Association between glucose levels and all-cause mortality in cancer survivors: findings from NHANES 1999-2018.

BACKGROUND: Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. METHODS: We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999-2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. RESULTS: In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value < 0.05). The threshold value for HbA1c was 5.4%, and the HRs (95% CI) below and above the threshold value were 0.917 (0.856,0.983) and 1.026 (1.010,1.043), respectively. Similar associations were found between fasting glucose and all-cause mortality in cancer survivors, and the threshold value was 5.7 mmol/L. CONCLUSIONS: HbA1c was nonlinearly associated with all-cause mortality in cancer survivors, and the critical value of HbA1c in decreased mortality was 5.4%, suggesting optimal glucose management in cancer survivors may be a key to preventing premature death in cancer survivors.

LncRNA Miat knockdown enhances pirarubicin-mediated anticancer sensitivity in breast cancer cells.

Pirarubicin (THP) is a widely used antitumor agent in clinical practice, but its reduced sensitivity during treatment has limited its use. The aim of this study was to investigate the role and mechanism of LncRNA Miat knockdown in improving THP sensitivity. We assessed the role of Miat overexpression/knockdown on THP-mediated 4T1 anticancer activity by CCK8, TUNEL, flow cytometry, wound healing assay, Transwell, Ca2+ , real time quantitative PCR (RT-qPCR) and Western blot. The results showed that Miat expression was higher in 4T1 mouse breast cancer cells than in HC11 mouse mammary epithelial cells, while THP decreased Miat expression in 4T1. Miat knockdown in combination with further reduced cell viability, promoted apoptosis and inhibited migration compared to THP alone. This may be related to the reduction of calcium ions in 4T1. In conclusion, Miat knockdown enhanced the sensitivity of THP to 4T1 by inhibiting calcium channels.

Comprehensive analysis of the roles of fatty acid transport related proteins in clear cell renal cell carcinoma.

OBJECTIVE: This study aimed to explore the clinical significance of fatty acid transport-related protein (FATRP) in patients with clear cell renal cell carcinoma(ccRCC). METHODS: RNA-seq data and corresponding clinical data of ccRCC were obtained from TCGA data portal. Seventeen key FATRP genes were comprehensively investigated using bioinformatics approaches to systematically investigate their expression patterns in ccRCC. In addition, the correlation between the expression levels of these genes and clinicopathological features in ccRCC was further explored. RESULTS: Among the 17 key FATRP genes, only FABP5, FABP6, and FABP7 could be regarded as ideal biomarkers for ccRCC, as they were highly expressed in ccRCC tumor tissues, and positively correlates with tumor progression and poor prognosis. FABP6 had the highest copy number variations (CNV) events (63.07 %), and ccRCC patients with FABP6 amplification had a better prognosis than the unaltered group. DNA methylation levels of FABP6 and FABP7 were downregulated in ccRCC tumor tissues compared to those in normal tissues. FABP5 showed the opposite results. Moreover, a novel four FATRP gene (FABP1, FABP5, FABP7, FATP2) and three clinical parameter (age, stage, and grade) prediction model was constructed and that comprised a significant independent prognostic signature. CONCLUSIONS: Only a few FATRP genes are upregulated in ccRCC tumor tissue, and positively correlate with tumor progression and poor prognosis. The accuracy of a single gene of these FATRP genes as predictors of progression and prognosis of ccRCC is limited. The performance of the novel prediction model proposed by this study was much better than that of any single gene.

Global, regional, and national time trends in cancer mortality attributable to high fasting plasma glucose: an age-period cohort analysis.

BACKGROUND: High fasting plasma glucose (HFPG) is the fastest-growing risk factor for cancer deaths worldwide. We reported the cancer mortality attributable to HFPG at global, regional, and national levels over the past three decades and associations with age, period, and birth cohort. METHODS: Data for this study were retrieved from the Global Burden of Disease Study 2019, and we used age-period-cohort modelling to estimate age, cohort and period effects, as well as net drift (overall annual percentage change) and local drift (annual percentage change in each age group). RESULTS: Over the past 30 years, the global age-standardized mortality rate (ASMR) attributable to HFPG has increased by 27.8%. The ASMR in 2019 was highest in the male population in high sociodemographic index (SDI) areas (8.70; 95% CI, 2.23-18.04). The net drift for mortality was highest in the female population in low SDI areas (2.33; 95% CI, 2.12-2.55). Unfavourable period and cohort effects were found across all SDI quintiles. Cancer subtypes such as "trachea, bronchus, and lung cancers", "colon and rectal cancers", "breast cancer" and "pancreatic cancer" exhibited similar trends. CONCLUSIONS: The cancer mortality attributable to HFPG has surged during the past three decades. Unfavourable age-period-cohort effects on mortality were observed across all SDI quintiles, and the cancer mortality attributable to HFPG is expected to continue to increase rapidly in the future, particularly in lower SDI locations. This is a grim global public health issue that requires immediate attention.

LncRNA Miat knockdown protects against pirarubicin-induced cardiotoxicity by targeting miRNA-129-1-3p.

Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. The aim of this study was to investigate the protective effect and mechanism of knockdown of lncRNA Miat in THP-induced cardiotoxicity. The extent of damage to immortalized cardiomyocytes in mice was assessed by CCK8, TUNEL, ROS, Ca2+ , RT-qPCR, and Western blot. The relative levels of Miat in THP-treated cardiomyocytes (HL-1) were measured. The protective effect of Miat on THP-treated HL-1 was assessed. The binding relationship between lncRNA Miat and mmu-miRNA-129-1-3p was verified by a dual luciferase reporter gene assay. The protective role of Miat/miRNA-129-1-3p in THP-induced HL-1 was explored by performing a rescue assay. THP reduced cell viability, induced apoptosis, triggered oxidative stress and calcium overload. Expression of Miat in HL-1 was significantly elevated after THP treatment. Miat knockdown significantly alleviated the cardiotoxicity of THP. MiR-129-1-3p is a direct target of Miat. Knockdown of miR-129-1-3p reversed the protective effect of Miat knockdown on HL-1. Miat knockdown can alleviate THP-induced cardiomyocyte injury by regulating miR-129-1-3p.

MiR-494-3p aggravates pirarubicin-induced cardiomyocyte injury by regulating MDM4/p53 signaling pathway.

OBJECTIVE: Pirarubicin (THP) is a widely used antitumor drug in clinical practice, but its cardiotoxicity limits its use. There is an urgent need to find drugs to alleviate the cardiotoxicity of THP. This study aimed to investigate the effect and mechanism of miR-494-3p on THP-induced cardiomyocytes. METHODS: THP induced immortalized mouse cardiomyocytes HL-1, silenced or overexpressed miR-494-3p. The effects of miR-494-3p on HL-1 contained in THP were investigated by CCK8, flow cytometry, ROS detection, JC-1 mitochondrial membrane potential detection, TUNEL cell apoptosis detection, RT-qPCR, and Western blot. RESULTS: miR-494-3p could reduce cell viability, increase oxidative damage, and promote cell apoptosis; at the same time, it inhibited the expression of MDM4, promoted the activation of p53, and promoted the expression of apoptosis-related proteins. MiR-494-3p inhibitors have the opposite effect. CONCLUSION: miR-494-3p can aggravate THP damage to HL-1, which may be achieved by downregulating MDM4 and promoting p53. miR-494-3p is one of the important miRNAs in THP-induced cardiotoxicity, which provides theoretical support for its possible use as a therapeutic target for THP-induced cardiovascular disease.

Effects of Chronic Remote Ischemic Conditioning on Atrial Fibrillation Burden in Patients with Permanent Pacemakers.

This study aimed to evaluate the effects of chronic remote ischemic conditioning (CRIC) on atrial fibrillation burden in patients with an implanted pacemaker. Sixty-six patients with permanent pacemakers were randomly divided into the CRIC group and control group after 4 weeks of screening. CRIC treatment was performed twice daily for 12 weeks. The remote ischemic conditioning protocol consisted of 4 × 5 minutes inflation/deflation of the blood pressure cuff applied in the upper arm to create intermittent arm ischemia. Sixty-one patients (31 patients in the CRIC group and 30 patients in the control group) completed the study. CRIC was well tolerated by patients after 12 weeks of treatment. The burden of atrial fibrillation (AF) in the CRIC group decreased significantly at 4 weeks compared with that at 0 weeks (14.7% ± 18.5% versus 17.0% ± 20.7%, P < 0.001), which further decreased at 12 weeks compared with that at 0 weeks (8.6% ± 10.2% versus 17.0% ± 20.7%, P < 0.001) and that at 4 weeks (8.6% ± 10.2% versus 14.7% ± 18.5%, P < 0.001), which was not observed in the control group. AF burden also reduced significantly after 12-week CRIC compared with that in the control group (8.6% ± 10.2% versus 17.6% ± 19.5%, P = 0.013). Repeated measurement ANOVA showed that the changes in AF burden were associated with CRIC instead of time (P < 0.01). In addition, there were trends that the longest duration of AF and cumulative numbers of atrial high-rate episodes (AHREs) reduced after 12-week CRIC. This study suggests that a 12-week course of CRIC treatment could reduce AF burden in patients with permanent pacemakers, supporting the widespread use of CRIC in the daily lives of these patients, which needs to be verified in the future.

Periostin promotes arterial calcification through PPARγ-related glucose metabolism reprogramming.

Extracellular matrix (ECM) exerts a series of biological functions and contributes to almost 30% of the osteogenic process. Periostin is a secreted protein that can alter ECM remodeling in response to vascular injury. However, the role of periostin in vascular calcification has yet to be fully investigated. As found in this study, recombinant periostin accelerated the thoracic aortas calcification, increased the expression of glycolysis key enzymes, and disturbed the normal oxidative phosphorylation (OXPHOS) ex vivo, which could be alleviated by the peroxisome proliferation-activated receptor γ (PPARγ) agonist pioglitazone. In vascular smooth muscle cells (VSMCs), periostin promoted VSMC-osteoblastic phenotype transition and calcium deposition and suppressed PPARγ expression. Mechanistically, periostin caused overactivation of glycolysis and mitochondrial dysfunction in VSMCs as assessed by extracellular acidification rate, oxygen consumption rate, and mitochondrial respiratory chain complex activities. Targeted glycolysis inhibitors reduced mitochondrial calcium overload, apoptosis, and periostin-induced VSMCs calcification. PPARγ agonists preserved glycolysis and OXPHOS in the stimulated microenvironment and reversed periostin-promoted VSMC calcification. Furthermore, plasma periostin, lactate, and matrix Gla protein levels were measured in 274 patients undergoing computed tomography to determine coronary artery calcium score (Agatston score). Plasma periostin and lactate levels were both linked to an Agatston score in patients with coronary artery calcification (CAC). There was also a positive correlation between plasma periostin and lactate levels. This study suggests that downregulation of PPARγ is involved in the mechanism by which periostin accelerates arterial calcification partly through excessive glycolysis activation and unbalanced mitochondrial homeostasis.NEW & NOTEWORTHY Periostin caused arterial calcification, overactivated glycolysis, and damaged OXPHOS. PPARγ agonists alleviated periostin-promoted arterial calcification and corrected abnormal glycolysis and unbalanced mitochondrial homeostasis. There exists a relationship between periostin and lactate in patients with CAC.

Rutin restrains the growth and metastasis of mouse breast cancer cells by regulating the microRNA-129-1-3p-mediated calcium signaling pathway.

Breast cancer is a common malignancy that is highly lethal. Due to the poor prognosis, more effective and efficient treatment methods are urgently needed. Rutin (RUT) is a traditional Chinese medicine reported to have a variety of pharmacological properties, including anticancer properties. However, the effects of RUT on breast cancer and its underlying molecular mechanism of action remain unclear. In the present study, we observed a significant downregulation of microRNA (miR)-129-1-3p in mouse breast cancer cells (4T1) compared with the expression in mouse normal breast epithelial cells (HC11). We also found that RUT could increase the expression of miR-129-1-3p in 4T1 cells and suppress cell proliferation. To elucidate the molecular mechanism of action of RUT, miR-129-1-3p mimics and its inhibitor were transfected into 4T1 cells. miR-129-1-3p overexpression could inhibit the proliferation, invasion, migration, and calcium overload of mouse breast cancer cells and also enhance apoptosis, whereas miR-129-1-3p knockdown had the opposite effects. Taken together, cell-based experiments indicated that RUT restrains the growth of mouse breast cancer cells by regulating the miR-129-1-3p/Ca2+ signaling pathway. This study also revealed the inhibitory effect of RUT on breast cancer cells at the noncoding RNA level and provided a theoretical foundation for the application of RUT as a drug to inhibit tumor growth.

Rutin treats myocardial damage caused by pirarubicin via regulating miR-22-5p-regulated RAP1/ERK signaling pathway.

Our experiments have previously demonstrated that rutin (RUT) can improve myocardial damage caused by pirarubicin (THP). However, the underlying molecular mechanisms remain uncertain. In this study, we developed an microRNA (miRNA) chip by replicating the rat model of THP-induced myocardial injury and identified miR-22-5p and the RAP1-member of RAS oncogene family/extracellular regulated protein kinases (RAP1/ERK) signaling pathway as an object of study. Also, in vivo experiments demonstrated that THP caused abnormal changes in the electrocardiogram, cardiac function, and histomorphology in rats (P < .01). THP also reduces the expression of miR-22-5p (P < .01) and increases the levels of RAP1/ERK signaling pathway-related proteins (P < .01, P < .05). RUT significantly improved THP-induced myocardial damage (P < .01), increased the expression of miR-22-5p (P < .01), and decreased the levels of RAP1/ERK signaling pathway-related proteins (P < .01, P < .05). In vitro studies confirmed that Rap1a is one of the target genes of miR-22-5p. miR-22-5p overexpression in cardiomyocytes can affect the RAP1/ERK pathway and reduce reactive oxygen species production and cardiomyocyte apoptosis caused by THP (P < .01), which is consistent with the effect of RUT. Our results indicate that RUT treats THP-induced myocardial damage, which may be achieved by upregulating miR-22-5p, causing changes in its target gene Rap1a and the RAP1/ERK pathway.

MicroRNA-129-1-3p protects cardiomyocytes from pirarubicin-induced apoptosis by down-regulating the GRIN2D-mediated Ca2+ signalling pathway.

Pirarubicin (THP), an anthracycline anticancer drug, is a first-line therapy for various solid tumours and haematologic malignancies. However, THP can cause dose-dependent cumulative cardiac damage, which limits its therapeutic window. The mechanisms underlying THP cardiotoxicity are not fully understood. We previously showed that MiR-129-1-3p, a potential biomarker of cardiovascular disease, was down-regulated in a rat model of THP-induced cardiac injury. In this study, we used Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses to determine the pathways affected by miR-129-1-3p expression. The results linked miR-129-1-3p to the Ca2+ signalling pathway. TargetScan database screening identified a tentative miR-129-1-3p-binding site at the 3'-UTR of GRIN2D, a subunit of the N-methyl-D-aspartate receptor calcium channel. A luciferase reporter assay confirmed that miR-129-1-3p directly regulates GRIN2D. In H9C2 (rat) and HL-1 (mouse) cardiomyocytes, THP caused oxidative stress, calcium overload and apoptotic cell death. These THP-induced changes were ameliorated by miR-129-1-3p overexpression, but exacerbated by miR-129-1-3p knock-down. In addition, miR-129-1-3p overexpression in cardiomyocytes prevented THP-induced changes in the expression of proteins that are either key components of Ca2+ signalling or important regulators of intracellular calcium trafficking/balance in cardiomyocytes including GRIN2D, CALM1, CaMKⅡδ, RyR2-pS2814, SERCA2a and NCX1. Together, these bioinformatics and cell-based experiments indicate that miR-129-1-3p protects against THP-induced cardiomyocyte apoptosis by down-regulating the GRIN2D-mediated Ca2+ pathway. Our results reveal a novel mechanism underlying the pathogenesis of THP-induced cardiotoxicity. The miR-129-1-3p/Ca2+ signalling pathway could serve as a target for the development of new cardioprotective agents to control THP-induced cardiotoxicity.

miR-30b Promotes spinal cord sensory function recovery via the Sema3A/NRP-1/PlexinA1/RhoA/ROCK Pathway.

Spinal cord injury (SCI) induces both motor and sensory dysfunctions. We wondered whether miR-30b could promote primary sensory neuron (PSN) axon growth in inhibitory microenvironment. The neurite growth was promoted by miR-30b agomir and inhibited by antagomir. MiR-30b targeted and degraded sema3A mRNA. MiR-30b regulated the formation of sema3A-NRP-1-PlexinA1 complex via targeting sema3A. The neurite length was induced by the miR-30b agomir, and the application of sema3A protein could reverse the effect of agomir. GTP-RhoA and ROCK expression were down-regulated by miR-30b. Neurite outgrowth that inhibited by sema3A and the miR-30b antagomir was increased by Y-27632. Agomir promoted neurite growth in NogoA inhibitory conditions, which indicated miR-30b could both enhance neuronal intrinsic regenerative ability and promote neurite growth against inhibitory microenvironment via Sema3A/NRP-1/PlexinA1/RhoA/ROCK axis. The agomir could also regulate Sema3A/NRP-1/PlexinA1/RhoA/ROCK axis in vivo and restore spinal cord sensory conductive function. In conclusion, miR-30b could be a novel target for sensation recovery after SCI.

Rutin protects against pirarubicin-induced cardiotoxicity by adjusting microRNA-125b-1-3p-mediated JunD signaling pathway.

Pirarubicin (THP), an anthracycline drug, is widely used as a basic therapeutic agent for the treatment of carcinoma and lymphatic malignant tumor. However, it exerts irreversible cardiotoxicity in varying degrees. At present, dexrazoxane (DZR) is the only cardioprotective agent used to treat anthracycline drug-induced cardiotoxicity, but it may reduce the anticancer effect of anthracycline drugs, causing severe granulocytopenia and other adverse reactions. Therefore, it is necessary to discover more effective and less toxic drugs for the treatment of THP-induced cardiotoxicity. The present study aimed to investigate the effects and possible mechanisms of rutin (RUT) against THP-induced cardiomyocyte injury. An in vitro cardiomyocyte injury model of THP-treated murine immortalized cardiomyocytes (HL-1) was used in this study. The results showed that RUT markedly increased the viability of HL-1 cells through protection against THP-induced cardiomyocyte injury. Furthermore, RUT significantly inhibited myocardial oxidative insult by adjusting the levels of intracellular reactive oxygen species (ROS). Our data also indicated that RUT activated JunD signaling pathways, thereby affecting the expression levels of some apoptotic proteins by decreasing miR-125b-1-3p expression level. In addition, intracellular ROS level significantly increased in HL-1 cells treated with THP after miR-125b-1-3p mimic transfection, whereas the expression of JunD was downregulated and that of some apoptotic proteins was upregulated. However, this effect was markedly reversed by RUT. Therefore, we inferred that the protective effect of RUT on THP cardiotoxicity was achieved through regulation of the JunD gene by miR-125b-1-3p. This experiment revealed the protective effect of RUT on THP-induced cardiotoxicity at the non-coding RNA level and provided a theoretical foundation for the application of RUT as a protective agent against THP cardiotoxicity.

Insulin secretion impairment induced by rosuvastatin partly though autophagy in INS-1E cells.

Statins are used extensively for the clinical treatment of cardiovascular diseases. Recent studies suggest that statins increase the risk of new-onset diabetes mellitus (NODM). However, the mechanisms of statin-induced NODM remain unclear. The present study investigated the effects of autophagy on insulin secretion impairment induced by rosuvastatin (RS) in rat insulinoma cells (INS-1E) cells. INS-1E cells were cultured and treated with RS at different concentrations (0.2-20 µM) for 24 h. Insulin secretion in INS-1E cells was detected by enzyme-linked immunosorbent assay, and the co-localization of microtubule-associated protein light chain 3 (LC3) and lysosome-associated membrane protein 2 (LAMP-2) was observed by immunofluorescence staining. Western blotting was used to assess the conversion of LC3 and p62. The results showed that the insulin secretion and cell viability decrease induced by RS treatment for 24 h occurred in a dose-dependent manner in INS-1E cells. RS significantly inhibited the expression of LC3-II but increased the protein expression of p62. Simultaneously, RS diminished the co-localization of LC3-II and LAMP-2 fluorescence signals. These results suggested that RS-inhibited autophagy in INS-1E cells. Rapamycin, an autophagy agonist, reversed the insulin secretion and cell viability suppression induced by RS in INS-1E cells. RS also decreased the phosphorylation of the mammalian target of rapamycin (mTOR). The results indicated that RS impairs insulin secretion in INS-1E cells, which may be partly due to the inhibition of autophagy via an mTOR-dependent pathway.

The inhibition of miR-17-5p promotes cortical neuron neurite growth via STAT3/GAP-43 pathway.

Spinal cord injury (SCI) is a devastating disease associated with locomotor function impair. The limited regenerative capability of the neural axon is one of the major factors that hinders the recovery of SCI. To enhance the regenerative ability of neuron is a promising strategy that repairs SCI. We previously proved miR-17-5p could target Signal Transducer and Activator of Transcription 3 (STAT3) in primary sensory neuron. We speculated that miR-17-5p was the miRNA that targets STAT3. The Dual-luciferase reporter assay indicated miR-17-5p could bind the 3'UTR of STAT3 mRNA. The RT-qPCR and Western blot assay showed miR-17-5p could not degenerate the mRNA of STAT3, but inhibit the expression of Signal Transducer and Activator of Transcription 3 (STAT3) via translation inhibition. MiR-17-5p inhibitor promoted the expression of STAT3, phosphorylated-STAT3 (p-STAT3) and Growth Associate Protein-43 (GAP-43), and this promotion was inhibited by STAT3 siRNA. MiR-17-5p mimics and inhibitor inhibited and promoted the neurite growth, respectively. MiR-17-5p inhibitor promoted the axon growth and AG490, the STAT3 phosphorylation inhibitor, inhibited this promotion. MiR-17-5p mimics inhibited the expression of STAT3, p-STAT3 and GAP-43, while the inhibitor promoted their expression. AG490 did not alter the expression of STAT3, while downregulated the expression both p-STAT3 and GAP-43 in miR-17-5p inhibitor&AG490 group. Taken together, these data indicated miR-17-5p could regulated cortical neuron axon growth via STAT3/GAP-43 pathway by targeting STAT3 mRNA 3'UTR. Therefore, miR-17-5p/STAT3/GAP-43 pathway plays a key role in regulating cortical neuron axon growth and could be a novel target to treat SCI.

Systematic analysis of long non-coding RNA and mRNA expression changes in ApoE-deficient mice during atherosclerosis.

Atherosclerosis plays an important role in the pathology of coronary heart disease, cerebrovascular disease, and systemic vascular disease. Long non-coding RNAs (lncRNAs) are involved in most biological processes and are deregulated in many human diseases. However, the expression alteration and precise role of lncRNAs during atherosclerosis are unknown. We report here the systematic profiling of lncRNAs and mRNAs in an ApoE-deficient (ApoE-/-) mouse model of atherosclerosis. Clariom D solutions for the mouse Affymetrix Gene Chip were employed to analyze the RNAs from control and ApoE-/- mice. The functions of the differentially expressed mRNAs and lncRNAs and the relationships of their expression with atherosclerosis were analyzed by gene ontology, co-expression network, pathway enrichment, and lncRNA target pathway network analyses. Quantitative real-time PCR (QRT-PCR) was used to determine the expression of mRNAs and lncRNAs. A total of 2212 differentially expressed lncRNAs were identified in ApoE-/- mice, including 1186 up-regulated and 1026 down-regulated lncRNAs (|FC| ≥ 1.1, p < 0.05). A total of 1190 differentially expressed mRNAs were found in the ApoE-/- mice with 384 up-regulated and 806 down-regulated (|FC| ≥ 1.1, p < 0.05). Bioinformatics analyses demonstrated extensive co-expression of lncRNAs and mRNAs and concomitant deregulation of multiple signaling pathways associated with the initiation and progression of atherosclerosis. The identified differentially expressed mRNAs and lncRNAs as well as the related signaling pathways may provide systematic information for understanding the pathogenesis and identifying biomarkers for the diagnosis, treatment, and prognosis of atherosclerosis.

To Explore the Protective Mechanism of PTEN-Induced Kinase 1 (PINK1)/Parkin Mitophagy-Mediated Extract of Periplaneta Americana on Lipopolysaccharide-Induced Cardiomyocyte Injury.

BACKGROUND Sepsis is defined as a systemic inflammatory response syndrome caused by an infection (suspicious or confirmed). Its essence is inflammatory mediators and cytokines mediated by host immune response. The present study aimed to investigate the role of Periplaneta americana extracts (XML) on PTEN-induced kinase 1 (PINK1)/Parkin mediated mitophagy in cardiomyocyte injury by sepsis. MATERIAL AND METHODS H9C2 cells were cultured and transfected with Mdivi-1 and Atg7 siRNA. The cell viability and drug toxicity were detected using Cell Counting Kit-8 assay. ELISA (enzyme-linked immunosorbent assay) was used to assess cardiac injury factors and inflammatory factors. Fluorescence levels of LC3 were detected using immunofluorescence assay. Then, the protein and mRNA expression levels were analyzed using western blot and qRT-PCR. Intracellular adenosine triphosphate (ATP) levels were measured using an ATP kit. Finally, flow cytometry was used to detected apoptosis. RESULTS The result showed that XML significantly increase cell viability in H9C2 cells. Compared with XML+LPS (lipopolysaccharide) group, the level of cTNI, CK-MB, interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α was significantly upregulation in LPS+XML+Mdivi-1 or LPS+XML+Atg7 siRNA group. In addition, the release of LC3 was significant decreased. The protein and mRNA expression of PINK1, Parkin, Nix, Beclin-1 was significantly increased, but decreased expression of Mitofusin1, Mitofusin2, Opa1, Drp1, and P62 in LPS+XML+Mdivi-1 or LPS+XML+Atg7 siRNA groups. More importantly, we found that cell apoptosis was induced by Mdivi-1 and Atg7 siRNA. CONCLUSIONS The study provided evidence that XML regulated the process of LPS-induced cardiomyocyte injury through mitophagy by the PINK1/Parkin pathway.

Risk Factors and Prevention Strategies of Nosocomial Infection in Geriatric Patients.

INTRODUCTION: To investigate the risk factors of nosocomial infections (NIs) in geriatric department and the effectiveness of the proposed prevention strategy. METHODOLOGY: We studied 3370 cases of elderly patients who were hospitalized more than 48 hours from January 2015 to December 2017 in the Geriatrics Department of Zhongda Hospital, Southeast University. In order to reduce the infection rate, nutritional risk screening (NRS 2002) was used to evaluate the nutritional status of the patients; enteral nutritional suspension (TPF-FOS) was provided to the patients who were assessed to be necessary. RESULTS: Before prevention strategy was taken, the nosocomial infection rate was 3.3% (80 among 2413 patients) in our department. The most frequent NIs were pneumonia (60 cases) followed by urinary tract infection (30 cases). It is worth noting that the elderly patients are often associated with multiple infections: in our study, 15 patients have pneumonia and UTI at the same time. After prevention strategy was taken, the nosocomial infection rate reduced to 1.15% (11 among 957 patients) in our department. CONCLUSIONS: NIs are common in elderly patients. The improvement of the nutritional status of patients is effective in reducing the risks of NIs.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Are Effective Predictors of Prognosis in Patients with Acute Mesenteric Arterial Embolism and Thrombosis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be valuable prognostic markers for a variety of pathological conditions including solid tumors, sepsis, and others. However, the prognostic values of the NLR and PLR in patients with acute mesenteric arterial embolism (AMAE) and acute mesenteric arterial thrombosis (AMAT) have not been elucidated. The aim of this study was to determine the predictive value of the NLR and PLR for poor prognosis in patients with AMAE and AMAT. METHODS: A total of 137 patients with AMAE (n = 77) or AMAT (n = 60) were divided into a poor outcome group (cases of intestinal necrosis or death) and a better outcome group (cases without intestinal necrosis who survived successfully), according to prognosis. Neutrophil, platelet, and lymphocyte counts were recorded before pharmacotherapy or surgery. The NLR and PLR were calculated, and logistic regression analysis was performed to test their prognostic values. RESULTS: The cutoff values for NLR and PLR were 11.05 and 156.26, respectively. The PLR was linearly associated with the NLR (R = 0.769, P < 0.001). NLR (odds ratio [OR] = 6.835, 95% confidence interval [CI] = 2.282-20.469, P = 0.001), PLR (OR = 4.871, 95% CI = 1.627-14.587, P = 0.005), and coronary heart disease (OR = 3.388, 95% CI = 1.156-9.929, P = 0.026) were found to be independent prognostic factors for the patients. CONCLUSIONS: NLR ≥ 11.05, PLR ≥ 156.26, and coronary heart disease were shown to be risk factors for poor prognosis in patients with AMAE and AMAT. According to these factors, patients can be divided into 3 prognostic groups: good, NLR < 11.05 with PLR < 156.26; moderate, NLR < 11.05 with PLR ≥ 156.26 or NLR ≥ 11.05 with PLR < 156.26; and poor, NLR ≥ 11.05 with PLR ≥ 156.26.

Cardioprotective effects of rutin in rats exposed to pirarubicin toxicity.

We established both an acute and chronic cardiac toxicity rat model, which showed pretreatment with rutin attenuated pirarubicin-induced myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. Rutin also significantly reduced serum levels of MDA, BNP, CK-MB, CTnT, and LDH and increased serum SOD levels. Treatment with rutin and dexrazoxane resulted in an increase in Bcl-2/Bax ratio (p < 0.05) and reduction in JNK and Caspase-3 protein levels, compared to the pirarubicin group (all p < 0.05). Furthermore, rutin at a dose of 50 mg/kg significantly attenuated the above-mentioned alterations. Our study suggests the antioxidant and anti-apoptotic properties of rutin may be responsible for the cardioprotective effects observed.