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Long non‐coding RNAs (LncRNAs), which are more than 200 nucleotides in length and with limited protein‐coding potential, play vital roles in the pathogenesis, tumorigenesis, and angiogenesis of cancers. Aberrant expression of lncRNAs has been detected in various carcinomas and may be correlated with oncogenesis by affecting related genes expression. Recently, an increasing number of studies have reported on long intergenic non‐protein coding RNA 460 (LINC00460) in human tumor fields. LINC00460 is upregulated in diverse cancer tissues and cells. The upregulated expression level of LINC00460 is correlated with larger tumor size, tumor node metastasis (TNM) stage, lymph node metastasis, and shorter overall survival. The regulatory mechanism of LINC00460 was complex and diverse. LINC00460 could act as a competitive endogenous RNA (ceRNA), directly bind with proteins or regulate multiple pathways, which affected tumor progression. Moreover, LINC00460 was also identified to increase drug resistance, and therefore, weaken the effectiveness of tumor treatment. It has become increasingly important to investigate the roles of LINC00460 in various cancers by different mechanisms. Therefore, a more comprehensive understanding of LINC00460 is crucial to expound on the cellular function and molecular mechanism of human cancers. In this review, we refer to studies concerning LINC00460 and provide the basis for the evaluation of LINC00460 as a predicted biomarker or potential therapeutic target in malignancies, and also provide ideas for the future research of lncRNAs similar to LINC00460., In recent years, the regulatory role of long noncoding RNAs (lncRNAs) in human tumors has been gradually recognized. In this review, we respectively showed how lncRNA LINC00460 affected progression of human tumors in different types by multiple mechanisms. A large number of previous researches have demonstrated that LINC00460 as an oncogene plays important roles in tumor growth, development, and metastasis. In view of the important role of LINC00460 in tumorigenesis and development as well as its significance as a biomarker, we summarized the specific role and molecular mechanism of LINC00460 in various tumors, convenient for readers integrally learning about the effect of LINC00460 on diverse cancers. We believe this review is valuable for all the researchers who are interested in human cancers and noncoding RNAs.

Background This study aimed to investigate the associations of sarcopenia and its defining components with cognitive function in community-dwelling oldest old (over 80 years old) in China. Methods Sarcopenia was diagnosed by the 2019 Asian Working Group for Sarcopenia (AWGS) criteria. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). Logistic and linear regression models were used to explore the associations of sarcopenia and its defining components with risk of mild cognitive impairment (MCI), and performance on multiple cognitive domains among 428 adults aged 80 years and older. Results The overall prevalence of sarcopenia was 35.5%, with 40.34% for men and 32.14% for women. The prevalence of MCI was higher among sarcopenic oldest old than non-sarcopenic oldest old (28.95% vs. 17.39%, p = 0.005). Multivariate logistic regression analyses showed that sarcopenia [odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.04–3.33], low handgrip strength (HS) [OR = 2.33, 95% CI: 1.40–3.87] and slow gait speed (GS) [OR = 2.31, 95% CI: 1.13–4.72] were significantly and independently associated with risk of MCI. Multivariate linear regression analyses showed that low HS was associated with worse performance in global cognitive function, visuospatial and executive function, naming and delayed recall. Conclusions Sarcopenia, low HS and low GS was significantly associated with MCI in community-dwelling oldest old. The associations between sarcopenia and its defining components with different cognitive subdomains could be further explored in the future.

Background The Pittsburgh Fatigability Scale (PFS) was developed to capture fatigue and demand in a single tool, filling a gap that no validated questionnaire existed to measure perceived fatigability. Since fatigability is a more sensitive measure of a person’s susceptibility to fatigue, we validated the simplified-Chinese version of the PFS among Chinese community-dwelling older adults. Methods This cross-sectional study was conducted in an urban community in Beijing between November 2018 and July 2019. The PFS was translated into simplified-Chinese by the translation, retro-translation method. Internal consistency of the Physical subscale of the PFS was evaluated by Cronbach’s alpha. Convergent validity and discriminant validity were evaluated against physical performance measures (i.e., Short Physical Performance Battery & Timed Up and Go Test) and daily living performance (i.e., Barthel Index & Instrumental activity of daily living). Results Our study included 457 participants, including 182 men (39.8%) and 275 women (60.2%). The age range of the included participants was 61–96 years (mean = 84.8 years, SD = 5.8 years). The simplified-Chinese version of PFS Physical scores showed strong internal consistency (Cronbach’s alpha = 0.81). Higher PFS Physical scores were associated with worse physical performance, and daily living performance (|correlation coefficient| range: 0.36–0.56, p p Conclusions The PFS simplified-Chinese version is a valid instrument to assess perceived physical fatigability in Chinese-speaking older adults with good convergent validity. Thus, the PFS, with low cost and greater feasibility, is a desired tool to measure fatigability in large population studies.

Sestrin2 (Sesn2) is a stress-inducible protein that plays a critical role in the response to ischemic stress. We recently recognized that Sesn2 may protect the heart against ischemic insults by reducing the generation of reactive oxygen species (ROS). After 45 min of ischemia followed by 24 h of reperfusion, myocardial infarcts were significantly larger in Sesn2 KO hearts than in wild-type hearts. Isolated cardiomyocytes from wild-type hearts treated with hypoxia and reoxygenation (H/R) stress showed significantly greater Sesn2 levels, compared with normoxic hearts (p 0.05). Intriguingly, the administration of adeno-associated virus 9-Sesn2 into Sesn2 knockout (KO) hearts rescued Sesn2 protein levels and significantly improved the cardiac function of Sesn2 KO mice exposed to ischemia and reperfusion. The rescued levels of Sesn2 in Sesn2 KO hearts significantly ameliorated ROS generation and the activation of ROS-related stress signaling pathways during ischemia and reperfusion. Moreover, the rescued Sesn2 levels in Sesn2 KO cardiomyocytes improved the maximal velocity of cardiomyocyte shortening by H/R stress. Rescued Sesn2 levels also improved peak height, peak shortening amplitude, and maximal velocity of the re-lengthening of Sesn2 KO cardiomyocytes subjected to H/R. Finally, the rescued Sesn2 levels significantly augmented intracellular calcium levels and reduced the mean time constant of transient calcium decay in Sesn2 KO cardiomyocytes exposed to H/R. Overall, these findings indicated that Sesn2 can act as an endogenous antioxidant to maintain intracellular redox homeostasis under ischemic stress conditions.

Background: With the increasing number of cases of breast cancer every year, the exploration of novel biomarkers has drawn attention. miR-331 has been demonstrated to play a role in various cancers, but its role in breast cancer is still unknown. Methods: In this study, we included 121 patients with breast cancer treated at Affiliated Hospital of Weifang Medical University. Breast cancer tissues and adjacent normal tissues were collected during the surgery. The expression of miR-331 in breast cancer tissues and cell lines was detected by qRT-PCR assay. Then, with the help of Kaplan-Meier survival and Cox regression analyses, the role of miR-331 in the prognosis of breast cancer was analyzed. Finally, the effect of miR-331 on cell proliferation, migration, and invasion was investigated with CCK-8 assay and transwell assay. Results: miR-331 was significantly upregulated in breast cancer tissues compared with normal tissues. The overexpression of miR-331 was associated with lymph node metastasis, TNM stage, and poor prognosis. From the results of Cox regression analyses, it was found that miR-331 served as an independent indicator in the prognosis of breast cancer. In addition, miR-331 was also found to be upregulated in breast cancer cells, which promoted cell proliferation, migration, and invasion of breast cancer. Conclusion: As shown from our data, miR-331 may be a potential prognostic biomarker in breast cancer. Moreover, the development and progression of breast cancer may involve miR-331. These findings suggest a novel therapeutic target for the treatment of breast cancer.

ObjectivesThe prevalence of childhood hypertension is rising in parallel with the increasing prevalence of overweight and obesity in children. How growth trajectories from childhood to puberty relate to high blood pressure (HBP) is not well defined. We aimed to characterise potential body mass index (BMI) dynamic changing trajectories from childhood to puberty and investigate their association with HBP.DesignA dynamic prospective cohort.SettingChina Health and Nutrition Survey 1991–2015.ParticipantsThere were 1907 participants (1027 men and 880 women) in this study.OutcomesThe primary outcome was HBP defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) exceeding the standards or diagnosis by medical records or taking antihypertensive medication.ResultsA model of cubic parameters with three groups was chosen, labelled as normal increasing group (85.16%, n=1624), high increasing group (9.81%, n=187) and resolving group (5.03%, n=96). Compared with the normal increasing group, the unadjusted HRs (95% CIs) for the resolving and high increasing groups were 0.91 (0.45 to 1.86) and 1.88 (1.26 to 2.81), respectively. After adjusting for baseline age, region, sex, baseline BMI z-score, baseline SBP and baseline DBP in model 3, the HRs (95% CIs) for the resolving and high increasing groups were 0.66 (0.30 to 1.45) and 1.56 (1.02 to 2.38).ConclusionsThese results indicate that the BMI trajectories from childhood to puberty have significant impact on HBP risk. Puberty is a crucial period for the development of HBP.

Perivascular adipose tissue (PVAT) is the connective tissue around most blood vessels throughout the body. It provides mechanical support and maintains vascular homeostasis in a paracrine/endocrine manner. Under physiological conditions, PVAT has anti-inflammatory effects, improves free fatty acid metabolism, and regulates vasodilation. In pathological conditions, PVAT is dysfunctional, secretes many anti-vasodilator factors, and participates in vascular inflammation through various cells and mediators; thus, it causes dysfunction involving vascular smooth muscle cells and endothelial cells. Inflammation is an important pathophysiological event in many vascular diseases, such as vascular aging, atherosclerosis, and hypertension. Therefore, the pro-inflammatory crosstalk between PVAT and blood vessels may comprise a novel therapeutic target for the prevention and treatment of vascular diseases. In this review, we summarize findings concerning PVAT function and inflammation in different pathophysiological backgrounds, focusing on the secretory functions of PVAT and the crosstalk between PVAT and vascular inflammation in terms of vascular aging, atherosclerosis, hypertension, diabetes mellitus, and other diseases. We also discuss anti-inflammatory treatment for potential vascular diseases involving PVAT.

Buthus martensii Karsch (BmK), is a kind of traditional Chinese medicine, which has been used for a long history for the treatment of many diseases, such as inflammation, pain and cancer. In this study, DKK-SP1/2/3 genes were screened and extracted from the cDNA library of BmK. The DKK-SP1/2/3 were expressed by using plasmid pSYPU-1b in E. coli BL21, and recombinant proteins were obtained by column chromatography. In the xylene-induced mouse ear swelling and carrageenan-induced rat paw swelling model, DKK-SP1 exerted a significant anti-inflammatory effect by inhibiting the expression of Nav1.8 channel. Meanwhile, the release of pro-inflammatory cytokines (COX-2, IL-6) was decreased significantly and the release of anti-inflammatory cytokines (IL-10) were elevated significantly. Moreover, DKK-SP1 could significantly decrease the Nav1.8 current in acutely isolated rat DRG neurons. In the acetic acid-writhing and ION-CCI model, DKK-SP2 displayed significant analgesic activity by inhibiting the expression of the Nav1.7 channel. Moreover, DKK-SP2 could significantly inhibit the Nav1.7 current in the hNav1.7-CHO cells.

Physiological reactive oxygen species (ROS) are important regulators of intercellular signal transduction. Oxidative and antioxidation systems maintain a dynamic balance under physiological conditions. Increases in ROS levels destroy the dynamic balance, leading to oxidative stress damage. Oxidative stress is involved in the pathogenesis of aging-related cardiovascular diseases (ACVD), such as atherosclerosis, myocardial infarction, and heart failure, by contributing to apoptosis, hypertrophy, and fibrosis. Oxidative phosphorylation in mitochondria is the main source of ROS. Increasing evidence demonstrates the relationship between ACVD and humanin (HN), an endogenous peptide encoded by mitochondrial DNA. HN protects cardiomyocytes, endothelial cells, and fibroblasts from oxidative stress, highlighting its protective role in atherosclerosis, ischemia–reperfusion injury, and heart failure. Herein, we reviewed the signaling pathways associated with the HN effects on redox signals, including Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2), chaperone-mediated autophagy (CMA), c-jun NH2 terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK), adenosine monophosphate-activated protein kinase (AMPK), and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3). Furthermore, we discussed the relationship among HN, redox signaling pathways, and ACVD. Finally, we propose that HN may be a candidate drug for ACVD.

Rationale: Hepatitis B virus (HBV) is a major risk factor for liver cancer, in which HBV covalently closed circular DNA (cccDNA) plays crucial roles. However, the effect of pseudogene-derived long noncoding RNAs (lncRNAs) acting as functional regulators of their ancestral gene expression on HBV replication and hepatocellular carcinoma (HCC) remains unclear. In this study, we speculated that the pseudogene-derived lncRNA PCNAP1 and its ancestor PCNA might modulate HBV replication and promote hepatocarcinogenesis. Methods: We investigated the roles of lncRNA PCNAP1 in contribution of HBV replication through modulating miR-154/PCNA/HBV cccDNA signaling in hepatocarcinogenesis by using CRISPR/Cas9, Southern blot analysis, confocal assays, et al. in primary human hepatocytes (PHH), HepaRG cells, HepG2-NTCP cells, hepatoma carcinoma cells, human liver-chimeric mice model, transgenetic mice model, in vitro tumorigenicity and clinical patients. Results: Interestingly, the expression levels of PCNAP1 and PCNA were significantly elevated in the liver of HBV-infectious human liver-chimeric mice. Clinically, the mRNA levels of PCNAP1 and PCNA were increased in the liver of HBV-positive/HBV cccDNA-positive HCC patients. Mechanistically, PCNA interacted with HBV cccDNA in a HBc-dependent manner. PCNAP1 enhanced PCNA through sponging miR-154 targeting PCNA mRNA 3'UTR. Functionally, PCNAP1 or PCNA remarkably enhanced HBV replication and accelerated the growth of HCC in vitro and in vivo. Conclusion: We conclude that lncRNA PCNAP1 enhances the HBV replication through modulating miR-154/PCNA/HBV cccDNA signaling and the PCNAP1/PCNA signaling drives the hepatocarcinogenesis. Our finding provides new insights into the mechanism by which lncRNA PCNAP1 enhances HBV replication and hepatocarcinogenesis.

Long noncoding RNA HULC is identified and highly expressed in hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) is a key driver of liver cancer. In the present study, we found that HULC remarkably elevated the levels of HBeAg, HBsAg, HBcAg, pgRNA, HBx, HBV DNA and covalently closed circular DNA (cccDNA), which activated the HBV replication in HBV-expressing hepatoma cells or de novo HBV-infected cell lines (PHH, HepG2-NTCP and dHepaRG). Mechanistically, HULC enhanced HBV cccDNA stability by down-regulating the APOBEC3B in hepatoma cells. HULC significantly up-regulated microRNA-539, which targeted the 3'UTR of APOBEC3B mRNA. Luciferase reporter gene assays revealed a putative STAT3-binding site located in the upstream of miR-539 promoter. Moreover, we identified that HULC was able to elevate HBx, which co-activated the STAT3 to stimulate the miR-539 promoter. Then, miR-539 down-regulated APOBEC3B and promoted HBV replication. Functionally, HULC enhanced the growth of hepatoma cells by activating HBV in vitro and in vivo, which could be blocked by overexpressing APOBEC3B. In conclusion, HULC activates HBV by modulating HBx/STAT3/miR-539/APOBEC3B signaling in HBV-related HCC.

Objective The aim of this study was to investigate the underlying mechanism whereby HBx modulates the targeting of NUSAP1 by miR-18b to enhance hepatocarcinogenesis.Methods We employed an integrated approach of bioinformatics analysis and molecular experiments in hepatoma cells, HBV transgenic mice, and clinical liver cancer tissues to investigate the role of HBx-regulated miR-18b in the development of liver cancer.Results In this study, we report that the HBx-mediated tumor suppressor miR-18b modulates hepatocarcinogenesis during the host-HBV interaction. The expression levels of miR-18b were lower in clinical HBV-positive liver cancer tissues and liver tissues of HBV-transgenic mice. Interestingly, HBx inhibited miR-18b expression by inducing the methylation of CpG islands in its promoter. Accordingly, we tested the hypothesis that HBx enhanced hepatocarcinogenesis by increasing the expression of target genes of miR-18b. Moreover, we identified nucleolar spindle-associated protein 1 (NUSAP1) as one of the target genes of miR-18b. NUSAP1 was expressed at high levels in liver cancer tissues. Interestingly, HBx up-regulated NUSAP1 by suppressing miR-18b. Functionally, miR-18b significantly inhibited the proliferation of hepatoma cells by depressing NUSAP1 levels in vivo and in vitro.Conclusions Thus, we conclude that the targeting of NUSAP1 mRNA by the tumor suppressor miR-18b is controlled by HBx-modulated promoter methylation during the host-virus interaction, leading to hepatocarcinogenesis. Our findings provide new insights into the mechanism by which HBx-mediated miRNAs modulate hepatocarcinogenesis.

Rationale: Hepatitis B virus (HBV) is a leading cause of liver diseases. HBV covalently closed circular DNA (cccDNA) is a critical obstacle of complete elimination by anti-HBV therapy. HBV cccDNA accumulates in nucleus as a chromatin-like cccDNA minichromosome assembled by histones and non-histones. However, the underlying mechanism of modulation of cccDNA minichromosome in hepatocytes is poorly understood. Methods: A human liver-chimeric mouse model was established. The cccDNA-ChIP, Southern blot analysis, confocal assays, RIP assays and RNA pull-down assays, et al. were performed to assess the mechanism of assembly and epigenetic regulation of cccDNA minichromosome in human liver-chimeric mouse model, human primary hepatocytes (PHH), dHepaRG, HepG2-NTCP cell lines and clinical liver tissues. Results: Importantly, the expression levels of HAT1, CAF-1 and lncRNA HULC were significantly elevated in the liver from HBV-infected human liver-chimeric mice. Strikingly, the depletion of HAT1 reduced HBV replication and cccDNA accumulation, and impaired the assembly of histone H3/H4 and the deposition of HBx and p300 onto cccDNA to form cccDNA minichromosome in the cells. Mechanically, chromatin assembly factor-1 (CAF-1) was involved in the events. Interestingly, HAT1 modified the acetylation of histone H3K27/H4K5/H4K12 on cccDNA minichromosome. Moreover, lncRNA HULC-scaffold HAT1/HULC/HBc complex was responsible for the modification on cccDNA minichromosome. Additionally, HBV activated HAT1 through HBx-co-activated transcriptional factor Sp1 in a positive feedback manner. Conclusion: HAT1 signaling contributes to assembly and epigenetic regulation of HBV cccDNA minichromosome.

BackgroundImmunotherapy, adjuvant chemotherapy, and prognosis of colorectal cancer are associated with MSI. Biopsy pathology cannot fully reflect the MSI status and heterogeneity of rectal cancer.PurposeTo develop a radiomic-based model to preoperatively predict MSI status in rectal cancer on MRI.AssessmentThe patients were divided into two cohorts (training and testing) at a 7:3 ratio. Radiomics features, including intensity, texture, and shape, were extracted from the segmented volumes of interest based on T2-weighted and ADC imaging.Statistical TestsIndependent sample t test, Mann-Whitney test, the chi-squared test, Receiver operating characteristic curves, calibration curves, decision curve analysis and multi-variate logistic regression analysisResultsThe radiomics models were significantly associated with MSI status. The T2-based model showed an area under the curve of 0.870 with 95% CI: 0.794–0.945 (accuracy, 0.845; specificity, 0.714; sensitivity, 0.976) in training set and 0.895 with 95% CI, 0.777–1.000 (accuracy, 0.778; specificity, 0.887; sensitivity, 0.772) in testing set. The ADC-based model had an AUC of 0.790 with 95% CI: 0.794–0.945 (accuracy, 0.774; specificity, 0.714; sensitivity, 0.976) in training set and 0.796 with 95% CI, 0.777–1.000 (accuracy, 0.778; specificity, 0.889; sensitivity, 0.772) in testing set. The combined model integrating T2 and ADC features showed an AUC of 0.908 with 95% CI: 0.845–0.971 (accuracy, 0.857; specificity, 0.762; sensitivity, 0.952) in training set and 0.926 with 95% CI: 0.813-1.000 (accuracy, 0.852; specificity, 1.000; sensitivity, 0.778) in testing set. Calibration curve showed that the combined score had a good calibration degree, and the decision curve demonstrated that the combined score was of benefit for clinical use.Data ConclusionRadiomics analysis of T2W and ADC images showed significant relevance in the prediction of microsatellite status, and the accuracy of combined model of ADC and T2W features was better than either alone.

Early growth response gene (EGR1) is a transcription factor known to be a downstream effector of B-cell receptor signaling and Janus kinase 1 (JAK1) signaling in diffuse large B-cell lymphoma (DLBCL). While EGR1 is characterized as a tumor suppressor in leukemia and multiple myeloma, the role of EGR1 in lymphoma is unknown. Here we demonstrate that EGR1 is a potential oncogene that promotes cell proliferation in DLBCL. IHC analysis revealed that EGR1 expression is elevated in DLBCL compared with normal lymphoid tissues and the level of EGR1 expression is higher in activated B cell–like subtype (ABC) than germinal center B cell–like subtype (GCB). EGR1 expression is required for the survival and proliferation of DLBCL cells. Genomic analyses demonstrated that EGR1 upregulates expression of MYC and E2F pathway genes through the CBP/p300/H3K27ac/BRD4 axis while repressing expression of the type I IFN pathway genes by interaction with the corepressor NAB2. Genetic and pharmacologic inhibition of EGR1 synergizes with the BRD4 inhibitor JQ1 or the type I IFN inducer lenalidomide in growth inhibition of ABC DLBCL both in cell cultures and xenograft mouse models. Therefore, targeting oncogenic EGR1 signaling represents a potential new targeted therapeutic strategy in DLBCL, especially for the more aggressive ABC DLBCL. Implications: The study characterizes EGR1 as a potential oncogene that promotes cell proliferation and defines EGR1 as a new molecular target in DLBCL, the most common non-Hodgkin lymphoma.

Introduction: The objective of this article was to detect the expression pattern and clinical value of miR-425-5p in diabetic retinopathy (DR) patients and investigate its effect on the proliferation and migration of human retinal microvascular endothelial cells (HRMECs) in a high glucose (HG) state. Methods: The serum miR-425-5p level of the subjects was determined using quantitative real-time PCR. The diagnostic value of serum miR-425-5p was validated using the receiver operating characteristic curve. Pearson analysis detected the correlation between clinical indicators and microRNA. The influence of miR-425-5p on cell proliferation and migration under HG conditions was calculated by using Cell Counting Kit-8 and Transwell assay. Results: Serum miR-425-5p levels showed a gradual increasing trend in the healthy control group, the diabetic mellitus patients without DR, and DR patients. Moreover, the levels of miR-425-5p in proliferative DR (PDR) patients were elevated than that of non-PDR (NPDR) patients. Furthermore, upregulated miR-425-5p had a high diagnostic value for DR patients and can distinguish PDR patients from NPDR patients. The expression of miR-425-5p was significantly positively correlated with the fasting plasma glucose, glycosylated hemoglobin (HbA1C), homeostasis model assessment of insulin resistance, and disease course of the patients. Under HG conditions, overexpression of miR-425-5p promoted HRMEC proliferation and migration, while inhibition of miR-425-5p led to opposite results. Conclusion: Present research confirmed that serum miR-425-5p levels in DR are marked by elevation. High expression of miR-425-5p can be used as a feasible diagnostic biomarker for DR patients and can predict the development and severity of DR. Moreover, inhibiting the expression of miR-425-5p levels under the condition of hyperglycemia may be used as a valuable therapeutic strategy for preventing the pathogenesis of DR.

Physiological reactive oxygen species (ROS) play an important role in cellular signal transduction. However, excessive ROS is an important pathological mechanism in most cardiovascular diseases (CVDs), such as myocardial aging, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction) and heart failure. Programmed cell death, hypertrophy and fibrosis may be due to oxidative stress. Sestrin 2 (Sesn2), a stress-inducible protein associated with various stress conditions, is a potential antioxidant. Sesn2 can suppress the process of heart damage caused by oxidative stress, promote cell survival and play a key role in a variety of CVDs. This review discusses the effect of Sesn2 on the redox signal, mainly via participation in the signaling pathway of nuclear factor erythroid 2-related factor 2, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin complex 1. It also discusses the effect of Sesn2's antioxidant activity on different CVDs. We speculate that Sesn2 plays an important role in CVDs by stimulating the process of antioxidation and promoting the adaptation of cells to stress conditions and/or the environment, opening a new avenue for related therapeutic strategies.

Background: Branched-chain amino acids (BCAAs), essential nutrients including leucine, isoleucine, and valine, serve as a resource for energy production and the regulator of important nutrient and metabolic signals. Recent studies have suggested that dysfunction of BCAA catabolism is associated with the risk of cardiovascular disease. Platelets play an important role in cardiovascular disease, but the functions of BCAA catabolism in platelets remain unknown. Methods: The activity of human platelets from healthy subjects before and after ingestion of BCAAs was measured. Protein phosphatase 2Cm specifically dephosphorylates branched-chain α-keto acid dehydrogenase and thereby activates BCAA catabolism. Protein phosphatase 2Cm–deficient mice were used to elucidate the impacts of BCAA catabolism on platelet activation and thrombus formation. Results: We found that ingestion of BCAAs significantly promoted human platelet activity (n=5; P P P ob/ob mice (n=4; P Conclusions: BCAA catabolism is an important regulator of platelet activation and is associated with arterial thrombosis risk. Targeting the BCAA catabolism pathway or lowering dietary BCAA intake may serve as a novel therapeutic strategy for metabolic syndrome–associated thrombophilia.

Hepatitis B virus (HBV) is a major risk factor for liver diseases, in which HBV covalently closed circular DNA (cccDNA), as the genomic form that templates viral transcription, plays crucial roles in sustaining viral persistence. Clinically, the excessive ethanol intake accelerates the progression of liver diseases with HBV infection. Here, we supposed that ethanol might trigger HBV cccDNA in the liver. Interestingly, we observed that the ethanol remarkably elevated the levels of HBeAg, HBsAg, HBV DNA and cccDNA in HBV-expressing hepatoma cells. Mechanically, the ethanol increased the levels of HBx and MSL2 in vivo and in HBV-expressing HepG2 cells, but not in HBV-free HepG2 cells. Moreover, the down-regulation of MSL2 by small interference RNA could block the ethanol-promoted HBV cccDNA in HepG2.2.15 cells. As a commonly administered treatment for HBV, the effect of IFNα on ethanol-triggered HBV cccDNA remains poorly understood. Strikingly, we showed that the treatment with IFN-α2b inhibited the ethanol-promoted cccDNA through depressing MSL2 in the cells. Thus, we conclude that IFN-α2b inhibits the ethanol-enriched HBV cccDNA through blocking a positive feedback loop of HBx/MSL2/cccDNA/HBV/HBx. Our finding provides new insights into the mechanism by which IFN-α2b inhibits ethanol-enhanced HBV cccDNA. Therapeutically, IFNα may contribute to the cccDNA induced by ethanol in liver.

The function of microRNA-27a (miR-27a) expression in cholangiocarcinoma (CCA) remains largely unclear; therefore, this study aimed to investigate the clinical significance and functional role of miR-27a in CCA. This study included 117 paired CCA tissues and adjacent normal tissues from CCA patients who received surgical resection. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression levels of miR-27a in CCA tissues and cell lines. A Kaplan-Meier curve and Cox regression analysis were used to determine overall prognostic performance. The effects of miR-27a on cell proliferation, migration, and invasion were measured by CCK-8 and Transwell assays. The expression levels of miR-27a in patients with CCA and cell lines were higher than those in adjacent normal tissues and normal cells, respectively. Additionally, miR-27a levels were found to be associated with lymph node metastasis and TNM stages. The overall survival time of CCA patients with high miR-27a expression was poorer than that of those with low miR-27a expression. Furthermore, miR-27a overexpression promoted CCA cell proliferation, migration, and invasion, whereas knockdown of miR-27a suppressed cell proliferation, migration, and invasion. Taken together, these results suggest the potential usefulness of miR-27a in the prognosis and progression of CCA.

As an inevitable biological process, cardiovascular aging is the greatest risk factor for cardiovascular diseases (CVDs). Sestrin 2 (Sesn2), a stress-inducible and age-related protein associated with various stress conditions, plays a pivotal role in slowing this process. It acts as an anti-aging agent, mainly through its antioxidant enzymatic activity and regulation of antioxidant signaling pathways, as well as by activating adenosine monophosphate-activated protein kinase and inhibiting mammalian target of rapamycin complex 1. In this review, we first introduce the biochemical functions of Sesn2 in the cardiovascular aging process, and describe how Sesn2 expression is regulated under various stress conditions. Next, we emphasize the role of Sesn2 signal transduction in a series of age-related CVDs, including hypertension, myocardial ischemia and reperfusion, atherosclerosis, and heart failure, as well as provide potential mechanisms for the association of Sesn2 with CVDs. Finally, we present the potential therapeutic applications of Sesn2-directed therapy and future prospects.

Aspirin can efficiently inhibit liver cancer growth, but the mechanism is poorly understood. In this study, we report that aspirin modulates glucose uptake through downregulating glucose transporter 1 (GLUT1), leading to the inhibition of hepatoma cell proliferation. Our data showed that aspirin significantly decreased the levels of reactive oxygen species (ROS) and glucose consumption in hepatoma cells. Interestingly, we identified that GLUT1 and HIF1α could be decreased by aspirin. Mechanically, we demonstrated that the -1008/-780 region was the regulatory element of transcriptional factor NF-κB in GLUT1 promoter by luciferase report gene assays. PDTC, an inhibitor of NF-κB, could suppress the expression of GLUT1 in HepG2 and H7402 cells, followed by affecting the levels of ROS and glucose consumption. CoCl(2)-activated HIF1α expression could slightly rescue the GLUT1 expression inhibited by aspirin or PDTC, suggesting that aspirin depressed GLUT1 through targeting NF-κB or NF-κB/HIF1α signaling. Moreover, we found that GLUT1 was highly expressed in clinical HCC tissues relating to their paired adjacent normal tissues. Importantly, we observed that high level of GLUT1 was significantly correlated with the poor relapse-free survival of HCC patients by analysis of public data. Functionally, overexpression of GLUT1 blocked the PDTC-induced or aspirin-induced inhibition of glucose metabolism in HepG2 cells. Conversely, aspirin failed to work when GLUT1 was stably knocked down in the cells. Administration of aspirin could depress the growth of hepatoma cells through controlling GLUT1 in vitro and in vivo. Thus, our finding provides new insights into the mechanism by which aspirin depresses liver cancer.

Objective This study aimed to investigate the relationship between BTB/POZ domain-containing protein 7 (BTBD7) and fibronectin (FN) expression in salivary adenoid cystic carcinoma (SACC) and the function of BTBD7 in proliferation, migration, and invasion of SACC cells. Study Design The BTBD7 and FN expression in SACC and nontumor salivary tissues as well as SACC cells were characterized by immunohistochemistry and immunofluorescence. The effect of BTBD7 silencing on the proliferation, migration, and invasion of SACC-LM cells were determined by wound healing and transwell invasion assays. Results The percentages of SACC with positive BTBD7 expression were significantly higher than those of SACC with FN expression. BTBD7 silencing significantly increased the relative levels of FN expression and inhibited the proliferation, migration, and invasion of SACC-LM cells. Conclusions The study data indicated that BTBD7 was inversely associated with FN expression in SACC. BTBD7 may inhibit FN expression, but it promotes the proliferation, migration, and invasion of SACC-LM cells. Hence, BTBD7 may be associated with metastasis and a new therapeutic target for intervention of SACC.

Methyltransferase-like 3 (METTL3) is involved in RNA metabolism through N6-methyladenosine (m6A) modification. However, whether METTL3 participates in the progression of breast cancer is unclear. Aberrant expression of Mammalian hepatitis B X-interacting protein (HBXIP) drives the aggressiveness of breast cancer. Here, we are interested in the potential links between HBXIP and METTL3 in breast cancer. We showed that the expression of METTL3 was positively related to that of HBXIP in clinical breast cancer tissues. Moreover, HBXIP could up-regulate METTL3 in breast cancer cells. Mechanistically, HBXIP modulated METTL3 by inhibiting miRNA let-7g, which down-regulated the expression of METTL3 by targeting its 3'UTR. Strikingly, we found that METTL3 promoted the expression of HBXIP through m6A modification. Furthermore, overexpressed HBXIP could rescue the inhibited-proliferation and enhanced-apoptosis induced by silencing of METTL3 in breast cancer cells. Thus, we conclude that HBXIP up-regulates METTL3 by suppressing let-7g, in which METTL3 increased HBXIP expression forming a positive feedback loop of HBXIP/let-7g/METTL3/HBXIP, leading to accelerated cell proliferation in breast cancer. Our finding provides new insights into the mechanism of the mutual regulation between HBXIP and METTL3 in the progression of breast cancer.

e23531 Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if anlotinib, a multitarget tyrosine kinase inhibitor, is efficacy and safety for the first-line treatment of these patients. Methods: This is an open-label, single-arm, multicenter, phase II clinical trial (NCT03792542) including 44 planned subjects. Eligible patients were aged 18-70 years old, diagnosed with locally advanced or metastatic soft-tissue sarcoma and had at least one measurable lesion according to RECIST 1.1. Other inclusion criteria included ECOG PS 0̃2, chemotherapy and anti-angiogenesis treatment naïve. Patients were administrated 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Here we report the results of a planned interim analysis. Results: From April 2019 to December 2020, 29 patients (16 males and 13 females) were enrolled from 7 hospitals in China. The median age is 57 (range 23-69). Pathological types included liposarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), fibrosarcoma (n = 5), synovial sarcoma (n = 4), and others (n = 7). At the data cutoff date on December 31, 2020, the median duration of treatment was 5.3 months, and the median PFS was not reached. 26 patients were eligible for the evaluation of tumor response.1 achieved partial response (PR) and the objective response rate (ORR) was 3.85% (1/26). 24 had stale disease (SD) and the disease control rate (DCR) was 96.2% (25/26). The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than 4 and 6 months, were 65.4% (17/26) and 38.5% (10/26) respectively. Most adverse events (AE) were grade 1 or 2. The most common grade 3 AE was hypertension (17.2%). No grade 4 AEs or treatment related death occurred in this study through the last follow-up. Conclusions: This interim analysis showed anlotinib of promising efficacy and favorable tolerance in the first-line treatment of locally advanced or metastatic soft- tissue sarcoma. Clinical trial information: NCT03792542.

Chronic hepatitis B virus (HBV) infection is a leading cause in the occurrence of hepatitis B, liver cirrhosis and liver cancer, in which nuclear HBV covalently closed circular DNA (cccDNA), the genomic form that templates viral transcription and sustains viral persistence, plays crucial roles. In the present study, we explored the hypothesis that HBV X protein (HBx)-elevated male-specific lethal 2 (MSL2) activated HBV replication via modulating cccDNA in hepatoma cells, leading to hepatocarcinogenesis. Immunohistochemical analysis revealed that the expression of MSL2 was positively associated with that of HBV and was increased in the liver tissues of HBV-transgenic mice and clinical HCC patients. Interestingly, microarray profiling identified that MSL2 was associated with those genes responding to virus. Mechanistically, MSL2 could maintain HBV cccDNA stability through degradation of APOBEC3B by ubiquitylation in hepatoma cells. Above all, HBx accounted for the up-regulation of MSL2 in stably HBx-transfected hepatoma cell lines and liver tissues of HBx-transgenic mice. Luciferase reporter gene assays revealed that the promoter region of MSL2 regulated by HBx was located at nt -1317/-1167 containing FoxA1 binding element. ChIP assay validated that HBx could enhance the binding property of FoxA1 to MSL2 promoter region. HBx up-regulated MSL2 via activating YAP/FoxA1 signaling. Functionally, silencing MSL2 was able to block the growth of hepatoma cells in vitro and in vivo. In conclusion, HBx-elevated MSL2 modulates HBV cccDNA in hepatoma cells to promote hepatocarcinogenesis, forming a positive feedback loop of HBx/MSL2/cccDNA/HBV. Our finding uncovers novel insights into the mechanism by which MSL2 as a promotion factor in host cells selectively activates extrachromosomal DNA. This article is protected by copyright. All rights reserved.

Objectives. To compare consumption of carbonated soft drinks among young adolescents in 53 low- and middle-income countries (LMICs). Methods. We used 2009 to 2013 Global School-based Student Health Survey data to assess 137 449 young adolescents aged 12 to 15 years with available data (via a standardized questionnaire) on frequency of carbonated soft drink consumption. Results. Overall, young adolescents reported having consumed carbonated soft drinks 1.39 times per day (95% confidence interval [CI] = 1.26, 1.51), and 54.3% of adolescents reported consuming a carbonated soft drink at least once per day. Frequency (times per day) varied greatly across countries, ranging from 0.52 (95% CI = 0.43, 0.60) in Kiribati to 2.39 (95% CI = 2.25, 2.53) in Suriname. Conclusions. Our data confirm that consumption of carbonated soft drinks is frequent among young adolescents in LMICs. Our findings highlight the need for interventions in these countries to reduce adolescents’ carbonated soft drink consumption.

Abnormal lipid metabolism is a hallmark of tumorigenesis. Hence, the alterations of metabolism enhance the development of hepatocellular carcinoma (HCC). Aspirin is able to inhibit the growth of cancers through targeting nuclear factor κB (NF-κB). However, the role of aspirin in disrupting abnormal lipid metabolism in HCC remains poorly understood. In this study, we report that aspirin can suppress the abnormal lipid metabolism of HCC cells through inhibiting acyl-CoA synthetase long-chain family member 1 (ACSL1), a lipid metabolism-related enzyme. Interestingly, oil red O staining showed that aspirin suppressed lipogenesis in HepG2 cells and Huh7 cells in a dose-dependent manner. In addition, aspirin attenuated the levels of triglyceride and cholesterol in the cells, respectively. Strikingly, we identified that aspirin was able to down-regulate ACSL1 at the levels of mRNA and protein. Moreover, we validated that aspirin decreased the nuclear levels of NF-κB in HepG2 cells. Mechanically, PDTC, an inhibitor of NF-κB, could down-regulate ACSL1 at the levels of mRNA and protein in the cells. Functionally, PDTC reduced the levels of lipid droplets, triglyceride and cholesterol in HepG2 cells. Thus, we conclude that aspirin suppresses the abnormal lipid metabolism in HCC cells via disrupting an NFκB-ACSL1 signaling. Our finding provides new insights into the mechanism by which aspirin inhibits abnormal lipid metabolism of HCC. Therapeutically, aspirin is potentially available for HCC through controlling abnormal lipid metabolism.

Until now, the relationship of obstructive sleep apnoea (OSA) with diabetic retinopathy (DR) was controversial. This meta-analysis was performed to obtain definitive conclusion on this topic. Relevant articles were searched on databases of Pubmed, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). The articles were selected according to inclusion and exclusion criteria. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship of OSA with risk of DR.I2andPvalue were used to assess the presence of heterogeneity.I2≥ 50% orP<0.05indicated significant heterogeneity. Sensitivity analysis was performed to evaluate the robustness of pooled results. Begg’s funnel plot and Egger’s regression analysis were adopted to assess publication bias. 6 eligible studies were selected in the present meta-analysis. The pooled results indicated that OSA was significantly associated with increased risk of DR (OR = 2.01, 95% CI = 1.49–2.72). Subgroup analysis based on type of diabetes mellitus suggested that OSA was related to DR in both Type 1 and Type 2 diabetes mellitus. Sensitivity analysis demonstrated that pooled results were robust. No significant publication bias was observed (P=0.128). The results indicate that OSA is related to increased risk of DR.

Branched chain α-keto acids (BCKAs) are endogenous metabolites of branched-chain amino acids (BCAAs). BCAA and BCKA are significantly elevated in pathologically stressed heart and contribute to chronic pathological remodeling and dysfunction. However, their direct impact on acute cardiac injury is unknown. Here, we demonstrated that elevated BCKAs significantly attenuated ischemia-reperfusion (I/R) injury and preserved post I/R function in isolated mouse hearts. BCKAs protected cardiomyocytes from oxidative stress-induced cell death in vitro. Mechanistically, BCKA protected oxidative stress induced cell death by inhibiting necrosis without affecting apoptosis or autophagy. Furthermore, BCKAs, but not BCAAs, protected mitochondria and energy production from oxidative injury. Finally, administration of BCKAs during reperfusion was sufficient to significantly attenuate cardiac I/R injury. These findings uncover an unexpected role of BCAAs metabolites in cardioprotection against acute ischemia/reperfusion injury, and demonstrate the potential use of BCKAs treatment to preserve ischemic tissue during reperfusion.

The stimulator of interferon genes (STING) protein has been shown to play a pivotal role in response to both cytosolic RNA and dsDNA to elicit interferon (IFN) production in mammals. However, the role of duck STING (DuSTING) in antiviral innate immunity, especially in anti-RNA virus infection, has yet to be elucidated. In this study, the function of DuSTING in IFN induction and its role in anti-RNA virus infections were studied. DuSTING was amplified via reverse transcription-polymerase chain reaction (RT-PCR) from Pekin duck, showing that its cDNA sequence contains an open reading frame (ORF) of 1,149 bp and encodes 382 amino acids (aa). Sequence alignment showed that DuSTING protein shares 71.1, 43.4, and 33.3% identity with chickens, humans, and zebra fish, respectively. Overexpression of DuSTING in duck embryo fibroblasts (DEFs) strongly activated IFN-β promotor activity. Deletion mutant analysis revealed that the first 42 aa containing the first transmembrane (TM) domains and the last 32 aa containing a part of the C-terminal tail (CTT) are essential for its IFN-β activation. In vitro experiments showed that the mRNA levels of DuSTING and IFNs were all upregulated when the DEFs were infected with H9N2 avian influenza virus (AIV) SH010, while overexpression of DuSTING inhibited the replication of this virus. In vivo studies showed that DuSTING mRNA was widely expressed in different tissues, and was up-regulated in the spleen and lung of ducks challenged with SH010. In conclusion, our results indicate that DuSTING is an essential IFN mediator and plays a role in anti-RNA virus innate immunity.

This study aimed to evaluate the efficacy of electroacupuncture (EA) on Ciliao (BL 32) and Zhongliao (BL 33) acupoints at different depths for the treatment of benign prostatic hyperplasia (BPH) through a single-blind randomized controlled trial. All 120 patients diagnosed with BPH were randomly allocated to an experimental group (deep insertion group, DI group, n = 60) and control group (shallow insertion group, SI group, n = 60) 3 times a week for 4 weeks. The observed results included the International Prostate Symptom Score (IPSS), Quality of Life score (QOL), maximum urine flow rate (Qmax), and postvoid residual urine volume (PVR). After treatment, at both depths, the BPH symptoms of patients were improved by EA. There were significant differences between the IPSS, QOL, and the effective rate of the experimental group and the control group (P<0.05). Although the observed PVR and Qmax were better than those before treatment, there was no statistical significance between two groups (P>0.05). Thus, EA with deep insertion can effectively improve the patients’ urinary symptoms and quality of life, and it will be suitable for clinical application.

Background Diagnosis of tuberculosis (TB) in children is challenging. Epidemiological data of childhood pulmonary tuberculosis (PTB) are urgently needed. Methods We described trends in epidemiology, clinical characteristics, and treatment outcomes in seven cities of Shandong province, China, during 2005–2017. Data were collected from the China Information System for Disease Control and Prevention. Results Among 6283 (2.4% of all PTB) PTB cases aged

TANK-binding kinase 1 (TBK1) is involved in innate immunity, prompting transcriptional induction of type I interferons in response to pathogenic infection. Many studies have focused on mammals but the function of TBK1 in chickens remains poorly defined. CRISPR/Cas9 system has made gene-knockout easy to accomplish. Although CRISPR/Cas9 has been used in chicken cells, low mutation efficiency limits its wide application in chickens. In this study, an effective gene-knockout system was developed based on the CRISPR/Cas9 system in chicken embryonic fibroblast DF-1. Two CRISPR/Cas9 plasmids were constructed, TBK1-g1 and TBK1-g2, which express gRNAs targeting different sequences of the chicken TBK1 gene. After transfection and enrichment with puromycin screening, the mutation rates as assessed via T7E1 assay were 88.05 and 89.55%, respectively, and subsequent sequence analysis showed mutation efficiencies of 86.67 and 93.33%. With the limiting-dilution method, a chTBK1 gene-deficiency monoclonal cell line was obtained and was named DF-1-TBK1-C3. The DF-1-TBK1-C3 cells exhibited normal morphology and maintained stable proliferation ability compared to wild-type cells. The gene-overexpression system and luciferase reporter assay showed that IFN-β induction induced by chSTING was almost completely blocked in DF-1-TBK1-C3 cells. With quantitative real-time PCR, we further confirmed the essential role of chTBK1 in the chSTING-mediated IFN-β induction. At last, the study demonstrated that the chTBK1 knockout system is also applicable in primary chick embryo fibroblasts (CEFs). In this study, an effective gene-knockout system was applied in chickens, a TBK1 gene-deleted DF-1 cell line was successfully created using this system, and with the chTBK1 knockout cells, chTBK1 was revealed to be indispensable in STING-mediated IFN-β activation in chicken cells.

Background Oral mucositis (OM), one of the most common side effects for cancer patients who have undergone chemotherapy, can cause severe impairment to patients' functional ability and impact their quality of life, resulting in delayed and/or incomplete treatment. Traditional Chinese medicine offers empirical herbal decoctions to gargle for the prevention of chemotherapy-induced OM; however, evidence for its clinical efficacy and safety is lacking. Therefore, we provide a protocol to evaluate the preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced OM. Methods We will comprehensively retrieve relevant articles published till August 15, 2020, in the following electronic databases: the Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, Chinese Science and Technique Journals Database, and the Wan-fang Database. Only randomized controlled trials will be included. We will use the criteria provided by the Cochrane Handbook for quality assessment and risk assessment of the included studies and use the RevMan 5.3 software for meta-analysis of the preventive effect and safety. Results This study will assess the preventive effect and safety of Chinese herbal medicine mouthwash in chemotherapy-induced OM. Conclusion This systematic review will provide evidence-based medical corroboration for the clinical application of the Chinese herbal medicine mouthwash in chemotherapy-induced OM. Prospero registration number CRD42020206614.

Background Cancer-related depression (CRD) is the most common mood disorder in patients with malignant tumors, negatively influencing the patient's daily life. Traditional Chinese medicine, as an alternative CRD therapy, has shown good treatment performance in recently years. Soothing liver-qi stagnation, as a classic therapy for depression, is based on traditional Chinese medicine theory. However, there is no evidence-based medical confirmation for the soothing liver-qi stagnation method for CRD treatment. Methods We will systematically search relevant articles from their inception to July 1, 2019 in the following electronic databases: the Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, Chinese Science and Technique Journals Database, and the Wan-fang Database. The primary outcome is the total scores of the Hamilton rating scale for depression and, the efficacy rate of reducing Hamilton rating scale for depression scores. The secondary outcomes are adverse reactions and quality of life as assessed by standard instruments. Two researchers will independently perform study selection, data extraction, and quality assessment. If there is any disagreement, it will be settled through third-party negotiations. We will assess the risk of bias and data synthesis using Review Manager (the Cochrane Collaboration) software, Version 5.3.0. Results This work will evaluate the clinical effectiveness and safety of the soothing liver-qi stagnation method for CRD. Conclusion This study may provide evidence-based medical corroboration for clinical application of the soothing liver-qi stagnation method for CRD treatment. Prospero registration number CRD42019145678.

Purpose: To develop and validate a delta-radiomics model for predicting a pathologic response after chemotherapy preoperatively in high-grade osteosarcoma (HOS). Materials and Methods: A total of 191 patients with HOS were enrolled retrospectively from November 2013 to November 2017 and received neoadjuvant chemotherapy. A cutoff time of November 2016 was used to divide the training set and validation set. All patients underwent diagnostic CTs before and after chemotherapy. By quantifying the tumor region on the two-phase CT images, 540 delta-radiomics features were calculated. A delta-radiomics signature was constructed using the lasso algorithm based on the training set. A radiomics nomogram was then developed from the multivariate logistic regression model by combining independent clinical factors and the delta-radiomics signature. The prediction accuracy was assessed according to receiver operating characteristic (ROC) and calibration curves. Results: The delta-radiomics signature, consisting of 8 selected features, showed significant differences between the pathologic good response (pGR) (necrosis fraction ≥90%) group and the non-pGR (necrosis fraction

Hand, foot and mouth disease (HFMD) has been a substantial burden throughout the Asia-Pacific countries over the past decades. For the purposes of disease prevention and climate change health impact assessment, it is important to understand the temperature–disease association for HFMD in different geographical locations. This study aims to assess the impact of temperature on HFMD incidence in an inland city and a coastal city and investigate the heterogeneity of temperature–disease associations. Daily morbidity data and meteorological variables of the study areas were collected for the period from 2007 to 2012. A total of 108,377 HFMD cases were included in this study. A distributed lag non-linear model (DLNM) with Poisson distribution was used to examine the nonlinear lagged effects of daily mean temperature on HFMD incidence. After controlling potential confounders, temperature showed significant association with HFMD incidence and the two cities demonstrated different impact modes ( I2= 96.1%, p &lt, 0.01). The results highlight the effect of temperature on HFMD incidence and the impact pattern may be modified by geographical localities. Our findings can be a practical reference for the early warning and intervention strategies of HFMD.

The glucose metabolism reprogramming is a hallmark of cancer. The oncoprotein hepatitis B X-interacting protein (HBXIP) functions in the development of breast cancer. In this study, we supposed that HBXIP might be involved in the glucose metabolism reprogramming in breast cancer. We showed that HBXIP led to increases in generation of intracellular glucose and lactate, as well as decreases in generation of reactive oxygen species. Expression of synthesis of cytochrome c oxidase 2 (SCO2) and pyruvate dehydrogenase alpha 1 (PDHA1), two factors of metabolic switch from oxidative phosphorylation to aerobic glycolysis, was suppressed by HBXIP. In addition, miR-183/182 and miR-96 directly inhibited the expression of SCO2 and PDHA1 through targeting their mRNA coding sequences (CDSs), respectively. Interestingly, HBXIP elevated the miR-183/96/182 cluster expression through hypoxia-inducible factor 1α (HIF1α). The stability of HIF1α was enhanced by HBXIP through disassociating interaction of von Hippel-Lindau protein (pVHL) with HIF1α. Moreover, miR-183 increased the levels of HIF1α protein through directly targeting CDS of VHL mRNA, forming a feedback loop of HIF1α/miR-183/pVHL/HIF1α. In function, HBXIP-elevated miR-183/96/182 cluster enhanced the glucose metabolism reprogramming in vitro. HBXIP-triggered glucose metabolism reprogramming promoted the growth of breast cancer in vivo. Thus, we conclude that the oncoprotein HBXIP enhances glucose metabolism reprogramming through suppressing SCO2 and PDHA1 in breast cancer.

Objectives: The aim of this study was to quantify the relationship between meteorological factors and the occurrence of hand, foot, and mouth disease (HFMD) among children in Shandong Province, China, at a county level, using spatial panel data models. Methods: Descriptive analysis was applied to describe the epidemic characteristics of HFMD from January 2008 to December 2012, and then a global autocorrelation statistic (Moran's I) was used to detect the spatial autocorrelation of HFMD in each year. Finally, spatial panel data models were performed to explore the association between the incidence of HFMD and meteorological factors. Results: Moran's I at the county level were high, from 0.30 to 0.45 (p

The objective of this study is to evaluate retrospectively the effectiveness of multiple-drug chemotherapeutics regimen that included high-dose methotrexate (HD-MTX) for treating primary osteosarcoma. 148 newly diagnosed patients with Stage I and II osteosarcoma who received HD-MTX/HD-MTX/DDP(cisplatin)/ADM(doxorubicin) and/or HD-MTX/IFO(Ifosfamide)/DDP/ADM before and after the surgery were retrospectively analyzed to measure the efficacy of this regimen. The significance of various variables as predictive prognostic factors of the patient survival rate was also evaluated. The overall 3-year survival rate of the patients was 79.73 %. The survival rate was improved to 85.71 % in the patients who received surgery and a complete 4-cycle chemotherapy. In addition, the rates of disease-free survival (DFS), local recurrence, and distant metastasis were 68.13, 3.30, and 10.81 %, respectively. Our analysis showed that completing 4-cycle chemotherapy produced a significant impact on the overall 3-year survival and DFS rates (P