Publications by authors named "Ping Yao"

331 Publications

Spindle-related brain activation in patients with insomnia disorder: An EEG-fMRI study.

Brain Imaging Behav 2021 Sep 9. Epub 2021 Sep 9.

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.

Sleep spindles have been implicated in sleep protection, depression and anxiety. However, spindle-related brain imaging mechanism underpinning the deficient sleep protection and emotional regulation in insomnia disorder (ID) remains elusive. The aim of the current study is to investigate the relationship between spindle-related brain activations and sleep quality, symptoms of depression and anxiety in patients with ID. Participants (n = 46, 28 females, 18-60 years) were recruited through advertisements including 16 with ID, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and 30 matched controls. Group differences in spindle-related brain activations were analyzed using multimodality data acquired with simultaneous electroencephalography and functional magnetic resonance imaging during sleep. Compared with controls, patients with ID showed significantly decreased bilateral spindle-related brain activations in the cingulate gyrus (familywise error corrected p ˂ 0.05, cluster size 4401 mm). Activations in the cingulate gyrus were negatively correlated with Pittsburgh Sleep Quality Index scores (r = -0.404, p = 0.005) and Self-Rating Anxiety Scale scores (r = -0.364, p = 0.013), in the pooled sample. These findings underscore the key role of spindle-related brain activations in the cingulate gyrus in subjective sleep quality and emotional regulation in ID.
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http://dx.doi.org/10.1007/s11682-021-00544-2DOI Listing
September 2021

High Red Meat Intake Exacerbates Dextran Sulfate-Induced Colitis by Altering Gut Microbiota in Mice.

Front Nutr 2021 20;8:646819. Epub 2021 Jul 20.

Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China.

Inflammatory bowel disease (IBD) is a serious hazard to public health, but the precise etiology of the disease is unclear. High intake of red meat diet is closely related to the occurrence of IBD. In this study, we investigated whether the high intake of red meat can increase the sensitivity of colitis and the underlying mechanism. Mice were fed with different levels of red meat for 8 weeks and then the colonic contents were analyzed by 16S rRNA sequencing. Then 3% dextran sulfate sodium was used to induce colitis in mice. We observed the severity of colitis and inflammatory cytokines. We found that high-dose red meat caused intestinal microbiota disorder, reduced the relative abundance of and , and increased the relative abundance of and . This in turn leads to an increase in colitis and inflammatory cytokine secretion. Moreover, we found that high red meat intake impaired the colon barrier integrity and decreased the expression of ZO-1, claudin, and occludin. We also found high red meat intake induced the production of more inflammatory cytokines such as IL-1β, TNF-α, IL-17, and IL-6 and inflammatory inducible enzymes such as COX-2 and iNOS in dextran sulfate sodium-induced colitis. These results suggest that we should optimize the diet and reduce the intake of red meat to prevent the occurrence of IBD.
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http://dx.doi.org/10.3389/fnut.2021.646819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329097PMC
July 2021

Insulin- and cholic acid-loaded zein/casein-dextran nanoparticles enhance the oral absorption and hypoglycemic effect of insulin.

J Mater Chem B 2021 Aug 30;9(31):6234-6245. Epub 2021 Jul 30.

State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai 200438, China.

Diabetes mellitus is the most common metabolic disease in the world. Herein, insulin- and cholic acid-loaded zein nanoparticles with dextran surfaces were fabricated to enhance the oral absorptions of insulin in the intestine and in the liver which is the primary action organ of endogenous insulin. In the nanoparticles, zein acted as cement to embed insulin, cholic acid and casein by hydrophobic interactions. The hydrophilic dextran conjugated to casein by the Maillard reaction was located on the nanoparticle surface. The nanoparticles had an insulin loading efficiency of 74.6%, a cholic acid loading efficiency of 55.1% and a hydrodynamic diameter of 267 nm. The dextran significantly increased the disperse stability of the nanoparticles, protected the loaded insulin from hydrolysis in digestive juices, and increased the trans-mucus permeability of the insulin. The embedded cholic acid molecules were consecutively exposed to the surface when the nanoparticles were gradually eroded by proteases. The exposed cholic acid promoted the absorptions of the nanoparticles in the ileum and liver via bile acid transporters. The effect of pretreated lymphatic transport inhibitor cycloheximide revealed that about half of the nanoparticles were transported via the intestinal lymphatic transport pathway and the other half of the nanoparticles were transported via portal blood absorption. The oral pharmacological bioavailability of the nanoparticles in type I diabetic mice was 12.5-20.5%. This study demonstrates that nanoparticles are a promising oral delivery system for insulin.
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http://dx.doi.org/10.1039/d1tb00806dDOI Listing
August 2021

The Impact of an Internet Use Promotion Programme on Communication, Internet Use, and the Extent of Social Networks among Low-Income Older Adults.

Ageing Int 2021 Jul 21:1-24. Epub 2021 Jul 21.

School of Health Studies, Northern Illinois University, Wirtz Hall 254, DeKalb, Illinois 60115 USA.

We examined whether an internet use promotion intervention influences low-income older adults' communication modes, internet use, and social networks using existing data collected for an intervention. Participants living in public senior housing facilities in the United States ( = 77) completed surveys before and after a 12-week computer and internet training. The six-item Lubben Social Network Scale (LSNS-6) was used to measure the extent of older adults' social networks. The primary mode of communication shifted from more traditional means to internet-based communications ( < .0005 in a Fisher's exact test). The frequency of internet use significantly increased ( < .00005 in a one-sided Sign test). Overall, the LSNS-6 score increased by 4.1 points ( < .00005 in a Welch's t-test). The LSNS-6 score increase was significantly larger among African Americans than Whites, controlling for gender ( < .05 in negative binomial regression). Moderate ( < .005) and frequent internet users ( < .05) had higher LSNS-6 scores than rare internet users at posttest when gender and race were controlled for in linear regression. Comparatively more improvement in the extent of social networks among African Americans suggests greater benefits of such interventions for population groups of disadvantaged backgrounds. Larger social networks among moderate and frequent internet users than rare users suggest positive impacts of internet communications on social networks.
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http://dx.doi.org/10.1007/s12126-021-09422-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294218PMC
July 2021

The Improved Lipid Accumulation Product is an Accurate Index for Predicting Metabolic Syndrome in the Xinjiang Population.

Biomed Environ Sci 2021 Jun;34(6):503-507

Department of Public Health, Shihezi University School of Medicine, Shihezi 832000, Xinjiang, China.

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http://dx.doi.org/10.3967/bes2021.070DOI Listing
June 2021

Dietary iron overload mitigates atherosclerosis in high-fat diet-fed apolipoprotein E knockout mice: Role of dysregulated hepatic fatty acid metabolism.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 Oct 7;1866(10):159004. Epub 2021 Jul 7.

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

The atherosclerosis "iron hypothesis" generates a fair amount of debate since it has been proposed. Here, we revisited the "iron hypothesis" by examining whether dietary iron overload would intensify iron deposition in plaques and thus lead to further exacerbation of atherosclerosis in apolipoprotein E knockout (ApoE KO) mice. ApoE KO mice were fed either a normal chow diet (ND) or a high fat diet (HFD) supplemented with or without 2% carbonyl iron (Fe) for 16 weeks. However, contrary to our assumption, dietary iron overloading did not intensify, but rather diminished the atherosclerotic lesion area by 65.3%, which was accompanied by significantly decreased serum total cholesterol, triglyceride and low-density lipoprotein cholesterol contents, together with hepatic lipid accumulation decline, despite the evident existence of aortic iron accumulation and the typical signs of iron overload in ApoE KO mice. Using isobaric tag for absolute quantification (iTRAQ) proteomics approach, hepatic CD36 and fatty acid binding proteins-mediated fatty acid (FA) uptake and trafficking impairment were identified as the key potential pathomechanisms by which iron overload diminishes atherosclerotic lesions. Furthermore, downstream hepatic FA de novo biosynthesis was enhanced and FA oxidation was inhibited to compensate for the FA deficiency triggered by iron overload-impaired fatty acid uptake and trafficking. Our findings suggested that dietary iron overload is not atherogenic in ApoE KO mice, and more research efforts are warranted to revisit the "iron hypothesis" of atherosclerosis.
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http://dx.doi.org/10.1016/j.bbalip.2021.159004DOI Listing
October 2021

Hsa_circ_0074371 Regulates Proliferation, Apoptosis, Migration, and Invasion via the miR-582-3p/LRP6 Axis in Trophoblast Cells.

Biochem Genet 2021 Jun 28. Epub 2021 Jun 28.

Department of Obstetrics, Ju County People's Hospital of Rizhao, Rizhao, 276500, China.

Fetal growth restriction (FGR) ranks second among causes of perinatal death. Circular RNA hsa_circ_0074371 (hsa_circ_0074371) is reported to be downregulated in FGR placentae. However, the role and regulatory mechanism of hsa_circ_0074371 in FGR pathogenesis are indistinct. Expression of hsa_circ_0074371, microRNA (miR)-582-3p, and low-density lipoprotein receptor-related protein 6 (LRP6) mRNA in FGR placentae and trophoblast cells (HTR-8/SVneo) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between hsa_circ_0074371 or LRP6 and miR-582-3p was verified by dual-luciferase reporter and/or RNA immunoprecipitation (RIP), RNA pull-down assays. The proliferation, cell cycle progression, apoptosis, migration, and invasion of HTR-8/SVneo cells were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, or transwell assays. Caspase3 activity was analyzed with a commercial kit. The protein levels of c-myc, cyclinD1, matrix metalloproteinase (MMP) 2, MMP9, and LRP6 were examined by western blotting. We observed that hsa_circ_0074371 and LRP6 were downregulated while miR-582-3p was upregulated in FGR placentae and HTR-8/SVneo cells. Hsa_circ_0074371 modulated LRP6 expression via sponging miR-582-3p. Hsa_circ_0074371 knockdown induced cell cycle arrest, apoptosis, and inhibited cell proliferation, migration, and invasion in HTR-8/SVneo cells. MiR-582-3p inhibitor reversed hsa_circ_0074371 silencing me on proliferation, migration, and invasion of HTR-8/SVneo cells. LRP6 overexpression overturned the inhibitory effect of miR-582-3p mimic on proliferation, migration, and invasion of HTR-8/SVneo cells. In conclusion, hsa_circ_0074371 downregulation inhibited proliferation, migration, and invasion of trophoblast cells via sponging miR-582-3p and decreasing LRP6 expression, providing a new mechanism related to FGR pathogenesis.
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http://dx.doi.org/10.1007/s10528-021-10095-2DOI Listing
June 2021

Quercetin and non-alcoholic fatty liver disease: A review based on experimental data and bioinformatic analysis.

Food Chem Toxicol 2021 Aug 2;154:112314. Epub 2021 Jun 2.

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Wuhan, 430030, China; Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address:

Quercetin, a polyphenol widely present in the plant kingdom, has received great interest due to pleiotropic effects. As evidenced by animal and cellular studies, quercetin exerts hepatoprotection against non-alcoholic fatty liver disease (NAFLD), particularly in hepatic steatosis and hepatitis. Mechanically, various hypotheses of such protective effects have been actively proposed, including improving fatty acid metabolism, anti-inflammation, anti-oxidant, modulating gut microbiota and bile acid, etc. Here, the role of quercetin in NAFLD was summarized. With a particular focus on molecular mechanism, we comprehensively discussed the pathways of quercetin on NAFLD based on the analysis from Gene Expression Omnibus (GEO) database and experimental evidence.
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http://dx.doi.org/10.1016/j.fct.2021.112314DOI Listing
August 2021

Protein S-Palmitoylation and Lung Diseases.

Adv Exp Med Biol 2021 ;1304:165-186

School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

S-palmitoylation of protein is a posttranslational, reversible lipid modification; it was catalyzed by a family of 23 mammalian palmitoyl acyltransferases in humans. S-palmitoylation can impact protein function by regulating protein sorting, secretion, trafficking, stability, and protein interaction. Thus, S-palmitoylation plays a crucial role in many human diseases including mental illness and cancers. In this chapter, we systematically reviewed the influence of S-palmitoylation on protein performance, the characteristics of S-palmitoylation regulating protein function, and the role of S-palmitoylation in pulmonary inflammation and pulmonary hypertension and summed up the treatment strategies of S-palmitoylation-related diseases and the research status of targeted S-palmitoylation agonists/inhibitors. In conclusion, we highlighted the potential role of S-palmitoylation and depalmitoylation in the treatment of human diseases.
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http://dx.doi.org/10.1007/978-3-030-68748-9_10DOI Listing
May 2021

Carbon monoxide alleviates senescence in diabetic nephropathy by improving autophagy.

Cell Prolif 2021 Jun 7;54(6):e13052. Epub 2021 May 7.

Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Laboratory of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objectives: Senescence, characterized by permanent cycle arrest, plays an important role in diabetic nephropathy (DN). However, the mechanism of renal senescence is still unclear, and the treatment targeting it remains to be further explored.

Materials And Methods: The DN mice were induced by HFD and STZ, and 3 types of renal cells were treated with high glucose (HG) to establish in vitro model. Senescence-related and autophagy-related markers were detected by qRT-PCR and Western blot. Further, autophagy inhibitors and co-immunoprecipitation were used to clarify the mechanism of CO. Additionally, the specific relationship between autophagy and senescence was explored by immunofluorescence triple co-localization and ELISA.

Results: We unravelled that senescence occurred in vivo and in vitro, which could be reversed by CO. Mechanistically, we demonstrated that CO inhibited the dysfunction of autophagy in DN mice partly through dissociating Beclin-1-Bcl-2 complex. Further results showed that autophagy inhibitors blocked the improvement of CO on senescence. In addition, the data revealed that autophagy regulated the degradation of senescence-related secretory phenotype (SASP) including Il-1β, Il-6, Tgf-β and Vegf.

Conclusions: These results suggested that CO protects DN mice from renal senescence and function loss via improving autophagy partly mediated by dissociating Beclin-1-Bcl-2 complex, which is possibly ascribed to the degradation of SASP. These findings bring new ideas for the prevention and treatment of DN and the regulation of senescence.
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http://dx.doi.org/10.1111/cpr.13052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168421PMC
June 2021

Quercetin Attenuates Atherosclerotic Inflammation by Inhibiting Galectin-3-NLRP3 Signaling Pathway.

Mol Nutr Food Res 2021 08 20;65(15):e2000746. Epub 2021 Jun 20.

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Scope: Atherosclerosis is the underlying pathogenesis of cardiovascular events caused by inflammation, and dietary intervention has been recommended as one fundamental prevention strategy. Herein, the anti-arteriosclerotic properties of quercetin are investigated by modulating galectin-3 (Gal-3)-NLR family, pyrin domain-containing 3 (NLRP3) pathway.

Methods And Results: Plaques from ApoE mice fed by high-fat diet (HFD) with or without quercetin (100 mg (kg·bw) ) for 16 weeks, and carotid plaques from patients with carotid stenosis are collected for histopathological examinations and molecular mechanism assays. Quercetin significantly alleviates atherosclerotic lesions and reduces lipid retention caused by HFD. Proteomic technology identified Gal--3 increased by HFD but lowered by quercetin. Furthermore, immunofluorescence and immunohistochemistry exhibit higher expressions of Gal-3 and NLRP3 in carotid plaques and plaques from HFD-fed mice, which are concurrently down-regulated by quercetin. Similar to TD139, quercetin dramatically suppresses NLRP3 inflammasome activation in oxidized low-density lipoprotein-laden macrophages, and accordingly alleviates cellular steatosis and IL-1β secretion, which is abolished by recombinant Gal-3. Co-immunoprecipitation shows Gal-3 binding to NLRP3 promotes inflammasome activation.

Conclusion: Gal-3 initiates inflammatory lesions by activating NLRP3 inflammasome which functions as a candidate target of quercetin exerting favorable anti-atherogenic effects. The findings highlight a promising strategy for atherosclerosis prevention and treatment by naturally-occurring quercetin.
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http://dx.doi.org/10.1002/mnfr.202000746DOI Listing
August 2021

Potential Mechanisms and Effects of Efferocytosis in Atherosclerosis.

Front Endocrinol (Lausanne) 2020 1;11:585285. Epub 2021 Feb 1.

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Atherosclerosis (AS) is the main pathological basis for the development of cardio-cerebrovascular diseases. Abnormal accumulation of apoptotic and necrotic cells resulted in plaque enlargement, necrotic core formation and plaque rupture in AS. Under physiological conditions, apoptotic cells (ACs) could be effectively phagocytized and cleared by phagocyte-mediated efferocytosis. In contrast, the clearance efficiency of ACs in AS plaque was much lower because of the impaired efferocytosis in AS. Recent findings have made great progress on the molecular mechanisms of efferocytosis process and dynamic regulation, and its dysfunction on organismal health. Yet, there are still few effective treatments for this process. This article reviews the mechanism of efferocytosis and the role of efferocytosis in AS, highlighting a novel therapeutic strategy for AS, which mainly prevents the progression of plaque by targeting efferocytosis.
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http://dx.doi.org/10.3389/fendo.2020.585285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883484PMC
June 2021

Prefabricated Expanded Flap Combined With Expanded Scalp Flap for Total Face Resurfacing.

Ann Plast Surg 2021 03;86(3S Suppl 2):S265-S268

From the Department of Plastic Surgery, Hangzhou Plastic Surgery Hospital, Hangzhou, Zhejiang, China.

Abstract: Reconstruction of total facial deformities and defects has been a major challenge of reconstructive surgery. Allotransplantation is limited by the number of donors and the need for life-long immunosuppression. Autotransplantation, where multiple autogenous tissue grafts from various donor sites are used to repair facial defects, inevitably leaves conspicuous patchwork scars. A prefabricated monoblock flap, although the preferred treatment modality, is limited by insufficient blood supply and the large size of the flap. In the Journal of Craniofacial Surgery (2014;25:21-25), Li et al applied the technique of flap prefabrication and stem cell-assisted tissue expansion to reconstruct total facial injuries, but the operations were complicated and the final expanded flap area was also uncertain. This article introduces an approach to reconstruct total facial injuries with a prefabricated expanded thoracic flap combined with an expanded scalp flap (called combined flaps), which not only solves the limitations of blood supply and expanded volume but also reduces patchwork scars. The approach is a simple, feasible, and effective surgical method for total face resurfacing.
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http://dx.doi.org/10.1097/SAP.0000000000002635DOI Listing
March 2021

Clinical effectiveness and safety of salvia miltiorrhiza depside salt combined with aspirin in patients with stable angina pectoris: A multicenter, pragmatic, randomized controlled trial.

Phytomedicine 2021 Jan 10;81:153419. Epub 2020 Dec 10.

Department of Epidemiology, University of California-Los Angeles, 405 Hilgard Avenue, California 90095, USA. Electronic address:

Background: Salvia Miltiorrhiza Depside Salt (SMDS) was extracted from Salvia miltiorrhiza with high-quality control of active principles. In 2005, China's FDA approved the use of SMDS for stable angina pectoris (SAP), but the evidence of SMDS combined with aspirin remains unclear.

Purpose: The aim of this study was to assess the clinical effectiveness and safety of SMDS combined with aspirin in patients with SAP.

Methods: A multicenter, pragmatic, three-armed parallel group and an individually randomized controlled superiority trial was designed. Participants aged 35 to 75 years old with SAP were recruited from four "Class Ⅲ Grade A" hospitals in China. Participants who were randomized into the SMDS group were treated with SMDS by intravenous drip. Participants in the control group received aspirin enteric-coated tablets (aspirin). Participants who were randomly assigned to the combination group received SMDS combined with aspirin. All participants received standard care from clinicians, without any restrictions. The primary outcome measure was thromboelastography (TEG). Secondary outcome measures included symptom score of the Seattle Angina Questionnaire (SAQ), visual analogue scale (VAS) score of traditional Chinese medicine (TCM) symptoms, platelet aggregation measured by light transmittance aggregometry (LTA), and fasting blood glucose. Effectiveness evaluation data were collected at baseline and ten days after treatment. Researchers followed up with participants for one month after treatment to determine whether adverse events (AEs) or adverse drug reactions (ADRs) such as bleeding tendency occurred. All statistical calculations were carried out with R 3.5.3 statistical analysis software.

Results: A total of 135 participants completed follow-up data on the primary outcome after ten days of treatment. Participants in the SMDS combined aspirin group had the highest improvement rate of sensitivity in AA% [p < 0.001, 95% CI (0.00-0.00)], from 30.6% before treatment to 81.6% after treatment. Participants with drug resistance (AA% < 20%) in the SMDS combined with aspirin group also had the highest sensitivity rate [p < 0.001, 95% CI (0.00-0.00)] after treatment (accounting for 81.0% of the combination group and 60.7% of the sensitive participants). The improvement of TCM symptoms in participants treated with SMDS combined with aspirin was significantly better than that of the aspirin group [MD = 1.71, 95% CI (0.15-3.27), p = 0.032]. There were no significant differences in other indexes (R, TPI, MA, K, CI, α value) of TEG, SAQ, platelet aggregation and fasting blood glucose among the three groups. No bleeding tendency or ADRs occurred in all participants.

Conclusion: SMDS combined with aspirin is a clinically effective and safe intervention to treat adults aged 35 and older with SAP. This trial shows that SMDS combined with aspirin can significantly improve the sensitivity rate of AA% in TEG and the VAS score of TCM symptoms. Further large samples and high-quality research are needed to determine if certain participants might benefit more from SMDS combined with aspirin. The study protocol was registered in the Clinical Trials USA registry (registration No. NCT02694848).
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http://dx.doi.org/10.1016/j.phymed.2020.153419DOI Listing
January 2021

PFAS exposure and overweight/obesity among children in a nationally representative sample.

Chemosphere 2021 Apr 3;268:128852. Epub 2020 Nov 3.

Department of Epidemiology and Biostatistics, College for Public Health & Social Justice, Saint Louis University, 3545 Lafayette Avenue, Saint Louis, MO, 63104, USA. Electronic address:

Purpose: Perfluoroalkyl substances (PFASs) are a class of manmade chemicals commonly used in consumer product manufacturing. Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are two of the most highly studied PFASs. Both are present in the blood of the most Americans. PFASs are associated with intermediate cardiovascular disease (CVD) outcomes, but their relationship with obesity, a risk factor for intermediate and advanced CVD, remains largely unconfirmed. In this context, we aimed to explore the relationship between PFASs and both overweight/obesity and abdominal obesity among children.

Methods: We examine associations between PFOA and PFOS levels, and Body Mass Index (BMI) and waist circumference (WC) in a representative sample (N = 2473) of US children, aged 12-18 years from the Centers for Disease Control and Prevention's National Health and Nutrition Examination Survey 1999-2012. Overweight/obesity is defined as age-, sex-specific BMI z-score ≥ 85th percentile; abdominal obesity is defined as age-, sex-specific waist circumference ≥90th percentile.

Results: Associations between PFASs and anthropometric outcomes show a dose-response relationship overall. For overweight/obese BMI z-score, findings indicate OR = 1.42 and 95% CI: 0.85-2.38 for quartile 2 of PFOA exposure; OR = 2.22 (95% CI: 1.20-4.13) for quartile 3 of PFOA exposure; and OR = 2.73 (95% CI:1.10-6.74) for quartile 4 of PFOA exposure.

Discussion: Findings indicate an association between elevated PFOA and overweight/obesity among children after multivariable adjustment.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128852DOI Listing
April 2021

Propranolol-induced inhibition of unconditioned stimulus-reactivated fear memory prevents the return of fear in humans.

Transl Psychiatry 2020 10 13;10(1):345. Epub 2020 Oct 13.

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Chinese Academy of Medical Sciences Research Unit (No.2018RU006), Peking University, Beijing, China.

Fear memories can be reactivated by a fear-associated conditioned stimulus (CS) or unconditioned stimulus (US) and then undergo reconsolidation. Propranolol administration during CS retrieval-induced reconsolidation can impair fear memory that is specific to the reactivated CS. However, from a practical perspective, the US is often associated with multiple CSs, and each CS can induce a fear response. The present study sought to develop and test a US-based memory retrieval interference procedure with propranolol to disrupt the original fear memory and eliminate all CS-associated fear responses in humans. We recruited 127 young healthy volunteers and conducted three experiments. All of the subjects acquired fear conditioning, after which they received the β-adrenergic receptor antagonist propranolol (40 mg) or placebo (vitamin C) and were exposed to the US or CS to reactivate the original fear memory. Fear responses were measured. Oral propranolol administration 1 h before US retrieval significantly decreased subsequent fear responses and disrupted associations between all CSs and the US. However, propranolol administration before CS retrieval only inhibited the fear memory that was related to the reactivated CS. Moreover, the propranolol-induced inhibition of fear memory reconsolidation that was retrieved by the US had a relatively long-lasting effect (at least 2 weeks) and was also effective for remote fear memory. These findings indicate that the US-based memory retrieval interference procedure with propranolol can permanently decrease the fear response and prevent the return of fear for all CSs in humans. This procedure may open new avenues for treating fear-related disorders.
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http://dx.doi.org/10.1038/s41398-020-01023-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555531PMC
October 2020

Altered thalamic connectivity in insomnia disorder during wakefulness and sleep.

Hum Brain Mapp 2021 01 13;42(1):259-270. Epub 2020 Oct 13.

Beijing City Key Lab for Medical Physics and Engineering, Institute of Heavy Ion Physics, School of Physics, Peking University, Beijing, China.

Insomnia disorder is the most common sleep disorder and has drawn increasing attention. Many studies have shown that hyperarousal plays a key role in the pathophysiology of insomnia disorder. However, the specific brain mechanisms underlying insomnia disorder remain unclear. To elucidate the neuropathophysiology of insomnia disorder, we investigated the brain functional networks of patients with insomnia disorder and healthy controls across the sleep-wake cycle. EEG-fMRI data from 33 patients with insomnia disorder and 31 well-matched healthy controls during wakefulness and nonrapid eye movement sleep, including N1, N2 and N3 stages, were analyzed. A medial and anterior thalamic region was selected as the seed considering its role in sleep-wake regulation. The functional connectivity between the thalamic seed and voxels across the brain was calculated. ANOVA with factors "group" and "stage" was performed on thalamus-based functional connectivity. Correlations between the misperception index and altered functional connectivity were explored. A group-by-stage interaction was observed at widespread cortical regions. Regarding the main effect of group, patients with insomnia disorder demonstrated decreased thalamic connectivity with the left amygdala, parahippocampal gyrus, putamen, pallidum and hippocampus across wakefulness and all three nonrapid eye movement sleep stages. The thalamic connectivity in the subcortical cluster and the right temporal cluster in N1 was significantly correlated with the misperception index. This study demonstrated the brain functional basis in insomnia disorder and illustrated its relationship with sleep misperception, shedding new light on the brain mechanisms of insomnia disorder and indicating potential therapeutic targets for its treatment.
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http://dx.doi.org/10.1002/hbm.25221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721231PMC
January 2021

Amphiphilic QP(DMAEMA--LMA)--POEGMA Random-Block Terpolymers as Nanocarriers for Insulin.

Biomedicines 2020 Oct 4;8(10). Epub 2020 Oct 4.

Department of Macromolecular Science, Fudan University, 2005 Songhu Road, Shanghai 200438, China.

We report on the utilization of the amphiphilic poly[quaternized (2-(-dimethylamino) ethyl methacrylate)]--(lauryl methacrylate))--poly[(oligo ethylene glycol) methyl ether methacrylate] QP(DMAEMA--LMA)--POEGMA cationic diblock terpolymer aggregates as nanocarriers for insulin delivery applications. QP(DMAEMA--LMA)--POEGMA random diblock terpolymer is derived from the chemical modification of the precursor amino diblock copolymer via quaternization, producing permanent positive charges on the macromolecular chain. The QP(DMAEMA--LMA)--POEGMA diblock terpolymer as well as its amino precursor investigated self-assemble in aqueous media, forming aggregates. In vitro cytotoxicity and in vivo biocompatibility studies on QP(DMAEMA--LMA)--POEGMA and its amino precursor aggregates, showed good cytocompatibility and biocompatibility. QP(DMAEMA--LMA)--POEGMA aggregates were chosen to be complexed with insulin due to their self-assembly features and the permanent positive charge in each amino group. QP(DMAEMA--LMA)--POEGMA aggregates were complexed with insulin through electrostatic interactions. Light scattering techniques were used in order to study the ability of the polymer aggregates to complex with insulin, to determine critical physicochemical parameters such as size, mass, and surface charge of the stable complexes and study the effect of salt addition on their properties. The results showed that in both cases, the complexation process was successful and as the insulin concentration increases, nanosized complexes of different physicochemical characteristics (mass, size, surface charge) and spherical morphology are formed. UV-Vis and fluorescence spectroscopy studies showed that no conformational changes of insulin occurred after the complexation.
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http://dx.doi.org/10.3390/biomedicines8100392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599562PMC
October 2020

Oxidative stress-dependent frataxin inhibition mediated alcoholic hepatocytotoxicity through ferroptosis.

Toxicology 2020 12 2;445:152584. Epub 2020 Oct 2.

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Alcoholic liver disease (ALD) is one of the severe liver diseases, resulting in high morbidity and mortality. However, frataxin, a mitochondrial protein mainly participating in iron homeostasis and oxidative stress, remains uncertain in the pathogenesis of ALD. In the present study, the role of frataxin in ALD was investigated. Ethanol (100 mM) decreased frataxin expression at 48 and 72 h in HepG2. Dramatically, in HepG2 overexpressing cytochrome P450 2E1 (HepG2), frataxin level was down-regulated with ethanol stimulation at 12 h. Moreover, chronically feeding ethanol to mice via Lieber-DeCarli liquid diet (30 % of total calories) for 15 weeks significantly inhibited frataxin expression. Ferroptosis signature proteins were dysregulated, accompanied by mitochondrial damage of morphology, enhanced malondialdehyde and decreased glutathione in the liver, as well as accumulation of reactive oxygen species and mitochondrial labile iron pool in primary hepatocytes. Notably, proteomics screening of frataxin deficient-HepG2 further suggested frataxin was associated with ferroptosis. Furthermore, the ferroptosis inhibitor ferrostatin-1 blocked the increase of lactate dehydrogenase release by ethanol in HepG2. Most importantly, frataxin deficiency enhanced ferroptosis driven by ethanol via evaluating the levels of lactate dehydrogenase, cell morphological changes, mitochondrial labile iron pool, and lipid peroxidation. Conversely, restoring frataxin alleviated the sensitivity to ferroptosis. In addition, frataxin overexpression mitigated the sensitivity of ethanol-induced ferroptosis in HepG2. Collectively, our study revealed that frataxin-mediated ferroptosis contributed to ALD, highlighting a potential therapeutic strategy for ALD.
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http://dx.doi.org/10.1016/j.tox.2020.152584DOI Listing
December 2020

Quercetin Alleviates Ferroptosis of Pancreatic β Cells in Type 2 Diabetes.

Nutrients 2020 Sep 27;12(10). Epub 2020 Sep 27.

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.

(1) Background: Pancreatic iron deposition has been found in the progression of type 2 diabetes (T2DM); however, whether ferroptosis contributes to the dysfunction of pancreatic β cells (PBC) remains enigmatic. Moreover, the potential protective effect of quercetin is also elusive; (2) Methods: T2DM mice model was established by multiple low dose streptozocin (STZ) injection, after which quercetin was intervened for 4 months; (3) Results: Substantially normalized glucose tolerance, diabetic symptoms, homeostasis model assessment for insulin resistance (HOMA-IR), and homeostasis model assessment for β cell (HOMA-β) index in comparison with the findings of T2DM control. Distorted pancreatic islets and especially shrunken mitochondria with cristae loss in PBC were observed in T2DM mice, which was ameliorated by quercetin. Meanwhile, quercetin lowered the iron level particularly in the islet in T2DM mice. In spite of compensatory xCT up-regulation, T2DM molding depleted glutathione (GSH), down-regulated glutathione peroxidase 4 (GPX4), and induced oxidative stress in pancreatic tissue, which was abolished partially by quercetin. More importantly, insulin secretion was worsened by ferroptosis-inducing erastin or RAS-selective lethal compounds 3 (RSL-3). Quercetin, ferroptosis inhibitor ferrostatin-1 and iron-chelating deferoxamine, rescued cell viability when cells were challenged with high-glucose; (4) Conclusions: Our findings identify that ferroptosis contributes to the PBC loss and dysfunction. Quercetin exerts beneficial effects on T2DM potentially by inhibiting pancreatic iron deposition and PBC ferroptosis, highlighting promising control strategies of T2DM by quercetin.
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http://dx.doi.org/10.3390/nu12102954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600916PMC
September 2020

Protamine and BSA-dextran complex emulsion improves oral bioavailability and anti-tumor efficacy of paclitaxel.

Drug Deliv 2020 Dec;27(1):1360-1368

State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai, China.

Food protein and polysaccharide complex emulsions are safe carriers of hydrophobic drugs and nutrients. To improve oral bioavailability and therapeutic/healthy efficacy of hydrophobic drugs and nutrients, herein, protamine (PRO), a cationic cell-penetrating peptide, was introduced into protein and polysaccharide complex emulsion. The electrostatic complex of PRO and BSA-dextran conjugate (BD) produced by Maillard reaction was used as emulsifier to produce oil-in-water emulsion (@BD/PRO). The BSA molecules were crosslinked at the oil-water interface by a heat treatment and the PRO chains were simultaneously anchored in the interface. BD emulsion (@BD) without PRO was produced for comparation. Paclitaxel (PTX), a hydrophobic antineoplastic drug, was encapsulated in the emulsions with 99% loading efficiency and 6.4% loading capacity. The emulsions had long-term stability. The bioavailability and H22 tumor inhibition efficacy of [email protected]/PRO were 40% and 70% higher than those of [email protected], respectively, after oral administration in the mice. More importantly, orally administrated [email protected]/PRO had the same anti-tumor efficacy as intravenously injected commercial PTX injection. No abnormality was observed in the main organs of the mice after consecutive oral administration of [email protected]/PRO. This study indicates that @BD/PRO is an excellent carrier of hydrophobic drugs/nutrients and is suitable for long-term oral administration.
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http://dx.doi.org/10.1080/10717544.2020.1825543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580837PMC
December 2020

Intensive Running Enhances NF-κB Activity in the Mice Liver and the Intervention Effects of Quercetin.

Nutrients 2020 Sep 11;12(9). Epub 2020 Sep 11.

Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Background: Emerging evidence has supported that intensive exercise induces weakened performance and immune and metabolic disorders. We systematically evaluated the effects of quercetin against hepatic inflammatory damage caused by repeated intensive exercise and explored the potential mechanism.

Methods: Male BALB/c mice were administered quercetin (100 mg/kg BW) for four weeks, and performed a treadmill running protocol of 28 m/min, 5° slope, 90 min/day concurrently for the last seven days.

Results: Quercetin administration reduced the leakage of aspartic acid and alanine aminotransferase and improved ultrastructural abnormalities such as swelling, and degeneration caused by high-intensity running in mice. Quercetin significantly decreased the hepatic and plasmatic levels of inflammatory cytokines IL-1β, IL-6, TNF-α, inducible nitric oxide synthase, cyclooxygenase-2 and intercellular adhesion molecule-1-provoked by over-exercise. Furthermore, diminished activation and nuclear translocation of NF-κB were found after quercetin treatment through inhibiting IKKα and Iκbα phosphorylation of intensive running mice.

Conclusion: Quercetin offers protection for mouse livers against intensive sports-induced inflammatory injury, and the suppression of the NF-κB signal transduction pathway may play a role in its anti-inflammatory effects. Our findings broaden our understanding of natural phytochemicals as a promising strategy to prevent excessive exercise damage.
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http://dx.doi.org/10.3390/nu12092770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551556PMC
September 2020

Narrative review on potential role of gut microbiota in certain substance addiction.

Prog Neuropsychopharmacol Biol Psychiatry 2021 03 6;106:110093. Epub 2020 Sep 6.

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, 430030 Wuhan, China; Department of Nutrition and Food Hygiene and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, 430030 Wuhan, China. Electronic address:

As a neuropsychiatric disorder, substance addiction represents a major public health issue with high prevalence and mortality in many countries. Recently, gut microbiota has been certified to play a part in substance addiction through various mechanisms. Hence, we mainly focused on three substance including alcohol, cocaine and methamphetamine in this review, and summarized their relationships with gut microbiota, respectively. Besides, we also concluded the possible treatments for substance addiction from the perspective of applying gut microbiota. This review aims to build a bridge between substance addiction and gut microbiota according to existing evidences, so as to excavate the possible bi-directional function of microbiota-gut-brain axis in substance addiction for developing therapeutic strategies in the future.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110093DOI Listing
March 2021

Corrigendum to "Circulating essential metals and lung cancer: Risk assessment and potential molecular effects" [Environ. Int. 127 (2019) 685-693].

Environ Int 2020 Oct 1;143:106072. Epub 2020 Sep 1.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.envint.2020.106072DOI Listing
October 2020

Effectiveness of exercise intervention on fall-related fractures in older adults: a systematic review and meta-analysis of randomized controlled trials.

BMC Geriatr 2020 09 4;20(1):322. Epub 2020 Sep 4.

Department of Orthopaedics, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, No. 6 Huanghe Road, Changshu, 215500, China.

Background: Exercise intervention can significantly improve physical function and bone strength; however, the effect of exercise on fall-related fractures in older adults remains controversial. This study aimed to assess the effectiveness of exercise intervention on fall-related fractures in older adults by conducting a meta-analysis of randomized controlled trials (RCTs).

Methods: PubMed, EMBASE, and Cochrane databases were systematically searched for RCTs through November 24, 2019 to investigate the effectiveness of exercise intervention on fall-related fractures in older adults. Pooled relative risk (RR) with 95% confidence interval (CI) was calculated using the random-effects model. Sensitivity, subgroup, and publication bias analyses were also conducted.

Results: A total of 7704 older adults and 428 fall-related fracture events from 20 RCTs were selected for the final meta-analysis. The follow-up duration across included trials ranged from 6.0 months to 7.0 years. The pooled RR suggested that exercise intervention was associated with a reduced fall-related fracture risk in older adults (RR: 0.74; 95% CI: 0.59-0.92; P = 0.007; I = 12.6%). The pooled conclusion was robust and not affected by any individual trial. Subgroup analysis revealed that the significant effect of exercise intervention on fall-related fractures was mainly detected when the study reported results from both male and female subjects, when it did not report the baseline body mass index, when individuals received both home- and center-based interventions, when the follow-up duration was > 1.0 year, and when it was a high-quality study.

Conclusions: Regular exercise intervention could prevent fall-related fractures in older adults. Further large-scale RCTs should be conducted to assess the effectiveness of different exercise programs on fall-related fractures at various sites.
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http://dx.doi.org/10.1186/s12877-020-01721-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650290PMC
September 2020

Healthy lifestyle and cancer risk among Chinese population in the Dongfeng-Tongji cohort.

Ann Med 2020 11 30;52(7):393-402. Epub 2020 Jul 30.

Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Studies on the association between healthy lifestyle and cancer risk are limited among the old Chinese population.

Methods: The healthy lifestyle score was derived from smoking, drinking, diet, body mass index and physical activity among 23734 retired employees from the Dongfeng-Tongji Cohort. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). The rate advancement periods (RAPs) and the population attributable risk percentage (PAR%) were estimated to indicate the benefits of removing risk lifestyle factors.

Results: During a median follow-up of 8.16 years, 2023 cancer cases were identified. Compared with 0-2 points of the healthy lifestyle score, the HRs were 0.87 (95% CI: 0.76, 0.99), 0.83 (95% CI: 0.73, 0.94), and 0.74 (95% CI: 0.64, 0.86) for 3, 4, and 5 points, respectively, with the corresponding RAPs of -4.40 (95% CI: -8.39, -0.41), -5.84 (95% CI: -9.77, -1.90), and -9.14 (95% CI: -14.03, -4.25), respectively. Approximately 15% of incident cancer cases among total population and 22% among men would be prevented by following all 5 healthy lifestyle factors.

Conclusions: The current study suggests that healthy lifestyle could reduce cancer risk in the retired Chinese population, especially in males. Key messages Healthy lifestyle derived by smoking, drinking, diet, body mass index and physical activity presented a strong protective effect on cancer risk among the retired Chinese population, especially in males. We employed the rate advancement periods and the population attributable risk percentage to indicate the benefits of adopting healthy lifestyle and we found that following all 5 healthy lifestyle factors could delay the risk of developing cancer by 9.14 years and prevent 15% of incident cancer cases.
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http://dx.doi.org/10.1080/07853890.2020.1798017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877923PMC
November 2020

Correlation between gastrointestinal symptoms and disease severity in patients with COVID-19: a systematic review and meta-analysis.

BMJ Open Gastroenterol 2020 07;7(1)

Gastroenterology, Xinjiang Medical University Affiliated First Hospital, Urumqi, Xinjiang, China

Objective: To study the correlation between gastrointestinal (GI) symptoms and disease severity in patients with COVID-19.

Design: We searched six databases including three Chinese and three English databases for all the published articles on COVID-19. Studies were screened according to inclusion and exclusion criteria. The relevant data were extracted and all the statistical analyses were performed using Revman5.3.

Result: In a meta-analysis of 9 studies, comprising 3022 patients, 479 patients (13.7%, 95% CI 0.125 to 0.149) had severe disease and 624 patients (14.7%, 95% CI 0.136 to 0.159) had GI symptoms. Of 624 patients with GI symptoms, 118 patients had severe disease (20.5%, 95% CI 0.133 to 0.276) and of 2397 cases without GI symptoms, 361 patients had severe disease (18.2%, 95% CI 0.129 to 0.235). Comparing disease severity of patients with and without GI symptoms, the results indicated: I²=62%, OR=1.21, 95% CI 0.94 to 1.56, p=0.13; there was no statistically significant difference between the two groups. The funnel plot was symmetrical with no publication bias.

Conclusion: Current results are not sufficient to demonstrate a significant correlation between GI symptoms and disease severity in patients with COVID-19.
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http://dx.doi.org/10.1136/bmjgast-2020-000437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359194PMC
July 2020

The influence of placebo administration on the first- night effect in patients with insomnia disorder.

Sleep Med 2020 08 12;72:138-143. Epub 2020 Mar 12.

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Peking University, Beijing, China. Electronic address:

Objective: We aimed to investigate the effects of placebo on the first-night effect (FNE) in insomniacs.

Methods: In sum, 36 patients with insomnia disorder who met the DSM-5 criteria were enrolled in this study. Sixteen patients with insomnia disorder were given two days of placebo intervention (placebo-administration group, PL). Twenty patients with insomnia disorder (drug-free group, DF) were not given any interventions. All participants underwent two consecutive nights of polysomnographic (PSG) testing in the sleep laboratory. Sleep diaries were recorded during one week at home before the PSG nights and on two subsequent nights.

Results: The results demonstrated that compared with the DF group, sleep onset latency (SOL), time in bed (TIB) and wake after sleep onset (WASO) significantly increased and sleep efficiency (SE) significantly decreased in the first sleep lab night in the PL group (all p < 0.05). Moreover, compared with the second night, significant differences were observed in lower self-reported total sleep time (TST) and more subjective WASO during the first night in the PL group (all p < 0.05). However, no significant difference was found in the duration and percentage of N1, N2, N3 and REM between the two groups.

Conclusion: In patients with insomnia disorder, placebo administration may increase the occurrence of worse sleep without causing a change in the duration and percentage of N1, N2, N3 and REM on the first sleep lab night. In some cases, a placebo may not serve as treatment but may result in a nocebo effect.
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http://dx.doi.org/10.1016/j.sleep.2020.03.002DOI Listing
August 2020

Influence of Inclination of Welding Torch on Weld Bead during Pulsed-GMAW Process.

Materials (Basel) 2020 Jun 10;13(11). Epub 2020 Jun 10.

School of Mechatronical Engineering, Beijing Institute of Technology, Beijing 100081, China.

This work is about the influence rule of inclination of welding torch on the formation and characteristics of weld bead during the pulsed-gas metal arc welding (GMAW) process based on the robotic operation. The inclination of welding torch was an important operation condition during the pulsed-GMAW process, because it can affect the formation and quality of weld bead, which was the output of the process. In this work, the different inclination modes and values were employed to conduct actual welding experiments, and some influence rules can be obtained according to examine the surface topography and cross section. Then, to obtain further rules, serious measurements for the geometry characteristic parameters were conducted and corresponding curve fitting equations between inclination angles and the bead width, penetration and bead height were obtained, and the largest error of these curve fitting equations was 0.117 mm, whose corresponding mean squared error (MSE) was 0.0103. Corresponding verification experiments validated the effectiveness of the curve fittings and showed the second order polynomials were proper, and the largest errors between measurements and curve fitting equations for inclination angle under backward mode were larger than those under forward mode, and were 0.10 mm and 0.15 mm, respectively, which corresponded to the penetration and were below 10%, therefore the equations can be used to predict the geometry of the weld bead. This work can benefit the process and operation optimization of the pulsed-GMAW process, both in the academic researches and actual industrial production.
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http://dx.doi.org/10.3390/ma13112652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321599PMC
June 2020

Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and β-cell repair of type 2 diabetes mice.

J Nanobiotechnology 2020 Apr 28;18(1):67. Epub 2020 Apr 28.

State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Polymers and Polymer Composite Materials, Department of Macromolecular Science, Fudan University, Shanghai, 200438, China.

Background: Exenatide is an insulinotropic peptide drug for type 2 diabetes treatment with low risk of hypoglycemia, and is administrated by subcutaneous injection. Oral administration is the most preferred route for lifelong treatment of diabetes, but oral delivery of peptide drug remains a significant challenge due to the absorption obstacles in gastrointestinal tract. We aimed to produce exenatide-loaded nanoparticles containing absorption enhancer, protectant and stabilizer using FDA approved inactive ingredients and easy to scale-up method, and to evaluate their long-term oral therapeutic effect in type 2 diabetes db/db mice.

Results: Two types of nanoparticles, named COM NPs and DIS NPs, were fabricated using anti-solvent precipitation method. In COM NPs, the exenatide was complexed with cholic acid and phosphatidylcholine to increase the exenatide loading efficiency. In both nanoparticles, zein acted as the cement and the other ingredients were embedded in zein nanoparticles by hydrophobic interaction. Casein acted as the stabilizer. The nanoparticles had excellent lyophilization, storage and re-dispersion stability. Hypromellose phthalate protected the loaded exenatide from degradation in simulated gastric fluid. Cholic acid promoted the intestinal absorption of the loaded exenatide via bile acid transporters. The exenatide loading efficiencies of COM NPs and DIS NPs were 79.7% and 53.6%, respectively. The exenatide oral pharmacological availability of COM NPs was 18.6% and DIS NPs was 13.1%. COM NPs controlled the blood glucose level of the db/db mice well and the HbA concentration significantly decreased to 6.8% during and after 7 weeks of once daily oral administration consecutively. Both DIS NPs and COM NPs oral groups substantially increased the insulin secretion by more than 60% and promoted the β-cell proliferation by more than 120% after the 7-week administration.

Conclusions: Both COM NPs and DIS NPs are promising systems for oral delivery of exenatide, and COM NPs are better in blood glucose level control than DIS NPs. Using prolamin to produce multifunctional nanoparticles for oral delivery of peptide drug by hydrophobic interaction is a simple and effective strategy.
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http://dx.doi.org/10.1186/s12951-020-00619-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189518PMC
April 2020
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