Publications by authors named "Yanqiu Liu"

89 Publications

Development of a novel ELISA to detect total factor D in the presence of high levels of PEGylated anti-factor D Fab.

Bioanalysis 2021 Sep 2. Epub 2021 Sep 2.

Bioanalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

PEGylated anti-Factor D Fab (PEG-aFD) was developed as a potential therapeutic for geographic atrophy, targeting factor D, the rate-limiting enzyme in the alternative complement pathway. An assay was needed to measure total factor D as a pharmacodynamic biomarker in human aqueous humor in the presence of high PEG-aFD concentrations. Commercial kit met sensitivity requirement, but not drug tolerance requirement. In-house ELISA met both drug tolerance and sensitivity requirements. Addition of 100 ng/ml PEG-aFD to the sample diluent enabled accurate measurement of human factor D in the presence of 2.5 mg/ml of PEG-aFD in the in-house ELISA. Accurate measurement of total factor D in human aqueous humor containing high concentrations of PEG-aFD was achieved by adding PEG-aFD to sample diluent.
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http://dx.doi.org/10.4155/bio-2021-0094DOI Listing
September 2021

P-Selectin Glycoprotein Ligand 1: A Potential HIV-1 Therapeutic Target.

Front Immunol 2021 9;12:710121. Epub 2021 Aug 9.

Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China.

Antiretroviral therapy (ART), which is a life-long therapeutic option, remains the only currently effective clinical method to treat HIV-1 infection. However, ART may be toxic to vital organs including the liver, brain, heart, and kidneys, and may result in systemic complications. In this context, to consider HIV-1 restriction factors from the innate immune system to explore novel HIV therapeutics is likely to be a promising investigative strategy. In light of this, P-selectin glycoprotein ligand 1 (PSGL-1) has recently become the object of close scrutiny as a recognized cell adhesion molecule, and has become a major focus of academic study, as researchers believe that PSGL-1 may represent a novel area of interest in the research inquiry into the field of immune checkpoint inhibition. In this article, we review PSGL-1's structure and functions during infection and/or inflammation. We also outline a comprehensive review of its role and potential therapeutic utility during HIV-1 infection as published in contemporary academic literature.
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http://dx.doi.org/10.3389/fimmu.2021.710121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380821PMC
August 2021

A More Universal Approach to Comprehensive Analysis of Thalassemia Alleles (CATSA).

J Mol Diagn 2021 Sep 20;23(9):1195-1204. Epub 2021 Jul 20.

Department of Molecular Genetics, Hunan Jiahui Genetics Hospital, Changsha, China; Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China. Electronic address:

The aim of the study was to assess the clinical utility of a third-generation sequencing (TGS) approach termed comprehensive analysis of thalassemia alleles (CATSA) for identifying both α and β thalassemia genetic carrier status. Prospective blood samples (n = 1759) with abnormal hemoglobin parameters were screened for pathogenic thalassemia variants by CATSA on the PacBio TGS platform. In 1159 individuals, a total of 1317 pathogenic thalassemia variants were identified and confirmed by independent PCR-based tests. Of the total thalassemia variants detected, the α-variant -- (35.4%) and β-variant c.126_129delCTTT (15%) were the most common. CATSA was also able to detect three types of rare HBA structural variants as well as five rare HBA2, three HBA1, and 10 HBB single-nucleotide variations/insertions and deletions. Compared with standard thalassemia variant PCR panel testing, CATSA identified all panel variants present, with no false-negative results. Carrier assignment was improved through identification of rare variants missed by the panel test. On the basis of allelic coverage, reliability, and accuracy, TGS with long-range PCR presents a comprehensive approach with the potential to provide a universal solution for thalassemia genetic carrier screening. It is proposed that CATSA has immediate clinical utility as an effective carrier screening approach for at-risk couples.
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http://dx.doi.org/10.1016/j.jmoldx.2021.06.008DOI Listing
September 2021

Drug discovery for X-linked adrenoleukodystrophy: An unbiased screen for compounds that lower very long-chain fatty acids.

J Cell Biochem 2021 May 30. Epub 2021 May 30.

Department of Neurogenetics, Hugo W. Moser Research Institute at Kennedy Krieger, Kennedy Krieger Institute, Baltimore, Maryland, USA.

X-linked adrenoleukodystrophy (XALD) is a genetic neurologic disorder with multiple phenotypic presentations and limited therapeutic options. The childhood cerebral phenotype (CCALD), a fatal demyelinating disorder affecting about 35% of patients, and the adult-onset adrenomyeloneuropathy (AMN), a peripheral neuropathy affecting 40%-45% of patients, are both caused by mutations in the ABCD1 gene. Both phenotypes are characterized biochemically by elevated tissue and plasma levels of saturated very long-chain fatty acids (VLCFA), and an increase in plasma cerotic acid (C26:0), along with the clinical presentation, is diagnostic. Administration of oils containing monounsaturated fatty acids, for example, Lorenzo's oil, lowers patient VLCFA levels and reduced the frequency of development of CCALD in presymptomatic boys. However, this therapy is not currently available. Hematopoietic stem cell transplant and gene therapy remain viable therapies for boys with early progressive cerebral disease. We asked whether any existing approved drugs can lower VLCFA and thus open new therapeutic possibilities for XALD. Using SV40-transformed and telomerase-immortalized skin fibroblasts from an XALD patient, we conducted an unbiased screen of a library of approved drugs and natural products for their ability to decrease VLCFA, using measurement of C26:0 in lysophosphatidyl choline (C26-LPC) by tandem mass spectrometry as the readout. While several candidate drugs were initially identified, further testing in primary fibroblast cell lines from multiple CCALD and AMN patients narrowed the list to one drug, the anti-hypertensive drug irbesartan. In addition to lowering C26-LPC, levels of C26:0 and C28:0 in total fibroblast lipids were reduced. The effect of irbesartan was dose dependent between 2 and 10 μM. When male XALD mice received orally administered irbesartan at a dose of 10 mg/kg/day, there was no reduction in plasma C26-LPC. However, irbesartan failed to lower mouse fibroblast C26-LPC consistently. The results of these studies indicate a potential therapeutic benefit of irbesartan in XALD that should be validated by further study.
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http://dx.doi.org/10.1002/jcb.30014DOI Listing
May 2021

Effects of Hypothermic Hypoxia/Reoxygenation Fibroblast Culture Medium Containing Sevoflurane on Cardiomyocytes.

Ther Hypothermia Temp Manag 2021 May 21. Epub 2021 May 21.

Department of Anesthesiology, Guiyang Fourth People's Hospital.

We established a model of hypothermic hypoxia/reoxygenation injury of fibroblasts, simulated the process of ischemia/reperfusion injury during cardiopulmonary bypass, and studied the effects of cardiac fibroblasts on cardiomyocyte activity, connexin 43 (Cx43), and calmodulin kinase II (CaMKII) expression. Furthermore, the effects of sevoflurane-treated fibroblast culture medium on cardiac activity, Cx43 protein, and CaMKII expression were observed. The results showed that the fibroblast culture medium damaged by hypothermic hypoxia/reoxygenation could reduce the beating frequency of cardiomyocytes, increase the mortality of cardiomyocytes, decrease the relative expression of Cx43, and increase the relative expression of CaMKII. However, sevoflurane containing hypothermic hypoxia/reoxygenation injury fibroblast culture medium can increase the beating frequency of cardiomyocytes, reduce the mortality of cardiomyocytes, increase the relative expression of Cx43 protein, and decrease the relative expression of CaMKII. The results suggest that the antiarrhythmic effects of sevoflurane on the expression of Cx43 and CaMKII are related to fibroblasts.
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http://dx.doi.org/10.1089/ther.2020.0049DOI Listing
May 2021

Protective roles of the TIR/BB-loop mimetic AS-1 in alkali-induced corneal neovascularization by inhibiting ERK phosphorylation.

Exp Eye Res 2021 06 9;207:108568. Epub 2021 Apr 9.

Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, People's Republic of China. Electronic address:

Hydrocinnamoyl-L-valylpyrrolidine (AS-1), a synthetic low-molecule mimetic of myeloid differentiation primary response gene 88 (MyD88), inhibits inflammation by disrupting the interaction between the interleukin-1 receptor (IL-1R) and MyD88. Here, we describe the effects of AS-1 on injury-induced increases in inflammation and neovascularization in mouse corneas. Mice were administered a subconjunctival injection of 8 μL AS-1 diluent before or after corneal alkali burn, followed by evaluation of corneal resurfacing and corneal neovascularization (CNV) by slit-lamp biomicroscopy and clinical assessment. Corneal inflammation was assessed by whole-mount CD45 immunofluorescence staining, and corneal hemangiogenesis and lymphangiogenesis following injury were evaluated by immunostaining for the vascular markers isolectin B4 (IB4) and the lymphatic vascularized marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), respectively. Additionally, corneal tissues were collected to determine the expression of 35 cytokines, and we detected activation of IL-1RI, MyD88, and mitogen-activated protein kinase (MAPK). The results showed that alkali conditions increased the number of CD45 cells and expression of vascular endothelial growth factor (VEGF)-A, VEGF-C, and LYVE1 in corneas, with these levels decreased in the AS-1-treated group. Moreover, AS-1 effectively prevented alkali-induced cytokine production, blocked interactions between IL-1RI and MyD88, and inhibited MAPK activation post-alkali burn. These results indicated that AS-1 prevented alkali-induced corneal hemangiogenesis and lymphangiogenesis by blocking IL-1RI-MyD88 interaction, as well as extracellular signal-regulated kinase phosphorylation, and could be efficacious for the prevention and treatment of corneal alkali burn.
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http://dx.doi.org/10.1016/j.exer.2021.108568DOI Listing
June 2021

[Prenatal diagnosis of a fetus with 8q13.3 microdeletion through chromosomal microarray analysis].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Mar;38(3):268-270

Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China.

Objective: To assess the value of chromosomal microarray analysis (CMA) for the prenatal diagnosis of a fetus with structural anomaly detected by ultrasonography.

Methods: The fetus and its parents were subjected to chromosomal karyotyping and CMA analysis.

Results: The fetus was found to carry a 46,XN,t(8;11)(q21.2;q13) translocation which was inherited from its mother. CMA has found no copy number variations (CNVs) in both parents but a de novo 2.00 Mb microdeletion in the fetus at 8q13.3.

Conclusion: CMA is capable of detecting microdeletions and microduplications in fetuses with translocations detected by karyotyping analysis.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200217-00086DOI Listing
March 2021

Numerical study of building pressure cycling to generate sub-foundation aerobic barrier for mitigating petroleum vapor intrusion.

Sci Total Environ 2021 Jul 15;779:146460. Epub 2021 Mar 15.

Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

In this study, the role of building pressure cycling (BPC) method in generating a subslab aerobic barrier at petroleum contaminated sites was examined numerically. The numerical model was first validated with field observations and then used to simulate BPC applications in petroleum vapor intrusion scenarios. The results indicated that, after a long-term BPC operation (60 days), a subslab aerobic barrier could be generated with an adequate air injection rate (10 L/min in this study). The effects on hydrocarbon soil gas concentration profiles are expected to last for weeks even after the BPC system is turned off. Moreover, our investigations showed that the performances of the BPC application are virtually independent of hydrocarbon's reaction rate constant. The simulated sub-foundation aerobic conditions expected during BPC were comparable to those observed in a field study where a subsurface pipe system at the same air injection rate was used to create a subslab aerobic barrier. Thus, BPC application can represent an interesting alternative approach to the subsurface delivery systems as it is expected to achieve similar performance but with lower installation costs.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146460DOI Listing
July 2021

Prostaglandin E promotes pathological retinal neovascularisation via EPR-EGFR-Gab1-AKT signaling pathway.

Exp Eye Res 2021 04 17;205:108507. Epub 2021 Feb 17.

Department of Ophthalmology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China; Center of Clinical Research, The Affiliated Wuxi People's Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214023, PR China. Electronic address:

Proliferative retinopathies, such as proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP) are major causes of visual impairment and blindness in industrialized countries. Prostaglandin E (PGE) is implicated in cellular proliferation and migration via E-prostanoid receptor (EPR). The aim of this study was to investigate the role of PGE/EPR signaling in the promotion of retinal neovascularisation. In a streptozotocin (STZ)-induced diabetic model and an oxygen-induced retinopathy (OIR) model, rats received an intravitreal injection of PGE, cay10598 (an EPR agonist) or AH23848 (an EPR antagonist). Optical coherence tomography, retinal histology and biochemical markers were assessed. Treatment with PGE or cay10598 accelerated pathological retinal angiogenesis in STZ and OIR-induced rat retina, which was ameliorated in rats pretreated with AH23848. Serum VEGF-A was upregulated in the PGE-treated diabetic rats vs non-treated diabetic rats and significantly downregulated in AH23848-treated diabetic rats. PGE or cay10598 treatment also significantly accelerated endothelial tip-cell formation in new-born rat retina. In addition, AH23848 treatment attenuated PGE-or cay10598-induced proliferation and migration by repressing the EGF receptor (EGFR)/Growth factor receptor bound protein 2-associated binder protein 1 (Gab1)/Akt/NF-κB/VEGF-A signaling network in human retinal microvascular endothelial cells (hRMECs). PGE/EPR signaling network is thus a potential therapeutic target for pathological intraocular angiogenesis.
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http://dx.doi.org/10.1016/j.exer.2021.108507DOI Listing
April 2021

A novel diphtheria toxin-based bivalent human EGF fusion toxin for treatment of head and neck squamous cell carcinoma.

Mol Oncol 2021 04 20;15(4):1054-1068. Epub 2021 Feb 20.

Division of Plastic and Reconstructive Surgery, Department of Surgery, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Epidermal growth factor receptor (EGFR) is often overexpressed in head and neck squamous cell carcinoma (HNSCC) and represents a top candidate for targeted HNSCC therapy. However, the clinical effectiveness of current Food and Drug Administration (FDA)-approved drugs targeting EGFR is moderate, and the overall survival rate for HNSCC patients remains low. Therefore, more effective treatments are urgently needed. In this study, we generated a novel diphtheria toxin-based bivalent human epidermal growth factor fusion toxin (bi-EGF-IT) to treat EGFR-expressing HNSCC. Bi-EGF-IT was tested for in vitro binding affinity, cytotoxicity, and specificity using 14 human EGFR-expressing HNSCC cell lines and three human EGFR-negative cancer cell lines. Bi-EGF-IT had increased binding affinity for EGFR-expressing HNSCC compared with the monovalent version (mono-EGF-IT), and both versions specifically depleted EGFR-positive HNSCC, but not EGFR-negative cell lines, in vitro. Bi-EGF-IT exhibited a comparable potency to that of the FDA-approved EGFR inhibitor, erlotinib, for inhibiting HNSCC tumor growth in vivo using both subcutaneous and orthotopic HNSCC xenograft mouse models. When tested in an experimental metastasis model, survival was significantly longer in the bi-EGF-IT treatment group than the erlotinib treatment group, with a significantly reduced number of metastases compared with mono-EGF-IT. In addition, in vivo off-target toxicities were significantly reduced in the bi-EGF-IT treatment group compared with the mono-EGF-IT group. These results demonstrate that bi-EGF-IT is more effective and markedly less toxic at inhibiting primary HNSCC tumor growth and metastasis than mono-EGF-IT and erlotinib. Thus, the novel bi-EGF-IT is a promising drug candidate for further development.
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http://dx.doi.org/10.1002/1878-0261.12919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024719PMC
April 2021

[Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Dec;37(12):1360-1363

Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330006, China.

Objective: To explore the genetic basis for a Chinese pedigree affected with N-acetylglutamate synthase deficiency.

Methods: Trio whole exome sequencing (WES) was carried out for the pedigree. Pathogenicity of the identified variant was predicted based on the latest recommendation of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided for subsequent pregnancy through Sanger sequencing.

Results: Trio WES showed that the proband has carried compound heterozygous c.68delG and c.796G>C variants of NAGS gene, for which the mother and father were respectively heterozygous carriers. Neither variant was reported previously. Based on the ACMG guidelines, the c.68delG variant was classified as "likely pathogenic" (PVS1+PM2), while the c.796G>C variant was classified as with "uncertain significance" (PM2+BP4). Sanger sequencing validated the above findings, and only detected the heterozygous c.796G>C variant in the amniotic fluid sample. The fetus was followed up till 6 month after birth with no obvious abnormality.

Conclusion: The compound heterozygous c.68delG and c.796G>C variants of the NAGS gene probably underlay the disorder in this pedigree, and the resulth asenabled genetic counseling and prenatal diagnosis for this pedigree.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200203-00055DOI Listing
December 2020

Development of an anti-drug antibody assay to detect anti-drug antibodies to protein and PEG in a PEGylated molecule.

Bioanalysis 2020 Dec 12;12(23):1671-1679. Epub 2020 Nov 12.

Department of Bioanalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

PEGylation technology is one of long-acting delivery (LAD) platforms used to increase half-life of protein therapeutics. However, PEGylation of anti-Factor D Fab (PEG-aFD) poses challenges for detecting anti-drug antibody (ADA) to both Fab and polyethylene glycol (PEG) portions. Although the bridging ELISA using traditional assay diluent containing Tween 20 is good for detecting ADA to Fab, it failed to detect ADA to PEG. Instead of only reducing Tween 20 in assay diluent, using a proprietary commercial buffer PEG50-1 as assay diluent successfully enabled the detection of ADA to both Fab and PEG with fit-for-purpose sensitivity and drug tolerance. Identification of appropriate assay diluent is critical for detection of ADA to both Fab and PEG in a PEGylated molecule.
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http://dx.doi.org/10.4155/bio-2020-0191DOI Listing
December 2020

Up-regulated microRNA-218-5p ameliorates the damage of dopaminergic neurons in rats with Parkinson's disease via suppression of LASP1.

Brain Res Bull 2021 01 1;166:92-101. Epub 2020 Nov 1.

Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450014, China. Electronic address:

Objective: Parkinson's disease (PD) is a frequent degenerative disease of the nervous system with undefined pathogenesis. This study explored the protective effect of microRNA (miR)-218-5p on dopaminergic neuron injury in substantia nigra (SN) of rats with PD through the regulation of LIM and SH3 domain protein 1 (LASP1).

Methods: The PD rat model was established by fixed point injection of 6-hydroxydopamine into the rats. The PD rats were injected with miR-218-5p overexpressed recombinant adeno-associated virus (rAAV) or LASP1 silenced rAAV to explore their roles in dopaminergic neurons in SN of rats with PD. The changes in pathological structure of SN were observed and the expression of tyrosine hydroxylase (TH) and deacetylvindoline acetyltransferase (DAT), the dopaminergic neuron apoptosis and oxidative stress factor in the SN were detected. The expression of miR-218-5p, LASP1, Bcl-2 and Bax in SN was detected. The targeting relationship between miR-218-5p and LASP1 was confirmed.

Results: Declined miR-218-5p and overexpressed LASP1 existed in the brain SN of PD rats. Up-regulated miR-218-5p or inhibited LASP1 improved the pathological damage of dopaminergic neurons and increased the number of TH and DAT positive cells in brain SN of PD rats. Furthermore, elevated miR-218-5p or depressed LASP1 inhibited the apoptosis, and oxidative stress of dopaminergic neurons in brain SN of PD rats. In addition, increased miR-218-5p repressed the expression of LASP1 in the brain SN of PD rats. LASP1 was proven to be a direct target of miR-218-5p.

Conclusion: The study highlights that up-regulated miR-218-5p could improve the damage of dopaminergic neurons in PD rats, which was related to the inhibition of LASP1.
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http://dx.doi.org/10.1016/j.brainresbull.2020.10.019DOI Listing
January 2021

Serum Prealbumin and Echocardiography Parameters Predict Mortality in Peritoneal Dialysis Patients.

Kidney Blood Press Res 2020 30;45(5):671-685. Epub 2020 Sep 30.

Department of Medical Ultrasound, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China,

Aim: Protein-energy malnutrition and cardiovascular (CV) disease predisposes patients with end-stage renal disease (ESRD) on dialysis to a high risk of early death, but the prognostic value of prealbumin (PAB) and echocardiographic indices in ESRD patients treated with maintenance peritoneal dialysis (PD) remains unclear.

Methods: A total of 211 PD patients (mean age 49.2 ± 15.4 years, 51.7% male) were prospectively studied. PAB and echocardiography parameters were recorded at baseline. Follow-up (mean ± SD: 33.7 ± 17.3 months) was conducted based on hospital records, clinic visits, and telephone reviews, to record death events and their causes.

Results: In the Cox proportional hazards model, PAB and the echocardiographic parameters listed below were found to be optimal predictors of all-cause mortality: PAB (p = 0.003), aortic root diameter (ARD) (p = 0.004), interventricular septum end-diastolic thickness (IVSd) (p = 0.046), and left ventricular end-diastolic diameter index (LVEDDI) (p = 0.029). Of the above-mentioned factors, PAB (p = 0.018), ARD (p = 0.031), and IVSd (p = 0.037) were independent predictors of CV mortality in PD patients. Of note, malnutrition, degradation of the aorta, and myocardial hypertrophy are also known death risk factors in the general population. The all-cause mortality and CV death rate significantly increased as the number of risk factors increased, reaching values as high as 40 and 22% in patients who had all of the risk factors, i.e., abnormal PAB, ARD, and IVSd (p < 0.001 and p = 0.011).

Conclusion: In PD patients, low serum PAB and abnormal echocardiographic parameters together were significantly associated with all-cause mortality and CV death, independently of other risk factors. These risk factors for death in PD are similar to those in the general population. Noticeably, the combination of echocardiographic parameters and PAB could provide additional predictive value for mortality in PD patients. In light of these findings, more studies in an optimal model containing PAB and echocardiographic parameters for the prediction of outcomes in ESRD are required.
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http://dx.doi.org/10.1159/000507331DOI Listing
May 2021

The pH-triggered polyglutamate brush co-delivery of MDR1 and survivin-targeting siRNAs efficiently overcomes multi-drug resistance of NSCLC.

Drug Dev Ind Pharm 2020 Nov 21;46(11):1862-1872. Epub 2020 Sep 21.

Department of Pharmacy, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, PR China.

Multi-drug resistance (MDR) is one of the major challenges in the successful chemotherapy of non-small cell lung cancer (NSCLC). Although RNA interference (RNAi) has been widely used to silence resistance-related genes, the effect remains unsatisfactory. In this study, we attempted to overcome MDR of NSCLC by simultaneously interfering with two RNAs that have different functions. A new pH-triggered polyglutamate brush polymer dimethylmaleic anhydride-poly(ethyleneglycol) monomethyl ether-b-polyglutamate-g-spermine (DMA-mPEG-b-PG-g-spermine, DPPGS) was designed and synthesized. The DPPGS/small interfering RNA (siRNA) complex nanoparticles (DPPGSN) were prepared. The results demonstrated that DPPGSN could be transformed from a negatively charged form into a positively charged form in the slightly acidic tumor extracellular environment. The siRNA targeting MDR1 mRNA (siMDR1) and siRNA targeting survivin mRNA (siSurvivin) could be efficiently co-delivered by DPPGS to simultaneously interfere with two genes ( 0.01). Furthermore, DPPGS co-delivery of siMDR1 and siSurvivin lowered the IC value of cisplatin (DDP) in A549/DDP ( 0.01) cells and increased the apoptosis rate of the cells ( 0.01). Therefore, co-delivery of siMDR1 and siSurvivin using DPPGS would be a promising approach for overcoming MDR of NSCLC.
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http://dx.doi.org/10.1080/03639045.2020.1822860DOI Listing
November 2020

Network construction of aberrantly expressed miRNAs and their target mRNAs in ventricular myocardium with ischemia-reperfusion arrhythmias.

J Cardiothorac Surg 2020 Aug 12;15(1):216. Epub 2020 Aug 12.

Department of Anesthesiology, Guizhou Medical University, Guiyang, Guizhou, 550000, China.

Background: Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, however, the effect of miRNAs on the progression of hypothermic ischemic-reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored.

Methods: Sprague-Dawley (SD) rats were randomly divided into two groups (n = 8): a normal control group (Group C) and a hypothermic ischemia-reperfusion group (Group IR), which were used to establish a Langendorff isolated cardiac perfusion model. According to the arrhythmia scoring system, rats in group IR were divided into a high-risk group (IR-H) and a low-risk group (IR-L). miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia-reperfusion and those of ventricular myocardium with hypothermic ischemia-RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia-RA were screened and verified. The target genes of these aberrantly expressed miRNAs were predicted using RNAhybrid and MiRanda software. Based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we determined the mRNA targets associated with these miRNAs and studied the miRNA-mRNA interaction during the cardiovascular disease progression. The aberrantly expressed miRNAs related to hypothermic ischemia-RA were validated by Real-time Quantitative polymerase chain reaction (RT-qPCR).

Results: Eight significantly aberrantly expressed miRNAs (rno-miR-122-5p, rno-miR-429, novel_miR-1, novel_miR-16, novel_miR-17, novel_miR-19, novel_miR-30, and novel_miR-43) were identified, among which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. The miRNA-mRNA interaction network graph showed that GJA1 gene was considered as the target of novel_miR-17.

Conclusions: Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia-RA. Specific miRNAs, such as novel_miR-17 and rno-miR-429 are probably new potential targets for further functional studies of hypothermic ischemia-RA.
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http://dx.doi.org/10.1186/s13019-020-01262-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425585PMC
August 2020

Immunoaffinity LC-MS/MS is more suitable than ELISA to quantify a PEGylated molecule in cynomolgus monkey serum.

Bioanalysis 2020 Aug 31;12(15):1061-1069. Epub 2020 Jul 31.

Department of Bioanalytical Sciences, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Polyethylene glycolylation (PEGylation) technology is a long-acting delivery platform used to increase the half-life of protein therapeutics. Quantitation of PEGylated anti-Factor D Fab (PEG-aFD) poses bioanalytical challenges. An ELISA was developed to determine total Fab concentration in cynomolgus monkey serum following intravitreal administration of PEG-aFD. However, assay characterization showed a low recovery of about 25% for free unconjugated Fab whereas recovery for PEG-conjugated Fab was within 80-120%. To overcome this challenge, an immunoaffinity liquid chromatography tandem mass spectrometry (IA LC-MS/MS) assay was developed, achieving recovery within 80-120% for both free and conjugated Fab. Immunoaffinity LC-MS/MS is more suitable than ELISA to accurately quantify the total protein concentration of PEG-aFD in cynomolgus monkey serum.
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http://dx.doi.org/10.4155/bio-2020-0097DOI Listing
August 2020

Identifying key genes and drug screening for preeclampsia based on gene expression profiles.

Oncol Lett 2020 Aug 9;20(2):1585-1596. Epub 2020 Jun 9.

Reproductive Sciences Institute, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.

Preeclampsia (PE) is characterized by gestational hypertension and proteinuria, and is a leading cause of maternal death and perinatal morbidity globally. Although the exact cause of PE remains unclear, several studies have suggested a role for abnormal expression of multiple genes. The aim of the present study was to identify key genes and related pathways, and to screen for drugs that regulate these genes for potential PE therapy. The GSE60438 dataset was acquired from the Gene Expression Omnibus database to analyze differentially expressed genes (DEGs). By constructing a protein-protein interaction network and performing reverse transcription-quantitative PCR verification, proteasome 26S subunit, non-ATPase 14, prostaglandin E synthase 3 and ubiquinol-cytochrome reductase core protein 2 were identified as key genes in PE. In addition, PE was found to be associated with 'circadian rhythm', 'fatty acid metabolism', 'DNA damage response detection of DNA damage', 'regulation of DNA repair' and 'endothelial cell development'. Through connectivity map analysis of DEGs, furosemide and droperidol were suggested to be therapeutic drugs that may target the hub genes for PE treatment. Results analysis of GSEA were included in the discussion section of this article. In conclusion, the current study identified novel key genes associated with the onset of PE and potential drugs for PE treatment.
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http://dx.doi.org/10.3892/ol.2020.11721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377100PMC
August 2020

Prolonged duration of repolarization and decreased conduction velocity in the atrial myocardium after hypothermic ischemia-reperfusion may be related to expressions of inward rectifier potassium channel 2.1 protein and connexin 40.

Perfusion 2021 03 10;36(2):146-153. Epub 2020 Jul 10.

School of Anesthesiology, Guizhou Medical University, Guiyang, P.R. China.

Objectives: The study aimed to determine the role of inward rectifier potassium channel 2.1 protein and connexin 40 expressions in regulating the duration of repolarization and conduction velocity of right atrial myocardium in rats following hypothermic ischemia-reperfusion.

Methods: The Langendorff isolated rat cardiac perfusion models were divided into control (C) and hypothermic ischemia-reperfusion groups, with 8 models in group C and 16 models in group ischemia-reperfusion. Depending on the incidence of atrial arrhythmia after reperfusion, the models in group ischemia-reperfusion were further divided into reperfusion non-atrial arrhythmia or reperfusion atrial arrhythmia subgroup. Right atrial monophasic action potential duration at 50% and 90% of repolarization after 30 minutes of continuous perfusion in group C and group ischemia-reperfusion (T), 105 minutes of continuous perfusion in group C or after 15 minutes of reperfusion in group ischemia-reperfusion (T) and 120 minutes of continuous perfusion in group C or 30 minutes of reperfusion in group ischemia-reperfusion (T) were recorded. Right atrial conduction velocity and effective refractory period were recorded at T. Then, the expressions of inward rectifier potassium channel 2.1 protein and connexin 40 in the right atrial myocardium were detected.

Results: Monophasic action potential duration at 50% and 90% were higher at T and T than those at T in subgroup reperfusion atrial arrhythmia (p < 0.05); monophasic action potential duration at 50% in subgroup reperfusion atrial arrhythmia were larger than group C and subgroup reperfusion non-atrial arrhythmia at T and T (p < 0.05); monophasic action potential duration at 90% in subgroup reperfusion atrial arrhythmia were larger than group C and subgroup reperfusion non-atrial arrhythmia at T and T (p < 0.05); effective refractory period in subgroup reperfusion atrial arrhythmia was greater than that in group C and subgroup reperfusion non-atrial arrhythmia, and the conduction velocity and the expressions of inward rectifier potassium channel 2.1 protein and connexin 40 were significantly lower than group C and subgroup reperfusion non-atrial arrhythmia (p < 0.05).

Conclusions: The prolonged duration of repolarization and a decrease in conduction velocity of the atrial myocardium occur in rats after hypothermic ischemia-reperfusion. These observed effects may be related to the downregulated expressions of connexin 40 and inward rectifier potassium channel 2.1.
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http://dx.doi.org/10.1177/0267659120934612DOI Listing
March 2021

[Analysis of a pedigree affected with propionic acidemia by trio whole exome sequencing].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Jul;37(7):751-754

Prenatal Diagnosis Center of Jiangxi Women and Children's Health Care Hospital, Nanchang, Jiangxi 330006, China.

Objective: To explore the clinical characteristics and genetic basis for a pedigree affected with propionic acidemia.

Methods: Trio whole exome sequencing (WES) was used to screen potential variants in the proband and his parents. Sanger sequencing was carried out for the elder sister of the proband, and prenatal diagnosis was carried out at 18th gestational week upon the next pregnancy of his mother.

Results: Two novel heterozygous variants, PCCA c.1845+1G>A and c.446delA, were detected by WES, for which his father and mother were respectively heterozygous carriers. His elder sister also inherited the PCCA c.1845+1G>A variant from her father, while the fetus was heterozygous for the PCCA c.1845+1G>A variant. Above results were confirmed by Sanger sequencing.

Conclusion: Identification of the PCCA c.1845+1G>A and c.446delA variants by WES has facilitated genetic counseling and prenatal diagnosis for this family.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.07.012DOI Listing
July 2020

Numerical study of the building pressure cycling method for evaluating vapor intrusion from groundwater contamination.

Environ Sci Pollut Res Int 2020 Oct 27;27(28):35416-35427. Epub 2020 Jun 27.

Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing, 210008, China.

Vapor intrusion (VI) risk assessments determine the cleanup level of groundwater in the absence of ingestion. In recent VI investigations, the building pressure cycling (BPC) method has been applied to help minimize ambiguity caused by temporal variability of indoor air samples that are important to risk assessments, and, consequently, determine groundwater cleanup level accurately. In this study, we use a three-dimensional numerical model to examine the dynamic migration of VOCs from groundwater after the application of BPC. First, we validated the numerical model with field measurements. Then, the verified model is used to investigate the effects of site-specific features in determining the performance of BPC operation. At last, we summarize past field applications of BPC to examine the simulated results. Our study indicates that the BPC-induced indoor depressurization can increase the building loading rate in the first 2-3 h, which would then drop to 2-3 times of that with natural conditions in most cases of groundwater contamination. In some cases involving a strong source, e.g., a vapor source above the capillary fringe or a groundwater source with sandy soil above the groundwater level, the normalized building loading rates can be maintained as high as 4-9 without decrease after the first 2-3 h. Significantly higher increase in building loading rate may indicate a potential presence of a preferential pathway between the groundwater contamination and concerned building.
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http://dx.doi.org/10.1007/s11356-020-09746-5DOI Listing
October 2020

Association between retinal arterial narrowing and left ventricular diastolic dysfunction in masked hypertensives.

J Clin Hypertens (Greenwich) 2020 06 19;22(6):1050-1058. Epub 2020 May 19.

Department of Cardiac ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Morphological change in retinal vessel diameters has been reported to be associated with negative cardiovascular outcomes, but its association with left ventricular diastolic dysfunction (LVDD) is not clear. This study aimed to examine the association between echocardiographic markers of LVDD and retinal vascular diameters, in untreated masked hypertension (MH). In this observational study, 105 MH patients without other cardiovascular risks were included (mean age 48.4 ± 5.7, female 72.4%). All individuals underwent extensive clinical and laboratory investigations, including echocardiography, ambulatory blood pressure monitoring, and retinal vascular diameters measured by optical coherence tomography. In the group, LVDD was diagnosed in 36 participants evaluated by left ventricular volume index, E/A and E/e' ratio. Compared to non-LVDD, LVDD subjects displayed narrower retinal arteriolar diameter (139.1 ± 33.8 vs 165.1 ± 29.1; adjusted P = .007) and wider retinal venular diameter (237.9 ± 42.2 vs 214.9 ± 44.8; adjusted P = .045). Significant and independent associations were demonstrated for retinal arteriolar narrowing and E/A ratio (adjusted β = 0.744, P = .031) and for retinal arteriolar diameter and E/e' ratio (adjusted β = -0.158, P = .001) after controlling for age, gender, body mass index, ambulatory systolic blood pressure, low-density lipoprotein cholesterol, and retinal venular diameter. In untreated MH subjects, retinal arteriolar diameter, a marker of microvascular damage, was independently associated with echocardiographic markers of diastolic dysfunction. These findings might underscore the hypothesis that microvascular disease could contribute to cardiac remodeling.
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http://dx.doi.org/10.1111/jch.13863DOI Listing
June 2020

[Application of next generation sequencing for preimplantation genetic test of 71 couples with one partner carrying a reciprocal or Robertsonian translocation].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 May;37(5):563-566

Prenatal Diagnosis Center, Jiangxi Women and Children's Health Care Hospital, Nanchang, Jiangxi 330006, China.

Objective: To assess the value of preimplantation genetic test (PGT) based on next generation sequencing (NGS) for achieving pregnancy for 71 couples with one partner carrying a reciprocal or Robertsonian translocation.

Methods: Following blastocyst biopsy, whole genome of single cell was amplified, and PGT was performed by NGS. The subjects included 60 couples with one partner carrying a reciprocal translocation and 11 with one partner carrying a Robertsonian translocation. The results of PGT, implantation and prenatal diagnosis for all of the couples were analyzed.

Results: In total 301 embryos were obtained for the 71 couples through 92 ovulation cycles, 287 (95.3%) of which were successfully diagnosed by NGS. Eighty-five euploidy embryos were identified for the reciprocal translocation carrier group. In 18 cycles, no euploid embryo was obtained. Cancellation rate for the cycles was 19.5%. For reciprocal translocation carrier group and Robertsonian translocation carrier group, the rates for implantation, early abortion, and clinical pregnancy were 89.3% (42/47), 25.5% (12/47), 63.8% (30/47), and 88.8% (8/9), 22.2% (2/9), and 66.6% (6/9), respectively. The result of prenatal diagnosis was consistent with the that of PGT.

Conclusion: PGT based on NGS can effectively identify euploid embryos and reduce recurrent abortions and termination of pregnancies, achieving a satisfactory rate for clinical pregnancy.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.05.017DOI Listing
May 2020

[The value of combined use of chromosomal karyotyping and chromosome microarray analysis for prenatal diagnosis].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Apr;37(4):392-396

Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Care Hospital, Nanchang, Jiangxi 330008, China.

Objective: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) for prenatal diagnosis.

Methods: G-banding karyotyping and CMA were simultaneously performed on 546 women who were subjected to amniocentesis during middle pregnancy.

Results: In total 82 cases were detected with chromosomal abnormalities. The two methods were consistent in 43 cases, which included 14 trisomy 21, 6 trisomy 18, 1 trisomy 13, 14 sex chromosomal aneuploidies, 4 chromosomal deletions, 3 chromosomal duplications and 1 sex chromosomal mosaicism. Fifteen fetuses with chromosomal abnormalities detected by CMA were missed by karyotyping analysis, which included 9 microdeletions and 6 microduplications. Sixteen fetuses with chromosomal abnormalities detected by karyotyping analysis were missed by CMA, which included 15 chromosomal translocations and 1 sex chromosomal mosaicism. In 7 cases, the results of karyotyping analysis and CMA were inconsistent. One supernumerary marker chromosome detected by karyotyping analysis was verified by CMA as 9p13.1p21.1 duplication.

Conclusion: Combined chromosomal karyotyping and CMA can significantly improve the detection rate for chromosomal abnormalities, which has a great value for prenatal diagnosis.
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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.04.007DOI Listing
April 2020

Mechanisms of bactericidal action and resistance of polymyxins for Gram-positive bacteria.

Appl Microbiol Biotechnol 2020 May 10;104(9):3771-3780. Epub 2020 Mar 10.

College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China.

Polymyxins are cationic antimicrobial peptides used as the last-line therapy to treat multidrug-resistant Gram-negative bacterial infections. The bactericidal activity of polymyxins against Gram-negative bacteria relies on the electrostatic interaction between the positively charged polymyxins and the negatively charged lipid A of lipopolysaccharide (LPS). Given that Gram-positive bacteria lack an LPS-containing outer membrane, it is generally acknowledged that polymyxins are less active against Gram-positive bacteria. However, Gram-positive bacteria produce negatively charged teichoic acids, which may act as the target of polymyxins. More and more studies suggest that polymyxins have potential as a treatment for Gram-positive bacterial infection. This mini-review discusses recent advances in the mechanism of the antibacterial activity and resistance of polymyxins in Gram-positive bacteria.Key Points• Teichoic acids play a key role in the action of polymyxins on Gram-positive bacteria.• Polymyxin kills Gram-positive bacteria by disrupting cell surface and oxidative damage.• Modification of teichoic acids and phospholipids contributes to polymyxin resistance in Gram-positive bacteria.• Polymyxins have potential as a treatment for Gram-positive bacterial infection.
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http://dx.doi.org/10.1007/s00253-020-10525-yDOI Listing
May 2020

PBP1a glycosyltransferase and transpeptidase activities are both required for maintaining cell morphology and envelope integrity in Shewanella oneidensis.

FEMS Microbiol Lett 2020 02;367(3)

College of Biotechnology and Bioengineering, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310014, Zhejiang Province, China.

In rod-shaped Gram-negative bacteria, penicillin binding protein 1a (PBP1a) and 1b (PBP1b) form peptidoglycan-synthesizing complexes with the outer membrane lipoprotein LpoA and LpoB, respectively. Escherichia coli mutants lacking PBP1b/LpoB are sicker than those lacking PBP1a/LpoA. However, we previously found that mutants lacking PBP1a/LpoA but not PBP1b/LpoB are deleterious in Shewanella oneidensis. Here, we show that S. oneidensis PBP1a (SoPBP1a) contains conserved signature motifs with its E. coli counterpart, EcPBP1a. Although EcPBP1a play a less prominent role in E. coli, it is capable of substituting for the SoPBP1a in a manner dependent on SoLpoA. In S. oneidensis, expression of PBP1b is lower than PBP1a, and therefore the additional expression of SoPBP1b at low levels can functionally compensate for the absence of SoPBP1a. Importantly, S. oneidensis PBP1a variants lacking either glycosyltransferase (GTase) or transpeptidase (TPase) activity fail to maintain normal morphology and cell envelope integrity. Similarly, SoPBP1b variants also fail to compensate for the loss of SoPBP1a. Furthermore, overproduction of variants of SoPBP1a, but not SoPBP1b, has detrimental effects on cell morphology in S. oneidensis wild type cells. Overall, our results indicate that the combined enzymatic activities of SoPBP1a are essential for cell wall homeostasis.
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http://dx.doi.org/10.1093/femsle/fnaa026DOI Listing
February 2020

A novel TAB2 nonsense mutation (p.S149X) causing autosomal dominant congenital heart defects: a case report of a Chinese family.

BMC Cardiovasc Disord 2020 01 20;20(1):27. Epub 2020 Jan 20.

Prenatal Diagnosis Center, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, 330006, Jiangxi, China.

Background: TAB2 is an activator of MAP 3 K7/TAK1, which is required for the IL-1 induced signal pathway. Microdeletions encompassing TAB2 have been detected in various patients with congenital heart defects (CHD), indicating that haploinsufficiency of TAB2 causes CHD. To date, seven variants within TAB2 were reported associated with CHD, only two of them are nonsense mutations.

Case Presentation: Here we describe a three-generation Chinese family that included five CHD patients with heart valvular defects, such as mitral or tricuspid valves prolapse or regurgitation, and aortic valve stenosis or regurgitation. Our proband was a pregnant woman presenting with mitral, tricuspid, and aortic defects; her first child experienced sudden cardiac death at the age of 2 years. Whole-exome sequencing of the proband revealed a novel nonsense variant in TAB2 (c.C446G, p.S149X), which results in the elimination of the majority of C-terminal amino acids of TAB2, including the critical TAK1-binding domain. The variant was identified in five affected patients but not in the eight unaffected family members using Sanger sequencing and was classified as "pathogenic" according to the latest recommendation on sequence variants laid out by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Conclusion: We described a family with CHD caused by a novel TAB2 nonsense mutation. Our study broadens the mutation spectrum of TAB2; to the best of our knowledge, this is the first report of a pathogenic mutation within TAB2 in a Chinese population.
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http://dx.doi.org/10.1186/s12872-019-01322-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971906PMC
January 2020

A Novel β-Thalassemia Mutation [IVS-I-6 (T>G), : c.92+6T>G] in a Chinese Family.

Hemoglobin 2020 Jan 15;44(1):55-57. Epub 2020 Jan 15.

Department of Prenatal Diagnostic Center, Jiangxi Maternal and Child health Hospital, Nanchang, Jiangxi Province, People's Republic of China.

β-Thalassemia (β-thal) is one of the most common inherited hemoglobin (Hb) disorders in southern China. Up to now, the mutation spectrum of β-thal has been increasingly broadened through various molecular methods. In this study, a 34-year-old female displaying microcytic, hypochromic anemia was first detected with a novel IVS-I-6 (T>G) (: c.92+6T>G) mutation by Sanger sequencing. Pedigree analysis performed on her family showed that her mother and her daughter, who had abnormal hematological indices, also carried this mutation, while her other family members with normal hematological phenotypes, were not detected to carry any mutation. Based on the observed symptoms in this Chinese family, we concluded that this novel mutation was associated with a mild β-thal phenotype.
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http://dx.doi.org/10.1080/03630269.2020.1714648DOI Listing
January 2020

A novel mutation in the CYP27A1 gene in a family with cerebrotendinous xanthomatosis.

Int J Neurosci 2020 Oct 23;130(10):972-975. Epub 2020 Jan 23.

Innovation Center for Neurological Disorders, Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Purpose Of The Study: Cerebrotendinous xanthomatosis (CTX) is an inherited disorder associated with abnormal deposition of cholestenol in the brain and other tissues. Here we report a Chinese family with two affected members of CTX.

Materials And Methods: Clinical data were collected. Gene analysis, MRI, neuropsychological assessments, and the biopsy of right Achilles tendon xanthoma were carried out.

Results: The two cases had similar symptoms for cataracts, chronic diarrhea, progressive cognitive impairment and a disturbance of gait, and were identified with the same compound heterozygous mutations, c.435G>T in exon 2 and c.562C>T in exon 3.

Conclusions: Cerebrotendinous xanthomatosis (CTX) is an inherited disorder associated with abnormal deposition of cholestenol in the brain and other tissues. Although CTX is a treatable disease, the time of beginning treatment is crucial for therapeutic effect. Unfortunately, it usually takes years even decades from initial symptoms to the diagnosis of CTX. The screening for 27-hydroxylase (CYP27A1) gene even before the occurrence of tendon xanthoma is important for early diagnosis.
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http://dx.doi.org/10.1080/00207454.2020.1713774DOI Listing
October 2020

Haplotype analysis on association between variants of interleukin 6 (IL-6) and late-onset Alzheimer's disease in a Chinese Han population.

Exp Gerontol 2020 03 23;131:110813. Epub 2019 Dec 23.

Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, China; Department of Neurology, PLA 960 Hospital, Zibo, Shandong 255300, China. Electronic address:

Objective: The aim of this study was to evaluate the influence of single nucleotide polymorphisms (SNPs) in interleukin-6 (IL-6) gene and the haplotype on late-onset Alzheimer's disease (LOAD).

Methods: A total of 896 participants were enrolled, including 446 LOAD patients and 450 controls. Total genomic DNA was extracted from the blood of participants and genotyping was then performed. Hardy-Weinberg equilibrium test was conducted in controls. Multivariate analysis was performed to determine the association between 4 SNPs (rs1800796, rs7802308, rs1800795 and rs13447446) in IL-6 gene and LOAD. Pairwise LD analysis was employed to identify the association between haplotype and LOAD.

Results: Multivariate logistic analysis showed that T allele of rs7802308 and G allele of rs1800796 were correlated with decreased risk of LOAD, adjusted ORs were 0.68 (95% CI: 0.50-0.91) and 0.71 (95% CI: 0.51-0.92), respectively. However, rs1800795 and rs13447446 were not associated with LOAD. Pairwise LD analysis among the 4 SNPs showed that only rs1800796 and rs1800795 in IL-6 gene was in heavy LD, the D' value was >0.75 (0.825). In all samples, the haplotype C-G was observed most frequently in two groups, with 55.79% and 49.46% in the LOAD patients and controls, respectively. The results also indicated that haplotype G-C was significantly associated with decreased LOAG risk.

Conclusions: T allele of rs7802308 and G allele of rs1800796 were correlated with decreased risk of LOAD. The haplotype G-C were also correlated with decreased risk of LOAD.
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http://dx.doi.org/10.1016/j.exger.2019.110813DOI Listing
March 2020
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