Publications by authors named "Jing Wang"

11,663 Publications

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Optimizing multicontrast MRI reconstruction with shareable feature aggregation and selection.

NMR Biomed 2021 May 11:e4540. Epub 2021 May 11.

School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, Australia.

This paper proposes a new method for optimizing feature sharing in deep neural network-based, rapid, multicontrast magnetic resonance imaging (MC-MRI). Using the shareable information of MC images for accelerated MC-MRI reconstruction, current algorithms stack the MC images or features without optimizing the sharing protocols, leading to suboptimal reconstruction results. In this paper, we propose a novel feature aggregation and selection scheme in a deep neural network to better leverage the MC features and improve the reconstruction results. First, we propose to extract and use the shareable information by mapping the MC images into multiresolution feature maps with multilevel layers of the neural network. In this way, the extracted features capture complementary image properties, including local patterns from the shallow layers and semantic information from the deep layers. Then, an explicit selection module is designed to compile the extracted features optimally. That is, larger weights are learned to incorporate the constructive, shareable features; and smaller weights are assigned to the unshareable information. We conduct comparative studies on publicly available T2-weighted and T2-weighted fluid attenuated inversion recovery brain images, and the results show that the proposed network consistently outperforms existing algorithms. In addition, the proposed method can recover the images with high fidelity under 16 times acceleration. The ablation studies are conducted to evaluate the effectiveness of the proposed feature aggregation and selection mechanism. The results and the visualization of the weighted features show that the proposed method does effectively improve the usage of the useful features and suppress useless information, leading to overall enhanced reconstruction results. Additionally, the selection module can zero-out repeated and redundant features and improve network efficiency.
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http://dx.doi.org/10.1002/nbm.4540DOI Listing
May 2021

Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers.

Nat Commun 2021 May 10;12(1):2606. Epub 2021 May 10.

Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Understanding resistance mechanisms to targeted therapies and immune checkpoint blockade in mutant KRAS lung cancers is critical to developing novel combination therapies and improving patient survival. Here, we show that MEK inhibition enhanced PD-L1 expression while PD-L1 blockade upregulated MAPK signaling in mutant KRAS lung tumors. Combined MEK inhibition with anti-PD-L1 synergistically reduced lung tumor growth and metastasis, but tumors eventually developed resistance to sustained combinatorial therapy. Multi-platform profiling revealed that resistant lung tumors have increased infiltration of Th17 cells, which secrete IL-17 and IL-22 cytokines to promote lung cancer cell invasiveness and MEK inhibitor resistance. Antibody depletion of IL-17A in combination with MEK inhibition and PD-L1 blockade markedly reduced therapy-resistance in vivo. Clinically, increased expression of Th17-associated genes in patients treated with PD-1 blockade predicted poorer overall survival and response in melanoma and predicated poorer response to anti-PD1 in NSCLC patients. Here we show a triple combinatorial therapeutic strategy to overcome resistance to combined MEK inhibitor and PD-L1 blockade.
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http://dx.doi.org/10.1038/s41467-021-22875-wDOI Listing
May 2021

Benzophenone-3 induced abnormal development of enteric nervous system in zebrafish through MAPK/ERK signaling pathway.

Chemosphere 2021 May 5;280:130670. Epub 2021 May 5.

Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address:

Hirschsprung disease (HSCR) is a congenital disease characterized by the absence of enteric neurons, which is derived from the failure of the proliferation, differentiation or migration of the enteric neural crest cells (ENCCs). HSCR is associated with multiple risk factors, including polygenic inheritance factors and environmental factors. Genetic studies have been extensively performed, whereas studies related to environmental factors remain insufficient. Benzophenone-3 (BP-3), one important component of the ultraviolet (UV) filters, has been proved to have cytotoxicity and neurotoxicity which might be associated with HSCR. In this study, we used zebrafish as a model to investigate the relationship between BP-3 exposure and the development of the enteric nervous system (ENS) in vivo. Embryos exposed to BP-3 showed an average of 46% reduction of the number of the enteric neurons number. Besides, the ENCCs specific markers (ret and hand2) were downregulated upon BP-3 exposure. Moreover, we identified potential targets of BP-3 through Network Pharmacology Analysis and Autodock and demonstrated that the attenuation of the MAPK/ERK signaling might be the potential mechanism underlying the inhibition of the ENS development by BP-3. Importantly, MAPK/ERK signaling agonist could be used to rescue the ENS defects of zebrafish induced by BP-3. Overall, we characterized the influence of BP-3 on ENS development in vivo and explored possible molecular mechanisms.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130670DOI Listing
May 2021

Activation of COL11A1 by PRRX1 promotes tumor progression and radioresistance in ovarian cancer.

Int J Radiat Biol 2021 May 10:1-29. Epub 2021 May 10.

Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanjing Medical University, No. 262, Zhongshanbei Road, Gulou District, Nanjing 210003, Jiangsu, China.

Purpose: Although radiotherapy is a common treatment option for all kinds of cancer patients, including ovarian cancer, a major obstacle limiting its application is the development of resistance. Therefore, it is urgently needed to clarify the mechanism of radio sensitivity modulation.

Materials And Methods: We obtained open datasets and analyzed the expression of collagen type XI alpha 1 (COL11A1) in ovarian cancer patients with different stages. Meanwhile, the correlation of COL11A1 and survival outcomes is determined by Kaplan-Meier analysis. The role of COL11A1 in cell proliferation was observed in an knockdown system. SKOV3 radioresistant cells were established to determine the role of COL11A1 on radioresistant in ovarian cancer.

Results And Discussion: COL11A1 were highly enriched in late-stage ovarian cancer tumor tissues and negatively correlated with survival outcomes in ovarian cancer. The functional analysis found that COL11A1 promoted ovarian cancer cell proliferation . Importantly, COL11A1 decreased the radiosensitivity in ovarian cancer by AKT activation. Paired related homeobox 1 (PRRX1) acted as an upstreaming transcription factor to regulate COL11A1 expression in ovarian cancer. Increased COL11A1 expression is related to low survival outcomes and radiosensitivity in ovarian cancer.

Conclusions: Targeting COL11A1 is a promising strategy for improving radiotherapy efficiency.
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http://dx.doi.org/10.1080/09553002.2021.1928780DOI Listing
May 2021

Usnic acid suppresses cervical cancer cell proliferation by inhibiting PD-L1 expression and enhancing T-lymphocyte tumor-killing activity.

Phytother Res 2021 May 10. Epub 2021 May 10.

Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, China.

The programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway is abnormally expressed in cervical cancer cells. Moreover, PD-1/PD-L1 blockade reduces the apoptosis and exhaustion of T cells and inhibits the development of malignant tumors. Usnic acid is a dibenzofuran compound originating from Usnea diffracta Vain and has anti-inflammatory, antifungal, and anticancer activities. However, the molecular mechanism of its antitumor effects has not been fully elucidated. In this work, we first observed that usnic acid decreased the expression of PD-L1 in HeLa cells and enhanced the cytotoxicity of co-cultured T cells toward tumor cells. Usnic acid inhibited PD-L1 protein synthesis by reducing STAT3 and RAS pathways cooperatively. It was subsequently shown that usnic acid induced MiT/TFE nuclear translocation through the suppression of mTOR signaling pathways, and promoted the biogenesis of lysosomes and the translocation of PD-L1 to the lysosomes for proteolysis. Furthermore, usnic acid inhibited cell proliferation, angiogenesis, migration, and invasion, respectively, by downregulating PD-L1, thereby inhibiting tumor growth. Taken together, our results show that usnic acid is an effective inhibitor of PD-L1 and our study provide novel insights into the mechanism of its anticancer targeted therapy.
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http://dx.doi.org/10.1002/ptr.7103DOI Listing
May 2021

The Impact of COVID-19 on Social Isolation in Long-term Care Homes: Perspectives of Policies and Strategies from Six Countries.

J Aging Soc Policy 2021 May 9:1-15. Epub 2021 May 9.

Professor, Rory Meyers College of Nursing, New York University, New York, New York, USA.

Preventing the spread of COVID-19 in long-term care homes is critical for the health of residents who live in these institutions. As a result, broad policies restricting visits to these facilities were put in place internationally. While well meaning, these policies have exacerbated the ongoing social isolation crisis present in long-term care homes prior to the COVID-19 pandemic. This perspective highlights the dominant COVID-19 LTC policies from six countries, and proposes five strategies to address or mitigate social isolation during the COVID-19 pandemic that can also be applied in a post-pandemic world.
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http://dx.doi.org/10.1080/08959420.2021.1924346DOI Listing
May 2021

Inhibition of ASC enhances the protective role of salvianolic acid A in traumatic brain injury via inhibition of inflammation and recovery of mitochondrial function.

Folia Neuropathol 2021 ;59(1):50-66

Department of Neurosurgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, The Third Affiliated Hospital of Shanxi Medical University, Taiyuan, China.

More than 50 million people are affected by traumatic brain injury (TBI) each year around the world, and nearly half of the population worldwide will have one or more TBI(s) in their lifetime. And in 2017, more than 1.39 billion people in China suffered from TBI, representing nearly 18% of the world population; these were mainly caused by road traffic incidents. Salvianolic acid A is a compound obtained from Salvia miltiorrhiza Bunge, which is one of the active components of many traditional Chinese medicines for the treatment of cardiovascular and cerebrovascular disease, with the effect of inhibition of inflammatory response. ASC is a critical factor in the activation of inflammation response process via promoting the maturation of caspase-1, and activation of NLPR3 under bacterial infection promotes the necrosis of cells in an ASC-dependent manner. However, few studies focus on the effect of ASC in a TBI model. In this study, we found that inhibition of ASC reduced the expression of inflammatory cytokines, and the concentration of calcium and ROS, while it increased the expression of mitochondrial function-related proteins. We further noticed that these effects were regulated by DLK2/MLK3/JNK signalling pathway and might contribute to the treatment of TBI.
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http://dx.doi.org/10.5114/fn.2021.105131DOI Listing
January 2021

Combination of Immune-Related Genomic Alterations Reveals Immune Characterization and Prediction of Different Prognostic Risks in Ovarian Cancer.

Front Cell Dev Biol 2021 23;9:653357. Epub 2021 Apr 23.

Department of Gynecology, The First Affiliated Hospital, Harbin Medical University, Harbin, China.

With the highest case-fatality rate among women, the molecular pathological alterations of ovarian cancer (OV) are complex, depending on the diversity of genomic alterations. Increasing evidence supports that immune infiltration in tumors is associated with prognosis. Therefore, we aim to assess infiltration in OV using multiple methods to capture genomic signatures regulating immune events to identify reliable predictions of different outcomes. A dataset of 309 ovarian serous cystadenocarcinoma patients with overall survival >90 days from The Cancer Genome Atlas (TCGA) was analyzed. Multiple estimations and clustering methods identified and verified two immune clusters with component differences. Functional analyses pointed out immune-related alterations underlying internal genomic variables potentially. After extracting immune genes from a public database, the LASSO Cox regression model with 10-fold cross-validation was used for selecting genes associated with overall survival rate significantly, and a risk score model was then constructed. Kaplan-Meier survival and Cox regression analyses among cohorts were performed systematically to evaluate prognostic efficiency among the risk score model and other clinical pathological parameters, establishing a predictive ability independently. Furthermore, this risk score model was compared among identified signatures in previous studies and applied to two external cohorts, showing better prediction performance and generalization ability, and also validated as robust in association with immune cell infiltration in bulk tissues. Besides, a transcription factor regulation network suggested upper regulatory mechanisms in OV. Our immune risk score model may provide gyneco-oncologists with predictive values for the prognosis and treatment management of patients with OV.
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http://dx.doi.org/10.3389/fcell.2021.653357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102990PMC
April 2021

A Conceptual Model to Improve Care for Individuals with Alzheimer's Disease and Related Dementias and Their Caregivers: Qualitative Findings in an Online Caregiver Forum.

J Alzheimers Dis 2021 May 3. Epub 2021 May 3.

Center on Smart and Connected Health Technologies, School of Nursing, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Background: As the population rapidly ages, a growing number of families are engaging in care for individuals living with Alzheimer's disease and related dementias (ADRD). The perceived challenges and burdens that face informal caregivers are enormous.

Objective: The objective of this study was to 1) explore from the family caregivers' perspective, the daily lives of individuals living with ADRD, and the challenges family caregivers encounter when caring for a family member with ADRD; and 2) to develop a comprehensive model with the endeavor to improve care for individuals with ADRD and their family caregivers.

Methods: Posts were extracted from the ALZConnected online caregiving forum in May 2019. Guided by a triangular model focused on Caregiver, Individual with ADRD, and Context of Care, two researchers independently analyzed 654 posts with a combination of deductive and inductive thematic analysis approach. Researchers all agreed on finalized codes and themes.

Results: Thematic analysis resulted in four themes: Individual with ADRD, Caregiver, Dynamic between Caregiver and Individual with ADRD, and Context of Care. The most frequently discussed topics among caregivers were informational and emotional support for caregivers, and the capabilities and functioning of individuals with ADRD.

Conclusion: Online forums provide a valuable platform for caregivers to support each other informationally and emotionally, share care strategies, and navigate caregiving burdens. An expanded model was derived to support a comprehensive and dynamic approach to improving care for both caregivers and individuals with ADRD. The unique nature of the caregiver forum data is worthy of further data mining using a novel analysis approach.
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http://dx.doi.org/10.3233/JAD-210167DOI Listing
May 2021

[Latest Progresses in Surgical Treatment of Median Arcuate Ligament Syndrome].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Apr;43(2):283-287

Department of Vascular Surgery,PUMC Hospital,CAMS and PUMC,Beijing 100730,China.

Median arcuate ligament syndrome(MALS)is compression of the celiac trunk by the median arcuate ligament.Median arcuate ligament release is the corner stone for the surgical treatment of MALS.Open surgery,laparoscopic surgery,and robot-assisted surgery have been developed,among which laparoscopic surgery has been proposed as the preferred approach in view of its minimal trauma and short hospital stay.Auxiliary celiac plexus neurolysis could further alleviate the patient's discomfort.Moreover,vascular reconstitution is of vital importance in the case of persistent stenosis in the celiac artery despite of median arcuate ligament decompression.Vascular reconstruction has satisfactory long-term patency rate,while endovascular treatment is less invasive.This article aims to summarize the consensuses and advances and shed light on the surgical treatment of MALS.
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http://dx.doi.org/10.3881/j.issn.1000-503X.11980DOI Listing
April 2021

First-Phase Ejection Fraction, a Measure of Preclinical Heart Failure, Is Strongly Associated With Increased Mortality in Patients With COVID-19.

Hypertension 2021 Jun 10;77(6):2014-2022. Epub 2021 May 10.

British Heart Foundation Centre, King's College London, United Kingdom (H.G., A.A.N., O.D., K.O., M.M., D.P., M.R., L. Faconti, A. Papachristidis, G.C.-W., A.M.S., P.C.).

Presence of heart failure is associated with a poor prognosis in patients with coronavirus disease 2019 (COVID-19). The aim of the present study was to examine whether first-phase ejection fraction (EF1), the ejection fraction measured in early systole up to the time of peak aortic velocity, a sensitive measure of preclinical heart failure, is associated with survival in patients hospitalized with COVID-19. A retrospective outcome study was performed in patients hospitalized with COVID-19 who underwent echocardiography (n=380) at the West Branch of the Union Hospital, Wuhan, China and in patients admitted to King's Health Partners in South London, United Kingdom. Association of EF1 with survival was performed using Cox proportional hazards regression. EF1 was compared in patients with COVID-19 and in historical controls with similar comorbidities (n=266) who had undergone echocardiography before the COVID-19 pandemic. In patients with COVID-19, EF1 was a strong predictor of survival in each patient group (Wuhan and London). In the combined group, EF1 was a stronger predictor of survival than other clinical, laboratory, and echocardiographic characteristics including age, comorbidities, and biochemical markers. A cutoff value of 25% for EF1 gave a hazard ratio of 5.23 ([95% CI, 2.85-9.60]; <0.001) unadjusted and 4.83 ([95% CI, 2.35-9.95], <0.001) when adjusted for demographics, comorbidities, hs-cTnI (high-sensitive cardiac troponin), and CRP (C-reactive protein). EF1 was similar in patients with and without COVID-19 (23.2±7.3 versus 22.0±7.6%, =0.092, adjusted for prevalence of risk factors and comorbidities). Impaired EF1 is strongly associated with mortality in COVID-19 and probably reflects preexisting, preclinical heart failure.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17099DOI Listing
June 2021

China county based COPD screening and cost-effectiveness analysis.

Ann Palliat Med 2021 Apr;10(4):4652-4660

Department of Pulmonary and Critical Care Medicine, Fengning Manchu Autonomous County Hospital of Chengde medical college, Chengde, China.

Background: Early diagnosis and treatment of chronic obstructive pulmonary disease (COPD) can improve pulmonary function and reduce the incidence of exacerbations of acute COPD, thereby improving the patient's quality of life. In China, due to limited medical resources, COPD patients often cannot be diagnosed and treated early, so the benefits of early screening of patients with COPD high risk still lack effective supporting data.

Methods: Based on the data collected through the "Dual-lung screening initiative" performed by the Datan Health Center in Fengning Manchu Autonomous County on July 12 and July 19, 2020, the patients with COPD high risk who underwent early COPD screening were evaluated. The screened patients were mainly smokers aged over 45 and those with long-term exposure to secondhand smoke, underlying lung diseases, a family history of lung diseases, or respiratory symptoms. After filling out the COPD-population screener (COPD-PS) questionnaire, those who had a score of above 5 were subjected to the portable pulmonary function test. Subjects with a forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio <0.7 were diagnosed with COPD. A cost-effectiveness analysis model was applied to assess the screening's economic efficiency. The model was constructed through a combination of a decision tree and a Markov model, which enabled the simulation of the disease progression of COPD high risk patients under the condition of being screened or not being screened, to evaluate the incremental cost-effectiveness ratio between the two conditions.

Results: A total of 700 questionnaires were issued for screening and 379 questionnaires were valid, and 92 patients were diagnosed with COPD (24.27%). The modeling results showed that among patients with COPD high risk, those receiving early screening had an increase in quality-adjusted life years (QALYs) by 0.28 units over those who did not, and a cost of 6,366.19 Renminbi (RMB) would be needed, which was much lower than the set willingness-to-pay threshold (70,888.99 RMB) [an equivalent of the 2019 per capita gross domestic product (GDP)].

Conclusions: For COPD high risk patients, receiving early screening has a cost-effective advantage over no screening. Therefore, early screening should be vigorously promoted to COPD high risk patients.
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http://dx.doi.org/10.21037/apm-21-812DOI Listing
April 2021

Epsilon toxin from Clostridium perfringens induces toxic effects on skin tissues and HaCaT and human epidermal keratinocytes.

Toxicon 2021 May 6. Epub 2021 May 6.

State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, AMMS, Beijing 100071, PR China. Electronic address:

Epsilon toxin (ETX) is a key pathogenic factor of C. perfringens type B and D, causing fatal enterotoxemia in sheep and goats. Excessive production of ETX increases intestinal permeability; its entrance into the bloodstream leads to severe edema in organs such as the brain and kidneys. At present, very few cell lines are known to be sensitive to ETX, with the most sensitive cell model for in vitro research being the MDCK cell line. Recently, more tissue-derived cell lines have been shown to be sensitive to ETX, but the mechanism of cytotoxicity remains unknown. Herein, for the first time, we aimed to evaluate the effects of ETX on HaCaT keratinocytes and human epidermal keratinocytes (HEKa). In addition, the median lethal dose of subcutaneous injection of ETX in mice was 109 ng/kg. At this dose, ETX rapidly entered the blood circulation, causing hemorrhage and edema in the brain and kidneys. ETX also increased the expression of aquaporin 3 in the muscle layer and hair follicles of the skin. We further showed the presence of the MAL protein in HaCaT keratinocytes and HEKa and skin tissues, supporting the hypothesis that it is a key element in the mechanism of cytotoxicity of ETX. In conclusion, skin cell lines were used for the first time as a model for studying the toxic effects of ETX, which will help elucidate the cytotoxicity induced by ETX and the related molecular mechanisms.
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http://dx.doi.org/10.1016/j.toxicon.2021.05.002DOI Listing
May 2021

Adalimumab Induces a Wound Healing Profile in Patients with Hidradenitis Suppurativa by Regulating Macrophage Differentiation and Matrix Metalloproteinase Expression.

J Invest Dermatol 2021 May 6. Epub 2021 May 6.

Immunology Discovery, AbbVie Bioresearch Center, 100 Research Drive, Worcester, MA 01605.

Adalimumab (ADA) is the only FDA-approved treatment for moderate-to-severe hidradenitis suppurativa (HS), whereas etanercept (ETN) and certolizumab-pegol (CZP) have been shown to be ineffective, suggesting that the mechanism of action of ADA is distinct in HS and may contribute to improved wound healing. Given that macrophages (Mφ) play pivotal roles throughout the wound healing process, an in-vitro Mφ differentiation assay was carried out to assess the impact of TNF-anti-TNF complexes on these cells. TNF-ADA complexes exhibited stronger inhibitory effects on inflammatory Mφ differentiation. Moreover, RNA sequencing revealed several unique wound healing profiles for TNF-ADA-treated inflammatory Mφs, which were not observed for those treated with either TNF-ETN or TNF-CZP, including the inhibition of the matrix metallopeptidase (MMP) pathway. In addition, ADA administration was found to significantly reduce the levels of inflammatory MMPs -1 and -9 while promoting wound healing MMP-13 and tissue inhibitor of metalloproteinases 2 (TIMP-2) levels in the circulation of those HS patients who responded to treatment. Our in-vitro findings demonstrate that TNF-ADA-treated inflammatory Mφs exhibit a distinct profile resembling wound healing. Moreover, ADA not only differentially regulates MMP expression in HS patients responding to the therapy but potentially induces a transition to a profile suggestive of wound healing.
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http://dx.doi.org/10.1016/j.jid.2021.04.010DOI Listing
May 2021

Paeoniflorin attenuates the allergic contact dermatitis response via inhibiting the IFN-γ production and the NF-κB/IκBα signaling pathway in T lymphocytes.

Int Immunopharmacol 2021 May 6;96:107687. Epub 2021 May 6.

Department of Dermatology, The Second Hospital of Dalian Medical University, Dalian, China; Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China. Electronic address:

Paeoniflorin (PF) has been demonstrated to have an anti-allergic and anti-inflammatory effect in the treatment of allergic contact dermatitis (ACD). However, its clinical application is hampered by the lacking of comprehensive mechanical explanation. This research aimed to study the effect of PF on the proliferation, apoptosis and cytokines secretion as well as the expression of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways of T lymphocytes activation in vitro and in vivo. We found that PF depressed human T lymphocytes activation via inhibition ofinterferon-gamma (IFN-γ) production and NF-κB/IκBα and p38 MAPK signaling pathway in vitro, also PF could attenuate such ACD responses by inhibiting the production of IFN-γ and NF-κB/IκBα pathway in T lymphocytes of ACD mouse model, suggesting that PF might be useful for the treatment of T cell-mediated allergic inflammatory disorders such as ACD. This would make PF a promising T cell-targeted drug candidate for further study because of its immunosuppressive and anti-inflammatory effects.
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http://dx.doi.org/10.1016/j.intimp.2021.107687DOI Listing
May 2021

Aberrant hypermethylation induced downregulation of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 correlate with tumorigenesis of glioma.

Life Sci 2021 May 6:119590. Epub 2021 May 6.

Department of Laboratory Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250000, China. Electronic address:

Aims: The expression of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 were found to be downregulated in glioma by RNA sequencing; however, the function and mechanism of both two genes in the development of glioma have not been studied.

Materials And Methods: QRT-PCR and western blot were used to determine the transcriptional and translational levels of moleculars. MSP and BSP assays were used to evaluate the methylation status of promoter CpG island. MTT, EdU, flow cytometry, and transwell assays were used to reveal biological effects. The in vivo mice model was used to validate the role of target genes in tumorigenesis.

Key Findings: The mRNA and protein expression of STXBP5 was significantly downregulated in glioma tissues and positively correlated with prognosis. STXBP5-AS1 was downregulated in glioma cells and tissues, and associated with tumor size and clinical stages. Both of two genes were significantly restored in cells treatment with 5-Aza. The promoter CpG island of STXBP5/STXBP5-AS1 was hypermethylated in glioma cells, but partially methylated in NHA cells. We found that promoter methylation frequency was significantly higher in glioma tissues. Functionally, overexpression of STXBP5 and STXBP5-AS1 inhibited cell proliferation, migration, and invasion and promoted apoptosis in vitro, whereas depletion of STXBP5 and STXBP5-AS1 showed opposite effects. Both the mRNA and protein expression of STXBP5 were positively regulated by STXBP5-AS1. Ectopic expression of STXBP5 and STXBP5-AS1 suppressed tumor formation in vivo.

Significance: Our findings suggested that epigenetically silenced STXBP5-AS1 and STXBP5 might act as novel tumor suppressors of glioma.
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http://dx.doi.org/10.1016/j.lfs.2021.119590DOI Listing
May 2021

Application of the curcumin-mediated photodynamic inactivation for preserving the storage quality of salmon contaminated with L. monocytogenes.

Food Chem 2021 Apr 28;359:129974. Epub 2021 Apr 28.

Department of Food Science, Foshan University, Foshan, 528000, China; College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China. Electronic address:

The effect of curcumin-mediated blue light-emitting diode (LED) photodynamic inactivation (PDI) for preserving the quality of salmon contaminated with Listeria monocytogenes was investigated by microbiological, physical, chemical and histological methods during sample storage at 4 ℃ and 25 ℃. The results showed that PDI decelerated the proliferation of L. monocytogenes on salmon during storage at 25 ℃, with the maximum inhibition reaching 4.0 log CFU/g (99.99%), compared to the negative control. Moreover, PDI greatly retarded the increase in pH (P < 0.05) and the production of TVB-N, retarded the accumulation of free fatty acids, and decelerated the degradation of proteins, ultimately preserving the high nutritional value of the salmon. In addition, PDI effectively prevented a change in colour and retarded the loss of water from the salmon, thereby conserving its texture and sensory properties. Therefore, PDI is a promising and valid non-thermal technology to use for fish preservation.
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http://dx.doi.org/10.1016/j.foodchem.2021.129974DOI Listing
April 2021

Systematic characterization of chemical constituents in Mahuang decoction by UHPLC tandem linear ion trap-Orbitrap mass spectrometry coupled with feature-based molecular networking.

J Sep Sci 2021 May 7. Epub 2021 May 7.

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

Comprehensive characterization of traditional Chinese medicine prescriptions has long been a hurdle due to the chemical complexity and the lack of analytical tools. Mahuang decoction is a well-known traditional Chinese medicine prescription widely used for sweating and relieving the exterior, relieving cough and asthma, but it was insufficiently chemically scrutinized. In this study, the chemical component information of Mahuang decoction was investigated by ultrahigh performance liquid chromatography tandem linear ion trap-Orbitrap mass spectrometry. A new data processing tool, feature-based molecular networking, was introduced for grouping and elucidating the compounds. In this way, 156 chemical components were identified or tentatively characterized, including alkaloids, triterpenoid saponins, flavanone-O-glycosides, flavone-C-glycosides and procyanidins. Thus, this research provides a solid foundation for further development of Mahuang decoction, and the adopted method is expected to be applied to other traditional Chinese medicine prescriptions. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jssc.202100121DOI Listing
May 2021

Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals.

Nat Commun 2021 May 7;12(1):2563. Epub 2021 May 7.

National Centre for Gene Research, CAS-JIC Centre of Excellence for Plant and Microbial Science (CEPAMS), Centre of Excellence for Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (CAS), Shanghai, China.

Non-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat-the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a 'self-poisoning' scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity.
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http://dx.doi.org/10.1038/s41467-021-22920-8DOI Listing
May 2021

The complete mitochondrial genome of Trifida elongate and comparative analysis of 43 leafhoppers.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Apr 28;39:100843. Epub 2021 Apr 28.

Institute of Entomology, Guizhou University, Guiyang 550025, China; Guizhou Key Laboratory for Plant Pest Management of Mountainous Region, Guizhou University, Guiyang 550025, China. Electronic address:

In this study, the mitochondrial genome of Trifida elongate was sequenced, and comparative analysis of T. elongate and other 43 leafhoppers was performed based on the mitochondrial genome. The mitochondrial genome sequence length of T. elongate was 14,924 bp. It comprised 13 protein-coding genes, 2 ribosomal RNA (rRNA) genes, 22 transport RNA (tRNA) genes, and 1 non-coding control region. The control region is located between the rrnS and trnI genes, is characterized by two tandem repeats and three simple sequence repeats. Phylogenetic analysis showed that T. elongate is closely related with Bolanusoides shaanxiensis and Limassolla lingchuanensis (bootstrap value = 92% and posterior probabilities = 1). Analysis of synonymous and non-synonymous nucleotide substitutions showed that Ka/Ks value of the 13 protein-coding genes of 8 subfamily leafhoppers were less than 1 ranging from 0.0315 to 0.9928. atp8 had the highest Ka/Ks value whereas cox1 had the lowest Ka/Ks value. This study provides information on the structure and sequence characteristics of the mitochondrial genome of T. elongata. Typhlocybinae is clustered with (Cicadellinae+(Idiocerinae+(Mileewinae+(Nirvaninae+(Evacanthinae+Ledrinae))))).
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http://dx.doi.org/10.1016/j.cbd.2021.100843DOI Listing
April 2021

Rubioncolin C, a natural naphthohydroquinone dimer isolated from Rubia yunnanensis, inhibits the proliferation and metastasis by inducing ROS-mediated apoptotic and autophagic cell death in triple-negative breast cancer cells.

J Ethnopharmacol 2021 May 4:114184. Epub 2021 May 4.

State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China. Electronic address:

Ethnopharmacological Relevance: Rubia yunnanensis Diels is a traditional Chinese medicine that has diverse pharmacological activities, including antituberculosis, antirheumatism and anticancers. Rubioncolin C (RC), a natural naphthohydroquinone dimer isolated from the roots and rhizomes of R. yunnanensis Diels, has shown potent antitumor activity. However, the antitumor activity and its potential mechanism of RC in triple negative breast cancer (TNBC) cell lines remained unclear.

Aim Of The Study: This study was aim to investigate the anti-proliferation and anti-metastasis activity as well as the potential mechanism of RC on triple-negative breast cancer cells in vitro and in vivo.

Materials And Methods: The sulforhodamine B assay, colony formation assay and cell cycle analysis were used to determine the anti-proliferative activity of RC on TNBC. The anti-metastatic activity in vitro of RC was detected through the scratch wound assay, cell migration and invasion assays and gelatin zymography. The flow cytometry, JC-1, GFP-LC3B plasmid transfection, MDC, Lysotracker red and Carboxy-HDCFDA, DHE, and MitoSOX™ Red staining were performed to investigate the effect of RC on apoptosis, autophagy and ROS level. The apoptosis inhibitor, autophagy inhibitors and ROS inhibitors were used to further verify the antitumor mechanism of RC. The protein levels related with cell cycle, apoptosis, and autophagy were examined with western blotting. In addition, the anti-tumor activity of RC in vivo was assessed in an experimental metastatic model.

Results: In the present study, RC suppressed the proliferation of TNBC cells in a time- and dose-dependent manner via regulating cell cycle. Further experiments showed that RC inhibited the migration and invasion of TNBC cells by downregulating MMPs and inhibiting EMT. Moreover, we demonstrated that RC induced obviously apoptotic and autophagic cell death, activated MAPK signaling pathway and inhibited mTOR/Akt/p70S6K and NF-κB signaling pathways. Furthermore, the excessive ROS was produced after treatment with RC. The antioxygen NAC and GSH could rescue the cell viability and reestablish the ability of cell metastasis, and inhibit the RC-induced apoptosis and autophagy. In a mice lung metastasis model of breast cancer, RC inhibited lung metastasis, and induced autophagy and apoptosis.

Conclusion: These findings clarified the antitumor mechanism of RC on TNBC cell lines and suggested that RC is a key active ingredient for the cancer treatment of R. yunnanensis, which would help RC develop as a new potential chemotherapeutic agent for TNBC treatment.
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http://dx.doi.org/10.1016/j.jep.2021.114184DOI Listing
May 2021

The Effects of a Novel Quarterly Cardiopulmonary Resuscitation Training Program on Hospital Basic Life Support Providers' Cardiopulmonary Resuscitation Skill Performance.

J Nurses Prof Dev 2021 May-Jun 01;37(3):131-137

This is a retrospective descriptive study of a novel cardiopulmonary resuscitation (CPR) training program. Using quarterly, brief CPR training at a skills station, hospital basic life support providers who failed to meet CPR performance measures during the first quarter quickly improved on the skills necessary to meet CPR measures. Those meeting CPR measures during the first quarter maintained that performance over time. Staff nurse educators should consider incorporating innovative CPR education strategies that focus on spaced learning with immediate feedback.
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http://dx.doi.org/10.1097/NND.0000000000000727DOI Listing
May 2021

Preparation of molecularly imprinted polymer with class-specific recognition for determination of 29 sulfonylurea herbicides in agro-products.

J Chromatogr A 2021 Apr 9;1647:462143. Epub 2021 Apr 9.

State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, 250353, China; Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211-Giza, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk University, 25240-Erzurum, Turkey. Electronic address:

Molecularly imprinting polymers with high selectivity toward 29 sulfonylurea herbicides were synthesized by precipitation polymerization, using metsulfuron-methyl and chlorsulfuron as the template molecule, 4-vinylpyridine as the function monomer, divinylbenzene as the crosslinking agent, and acetonitrile as porogen. The imprinted polymers were characterized and measured by scanning electron microscopy (SEM) and equilibrium adsorption experiments. The molecularly imprinted polymers displayed specific recognition for the tested 29 sulfonylurea herbicides, and the maximum apparent binding capacity was found to be 18.81 mg/g. The synthesized polymer was used as a solid-phase extraction (SPE) column coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for determination of the tested analytes in agro-products. Within the range of 2-100 μg/L, the tested analytes have achieved a good linear association with correlation coefficient (R) > 0.999. The calculated limits of detection (LODs, S/N=3) as along with limits of quantification (LOQs, S/N=10) were in the ranges of 0.005-0.07 μg/L and 0.018-0.23 μg/L, respectively. Under different spiking levels, the recovery rates were ranged from 74.8% - 110.5%, and the relative standard deviation (RSDs) were < 5.3%. Finally, the feasibility of the proposed methodology was successfully applied for detection of sulfonylurea herbicides in crops, vegetables, and oils samples.
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http://dx.doi.org/10.1016/j.chroma.2021.462143DOI Listing
April 2021

Emerging immune checkpoints in the tumor microenvironment: Implications for cancer immunotherapy.

Cancer Lett 2021 May 3;511:68-76. Epub 2021 May 3.

Children's Hospital of Fudan University, National Children's Medical Center, And Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. Electronic address:

Immune checkpoints within the tumor microenvironment (TME) play important roles in modulating host antitumor immunity. Checkpoint-based immunotherapies (e.g. immune checkpoint inhibitors) have revolutionized cancer therapy. However, there are still many drawbacks with current checkpoint immunotherapies in clinical practice, such as unresponsiveness, resistance, tumor hyperprogression, autoimmune-related adverse events, and limited efficacy with some solid malignances. These drawbacks highlight the need to further investigate the mechanisms underlying the therapeutic effects, as well as the need to identify new targets for cancer immunotherapy. With the discovery of emerging immune checkpoints in the TME, the development of strategies targeting the pivotal immunomodulators for cancer treatment has been significantly advanced in the past decade. In this review, we summarize and classify the novel emerging immune checkpoints beyond the extensively studied ones (e.g. PD-1, PD-L1, CTLA-4, LAG-3 and TIM-3) in the TME, and provide an update on the clinical trials targeting these key immune molecules.
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http://dx.doi.org/10.1016/j.canlet.2021.04.021DOI Listing
May 2021

Electric field control of magnetism through modulating phase separation in (011)-NdSrMnO/PMN-PT heterostructures.

Nanoscale 2021 May;13(17):8030-8037

Beijing National Laboratory for Condensed Matter Physics and State Key Laboratory of Magnetism, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China. and Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China.

Large and non-volatile electric field control of magnetization is promising to develop memory devices with reduced energy consumption. Herein, we report the electric field control of magnetization with a non-volatile memory effect in an intermediate band Nd0.5Sr0.5MnO3 film grown on a (011)-cut 0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMN-PT) single crystal. Applying an electric field across the ferroelectric PMN-PT increases the magnetization of the Nd0.5Sr0.5MnO3 film along both in-plane [100] and [011[combining macron]] directions. Moreover, the magnetization does not recover to its original state after withdrawal of the electric field at temperatures below 70 K, demonstrating a non-volatile memory effect. Detailed investigation showed that (011)-PMN-PT exhibits an anisotropic in-plane strain due to an electric field-induced rhombohedral to orthorhombic phase transition. This electric field-induced anisotropic strain can dynamically transfer to Nd0.5Sr0.5MnO3 film and modulate the magnetization of the Nd0.5Sr0.5MnO3 film through adjusting its phase balance between ferromagnetic (FM) and charge-orbital ordered antiferromagnetic (COO AFM) phases. The non-volatile memory effect can be ascribed to the competition of thermal energy and energy barriers between the FM and COO AFM phases at low temperatures. This work broadens the knowledge of electric field control of magnetism in the intermediate band-manganite ferromagnetic/ferroelectric multiferroic heterostructures, and may also pave a way for the control of antiferromagnetism and to design antiferromagnet-based memories.
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http://dx.doi.org/10.1039/d1nr00242bDOI Listing
May 2021

Molecular Characterization of Complement Component 3 (C3) in the Pearl Oyster Improves Our Understanding of the Primitive Complement System in Bivalve.

Front Immunol 2021 19;12:652805. Epub 2021 Apr 19.

College of Fisheries, Guangdong Ocean University, Zhanjiang, China.

As the central component in the complement system, complement component 3 (C3) plays essential roles in both the innate and adaptive immune responses. Here, a C3 gene (designated as ) was obtained from the pearl oyster by RT-PCR and rapid amplification of cDNA ends (RACE). The cDNA consists of 5,634 bp with an open reading frame (ORF) of 5,193 bp encoding a protein of 1,730 amino acids with a 19 residue signal peptide. The deduced pf-C3 protein possessed the characteristic structural features present in its homologs and contained the A2M_N_2, ANATO, A2M, A2M_comp, A2M_recep, and C345C domains, as well as the C3 convertase cleavage site, thioester motif, and conserved Cys, His, and Glu residues. Phylogenetic analysis revealed that pf-C3 is closely related to the C3s from other mollusks. mRNA was expressed in all examined tissues including gill, digestive gland, adductor muscle, mantle and foot, while the highest expression was found in the digestive gland. Following the challenge with , expression was significantly induced in hemocytes. Luciferase reporter assays indicated that pf-C3a could activate the NF-B signal pathway in HEK293T cells. Further knockdown of by specific siRNA could significantly reduce the phagocytosis of by hemocytes . These results would help increase understanding of the function of C3 in the invertebrate immune system and therefore provide new insights into the roles of the primitive complement system in invertebrates.
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http://dx.doi.org/10.3389/fimmu.2021.652805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089394PMC
April 2021

Comprehensive Molecular Characterization of Chinese Patients with Glioma by Extensive Next-Generation Sequencing Panel Analysis.

Cancer Manag Res 2021 29;13:3573-3588. Epub 2021 Apr 29.

Department of Neurosurgery, Peking University International Hospital, Beijing, People's Republic of China.

Background: Tremendous efforts have been made to explore biomarkers for classifying and grading glioma. However, the majority of the current understanding is based on public databases that might not accurately reflect the Asian population. Here, we investigated the genetic landscape of Chinese glioma patients using a validated multigene next-generation sequencing (NGS) panel to provide a strong rationale for the future classification and prognosis of glioma in this population.

Methods: We analyzed 83 samples, consisting of 71 initial treatments and 12 recurrent surgical tumors, from 81 Chinese patients with gliomas by performing multigene NGS with an Acornmed panel targeting 808 cancer-related hotspot genes, including genes related to glioma (hotspots, selected exons or complete coding sequences) and full-length SNPs located on chromosomes 1 and 19.

Results: A total of 76 (91.57%) glioma samples had at least one somatic mutation. The most commonly mutated genes were , and . Approximately one-third of cases exhibited more than one copy number variation. Of note, this study identified the amplification of genes, such as and , which were significantly associated with glioblastoma but had not been previously used for clinical classification (P<0.05). Significant differences in genomic profiles between different pathological subtypes and WHO grade were observed. Compared to the MSKCC database primarily comprised of Caucasians, mutations and amplifications exhibited higher mutation rates, whereas mutations and and copy number variations presented a lower mutation rate in Chinese patients with glioma (P<0.05).

Conclusion: Our multigene NGS in the simultaneous evaluation of multiple relevant markers revealed several novel genetic alterations in Chinese patients with glioma. NGS-based molecular analysis is a reliable and effective method for diagnosing brain tumors, assisting clinicians in evaluating additional potential therapeutic options, such as targeted therapy, for glioma patients in different racial/ethnic groups.
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http://dx.doi.org/10.2147/CMAR.S291681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092857PMC
April 2021

Macrophage Response Driven by Extracellular ATP.

Biol Pharm Bull 2021 ;44(5):599-604

Laboratory of Bioresponse Regulation, Graduate School of Pharmaceutical Sciences, Osaka University.

The purine nucleotide ATP is a fundamental unit in cellular energy metabolism. Extracellular ATP and its metabolites are also ligands for a family of receptors, known as purinergic receptors, which are expressed ubiquitously in almost every cell type. In the immune system, extracellular ATP and its signals regulate the migration and activation of immune cells to orchestrate the induction and resolution of inflammation. In this review, we provide an overview of purinergic receptors and their downstream signaling related to macrophage activation. We also discuss the roles of purinergic signaling for macrophage functions in physiological and pathological conditions.
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http://dx.doi.org/10.1248/bpb.b20-00831DOI Listing
January 2021

Prevalence and Risk Factors for Anxiety and Depression in Patients With COVID-19 in Wuhan, China.

Psychosom Med 2021 05;83(4):368-372

From the Surgery Intensive Care Unit (Li, Liu, Wang, Zhang, Gong, Duan) China-Japan Friendship Hospital; and Peking University Institute of Mental Health (Sun), National Clinical Research Center for Mental Disorders, Beijing, China.

Objective: Infectious diseases can cause psychological changes in patients. This study aimed to evaluate the prevalence and related risk factors for anxiety and depression in patients with COVID-19.

Methods: A cross-sectional study was performed on patients with COVID-19 admitted to the Sino-French New City branch of Wuhan Tongji Hospital from January to February 2020. The Zung Self-Rating Anxiety and Depression Scales were used to evaluate the prevalence of anxiety and depression. Demographic, clinical, and sociological data were also collected. Multivariable logistic regression analysis was used to identify independent risk factors of anxiety and depression in patients with COVID-19.

Results: In the current study, 183 patients were enrolled (mean age = 53 ± 9 years; 41.1% women). The prevalences of anxiety and depression were 56.3% and 39.3%, respectively. Logistic regression analysis revealed that older age, female sex, being divorced or widowed, COVID-19 disease duration, renal disease, and depression were identified as independent risk factors for anxiety in patients with COVID-19. Factors that were associated with depression were female sex, being widowed, COVID-19 disease duration, and anxiety.

Conclusions: This study demonstrates a high prevalence of anxiety and depression in patients with COVID-19 at the peak of the epidemic in Wuhan, China. The identification of demographic, clinical, and social factors may help identify health care professionals to provide psychological care as part of treatment for patients with COVID-19 and other life-threatening infectious diseases.
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http://dx.doi.org/10.1097/PSY.0000000000000934DOI Listing
May 2021

Intratympanic gentamicin injection for refractory ménière's disease (MD) has potential effect in preventing contralateral MD occurrence.

Acta Otolaryngol 2021 May 5:1-6. Epub 2021 May 5.

ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China.

Background: Ménière's disease (MD), characterized by episodic vertigo attacks and fluctuating progressive hearing loss, is treated by low-dose intratympanic gentamicin (ITG) injections. Whether ITG causes hearing loss is controversial, and knowledge about its effects on the contralateral hearing and vestibular function is lacking.

Aims/objectives: We aimed to evaluate the effect of ITG on bilateral auditory and otolith organ function in patients with unilateral refractory MD.

Material And Methods: The data of 30 patients was collected, including history, and pure tone audiometry and vestibular-evoked myogenic potentials (VEMPs) results before and one month after ITG treatment. Changes in vertigo were assessed at a two-year follow-up.

Results: One month after ITG injection, auditory thresholds between 125 Hz and 8 kHz on the injection side remained unchanged but have improved on the contralateral side at 125 Hz, 250 Hz, 1 kHz. The cervical and ocular VEMP solicitation rates on the injection side were lower than before the injection. Two years after treatment, vertigo was improved in 88.5% and complete controlled in 76.7% patients respectively.

Conclusions And Significance: The intractable vertigo of MD can be effectively controlled by ITG injection. This can improve the low and medium frequency hearing level in the contralateral ear, suggesting that it might help prevent contralateral MD occurrence.
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http://dx.doi.org/10.1080/00016489.2021.1915499DOI Listing
May 2021