Publications by authors named "Hong Ding"

486 Publications

[Consensus on collaborative ethical review of multi-center clinical trials of new drugs of traditional Chinese medicine (version 1.0)].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(7):1696-1700

the First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510407, China.

At present, the issues regarding multi-center clinical trials of new drugs of traditional Chinese medicine(TCM) remain: the lack of agreement on the content and scope of the ethical review among the ethics committee members of the center and the participating units results in repeated review, which leads to a time-consuming ethical review process. Moreover, the review capabilities of the ethics committees of various research centers are uneven, which is not necessarily beneficial to the protection of subjects' rights and safety. In view of the existing problems, to improve the efficiency of ethical review of multi-center clinical trials of new drugs of TCM and avoid repeated reviews, the TCM Clinical Evaluation Professional Committee of Chinese Pharmaceutical Association organized experts to formulate the "Consensus on collaborative ethical review of multi-center clinical trials of new drugs of TCM(version 1.0)"(hereinafter referred to as "Consensus"). The "Consensus" is formulated in accordance with the requirements of relevant documents such as but not limited to "the opinions on deepening the reform of the evaluation and approval system to encourage the innovation of pharmaceutical medical devices", "the regulations of ethical review of biomedical research involving human subjects". The "Consensus" covers the scope of application, formulation principles, conditions for the ethics committee of the center, sharing of ethical review resources, scope and procedure of collaborative review, rights and obligations, etc. The aims of the "Consensus" is to preliminarily explore and establish a scientific and operable ethical review procedure. Additionally, on the basis of fully protecting the rights and interests of the subjects, a collaborative ethical review agreement needs to be signed to clarify the ethical review responsibilities of all parties, to avoid repeated review, and to improve the efficiency and quality of ethical review in multi-center clinical trials of new drugs of TCM.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210304.501DOI Listing
April 2021

[Data collection, quality and evidence formation for human use experience of traditional Chinese medicine].

Zhongguo Zhong Yao Za Zhi 2021 Apr;46(7):1681-1685

the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine Changsha 410007, China.

Collecting and summarizing human use experience(HUE) data, forming high-quality data and evidences that can be used for evaluation are the key links of HUE research on traditional Chinese medicine(TCM). The collection, collation and summary of human experience data were discussed in this paper. It is pointed out that the collection of HUE should be focus on the source of prescription of new traditional Chinese medicines, and be summarized based on dialectical thinking, experience in medication, characte-ristics of prescription and clinical application. The collected contents include prescription, process, clinical location and applicable population, efficacy data and safety data, etc. The methods include interview, clinical data summary and data mining. When the data formed based on HUE information is used as drug registration information, it is necessary to ensure that the data source is legal and compliant, and the ownership of intellectual property is clear.Data sources should meet the requirements of medical ethics. To avoid conflict of interest, data analysis should be conducted by an independent third party. It is necessary to develop the quality control measures of HUE data to ensure the data traceability, integrity, consistency and accuracy, and avoid data bias.The data of HUE should include the key data such as accurate clinical location and applicable population, recognized clinical efficacy and safety.After the formation of HUE, the statistical analysis plan of empirical data of human use should be formulated. Through strict data processing, statistical analysis and clinical interpretation, HUE can be produced for evaluation.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20210122.501DOI Listing
April 2021

A narrative review of COVID-19: magnesium isoglycyrrhizinate as a potential adjuvant treatment.

Ann Palliat Med 2021 Apr 9;10(4):4777-4798. Epub 2021 Apr 9.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.

Coronavirus disease 2019 (COVID-19) has become a global pandemic affecting more than 200 countries with 87 million patients worldwide as of January 7, 2021. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replicates in a large amount and reaches high-titer levels in a short time after the infection. COVID-19 caused by SARS-CoV-2 shows clinical symptoms mainly including fever, fatigue, dry cough, and dyspnea. In more severe COVID-19 patients, viral pneumonia characterized by bilateral ground glass or patchy opacity, may lead to acute respiratory distress syndrome (ARDS), cytokine storm, multi-organ damage, and even death. Unfortunately, there is no effective therapy for COVID-19 until now. Magnesium isoglycyrrhizinate (MgIG), a magnesium salt of 18-α glycyrrhizic acid stereoisomer, belongs to the fourth generation of glycyrrhizic acid preparation. MgIG has various pharmacological activities including anti-inflammation, anti-oxidation, anti-virus, and immunoregulation, showing the protection against the injury of the vital organs (such as kidney, heart, and lung). Clinically, MgIG injection is usually used as a hepatoprotective agent to treat liver diseases. This narrative review summarizes the research and application of MgIG, and provides the evidence supporting the recommended MgIG as supportive therapy in the "Management Standard for Mild and Common Patients of Coronavirus Disease 2019 (COVID-19) (Second Edition)", which is jointly issued by National Health Commission of People's Republic of China and National Administration of Traditional Chinese Medicine.
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http://dx.doi.org/10.21037/apm-20-1971DOI Listing
April 2021

PRMT1 is a novel molecular therapeutic target for clear cell renal cell carcinoma.

Theranostics 2021 12;11(11):5387-5403. Epub 2021 Mar 12.

Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Epigenetic alterations are common events in clear cell renal cell carcinoma (ccRCC), and protein arginine methyltransferase 1 (PRMT1) is an important epigenetic regulator in cancers. However, its role in ccRCC remains unclear. We investigated PRMT1 expression level and its correlations to clinicopathological factors and prognosis in ccRCC patients based on ccRCC tissue microarrays (TMAs). Genetic knockdown and pharmacological inhibition using a novel PRMT1 inhibitor DCPT1061 were performed to investigate the functional role of PRMT1 in ccRCC proliferation. Besides, we confirmed the antitumor effect of PRMT1 inhibitor DCPT1061 in ccRCC cell-derived tumor xenograft (CDX) models as well as patient-derived tumor xenograft (PDX) models. We found PRMT1 expression was remarkably upregulated in tumor tissues and associated with poor pathologic characters and outcomes of ccRCC patients. Furthermore, genetic knockdown and pharmacological inhibition of PRMT1 by a novel potent inhibitor DCPT1061 dramatically induced G1 cell cycle arrest and suppressed ccRCC cell growth. Mechanistically, RNA sequencing and further validation identified Lipocalin2 (LCN2), a secreted glycoprotein implicated in tumorigenesis, as a crucial regulator of ccRCC growth and functional downstream effector of PRMT1. Epigenetic silencing of LCN2 autocrine secretion by PRMT1 deficiency decreased downstream p-AKT, leading to reduced p-RB and cell growth arrest through the neutrophil gelatinase associated lipocalin receptor (NGALR). Moreover, PRMT1 inhibition by DCPT1061 not only inhibited tumor growth but also sensitized ccRCC to sunitinib treatment by attenuating sunitinib-induced upregulation of LCN2-AKT-RB signaling. Taken together, our study revealed a PRMT1-dependent epigenetic mechanism in the control of ccRCC tumor growth and drug resistance, indicating PRMT1 may serve as a promising target for therapeutic intervention in ccRCC patients.
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http://dx.doi.org/10.7150/thno.42345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039964PMC
March 2021

P300/CBP inhibition sensitizes mantle cell lymphoma to PI3Kδ inhibitor idelalisib.

Acta Pharmacol Sin 2021 Apr 13. Epub 2021 Apr 13.

Drug Discovery and Design Center, The Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Here we report that a p300/CBP inhibitor, A-485, could overcome resistance to idelalisib in MCL cells in vitro and in vivo. A-485 was discovered in a combinational drug screening from an epigenetic compound library containing 45 small molecule modulators. We found that A-485, the highly selective catalytic inhibitor of p300 and CBP, was the most potent compound that enhanced the sensitivity of MCL cell line Z-138 to idelalisib. Combination of A-485 and idelalisib remarkably decreased the viability of three MCL cell lines tested. Co-treatment with A-485 and idelalisib in Maver-1 and Z-138 MCL cell xenograft mice for 3 weeks dramatically suppressed the tumor growth by reversing the unsustained inhibition in PI3K downstream signaling. We further demonstrated that p300/CBP inhibition decreased histone acetylation at RTKs gene promoters and reduced transcriptional upregulation of RTKs, thereby inhibiting the downstream persistent activation of MAPK/ERK signaling, which also contributed to the pathogenesis of MCL. Therefore, additional inhibition of p300/CBP blocked MAPK/ERK signaling, which rendered maintaining activation to PI3K-mTOR downstream signals p-S6 and p-4E-BP1, thus leading to suppression of cell growth and tumor progression and eliminating the intrinsic resistance to idelalisib ultimately. Our results provide a promising combination therapy for MCL and highlight the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor.
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http://dx.doi.org/10.1038/s41401-021-00643-2DOI Listing
April 2021

Discovery of [Formula: see text] rotation anomaly in topological crystalline insulator SrPb.

Nat Commun 2021 Apr 6;12(1):2052. Epub 2021 Apr 6.

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing, China.

Topological crystalline insulators (TCIs) are insulating electronic states with nontrivial topology protected by crystalline symmetries. Recently, theory has proposed new classes of TCIs protected by rotation symmetries [Formula: see text], which have surface rotation anomaly evading the fermion doubling theorem, i.e., n instead of 2n Dirac cones on the surface preserving the rotation symmetry. Here, we report the first realization of the [Formula: see text] rotation anomaly in a binary compound SrPb. Our first-principles calculations reveal two massless Dirac fermions protected by the combination of time-reversal symmetry [Formula: see text] and [Formula: see text] on the (010) surface. Using angle-resolved photoemission spectroscopy, we identify two Dirac surface states inside the bulk band gap of SrPb, confirming the [Formula: see text] rotation anomaly in the new classes of TCIs. The findings enrich the classification of topological phases, which pave the way for exploring exotic behavior of the new classes of TCIs.
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http://dx.doi.org/10.1038/s41467-021-22350-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024327PMC
April 2021

18β-Glycyrrhetinic acid alleviates demyelination by modulating the microglial M1/M2 phenotype in a mouse model of cuprizone-induced demyelination.

Neurosci Lett 2021 Apr 1;755:135871. Epub 2021 Apr 1.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, PR China. Electronic address:

This research aimed to examine the nutritious supplementary function of 18β-Glycyrrhetinic acid (18β-GA) in moderating the myelin sheath destruction and behavioral impairments observed in the cuprizone model of demyelination. Mice were fed daily on food containing cuprizone (0.3 %) and given doses of 18β-GA (5 or 1 mg/kg) for a period of five weeks. The groups treated with 18β-GA exhibited improvements in exploratory behavior, locomotive activity, and weight. As assessed using luxol-fast blue and myelin basic protein (MBP) staining, which were used to detect demyelination in the brain, 18β-GA both reduced and prevented instances of cuprizone-induced demyelinating lesions; treatment with 18β-GA also caused the MBP level in the corpus callosum to increase. Furthermore, alongside these positive results following 18β-GA treatment, microglial polarisation was also observed to shift towards the beneficial M2 phenotype. The results of this research thus indicate the potential clinical application of 18β-GA for the prevention of myelin damage and behavioral dysfunction.
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http://dx.doi.org/10.1016/j.neulet.2021.135871DOI Listing
April 2021

Unraveling the Orbital Physics in a Canonical Orbital System KCuF_{3}.

Phys Rev Lett 2021 Mar;126(10):106401

Diamond Light Source, Harwell Campus, Didcot OX11 0DE, United Kingdom.

We explore the existence of the collective orbital excitations, orbitons, in the canonical orbital system KCuF_{3} using the Cu L_{3}-edge resonant inelastic x-ray scattering. We show that the nondispersive high-energy peaks result from the Cu^{2+}  dd orbital excitations. These high-energy modes display good agreement with the ab initio quantum chemistry calculation, indicating that the dd excitations are highly localized. At the same time, the low-energy excitations present clear dispersion. They match extremely well with the two-spinon continuum following the comparison with Müller ansatz calculations. The localized dd excitations and the observation of the strongly dispersive magnetic excitations suggest that the orbiton dispersion is below the resolution detection limit. Our results can reconcile with the strong local Jahn-Teller effect in KCuF_{3}, which predominantly drives orbital ordering.
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http://dx.doi.org/10.1103/PhysRevLett.126.106401DOI Listing
March 2021

Synthetic Approaches to the New Drugs Approved during 2019.

J Med Chem 2021 Apr 30;64(7):3604-3657. Epub 2021 Mar 30.

Pfizer Worldwide Research and Development, 445 Eastern Point Road, Groton, Connecticut 06340, United States.

New drugs introduced to the market are privileged structures having affinities for biological targets implicated in human diseases and conditions. These new chemical entities (NCEs), particularly small molecules and antibody-drug conjugates, provide insight into molecular recognition and simultaneously function as leads for the design of future medicines. This review is part of a continuing series presenting the most likely process-scale synthetic approaches to 40 NCEs approved for the first time anywhere in the world in 2019.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00208DOI Listing
April 2021

Mediation role of perceived social support and burnout on financial satisfaction and turnover intention in primary care providers: a cross-sectional study.

BMC Health Serv Res 2021 Mar 19;21(1):252. Epub 2021 Mar 19.

School of Health Service Management, Anhui Medical University, No.81 Meishan Road, Shushan District, Hefei, 230032, China.

Background: Turnover intention is a major cause of reduced team morale and low work efficiency. It hinders work performance and reduces the quality of medical services. This study aimed to investigate the relationship between financial satisfaction and turnover intention and its mediators among primary care providers.

Methods: Multi-stage random cluster sampling was used to select 1241 participants from four counties and three districts in Anhui province, China. Data were collected using a self-administered questionnaire. Turnover intention was assessed with a turnover intention assessment scale. Perceived social support and burnout were measured with the 12-item Perceived Social Support Scale and the Chinese version of the Maslach Burnout Inventory, respectively. Structural equation modeling was used for data analysis.

Results: The findings showed high turnover intention among primary care providers (mean score 14.16 ± 4.337), and most providers reported low financial satisfaction (mean score 2.49 ± 0.990). The mean perceived social support score was 64.93 ± 13.229, and only 6.1% of primary care providers reported no burnout. Compared with participants with high financial satisfaction, those with low financial satisfaction were more likely to report higher turnover intention (β = - 0.216, p < 0.001), less perceived social support (β = 0.181, p < 0.001), and more severe burnout (β = - 0.123, p < 0.05). Turnover intention may be related to perceived social support (β = - 0.147, p < 0.001) and burnout (β = 0.239, p < 0.001). Furthermore, the effect of financial satisfaction on turnover intention was significantly mediated by perceived social support (β = - 0.027, p < 0.001) and burnout (β = - 0.029, p < 0.05).

Conclusions: Turnover intention is associated with financial satisfaction, with this association mediated by perceived social support and burnout. A reasonable mechanism needs to be established to improve financial satisfaction and perceived social support and reduce burnout among primary care providers.
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http://dx.doi.org/10.1186/s12913-021-06270-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980677PMC
March 2021

Insulin injections inhibits PTZ-induced mitochondrial dysfunction, oxidative stress and neurological deficits via the SIRT1/PGC-1α/SIRT3 pathway.

Biochim Biophys Acta Mol Basis Dis 2021 Jun 13;1867(6):166124. Epub 2021 Mar 13.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China. Electronic address:

With an associated 20% death risk, epilepsy mainly involves seizures of an unpredictable and recurrent nature. This study was designed to evaluate the neuroprotective effects and underlying mechanisms of insulin on mitochondrial disruption, oxidative stress, cell apoptosis and neurological deficits after epilepsy seizures. Mice were exposed to repetitive injections of pentylenetetrazol at a dose of 37 mg per kg. The influence of insulin was assessed by many biochemical assays, histopathological studies and neurobehavioral experiments. The administration of insulin was proven to increase the latency of seizures while also decreasing their intensity. It also caused a reversal of mitochondrial dysfunction and ameliorated oxidative stress. Additionally, insulin pretreatment upregulated Bcl-2, downregulated Bax, and then played a neuroprotective role against hippocampal neuron apoptosis. Furthermore, when insulin was administered, SIRT1/PGC-1α/SIRT3 signals were activated, possibly due to the fact that insulin's neuroprotective and anti-mitochondrial damage characteristics added to its observed antiepileptic functions. Finally, insulin treatment is thus extremely valuable for effecting improvements in neurological functions, as has been estimated in a series of functional tests. In conclude, the results of this study consequently demonstrate insulin to have significant potential for future application in epilepsy management.
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http://dx.doi.org/10.1016/j.bbadis.2021.166124DOI Listing
June 2021

A Comprehensive Review of Viral Characteristics, Transmission, Pathophysiology, Immune Response, and Management of SARS-CoV-2 and COVID-19 as a Basis for Controlling the Pandemic.

Front Immunol 2021 26;12:631139. Epub 2021 Feb 26.

Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, Doha, Qatar.

COVID-19 emerged from China in December 2019 and during 2020 spread to every continent including Antarctica. The coronavirus, SARS-CoV-2, has been identified as the causative pathogen, and its spread has stretched the capacities of healthcare systems and negatively affected the global economy. This review provides an update on the virus, including the genome, the risks associated with the emergence of variants, mode of transmission, immune response, COVID-19 in children and the elderly, and advances made to contain, prevent and manage the disease. Although our knowledge of the mechanics of virus transmission and the immune response has been substantially demystified, concerns over reinfection, susceptibility of the elderly and whether asymptomatic children promote transmission remain unanswered. There are also uncertainties about the pathophysiology of COVID-19 and why there are variations in clinical presentations and why some patients suffer from long lasting symptoms-"." To date, there are no significantly effective curative drugs for COVID-19, especially after failure of hydroxychloroquine trials to produce positive results. The RNA polymerase inhibitor, remdesivir, facilitates recovery of severely infected cases but, unlike the anti-inflammatory drug, dexamethasone, does not reduce mortality. However, vaccine development witnessed substantial progress with several being approved in countries around the globe.
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http://dx.doi.org/10.3389/fimmu.2021.631139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952616PMC
March 2021

Increased portal vein diameter is predictive of portal vein thrombosis development in patients with liver cirrhosis.

Ann Transl Med 2021 Feb;9(4):289

Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Cirrhotic patients with portal vein thrombosis (PVT) may have a high risk of hepatic decompensation and increased mortality. This study aimed to investigate if increased portal vein diameter is associated with PVT development.

Methods: A total of 174 cirrhotic patients were enrolled between February 1 and August 31, 2017. All participants were divided into PVT (n=62) and non-PVT (n=112) groups based on the thrombus that was detected by ultrasonography and confirmed by computed tomography angiography (CTA).

Results: The study participants, aged 54.7±10.5 years (PVT) and 55.8±11.6 years (non-PVT), were included in this analysis. The Child-Pugh score of PVT or non-PVT was 6.6±1.3 and 5.8±0.9, respectively. Hepatitis B virus (HBV) is the primary etiological agent of cirrhosis. Logistic regression, receiver operating characteristic (ROC), and nomograph analysis designated portal diameter as the strongest independent risk factor for predicting PVT development [odds ratio (OR): 3.96, area under the ROC curve (AUC): 0.88; P<0.01], and the cutoff with predictive value for PVT development was >12.5 mm. No differences were observed in the overall survival (OS) in cirrhosis with or without PVT or stratifying on portal diameter based on the cutoff value.

Conclusions: Increased portal diameter is associated with an increased risk of PVT development. Patients with cirrhosis and increased portal diameter are a high-risk subgroup that may need thromboprophylaxis.
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http://dx.doi.org/10.21037/atm-20-4912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944309PMC
February 2021

Study on the neuroprotective effects of Genistein on Alzheimer's disease.

Brain Behav 2021 May 11;11(5):e02100. Epub 2021 Mar 11.

Department of Traditional Chinese Medicine, the Second Hospital of Jilin University, Changchun, China.

Along with the aging of the world population, the incidence rate of Alzheimer's disease (AD) has been increasing. At present, AD has become one of the most serious problems faced by modern medicine. Studies have shown that estrogen has a positive effect on AD, but estrogen has the side effect of leading to tumors. Recent in vivo studies have shown that genistein, one of the selective estrogen receptor modulators (SERMs), can improve brain function through the blood-brain barrier (BBB), antagonize the toxicity of amyloid β-protein (Aβ), that is, to inhibit neurotoxicity due to aggregation of beta amyloid protein, and have neuroprotective effects. In addition, the use of Gen can avoid the risk of endometrial cancer and breast cancer caused by estrogen therapy while exerting an estrogen-like effect, which has some potential for the delay and treatment of AD.
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http://dx.doi.org/10.1002/brb3.2100DOI Listing
May 2021

Observation of magnetic adatom-induced Majorana vortex and its hybridization with field-induced Majorana vortex in an iron-based superconductor.

Nat Commun 2021 Mar 1;12(1):1348. Epub 2021 Mar 1.

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing, China.

Braiding Majorana zero modes is essential for fault-tolerant topological quantum computing. Iron-based superconductors with nontrivial band topology have recently emerged as a surprisingly promising platform for creating distinct Majorana zero modes in magnetic vortices in a single material and at relatively high temperatures. The magnetic field-induced Abrikosov vortex lattice makes it difficult to braid a set of Majorana zero modes or to study the coupling of a Majorana doublet due to overlapping wave functions. Here we report the observation of the proposed quantum anomalous vortex with integer quantized vortex core states and the Majorana zero mode induced by magnetic Fe adatoms deposited on the surface. We observe its hybridization with a nearby field-induced Majorana vortex in iron-based superconductor FeTeSe. We also observe vortex-free Yu-Shiba-Rusinov bound states at the Fe adatoms with a weaker coupling to the substrate, and discover a reversible transition between Yu-Shiba-Rusinov states and Majorana zero mode by manipulating the exchange coupling strength. The dual origin of the Majorana zero modes, from magnetic adatoms and external magnetic field, provides a new single-material platform for studying their interactions and braiding in superconductors bearing topological band structures.
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http://dx.doi.org/10.1038/s41467-021-21646-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921435PMC
March 2021

Current status and related factors of turnover intention of primary medical staff in Anhui Province, China: a cross-sectional study.

Hum Resour Health 2021 Feb 27;19(1):23. Epub 2021 Feb 27.

School of Health Management, Anhui Medical University, No. 81, Meishan Road Shushan District, Hefei, 230032, Anhui, China.

Background: The shortage of primary medical staff is an important issue in the management of health human resources, and it is also a problem that all countries in the world need to face together. Since 2009, China has implemented a new series of medical system reforms and the shortage and loss of primary medical staff have been alleviated accordingly. However, China has a large population and it is difficult to distribute health human resources evenly across regions. This study aimed to explore the current status of turnover intention and its relationship with psychological capital, social support, and job burnout, as well as how these factors influence turnover intention of primary medical staff in Anhui province, China.

Methods: Using structured questionnaires to collect data, including demographic characteristics, turnover intention, psychological capital, social support, and Chinese Maslach Burnout Inventory scale. A total of 1152 primary medical workers of Anhui were investigated. Data were analyzed by t-test, analysis of variance (ANOVA), Pearson correlation analysis, and multiple linear regression model.

Results: Total scores of turnover intention, psychological capital, social support, and job burnout of subjects were 14.15 ± 4.35, 100.09 ± 15.98, 64.93 ± 13.23 and 41.07 ± 9.437, respectively. Multiple linear regression showed the related factors of turnover intention were age, job position, work unit, and scores of job burnout. Pearson correlation showed psychological capital and social support were negatively correlated with turnover intention, while the score of job burnout was positively correlated with turnover intention.

Conclusion: The improvement of psychological capital and social support and the reduction of job burnout may play an important role in reducing turnover intention of primary medical staff. Primary medical managers should strengthen the humanistic care for primary medical staff, optimize the incentive mechanism, and improve internal management of medical institutions for stability.
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http://dx.doi.org/10.1186/s12960-021-00563-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910782PMC
February 2021

Fatigue Performance and Stress Distribution of Endodontically Treated Premolars Restored with Direct Bulk-fill Resin Composites.

J Adhes Dent 2021 ;23(1):67-75

Purpose: To investigate the fatigue performance and stress distribution of endodontically treated maxillary premolars with occlusal (O), mesio-occlusal (MO), or mesio-occluso-distal (MOD) cavities filled directly with bulk-fill composite.

Materials And Methods: Besides the intact teeth (control group), sixty sound maxillary first premolars, standardized by size and morphology, were subjected to root canal treatment and randomly allocated to three groups throughout cavity preparations (O/MO/MOD). All cavities were restored with a bulk-fill composite (Tetric N-Ceram Bulk fill) and universal adhesive (Tetric N-Bond Universal) using etch-and-rinse mode. Half of the specimens of each group underwent 20,000 thermocycles (5°C-55°C). All specimens were subjected to a 50-N load perpendicular to their buccal bevels on the palatal cusps for 1,200,000 cycles. The survival curve and fracture mode were analyzed by log-rank and Fisher's exact tests, respectively. Finite element analysis (FEA) was conducted to simulate the working condition of premolars with O/MO/MOD cavities. The von Mises stress and the first principal stress were calculated for three FEA models.

Results: Premolars with O cavity restorations exhibited better stress distributions than did those with MO and MOD cavity restorations. Compared to the intact premolars, no significant difference was detected in the fatigue performance of O/MO/MOD restorations, regardless of whether they underwent thermocycling. Only one specimen presented unrestorable fracture, while the rest of the fractured premolars were restorable.

Conclusion: The cavity design of endodontic premolars restored with a bulk-fill composite has no influence on the stress distribution or fatigue survival, with a biomechanical performance similar to that of an intact tooth.
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http://dx.doi.org/10.3290/j.jad.b906631DOI Listing
February 2021

Effects and safety of herbal medicines among community-dwelling residents during COVID-19 pandemic: A large prospective, randomized controlled trial (RCT).

Phytomedicine 2021 May 5;85:153403. Epub 2020 Nov 5.

Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address:

Background: Since the declaration of COVID-19 as a global pandemic by the World Health Organization, countries are struggling with a shortage of medical capacities. It would be essential if the risk for preventable comorbidities, such as the common cold, can be reduced or prevented, so that the scarce medical resources and facilities can be focused on COVID-19.

Purpose: To evaluate the effects of two herbal medicines (Jinhaoartemisia antipyretic granules and Huoxiangzhengqi oral liquids) in reducing the risk of the common cold in community-dwelling residents in China during the COVID-19 outbreak.

Study Design: A prospective open-label, parallel-group, cluster-randomized controlled trial (RCT), was conducted in Chengdu, China.

Methods: A total of 22,065 participants from 11 communities were recruited during a period of one month. The trial started on 30 January and participants were followed up till 29 February 2020. Participants were randomly assigned to receive either a five-day herbal medicine therapy plus a reference manual or a reference manual only if they were allocated to the control group. The primary endpoint was the occurrence of patient-reported common cold symptoms. The secondary endpoint was the time in days from the receipt of herbal drugs/reference manual and the occurrence of the common cold symptoms.

Results: Use of herbal medicine reduced the risk of the common cold by 89.6% (95% CI, 52.9% to 97.7%) in all community-dwelling residents, and by 94.0% (95% CI, 52.1% to 99.2%) in residents aged between 16 and 59 years old. Sensitivity analyses showed similar results.

Conclusion: This community-based RCT found that the use of a herbal medicine therapy (Jinhaoartemisia antipyretic granules and Huoxiangzhengqi oral liquids) could significantly reduce the risks of the common cold among community-dwelling residents, suggesting that herbal medicine may be a useful approach for public health intervention to minimize preventable morbidity during COVID-19 outbreak.
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http://dx.doi.org/10.1016/j.phymed.2020.153403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642754PMC
May 2021

Quantitative evaluation of liver fibrosis based on ultrasound radio frequency signals: An animal experimental study.

Comput Methods Programs Biomed 2021 Feb 2;199:105875. Epub 2020 Dec 2.

Department of Electronic Engineering, Fudan University, No. 220, Handan Road, Shanghai 200433, China. Electronic address:

Background: Chronic liver disease is an important cause of liver failure and death worldwide, and liver fibrosis is a common pathological process of most chronic liver diseases. There still lacks a useful tool for evaluating liver fibrosis progression precisely and non-invasively. The purpose of this study was to explore the use of ultrasound radio frequency (RF) signals combined with deep learning approach to evaluate the degree of liver fibrosis quantitatively.

Methods: In this study, by extracting the output of deep learning models as a prediction value, a quantitative liver fibrosis prediction method was achieved based on the bidirectional long short-term memory (Bi-LSTM) network to analyze radio frequency (RF) signals. The dataset consisted of 160 sets of ultrasound RF signals of rat livers, including five fibrosis stages 0-4, upon pathological diagnosis. In total, 150 sets of RF signals were used to train four deep learning classification models, the output of which contained quantitative information. In each training stage of the four models, a large number of signal segments were extracted from the 150 sets and divided randomly into training and validation sets in a ratio of 80:20. Ten sets of RF data using the gold standard of quantitative fibrosis parameter (q-FP) of liver tissues were left for independent testing. To validate the proposed method, correlation analysis was carried out between q-FP and the quantitative prediction results based on the independent test data.

Results: The accuracy of the four deep learning networks using the training and validation data was above 0.83 and 0.80, and the corresponding areas under the receiver operating characteristic curves were higher than 0.95 and 0.93, respectively. For the quantitative analysis in the independent test set, the determination coefficient, R, of the linear regression analysis between the quantitative prediction results and q-FP was above 0.93. liver fibrosis is a common pathological process of most chronic liver diseases.

Conclusions: This study indicates that a prediction system based on ultrasound RF signals and a deep learning approach is promising for realizing quantitative and visualized diagnosis of liver fibrosis, which would be of great value in monitoring liver fibrosis non-invasively.
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http://dx.doi.org/10.1016/j.cmpb.2020.105875DOI Listing
February 2021

Discovery of selective CDK9 degraders with enhancing antiproliferative activity through PROTAC conversion.

Eur J Med Chem 2021 Feb 10;211:113091. Epub 2020 Dec 10.

State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address:

Cyclin-dependent kinase 9 (CDK9) is an increasingly important potential cancer treatment target. Nowadays, developing selective CDK9 inhibitors has been extremely challenging as its ATP-binding sites are similar with other CDKs. Here, we report that the CDK9 inhibitor BAY-1143572 is converted into a series of proteolysis targeting chimeras (PROTACs) which leads to several compounds inducing the degradation of CDK9 in acute myeloid leukemia cells at a low nanomolar concentration. In addition, the most potent PROTAC molecule B03 could inhibit cell growth more effectively than warhead alone, with little inhibition of other kinases. This enhanced antiproliferative activity is mediated by a slight increase in kinase inhibitory activity and an increase in the level of apoptosis induction. Moreover, B03 could induce the degradation of CDK9 in vivo. Our work provides evidence that B03 represents a lead for further development and that CDK9 degradation is a potential valuable therapeutic strategy in acute myeloid leukemia.
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http://dx.doi.org/10.1016/j.ejmech.2020.113091DOI Listing
February 2021

Topical application with conjugated linoleic acid ameliorates 2, 4-dinitrofluorobenzene-induced atopic dermatitis-like lesions in BALB/c mice.

Exp Dermatol 2021 Feb 6;30(2):237-248. Epub 2021 Jan 6.

School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.

Atopic dermatitis (AD) is a multifactorial chronic inflammatory skin disease characterized by skin barrier dysfunction, eczematous lesions, pruritus, and abnormal immune responses. In this study, we assessed the therapeutic effect of topical applied conjugated linoleic acid (CLA) on a murine AD model that was developed by repetitive applications of 2, 4-dinitrofluorobenzene (DNFB). 2% or 5% CLA could markedly ameliorate AD-like skin lesions, scratching behaviour and skin inflammation as evidenced by the reduced inflammatory blood cells, IgE and Th2-related cytokine levels, and the infiltration of mast cells and inflammatory cells to the dermal tissues. Moreover, topical application with CLA modulated skin barrier repair including maintaining a balanced skin pH and increasing skin hydration, partially mediated by upregulating skin barrier-related protein, filaggrin (FLG). In addition, topical CLA significantly dose-dependently inhibited pro-inflammatory cytokines including interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α and pro-inflammatory enzyme expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in inflamed mice skin. Its anti-inflammatory effect was associated with the inhibition of DNFB-stimulated IκBα and NF-κB p65 phosphorylation in mouse skin. Taken together, our results suggest that locally applied CLA exerts potentially protective effects against AD lesional skin at least in part, due to regulation of skin barrier function and inflammatory response.
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http://dx.doi.org/10.1111/exd.14242DOI Listing
February 2021

The Potential of Glycyrrhizinate in the Management of COVID-19: A Systematic Review of the Efficacy and Safety of Glycyrrhizin Preparations in the Treatment of SARS and MERS.

Am J Chin Med 2020 13;48(7):1539-1552. Epub 2020 Nov 13.

Department of Pharmacy, Peking University Third Hospital, Beijing 100191, P. R. China.

The SARS-CoV-2 outbreak in 2019 highlighted the fact that no specific medications providing effective treatment have been identified and approved. We explored the possibilities for COVID-19 by systematically reviewing evidence on the efficacy and safety of glycyrrhizin preparations for SARS and MERS. Electronic databases were systematically searched from inception to February 2020 for eligible studies that evaluated the efficacy and safety of glycyrrhizin preparations for SARS and MERS. A quantitative analysis or descriptive analysis was applied. Five retrospective cohort studies were included, and NOS scores ranged from 5-7 points. The clinical symptoms of dry cough, chest distress and dyspnoea improved quickly, and elevated serum levels of aminotransferase decreased after compound glycyrrhizin treatment. The SARS-CoV antibody appeared earlier in the treated group than in the control group ([Formula: see text][Formula: see text]d). Compared to that with conventional medications, the average period from peak to 50% improvement of lesions, in terms of X-ray manifestations, was shorter with compound glycyrrhizin treatment ([Formula: see text]2.1[Formula: see text]d), and treatment reduced the dosage ([Formula: see text][Formula: see text]mg/d) and duration of the corticosteroids used, without other serious adverse reactions. Based on the available evidence regarding glycyrrhizin preparations for treating SARS and MERS, we infer that compound glycyrrhizin could be an optional therapeutic strategy for SARS-CoV-2 infections, especially those complicated with liver damage. Further research using well-designed randomized clinical trials (RCTs) is warranted to determine the dosage and duration of use of compound glycyrrhizin and to monitor its specific adverse effects.
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http://dx.doi.org/10.1142/S0192415X20500767DOI Listing
December 2020

The synergy effect of arbuscular mycorrhizal fungi symbiosis and exogenous calcium on bacterial community composition and growth performance of peanut (Arachis hypogaea L.) in saline alkali soil.

J Microbiol 2021 Jan 17;59(1):51-63. Epub 2020 Nov 17.

Shandong Peanut Research Institute, Shandong Academy of Agricultural Sciences, Qingdao, Shandong, 266100, P. R. China.

Peanut (Arachis hypogaea. L) is an important oil seed crop. Both arbuscular mycorrhizal fungi (AMF) symbiosis and calcium (Ca) application can ameliorate the impact of saline soil on peanut production, and the rhizosphere bacterial communities are also closely correlated with peanut salt tolerance; however, whether AMF and Ca can withstand high-salinity through or partially through modulating rhizosphere bacterial communities is unclear. Here, we used the rhizosphere bacterial DNA from saline alkali soil treated with AMF and Ca alone or together to perform high-throughput sequencing of 16S rRNA genes. Taxonomic analysis revealed that AMF and Ca treatment increased the abundance of Proteobacteria and Firmicutes at the phylum level. The nitrogen-fixing bacterium Sphingomonas was the dominant genus in these soils at the genus level, and the soil invertase and urease activities were also increased after AMF and Ca treatment, implying that AMF and Ca effectively improved the living environment of plants under salt stress. Moreover, AMF combined with Ca was better than AMF or Ca alone at altering the bacterial structure and improving peanut growth in saline alkali soil. Together, AMF and Ca applications are conducive to peanut salt adaption by regulating the bacterial community in saline alkali soil.
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http://dx.doi.org/10.1007/s12275-021-0317-3DOI Listing
January 2021

A new Majorana platform in an Fe-As bilayer superconductor.

Nat Commun 2020 Nov 10;11(1):5688. Epub 2020 Nov 10.

Beijing National Laboratory for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, 100190, Beijing, China.

Iron-chalcogenide superconductors have emerged as a promising Majorana platform for topological quantum computation. By combining topological band and superconductivity in a single material, they provide significant advantage to realize isolated Majorana zero modes. However, iron-chalcogenide superconductors, especially Fe(Te,Se), suffer from strong inhomogeneity which may hamper their practical application. In addition, some iron-pnictide superconductors have been demonstrated to have topological surface states, yet no Majorana zero mode has been observed inside their vortices, raising a question of universality about this new Majorana platform. In this work, through angle-resolved photoemission spectroscopy and scanning tunneling microscopy/spectroscopy measurement, we identify Dirac surface states and Majorana zero modes, respectively, for the first time in an iron-pnictide superconductor, CaKFeAs. More strikingly, the multiple vortex bound states with integer-quantization sequences can be accurately reproduced by our model calculation, firmly establishing Majorana nature of the zero mode.
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http://dx.doi.org/10.1038/s41467-020-19487-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655862PMC
November 2020

A Review of the Progress and Challenges of Developing a Vaccine for COVID-19.

Front Immunol 2020 14;11:585354. Epub 2020 Oct 14.

Departments of Medical Education and Pharmacology, Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.

A novel coronavirus, which has been designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in December 2019 in Wuhan China and causes the highly infectious disease referred to as COVID-19. COVID-19 has now spread worldwide to become a global pandemic affecting over 24 million people as of August 26th, 2020 and claimed the life of more than 800,000 people worldwide. COVID-19 is asymptomatic for some individuals and for others it can cause symptoms ranging from flu-like to acute respiratory distress syndrome (ARDS), pneumonia and death. Although it is anticipated that an effective vaccine will be available to protect against COVID-19, at present the world is relying on social distancing and hygiene measures and repurposed drugs. There is a worldwide effort to develop an effective vaccine against SARS-CoV-2 and, as of late August 2020, there are 30 vaccines in clinical trials with over 200 in various stages of development. This review will focus on the eight vaccine candidates that entered Phase 1 clinical trials in mid-May, including AstraZeneca/Oxford's AZD1222, Moderna's mRNA-1273 and Sinovac's CoronaVac vaccines, which are currently in advanced stages of vaccine development. In addition to reviewing the different stages of vaccine development, vaccine platforms and vaccine candidates, this review also discusses the biological and immunological basis required of a SARS-CoV-2 vaccine, the importance of a collaborative international effort, the ethical implications of vaccine development, the efficacy needed for an immunogenic vaccine, vaccine coverage, the potential limitations and challenges of vaccine development. Although the demand for a vaccine far surpasses the production capacity, it will be beneficial to have a limited number of vaccines available for the more vulnerable population by the end of 2020 and for the rest of the global population by the end of 2021.
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http://dx.doi.org/10.3389/fimmu.2020.585354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591699PMC
December 2020

A case series evaluating the impact of a combination treatment for acne vulgaris containing linoleic acid, linolenic acid, and lecithin.

Dermatol Ther 2020 11 17;33(6):e14505. Epub 2020 Nov 17.

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan University, Wuhan, Hubei, China.

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http://dx.doi.org/10.1111/dth.14505DOI Listing
November 2020

Prenatal exposure of female mice to perfluorononanoic acid delays pubertal activation of the reproductive endocrine axis through enhanced hepatic FGF21 production.

Chemosphere 2021 Apr 27;269:128776. Epub 2020 Oct 27.

Department of Physiology, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

The developmental toxicity of perfluorononanoic acid (PFNA), a ubiquitous environmental contaminant, has been associated with the activation of PPARα. This study investigated influence of prenatal exposure to PFNA in pubertal activation of reproductive endocrine axis in female mice and explored underlying molecular mechanisms. Herein, we show that when PFNA (3 mg kg body weight) was orally administered during gestational days 1-18, dams showed an increase in liver weight and hepatic FGF21 synthesis via PPARα activation, and their female offspring (PFNA mice) showed an increase in liver weight and hepatic FGF21 synthesis from postnatal day (PND) 1 to PND21, which were corrected by the administration of the PPARα antagonist GW6471 from PND1-14 (pup-GW). Expression of vasopressin (VAP) in the hypothalamic suprachiasmatic nucleus (SCN) was reduced in PND14-30 PFNA mice, and could be rescued by pup-GW. Pubertal activation of kisspeptin neurons in anteroventral periventricular nucleus (AVPV) and hypothalamic GnRH neurons in PND21-30 PFNA mice was obviously suppressed, but were recovered by pup-GW or PND21-30 application of VAP. The times of vaginal opening and first estrus were delayed in PFNA mice with a decrease in ovary size and the numbers of primary, secondary and antral follicles, and corpora lutea, which were relieved by pup-GW or application of VAP. The findings indicate that prenatal exposure to PFNA through increased FGF21 production in postnatal female offspring impedes postnatal activation of SCN-VAP neurons, which suppresses pubertal onset in AVPV-kisspeptin neurons and reproductive endocrine axis, leading to delayed puberty and dysfunction of ovaries.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128776DOI Listing
April 2021

Enhancement patterns of small hepatocellular carcinoma (≤ 30 mm) on contrast-enhanced ultrasound: Correlation with clinicopathologic characteristics.

Eur J Radiol 2020 Nov 8;132:109341. Epub 2020 Oct 8.

Department of Ultrasound, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, 200032, Shanghai, China; Shanghai Institute of Medical Imaging, No.180 Fenglin Road, 200032, Shanghai, China. Electronic address:

Purpose: To analyze the correlation between enhancement patterns of small hepatic carcinomas (HCCs; ≤ 30 mm) on contrast-enhanced ultrasound (CEUS) and the clinicopathologic characteristics.

Methods: The retrospective study included 346 inpatients (288 males and 58 females) with 372 pathologically confirmed small HCCs between January 2017 and December 2018. All patients underwent CEUS examination before pathological examination. Statistical analysis was used to determine the correlation between enhancement patterns of small HCCs on CEUS and clinicopathologic characteristics including serum alpha-feto-protein level, protein induced by vitamin K absence or antagonist-II (PIVKA-II) level, primary or recurrent HCC condition, tumor number, tumor differentiation, tumor size, liver background and microvascular invasion (MVI).

Results: Three hundred forty-seven out of 372 (93.3 %) HCCs manifested arterial phase hyper-enhancement (APHE). The arterial enhancement patterns were correlated with the tumor differentiation (odds ratio = 10.336, P = 0.000). Moderately- or poorly-differentiated HCCs were more likely to display APHE than well-differentiated HCCs (96.2 % vs 58.6 %, P < 0.001). Two hundred ninety-five of 372 (79.3 %) HCCs showed washout in the portal venous/late phase. Washout was correlated with serum PIVKA-II level, tumor size, tumor differentiation, and MVI on univariate analysis (P < 0.05). Logistic regression analysis revealed that only tumor size was significantly associated with washout of small HCCs (odds ratio = 2.335, P = 0.006). Large HCCs (20-30 mm) displayed a higher proportion of washout compared with that of HCCs ≤ 20 mm.

Conclusions: Enhancement patterns of small HCCs on CEUS were significantly correlated with tumor size and tumor differentiation among all clinicopathologic characteristics.
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http://dx.doi.org/10.1016/j.ejrad.2020.109341DOI Listing
November 2020

Current ultrasound-related strategies for assessing liver fibrosis in chronic liver disease.

Chin Med J (Engl) 2020 Nov;133(22):2762-2764

Department of Ultrasound, Huashan Hospital, Fudan University, Shanghai 200040, China.

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http://dx.doi.org/10.1097/CM9.0000000000001136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725523PMC
November 2020

Continuous participation in social activities as a protective factor against depressive symptoms among older adults who started high-intensity spousal caregiving: findings from the China health and retirement longitudinal survey.

Aging Ment Health 2020 Sep 21:1-9. Epub 2020 Sep 21.

Department of Sociology, Central South University, Changsha, Hunan Province, China.

Objectives: Previous studies documented that caregiving affects the mental health of spousal caregivers, and social participation is a favorable contributor to late-life well-being. However, it remains unclear whether changing social participation influences caregivers' mental health during their transition into spousal caregiving. The present study investigated the influence of transitioning into spousal caregiving, continuity and changes in social participation, and their interactions on older adults' depressive symptoms over time.

Method: Information on caregiving transitions and social participation for 2,436 baseline noncaregivers was drawn from the 2011‒2015 China Health and Retirement Longitudinal Survey. Generalized estimating equations were used for estimating the effects of caregiving transitions (transition into low-intensity caregiving, transition into high-intensity caregiving versus no caregiving) and changing social participation (increased participation, decreased participation, continuous participation versus no participation) on follow-up depressive symptoms.

Results: Individuals who transitioned into spousal care provision over a four-year period reported more elevated depressive symptoms than those who remained noncaregivers. Individuals who continued or increased social participation reported fewer depressive symptoms than those who reported no participation over the four-year period. Increases in depressive symptoms were less severe among individuals who maintained continuous or increased social participation when transitioning into high-intensity care provision than among their counterparts who were not continuously involved in social participation during the transition.

Conclusions: Continuous social participation protected against adverse psychological consequences during the transition into high-intensity spousal caregiving. Clinical attention should be directed at supporting spousal caregivers who meet difficulties in maintaining social participation when starting a demanding caregiving role.
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http://dx.doi.org/10.1080/13607863.2020.1822283DOI Listing
September 2020