Newly graphene/polypyrrole (rGO/PPy) modified carbon felt as bio-cathode in bio-electrochemical systems (BESs) achieving complete denitrification.

Nitrate reduction in bio-electrochemical systems (BESs) has attracted wide attention due to its low sludge yields and cost-efficiency advantages. However, the high resistance of traditional electrodes is considered to limit the denitrification performance of BESs. Herein, a new graphene/polypyrrole (rGO/PPy) modified electrode is fabricated via one-step electrodeposition and used as cathode in BES for improving nitrate removal from wastewater. The formation and morphological results support the successful formation of rGO/PPy nanohybrids and confirm the part covalent bonding of Py into GO honeycomb lattices to form a three-dimensional cross-linked spatial structure. The electrochemical tests indicate that the rGO/PPy electrode outperforms the unmodified electrode due to the 3.9-fold increase in electrochemical active surface area and 6.9-fold decrease in the charge transfer resistance (Rct). Batch denitrification activity tests demonstrate that the BES equipped with modified rGO/PPy biocathode could not only achieve the full denitrification efficiency of 100% with energy recovery (15.9 × 10-2 ± 0.14 A/m2), but also favor microbial attach and growth with improved biocompatible surface. This work provides a feasible electrochemical route to fabricate and design a high-performance bioelectrode to enhance denitrification in BESs.

Influencing factors, gender differences and the decomposition of inequalities in cognitive function in Chinese older adults: a population-based cohort study.

BACKGROUND: Evidence remains limited and inconsistent for assessing cognitive function in Chinese older adults (CFCOA) and inequalities in cognitive function in Chinese older adults (ICFCOA) and exploring their influencing factors and gender differences. This study aimed to identify influencing factors and inequality in CFCOA to empirically explore the existence and sources of gender differences in such inequality and analyse their heterogeneous effects. METHODS: Based on data from the China Health and Retirement Longitudinal Study (CHARLS) for three periods from 2011 to 2015, recentered influence function unconditional quantile regression (RIF-UQR) and recentered influence function ordinary least squares (RIF-OLS) regression were applied to assess influencing factors of CFCOA, while grouped treatment effect estimation, Oaxaca-Blinder decomposition, and propensity score matching (PSM) methods were conducted to identify gender differences in ICFCOA and influencing factors, respectively. RESULTS: The results showed heterogeneous effects of gender, age, low BMI, subjective health, smoking, education, social interactions, physical activity, and household registration on CFCOA. Additionally, on average, ICFCOA was about 19.2-36.0% higher among elderly females than among elderly males, mainly due to differences in characteristic effects and coefficient effects of factors such as marital status and education. CONCLUSIONS: Different factors have heterogeneous and gender-differenced effects on CFCOA and ICFCOA, while the formation and exacerbation of ICFCOA were allied to marital status and education. Considering the severe ageing and the increasing incidence of cognitive decline, there is an urgent need for the government and society to adopt a comprehensive approach to practically work for promoting CFCOA and reducing ICFCOA.

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti-triple-negative breast cancer efficacy in vitro and in vivo.

Triple-negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 µM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α-tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c-Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α-tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well-tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/ß-catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2-targeting drugs.

High-Mannose-Type Glycan of Basigin in Endothelial Cells Is Essential for the Opening of the Blood-Brain Barrier Induced by Hypoxia, Cyclophilin A, or Tumor Necrosis Factor-α.

Pathologic opening of the blood-brain barrier accelerates the progression of various neural diseases. Basigin, as an essential molecule for the opening of the blood-brain barrier, is a highly glycosylated transmembrane molecule specified in barrier-forming endothelial cells. This study analyzed the involvement of basigin in the regulation of the blood-brain barrier focusing on its glycosylation forms. First, basigin was found to be expressed as cell surface molecules with complex-type glycan as well as those with high-mannose-type glycan in barrier-forming endothelial cells. Monolayers of endothelial cells with suppressed expression of basigin with high-mannose-type glycan were then prepared and exposed to pathologic stimuli. These monolayers retained their barrier-forming properties even in the presence of pathologic stimuli, although their expression of basigin with complex-type glycan was maintained. In vivo, the blood-brain barrier in mice pretreated intravenously with endoglycosidase H was protected from opening under pathologic stimuli. Pathologically opened blood-brain barrier in streptozotocin-injected mice was successfully closed by intravenous injection of endoglycosidase H. These results show that high-mannose-type glycan of the basigin molecule is essential for the opening of the blood-brain barrier and therefore a specific target for protection as well as restoration of pathologic opening of the blood-brain barrier.

Long non-coding RNA LINC00491 accelerates head and neck squamous cell carcinoma progression through regulating miR-508-3p/SATB1 axis and activating Wnt signaling pathway.

Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck epidermis. Accumulating long non-coding RNAs (lncRNAs) have been proven to be involved in the occurrence and development of HNSCC. LncRNA long intergenic non-protein coding RNA 491 (LINC00491) has been confirmed to regulate the progression of some cancers. In our study, we aimed to explore the potential biological function of LINC00491 and expound the regulatory mechanism by which LINC00491 affects the progression of HNSCC. RT-qPCR was utilized to analyze the expression of LINC00491 in HNSCC cell lines and the normal cell line. Functionally, we carried out a series of assays to measure cell proliferation, apoptosis, migration and invasion, such as EdU assay, colony formation, wound healing and western blot assays. Also, mechanism assays including RNA pull down and RIP were also implemented to investigate the interaction of LINC00491 and RNAs. As a result, we discovered that LINC00491 was highly expressed in HNSCC cells. In addition, LINC00491 depletion suppressed cell proliferation, migration and EMT process. Furthermore, we discovered that LINC00491 could bind to miR-508-3p. MiR-508-3p overexpression can restrain HNSCC cell growth. Importantly, miR-508-3p can target SATB homeobox 1 (SATB1) in HNSCC cells. Further, Wnt signaling pathway was proved to be activated by LINC00491 through SATB1 in HNSCC cells. In a word, LINC00491 accelerated HNSCC progression through regulating miR-508-3p/SATB1 axis and activating Wnt signaling pathway.

Integrated machine learning and bioinformatic analyses used to construct a copper-induced cell death-related classifier for prognosis and immunotherapeutic response of hepatocellular carcinoma patients.

Background: Copper as phytonutrient has powerful activity against health diseases. A newly discovered mechanism of cell death that affects energy metabolism by copper ("cuproptosis") can induce multiple cuproptosis-related genes. Hepatocellular carcinoma (HCC) is a poorly prognosed widespread cancer having danger of advanced metastasis. Therefore, earlier diagnosis followed by the specific targeted therapy are required for improved prognosis. The work herein constructed scoring system built on ten cuproptosis-related genes (CRGs) to predict progression of tumor and metastasis more accurately and test patient reaction toward immunotherapy. Methods: A comprehensive assessment of cuproptosis patterns in HCC samples from two databases and a real-world cohort was performed on ten CRGs, that were linked to immune cell infiltration signatures of TME (tumor microenvironment). Risk signatures were created for quantifying effect of cuproptosis on HCC, and the effects of related genes on cellular function of HCC were investigated, in addition to the effects of immunotherapy and targeted therapy drugs. Results: Two distinct cuproptosis-associated mutational patterns were identified, with distinct immune cell infiltration characteristics and survival likelihood. Studies have shown that assessment of cuproptosis-induced tumor mutational patterns can help predict tumor stage, phenotype, stromal activity, genetic diversity, and patient prognosis. High risk scores are characterized by lower survival and worse treatment with anti-PD-L1/CTAL4 immunotherapy and first-line targeted drugs. Cytological functional assays show that CDKN2A and GLS promote proliferation, migration and inhibit copper-dependent death of HCC cells. Conclusion: HCC patients with high-risk scores exhibit significant treatment disadvantage and survival rates. Cuproptosis plays a non-negligible role in the development of HCC. Quantifying cuproptosis-related designs of tumors will aid in phenotypic categorization, leading to efficient personalized and targeted therapeutics and precise prediction of prognosis and metastasis.

360° open-ended and navigated magnetic resonance-guided microwave ablation for hepatic tumors in risk areas.

Context: Image-guided local ablation has becoming a promising treatment option for patients unsuitable for surgical resection. Currently, magnetic resonance (MR) imaging has been used as guidance for ablation due to its good soft-tissue contrast, high image quality and absence of ionizing radiation. However, the limited operating space and interrupted and delayed imaging of the conventional MR equipment increased the difficulty of puncture during operation. Therefore, we utilized an easy-to-use optical navigation system with a 0.4 T 360° open MR system to perform MR-guided microwave ablation (MWA) to treat liver tumor patients in risk areas. Aim: To evaluate the safety and efficacy of MR-guided MWA in treating liver tumors using a 0.4 T open and navigated MR system. Materials and Methods: A retrospective analysis was performed on 19 liver tumor patients who underwent MR-guided MWA between August 2014 and August 2017. The complications, complete ablation, and long-term outcomes were analyzed and evaluated. Results: It was found that navigated MRI guidance allowed for precise needle placement in the targeted tumor, and ablation was successfully performed in all patients without serious intraoperative complications and death. Additionally, complete ablation was reached at 94.74% (18/19), with only one patient discovered with residual tumor, and therefore received another MWA session within three months. Conclusion: 360° open MR system combined with navigation systems conveniently enhanced the operation of MR-guided ablation, producing effective outcomes. Therefore, this option may be a safe and effective therapy for liver tumors in patients, especially for those situated in risk areas and those not visible to identify by ultrasound or computerized tomography.

Impaired Proteolysis of Noncanonical RAS Proteins Drives Clonal Hematopoietic Transformation.

Recently, screens for mediators of resistance to FLT3 and ABL kinase inhibitors in leukemia resulted in the discovery of LZTR1 as an adapter of a Cullin-3 RING E3 ubiquitin ligase complex responsible for the degradation of RAS GTPases. In parallel, dysregulated LZTR1 expression via aberrant splicing and mutations was identified in clonal hematopoietic conditions. Here we identify that loss of LZTR1, or leukemia-associated mutants in the LZTR1 substrate and RAS GTPase RIT1 that escape degradation, drives hematopoietic stem cell (HSC) expansion and leukemia in vivo. Although RIT1 stabilization was sufficient to drive hematopoietic transformation, transformation mediated by LZTR1 loss required MRAS. Proteolysis targeting chimeras (PROTAC) against RAS or reduction of GTP-loaded RAS overcomes LZTR1 loss-mediated resistance to FLT3 inhibitors. These data reveal proteolysis of noncanonical RAS proteins as novel regulators of HSC self-renewal, define the function of RIT1 and LZTR1 mutations in leukemia, and identify means to overcome drug resistance due to LZTR1 downregulation. SIGNIFICANCE: Here we identify that impairing proteolysis of the noncanonical RAS GTPases RIT1 and MRAS via LZTR1 downregulation or leukemia-associated mutations stabilizing RIT1 enhances MAP kinase activation and drives leukemogenesis. Reducing the abundance of GTP-bound KRAS and NRAS overcomes the resistance to FLT3 kinase inhibitors associated with LZTR1 downregulation in leukemia. This article is highlighted in the In This Issue feature, p. 2221.

Ten-Eleven Translocation Ablation Impairs Cardiac Differentiation of Mouse Embryonic Stem Cells.

Ten-eleven Translocation (TET) dioxygenases mediated DNA methylation oxidation plays an important role in regulating the embryonic stem cells (ESCs) differentiation. Herein, we utilized a CRISPR/Cas9 based genome editing method to generate single, double, and triple Tet-deficient mouse ESCs (mESCs) and differentiated these cells toward cardiac progenitors. By using emerald green fluorescent protein (GFP; emGFP) expression under the control of Nkx2.5 promoter as marker for cardiac progenitor cells, we discovered that Tet1 and Tet2 depletion significantly impaired mESC-to-cardiac progenitor differentiation. Single-cell RNA-seq analysis further revealed that Tet deletion resulted in the accumulation of mesoderm progenitors to hamper cardiac differentiation. Re-expression of the Tet1 catalytic domain (Tet1CD) rescued the differentiation defect in Tet-triple knockout mESCs. Dead Cas9 (dCas9)-Tet1CD mediated loci-specific epigenome editing at the Hand1 loci validated the direct involvement of Tet-mediated epigenetic modifications in transcriptional regulation during cardiac differentiation. Our study establishes that Tet-mediated epigenetic remodeling is essential for maintaining proper transcriptional outputs to safeguard mESC-to-cardiac progenitor differentiation.

Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors.

BACKGROUND: Covalent (irreversible) Bruton's tyrosine kinase (BTK) inhibitors have transformed the treatment of multiple B-cell cancers, especially chronic lymphocytic leukemia (CLL). However, resistance can arise through multiple mechanisms, including acquired mutations in BTK at residue C481, the binding site of covalent BTK inhibitors. Noncovalent (reversible) BTK inhibitors overcome this mechanism and other sources of resistance, but the mechanisms of resistance to these therapies are currently not well understood. METHODS: We performed genomic analyses of pretreatment specimens as well as specimens obtained at the time of disease progression from patients with CLL who had been treated with the noncovalent BTK inhibitor pirtobrutinib. Structural modeling, BTK-binding assays, and cell-based assays were conducted to study mutations that confer resistance to noncovalent BTK inhibitors. RESULTS: Among 55 treated patients, we identified 9 patients with relapsed or refractory CLL and acquired mechanisms of genetic resistance to pirtobrutinib. We found mutations (V416L, A428D, M437R, T474I, and L528W) that were clustered in the kinase domain of BTK and that conferred resistance to both noncovalent BTK inhibitors and certain covalent BTK inhibitors. Mutations in BTK or phospholipase C gamma 2 (PLCγ2), a signaling molecule and downstream substrate of BTK, were found in all 9 patients. Transcriptional activation reflecting B-cell-receptor signaling persisted despite continued therapy with noncovalent BTK inhibitors. CONCLUSIONS: Resistance to noncovalent BTK inhibitors arose through on-target BTK mutations and downstream PLCγ2 mutations that allowed escape from BTK inhibition. A proportion of these mutations also conferred resistance across clinically approved covalent BTK inhibitors. These data suggested new mechanisms of genomic escape from established covalent and novel noncovalent BTK inhibitors. (Funded by the American Society of Hematology and others.).

The effect of gut microbiota dysbiosis on patients with preeclampsia.

Purpose: To compare the difference of gut microbiota between preeclampsia (PE) and healthy normal pregnant women, providing new therapeutic strategy for preeclampsia. Methods: Forty-one PE patients and 45 age- and pre-pregnancy body mass index- matched healthy controls were enrolled from Nov 2021 to May 2022 in this retrospective case-control study. Fecal microbiota was detected by 16S rRNA gene sequencing, followed by bioinformatics analysis including microbial α diversity, microbial ß diversity, and linear discriminant analysis effect size (LEfSe) analysis. Serum inflammatory factors were also detected and compared between the two groups. Results: There were significant differences in Bacteroidetes (2.68% in PE patients vs 11.04% in healthy controls, P < 0.001), Proteobacteria (4.04% in PE patients vs 1.22% in healthy controls, P = 0.041), and Fusobacteria (1.07% in PE patients vs 0.01% in healthy controls, P = 0.042) between the two groups at the phylum level. Microbial α diversity was lower in PE patients than that in healthy controls. In addition, there was significant difference in microbial ß diversity between the two groups. LEfSe analysis showed that there are 24 different taxa between the two groups. The levels of proinflammatory factors including serum tumor necrosis factor-α and Interleukin-6 were statistically significant higher in PE patients than those in healthy controls (both P < 0.001), while there were no significant differences in the levels of serum anti-inflammatory factors including Interleukin-4 and Interleukin-10 between the two groups (P = 0.234 and P = 0.096, respectively). Conclusion: PE patients demonstrated gut microbiota disturbances and increasing serum proinflammatory factors, leading to a better understanding of the relationship between the gut microbiota dysbiosis and PE.

Ultrasound-guided percutaneous microwave ablation for hepatocellular carcinoma originating in the caudate lobe: A pilot clinical study.

OBJECTIVE: This study aimed to evaluate the efficacy, feasibility, and tolerability of ultrasound (US)-guided percutaneous microwave ablation (MWA) for treating hepatocellular carcinoma (HCC) originating in the caudate lobe. MATERIALS AND METHODS: The treatment and survival parameters of 32 patients with HCC in the caudate lobe, who met the inclusion criteria and had received US-guided percutaneous MWA in our department from November 2010 to October 2015, were retrospectively analyzed. Imaging examination (contrast-enhanced computed tomography or magnetic resonance) 1 month after MWA was used to evaluate the efficacy of US-guided MWA. RESULTS: Thirty-two patients underwent percutaneous MWA for caudate lobe HCC. The average tumor size was 3.42 ± 0.27 (range: 1-6.8) cm. The initial complete ablation (CA) rate was 87.5% (28/32), and the total CA rate was 96.88% (31/32). Furthermore, the median length of hospitalization was 4 days (range: 2-10 days), and no major complication was observed in this study. The overall survival rates were 87.5%, 50%, and 28.13% at 1, 2, and 3 years, respectively. The progression-free survival after MWA was 93.75%, 53.15%, and 28.13% at 6, 12, and 18 months, respectively. CONCLUSIONS: US-guided percutaneous MWA was a safe and effective treatment. It is a promising alternative therapy for HCC originating in the caudate lobe.

Periostin deficiency reduces diethylnitrosamine-induced liver cancer in mice by decreasing hepatic stellate cell activation and cancer cell proliferation.

Periostin is a critical extracellular regulator in the pathogenesis of liver disorders such as hepatosteatosis, non-alcoholic steatohepatitis, inflammation, and fibrosis. Periostin is also involved in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanisms of periostin in hepatic stellate cell (HSC) activation and tumor cell proliferation in the pathogenesis of HCC remain largely unknown. We demonstrate that periostin is markedly upregulated in diethylnitrosamine (DEN)-induced mouse HCC tissues and that periostin knockout impairs DEN-induced HCC development. Periostin is predominantly derived from activated HSCs and periostin deficiency in HSCs impairs HSC activation and inhibits HSC-promoted HCC cell proliferation in vitro and tumor growth in vivo. Mechanistically, periostin promotes HSC activation through the integrin-FAK-STAT3-periostin pathway and augments HCC cell proliferation by activating ERK. There are positive correlations between periostin and HSC activation and cell proliferation in HCC clinical samples. Collectively, our findings demonstrate that HSC-derived periostin promotes HCC development by enhancing HSC activation through an autocrine periostin-integrin-FAK-STAT3-periostin circuit and by augmenting HCC cell proliferation via the ERK pathway in a paracrine manner. Thus, periostin is a multifaceted extracellular regulator in the development of HCC. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

EGFR activation limits the response of liver cancer to lenvatinib.

Hepatocellular carcinoma (HCC)-the most common form of liver cancer-is an aggressive malignancy with few effective treatment options1. Lenvatinib is a small-molecule inhibitor of multiple receptor tyrosine kinases that is used for the treatment of patients with advanced HCC, but this drug has only limited clinical benefit2. Here, using a kinome-centred CRISPR-Cas9 genetic screen, we show that inhibition of epidermal growth factor receptor (EGFR) is synthetic lethal with lenvatinib in liver cancer. The combination of the EGFR inhibitor gefitinib and lenvatinib displays potent anti-proliferative effects in vitro in liver cancer cell lines that express EGFR and in vivo in xenografted liver cancer cell lines, immunocompetent mouse models and patient-derived HCC tumours in mice. Mechanistically, inhibition of fibroblast growth factor receptor (FGFR)  by lenvatinib treatment leads to feedback activation of the EGFR-PAK2-ERK5 signalling axis, which is blocked by EGFR inhibition. Treatment of 12 patients with advanced HCC who were unresponsive to lenvatinib treatment with the combination of lenvatinib plus gefitinib (trial identifier NCT04642547) resulted in meaningful clinical responses. The combination therapy identified here may represent a promising strategy for the approximately 50% of patients with advanced HCC who have high levels of EGFR.

Pathologic Diagnosis and Genetic Analysis of Sequential Biopsy Following Coaxial Low-Power Microwave Thermal Coagulation For Pulmonary Ground-Glass Opacity Nodules.

PURPOSE: To evaluate the feasibility, safety, and diagnostic performance of sequential core-needle biopsy (CNB) technique following coaxial low-power microwave thermal coagulation (MTC) for ground-glass opacity (GGO) nodules. MATERIALS AND METHODS: From December 2017 to July 2019, a total of 32 GGOs (with diameter of 12 ± 4 mm) in 31 patients received two times of CNBs, both prior to and immediately after MTC at a power of 20 watts. The frequency and type of complications associated with CNBs were examined. The pathologic diagnosis and genetic analysis were performed for specimens obtained from the two types of biopsy. RESULTS: The technical success rates of pre- and post-MTC CNBs were 94% and 100%, respectively. The complication rate was significantly lower with post-MTC CNB as compared to pre-MTC CNB (42% versus 97%, p < 0.001). Larger amount of specimens could be obtained by post-MTC CNB. The pathological diagnosis rate of post-MTC CNB was significantly higher than that of pre-MTC CNB (100% versus 75%, p = 0.008), whereas the success rates of genetic analysis were comparable between the two groups (100% versus 84%, p = 0.063). Regular ablation could be further performed after post-MTC CNB to achieve local tumor control. CONCLUSION: Sequential biopsy following coaxial low-power MTC can reduce the risk of complications and provide high-quality specimens for pulmonary GGOs. Combining this technique with standard ablation allows for simultaneous diagnosis and treatment within a single procedure.

SARS-CoV-2 spike D614G change enhances replication and transmission.

During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.

Long-term results of percutaneous microwave ablation for colorectal liver metastases.

BACKGROUND: Radiofrequency ablation (RFA) has been used for therapy of colorectal liver metastases (CRLMs) several years, with considerable data confirming its safety and efficacy. However, there are few studies focusing on the long-term results of percrtaneous microwave ablation (PMWA) for CRLMs. The aim of this study was to evaluate the long-term survival and prognostic factors in patients with CRLMs undergoing PMWA. METHODS: We retrospectively analyzed treatment and survival parameters of 210 patients with CRLMs who had received PMWA in a single center from January 2010 to December 2017. Prognostic factors for survival were evaluated by means of univariate and multivariate analyses. RESULTS: The median follow-up time after PMWA was 48 months. The median overall survival (OS) time were 40.0 months (95% CI, 31.4 to 48.5 months), with 1-, 2, 3-, 4, and 5-year cumulative survival rates of 98.6%, 73.3%, 53.3%, 42.2%, and 32.9%, respectively. Tumor number (P = 0.004; HR: 1.838; CI: 1.213- 2.784), main tumor size (P = 0.017; HR: 1.631; CI: 1.093- 2.436), and serum CEA level (P = 0.032; HR: 1.559; CI: 1.039-2.340) were found as independent predictors of OS. The median OS time for patients with resectable lesions was 60.91 months (95% CI, 51.36 to 70.47 months), with 5-year cumulative survival rates of 53.5%. CONCLUSION: PMWA is a safe and effective treatment for CRLMs, with a favorable long-term outcome. Multiple lesions, main tumor diameter>3 cm, and serum CEA >30 ng/ml have a significant negative effect on OS.

LncRNA Lnc712 Promotes Tumorigenesis in Hepatocellular Carcinoma by Targeting miR-142-3p/Bach-1 Axis.

BACKGROUND: It is known that Lnc712 plays an important role in the pathogenesis of breast cancer. However, whether it is involved in hepatocellular carcinoma (HCC) remains unknown. In this study, we aimed to investigate the role and underlying mechanism of Lnc712 in HCC. METHODS: Sixty-four HCC patients were enrolled and followed up for 5 years to analyze the prognostic value of Lnc712 for HCC. HCC cells were transfected with Lnc712 expression vector, Bach-1 expression vector (or siRNA) and miR-142-3p mimic (or inhibitor) to explore the interactions among Lnc712, miR-142-3p and Bach-1. Cell proliferation, migration, invasion and cell cycle were analyzed by CCK-8 assay, transwell assay, wound healing assay and flow cytometry assay, respectively. RESULTS: The expression of Lnc712 was upregulated in HCC, and the upregulated Lnc712 expression was significantly related to poor overall survival in HCC patients. In HCC cells, Lnc712 interacted with miR-142-3p and upregulated Bach-1, a target of miR-142-3p. In addition, Lnc712 promoted HCC cell proliferation, migration, invasion and cell cycle, while its effects were abolished by miR-142-3p mimic. Moreover, miR-142-3p mimic enhanced HCC cell proliferation, migration, invasion and cell cycle, while its effects were abolished by Bach-1 overexpression. miR-142-3p inhibitor repressed cell proliferation, migration, invasion and cell cycle in HCC cells, while its effects were abolished by Bach-1 knockdown. Furthermore, Lnc712 knockdown remarkably inhibited HCC tumor growth in nude mice. CONCLUSION: Lnc712 may promote the development of HCC by targeting the miR-142-3p/Bach-1 axis.

Socioeconomic status, social capital, health risk behaviors, and health-related quality of life among Chinese older adults.

BACKGROUND: There is limited knowledge on the mediating role of different health risk behavior on the relationship between social capital, socioeconomic status (SES), and health-related quality of life (HRQoL) in Chinese older adults. We conducted this study to (a) investigate the condition of health risk behaviors of the Chinese elderly, and (b) assess the relationship between SES, social capital, health risk behaviors, and HRQoL. METHODS: A sample of 4868 adults aged 60 years and older were included in this study, from the China's Health-related Quality of Life Survey for Older Adults 2018. Participants' demographic characteristics, SES (education level, family income), health risk behaviors (smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder) were collected. Social capital and HRQoL were assessed by the 16-item Personal Social Capital Scale (PSCS-16) and WHOQOL-Old, respectively. Structural equation modeling (SEM) was applied to examine the associations between variables. RESULTS: The proportion of smoking, alcohol consumption, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder were 32.1, 36.3, 62.5, 45.7, 31.8, and 45.5%, respectively. Significant differences were observed in education level, family income, and social capital between elderly individuals with and without each of the six health risk behavior (all p-values < 0.05). Elderly individuals who reported smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder had significantly lower HRQoL than those without these unhealthy behaviors (all p-values < 0.05). SEM analysis showed that SES and social capital positively associated with alcohol consumption. Social capital negatively associated with smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder. SES negatively associated with smoking, physical inactivity, unhealthy dietary behavior, unhealthy weight, and sleep disorder. Smoking, physical inactivity, unhealthy dietary behavior, and sleep disorder correlated with poorer HRQoL. CONCLUSIONS: Chinese older adults demonstrated a high incidence of health risk behaviors, especially for physical inactivity (62.5%) and unhealthy dietary behavior (45.7%). Social capital and SES were correlated with the elderly's HRQoL, as well as with the health risk behaviors. Health risk behaviors played potential mediating role on the relationship between social capital, SES, and HRQoL in Chinese older adults.