Publications by authors named "Rong Tian"

274 Publications

CircPRDM2 Contributes to Doxorubicin Resistance of Osteosarcoma by Elevating EZH2 via Sponging miR-760.

Cancer Manag Res 2021 2;13:4433-4445. Epub 2021 Jun 2.

Department of Spine Surgery, Tianjin Union Medical Center, Tianjin, 300121, People's Republic of China.

Background: Circular RNAs (circRNAs) are implicated in the chemoresistance of human cancers. However, the functions of circRNA PR/SET domain 2 (circPRDM2) in the resistance of osteosarcoma (OS) to doxorubicin (DXR) are unknown.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was conducted to determine the levels of circPRDM2, microRNA-760 (miR-760) and enhancer of zeste homolog 2 (EZH2). RNase R assay was used to analyze the characteristics of circPRDM2. IC50 of DXR was estimated by Cell Counting Kit-8 (CCK-8) assay. Colony formation assay was performed for cell colony formation ability. Wound-healing assay and transwell assay were utilized for cell migration and invasion. Flow cytometry analysis was conducted for cell apoptosis. Western blot assay was employed for protein levels. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were adopted to analyze the relationships among circPRDM2, miR-760 and EZH2. Murine xenograft model assay was utilized to explore DXR resistance in vivo.

Results: CircPRDM2 level was enhanced in DXR-resistant OS tissues and cells. CircPRDM2 deficiency inhibited IC50 of DXR, colony formation, migration and invasion and facilitated apoptosis in DXR-resistant OS cells in vitro. CircPRDM2 was identified as the sponge for miR-760. MiR-760 inhibition reversed the inhibitory effects of circPRDM2 knockdown on DXR resistance and cell progression in DXR-resistant OS cells. Moreover, EZH2 was identified as the target gene of miR-760 and EZH2 overexpression abolished miR-760-mediated impacts on DXR sensitivity and malignant behaviors in DXR-resistant OS cells. Also, circPRDM2 silencing improved DXR sensitivity in vivo.

Conclusion: Our study demonstrated the role of circPRDM2/miR-760/EZH2 axis in enhancing DXR resistance.
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http://dx.doi.org/10.2147/CMAR.S295147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180268PMC
June 2021

Baicalein inhibits invasion and promotes apoptosis in glioma cells through the PI3K/Akt pathway.

J BUON 2021 Mar-Apr;26(2):395-401

Department of Neurosurgery, the Third Medical Center, Chinese PLA (People's Liberation Army) General Hospital, Beijing, China.

Purpose: The purpose of this study was to elucidate the role of Baicalein in accelerating invasiveness and inducing apoptosis of glioma cells through the phosphatidilinositol 3-kinase/protein kinase B (PI3K/Akt) pathway.

Methods: U251 glioma cells were treated with different doses of Baicalein (10, 20 or 40 μM) for different time periods (12, 24, 36 or 48 h). Changes in viability, clonality, cell cycle distribution and apoptosis in Baicalein-treated U251 cells were assessed. Meanwhile, relative levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in U251 cells were detected. Western blot was conducted to examine protein levels of p-Akt and Akt in Baicalein-treated U251 cells.

Results: Baicalein treatment attenuated dose-dependently and time-dependently the viability and clonality in U251 cells. It induced cell cycle arrest in G0/G1 phase and cell apoptosis of U251 cells. After Baicalein treatment, the relative levels of MMP-2 and MMP-9 were dose-dependently downregulated. Baicalein treatment activated the PI3K/Akt pathway. Notably, inhibitory effects of Baicalein treatment on MMP levels and invasiveness in glioma were blocked by the application of LY294002 (PI3K/Akt inhibitor), and stimulated by the application of IGF-1 (PI3K/Akt activator).

Conclusions: Baicalein treatment is able to suppress invasiveness and induce apoptosis of glioma cells through inactivating the PI3K/Akt pathway.
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June 2021

Investigating F-FDG PET/CT Parameters as Prognostic Markers for Differentiated Thyroid Cancer: A Systematic Review.

Front Oncol 2021 13;11:648658. Epub 2021 May 13.

Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China.

The aim of this study was to determine whether F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) parameters might be prognostic markers for patients with differentiated thyroid carcinoma (DTC). We searched for eligible articles in PubMed, EMBASE (Ovid), Cochrane Library, and ClinicalTrials.gov from inception to February 2021. We included studies addressing the association between F-FDG PET/CT parameters and clinical outcomes among patients with DTC. Quality assessment was performed using the Quality in Prognosis Studies (QUIPS) tool. A total of 25 studies including 2,954 patients (1,994 females, 67.5%) were included; 2,416 patients (81.8%) had papillary thyroid carcinoma (PTC), and the mean or median follow-up time ranged from 19.1 months to 17.1 years. Thirteen (52.0%) studies were assessed as "unclear" for the domain of study participation. The most common timing of PET/CT scans was after thyroidectomy (in 20 of 25 studies, 80%), especially in patients with an elevated thyroglobulin (Tg) and a negative radioiodine whole-body scan (WBS). The most common PET parameter was FDG uptake. Twelve of 17 (70.6%) and 12 of 12 (100%) studies showed an association between PET/CT parameters and disease progression and survival in patients with DTC, respectively. F-FDG PET/CT parameters alone or combined with other variables can serve as prognostic markers to identify DTC patients with poor outcomes, especially in the setting of an elevated Tg and a negative WBS. Future research is needed to confirm these findings and to examine the prognostic value of PET/CT parameters for DTC patients, considering the heterogeneity in PET/CT parameters, unclear information of patients, and PET/CT-adapted treatment modifications.
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http://dx.doi.org/10.3389/fonc.2021.648658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158293PMC
May 2021

Association between hearing loss and frailty: a systematic review and meta-analysis.

BMC Geriatr 2021 05 25;21(1):333. Epub 2021 May 25.

Medical School, University of Western Australia, 35 Stirling Highway, Western Australia, 6009, Perth, Australia.

Background: Frailty is associated with poor health outcomes in later life. Recent studies suggested that hearing loss may be a potentially modifiable risk factor associated with frailty.

Methods: This systematic review and meta-analysis aimed to investigate the association between hearing loss and frailty in observational studies of adults aged 50 years or over. We included observational studies with participants ≥ 50 years old that have clear descriptions of hearing and frailty measurement methods. Meta-analyses were conducted using measurement of risk and 95 % confidence interval of each individual study. Quality assessment, risk of bias, heterogeneity and sensitivity analyses were also conducted. Our study followed PRISMA guidelines.

Results: Our search identified 4508 manuscripts published in English between 1 and 2000 and 9 February 2021. Sixteen articles reported acceptable measurements of both hearing loss and frailty. Two papers were not suitable for meta-analysis. Twelve sets of cross-sectional data involving 12,313 participants, and three sets of longitudinal data involving 3042 participants were used in the meta-analysis. Hearing loss was associated with an 87 % increase in the risk of frailty among cross-sectional studies (risk ratio [RR] 1.87; 95 %CI 1.63-2.13) and 56 % among longitudinal studies (RR 1.56; 95 %CI 1.29-1.88). There was considerable heterogeneity among studies, but their quality rating, sample size or approach used to assess hearing loss did not change the results substantially.

Conclusions: The findings of this systematic review and meta-analysis of observational studies suggest that hearing loss increases the risk of frailty in later life. Whether this relationship is causal remains to be determined.
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http://dx.doi.org/10.1186/s12877-021-02274-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147347PMC
May 2021

FDG PET/CT Findings of a Primary Paravertebral Liposarcoma.

Clin Nucl Med 2021 May 26. Epub 2021 May 26.

From the Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Abstract: Liposarcoma is a soft tissue tumor that commonly appears in the retroperitoneum and the extremities. Herein, we presented the imaging findings of a 68-year-old man with a paravertebral liposarcoma involving the adjacent vertebral bodies, appendices, and ribs. MRI revealed this mass located in the left side of T9 to T10 vertebral bodies. FDG PET/CT demonstrated the mass with intense FDG uptake. Finally, the pathological findings were consistent with a diagnosis of a primary paravertebral liposarcoma.
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http://dx.doi.org/10.1097/RLU.0000000000003734DOI Listing
May 2021

Proteomic insights into protostane triterpene biosynthesis regulatory mechanism after MeJA treatment in Alisma orientale (Sam.) Juz.

Biochim Biophys Acta Proteins Proteom 2021 Aug 12;1869(8):140671. Epub 2021 May 12.

School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Protostane triterpenes in Alisma orientale (Sam.) Juz. have unique structural features with distinct pharmacological activities. Previously we have demonstrated that protostane triterpene biosynthesis could be regulated by methyl jasmonate (MeJA) induction in A. orientale. Here, proteomic investigation reveals the MeJA mediated regulation of protostane triterpene biosynthesis. In our study, 281 differentially abundant proteins were identified from MeJA-treated compared to control groups, while they were mainly associated with triterpene biosynthesis, α-linolenic acid metabolism, carbohydrate metabolism and response to stress/defense. Key enzymes 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), squalene epoxidase (SE), oxidosqualene cyclase (OSC) and cytochrome P450s which potentially involved in protostane triterpene biosynthesis were significantly enriched in MeJA-treated group. Basic Helix-loop-helix (bHLH), MYB, and GRAS transcription factors were enhanced after MeJA treatment, and they also improved the expressions of key enzymes in Mevalonate pathway and protostane triterpene. Then, MeJA also could increase the expression of α-galactosidase (α-GAL), thereby promoting carbohydrate decomposition, and providing energy and carbon skeletons for protostane triterpene precursor biosynthesis. As well, exogenous MeJA treatment upregulated 13-lipoxygenase (13-LOX), allene oxide synthase (AOS) and allene oxide cyclase (AOC) involved in α-linolenic acid metabolism, leading to the accumulation of endogenous MeJA and activation of the protostane triterpene biosynthesis transduction. Finally, MeJA upregulated stress/defence-related proteins, as to enhance the defence responses activity of plants. These results were further verified by quantitative real-time PCR analysis of 19 selected genes and content analysis of protostane triterpene. The results provide some new insights into the role of MeJA in protostane triterpene biosynthesis.
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http://dx.doi.org/10.1016/j.bbapap.2021.140671DOI Listing
August 2021

Increasing fatty acid oxidation elicits a sex-dependent response in failing mouse hearts.

J Mol Cell Cardiol 2021 May 12;158:1-10. Epub 2021 May 12.

Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Republican Street 850, 98109 Seattle, WA, USA. Electronic address:

Background: Reduced fatty acid oxidation (FAO) is a hallmark of metabolic remodeling in heart failure. Enhancing mitochondrial long-chain fatty acid uptake by Acetyl-CoA carboxylase 2 (ACC2) deletion increases FAO and prevents cardiac dysfunction during chronic stresses, but therapeutic efficacy of this approach has not been determined.

Methods: Male and female ACC2 f/f-MCM (ACC2KO) and their respective littermate controls were subjected to chronic pressure overload by TAC surgery. Tamoxifen injection 3 weeks after TAC induced ACC2 deletion and increased FAO in ACC2KO mice with pathological hypertrophy.

Results: ACC2 deletion in mice with pre-existing cardiac pathology promoted FAO in female and male hearts, but improved cardiac function only in female mice. In males, pressure overload caused a downregulation in the mitochondrial oxidative function. Stimulating FAO by ACC2 deletion caused unproductive acyl-carnitine accumulation, which failed to improve cardiac energetics. In contrast, mitochondrial oxidative capacity was sustained in female pressure overloaded hearts and ACC2 deletion improved myocardial energetics. Mechanistically, we revealed a sex-dependent regulation of PPARα signaling pathway in heart failure, which accounted for the differential response to ACC2 deletion.

Conclusion: Metabolic remodeling in the failing heart is sex-dependent which could determine the response to metabolic intervention. The findings suggest that both mitochondrial oxidative capacity and substrate preference should be considered for metabolic therapy of heart failure.
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http://dx.doi.org/10.1016/j.yjmcc.2021.05.004DOI Listing
May 2021

Cardiac Energy Metabolism in Heart Failure.

Circ Res 2021 May 13;128(10):1487-1513. Epub 2021 May 13.

Division of Endocrinology and Metabolism, University of Iowa Carver College of Medicine, Iowa City (E.D.A.).

Alterations in cardiac energy metabolism contribute to the severity of heart failure. However, the energy metabolic changes that occur in heart failure are complex and are dependent not only on the severity and type of heart failure present but also on the co-existence of common comorbidities such as obesity and type 2 diabetes. The failing heart faces an energy deficit, primarily because of a decrease in mitochondrial oxidative capacity. This is partly compensated for by an increase in ATP production from glycolysis. The relative contribution of the different fuels for mitochondrial ATP production also changes, including a decrease in glucose and amino acid oxidation, and an increase in ketone oxidation. The oxidation of fatty acids by the heart increases or decreases, depending on the type of heart failure. For instance, in heart failure associated with diabetes and obesity, myocardial fatty acid oxidation increases, while in heart failure associated with hypertension or ischemia, myocardial fatty acid oxidation decreases. Combined, these energy metabolic changes result in the failing heart becoming less efficient (ie, a decrease in cardiac work/O consumed). The alterations in both glycolysis and mitochondrial oxidative metabolism in the failing heart are due to both transcriptional changes in key enzymes involved in these metabolic pathways, as well as alterations in NAD redox state (NAD and nicotinamide adenine dinucleotide levels) and metabolite signaling that contribute to posttranslational epigenetic changes in the control of expression of genes encoding energy metabolic enzymes. Alterations in the fate of glucose, beyond flux through glycolysis or glucose oxidation, also contribute to the pathology of heart failure. Of importance, pharmacological targeting of the energy metabolic pathways has emerged as a novel therapeutic approach to improving cardiac efficiency, decreasing the energy deficit and improving cardiac function in the failing heart.
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http://dx.doi.org/10.1161/CIRCRESAHA.121.318241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136750PMC
May 2021

Prognostic value of lymph node ratio in children and adolescents with papillary thyroid cancer.

Clin Endocrinol (Oxf) 2021 Apr 29. Epub 2021 Apr 29.

Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China.

Objective: Neck lymph node (LN) metastasis is a common feature of paediatric papillary thyroid cancer, and LN ratio (LNR) is defined as the ratio of the number of positive LNs excised to the total number of removed. Unlike in adults, few data are available regarding the clinical implication of LNR in the paediatric population. Our purpose was to investigate the association of LNR with clinical outcomes in paediatric papillary thyroid cancer.

Design & Methods: The study retrospectively reviewed 136 consecutive children and adolescents with papillary thyroid cancer and LN involvement but no initial distant metastasis. Initial treatment, included in all patients a total thyroidectomy with central and/or lateral neck dissection followed by radioactive iodine ablation. Within the neck dissections, total number of LNs removed, total positive LNs and LN ratios were determined. The effect of clinicopathologic characteristics and intraoperative findings on persistent and recurrent diseases were analysed by univariate and multivariate analyses.

Results: Median number of positive LNs was 9, and median LNR was 0.4. During a median follow-up of 49 months (range, 12.0-139 months), persistent disease occurred in 43 (31.6%) patients. The multivariable analysis showed that age and LNR were the independent factors predictive of persistent disease. Patients with a LNR >0.34 exhibited a threefold higher risk of persistent disease after initial therapy than the counterparts (P = .02).

Conclusion: Our findings suggest that LNR was an independent determinant predictive of persistent disease after initial therapy in children and adolescents with papillary thyroid cancer.
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http://dx.doi.org/10.1111/cen.14491DOI Listing
April 2021

GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration.

Sci Rep 2021 Apr 21;11(1):8669. Epub 2021 Apr 21.

Department of Molecular, Cell, Developmental Biology, School of Life Science, University of California Los Angeles, Los Angeles, CA, USA.

The mammalian heart switches its main metabolic substrate from glucose to fatty acids shortly after birth. This metabolic switch coincides with the loss of regenerative capacity in the heart. However, it is unknown whether glucose metabolism regulates heart regeneration. Here, we report that glucose metabolism is a determinant of regenerative capacity in the neonatal mammalian heart. Cardiac-specific overexpression of Glut1, the embryonic form of constitutively active glucose transporter, resulted in an increase in glucose uptake and concomitant accumulation of glycogen storage in postnatal heart. Upon cryoinjury, Glut1 transgenic hearts showed higher regenerative capacity with less fibrosis than non-transgenic control hearts. Interestingly, flow cytometry analysis revealed two distinct populations of ventricular cardiomyocytes: Tnnt2-high and Tnnt2-low cardiomyocytes, the latter of which showed significantly higher mitotic activity in response to high intracellular glucose in Glut1 transgenic hearts. Metabolic profiling shows that Glut1-transgenic hearts have a significant increase in the glucose metabolites including nucleotides upon injury. Inhibition of the nucleotide biosynthesis abrogated the regenerative advantage of high intra-cardiomyocyte glucose level, suggesting that the glucose enhances the cardiomyocyte regeneration through the supply of nucleotides. Our data suggest that the increase in glucose metabolism promotes cardiac regeneration in neonatal mouse heart.
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http://dx.doi.org/10.1038/s41598-021-88159-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060418PMC
April 2021

FDG PET/CT Showing a Primary Lymphoma of the Sternoclavicular Joint.

Clin Nucl Med 2021 Jul;46(7):603-604

From the Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Abstract: We presented a case of primary lymphoma of the sternoclavicular joint. A 67-year-old woman with a history of swelling at the sternoclavicular joint region was considered as osteoarthritis initially. Chest CT found a soft tissue mass around the sternoclavicular joint. Biopsy demonstrated diffuse large B-cell lymphoma. The subsequent FDG PET/CT revealed FDG-avid articular destruction with surrounding soft tissue mass without any other abnormal findings, suggesting a primary extranodal lymphoma of sternoclavicular joint.
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http://dx.doi.org/10.1097/RLU.0000000000003646DOI Listing
July 2021

Myeloperoxidase Targets Apolipoprotein A-I for Site-Specific Tyrosine Chlorination in Atherosclerotic Lesions and Generates Dysfunctional High-Density Lipoprotein.

Chem Res Toxicol 2021 Apr 16. Epub 2021 Apr 16.

Key Laboratory of Functional Small Organic Molecule, Ministry of Education; Jiangxi Key Laboratory of Green Chemistry, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China.

We previously demonstrated that apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), is an important target for myeloperoxidase (MPO)-catalyzed tyrosine chlorination in the circulation of subjects with cardiovascular diseases. Oxidation of apoA-I by MPO has been reported to deprive HDL of its protective properties. However, the potential effects of MPO-mediated site-specific tyrosine chlorination of apoA-I on dysfunctional HDL formation and atherosclerosis was unclear. Herein, Tyr192 in apoA-I was found to be the major chlorination site in both lesion and plasma HDL from humans with atherosclerosis, while MPO binding to apoA-I was demonstrated by immunoprecipitation studies in vivo. In vitro, MPO-mediated damage of lipid-free apoA-I impaired its ability to promote cellular cholesterol efflux by the ABCA1 pathway, whereas oxidation to lipid-associated apoA-I inhibited lecithin:cholesterol acyltransferase activation, two key steps in reverse cholesterol transport. Compared with native apoA-I, apoA-I containing a Tyr192 → Phe mutation was moderately resistant to oxidative inactivation by MPO. In high-fat-diet-fed apolipoprotein E-deficient mice, compared with native apoA-I, subcutaneous injection with oxidized apoA-I (MPO treated) failed to mediate the lipid content in aortic plaques while mutant apoA-I (Tyr192 → Phe) showed a slightly stronger ability to reduce the lipid content in vivo. Our observations suggest that oxidative damage of apoA-I and HDL involves MPO-dependent site-specific tyrosine chlorination, raising the feasibility of producing MPO-resistant forms of apoA-I that have stronger antiatherosclerotic activity in vivo.
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http://dx.doi.org/10.1021/acs.chemrestox.1c00086DOI Listing
April 2021

Assessment of the prognostic value of interim fluorodeoxyglucose positron emission tomography/computed tomography in nasal-type extranodal natural killer/T-cell lymphoma.

Quant Imaging Med Surg 2021 Apr;11(4):1220-1233

Department of Medical Oncology, Cancer Center, West China Hospital of Sichuan University, Chengdu, China.

Background: The prognostic value of interim positron emission tomography/computed tomography (PET/CT) for nasal-type extranodal natural killer/T-cell lymphoma (ENKTL) is controversial. We evaluated the prognostic value of interim PET/CT in ENKTL patients to facilitate risk stratification and guide clinical treatment.

Methods: Patients with ENKTL who received first-line chemotherapy based on L-asparaginase/pegaspargase with/without involved-field radiotherapy were recruited for this study. Pretreatment and interim PET/CT evaluations were performed. Interim PET/CT was evaluated via the maximum standardized uptake value (SUVmax) and the Deauville 5-point scale (DS); and the capacity to predict progression-free survival (PFS) and overall survival (OS) was evaluated. Receiver operating characteristic (ROC) curves were used to determine the optimal SUVmax cutoff. Fisher's exact test was used to analyze relationships between interim PET/CT results and clinical characteristics. Univariate and multivariate analyses were performed to examine the independent effects of interim PET/CT. The Cochran-Mantel-Haenszel test was used to assess the prognostic value of interim PET/CT at different timepoints.

Results: Overall, 129 ENKTL patients were enrolled. The optimal interim PET/CT SUVmax cut-off was 4.95. The median follow-up was 34 [2-90] months, in the low SUVmax group (≤4.95), the 2-year PFS and OS rates were 76.3% and 88.0%, respectively; in the high SUVmax group (>4.95), the PFS and OS rates were 15.6% and 44.5%, respectively. Likewise, for the DS 1-3 group, the PFS and OS rates were 78.9% and 91.2%, respectively; and in the DS 4 or 5 group, the rates of PFS and OS were 49.7% and 69.0%, respectively. In univariate analysis, interim PET/CT evaluation based on SUVmax and DS scores were both PFS and OS predictors. In multivariate analysis, SUVmax was independently significantly associated with PFS (P<0.001) and OS (P=0.002), and DS was independently significantly associated with PFS (P=0.004) but not OS (P=0.204). In the Cochran-Mantel-Haenszel testing, the SUVmax and DS were significantly associated with PFS and OS after adjustments for the interim PET/CT timing.

Conclusions: Interim PET/CT was of prognostic value concerning ENKTL. The SUVmax is an independent prognostic indicator of PFS and OS, while the DS is an independent prognostic indicator of PFS but not OS. The SUVmax is of greater prognostic value than DS.
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http://dx.doi.org/10.21037/qims-20-620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930694PMC
April 2021

Spatio-temporal distribution and source identification of heavy metals in particle size fractions of road dust from a typical industrial district.

Sci Total Environ 2021 Aug 16;780:146357. Epub 2021 Mar 16.

School of Information and Safety Engineering, Zhongnan University of Economics and Law, Wuhan 430073, China; Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan 430073, China.

Seasonally distribution and source apportionment of Cr, Mn, Ni, Cu, Zn, Cd, and Pb in the road dust (RD) with the four size fraction sizes (<45 μm, 45-63 μm, 63-150 μm and all sizes) in a typical industrial district were investigated using a combination of Moran index, Principal component analysis (PCA), and Positive matrix factorization (PMF). Results showed that from winter to summer, the proportion of the <45 μm fraction dust in the total RD mass increased from 6.72% to 15.92% and that of 63-150 μm dust particles decreased from 31.13% to 21.76%. The proportion of the enrichment factors (EF) at moderate pollution level in winter was higher than that in summer, especially for Cu, Cd and Pb. Further, the heavy metals were relatively enriched in particles 63-150 μm in summer, while in particles <45 μm in winter. Spatially, the distribution of heavy metal concentrations was more concentrated in the winter and showed low levels of regional diffusion. Based on the pollution mapping and PCA-PMF, the integrated source appointment showed that the industrial sources are the main sources of Zn, Cd and Pb, and their contributions are higher at a particle below 45 μm in winter. The construction source significantly influenced Cr, Mn and Cu in summer with little diversity among particle size ranges. Therefore, the <45 μm particles from industrial emission in winter is suggested to be under priority control. And the industrial transformation demonstration area in the Qingshan district should upgrade heavy pollution industry lines and strengthen the monitoring of soot emissions. Further, emissions from coal-fired enterprises should be restricted in winter. Besides, the attention should be paid to avoid urban traffic jams around construction projects and increase enclosed construction ratio.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146357DOI Listing
August 2021

Clinical applications of single-photon emission computed tomography/computed tomography in post-ablation iodine scintigraphy in children and young adults with differentiated thyroid carcinoma.

Pediatr Radiol 2021 Mar 24. Epub 2021 Mar 24.

Department of Nuclear Medicine, West China Hospital, Sichuan University, No 37. Guoxue Alley, Chengdu, 610041, China.

Background: The utility of integrated single-photon emission computed tomography/computed tomography (SPECT/CT) in children and young adults with differentiated thyroid carcinoma is incompletely studied.

Objective: To determine the value of adding SPECT/CT to conventional whole-body scintigraphy in post-ablation iodine-131 (I) scintigraphy for children and young adults with differentiated thyroid carcinoma.

Materials And Methods: Planar scintigraphy and SPECT/CT were performed on 42 post-surgical children and young adults (32 female, 10 male; mean age 14.3±4.9 years, range 7-20 years) with differentiated thyroid carcinoma (39 papillary, 2 follicular, 1 mixed) 5 days after the therapeutic administration of 1.9-7.4 GBq of I. Planar and SPECT/CT images were interpreted independently, and sites of uptake were categorized as positive or equivocal with respect to thyroid bed, lymph node and distant metastasis uptake. An experienced thyroid endocrinologist used a combination of surgical histopathology and scintigraphic findings to determine whether the addition of SPECT/CT would change patient management.

Results: Planar scintigraphy evidenced 88 radioiodine-avid foci and SPECT/CT confirmed all foci. No additional foci were disclosed by SPECT/CT. SPECT/CT correctly classified 16/88 (18%) foci that were unclear or wrongly classified at planar scintigraphy. Globally, SPECT/CT showed an incremental value over planar scintigraphy in 9 (21.4%) patients and changed therapeutic management in 3 (7.1%; 95% confidence interval, 2-20%) patients.

Conclusion: SPECT/CT improved localization and characterization of focal I uptake on post-ablation whole-body scintigraphy in children and young adults with differentiated thyroid carcinoma. Further prospective evaluation in a larger series is justified to prove the effect of post-ablation SPECT/CT-based management decisions.
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http://dx.doi.org/10.1007/s00247-021-05039-2DOI Listing
March 2021

The use of systematic review evidence to support the development of guidelines for positron emission tomography: a cross-sectional survey.

Eur Radiol 2021 Mar 8. Epub 2021 Mar 8.

Chinese Evidence-based Medicine Centre, Cochrane China Centre and MAGIC China Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Objectives: To examine to what degree guidelines for PET and PET/CT used systematic review evidence.

Methods: The latest version of guidelines for PET, PET/CT or PET/MRI published in English in PubMed until December 2019 was analysed in two categories: (1) for indications, if mainly discussing the appropriate use of PET in diverse conditions; (2) for procedures, if providing step-by-step instructions for imaging. We surveyed the general characteristics and the use of systematic review evidence for developing recommendations across all guidelines, and surveyed the citation of evidence for five recommendation topics in guidelines for procedures.

Results: Forty-seven guidelines, published between 2004 and 2020, were included. Guidelines for indications were developed mainly on systematic reviews (13 of 19, 68.4%). Among those, 12 (63.2%) reported the level of evidence, 4 (21.1%) reported the strength of recommendations, 3 (15.8%) described external review and 7 (36.8%) involved methodologists. Guidelines for procedures were seldom developed on systematic reviews (1 of 27, 3.7%). Among those, 1 (3.7%) reported the level of evidence, 1 (3.7%) reported the strength of recommendations, 3 (11.1%) described external review and 1 (3.7%) involved methodologists. Systematic review evidence was cited by 2 (7.4%) procedure guidelines per recommendation topic in median.

Conclusion: The use of systematic review evidence for developing recommendations among PET or PET/CT guidelines was suboptimal. While our survey is an icebreaking attempt to explore a key element (i.e. use of systematic review evidence) for developing nuclear medicine guidelines, assessments of other domains of guideline quality may help capture the entire picture.

Key Points: • The use of systematic review evidence for developing recommendations among guidelines for PET or PET/CT was suboptimal. • Only 13 (68.4%) guidelines for indications and 1 (3.7%) guideline for procedures systematically reviewed the literature during guideline development. • For each recommendation topic we examined, only a median of 2 (7.4%) procedure guidelines cited systematic review evidence.
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http://dx.doi.org/10.1007/s00330-021-07756-6DOI Listing
March 2021

Metabolism and Inflammation in Cardiovascular Health and Diseases: Mechanisms to Therapies.

J Mol Cell Cardiol 2021 Mar 2. Epub 2021 Mar 2.

Department of Internal Medicine (Cardiology), University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

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http://dx.doi.org/10.1016/j.yjmcc.2021.02.011DOI Listing
March 2021

Metabolomics analysis of dandelions from different geographical regions in China.

Phytochem Anal 2021 Feb 28. Epub 2021 Feb 28.

School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, 210023, P. R. China.

Introduction: Dandelion (Taraxacum mongolicum Hand.-Mazz.) is a perennial herb with diverse pharmacological effects. The development and utilization of dandelion have attracted much attention.

Objectives: Our aims were to provide a reference basis for the identification of the origin of dandelions and to study the influence of their origin on their quality. Methods High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze metabolites from dandelions from four different geographical regions in China, namely Gansu, Henan, Shanxi, and Jiangsu. Metabolite analysis was performed using orthogonal partial least-squares discriminant analysis, and to identify potential metabolic pathways, MBRole was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.

Results: Principal component analysis revealed that the chemical components of dandelions sampled from the four regions showed noticeable differences. Twenty-six, six, six, eight, eight, and fifteen differentially produced metabolites were identified upon comparison between Gansu and Jiangsu, Gansu and Shanxi, Gansu and Henan, Henan and Shanxi, Henan and Jiangsu, and Shanxi and Jiangsu, respectively. These differentially produced metabolites were mainly phenolic compounds. Further, KEGG pathway enrichment analysis showed that the main metabolic pathways involved were biosynthesis of phenylpropanoids and flavonoids.

Conclusion: The methods reported herein can be used to identify the origin of dandelions; moreover, our results can serve as a reference basis for future studies.
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http://dx.doi.org/10.1002/pca.3033DOI Listing
February 2021

Acetylation of muscle creatine kinase negatively impacts high-energy phosphotransfer in heart failure.

JCI Insight 2021 02 8;6(3). Epub 2021 Feb 8.

Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, and.

A hallmark of impaired myocardial energetics in failing hearts is the downregulation of the creatine kinase (CK) system. In heart failure patients and animal models, myocardial phosphocreatine content and the flux of the CK reaction are negatively correlated with the outcome of heart failure. While decreased CK activity is highly reproducible in failing hearts, the underlying mechanisms remains elusive. Here, we report an inverse relationship between the activity and acetylation of CK muscle form (CKM) in human and mouse failing hearts. Hyperacetylation of recombinant CKM disrupted MM homodimer formation and reduced enzymatic activity, which could be reversed by sirtuin 2 treatment. Mass spectrometry analysis identified multiple lysine residues on the MM dimer interface, which were hyperacetylated in the failing hearts. Molecular modeling of CK MM homodimer suggested that hyperacetylation prevented dimer formation through interfering salt bridges within and between the 2 monomers. Deacetylation by sirtuin 2 reduced acetylation of the critical lysine residues, improved dimer formation, and restored CKM activity from failing heart tissue. These findings reveal a potentially novel mechanism in the regulation of CK activity and provide a potential target for improving high-energy phosphoryl transfer in heart failure.
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http://dx.doi.org/10.1172/jci.insight.144301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934860PMC
February 2021

Protective Effect of a bi-specific Fc-fusion protein on the barrier of hRPE cells.

Ophthalmic Res 2021 Feb 5. Epub 2021 Feb 5.

To evaluate the protective effects of IBI302, a bi-specific Fc-fusion protein that theoretically can bind vascular endothelial growth factor (VEGF), complement C3b and C4b in the cultured human retinal pigment epithelial (hRPE) cells. Primary hRPE cells were isolated and cultured to monolayer barrier. hRPE monolayers were divided into control group, VEGF-Trap group, complement receptor 1 (CR1) group, and IBI302 group. Identification of hRPE cells, barrier function, inflammation factors and immune response products were tested by immunofluorescent staining, transepithelial resistance (TER) and ELISA. IBI302 treatment significantly improved TER of hRPE cells after complement-activated oxidative stress compared with control group, VEGF-Trap group, and CR1 group. The maximum effect of IBI302 on protecting hRPE cell viability was observed at the concentration of 1μg/ml. Elevated expression of VEGF, CCL2, C3a, C5a and MAC were inhibited by IBI302. IBI302 could protect the barrier function of hRPE cells. IBI302 might be a potentially effective drug for the RPE barrier-associated ocular diseases.
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http://dx.doi.org/10.1159/000515053DOI Listing
February 2021

Use of radiomics based on F-FDG PET/CT and machine learning methods to aid clinical decision-making in the classification of solitary pulmonary lesions: an innovative approach.

Eur J Nucl Med Mol Imaging 2021 Feb 5. Epub 2021 Feb 5.

Department of Nuclear Medicine, West China Hospital, Sichuan University, 37# GuoXueLane, Chengdu, 610041, China.

Purpose: This study was designed and performed to assess the ability of F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and computed tomography (CT) radiomics features combined with machine learning methods to differentiate between primary and metastatic lung lesions and to classify histological subtypes. Moreover, we identified the optimal machine learning method.

Methods: A total of 769 patients pathologically diagnosed with primary or metastatic lung cancers were enrolled. We used the LIFEx package to extract radiological features from semiautomatically segmented PET and CT images within the same volume of interest. Patients were randomly distributed in training and validation sets. Through the evaluation of five feature selection methods and nine classification methods, discriminant models were established. The robustness of the procedure was controlled by tenfold cross-validation. The model's performance was evaluated using the area under the receiver operating characteristic curve (AUC).

Results: Based on the radiomics features extracted from PET and CT images, forty-five discriminative models were established. Combined with appropriate feature selection methods, most classifiers showed excellent discriminative ability with AUCs greater than 0.75. In the differentiation between primary and metastatic lung lesions, the feature selection method gradient boosting decision tree (GBDT) combined with the classifier GBDT achieved the highest classification AUC of 0.983 in the PET dataset. In contrast, the feature selection method eXtreme gradient boosting combined with the classifier random forest (RF) achieved the highest AUC of 0.828 in the CT dataset. In the discrimination between squamous cell carcinoma and adenocarcinoma, the combination of GBDT feature selection method with GBDT classification had the highest AUC of 0.897 in the PET dataset. In contrast, the combination of the GBDT feature selection method with the RF classification had the highest AUC of 0.839 in the CT dataset. Most of the decision tree (DT)-based models were overfitted, suggesting that the classification method was not appropriate for practical application.

Conclusion: F-FDG PET/CT radiomics features combined with machine learning methods can distinguish between primary and metastatic lung lesions and identify histological subtypes in lung cancer. GBDT and RF were considered optimal classification methods for the PET and CT datasets, respectively, and GBDT was considered the optimal feature selection method in our analysis.
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http://dx.doi.org/10.1007/s00259-021-05220-7DOI Listing
February 2021

Generation of a Bovine Serum Albumin-Diligand Complex for the Protection of Bioactive Quercetin and Suppression of Heme Toxicity.

Chem Res Toxicol 2021 Mar 19;34(3):920-928. Epub 2021 Jan 19.

Key Laboratory of Functional Small Organic Molecule, Ministry of Education; College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi China.

As an abundant protein in milk and blood serum, bovine serum albumin (BSA) contains various sites to bind a lot of bioactive components, generating BSA-monoligand complex. Demonstration of the interaction between BSA and bioactive components (such as heme, flavonoids) is important to develop effective carrier for the protection of bioactive ligands and to reduce cytotoxicity of heme. Herein, the bindings of BSA to quercetin and/or heme were investigated by multispectroscopic and molecular docking methods. The fluorescence of protein was significantly quenched by both quercetin and heme in a static mode (i.e., generation of BSA-ligand complex). Although quercetin had lower affinity to protein than heme, the interactions of both compounds with protein did locate in site I (i.e., subdomain IIA). BSA-diligand complex was successfully generated after the coaddition of quercetin and heme. The cytotoxicity of free heme to endothelial cells was reduced in the BSA-diligand complex relative to that of heme or BSA-monoligand complex, while the stability of bioactive quercetin was promoted in the complex relative to free flavonoid. The complex provided a better inhibition on the cytotoxicity of heme than BSA-monoligand complex, in which the copresence of quercetin played a vital role.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00537DOI Listing
March 2021

Quercetin Attenuated Myeloperoxidase-Dependent HOCl Generation and Endothelial Dysfunction in Diabetic Vasculature.

J Agric Food Chem 2021 Jan 4;69(1):404-413. Epub 2021 Jan 4.

MOE Key Laboratory of Functional Small Organic Molecule, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.

Myeloperoxidase (MPO)-dependent hypochlorous acid (HOCl) generation plays crucial roles in diabetic vascular complications. As a natural polyphenol, quercetin has antioxidant properties in various diabetic models. Herein, we investigated the therapeutic mechanism for quercetin on MPO-mediated HOCl generation and endothelial dysfunction in diabetic vasculature. In vitro, the presence of MPO could amplify high glucose-induced endothelial dysfunction which was significantly inhibited by the NADPH oxidase inhibitor, HOCl or HO scavengers, revealing the contribution of MPO/HO/HOCl to vascular endothelial injury. Furthermore, quercetin effectively inhibited MPO/high glucose-mediated HOCl generation and cytotoxicity to vascular endothelial cells. The inhibitive effect on MPO activity was related to the fact that quercetin reduced high glucose-induced HO generation in endothelial cells and directly acted as a competitive substrate for MPO, thus limiting MPO/HO-dependent HOCl production. Moreover, quercetin could attenuate HOCl-caused endothelial dysfunction in endothelial cells and isolated aortas. In vivo, dietary quercetin significantly inhibited aortic endothelial dysfunction in diabetic mice, while this compound simultaneously suppressed vascular MPO expression and activity. Therefore, it was demonstrated herein that quercetin inhibited endothelial injury in diabetic vasculature via suppression of MPO/high glucose-dependent HOCl formation.
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http://dx.doi.org/10.1021/acs.jafc.0c06335DOI Listing
January 2021

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus.

Chin Med 2020 Dec 21;15(1):128. Epub 2020 Dec 21.

Department of Natural Medicine, School of Pharmacy, Fudan University, No. 826, Zhangheng Road, Shanghai, 201203, People's Republic of China.

Background: Infections induced by influenza viruses, as well as coronavirus disease 19 (COVID-19) pandemic induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) led to acute lung injury (ALI) and multi organ failure, during which traditional Chinese medicine (TCM) played an important role in treatment of the pandemic. The study aimed to investigate the effect of Indigo Naturalis on ALI induced by influenza A virus (IAV) in mice.

Method: The anti-influenza and anti-inflammatory properties of aqueous extract of Indigo Naturalis (INAE) were evaluated in vitro. BALB/c mice inoculated intranasally with IAV (H1N1) were treated intragastrically with INAE (40, 80 and 160 mg/kg/day) 2 h later for 4 or 7 days. Animal lifespan and mortality were recorded. Expression of high mobility group box-1 protein (HMGB-1) and toll-like receptor 4 (TLR4) were evaluated through immunohistological staining. Inflammatory cytokines were also monitored by ELISA.

Result: INAE inhibited virus replication on Madin-Darby canine kidney (MDCK) cells and decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated peritoneal macrophages in vitro. The results showed that oral administration of 160 mg/kg of INAE significantly improved the lifespan (P < 0.01) and survival rate of IAV infected mice, improved lung injury and lowered viral replication in lung tissue (P < 0.01). Treatment with INAE (40, 80 and 160 mg/kg) significantly increased liver weight and liver index (P < 0.05), as well as weight and organ index of thymus and spleen at 160 mg/kg (P < 0.05). Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels were reduced by INAE administration (P < 0.05). The expression of HMGB-1 and TLR4 in lung tissue were also suppressed. The increased production of myeloperoxidase (MPO) and methylene dioxyamphetamine (MDA) in lung tissue were inhibited by INAE treatment (P < 0.05). Treatment with INAE reduced the high levels of interferon α (IFN-α), interferon β (IFN-β), monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted factor (RANTES), interferon induced protein-10 (IP-10), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) (P < 0.05), with increased production of interferon γ (IFN-γ) and interleukin-10 (IL-10) (P < 0.05).

Conclusion: The results showed that INAE alleviated IAV induced ALI in mice. The mechanisms of INAE were associated with its anti-influenza, anti-inflammatory and anti-oxidation properties. Indigo Naturalis might have clinical potential to treat ALI induced by IAV.
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http://dx.doi.org/10.1186/s13020-020-00415-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750395PMC
December 2020

New Frontiers in Molecular Imaging Using Peptide-Based Radiopharmaceuticals for Prostate Cancer.

Front Chem 2020 1;8:583309. Epub 2020 Dec 1.

Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China.

The high incidence of prostate cancer (PCa) increases the need for progress in its diagnosis, staging, and precise treatment. The overexpression of tumor-specific receptors for peptides in human cancer cells, such as gastrin-releasing peptide receptor, natriuretic peptide receptor, and somatostatin receptor, has indicated the ideal molecular basis for targeted imaging and therapy. Targeting these receptors using radiolabeled peptides and analogs have been an essential topic on the current forefront of PCa studies. Radiolabeled peptides have been used to target receptors for molecular imaging in human PCa with high affinity and specificity. The radiolabeled peptides enable optimal quick elimination from blood and normal tissues, producing high contrast for positron emission computed tomography and single-photon emission computed tomography imaging with high tumor-to-normal tissue uptake ratios. Owing to their successful application in visualization, peptide derivatives with therapeutic radionuclides for peptide receptor radionuclide therapy in PCa have been explored in recent years. These developments offer the promise of personalized, molecular medicine for individual patients. Hence, we review the preclinical and clinical literature in the past 20 years and focus on the newer developments of peptide-based radiopharmaceuticals for the imaging and therapy of PCa.
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http://dx.doi.org/10.3389/fchem.2020.583309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736158PMC
December 2020

18F-FDG PET/CT Imaging of Pancreatic and Adrenal Metastases in a Patient With Mesenchymal Chondrosarcoma.

Clin Nucl Med 2021 Mar;46(3):231-232

From the Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu.

Abstract: Metastases of mesenchymal chondrosarcoma to either the pancreas or the adrenal glands are rare. We hereby presented the 18F-FDG PET/CT images of a 21-year-old man initially diagnosed with chondrosarcoma of the right 11th rib. His 18F-FDG PET/CT scan after radiotherapy demonstrated 2 hypermetabolic lesions in the right adrenal gland and the pancreas, respectively. These 2 lesions were later confirmed by biopsy to be metastatic mesenchymal chondrosarcoma.
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http://dx.doi.org/10.1097/RLU.0000000000003468DOI Listing
March 2021

Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF.

Circ Res 2021 Jan 12;128(2):232-245. Epub 2020 Nov 12.

Laboratory of Mitochondrial and Metabolism, Department of Anesthesiology, National Clinical Research Center for Geriatrics (Y.D., M.X., Q.L., W.O., Y. Zhang, H.Y., Y. Zheng, Y.L., C.J., G.C., D.D., W.Z., S.W., M.G., T.L.), West China Hospital of Sichuan University, Chengdu.

Rationale: Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF.

Objective: This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model.

Methods And Results: By combining the age, long-term high-fat diet, and desoxycorticosterone pivalate challenge in a mouse model, we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of IL (interleukin)-1β/IL-18 and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing β-hydroxybutyrate level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokine-triggered mitochondrial dysfunction and fibrosis. Moreover, β-hydroxybutyrate downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of CS (citrate synthase) and inhibition of fatty acid uptake.

Conclusions: Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis, which can be ameliorated by promoting β-hydroxybutyrate abundance.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.317933DOI Listing
January 2021

More evidence is warranted to establish the role of 18FDG-PET/CT in FUO investigations among children.

Clin Infect Dis 2020 Oct 16. Epub 2020 Oct 16.

Chinese Evidence-based Medicine Center, West China Hospital, Sichuan University.

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http://dx.doi.org/10.1093/cid/ciaa1574DOI Listing
October 2020

Rhodium(III)-Catalyzed Asymmetric [4+1] and [5+1] Annulation of Arenes and 1,3-Enynes: A Distinct Mechanism of Allyl Formation and Allyl Functionalization.

Angew Chem Int Ed Engl 2020 12 7;59(50):22706-22713. Epub 2020 Oct 7.

School of Chemistry and Chemical Engineering, Shaanxi Normal University (SNNU), Xi'an, 710062, China.

We report chiral Rh cyclopentadienyl-catalyzed enantioselective synthesis of lactams and isochromenes through oxidative [4+1] and [5+1] annulation, respectively, between arenes and 1,3-enynes. The reaction proceeds through a C-H activation, alkenyl-to-allyl rearrangement, and a nucleophilic cyclization cascade. The mechanisms of the [4+1] annulations were elucidated by a combination of experimental and computational methods. DFT studies indicated that, following the C-H activation and alkyne insertion, a Rh alkenyl intermediate undergoes δ-hydrogen elimination of the allylic C-H via a six-membered ring transition state to produce a Rh enallene hydride intermediate. Subsequent hydride insertion and allyl rearrangement affords several rhodium(III) allyl intermediates, and a rare Rh η ene-allyl species with π-agostic interaction undergoes SN '-type external attack by the nitrogen nucleophile, instead of C-N reductive elimination, as the stereodetermining step.
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http://dx.doi.org/10.1002/anie.202010832DOI Listing
December 2020

Quercetin Inhibited Endothelial Dysfunction and Atherosclerosis in Apolipoprotein E-Deficient Mice: Critical Roles for NADPH Oxidase and Heme Oxygenase-1.

J Agric Food Chem 2020 Sep 21;68(39):10875-10883. Epub 2020 Sep 21.

College of Chemistry and Chemical Engineering, MOE Key Laboratory of Functional Small Organic Molecule, Jiangxi Normal University, No. 99 Ziyang Road, Nanchang 330022, Jiangxi, People's Republic of China.

NADPH oxidase-dependent superoxide (O) production and oxidative stress play important roles in endothelial dysfunction and atherosclerosis. Herein, we investigated the potential effects of dietary quercetin, a flavonoid derived in the diet from vegetables and fruit, on vascular endothelial function and atherosclerosis in the high-fat diet (HFD)-fed apolipoprotein E-deficient (ApoE) mice. Dietary quercetin treatment significantly suppressed endothelial dysfunction and aortic atherosclerosis in HFD-fed ApoE mice ( < 0.05, all cases). Mechanistic studies demonstrated that dietary quercetin significantly attenuated p47phox expression and inhibited NADPH oxidase-derived oxidative stress in the aortas of HFD-fed ApoE mice, while the expression and activity of antioxidant enzyme heme oxygenase-1 (HO-1) was enhanced after quercetin treatment ( < 0.05, all cases). In vitro, it was found that quercetin significantly attenuated NADPH oxidase-derived O formation (75 ± 5.6% for quercetin versus 100 ± 6.0% for the control group, < 0.01) in endothelial cells through induction of HO-1. In addition, the favorable effects of quercetin on oxidant (i.e., HO)-induced endothelial dysfunction could be eliminated by tin protoporphyrin IX (an HO-1 inhibitor) or HO-1-specific siRNA. Our results demonstrated the critical roles of NADPH oxidase and HO-1 for the indirect antioxidant properties of quercetin in vascular diseases.
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http://dx.doi.org/10.1021/acs.jafc.0c03907DOI Listing
September 2020