Publications by authors named "Jing Li"

10,603 Publications

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EphA4 is highly expressed in the atria of heart and its deletion leads to atrial hypertrophy and electrocardiographic abnormalities in rats.

Life Sci 2021 May 8:119595. Epub 2021 May 8.

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing 100021, China. Electronic address:

Aims: EphA4 is a member of the Eph receptor family, and expressed mainly in central nervous system (CNS), which is involved in CNS development and multiple diseases. Due to the variability in EphA4 expression, we wondered if EphA4 is expressed in other tissues, and what role does EphA4 play?

Materials And Methods: We generated an EphA4 knockout (KO) rat line with red fluorescent marker protein encoded by the mCherry cassette inserted downstream of the EphA4 promoter as a reporter. Using this system, we observed high expression of EphA4 in the heart atria and in the brain.

Key Findings: EphaA4 KO rats (EphA4) developed obvious atrial hypertrophy with an increased atria-to-heart weight ratio and atrial cardiomyocyte cross-sectional area at six months of age. EphA4 rats had reduced atrial end diastolic volume (EDV), atrial ejection fraction (EF) and left ventricular EF. They also exhibited increased amplitude of QRS complexes and QT intervals, with invisible p waves. RNA sequencing revealed that EphA4 KO altered the transcription of multiple genes involved in regulation of transcription and translation, ion binding, metabolism and cell adhesion. Deletion of EphA4 reduced IGF1 mRNA and protein expression, which is involved in cardiac remodeling.

Significance: Our data demonstrated that EphA4 was highly expressed in the atria and that its deletion caused atrial dysfunction. Our findings also suggested that the EphA4 KO rat could be a potential model for studies on atrial remodeling.
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http://dx.doi.org/10.1016/j.lfs.2021.119595DOI Listing
May 2021

Compromised long-lived memory CD8+ T cells are associated with reduced IL-7 responsiveness in HIV-infected immunological non-responders.

Eur J Immunol 2021 May 11. Epub 2021 May 11.

Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long-lived memory CD8 T cells (LLMCs) are essential executors of long-term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological non-responders (INRs). We found that both TNs and INRs showed severely compromised LLMCs compared with HCs and CRs, respectively. The decrease of LLMCs in TNs correlated positively with the reduction of their precursors, namely memory precursor effector T cells (MPECs), which might be associated with elevated pro-inflammatory cytokines. Strikingly, INRs showed an accumulation of MPECs, which exhibited diminished responsiveness to interleukin 7 (IL-7), thereby indicating abrogated differentiation into LLMCs. Moreover, in vitro studies showed that treatment with dexamethasone could improve the IL7-phosphorylated (p)-signal transducer and activator of transcription (STAT5) response by upregulating the expression of the interleukin 7 receptor (IL-7Rα) on MPECs in INRs. These findings provide insights that will encourage the development of novel therapeutics to improve immune function in PLWH. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/eji.202149203DOI Listing
May 2021

Use of Vascularized Fibular Epiphyseal Transfer with Massive Bone Allograft for Proximal Humeral Reconstruction in Children with Bone Sarcoma.

Ann Surg Oncol 2021 May 11. Epub 2021 May 11.

Department of Orthopedics, Xi Jing Hospital, Air force Medical University, Xi'an, Shaanxi, People's Republic of China.

Background: The vascularized fibula epiphyseal transfer provides a reconstructive option for longitudinal growth after oncologic resection of the proximal humerus in pediatric patients. However, postoperative fractures and poor shoulder function are common. The purpose of this review was to introduce a composite approach in oncologic reconstruction of the proximal humerus and assess its clinical outcomes.

Methods: We retrospectively investigated five children (3 osteosarcoma and 2 Ewing's sarcoma) who underwent biological reconstruction with combination of vascularized fibula epiphyseal transfer and massive bone allograft after oncologic resection of the proximal humerus. The mean follow-up was 46.8 months.

Results: All patients were alive at the last follow-up. There was no graft fracture, hardware failure, or infection. The mean time of osseous union was 2.9 months at fibula-humerus junction and 6.2 months at allograft-humerus junction. Hypertrophy and axial growth were evident in all, except one patient who has avascular necrosis of the fibula head. The mean hypertrophy index was 51.5%, and the mean growth was 4.4 mm per annum. The mean arm discrepancy was 4.6 cm. All reconstruction was in situ with the average abduction of 113° and forward flexion of 69°. The mean Musculoskeletal Tumor Society (MSTS) score was 85.4% at the final follow-up. All patients experienced dropped foot and resolved spontaneously.

Conclusions: The combination of vascularized fibula epiphyseal transfer with massive allograft bone provides a reliable oncologic reconstruction of proximal humerus in children. It not only offers the ability of longitudinal growth, hypertrophy, and osseous union but also diminishes reconstructive complications and improves shoulder function.

Level Of Evidence: Therapeutic Level IV.
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http://dx.doi.org/10.1245/s10434-021-10032-yDOI Listing
May 2021

The prognostic significance of electrocardiography findings in patients with coronavirus disease 2019: A retrospective study.

Clin Cardiol 2021 May 11. Epub 2021 May 11.

Department of Cardiology, Intervention Cardiology Center, Wuhan No.1 Hospital, No.215 Zhongshan Avenue, QiaoKou District, Wuhan, China.

Background: Coronavirus disease 2019 (COVID-19) has reached a pandemic level. Cardiac injury is not uncommon among COVID-19 patients. We sought to describe the electrocardiographic characteristics and to identify the prognostic significance of electrocardiography (ECG) findings of patients with COVID-19.

Hypothesis: ECG abnormality was associated with higher risk of death.

Methods: Consecutive patients with laboratory-confirmed COVID-19 and definite in-hospital outcome were retrospectively included. Demographic characteristics and clinical data were extracted from medical record. Initial ECGs at admission or during hospitalization were reviewed. A point-based scoring system of abnormal ECG findings was formed, in which 1 point each was assigned for the presence of axis deviation, arrhythmias, atrioventricular block, conduction tissue disease, QTc interval prolongation, pathological Q wave, ST-segment change, and T-wave change. The association between abnormal ECG scores and in-hospital mortality was assessed in multivariable Cox regression models.

Results: A total of 306 patients (mean 62.84 ± 14.69 years old, 48.0% male) were included. T-wave change (31.7%), QTc interval prolongation (30.1%), and arrhythmias (16.3%) were three most common found ECG abnormalities. 30 (9.80%) patients died during hospitalization. Abnormal ECG scores were significantly higher among non-survivors (median 2 points vs 1 point, p < 0.001). The risk of in-hospital death increased by a factor of 1.478 (HR 1.478, 95% CI 1.131-1.933, p = 0.004) after adjusted by age, comorbidities, cardiac injury and treatments.

Conclusions: ECG abnormality was common in patients admitted for COVID-19 and was associated with adverse in-hospital outcome. In-hospital mortality risk increased with increasing abnormal ECG scores.
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http://dx.doi.org/10.1002/clc.23628DOI Listing
May 2021

Nasopharyngeal Microbiomes in Donkeys Shedding Subspecies in Comparison to Healthy Donkeys.

Front Vet Sci 2021 22;8:645627. Epub 2021 Apr 22.

Equine Clinical Diagnostic Center, College of Veterinary Medicine, China Agricultural University, Beijing, China.

subsp. equi () is the pathogen causing strangles, a highly infectious disease that can affect equids including donkeys of all ages. It can persistently colonize the upper respiratory tract of animals asymptomatically for years, which serves as a source of infection. Several strangles outbreaks have been reported in the donkey industry in China in the last few years and pose a great threat to health, production, and the welfare of donkeys. Nasopharyngeal swab samples for culture and PCR are used widely in strangles diagnosis. Additionally, microbiomes within and on the body are essential to host homoeostasis and health. Therefore, the microbiome of the equid nasopharynx may provide insights into the health of the upper respiratory tract in animals. There has been no study investigating the nasopharyngeal microbiome in healthy donkeys, nor in donkeys shedding . This study aimed to compare nasopharyngeal microbiomes in healthy and carrier donkeys using 16S rRNA gene sequencing. Nasopharyngeal samples were obtained from 16 donkeys recovered from strangles (group S) and 14 healthy donkeys with no history of strangles exposure (group H). Of those sampled, 7 donkeys were determined to be carriers with positive PCR and culture results in group S. In group H, all 14 donkeys were considered free of strangles based on the history of negative exposure, negative results of PCR and culture. Samples from these 21 donkeys were used for microbial analysis. The nasopharyngeal microbiome composition was compared between the two groups. At the phylum level, relative abundance of Proteobacteria was predominantly higher in the carrier donkeys than in healthy donkeys ( < 0.01), while Firmicutes and Actinobacteria were significantly less abundant in the carrier donkeys than in healthy donkeys ( < 0.05). At the genus level, was detected in the upper respiratory tract of donkeys for the first time and dominated in carrier donkeys. It is suspected to suppress other normal flora of URT microbiota including spp., spp., and spp. We concluded that the nasopharyngeal microbiome in carrier donkeys still exhibited microbial dysbiosis, which might predispose them to other airway diseases.
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http://dx.doi.org/10.3389/fvets.2021.645627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100518PMC
April 2021

Myofibroblast-Derived Exosome Induce Cardiac Endothelial Cell Dysfunction.

Front Cardiovasc Med 2021 23;8:676267. Epub 2021 Apr 23.

Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States.

Endothelial cells (ECs) play a critical role in the maintenance of vascular homeostasis and in heart function. It was shown that activated fibroblast-derived exosomes impair cardiomyocyte function in hypertrophic heart, but their effect on ECs is not yet clear. Thus, we hypothesized that activated cardiac fibroblast-derived exosomes (FB-Exo) mediate EC dysfunction, and therefore modulation of FB-exosomal contents may improve endothelial function. Exosomes were isolated from cardiac fibroblast (FB)-conditioned media and characterized by nanoparticle tracking analysis and electron microscopy. ECs were isolated from mouse heart. ECs were treated with exosomes isolated from FB-conditioned media, following FB culture with TGF-β1 (TGF-β1-FB-Exo) or PBS (control) treatment. TGF-β1 significantly activated fibroblasts as shown by increase in collagen type1 α1 (α), periostin (), and fibronectin () gene expression and increase in Smad2/3 and p38 phosphorylation. Impaired endothelial cell function (as characterized by a decrease in tube formation and cell migration along with reduced α, and gene expression) was observed in TGF-β1-FB-Exo treated cells. Furthermore, TGF-β1-FB-Exo treated ECs showed reduced cell proliferation and increased apoptosis as compared to control cells. TGF-β1-FB-Exo cargo analysis revealed an alteration in fibrosis-associated miRNAs, including a significant increase in miR-200a-3p level. Interestingly, miR-200a-3p inhibition in activated FBs, alleviated TGF-β1-FB-Exo-mediated endothelial dysfunction. Taken together, this study demonstrates an important role of miR-200a-3p enriched within activated fibroblast-derived exosomes on endothelial cell biology and function.
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http://dx.doi.org/10.3389/fcvm.2021.676267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102743PMC
April 2021

Facing coronavirus disease 2019: What do we know so far? (Review).

Exp Ther Med 2021 Jun 20;21(6):658. Epub 2021 Apr 20.

Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Although the World Health Organization declared the outbreak of coronavirus disease 2019 (COVID-19), which originated in China, as a public health emergency of international concern as early as January 30, 2020, the current COVID-19 epidemic is spreading rapidly. As of April 19, 2020, total of 2,392,165 confirmed cases had been reported in 211 countries and regions, with 614,421 (25.68%) cured cases and 164,391 (6.87%) deaths. Scientists and clinicians have made great efforts to learn much about COVID-19 so that it can be controlled as soon as possible. Herein, this review will discuss the epidemiology, pathology, clinical features, diagnosis and treatment of COVID-19 based on the current evidence.
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http://dx.doi.org/10.3892/etm.2021.10090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097225PMC
June 2021

Effect of lipopolysaccharide on calcification of human umbilical artery smooth muscle cells co-cultured with human periodontal ligament cells.

Exp Ther Med 2021 Jun 20;21(6):655. Epub 2021 Apr 20.

Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Periodontitis is an independent risk factor for coronary heart disease. lipopolysaccharide (Pg-LPS) was considered to be one of the main virulence factors. In addition, vascular smooth muscle cells transform into osteoblast-like cells in an arterial calcification process under chronic inflammatory conditions. The present study aimed to determine the calcification induced by Pg-LPS in human umbilical artery smooth muscle cells (HUASMCs) co-cultured with human periodontal ligament cells (HPDLCs). An co-culture system was established using Transwell inserts. HUASMC proliferation and alkaline phosphatase (ALP) activity were measured with a Cell Counting Kit-8 and an ALP kit, respectively. Calcium nodule formation was detected using alizarin red S staining. The effects of Pg-LPS on the mRNA expression of the calcification genes of ALP, core-binding factor α1 (Runx2) and bone sialoprotein (BSP) were assessed using reverse transcription-quantitative PCR. The results indicated that Pg-LPS increased HUASMC proliferation and ALP activity. Furthermore, among all of the groups, calcium nodule formation was most extensive in co-cultured cells in the mineralization-inducing medium containing Pg-LPS. In addition, the expression of specific osteogenic genes (Runx2, ALP and BSP) significantly increased in the presence of Pg-LPS and mineralization-inducing medium, which was further enhanced in co-culture with HPDLCs. In conclusion, co-culture with HPDLCs increased the effect of Pg-LPS to stimulate the calcification of HUASMCs. It was suggested that besides the inflammation, periodontitis may promote the occurrence of vascular calcification. The study indicated that periodontal treatment of subgingival scaling to reduce and/or control may decrease the occurrence or severity of vascular calcification.
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http://dx.doi.org/10.3892/etm.2021.10087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097230PMC
June 2021

Predictive Factors for Live Birth in Fresh Fertilization/Intracytoplasmic Sperm Injection Treatment in Poor Ovarian Reserve Patients Classified by the POSEIDON Criteria.

Front Endocrinol (Lausanne) 2021 12;12:630832. Epub 2021 Apr 12.

Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

The mechanisms underlying poor ovarian response (POR) in assisted reproductive technology remain unclear, there is no consensus on the management of poor responders, the POSEIDON stratification classifies infertility patients into "expected" or "unexpected" groups to provide a more nuanced picture of POR, but few researchers have discussed the independent predictive factors (smoothed plots and the threshold effect) for live birth in POR patients classified by the new criteria. We conducted a retrospective cohort study using clinical data from 6,580 POR patients classified by the POSEIDON criteria in the First Affiliated Hospital of Zhengzhou University, and explored the live birth based on the results before and after the threshold inflection point of each independent influencing factor. Among 6,580 poor ovarian reserve patients classified by the POSEIDON criteria, 1,549 (23.54%) had live births, and 5,031 (76.46%) did not have live births. Multivariate logistic regression analysis showed that female age (OR 0.901; 95% CI 0.887~0.916; P < 0.001), body mass index (OR 0.963; 95% CI 0.951~0.982; P < 0.001), antral follicle counting (OR 1.049; 95% CI 1.009~1.042; P < 0.001) and controlled ovarian hyperstimulation protocol were independent factors predicting live birth in patients with POR. The threshold effect analysis found that the inflection point of female age was 34 years old, and when age was > 34 years old, the probability of live birth in POR patients dropped sharply (OR 0.7; 95% CI 0.7~0.8; P < 0.001). The inflection point of BMI was 23.4 kg/m, and BMI had a negative correlation with live birth (OR 0.963; 95% CI 0.951~0.982; P < 0.001). The threshold inflection point of AFC was 8n. Female age, BMI, AFC and COH protocol were independent predictive factors associated with live birth in POR patients classified by the POSEIDON criteria. The smooth curve fit and threshold effect analyses provide clinical management strategies for these patients. In addition, the early-follicular-phase long-acting GnRH-agonist long protocol seems to have a higher live birth rates than other protocols. It is worth highlighting that BMI should be considered as well in the POSEIDON criteria.
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http://dx.doi.org/10.3389/fendo.2021.630832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099421PMC
April 2021

Development of a fluorescence-based assay for screening of urate transporter 1 inhibitors using 6-carboxyfluorescein.

Anal Biochem 2021 May 6:114246. Epub 2021 May 6.

MOE International Joint Research Laboratory on Synthetic Biology and Medicines, School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, P. R. China. Electronic address:

The urate transporter 1 (URAT1) inhibitors were considered a very promising class of uricosuric agents for the treatment of hyperuricemia and gout. In vitro activity testing of these compounds has been conducted by radio-labeling uric acid for a long time. However, relatively few offer the convenience and speed of fluorescence-based assays. Herein, we report the development of a non-radioactive cell-based method for the screening of URAT1 inhibitors using the human embryonic kidney 293T cells stably expressing human URAT1, and 6-carboxyfluorescein (6-CFL) as a substrate. The URAT1-mediated transport of 6-CFL was time dependent and saturable (Km = 239.5 μM, Vmax = 6.2 pmol/well/min, respectively). Molecules known to interact with organic anion transporters, including benzbromarone, probenecid, and lesinurad, demonstrated concentration-dependent inhibition of 6-CFL transport by URAT1. Moreover, we screened a small subset of compounds, and identified compound 4 as a promising URAT1 inhibitor. This in vitro assay may be employed to screen for novel URAT1 inhibitors, which are effective against hyperuricemia.
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http://dx.doi.org/10.1016/j.ab.2021.114246DOI Listing
May 2021

Clinical characteristics and prognosis of patients with isolated thrombotic vs. obstetric antiphospholipid syndrome: a prospective cohort study.

Arthritis Res Ther 2021 May 8;23(1):138. Epub 2021 May 8.

Department of Rheumatology and Clinical Immunology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Background: Several studies suggested that thrombotic and obstetric antiphospholipid syndromes could be independent identities, but few have systematically compared their clinical characteristics and prognosis.

Objective: The objective of this study is to identify key differences between thrombotic APS (tAPS) and obstetric APS (oAPS).

Methods: This single-center, prospective study included consecutive patients with primary antiphospholipid syndrome (APS) receiving treatment at the Peking Union Medical College Hospital during a period from 2013 to 2020.

Results: Screening of the database yielded a total of 244 women with positive antiphospholipid antibody (aPL). Among the 105 women with primary APS, 39 (37.14%) had isolated tAPS (ItAPS), 44 (41.90%) had isolated oAPS (IoAPS), and 9 (8.57%) had both tAPS and tAPS+oAPS. In comparison to those with IoAPS, patients with ItAPS had older age (41.92 ± 11.97 vs. 33.16 ± 4.22 years, P < 0.01), higher rate of cardiovascular risk (at least one positive of coronary heart disease, hypertension, obesity, diabetes, and hyperlipidemia) (41.03% vs. 6.82%, P < 0.01), and higher frequency of thrombocytopenia (43.59% vs. 20.45%, P < 0.05). Antibody profiles were generally similar among the groups, but isolated anti-β2GPI positivity was more common in patients with IoAPS (52.27% vs. 17.94% for ItAPS, P = 0.01). Triple aPL positivity was more common in patients with both tAPS and oAPS (66.67% vs. 46.15% for ItAPS vs. 25% for IoAPS, P = 0.022). Blood homocysteine was higher in patients with ItAPS (11.20 vs. 9.90 μmol/L for IoAPS, P < 0.05), but there were no differences in inflammatory markers or complements. Recurrence rate of thrombosis was higher in patients with ItAPS (33.33% vs. 2.27% for IoAPS, P ≤ 0.001) with a mean follow-up of 61 months.

Conclusion: Despite generally similar antibody and biochemical profiles, patients with ItAPS had much higher risk of recurrent thrombosis than IoAPS, supporting distinct mechanisms of pathogenesis.
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http://dx.doi.org/10.1186/s13075-021-02515-wDOI Listing
May 2021

Preparation of loratadine nanocrystal tablets to improve the solubility and dissolution for enhanced oral bioavailability.

J Pharm Pharmacol 2021 May 8. Epub 2021 May 8.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.

Objectives: Loratadine is a selective H1 receptor inhibitor that has been widely used in the clinical treatment of allergic diseases. Here we aimed to develop a novel solid loratadine nanocrystal to increase the low and pH-dependent water solubility for bioavailability enhancement.

Methods: Loratadine solid nanocrystal was developed through high-speed shear-high pressure homogenization followed by freeze-drying, which was further prepared into tablets through direct compression. The formulation and process parameter were screened. Furthermore, the characterization and oral bioavailability of loratadine nanocrystal were studied.

Key Findings: The loratadine nanocrystal had the satisfactory particle size of 425.9 nm and great redispersibility, which was mainly attributed to the addition of Pluronic F127 and polyvinylpyrrolidone K17 as the stabilizer. The saturation solubility of the loratadine nanocrystal was increased to 3.81, 3.22 and 2.57-fold that of the crude drug in water, pH 6.8 and pH 4.5 buffer respectively. Furthermore, the pharmacokinetic studies in rats revealed that the AUC (0-∞) of the nanocrystal tablets was 2.38-fold that of raw tablets and 1.94-fold that of commercial tablets, respectively.

Conclusions: The nanocrystal tablets could significantly improve the oral bioavailability of loratadine, which would also be a promising approach to enhance the solubility of insoluble drugs.
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http://dx.doi.org/10.1093/jpp/rgab043DOI Listing
May 2021

LIMIT is an immunogenic lncRNA in cancer immunity and immunotherapy.

Nat Cell Biol 2021 May 6. Epub 2021 May 6.

Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Major histocompatibility complex-I (MHC-I) presents tumour antigens to CD8 T cells and triggers anti-tumour immunity. Humans may have 30,000-60,000 long noncoding RNAs (lncRNAs). However, it remains poorly understood whether lncRNAs affect tumour immunity. Here, we identify a lncRNA, lncRNA inducing MHC-I and immunogenicity of tumour (LIMIT), in humans and mice. We found that IFNγ stimulated LIMIT, LIMIT cis-activated the guanylate-binding protein (GBP) gene cluster and GBPs disrupted the association between HSP90 and heat shock factor-1 (HSF1), thereby resulting in HSF1 activation and transcription of MHC-I machinery, but not PD-L1. RNA-guided CRISPR activation of LIMIT boosted GBPs and MHC-I, and potentiated tumour immunogenicity and checkpoint therapy. Silencing LIMIT, GBPs and/or HSF1 diminished MHC-I, impaired antitumour immunity and blunted immunotherapy efficacy. Clinically, LIMIT, GBP- and HSF1-signalling transcripts and proteins correlated with MHC-I, tumour-infiltrating T cells and checkpoint blockade response in patients with cancer. Together, we demonstrate that LIMIT is a cancer immunogenic lncRNA and the LIMIT-GBP-HSF1 axis may be targetable for cancer immunotherapy.
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http://dx.doi.org/10.1038/s41556-021-00672-3DOI Listing
May 2021

Sleep quality in relation to social support and resilience among rural empty-nest older adults in China.

Sleep Med 2021 Apr 1;82:193-199. Epub 2021 Apr 1.

School of Nursing, Jilin University, Changchun 130021, China. Electronic address:

Background: Population ageing is a global problem, and one of the adverse effects in China is the rural empty-nest phenomenon, which is increasingly prominent. Recently, the sleep problems of rural empty nesters have gradually aroused attention. The purpose of this article was to investigate sleep quality and its influencing factors in rural empty nesters and explore the correlation between social support, resilience and sleep quality in the target population.

Methods: This study investigated 250 empty nesters in six rural areas. Information on sociodemographics, sleep quality, social support and resilience was collected. Univariate analysis and multivariate analysis were used to determine the influencing factors of sleep quality. The Spearman correlation coefficient was used to evaluate the linear associations between social support, resilience and sleep quality. The mediating effect of resilience between social support and sleep quality was measured by bootstrap-mediated analysis.

Results: The sleep quality score among rural empty nesters was 6.74 ± 3.80. Sleep quality was influenced significantly by marital status, monthly income, number of chronic diseases and frequency of communication with children. Besides, social support and resilience were significantly positively correlated with sleep quality. Resilience was not the only mediating variable between social support and sleep quality.

Conclusion: The sleep quality of rural empty nesters was poorer than those of the general rural older adults and affected by multiple factors. Moreover, social support and resilience had a positive impact on the sleep quality of rural empty nesters, which provided new ideas for exploring specific measures to improve their sleep quality in the future.
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http://dx.doi.org/10.1016/j.sleep.2021.03.026DOI Listing
April 2021

The role and mechanism of Hyperoside against myocardial infarction in mice by regulating autophagy via NLRP1 inflammation pathway.

J Ethnopharmacol 2021 May 3:114187. Epub 2021 May 3.

Department of Pharmacology, School of Basic Medicine, Anhui Medical University, No.81 Meishan Road, Hefei, 230032, People's Republic of China. Electronic address:

Ethnopharmacological Relevance: The genus Hypericum are widely distributed in China. Hypericum perforatum L. (genus Hypericum, family Hypericaceae) has a long history as a traditional Chinese medicine, which was traditionally used for the treatment of emotional distress, cardiothoracic depression, and acute mastitis. Hyperoside (Hyp) extracted from Hypericum perforatum L. has been affirmed to exert therapeutic effects on cardiovascular diseases, with widespread existence in plants of genus Hypericum. Hyp could also be extracted from Crataegus pinnatifida Bunge (genus Crataegus pinnatifida Bunge, family Rosaceae), another traditional Chinese medicine that traditionally prevented and treated heart disease in China. The cardioprotection and mechanism of Hyp comprise anti-inflammation, anti-fibrosis, activation of autophagy, and reversal of cardiac remodeling.

Aim Of The Study: This study aimed to explore the Hyp effect against MI and its underlying mechanism.

Materials And Methods: The MI model was constructed in the KM mice via a ligating surgery of the left anterior descending (LAD) coronary artery. Subsequently, the mice were divided into following seven groups: Sham group, MI group, MI+Hyp 9mg/kg group, MI+Hyp18mg/kg group, MI+Hyp36mg/kg group, MI+Fosinopril group, and MI+Hyp-36mg/kg+3-MA group. Each group was treated with Hyp in different concentrations or positive medicine for two weeks except for the sham group. After two weeks, we examined the cardiac function, electrocardiogram (ECG), myocardial hypertrophy in the non-infarct area, collagen volume fraction (CVF), perivascular collagen area (PVCA) in the infarct area, and several serum cytokines. Autophagy and inflammation in cardiomyocytes were assessed via measuring autophagy-associated proteins and NLRP1 inflammasome pathway related proteins.

Results: Hyp reversed LV remodeling and adverse ECG changes through reducing CVF and myocardial hypertrophy. Additionally, Hyp treatment could reduce inflammation levels in cardiomyocytes, compared with those in MI group. Moreover, NLRP1inflammation pathway was activated after MI. Up-regulation of autophagic flux suppressed NLRP1 inflammation pathway after Hyp treatment. However, co-treatment with 3-MA abrogated above effects of Hyp.

Conclusions: Hyp had obvious protective effect on heart injury in MI mice. Echocanrdiographic and histological measurements demonstrated that Hyp treatment improved cardiac function, and ameliorated myocardial hypertrophy and fibrinogen deposition after MI. The partial mechanism is that Hyp could up-regulate autophagy after MI. Furthermore, the promotion of autophagic flux would suppress NLRP1 inflammation pathway induced by MI.
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http://dx.doi.org/10.1016/j.jep.2021.114187DOI Listing
May 2021

mRNA modifications in cardiovascular biology and disease: with a focus on m6A modification.

Cardiovasc Res 2021 May 6. Epub 2021 May 6.

Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL, United States.

Among several known RNA modifications, N6-methyladenosine (m6A) is the most studied RNA epitranscriptomic modification and controls multiple cellular functions during development, differentiation, and disease. Current research advancements have made it possible to examine the regulatory mechanisms associated with RNA methylation and reveal its functional consequences in the pathobiology of many diseases, including heart failure. m6A methylation has been described both on coding (mRNA) and non-coding RNA species including rRNA, tRNA, small nuclear RNA and circular RNAs. The protein components which catalyze the m6A methylation are termed methyltransferase or "m6A writers." The family of proteins that recognize this methylation are termed "m6A readers" and finally the enzymes involved in the removal of a methyl group from RNA are known as demethylases or "m6A erasers." At the cellular level, different components of methylation machinery are tightly regulated by many factors to maintain the m6A methylation dynamics. The m6A methylation process impacts different stages of mRNA metabolism and the biogenesis of long non-coding RNA and miRNA. Although, mRNA methylation was initially described in the 1970s, its regulatory roles in various diseases, including cardiovascular diseases are broadly unexplored. Recent investigations suggest the important role of m6A mRNA methylation in both hypertrophic and ischemic heart diseases. In the present review, we evaluate the significance of m6A methylation in the cardiovascular system, in cardiac homeostasis and disease, all of which may help to improve therapeutic intervention for the treatment of heart failure.
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http://dx.doi.org/10.1093/cvr/cvab160DOI Listing
May 2021

Senescence Osteoblast-Derived Exosome-Mediated miR-139-5p Regulates Endothelial Cell Functions.

Biomed Res Int 2021 15;2021:5576023. Epub 2021 Apr 15.

Department of Physiology, Guangxi Medical University, Nanning, China.

The pathogenesis of osteoporosis is considered extremely intricate. Osteoblast differentiation and angiogenesis can greatly affect bone development and formation, given their coupling role in these processes. Exosome-mediated miRNA regulates cellular senescence, proliferation, and differentiation. However, whether senescent osteoblasts can regulate the senescence of vascular endothelial cell by miRNA through exosomal pathway remains unclear. In this study, senescent osteoblasts could regulate endothelial cell function, promote cell senescence and apoptosis, and decrease cell proliferation via exosomal pathway. miR-139-5p showed high expression in senescent osteoblasts and their exosomes. After senescent osteoblast-derived exosome treatment, miR-139-5p was also upregulated in endothelial cells. Furthermore, transfection of miR-139-5p mimic promoted the senescence and apoptosis of vascular endothelial cells and inhibited their proliferation and migration, whereas transfection of miR-139-5p inhibitor rescued the effect of D-galactose. Using double luciferase assay, TBX1 was confirmed to be a direct target gene of miR-139-5p. In conclusion, senescent osteoblast-derived exosome-mediated miR-139-5p regulated endothelial cell function via exosomal pathway. Our study revealed the role of osteoblast-derived exosomes in the bone environment during aging, providing a clue for inventing a new target therapy.
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http://dx.doi.org/10.1155/2021/5576023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064779PMC
April 2021

Anti-diabetic Role of Adropin in Streptozotocin Induced Diabetic Rats via Alteration of PI3K/Akt and Insulin Signaling Pathway.

J Oleo Sci 2021 ;70(5):657-664

Department of Endocrinology, Zhengzhou Central Hospital Affiliated to Zhengzhou University.

Diabetes mellitus (DM) is a hyperglycemia-related multifactorial condition with an elevated risk of microvascular and microvascular complications associated with this disease. The current experimental study was to examine the antidiabetic activity of streptozotocin (STZ)-induced adropin against diabetic rats by altering the PI3K/Akt and insulin signaling pathways. STZ (60 mg/kg) was used for the induction of DM and rats were divided into different groups and received the adropin (20, 40 and 80 mg/kg) and glibenclamide (10 mg/kg) till 28 days. Body weight, plasma insulin, blood glucose and food intake were estimated, respectively. Biochemical enzymes, carbohydrate enzymes, lipid parameters, AMPK and insulin signalling pathway parameters were estimated. GLUT4 and PPARγ expression were also estimated. Oral administration of adropin significantly (p < 0.001) increased the glycogen, glucose-6-phosphatase dehydrogenase, insulin, hexokinase and belittled the blood glucose level, fructose 1-6-biphosphatase, glucose-6-phosphatase at dose dependent manner. Adropin significantly (p < 0.001) reduced the level of triglyceride, cholesterol, low density lipoprotein, very low density lipoprotein and increased the level of high density lipoprotein at dose dependent manner. Adropin significantly (p < 0.001) activated the Akt, IRS-2, IRS-1, IR, p-AKT and PI3k, which are the key modulator molecules of PI3K/Akt, AMPK and insulin signalling pathway in DM rats. The current experimental study confirms the anti-diabetic effect of adropin on DM rats induced by AMPK and insulin signalling pathway against STZ.
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http://dx.doi.org/10.5650/jos.ess21019DOI Listing
January 2021

DeepNetBim: deep learning model for predicting HLA-epitope interactions based on network analysis by harnessing binding and immunogenicity information.

BMC Bioinformatics 2021 May 5;22(1):231. Epub 2021 May 5.

Department of Bioinformatics and Biostatistics, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Background: Epitope prediction is a useful approach in cancer immunology and immunotherapy. Many computational methods, including machine learning and network analysis, have been developed quickly for such purposes. However, regarding clinical applications, the existing tools are insufficient because few of the predicted binding molecules are immunogenic. Hence, to develop more potent and effective vaccines, it is important to understand binding and immunogenic potential. Here, we observed that the interactive association constituted by human leukocyte antigen (HLA)-peptide pairs can be regarded as a network in which each HLA and peptide is taken as a node. We speculated whether this network could detect the essential interactive propensities embedded in HLA-peptide pairs. Thus, we developed a network-based deep learning method called DeepNetBim by harnessing binding and immunogenic information to predict HLA-peptide interactions.

Results: Quantitative class I HLA-peptide binding data and qualitative immunogenic data (including data generated from T cell activation assays, major histocompatibility complex (MHC) binding assays and MHC ligand elution assays) were retrieved from the Immune Epitope Database database. The weighted HLA-peptide binding network and immunogenic network were integrated into a network-based deep learning algorithm constituted by a convolutional neural network and an attention mechanism. The results showed that the integration of network centrality metrics increased the power of both binding and immunogenicity predictions, while the new model significantly outperformed those that did not include network features and those with shuffled networks. Applied on benchmark and independent datasets, DeepNetBim achieved an AUC score of 93.74% in HLA-peptide binding prediction, outperforming 11 state-of-the-art relevant models. Furthermore, the performance enhancement of the combined model, which filtered out negative immunogenic predictions, was confirmed on neoantigen identification by an increase in both positive predictive value (PPV) and the proportion of neoantigen recognition.

Conclusions: We developed a network-based deep learning method called DeepNetBim as a pan-specific epitope prediction tool. It extracted the attributes of the network as new features from HLA-peptide binding and immunogenic models. We observed that not only did DeepNetBim binding model outperform other updated methods but the combination of our two models showed better performance. This indicates further applications in clinical practice.
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http://dx.doi.org/10.1186/s12859-021-04155-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097772PMC
May 2021

Self-Assembling Nanoparticle Vaccines Displaying the Receptor Binding Domain of SARS-CoV-2 Elicit Robust Protective Immune Responses in Rhesus Monkeys.

Bioconjug Chem 2021 May 5. Epub 2021 May 5.

Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming 650118, China.

SARS-CoV-2 caused the COVID-19 pandemic that lasted for more than a year. Globally, there is an urgent need to use safe and effective vaccines for immunization to achieve comprehensive protection against SARS-CoV-2 infection. Focusing on developing a rapid vaccine platform with significant immunogenicity as well as broad and high protection efficiency, we designed a SARS-CoV-2 spike protein receptor-binding domain (RBD) displayed on self-assembled ferritin nanoparticles. In a 293i cells eukaryotic expression system, this candidate vaccine was prepared and purified. After rhesus monkeys are immunized with 20 μg of RBD-ferritin nanoparticles three times, the vaccine can elicit specific humoral immunity and T cell immune response, and the neutralizing antibodies can cross-neutralize four SARS-CoV-2 strains from different sources. In the challenge protection test, after nasal infection with 2 × 10 CCID50 SARS-CoV-2 virus, compared with unimmunized control animals, virus replication in the vaccine-immunized rhesus monkeys was significantly inhibited, and respiratory pathology observations also showed only slight pathological damage. These analyses will benefit the immunization program of the RBD-ferritin nanoparticle vaccine in the clinical trial design and the platform construction to present a specific antigen domain in the self-assembling nanoparticle in a short time to harvest stable, safe, and effective vaccine candidates for new SARS-CoV-2 isolates.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00208DOI Listing
May 2021

A colorimetric optical thermometry of host-sensitized Pr-doped niobate phosphors based on electronic-rich-site strategy.

Dalton Trans 2021 May 4. Epub 2021 May 4.

Department of Chemistry, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China.

Most praseodymium-doped red-emitting phosphors need high-temperature synthesis conditions with a reducing atmosphere. The niobate matrix selected in this work provides a sufficient electron-rich-site environment for praseodymium through charge migration, and praseodymium can be self-reduced in air atmosphere, which is safe and environmentally friendly. By building the [NbO6] group → Pr3+ energy transfer and finely modifying the doping concentration of Pr3+ ions, we constructed a dual-luminescence-system of the [NbO6] group and Pr3+. Thereby, optical temperature measurement based on fluorescence intensity ratio (FIR) technology of Pr3+ ions and [NbO6] groups was carried out using non-thermal coupling pairs, through the Boltzmann fitting and integral calculation, the maximum Sr and Sa values were 2.25% K-1 and 0.0049 K-1 at 403 K and 443 K, respectively, the Sr value is four times that obtained from the thermal coupling of Pr3+ ions, which exceeded most values previously reported for the fluorescence powder. Accordingly, we also studied the thermal sensitivity of Er3+ ions and Eu3+ ions mono-doped CaNb2O6 substrates. Results reveal that CaNb2O6:Pr3+/Er3+/Eu3+ phosphors have splendid temperature sensitivity and have far-reaching application prospects in the field of temperature measurements.
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http://dx.doi.org/10.1039/d1dt00933hDOI Listing
May 2021

Predictors of fatal outcomes of hospitalized COVID-19 patients with pre-existing hypertension in China.

Clin Respir J 2021 May 3. Epub 2021 May 3.

State Key Laboratory of Respiratory Diseases, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Background: Coronavirus disease 2019 (COVID-19) is an emerging, rapidly evolving pandemic, hypertension is one of the most common co-existing chronic conditions and a risk factor for mortality. Nearly one third of the adult population are hypertensive worldwide, it is urgent to identify the factors that determine the clinical course and outcomes of COVID-19 patients with hypertension.

Methods And Results: 148 COVID-19 patients with pre-existing hypertension with clarified outcomes (discharge or deceased) from a national cohort in China were included in this study, of whom 103 were discharged and 45 died in hospital. Multivariate regression showed higher odds of in-hospital death associated with high-sensitivity cardiac troponin (hs-cTn) > 28 pg/mL (hazard ratio [HR]: 3.27, 95% confidence interval [CI]: 1.55-6.91) and interleukin-6 (IL-6) > 7 pg/mL (HR: 3.63, 95% CI:1.54-8.55) at admission. Patients with uncontrolled blood pressure (BP) (n = 52) which were defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg for more than once (≥ 2 times) during hospitalization, were more likely to have ICU admission (P=0.037), invasive mechanical ventilation (P=0.028), and renal injury (P=0.005). A stricter BP control with the threshold of 130/80 mmHg was associated with lower mortality. Treatment with renin-angiotensin-aldosterone system (RAAS) suppressors, including angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB) and spironolactone, was associated with lower rate of ICU admission compared to other types of anti-hypertensive medications (8 (22.9%) Vs. 25 (43.1%), P=0.048).

Conclusion: Among COVID-19 patients with pre-existing hypertension, elevated hs-cTn and IL-6 could help clinicians to identify patients with fatal outcomes at an early stage, blood pressure control is associated with better clinical outcomes, and RAAS suppressors do not increase mortality and may decrease the need of ICU admission.
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http://dx.doi.org/10.1111/crj.13382DOI Listing
May 2021

Population genomics provides insights into the evolution and adaptation to humans of the waterborne pathogen Mycobacterium kansasii.

Nat Commun 2021 05 3;12(1):2491. Epub 2021 May 3.

Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Medical College and School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii's success and its ongoing adaptation to the human host.
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http://dx.doi.org/10.1038/s41467-021-22760-6DOI Listing
May 2021

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Drug Metab Dispos 2021 May 3. Epub 2021 May 3.

Drug Metabolism and Pharmacokinetics, Alnylam Pharmaceuticals Inc., United States

Givosiran is a N-acetylgalactosamine (GalNAc)-conjugated RNA interference (RNAi) therapeutic that targets 5'-aminolevulinate synthase 1 () messenger RNA (mRNA) in the liver and is currently marketed for the treatment of acute hepatic porphyria (AHP). Herein, nonclinical pharmacokinetic (PK) and absorption, distribution, metabolism, and excretion (ADME) properties of givosiran were characterized. Givosiran was completely absorbed after subcutaneous (SC) administration with relatively short plasma elimination t (less than 4 hours). Plasma exposure increased approximately dose proportionally with no accumulation after repeat doses. Plasma protein binding (PPB) was concentration dependent across all species tested and was around 90% at clinically relevant concentration in human. Givosiran predominantly distributed to the liver by asialoglycoprotein receptor (ASGPR)-mediated uptake, and the elimination t in the liver was significantly longer (~1 week). Givosiran was metabolized by nucleases, not cytochrome P450 (CYP) isozymes, across species with no human unique metabolites. Givosiran metabolized to form one primary active metabolite with the loss of 1 nucleotide from the 3' end of antisense strand, AS(N‑1)3' givosiran which was equipotent to givosiran. Renal and fecal excretion were minor routes of elimination of givosiran as approximately 10% and 16% of the dose was recovered intact in excreta of rats and monkeys, respectively. Givosiran is not a substrate, inhibitor, or inducer of CYP isozymes, and it is not a substrate or inhibitor of uptake and most efflux transporters. Thus, givosiran has a low potential of mediating drug-drug interactions involving CYP isozymes and drug transporters. Nonclinical PK and ADME properties of givosiran, the first approved GalNAc-conjugated RNAi therapeutic, were characterized. Givosiran shows similar PK and ADME properties across rats and monkeys in vivo and across human and animal matrices in vitro. SC administration results in adequate exposure of givosiran to the target organ (liver). These studies support the interpretation of toxicology studies, help characterize the disposition of givosiran in humans, and support the clinical use of givosiran for the treatment of AHP.
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http://dx.doi.org/10.1124/dmd.121.000381DOI Listing
May 2021

Association of 5-HTR2A -1438A/G polymorphism with anorexia nervosa and bulimia nervosa: A meta-analysis.

Neurosci Lett 2021 Apr 30;755:135918. Epub 2021 Apr 30.

Molecular Biology Laboratory, Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310013, China. Electronic address:

Although a number of studies have been conducted on the association of -1438A/G polymorphism in serotonin 2A receptor (5-HTR2A) gene with anorexia nervosa (AN) and bulimia nervosa (BN), the results remained inconsistent. We thus performed a meta-analysis to clarify the effects of -1438A/G polymorphism on the risk of AN and BN. PubMed, Embase, the Cochrane Library, CNKI, Weipu and Wanfang databases were searched for eligible studies. Pooled odds ratio (OR) and 95 % confidence interval (CI) were calculated to estimate the strength of the association. Subgroup analysis was also performed by ethnicity. In total, 17 studies were included for the meta-analysis, of which 15 studies containing 2028 cases and 2725 controls were used for AN analysis and 7 studies containing 505 cases and 1129 controls for BN analysis. The results showed -1438A/G polymorphism was significantly associated with the risk of AN in four genetic models (allele model, A vs. G: OR = 1.31, 95 % CI = 1.11-1.64, P = 0.003; recessive model, AA vs. GA + GG: OR = 1.69, 95 % CI = 1.28-2.23, P = 0.000; dominant model, AA + GA vs. GG: OR = 1.35, 95 % CI = 1.02-1.79, P = 0.037; co-dominant model, AA vs. GG: OR = 1.94, 95 % CI = 1.29-2.92, P = 0.002) in Caucasians, but not in Asians. We failed to observe a significant association between -1438A/G polymorphism and the risk of BN either in overall or in Caucasian population. The present meta-analysis indicated that A allele and AA genotype of 5-HTR2A -1438A/G polymorphism may contribute to higher risk of AN, especially in Caucasians. However, this polymorphism was not associated with the susceptibility to BN.
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http://dx.doi.org/10.1016/j.neulet.2021.135918DOI Listing
April 2021

Functional connectivity abnormalities underlying mood disturbances in male abstinent methamphetamine abusers.

Hum Brain Mapp 2021 May 3. Epub 2021 May 3.

Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.

Anxiety and depression are the most common withdrawal symptoms of methamphetamine (METH) abuse, which further exacerbate relapse of METH abuse. To date, no effective pharmacotherapy exists for METH abuse and its withdrawal symptoms. Therefore, understanding the neuromechanism underlying METH abuse and its withdrawal symptoms is essential for developing clinical strategies and improving patient care. The aims of this study were to investigate brain network abnormalities in METH abusers (MAs) and their associations with affective symptoms. Forty-eight male abstinent MAs and 48 age-gender matched healthy controls were recruited and underwent resting state functional magnetic resonance imaging (fMRI). The severity of patient anxiety and depressive symptoms were measured by Hamilton anxiety and depression rating scales, which decreased across the duration of abstinence. Independent component analysis was used to investigate the brain network functional connectivity (FC) properties. Compared with healthy controls, MAs demonstrated hypo-intra-network FC in the cerebellar network and hyper-intra-network FC in the posterior salience network. A whole-brain regression analysis revealed that FC strength of clusters located in the right rostral anterior cingulate cortex (rACC) within the ventromedial network (VMN) was associated with affective symptoms in the patients. Importantly, the intra-network FC strength of the rACC in VMN mediated the association between abstinence duration and the severity level of affective symptoms. Our results demonstrate alterations in brain functional networks underlying METH abuse, and that the FC of rACC within VMN serve as a neural substrate in the association between abstinence length and affective symptom severity in the MAs.
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http://dx.doi.org/10.1002/hbm.25439DOI Listing
May 2021

Preterm Birth Prevention in Appalachia: Restructuring Prenatal Care to Address Rural Health Disparities and Establish Perinatal Health Equity.

Health Equity 2021 21;5(1):203-209. Epub 2021 Apr 21.

Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky, USA.

This perspective piece reflects off previously published qualitative work to explore (1) themes surrounding equitable prenatal care in Appalachia and (2) strategies to restructure care delivery in a population with disparate rates of preterm birth (PTB). This study reflects in-depth interviews with 22 Appalachian women who experienced PTB and 14 obstetric providers. Our findings underscore the need for greater cultural humility in prenatal care, heightened awareness of social determinants of health, and strategic planning to establish equity in birth outcomes. Prenatal care must undergo a paradigm shift to include a comprehensive discussion of cultural humility, social disparities, and health equity.
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http://dx.doi.org/10.1089/heq.2020.0064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080929PMC
April 2021

A Survey of Smallholder Farms Regarding Demographics, Health Care, and Management Factors of Donkeys in Northeastern China.

Front Vet Sci 2021 14;8:626622. Epub 2021 Apr 14.

Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.

Essential information on the population dynamics and the health and welfare of Chinese donkeys is scarce. The objectives of this study were to describe the demographic characteristics, management and health care of a sample of donkeys under smallholder farm conditions of northeastern China. A cross-sectional survey of 731 randomly selected donkey owners on smallholder farms (1,658 donkeys) in 40 villages of northeastern China was conducted. Data on the composition and management of the donkeys and their routine health care were analyzed. The surveyed donkey population consisted of mostly (83.8%) jenny/filly donkeys with a mean age of 6.2 ± 5.0 years. Most (91.2%) of the farms kept 1-4 donkeys. The majority of donkeys were used for breeding and labor. Most (93.8%) of the farms did not have bedding, and their mean stable size was 17.7 ± 10.1 m. All of the animals were turned out for at least part of the year. The mean size of the turnout areas on the farms was 17.8 m. The condition of 12.5% of the donkeys was evaluated as "poor" with a body condition score of 1 on a scale of 5. More than one third (37.9%) of the donkeys had never been dewormed. Also, none of them were ever vaccinated or received dental care from a veterinarian. Their hoofs were trimmed once (45.9%) or twice (27.6%) a year. Forty percent of the donkeys were reported to suffer from at least one medical problem in the preceding year. The most common medical problems were colic, respiratory disorders and skin conditions. Owners seemed to underestimate some of the most prevalent diseases in donkeys, suggesting that their knowledge of the management of donkeys, including routine healthcare practices should be improved to ensure the health and welfare of donkeys in northeastern China.
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http://dx.doi.org/10.3389/fvets.2021.626622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079733PMC
April 2021

Evaluation of hemodynamic changes in nonarteritic anterior ischemic optic neuropathy using multimodality imaging.

Quant Imaging Med Surg 2021 May;11(5):1932-1945

Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Background: Nonarteritic anterior ischemic optic neuropathy (NAION) patients experience hypo-perfusion in the short posterior ciliary arteries (SPCAs), however, the cause of hypo-perfusion is unclear. Real-time dynamic hemodynamic observations may provide clues into specific NAION pathogenic mechanisms. We aim to analyze hemodynamic changes occurring in NAION using multimodality imaging. Our specific focus is identifying pathogenic mechanisms underlying SPCA insufficiency in NAION.

Methods: Three-dimensional arterial spin labeling (3D ASL) magnetic resonance imaging (MRI) and three-dimensional time-of-flight (3D-TOF) magnetic resonance angiography (MRA) were performed on 25 NAION patients (50 eyes) and 22 (44 eyes) normal cases were recruited. The diameter of the initial part of the ophthalmic artery and internal carotid artery siphon were measured using MRA. Blood vessel identification and blood flow (BF) were detected using 3D ASL MRI. We measured BF values of the optic nerve head (ONH) region of the retina/choroid complex, optic nerve (ON), temporal lobe, and occipital lobe.

Results: We studied 32 NAION affected eyes, 18 NAION uninvolved eyes, and 44 normal eyes. Diameter of the initial part of ophthalmic artery in the NAION affected eyes was significantly larger than the uninvolved eyes (P=0.026). Diameter of the NAION eyes was 1.33±0.19 mm [mean ± standard deviation (SD)], uninvolved eyes were 1.15±0.21 mm. At a photolabeling delay times (PLD) of 1,500 and 2,500 ms, BF of the ONH and ON in NAION affected eyes was significantly less than uninvolved and normal eyes (pONH <0.001 both at 1,500 and 2,500 ms, pON <0.001 and pON =0.001 at 1,500 and 2,500 ms, respectively). ONH of uninvolved eyes was also significantly less than normal eyes. Additionally, BF of the ONH region correlated with temporal lobe BF, with an R=0.3231 and 0.2397 at 1,500 and 2,500 ms, respectively. BF of the ONH region also correlated with occipital lobe BF, with an R=0.2534 and 0.4397 at 1,500 and 2,500 ms, respectively. ON and temporal lobe BF also correlated, with an R=0.226 and 0.1504 at 1,500 and 2,500 ms, respectively.

Conclusions: Abnormal hemodynamics of small cerebral vessels existed prior to the onset of NAION. A candidate mechanism underlying NAION appears to be transient insufficiency of blood supply and decompensation of ocular vascular regulation.
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http://dx.doi.org/10.21037/qims-20-699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047350PMC
May 2021

Accelerating Epidemiological Investigation Analysis by Using NLP and Knowledge Reasoning: A Case Study on COVID-19.

AMIA Annu Symp Proc 2020 25;2020:1258-1267. Epub 2021 Jan 25.

IBM Research, Beijing, China.

COVID-19 is threatening the health of the entire human population. In order to control the spread of the disease, epidemiological investigations should be conducted, to trace the infection source of each confirmed patient and isolate their close contacts. However, the analysis on a mass of case reports in epidemiological investigation is extremely time-consuming and labor-intensive. This paper presents an end-to-end framework for automatic epidemiological case report analysis and inference, in which a Tuple-based Multi-Task Neural Network (TMT-NN) is designed and implemented for jointly recognizing epidemiological entities and relations from case reports, and an epidemiological knowledge graph and its corresponding inference engine are built to uncover the infection modes, sources and pathways. Preliminary experiments demonstrate the promising results, and we published a real data set of COVID-19 epidemiological investigation corpora at Github, as well as contributing our COVID-19 epidemiological knowledge graph to the open community OpenKG.cn.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075493PMC
May 2021