Publications by authors named "Weihua Zhang"

462 Publications

Selective Leaching of Rare Earth Elements from Ion-Adsorption Rare Earth Tailings: A Synergy between CeO Reduction and Fe/Mn Stabilization.

Environ Sci Technol 2021 Jul 26. Epub 2021 Jul 26.

School of Environmental Science and Engineering, Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology, Guangdong Provincial Engineering Research Center for Heavy Metal Contaminated Soil Remediation, Sun Yat-sen University, Guangzhou, Guangdong 510006, P.R. China.

The increasing demand for rare earth elements (REEs) motivates the development of novel strategies for cost-effective REE recovery from secondary sources, especially rare earth tailings. The biggest challenges in recovering REEs from ion-adsorption rare earth tailings are incomplete extraction of cerium (Ce) and the coleaching of iron (Fe) and manganese (Mn). Here, a synergistic process between reduction and stabilization was proposed by innovatively using elemental sulfur (S) as reductant for converting insoluble CeO into soluble Ce(SO) and transforming Fe and Mn oxides into inert FeFeO and MnFeO spinel minerals. After the calcination at 400 °C, 97.0% of Ce can be dissolved using a diluted sulfuric acid, along with only 3.67% of Fe and 23.3% of Mn leached out. Thermodynamic analysis reveals that CeO was indirectly reduced by the intermediates MnSO and FeS in the system. Density functional theory calculations indicated that Fe(II) and Mn(II) shared similar outer electron arrangements and coordination environments, favoring Mn(II) over Ce(III) as a replacement for Fe(II) in the FeO octahedral structure of FeFeO. Further investigation on the leaching process suggested that 0.5 mol L HSO is sufficient for the recovery of REEs (97.0%). This research provides a promising strategy to selectively recover REEs from mining tailings or secondary sources via controlling the mineral phase transformation.
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http://dx.doi.org/10.1021/acs.est.1c03106DOI Listing
July 2021

Efficacy comparison between microwave ablation combined with radiation therapy and radiation therapy alone for locally advanced nonsmall-cell lung cancer.

J Cancer Res Ther 2021 Jul;17(3):715-719

The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences), Jinan, China.

Purpose: Comparing the efficacy and complications of microwave ablation (MA) combined with intensity-modulated radiation therapy (IMRT) and IMRT alone for locally advanced peripheral nonsmall-cell lung cancer (NSCLC).

Methods: Retrospective analysis was conducted on 76 patients with locally advanced peripheral NSCLC undergoing chemotherapy and metastatic lymph node radiation therapy from June 2014 to June 2016. Either MA or IMRT was used to treat primary lesions. Thirty-four cases were treated with MA (MA group), 42 cases were treated with IMRT (IMRT group), and comparisons were made of the 1-3-year progression-free survival (PFS) and complications of the two groups.

Results: The PFS of the MA group at 1, 2, and 3 years were 70.59% (24/34), 47.06% (16/34), and 35.29% (12/34), and the PFS of the IMRT group at the same intervals were 71.43% (30/42), 52.38% (22/42), and 35.71% (15/42), with no significant difference (χ = 0.006, P = 0.936) (χ = 0.213, P = 0.645) (χ = 0.001, P = 0.970). Radiation-induced lung injury (RILI) occurred in 14.70% (5/34) of MA group patients, which was significantly lower than in the IMRT group 40.48% (17/42), but without grade II or above RILI.

Conclusion: MA combined with IMRT in the treatment of locally advanced peripheral NSCLC was not inferior to the clinical effect of radiation therapy alone, and radiation lung injury incidence was also lower.
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http://dx.doi.org/10.4103/jcrt.JCRT_633_20DOI Listing
July 2021

Immunotherapies for Anti-N-M-methyl-D-aspartate Receptor Encephalitis: Multicenter Retrospective Pediatric Cohort Study in China.

Front Pediatr 2021 29;9:691599. Epub 2021 Jun 29.

Division of Pediatric Neurology, Pediatrics Department, Peking University First Hospital, Beijing, China.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been discovered for more than a decade, but the establishment of standardized immunotherapy protocol for pediatric patients still needs more clinical evidence. A multicenter, retrospective study was conducted on pediatric patients diagnosed with anti-NMDAR encephalitis between November 2011 and December 2018. The clinical records including clinical manifestations, immunotherapy strategies, and outcomes were collected and analyzed. A total of 386 patients were included in our study and the median onset age was 8.00 (IQR 4.83-10.90) years. All patients received first-line immunotherapy and the majority (341, 88.3%) used the standard combination of methylprednisolone pulses (MEP) and intravenous immunoglobulins (IVIG), but 211 patients did not show satisfactory improvement (mRS ≥ 3). Mainly three treatment strategies were applied after first-line immunotherapy: second-line immunotherapy, repetitive first-line immunotherapy, and maintaining oral prednisolone. For patients with mRS ≥ 4 after first-line immunotherapy, the incidence of poor outcome (mRS ≥ 3) in oral prednisolone group was higher than that in other treatment groups ( = 0.039). No difference in complete recovery rate (mRS = 0) was found between patients receiving second-line and repetitive first-line immunotherapy, or patients using long-term and short-term prednisolone. Out of 149 patients who received anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab) test, 27 (18.12%) were positive. Patients with concomitantly positive MOG-Ab showed milder conditions compared to patients with typical anti-NMDAR encephalitis and were more inclined to relapses. We also identified female, MOG-Ab positive, and not receiving second-line and/or repetitive first-line immunotherapy were risk factors for relapses. For patients with mRS ≥ 4 after first-line immunotherapy and patients with concomitantly positive MOG-Ab, second-line immunotherapy is recommended. When second-line immunotherapy is not applicable, repetitive first-line immunotherapy can be considered as an option. Both second-line and repetitive first-line immunotherapy are beneficial to reduce relapse rate. The duration of sequential oral prednisolone can be shortened after fully evaluating patients' conditions.
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http://dx.doi.org/10.3389/fped.2021.691599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276978PMC
June 2021

Efficacy of Drug-Eluting Beads Transarterial Chemoembolization Plus Apatinib Compared with Conventional Transarterial Chemoembolization Plus Apatinib in the Treatment of Unresectable Hepatocellular Carcinoma.

Cancer Manag Res 2021 6;13:5391-5402. Epub 2021 Jul 6.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

Objective: The aim of the study was to compare the efficacy and safety of drug-eluting beads TACE plus apatinib (D-TACE-A) with those of conventional TACE plus apatinib (C-TACE-A) for the treatment of unresectable HCC.

Methods: We retrospectively reviewed 187 consecutive patients who received TACE plus apatinib in our institution from January 1, 2017, to July 1, 2019. Among them, 91 patients received C-TACE-A, and 96 patients received D-TACE-A. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and disease control rate (DCR). Propensity score matching (PSM) was used to reduce selection bias.

Results: Before PSM, the median OS was 15 months (95% CI: 12.5-17.5) and 13 months (95% CI: 11.1-14.9; P=0.480) in the C-TACE-A and D-TACE-A groups, respectively. The median PFS was 7 months (95% CI: 5.9-8.1) in the C-TACE-A group and 7 months (95% CI: 5.6-8.4; p=0.677) in the D-TACE-A group. The DCR was 81.3% in the C-TACE-A group and 72.9% in the D-TACE-A group. Cox regression analysis showed that D-TACE-A did not increase mortality risk or tumor recurrence risk. After PSM, there was no statistically significant difference in median OS or PFS between the two groups. In the subgroup analysis, after adjusting for relative factors, D-TACE-A increased the mortality risk more than C-TACE-A in patients with BCLC stage C (HR: 1.678, 95% CI: 1.129-2.495; P=0.011), but D-TACE-A lowered the tumor recurrence risk compared with C-TACE-A in patients with Child-Pugh B (HR: 0.210, 95% CI: 0.082-0.538; P=0.001) and cirrhosis (HR: 0.481, 95% CI: 0.293-0.791; P=0.004). Grade III and IV adverse events in patients with D-TACE-A were similar to those in patients treated with C-TACE-A (P>0.05).

Conclusion: Patients with unresectable HCC treated with D-TACE-A might not show increased survival compared with patients treated with C-TACE-A. Advanced HCC patients without cirrhosis may receive greater survival benefits from C-TACE-A than D-TACE-A.
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http://dx.doi.org/10.2147/CMAR.S314762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275036PMC
July 2021

Transplantation of a vascularized pedicle of hemisected spinal cord to establish spinal cord continuity after removal of a segment of the thoracic spinal cord: A proof-of-principle study in dogs.

CNS Neurosci Ther 2021 Jun 28. Epub 2021 Jun 28.

Global Initiative to Cure Paralysis (GICUP), Columbus, OH, USA.

Introduction: Glial scar formation impedes nerve regeneration/reinnervation after spinal cord injury (SCI); therefore, removal of scar tissue is essential for SCI treatment.

Aims: To investigate whether removing a spinal cord and transplanting a vascularized pedicle of hemisected spinal cord from the spinal cord caudal to the transection can restore motor function, to aid in the treatment of future clinical spinal cord injuries. We developed a canine model. After removal of a 1-cm segment of the thoracic (T10-T11) spinal cord in eight beagles, a vascularized pedicle of hemisected spinal cord from the first 1.5 cm of the spinal cord caudal to the transection (cut along the posterior median sulcus of the spinal cord) was transplanted to bridge the transected spinal cord in the presence of a fusogen (polyethylene glycol, PEG) in four of the eight dogs. We used various forms of imaging, electron microscopy, and histologic data to determine that after our transplantation of a vascular pedicled hemisection to bridge the transected spinal cord, electrical continuity across the spinal bridge was restored.

Results: Motor function was restored following our transplantation, as confirmed by the re-establishment of anatomic continuity along with interfacial axonal sprouting.

Conclusion: Taken together, our findings suggest that SCI patients-who have previously been thought to have irreversible damage and/or paralysis-may be treated effectively with similar operative techniques to re-establish electrical and functional continuity following SCI.
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http://dx.doi.org/10.1111/cns.13696DOI Listing
June 2021

Transcriptome and metabolite analysis related to branch development in two genotypes of Eucalyptus urophylla.

Mol Genet Genomics 2021 Jun 22. Epub 2021 Jun 22.

Guangdong Provincial Key Laboratory of Silviculture, Protection and Utilization, Guangdong Academy of Forestry, Guangzhou, 510520, China.

Branching in long-lived plants can cause scarring at the base and affect wood density, which greatly inhibits wood yield and quality. Eucalyptus urophylla is one of the most important commercial forest tree species in South China, with diverse branch number and branch angles under different genetic backgrounds. However, the main elements and regulatory mechanisms associated with different branching traits in E. urophylla remain unclear. To identify the factors that may influence branching, the transcriptome and metabolome were performed on the shoot apex (SA), lateral shoot apex (LSA), and stem segment at the 5th axillary bud from the shoot apex (S1) in lines ZQUC14 (A) and LDUD26 (B), with A exhibiting a smaller Ba than B. A total of 307.3 million high-quality clean reads and nine hormones were identified from six libraries. Several differentially expressed regulatory factors were identified between the two genotypes of E. urophylla. The Kyoto Encyclopedia of Genes and Genomes pathways were enriched in plant hormone signal transduction, plant hormone biosynthesis and their transport pathways. Furthermore, gene expression pattern analysis identified genes that were significantly downregulated or upregulated in S1 relative to the SA and LSA segments, and the plant hormone signal transduction pathway was constructed to explain branching development. This study clarified the main plant hormones and genes underlying branch numbers and angles of E. urophylla, confirmed that ABA and SA could promote a larger branch angle and smaller branch number, while IAA has an opposite function. Numbers of key candidate genes involved in plant hormone signal transduction were found in the positive regulation of branch formation. These novel findings should aid molecular breeding of branching in Eucalyptus.
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http://dx.doi.org/10.1007/s00438-021-01803-zDOI Listing
June 2021

PKCδ-mediated SGLT1 upregulation confers the acquired resistance of NSCLC to EGFR TKIs.

Oncogene 2021 Jul 21;40(29):4796-4808. Epub 2021 Jun 21.

Center for Molecular Medicine, Research Center for Cancer Biology, and Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.

The tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have been widely used for non-small cell lung cancer (NSCLC) patients, but the development of acquired resistance remains a therapeutic hurdle. The reduction of glucose uptake has been implicated in the anti-tumor activity of EGFR TKIs. In this study, the upregulation of the active sodium/glucose co-transporter 1 (SGLT1) was found to confer the development of acquired EGFR TKI resistance and was correlated with the poorer clinical outcome of the NSCLC patients who received EGFR TKI treatment. Blockade of SGLT1 overcame this resistance in vitro and in vivo by reducing glucose uptake in NSCLC cells. Mechanistically, SGLT1 protein was stabilized through the interaction with PKCδ-phosphorylated (Thr678) EGFR in the TKI-resistant cells. Our findings revealed that PKCδ/EGFR axis-dependent SGLT1 upregulation was a critical mechanism underlying the acquired resistance to EGFR TKIs. We suggest co-targeting PKCδ/SGLT1 as a potential strategy to improve the therapeutic efficacy of EGFR TKIs in NSCLC patients.
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http://dx.doi.org/10.1038/s41388-021-01889-0DOI Listing
July 2021

Helenalin Facilitates Reactive Oxygen Species-Mediated Apoptosis and Cell Cycle Arrest by Targeting Thioredoxin Reductase-1 in Human Prostate Cancer Cells.

Med Sci Monit 2021 Jun 14;27:e930083. Epub 2021 Jun 14.

Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland).

BACKGROUND Helenalin is a pseudoguaianolide natural product with anti-cancer activities. This study investigated the underlying mechanism of the anti-prostate cancer effects of helenalin in vitro. MATERIAL AND METHODS CCK-8 assay was performed to detect the optimal concentrations of helenalin in DU145 and PC-3 cells. After exposure to helenalin and/or reactive oxygen species (ROS) inhibitor, ROS production was assessed by DCFH-DA staining. Thioredoxin reductase-1 (TrxR1) expression was detected by RT-qPCR and western blot. Moreover, apoptosis and cell cycle were evaluated by flow cytometry. Following TrxR1 knockdown or overexpression, TrxR1 expression, ROS generation, apoptosis, cell cycle, migration, and invasion were examined in cells co-treated with helenalin. RESULTS Helenalin distinctly repressed the viability of prostate cancer cells in a concentration-dependent manner. We chose 8 μM and 4 μM as the optimal concentrations of helenalin for DU145 and PC-3 cells, respectively. Helenalin treatment markedly triggered ROS production and lowered TrxR1 expression, which was ameliorated by ROS inhibitor. Exposure to helenalin facilitated apoptosis as well as G0/G1 cell cycle arrest, which was reversed by ROS inhibitor. Helenalin relieved the inhibitory effect of TrxR1 on ROS production. Furthermore, helenalin ameliorated the decrease in apoptosis rate and the shortening of G0/G1 phase as well as the increase in migration and invasion induced by TrxR1 overexpression. CONCLUSIONS Our findings revealed that helenalin accelerated ROS-mediated apoptosis and cell cycle arrest via targeting TrxR1 in human prostate cancer cells.
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http://dx.doi.org/10.12659/MSM.930083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212699PMC
June 2021

Variables associated with patient-reported outcomes in patients with myeloproliferative neoplasms.

Leuk Lymphoma 2021 Jun 8:1-13. Epub 2021 Jun 8.

Peking University People's Hospital, Beijing, China.

We explored variables associated with patient-reported outcomes (PROs) including symptom burden, impact on daily life and work, obstacles during therapy, satisfaction level with therapy, and health-related quality of life in 1500 respondents with myeloproliferative neoplasms (MPNs) including essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF) in a multicenter, cross-sectional study across China, a representative of the developing countries. In multivariate analyses, urban household registration and higher education level were significantly-associated with no symptoms at diagnosis in respondents with ET or MF. mutation was significantly-associated with lower MPN-10 scores in respondents with MF. Higher MPN-10 scores were significantly-associated with negative impact on daily life and work as well as lower satisfaction level in respondents with ET, PV and MF. Receiving ruxolitinib was significantly-associated with high satisfaction and satisfaction in respondents with MF. In addition, other demographics and clinical variables were also impacting PROs.
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http://dx.doi.org/10.1080/10428194.2021.1933481DOI Listing
June 2021

Androgen Deprivation Therapy for Patients with Androgen-Receptor-Positive Metastatic Salivary Duct Carcinoma: A Case Report and Review of the Literature.

Onco Targets Ther 2021 28;14:3481-3486. Epub 2021 May 28.

Department of Oncology, The First Hospital of Nanchang, Nanchang, Jiangxi, 330008, People's Republic of China.

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy with high rates of recurrence and metastasis. There are no standard treatment options available for patients with recurrence and metastases. The case of a 61-year-old male with SDC of the left parotid gland is presented in this study. The results revealed that the patient's tumour had strong positive staining for androgen receptor (AR) expression, mutations in HRAS and PIK3CA but not in other related genes, and no gene amplification of HER-2. After the primary therapy of parotidectomy with neck dissection and postoperative radiation, bone metastases were found in the ribs, pelvis and spine. Androgen deprivation therapy (ADT) involving combined androgen blockade (CAB) was effective as the first-line therapy for the patient's metastases and resulted in a progression-free survival (PFS) of over 7 months to date. In conclusion, androgen deprivation therapy is recommended for patients with recurrent or metastatic SDC positive for androgen receptor expression.
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http://dx.doi.org/10.2147/OTT.S304900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169051PMC
May 2021

The platelet derived growth factor BB promotes osteogenic differentiation of periodontal ligament stem cells via the Wnt/β-catenin signaling pathway.

Arch Oral Biol 2021 May 23;129:105162. Epub 2021 May 23.

Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, 200001, PR China; Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Fudan University, Shanghai, 200001, PR China. Electronic address:

Objective: To determine the role of platelet derived growth factor BB in the regulation of cell cycle, migration and differentiation of stem cells.

Design: The gene was overexpressed in periodontal ligament stem cells using lentiviral vectors. Normal stem cells and empty lentiviral vectors-transfected were used as controls. Real time-PCR, western blotting, Cell Counting Kit-8 assay, flow cytometry, cell scratch test, Alkaline phosphatase activity assay, cell cycle analyses were conducted to assess the biological properties of stem cells. In addition, the effect of platelet derived growth factor BB on the Wnt/β-catenin signaling pathway were assessed by western blotting and immunofluorescent staining.

Results: The gene was successfully overexpressed in periodontal ligament stem cells. The Cell Counting Kit-8, scratch test and cell cycle experiments proved that platelet derived growth factor BB promoted stem cells proliferation, migration and cell cycle progression. The Real time-PCR results showed that the Osterix (OSX) and Bone Morphogenetic Protein 2 (BMP2) genes in the overexpression group were significantly higher than those in the control group, but the Peroxisome Proliferators-activated Receptors (PPARγ) and Glycogen Synthase Kinase-3β (GSK-3β) gene were lower than that in the control group. Western blotting results also indicated that the Collagen Type 1 (COL-1), BMP2, Wnt1 and β-catenin proteins were increased in the overexpression group. In addition, the expression level of β-catenin protein in the cell nuclei was higher than that in the control group.

Conclusions: In conclusion, overexpression of platelet derived growth factor BB promoted cell proliferation, migration, cell cycle progression and decreased adipogenic differentiation. Furthermore, platelet derived growth factor BB regulated osteogenic differentiation of stem cells through the Wnt/β-catenin signaling pathway.
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http://dx.doi.org/10.1016/j.archoralbio.2021.105162DOI Listing
May 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Interferometric scattering of a single plasmonic nanoparticle cluster assembled in a nanostructured template.

Opt Express 2021 Apr;29(9):12976-12983

In this work, we investigate the light scattering of a single Au nanoparticle cluster assembled in a nanostructured substrate and study how the substrate geometry influences the scattering spectrum. An explicit model was built with the help of the Green's tensor theory, showing that there are two distinct types of substrate effects, namely, the interferometric scattering caused by the local corrugation and the spectral modulation caused by the global features (i.e., the layered substrate in this work). The result predicted by the model agrees with the experimental results well, providing a simple yet quantitative tool for the spectral interpretation of plasmonic nanostructures with complex substrates.
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http://dx.doi.org/10.1364/OE.420801DOI Listing
April 2021

Wavelength-dependent laser-induced dynamic nano-annealing of single plasmonic antennas.

Nanoscale 2021 May;13(19):8991-8997

College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, MOE Key Laboratory of Intelligent Optical Sensing and Manipulation, State Key Laboratory of Analytical Chemistry for Life Sciences, Nanjing University, Nanjing 210093, China.

In this work, we studied the wavelength-dependent laser-induced dynamic annealing of single plasmonic nano-antennas using in situ white light spectroscopy. Unexpected back-and-forth motions of rapidly melted single nano-antennas were observed upon excitation with a 532 nm laser, while only gradual opening of nanogaps was found in the case of a 405 nm laser. Theoretical analyses indicate that the dramatic nano-annealing phenomenon was caused by a series of laser-induced multiphysical processes at the nanoscale. It not only leads to the local heating effect, but also induces complex behaviors such as self-accelerated melting, asymmetry-induced nano-photophoretic forces and optical forces. Our work demonstrates the complexity of light-matter interactions at the nanoscale, and provides new possibilities for shaping and manipulating plasmonic nanostructures.
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http://dx.doi.org/10.1039/d0nr09078fDOI Listing
May 2021

Community structure of environmental microorganisms associated with COVID-19 affected patients.

Aerobiologia (Bologna) 2021 May 4:1-9. Epub 2021 May 4.

College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100853 China.

To clarify the characteristics and distribution of hospital environmental microbiome associated with confirmed COVID-19 patients. Environmental samples with varying degrees of contamination which were associated with confirmed COVID-19 patients were collected, including 13 aerosol samples collected near eight patients in different wards, five swabs from one patient's skin and his personal belongings, and two swabs from the surface of positive pressure respiratory protective hood and the face shield from a physician who had close contact with one patient. Metagenomic next-generation sequencing (mNGS) was used to analyze the composition of the microbiome. One of the aerosol samples (near patient 4) was detected positive for COVID-19, and others were all negative. The environmental samples collected in different wards possessed protean compositions and community structures, the dominant genera including , , , , , and . Top 10 of genera accounted for more than 76.72%. Genera abundance and proportion of human microbes and pathogens radiated outward from the patient, while the percentage of environmental microbes increased. The abundance of the pathogenic microorganism of medical supplies is significantly higher than other surface samples. The microbial compositions of the aerosol collected samples nearby the patients were mostly similar to those from the surfaces of the patient's skin and personal belongings, but the abundance varied greatly. The positive rate of COVID-19 RNA detected from aerosol around patients in general wards was quite low. The ward environment was predominantly inhabited by species closely related to admitted patients. The spread of hospital microorganisms via aerosol was influenced by the patients' activity.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10453-021-09708-5.
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http://dx.doi.org/10.1007/s10453-021-09708-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093081PMC
May 2021

The efficacy of radiofrequency ablation versus cryoablation in the treatment of single hepatocellular carcinoma: A population-based study.

Cancer Med 2021 Jun 7;10(11):3715-3725. Epub 2021 May 7.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC), but it is difficult to use against tumors in some locations and often leads to incomplete ablation as a result of the heat-sink effect. This study was conducted to evaluate the efficacy of cryoablation compared with that of RFA in the treatment of single HCC.

Methods: This retrospective study was conducted based on the Surveillance, Epidemiology, and End Results (SEER) database. From 2004 to 2015, patients aged 40 to 79 diagnosed with HCC were included in the study. A propensity score matching (PSM) model was used to reduce selection biases.

Results: Before PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the RFA group were slightly longer than those in the cryoablation group (p > 0.05). In the subgroup analysis, the mOS and mCSS of patients with tumor sizes <3, 3-5, and >5 cm who received RFA treatment were longer than those of patients given cryoablation treatment, but there was no significant difference (p > 0.05). Similar results were presented in patients at American Joint Committee on Cancer (AJCC) stages I and II. After PSM, the mOS and mCSS were slightly better in the RFA group than the cryoablation group but without significant differences. Univariate and multivariate analysis showed that cryoablation treatment was not an unfavorable factor for OS and CSS before or after PSM (p > 0.05). In the multivariable competing risk model, non-cancer-specific death was taken as a competing factor and cryoablation was also not unfavorable for the survival of patients before and after PSM (p > 0.05).

Conclusion: Cryoablation is non-inferior to RFA therapy for single HCC patients without lymph node invasion or distant metastasis.
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http://dx.doi.org/10.1002/cam4.3923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178489PMC
June 2021

Case Report: Autoimmune Encephalitis Associated With Anti-glutamic Acid Decarboxylase Antibodies: A Pediatric Case Series.

Front Neurol 2021 12;12:641024. Epub 2021 Apr 12.

Department of Neurology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China.

Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extralimbic encephalitis. There have been some case reports and investigations regarding anti-GAD65 antibody-associated encephalitis in adult populations, but pediatric cases are rare. We retrospectively analyzed the clinical data of three anti-GAD65 antibody-positive patients to explore the diversity and clinical features of anti-GAD65 antibody-associated pediatric autoimmune encephalitis. The clinical data of a series of three patients positive for anti-GAD65 antibody were retrospectively analyzed. GAD65 antibodies were determined in serum and CSF using a cell-based assay. All three patients were female, and the onset ages were 4 years and 9 months, 6 years, and 16 years old. Their clinical phenotypes included autoimmune limbic encephalitis, extralimbic encephalitis, and encephalitis combining limbic and extralimbic encephalitis. The clinical symptoms included seizures, memory deficits, drowsiness, dysautonomia, and headache. All patients had abnormal carinal MRI and EEG. All patients received immunotherapy and had transiently good responsiveness, but one patient then experienced relapse. In follow-up, one patient with extralimbic encephalitis recovered completely, while two patients with limbic involvement had poor outcomes with refractory focal epilepsy. In addition to limbic encephalitis, extralimbic encephalitis is also an important phenotype in patients who are positive for anti-GAD65 antibodies. Early diagnosis and immunotherapy can improve the symptoms. However, patients with limbic encephalitis often have refractory epilepsy in the chronic phase and have a poor long-term outcome.
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http://dx.doi.org/10.3389/fneur.2021.641024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072212PMC
April 2021

Enhanced efficiency of printable mesoscopic perovskite solar cells using ionic liquid additives.

Chem Commun (Camb) 2021 Apr;57(33):4027-4030

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

The crystallization mechanism of the perovskite crystals inside the mesopores of printable mesoscopic perovskite solar cells is demonstrated by in situ grazing-incidence X-ray diffraction. Ionic liquids can universally tune the crystallization process of different perovksites in the mesopores regradless of the precursor solvents, resulting in enhanced efficiency.
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http://dx.doi.org/10.1039/d1cc00169hDOI Listing
April 2021

Clinical Features and Outcomes of Anti-N-Methyl-d-Aspartate Receptor Encephalitis in Infants and Toddlers.

Pediatr Neurol 2021 Jun 12;119:27-33. Epub 2021 Mar 12.

Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Department of Neurology, Beijing, China. Electronic address:

Objective: We describe the clinical features and outcomes of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis in infants and toddlers.

Methods: This was a single-center retrospective study. Infants and toddlers who met the diagnostic criteria for anti-NMDAR encephalitis were recruited for the study. Data on clinical features, treatment, and long-term outcomes were collected retrospectively.

Results: A total of 41 patients (age range: six to 34 months; median age: 23 months; female: 19) were enrolled in this study. Nineteen (46%) patients exhibited classical anti-NMDAR encephalitis, whereas 22 (54%) patients exhibited anti-NMDAR encephalitis after viral encephalitis. There was a high presentation of movement disorders (100%), developmental regression (90%), abnormal behaviors (90%). All patients were administered first-line therapy, with only 17% of them being administered second-line immunotherapy. Two patients succumbed to the disease, whereas none of them relapsed. At the long-term follow-up (more than one year), 20 of 35 (57%) exhibited satisfactory outcomes (modified Rankin Scale ≤2). Compared with patients with classical anti-NMDAR encephalitis (n = 18), patients after viral encephalitis (n = 17) were more likely to have worse clinical outcomes. They exhibited a higher modified Rankin Scale/Pediatric Cerebral Performance Category score and more frequent seizures. A predictor of poor outcome was presentation after viral encephalitis (odds ratio 35.7, 95% confidence interval 4.64 to 275.03, P = 0.001).

Conclusion: Anti-NMDAR encephalitis in infants and toddlers clinically presents with movement disorders, developmental regression, and abnormal behaviors. Interestingly, this group had a higher proportion of patients after viral encephalitis, which is regarded as the only risk factor for poor outcomes.
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http://dx.doi.org/10.1016/j.pediatrneurol.2021.02.009DOI Listing
June 2021

Case Report: Genetic and Clinical Features of Maternal Uniparental Isodisomy-Induced Thiamine-Responsive Megaloblastic Anemia Syndrome.

Front Pediatr 2021 19;9:630329. Epub 2021 Mar 19.

Caihong Hospital, Xianyang, China.

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive hereditary disease due to mutations in . Some cases show familial inheritance. A female patient (from a gravida 1, para 1 mother) of 3.5 years of age was admitted to the Pediatric Hematology Department of Xianyang Caihong Hospital in June 2019. The patient had severe anemia, acupoint-size bleeding spots, and a few ecchymoses all over her body, as well as astigmatism and hyperopia. Hearing was normal. The patient had diabetes. Bone marrow biopsy suggested a myelodysplastic syndrome. The patient had a c.515G>A (p.G172D) homozygous mutation of (NM_006996), indicating TRMA. Genetic testing revealed that the two alleles were inherited from her mother alone due to maternal uniparental isodisomy (UPD). The patient was treated with thiamine and a subcutaneous injection of insulin. The patient recovered well and was discharged. She continued thiamine and insulin at the same dose and was followed once a month. The last follow-up on September 15, 2020, showed no anemia or bleeding. She had a sound hearing and normal blood routine and fasting glucose levels. Hyperopia and astigmatism did not improve. The patient had TRMA induced by the c.515G>A (p.G172D) homozygous mutation of inherited through maternal UPD. The genetic diagnosis of TRMA is of significance for guiding clinical treatment. Early treatment with exogenous thiamine can improve some of the clinical features of TRMA.
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http://dx.doi.org/10.3389/fped.2021.630329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017196PMC
March 2021

Construction and Theoretical Calculation of an Ultra-High-Performance LiVPOF/C Cathode by B-Doped Pyrolytic Carbon from Poly(vinylidene Fluoride).

ACS Appl Mater Interfaces 2021 Apr 26;13(13):15190-15204. Epub 2021 Mar 26.

College of Materials Science and Engineering, Hunan University, Changsha 410082, China.

B-doped pyrolytic carbon from poly(vinylidene fluoride) (PVDF) was used to enhance the performance of a LiVPOF/C cathode, which is much cheaper than carbon nanotubes and graphene. The carbon layer in LVPF/C-B becomes more and more regular compared with the undoped sample. The electronic conductivity, diffusion coefficient, and rate and cycle performance of the B-doped cathode are greatly improved. The capacities of LVPF/C-B at 0.2C, 5C, and 15C are 148.1, 132.9, and 125.6 mAh·g, which may be the best reported magnitude. The crystallite structure of LiVPOF/C is well maintained after 300 charge and discharge cycles. The carbonization process of PVDF is greatly accelerated. These improvements are attributed to the changes in chemical and electronic structures. The generation of BCO and BCO results in many defective active sites, and BC promotes the growth of a six-membered carbon ring. According to the first-principles approach based on density functional theory, the state density around the Fermi level of the B-doped pyrolytic carbon is increased. The electronic structure of pyrolytic carbon is transformed from a P-type semiconductor to a metal-like structure through the generation of pyridinic-like and graphitic-like B. Therefore, the electronic conductivity of LiVPOF/C is increased.
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http://dx.doi.org/10.1021/acsami.0c22958DOI Listing
April 2021

Efficacy and safety of astragalus injection combined with Western medicine in the treatment of early diabetic nephropathy: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Mar;100(12):e25096

Department of TCM, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing.

Background: Diabetic nephropathy (DN) is the most common microvascular complication of diabetes. Its clinical manifestation is proteinuria, and it is a common cause of renal failure. At present, angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists are often used to treat early DN, and they have good curative effect. On this basis, the treatment of early DN with the combination of astragalus injection is becoming more and more widespread. Therefore, the purpose of this study is to prove the efficacy and safety of astragalus injection combined with Western medicine in the treatment of early DN, and to provide reference value for clinical practice in the future.

Methods: English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (China National Knowledge Infrastructur, Wanfang, VP Information Chinese Journal Service Platform, China Biology Medicine disc) will be searched by computer. From the establishment of the database to February 2021, a randomized controlled trial of astragalus injection combined with Western medicine in the treatment of early DN will be conducted. Two researchers independently evaluate the quality of the included study and extract the data. Included literature is analyzed by Meta with RevMan5.3 software.

Results: In this study, the efficacy and safety of astragalus injection combined with Western medicine in the treatment of early DN are evaluated by serological indexes such as Urinary albumin excretion rates (UAER), serum creatinine and blood urea nitrogen, as well as the adverse reactions of drugs.

Conclusion: This study will provide reliable evidence-based evidence for astragalus injection combined with Western medicine for the treatment of early DN.

Osf Registration Number: DOI 10.17605/OSF.IO/A9JGP.
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http://dx.doi.org/10.1097/MD.0000000000025096DOI Listing
March 2021

Does self-reported symptom questionnaire play a role in nonadherence to colonoscopy for risk-increased population in the Tianjin colorectal cancer screening programme?

BMC Gastroenterol 2021 Mar 9;21(1):117. Epub 2021 Mar 9.

Department of Epidemiology and Health Statistics, Tianjin Medical University, Tianjin, China.

Background: A colorectal cancer screening programme (CCSP) was implemented from 2012 to 2017 in Tianjin, China. Residents with a positive faecal immunochemical test (FIT) or positive self-reported symptom questionnaire (SRSQ) were recommended to undergo colonoscopy. The objective was to investigate the potential factors associated with nonadherence to colonoscopy among a risk-increased population.

Methods: Data were obtained from the CCSP database, and 199,522 residents with positive FIT or positive SRSQ during two screening rounds (2012-2017) were included in the analysis. Logistic regression analysis was performed to assess the association between nonadherence to colonoscopy and potential predictors.

Results: A total of 152,870 (76.6%) individuals did not undergo colonoscopy after positive FIT or positive SRSQ. Residents with positive SRSQ but without positive FIT were more likely not to undergo colonoscopy (negative FIT: OR, 2.35; 95% CI, 2.29-2.41, no FIT: OR, 1.27; 95% CI, 1.24-1.31). Patients without a cancer history were less likely to undergo colonoscopy even if they received risk-increased reports based on the SRSQ.

Conclusion: In the CCSP, seventy-seven percent of the risk-increased population did not undergo colonoscopy. FIT should be recommended since positive FIT results are related to improved adherence to colonoscopy. Residents with negative FIT but positive SRSQ should be informed of the potential cancer risk to ensure adherence to colonoscopy.
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http://dx.doi.org/10.1186/s12876-021-01701-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944887PMC
March 2021

Reasonable driving speed limits based on recognition time in a dynamic low-visibility environment related to fog-A driving simulator study.

Accid Anal Prev 2021 May 8;154:106060. Epub 2021 Mar 8.

School of Civil and Hydraulic Engineering, Hefei University of Technology, Hefei 230009, Anhui, PR China. Electronic address:

To determine a reasonable speed limit and ensure traffic safety in a dynamic low-visibility environment with fog, a driving simulator study was conducted. A total of 31 young participants were recruited, and each completed 5 driving simulator trials under varying visibility conditions and speed levels during the daytime. The combined coupling effect of the visibility and driving speed on drivers' recognition times was explored, and a quantitative model of the recognition time, visibility, and driving speed was established. A determination method and suggested value of a reasonable driving speed limit in dynamic low-visibility conditions were proposed based on the stopping sight distance model. The results show that there are significant differences in the recognition times of drivers under different visibility and speed conditions. The reasonable driving speed limit values in dynamic low-visibility conditions should be based on visibility changes. When the stopping sight distance is 75 m and the visibility is less than 35 m, the speed limit should be 20 km/h. When the visibility is between 35 m and 60 m, the speed limit should be 30 km/h. When the visibility is between 60 m and 140 m, the speed limit should be 50 km/h. When the visibility is greater than 140 m, the speed limit should be 60 km/h. These research results can provide a theoretical reference for the formulation of a VSL in a dynamic low-visibility environment related to fog and reduce crash risk in conditions of inadequate visibility in fog.
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http://dx.doi.org/10.1016/j.aap.2021.106060DOI Listing
May 2021

Clocking Dissociative Above-Threshold Double Ionization of H_{2} in a Multicycle Laser Pulse.

Phys Rev Lett 2021 Feb;126(6):063201

State Key Laboratory of Precision Spectroscopy, East China Normal University, Shanghai 200241, China.

The dissociative above-threshold double ionization (ATDI) of H_{2} in strong laser fields involves the sequential releasing of two electrons at specific instants with the stretching of the molecular bond. By mapping the releasing instants of two electrons to their emission directions in a multicycle polarization-skewed femtosecond laser pulse, we experimentally clock the dissociative ATDI of H_{2} via distinct photon-number-resolved pathways, which are distinguished in the kinetic energy release spectrum of two protons measured in coincidence. The timings of the experimentally resolved dissociative ATDI pathways are in good accordance with the classical predictions. Our results verify the multiphoton scenario of the dissociative ATDI of H_{2} in both time and energy fashion, strengthening the understanding of the strong-field phenomenon and providing a robust tool with a subcycle time resolution to clock abundant ultrafast dynamics of molecules.
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http://dx.doi.org/10.1103/PhysRevLett.126.063201DOI Listing
February 2021

MicroRNA-365 induces apoptosis and inhibits invasion of human myeloma cells by targeting homeobox A9 (HOXA9).

Environ Toxicol Pharmacol 2021 Jul 20;85:103627. Epub 2021 Feb 20.

Department of Hematology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710068, China. Electronic address:

The aberrant micro-RNA (miR) expression has been reported to play a vital role in proliferation and tumorigenesis and of several human cancers. MicroRNA-365 (miR-365) has been shown to exhibit tumor-suppressive or oncogenic role in several human cancers. Nonetheless, little is known about its growth regulatory role in human multiple myeloma. The present study characterized the regulatory control exercised by miR-365 in multiple myeloma. The results showed significant (P < 0.05) upregulation of miR-365 in myeloma tissues and cell lines. Overexpression of miR-365 significantly (P < 0.05) suppressed the proliferation and inhibition of miR-365 promoted the proliferation of the human myeloma cells. The tumor-suppressive effects of miR-365 were found to be the result of apoptosis in the IM-9 myeloma cells. The miR-365 overexpression also suppressed the invasion of the IM-9 myeloma cells. The homeobox gene, HOXA9 was identified as the molecular regulatory target of miR-365 in human myeloma. The overexpression of miR-365 was shown to cause suppression of HOXA9. The silencing of HOXA9 could also suppress the growth of the IM-9 myeloma cells while as the overexpression of HOXA9 could abolish the tumor-suppressive effects of miR-365. The in vivo study revealed that miR-365 inhibits the growth of the xenografted tumors. Nonetheless, the inhibition of miR-365 promotes the growth of the xenografted tumors. To sum up, the current study suggests the tumor-suppressive effects of miR-365 in human myeloma and highlights the applicability of miR-365 as vital therapeutic target against this fatal malignancy.
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http://dx.doi.org/10.1016/j.etap.2021.103627DOI Listing
July 2021

Efficiency of non-invasive prenatal screening in pregnant women at advanced maternal age.

BMC Pregnancy Childbirth 2021 Jan 26;21(1):86. Epub 2021 Jan 26.

Women's Hospital, School of Medicine, Zhejiang University, Zhejiang, 310006, Hangzhou, China.

Background: Non-invasive prenatal screening (NIPS) is widely used as the alternative choice for pregnant women at high-risk of fetal aneuploidy. However, whether NIPS has a good detective efficiency for pregnant women at advanced maternal age (AMA) has not been fully studied especially in Chinese women.

Methods: Twenty-nine thousand three hundred forty-three pregnant women at AMA with singleton pregnancy who received NIPS and followed-up were recruited. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), receiver operating characteristic (ROC) curves and the Youden Index for detecting fetal chromosomal aneuploidies were analyzed. The relationship between maternal age and common fetal chromosomal aneuploidy was observed.

Results: The sensitivity, specificity, PPV, NPV of NIPS for detecting fetal trisomy 21 were 99.11, 99.96, 90.98, and 100%, respectively. These same parameters for detecting fetal trisomy 18 were 100, 99.94, 67.92, and 100%, respectively. Finally, these parameters for detecting trisomy 13 were 100, 99.96, 27.78, and 100%, respectively. The prevalence of fetal trisomy 21 increased exponentially with maternal age. The high-risk percentage incidence rate of fetal trisomy 21 was significantly higher in the pregnant women at 37 years old or above than that in pregnant women at 35 to 37 years old. (Youden index = 37).

Conclusion: It is indicated that NIPS is an effective prenatal screening method for pregnant women at AMA.
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http://dx.doi.org/10.1186/s12884-021-03570-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836475PMC
January 2021

Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002).

J Hematol Oncol 2021 01 12;14(1):12. Epub 2021 Jan 12.

Department of Hematology, The First Hospital of Lanzhou University, Lanzhou, China.

Background: Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients.

Methods: We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria.

Results: Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30-22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2-51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related.

Conclusions: In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population.

Trial Registration: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.
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http://dx.doi.org/10.1186/s13045-021-01033-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802130PMC
January 2021

DNA methylation and lipid metabolism: an EWAS of 226 metabolic measures.

Clin Epigenetics 2021 01 7;13(1). Epub 2021 Jan 7.

Center for Life Course Health Research, University of Oulu, Oulu University Hospital, Oulu, Finland.

Background: The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances.

Results: We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations.

Conclusion: Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms.
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http://dx.doi.org/10.1186/s13148-020-00957-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789600PMC
January 2021
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