (miR­128­3p) and cyclin G1 (CCNG1) were examined by reverse transcription­quantitative PCR. Cell viability, apoptosis, migration and invasion were detected to analyze cellular progression. Glycolytic metabolism was assessed by detecting the levels of glucose consumption and lactate production. CCNG1 and hexokinase 2 protein levels were measured by western blotting. Dual­luciferase reporter assay, RNA immunoprecipitation and RNA pull­down assays were performed to affirm the interaction between two molecules. OIP5­AS1 was found to be upregulated in OC tissues and cells. Knockdown of OIP5­AS1 suppressed cell viability, migration, invasion and glycolysis while promoting apoptosis in OC cells. OIP5­AS1 interacted with miR­128­3p and functioned as an oncogene by sequestering miR­128­3p. In addition, CCNG1 was a target gene for miR­128­3p and miR­128­3p regulated the CCNG1­induced effects on OC cells by downregulating CCNG1. OIP5­AS1 upregulated the expression of CCNG1 via targeting miR­128­3p. OIP5­AS1 knockdown also inhibited tumor growth of OC in vivo by modulating the expression of miR­128­3p and CCNG1. Collectively, these data illustrated that the oncogenic role of OIP5­AS1 in OC was associated with the miR­128­3p/CCNG1 axis at least in part. OIP5­AS1 might be a probable diagnostic and therapeutic biomarker for the treatment of OC patients.

The ancient wave of polyploidization events in flowering plants and their facilitated adaptation to environmental stress.

Flowering plants, or angiosperms, consist of more than 300,000 species, far more than any other land plant lineages. The accumulated evidence indicates that multiple ancient polyploidy events occurred around 100 to 120 million years ago during the Cretaceous and drove the early diversification of four major clades of angiosperms: gamma whole-genome triplication in the common ancestor of core eudicots, tau whole-genome duplication during the early diversification of monocots, lambda whole-genome duplication during the early diversification of magnoliids, and pi whole-genome duplication in the Nymphaeales lineage. These four polyploidy events have played essential roles in the adaptive evolution and diversification of major clades of flowering plants. Here, we specifically review the current understanding of this wave of ancient whole-genome duplications and their evolutionary significance. Notably, although these ancient whole-genome duplications occurred independently, they have contributed to the expansion of many stress-related genes (e.g., heat shock transcription factors and Arabidopsis response regulators)，and these genes could have been selected for by global environmental changes in the Cretaceous. Therefore, this ancient wave of paleopolyploidy events could have significantly contributed to the adaptation of angiosperms to environmental changes, and potentially promoted the wide diversification of flowering plants.

Appraising the Value of Serum and Serum-Derived Exosomal LncRNA-EXOC7 as a Promising Biomarker in Cervical Cancer.

BACKGROUND: The abnormally expressed long non-coding RNAs (lncRNAs) are closely related to the onset and progression of various malignant tumors. In this study, we aimed to explore the value of serum and serum-derived exosomal lncRNA-EXOC7 (long non-coding RNA exocyst complex component 7) in the diagnosis and monitoring of cervical cancer (CC). METHODS: The expression of lncRNA-EXOC7 in serum and serum-derived exosomes in CC patients was detected by quantitative real-time PCR (qRT-PCR), and the correlations between lncRNA-EXOC7 expression and clinicopathological characteristics were analyzed by Spearman's and Chi-square tests. RESULTS: Serum vesicles were successfully isolated and identified. The expression of lncRNA-EXOC7 in serum and serum-derived exosomes in CC patients was markedly elevated compared with that in healthy controls. The AUCs of serum and exosomal lncRNA-EXOC7 in distinguishing CC patients from healthy controls were 0.9388 and 0.8982, respectively. The expression of lncRNA-EXOC7 in serum and exosomes was correlated with the FIGO stage of CC (p = 0.041 or 0.010), and positively correlated with levels of CYFRA211, TPS, and SCC (all with p < 0.05). Serum and exosomal lncRNA-EXOC7 was related to the treatment and recurrence of CC; that means, it was significantly repressed after treatment and up-regulated at the time of recurrence. CONCLUSIONS: Serum and exosomal lncRNA-EXOC7 can be used as an important biomarker for the diagnosis, the evaluation of curative effect and the detection of recurrence of CC.

Cancer Cell enters reversible quiescence through Intracellular Acidification to resist Paclitaxel Cytotoxicity.

Cancer cells can enter quiescent or dormant state to resist anticancer agents while maintaining the potential of reactivation. However, the molecular mechanism underlying quiescence entry and reactivation remains largely unknown. In this paper, cancer cells eventually entered a reversible quiescent state to resist long-term paclitaxel (PTX) stress. The quiescent cells were characterized with Na+/H+ exchanger 1 (NHE1) downregulation and showed acidic intracellular pH (pHi). Accordingly, decreasing pHi by NHE1 inhibitor could induce cell enter quiescence. Further, acidic pHi could activate the ubiquitin-proteasome system and inhibiting proteasome activity by MG132 prevented cells entering quiescence. In addition, we show that after partial release, the key G1-S transcription factor E2F1 protein level was not recovered, while MCM7 protein returned to normal level in the reactivated cells. More importantly, MCM7 knockdown inhibited G1/S genes transcription and inhibited the reactivated proliferation. Taken together, this study demonstrates a regulatory function of intracellular acidification and subsequent protein ubiquitination on quiescence entry, and reveals a supportive effect of MCM7 on the quiescence-reactivated proliferation.

Potency and Selectivity of SMAC/DIABLO Mimetics in Solid Tumor Therapy.

Aiming to promote cancer cell apoptosis is a mainstream strategy of cancer therapy. The second mitochondria-derived activator of caspase (SMAC)/direct inhibitor of apoptosis protein (IAP)-binding protein with low pI (DIABLO) protein is an essential and endogenous antagonist of inhibitor of apoptosis proteins (IAPs). SMAC mimetics (SMs) are a series of synthetically chemical compounds. Via database analysis and literature searching, we summarize the potential mechanisms of endogenous SMAC inefficiency, degradation, mutation, releasing blockage, and depression. We review the development of SMs, as well as preclinical and clinical outcomes of SMs in solid tumor treatment, and we analyze their strengths, weaknesses, opportunities, and threats from our point of view. We also highlight several questions in need of further investigation.

Effects of passive music therapy on anxiety and vital signs in lung cancer patients undergoing peripherally inserted central catheter placement procedure.

PURPOSE: To evaluate the effects of passive music therapy on anxiety and vital signs among lung cancer patients at their first peripherally inserted central catheter placement procedure in China. METHODS: A randomized controlled clinical trial was conducted in the cancer center of a hospital in Chengdu from May to December 2017. A total of 304 lung cancer patients who met the inclusion and exclusion criteria were recruited and randomly assigned to experimental (n = 152) and control (n = 152) group, respectively. The control group only received standard care, while the experimental group received standard care and passive music therapy during peripherally inserted central catheter placement (30-45 min) and after catheterization, until discharged from the hospital (twice a day, 30 min once). Measures include anxiety and vital signs (blood pressure, heart rate, and respiratory rate). RESULTS: Repetitive measurement and analysis of variance showed that the patients in experimental group had a statistically significant decrease in anxiety, diastolic blood pressure, and heart rate over time compared to the control group, but no significant difference was identified in systolic blood pressure and respiratory rate. CONCLUSION: Passive music therapy can efficiently relieve the anxiety of lung cancer patients during peripherally inserted central catheter placement. It also can lower the patient's diastolic blood pressure and slow down the heart rate. So, music therapy benefits patients with peripherally inserted central catheter.

The Patatin-Like Phospholipase Domain Containing Protein 7 Facilitates VLDL Secretion by Modulating ApoE Stability.

BACKGROUND AND AIMS: The regulation of hepatic very-low-density lipoprotein (VLDL) secretion is vital for lipid metabolism whose pathogenetic status is involved in fatty liver disease and dyslipidemia seen in hepatic steatosis. Accumulated evidence suggest that apolipoprotein E (ApoE) is closely related to hepatic VLDL secretion. Here, we report that the expression of patatin-like phospholipase domain containing protein 7 (PNPLA7) is strongly induced by hepatic steatosis and positively correlates with plasma triacylglycerol (TAG) levels in the human subjects, whereas the role of PNPLA7 in hepatic VLDL secretion is unknown. APPROACH AND RESULTS: Herein, with genetic manipulation in the mice, the deficiency of hepatic PNPLA7 expression resulted in reduced VLDL secretion accompanied by enhanced hepatic lipid accumulation and decreased hepatic ApoE expression. Furthermore, knockdown of PNPLA7 in the livers of the db/db mice also resulted in significant reduction in plasma TAG level but aggravated hepatic steatosis. Importantly, we observed that PNPLA7 interacted with ApoE and presumably at the site of endoplasmic reticulum. Mechanistically, we have shown that PNPLA7 could modulate polyubiquitination and proteasomal-mediated degradation of ApoE. Overexpressed ApoE restored the impaired VLDL-TAG metabolism in PNPLA7-knockdown primary hepatocytes. CONCLUSION: PNPLA7 plays a critical role in regulating hepatic VLDL secretion by modulating ApoE stability through its interaction with ApoE.

Alcohol accumulation promotes esophagitis via pyroptosis activation.

Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to multitudinous stimulations and inducing chronic inflammation. Esophagitis is a response to inflammation of the esophageal squamous mucosa. Our study clarified that alcohol accumulation could aggravate the progress of esophagitis by inducing pyroptosis; however, Ac-YVAD-CMK, an inhibitor of caspase-1, could effectively suppress the expression of IL-1ß and IL-18 both in vivo and in vitro, reducing the inflammatory response, which is promised to be an agent to inhibit the progression of esophagitis. Additionally, caspase-1-derived pyroptosis is involved in esophageal cancer.