Publications by authors named "Haiyan Yang"

344 Publications

Trans-jugular intrahepatic portosystemic shunt in patients with hepatic cellular carcinoma: A preliminary study.

J Cancer Res Ther 2021 Jul;17(3):784-789

Interventional Oncology Institute, Shandong University; Department of Sterilization and Supply, The Second Hospital of Shandong University, Jinan, Shandong Province, China.

Purpose: To analyze the effects of trans-jugular intrahepatic portosystemic shunt (TIPS) on portal hypertension and liver function in patients with hepatocellular carcinoma (HCC).

Materials And Methods: Thirteen patients with hemorrhage caused by portal hypertension and HCC who received TIPS and antitumor treatment were retrospectively analyzed. Trans-arterial chemoembolization, microwave ablation, target therapy, and immunetherapy or combined therapy were performed to treat HCC. Child-Pugh score was applied to estimate liver functions before and after TIPS. Shunting patency, overall survival (OS), and progression-free survival were analyzed.

Results: The median age was 58 (interquartile range: 52.5-62.5) years. The ratio with ascites before and after TIPS was 84.6% (11/13) and 7.7% (1/13), with P < 0.001. The ratio with Child-Pugh A before and after TIPS were 61.5% (8/13) and 84.6% (11/13) respectively, with P = 0.179. Mean portal vein pressure before and after TIPS was 27.85 ± 7.02 mmHg and 16.23 ± 6.61 mmHg, respectively, with P = 0.001. Two-year shunting patency rate was 61.5%. Median OS was 29.8 ± 11.5 months (95% confidence interval [CI] 22.8-36.7), and median progression-free survival was 20.2 ± 13.2 months (95% CI 12.2-28.1).

Conclusion: TIPS could reduce ascites, down-regulate the Child-Pugh score, and give a chance for further anti-tumor therapy.
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http://dx.doi.org/10.4103/jcrt.jcrt_467_21DOI Listing
July 2021

-Mediated Specific Delivery of Nanoparticles for Tumor Therapy.

Int J Nanomedicine 2021 6;16:4643-4659. Epub 2021 Jul 6.

State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Key Laboratory of Biomedical Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Purpose: Hypoxia is considered to be obstructive to tumor treatment, but the reduced oxygen surroundings provide a suitable habitat for (BF) to colonize. The anaerobe BF selectively colonizes into tumors following systemic injection due to its preference for the hypoxia in the tumor cores. Therefore, BF may be a potential targeting agent which could be used effectively in tumor treatment. We aimed to determine whether a novel BF-mediated strategy, that was designed to deliver AP-PFH/PLGA NPs (aptamers CCFM641-5-functionalized Perfluorohexane (PFH) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles) by aptamer-directed approach into solid tumor based on the tumor-targeting ability of BF, could improve efficiency of high intensity focused ultrasound (HIFU) treatment of breast cancer.

Methods: We synthesized AP-PFH/PLGA NPs using double emulsion method and carbodiimide method. Then, we evaluated targeting ability of AP-PFH/PLGA NPs to BF . Finally, we studied the efficacy of HIFU ablation based on BF plus AP-PFH/PLGA NPs (BF-mediated HIFU ablation) in tumor.

Results: The elaborately designed AP-PFH/PLGA NPs can target BF colonized in tumor to achieve high tumor accumulation, which can significantly enhance HIFU therapeutic efficiency. We also found that, compared with traditional chemotherapy, this therapy not only inhibits tumor growth, but also significantly prolongs the survival time of mice. More importantly, this treatment strategy has no obvious side effects.

Conclusion: We successfully established a novel therapy method, BF-mediated HIFU ablation, which provides an excellent platform for highly efficient and non-invasive therapy of tumor.
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http://dx.doi.org/10.2147/IJN.S315650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275162PMC
July 2021

Prognosis and Concurrent Genomic Alterations in Patients With Advanced NSCLC Harboring MET Amplification or MET Exon 14 Skipping Mutation Treated With MET Inhibitor: A Retrospective Study.

Front Oncol 2021 24;11:649766. Epub 2021 Jun 24.

Department of Lung Cancer and Gastroenterology, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, China.

Background: MET amplification or METex14 skipping mutations are uncommon oncogenic events in NSCLC patients. Clinicopathological characteristics, concurrent gene alterations, and prognosis of MET TKIs in these patients are yet to be elucidated.

Methods: We retrospectively analyzed the genomic profiles of 43 MET amplifications or 31 METex14 skipping mutations in NSCLC patients with no previous treatment with EGFR TKIs. Survival outcomes were analyzed in evaluable patients receiving MET TKI treatment: MET amplification cohort (n = 29) and METex14 skipping mutation cohort (n = 29).

Results: Among evaluable patients, a shorter PFS was observed in the MET amplification cohort than in the METex14 skipping mutation cohort (7.0 months 11.0 months, P = 0.043). Concurrent mutations in both cohorts resulted in a statistically significant shorter PFS (MET amplification: 3.5 months 8.0 months, P = 0.038, METex14 skipping mutation: 7.0 NR months, P = 0.022). However, a statistically significant OS (17.0 months 20.0 months, P = 0.044) was only observed in the MET amplification cohort. TP53, the most common concurrent mutation in both cohorts, was associated with worse survival outcomes as compared to the wild type. The MET amplification cohort with a concurrent PIK3CA mutation exhibited primary resistance to MET TKIs and showed disease progression (80%).

Conclusion: MET TKIs could be a better treatment option for patients with METex14 skipping mutations. Concurrent mutations may deteriorate the PFS of MET TKIs in NSCLC patients with MET amplification or METex14 skipping mutations. PIK3CA mutations may confer primary resistance to MET TKIs in patients with MET amplification.
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http://dx.doi.org/10.3389/fonc.2021.649766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264054PMC
June 2021

Pathological Features of Enterovirus 71-Associated Brain and Lung Damage in Mice Based on Quantitative Proteomic Analysis.

Front Microbiol 2021 18;12:663019. Epub 2021 Jun 18.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.

The outbreaks of enterovirus 71 (EV71)-associated hand, foot, and mouth disease (HFMD) have emerged as an emergency of global health due to its association with fatal encephalitis and subsequent neurogenic pulmonary edema; however, the molecular characteristics and pathological features underlying EV71-associated encephalitis and pulmonary edema remain largely unknown. In this study, we performed a proteomic analysis of fresh brain and lung tissues from EV71-infected mice at 7 days post infection. We detected a perturbed expression of 148 proteins in the brain and 78 proteins in the lung after EV71 expression. Further analysis showed that the dysregulated proteins in the brain are involved in a variety of fundamental biological pathways, including complement and coagulation cascades, innate and adaptive immune responses, platelet activation, and nitrogen metabolism, and those proteins in the lung participate in innate and adaptive immune responses, phagosome, arginine biosynthesis, and hypoxia-inducible factor 1 signaling pathway. Our results suggested that immune activation, complement and coagulation dysfunction, platelet activation, imbalance of nitrogen metabolism, and hypoxia could be involved in the pathogenesis of EV71, which explains the major clinical manifestation of hyperinflammatory status of severe HFMD cases. Our study provides further understanding of the molecular basis of EV71 pathogenesis.
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http://dx.doi.org/10.3389/fmicb.2021.663019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249819PMC
June 2021

Effect of the traditional Chinese medicine Pinggan-Qianyang decoction on SIRT1-PTEN signaling in vascular aging in spontaneously hypertensive rats.

Hypertens Res 2021 Jun 29. Epub 2021 Jun 29.

International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.

Age-related functional decline is a physiological phenomenon that occurs in all organ systems. However, the acceleration and early occurrence of this process are observed in cardiovascular pathologies, including hypertension. This study aimed to investigate SIRT1-PTEN signaling in aortic tissue from spontaneously hypertensive rats (SHRs) and changes in SIRT1 and PTEN expression following treatment with Pinggan-Qianyang decoction (PGQYD) and explore the mechanism involved in the treatment of hypertensive vascular aging with traditional Chinese medicine. In this study, we used two rat models: spontaneously hypertensive rats (SHRs) at 14 and 64 weeks of age and WKY rats at 64 weeks of age. The degree of irritability and rotation tolerance time were evaluated to determine the effects of PGQYD on animal behavior. The morphology of the thoracic aorta was examined by hematoxylin-eosin (HE) and Masson staining and electron microscopy. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and superoxide dismutase (SOD) and anti-superoxide anion content were detected. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe the thoracic aorta during vascular aging. RT-qPCR, immunofluorescence, and Western blot analysis were performed to detect changes in the mRNA and protein expression of p53, p21, SIRT1, and PTEN in rat aortic tissues. Behavioral tests and histological and morphological analyses showed the remarkable amelioration of vascular aging after PGQYD treatment compared with that in the older SHRs. Moreover, PGQYD significantly decreased vascular aging in SHRs, as indicated by reduced SA-β-Gal staining, NADPH oxidase activity, and p53 and p21 expression, and increased anti-superoxide anion and SOD content. Furthermore, PGQYD increased SIRT1 and PTEN expression, but the downregulated expression of SIRT1 induced by a SIRT1 inhibitor abolished the PGQYD-induced antiaging effects on gene expression and antioxidant activity and enhanced PTEN expression. PGQYD could ameliorate vascular aging effects in SHRs, which may have been mediated via the regulation of SIRT1-PTEN signaling in aortic tissue.
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http://dx.doi.org/10.1038/s41440-021-00682-6DOI Listing
June 2021

An updated meta-analysis on the relationship between obesity and COVID-19 mortality.

Metabolism 2021 Jun 29;122:154820. Epub 2021 Jun 29.

Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China.

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http://dx.doi.org/10.1016/j.metabol.2021.154820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239205PMC
June 2021

Tracking spatio-temporal dynamics of fluorescence characteristics of Huangpu River, China by parallel factor analysis: Correlation with disinfection by-product precursor and pesticide level variations.

Chemosphere 2021 Jun 12;283:131198. Epub 2021 Jun 12.

Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100085, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

The components and characteristics of dissolved organic matter (DOM), the main precursor of toxic disinfection by-products (DBPs), have attracted increasing attention in water sources. In this study, fluorescence excitation-emission matrix (EEM) coupled with parallel factor (PARAFAC) analysis was used to investigate the DOM fluorescence characteristics of river water along the Huangpu River, China. Four fluorescence components were identified, including two protein-like components (C1 and C2) and two humic-like components (C3 and C4). The fluorescence characteristics showed spatial and temporal variations with the highest total fluorescence intensities observed in autumn, and the increased relative abundance of humic-like substance in the metropolitan area of Shanghai. Fluorescence index and biological index indicated that the DOM of Huangpu River water had both terrestrial and microbial origins and mainly autochthonous characteristic. Moreover, the formation potentials (FPs) of DBP for Huangpu River water were determined, and trihalomethanes were the predominant species formed in all samples. The correlation analysis further showed that PARAFAC C4 (microbial humic-like fluorescence) significantly correlated with the FP of N-DBPs, providing an insight for drinking water treatment to control specific DBPs precursor. In addition, the humic-like components also correlated with the concentrations of triazole and organophosphate pesticides detected in the Huangpu River. These results indicated that fluorescence-PARAFAC analysis is a promising tool to assess the DBPFPs and pesticide occurrence in surface waters.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131198DOI Listing
June 2021

Physical field simulation of the ultrasonic radiation method: An investigation of the vessel, probe position and power.

Ultrason Sonochem 2021 Aug 9;76:105626. Epub 2021 Jun 9.

School of Physics and Information Technology, Shaanxi Normal University, Xi'an 710062, China.

In this paper, the effects of ultrasonic probe position, vessel shape, and ultrasonic input power on the sound pressure distribution in the reactor were investigated by solving the Helmholtz equation using COMSOL Multiphysis software. Three different types of glass containers were used in the study, which are beaker, Erlenmeyer flask, and round bottom flask. The maximum value of sound pressure in the three containers will gradually increase when the distance between the probe and the bottom of the container decreases. When the distance decreases, the area of the high acoustic pressure region in the round bottom flask does not change significantly, while the area of the high acoustic pressure region in the beaker and Erlenmeyer flask increases sharply, which means that the use of the round bottom flask can reduce the influence of the dead zone on the preparation of nanomaterials. In addition, the change in power increases the value of the peak negative acoustic pressure in the vessel, enhancing the response efficiency of ultrasonic cavitation.
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http://dx.doi.org/10.1016/j.ultsonch.2021.105626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209746PMC
August 2021

Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination.

Front Microbiol 2021 28;12:658093. Epub 2021 May 28.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.

Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to children's health. However, compared with enterovirus 71 detected frequently in fatal cases, limited attention has been paid to CVA2 infections because of its benign clinical course. In the present study, we identified three CVA2 strains from HFMD infections and used the cell-adapted CVA2 strain HN202009 to inoculate 5-day-old BALB/c mice intramuscularly. These mice developed remarkably neurological symptoms such as ataxia, hind-limb paralysis, and death. Histopathological determination showed neuronophagia, pulmonary hemorrhage, myofiberlysis and viral myocarditis. Viral replication was detected in multiple organs and tissues, and CVA2 exhibited strong tropism to muscle tissue. The severity of illness was associated with abnormally high levels of inflammatory cytokines, including interleukin (IL)-6, IL-10, tumor necrosis factor α, and monocyte chemotactic protein 1, although the blockade of these proinflammatory cytokines had no obvious protection. We also tested whether an experimental formaldehyde-inactivated CVA2 vaccine could induce protective immune response in adult mice. The CVA2 antisera from the vaccinated mice were effective against CVA2 infection. Moreover, the inactivated CVA2 vaccine could successfully generate immune protection in neonatal mice. Our results indicated that the neonatal mouse model could be a useful tool to study CVA2 infection and to develop CVA2 vaccines.
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http://dx.doi.org/10.3389/fmicb.2021.658093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192712PMC
May 2021

Neuroprotective effect of aspirin combined with ginkgolide injection on cerebral ischemic stroke rats and its effect on ERK12 signal pathway.

Saudi J Biol Sci 2021 Jun 15;28(6):3193-3197. Epub 2021 Apr 15.

Department of Emergency, Yantaishan Hospital, Yantai 264000, China.

The main aim of this study was to evaluate the neuroprotective effect of aspirin combined with ginkgolide injection on cerebral ischemic stroke model rats and its effect on extracellular regulated protein kinase 1/2 (REK1/2) signaling pathway, and to clarify the possible mechanism of aspirin combined with ginkgolide injection on neuroprotective mechanism. Experimental rats were randomly divided into sham group, model group, aspirin group, ginkgolide group and combination group (aspirin + ginkgolide injection) (n = 20). The results revealed scores of neurological dysfunction and infarct volume in aspirin group, ginkgolide group and combination group rats were lower than those in model group ( < 0.05). Score of neurological dysfunction and the volume of cerebral infarction in combination group rats were lower than those in aspirin group and ginkgolide group ( < 0.05). Combination of aspirin and ginkgolide injection could better reduce brain water content, reduce apoptosis rate of cortical cells  < 0.05, reduce expression levels of caspase-3, Bax and p-REK1/2 proteins in ischemic brain tissue  < 0.05, and increase expression level of Bcl-2 protein than aspirin and ginkgolide injection alone  < 0.05). In conclusion, the synergistic neuroprotective effect of aspirin and ginkgolide injection on cerebral ischemic stroke rats is better than that of aspirin and ginkgolide injection alone. The mechanism of action may be that the two compounds can play a synergistic role and inhibit the activation of REK1/2 signaling pathway, thus inhibiting apoptosis of nerve cells and exerting neuroprotective effect.
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http://dx.doi.org/10.1016/j.sjbs.2021.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176056PMC
June 2021

A phase I study of the safety and activity of K-001 in patients with advanced pancreatic ductal adenocarcinoma.

BMC Cancer 2021 Jun 7;21(1):672. Epub 2021 Jun 7.

Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that lack of effective therapeutic drugs. K-001 is an oral antitumor drug made from active ingredients of marine microorganisms. The current study aimed to evaluate safety and antitumor activity of K-001 in patients with advanced PDAC.

Methods: In this phase I, open-label trial, patients with advanced PDAC were recruited to a dose-escalation study in a standard 3 + 3 design. K-001 was administered twice daily in four-week cycles, and dose escalation from 1350 mg to 2160 mg was evaluated twice daily. Physical examination and laboratory tests were done at screening and then weekly. The safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) of K-001 were assessed while tumor response was estimated by Response Evaluation Criteria in Solid Tumor (RECIST).

Results: Eighteen patients with advanced PDAC were screened, and twelve eligible patients were analyzed in the study. No DLT was observed. Totally, 47 adverse events (AEs) presented, and 14 drug-related AEs were reported in 7 patients, including 8 grade 1 events (57.1%) and 6 grade 2 events (42.9%). There was no grade 3 or 4 drug-related AE. In these 14 drug-related AEs, the most frequent ones were dyspepsia (21.4%), followed by flatulence, constipation, and hemorrhoid bleeding (above 10% of each). Among all 12 patients, 10 patients (83.3%) maintained stable disease (SD), and 2 patients (16.7%) had progressive disease (PD). The objective response rate (ORR) was 0% and the disease control rate (DCR) was 83.3%.

Conclusions: K-001 manifests satisfactory safety and tolerability, as well as meaningful antitumor activity in advanced PDAC patients. Further evaluation of K-001 in phase II/III appears warranted.

Trial Registration: NCT02720666 . Registered 28 Match 2016 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12885-021-08375-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183060PMC
June 2021

Is Cancer an Independent Risk Factor for Fatal Outcomes of Coronavirus Disease 2019 Patients?

Arch Med Res 2021 May 24:2670. Epub 2021 May 24.

Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Background: Coronavirus disease 2019 (COVID-19), caused by a novel virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought new challenges for global health systems.

Objective: The objective of this study was to investigate whether pre-diagnosed cancer was an independent risk factor for fatal outcomes of coronavirus disease 2019 (COVID-19) patients.

Method: A comprehensive search was conducted in major databases of PubMed, Web of Science, and EMBASE to identify all published full-text studies as of January 20, 2021. Inter-study heterogeneity was assessed using Cochran's Q-statistic and I² test. A meta-analysis of random- or fixed-effects model was used to estimate the effect size. Publication bias, sensitivity analysis and subgroup analysis were also carried out.

Results: The confounders-adjusted pooled effects (pooled odds ratio [OR] = 1.47, 95% confidence interval [CI]: 1.31-1.65; pooled hazard ratio [HR] = 1.37, 95% CI: 1.21-1.54) indicated that COVID-19 patients with pre-diagnosed cancer were more likely to progress to fatal outcomes based on 96 articles with 6,518,992 COVID-19 patients. Further subgroup analyses by age, sample size, the proportion of males, region, study design and quality rating exhibited consistent findings with the overall effect size.

Conclusion: Our analysis provides the objective findings based on the adjusted effect estimates that pre-diagnosed cancer is an independent risk factor for fatal outcome of COVID-19 patients. During the current COVID-19 pandemic, health workers should pay particular attention to cancer care for cancer patients and should prioritize cancer patients for vaccination.
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http://dx.doi.org/10.1016/j.arcmed.2021.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142843PMC
May 2021

CRISPR/Cas12-Based Ultra-Sensitive and Specific Point-of-Care Detection of HBV.

Int J Mol Sci 2021 May 3;22(9). Epub 2021 May 3.

College of Public Health, Zhengzhou University, Zhengzhou 450000, China.

Hepatitis B remains a major global public health challenge, with particularly high prevalence in medically disadvantaged western Pacific and African regions. Although clinically available technologies for the qPCR detection of HBV are well established, research on point-of-care testing has not progressed substantially. The development of a rapid, accurate point-of-care test is essential for the prevention and control of hepatitis B in medically disadvantaged rural areas. The development of the CRISPR/Cas system in nucleic acid detection has allowed for pathogen point-of-care detection. Here, we developed a rapid and accurate point-of-care assay for HBV based on LAMP-Cas12a. It innovatively solves the problem of point-of-care testing in 10 min, particularly the problem of sample nucleic acid extraction. Based on LAMP-Cas12a, visualization of the assay results is presented by both a fluorescent readout and by lateral flow test strips. The lateral flow test strip technology can achieve results visible to the naked eye, while fluorescence readout can achieve real-time high-sensitivity detection. The fluorescent readout-based Cas12a assay can achieve HBV detection with a limit of detection of 1 copy/μL within 13 min, while the lateral flow test strip technique only takes 20 min. In the evaluation of 73 clinical samples, the sensitivity and specificity of both the fluorescence readout and lateral flow test strip method were 100%, and the results of the assay were fully comparable to qPCR. The LAMP-Cas12a-based HBV assay relies on minimal equipment to provide rapid, accurate test results and low costs, providing significant practical value for point-of-care HBV detection.
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http://dx.doi.org/10.3390/ijms22094842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125043PMC
May 2021

An updated meta-analysis on the association between tuberculosis and COVID-19 severity and mortality.

J Med Virol 2021 Jun 1. Epub 2021 Jun 1.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.

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http://dx.doi.org/10.1002/jmv.27119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242817PMC
June 2021

Smoking is independently associated with an increased risk for COVID-19 mortality: A systematic review and meta-analysis based on adjusted effect estimates.

Nicotine Tob Res 2021 May 28. Epub 2021 May 28.

Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, China.

Introduction: Smoking can cause muco-ciliary clearing dysfunction and poor pulmonary immunity, leading to more severe infection. We performed this study to explore the association between smoking and mortality of coronavirus disease 2019 (COVID-19) patients utilizing a quantitative meta-analysis on the basis of adjusted effect estimates.

Methods: We conducted a systematic search of the online databases including PubMed, Web of Science, Scopus and Embase. Only articles reporting adjusted effect estimates on the association between smoking and the risk of mortality among COVID-19 patients in English were included. Newcastle-Ottawa scale (NOS) was fitted to assess the risk of bias. A random-effects model was applied to calculate the pooled effect with the corresponding 95% confidence interval (CI).

Results: A total of 73 articles with 863,313 COVID-19 patients were included in this meta-analysis. Our results indicated that smoking was significantly associated with an increased risk for death in patients with COVID-19 (pooled relative risk = 1.19, 95% CI = 1.12-1.27). Sensitivity analysis indicated that our results were stable and robust.

Conclusion: Smoking was independently associated with an increased risk for mortality in COVID-19 patients.
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http://dx.doi.org/10.1093/ntr/ntab112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244809PMC
May 2021

Protective and therapeutic experience of perioperative safety in extremely elderly patients with biliary diseases.

Medicine (Baltimore) 2021 05;100(21):e26159

Department of General Surgery, Beijing Electric Power Hospital, State Grid Corporation of China, Capital Medical University, Beijing, PR China.

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http://dx.doi.org/10.1097/MD.0000000000026159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154467PMC
May 2021

circSVIL regulates bovine myoblast development by inhibiting STAT1 phosphorylation.

Sci China Life Sci 2021 May 20. Epub 2021 May 20.

Key laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.

Circular RNAs (circRNAs), a novel class of non-coding RNAs with a loop structure, have recently been shown to participate in various pathophysiological processes. However, the precise role of circRNAs in myoblasts remains unclear. In this report, circSVIL was screened and identified from our previous sequencing analysis; we then performed gain- and loss-of-function experiments on bovine myoblasts by CCK8, EdU, flow cytometry, qRT-PCR, and Western blotting. The results indicate that circSVIL facilitates bovine myoblast proliferation and inhibits cell apoptosis. Using mechanism assays such as bioinformatics prediction, RNA immunoprecipitation (RIP), and cytoplasmic separation, we demonstrate that circSVIL could interact with STAT1 and inhibit STAT1 phosphorylation, thereby restraining STAT1's nuclear translocation and affecting its downstream signal cascade. Our results may elucidate a new regulatory pathway for bovine skeletal muscle development.
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http://dx.doi.org/10.1007/s11427-020-1908-2DOI Listing
May 2021

CRISPR/Cas System: A Potential Technology for the Prevention and Control of COVID-19 and Emerging Infectious Diseases.

Front Cell Infect Microbiol 2021 23;11:639108. Epub 2021 Apr 23.

College of Public Health, Zhengzhou University, Zhengzhou, China.

The continued global pandemic of coronavirus disease 2019 (COVID-19) poses a serious threat to global public health and social stability and it has become a serious global public health problem. Unfortunately, existing diagnostic and therapeutic approaches for the prevention and control of COVID-19 have many shortcomings. In recent years, the emerging CRISPR/Cas technology can complement the problems of traditional methods. Biological tools based on CRISPR/Cas systems have been widely used in biomedicine. In particular, they are advantageous in pathogen detection, clinical antiviral therapy, drug, and vaccine development. Therefore, CRISPR/Cas technology may have great potential for application in the prevention and control of COVID-19 and emerging infectious diseases in the future. This article summarizes the existing applications of CRISPR/Cas technology in infectious diseases with the aim of providing effective strategies for the prevention and control of COVID-19 and other emerging infectious diseases in the future.
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http://dx.doi.org/10.3389/fcimb.2021.639108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102830PMC
June 2021

Comprehensive evaluation of water resources carrying capacity and analysis of obstacle factors in Weifang City based on hierarchical cluster analysis-VIKOR method.

Environ Sci Pollut Res Int 2021 May 6. Epub 2021 May 6.

China Academy of Urban Planning and Design, Beijing, 100044, China.

This study uses hierarchical cluster analysis (HCA) to screen the evaluation indexes and establishes a comprehensive evaluation index system for water resources carrying capacity (WRCC), based on the VIKOR method and the obstacle degree model for the identification of the main factors affecting the WRCC of Weifang City. The results show that the WRCC of Weifang City has steadily increased from 2008 to 2018. The subsystems referred to society and water environment are currently the main obstacles affecting Weifang's WRCC, but there is still space for improvement in the future. The areas with low WRCC was Kuiwen District in 2018, which was in a seriously overloaded state, mostly affected by the water resources subsystem. The implementation of measures such as efficiently improving the level of water resources management and the development of water conservancy projects is prominent in water resource planning in Kuiwen District. This study analyzes the current situation of water resources management in order to consider it in strategic decision-making in promoting the improvement of WRCC, which in turn may ensure the realization of a green and sustainable development strategy in the future for Weifang City.
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http://dx.doi.org/10.1007/s11356-021-14236-3DOI Listing
May 2021

Curcumin induces apoptosis and inhibits the growth of adrenocortical carcinoma: Identification of potential candidate genes and pathways by transcriptome analysis.

Oncol Lett 2021 Jun 15;21(6):476. Epub 2021 Apr 15.

Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

Adrenocortical carcinoma (ACC) is an endocrine tumour with high malignancy, high invasiveness and poor prognosis. Curcumin, a major component in turmeric, has been reported to have good efficacy and biological safety in treating cancer. However, the role and mechanism of curcumin in ACC have not yet been fully investigated and were thus the focus of this study. , ACC SW-13 and NCI-H295R cells were treated with curcumin and their viability, migration and invasion were assessed by CCK-8 and Transwell assays. Apoptosis was detected via flow cytometry and western blotting. High-throughput sequencing and comprehensive bioinformatics analyses were performed to elucidate the molecular processes underlying curcumin activity. , SW-13 cells were injected into nude mice, and the tumour volumes and weights were observed after 2 weeks of curcumin treatment. Organelle changes were observed by electron microscopy, and potential candidate genes and pathways were analysed by RT-qPCR and western blotting. The role of the CHOP target gene in curcumin-induced ACC cell apoptosis was verified via lentiviral transfection experiments. Curcumin inhibited the viability, migration and invasion, and induced the apoptosis of ACC cells. Transcriptome sequencing analysis showed that curcumin treatment markedly changed the gene expression levels. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the MAPK and endoplasmic reticulum (ER) stress pathways were the predominant pathways associated with curcumin-induced apoptosis of ACC cells. Subsequent and results demonstrated that the JNK, p38 MAPK and ER stress pathways were activated in curcumin-treated ACC cells, and that C/EBP homologous protein induction was responsible for curcumin-induced apoptosis of ACC cells. In summary, curcumin induced ACC cell apoptosis and inhibited tumour growth by activating the JNK, p38 MAPK and ER stress pathways. Thus, curcumin may be a potential therapeutic drug for ACC.
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http://dx.doi.org/10.3892/ol.2021.12737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063251PMC
June 2021

Uric acid participating in female reproductive disorders: a review.

Reprod Biol Endocrinol 2021 Apr 27;19(1):65. Epub 2021 Apr 27.

School of Medicine, Zhejiang University, No.866 Yuhantang Road, 310058, Hangzhou, People's Republic of China.

Uric acid (UA) is the end metabolic product of purine metabolism. Early on, UA was considered to be a metabolite with a certain antioxidant capacity. As research has progressed, other properties of UA have been explored, and its association with many diseases has been found. The association between UA and kidney disease and cardiovascular disease is well established; however, there is still a paucity of reviews on the association between UA and the female reproductive system. An increasing number of epidemiological studies have shown elevated serum UA levels in patients with polycystic ovary syndrome (PCOS), endometriosis, etc. Additionally, serum UA can be used as a predictor of pregnancy complications and adverse foetal outcomes. An increasing number of animal experiments and clinical studies have revealed possible mechanisms related to the involvement of UA in certain female reproductive disorders: oxidative stress, chronic inflammation, mitochondrial dysfunction, etc. This article reviews the current mainstream mechanisms regarding the pathogenesis of UA and the role of UA in certain specific female reproductive disorders (direct involvement in the development of certain diseases or enhancement of other risk factors) in the hope of contributing to clinical prevention, diagnosis, treatment and improvement in prognosis.
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http://dx.doi.org/10.1186/s12958-021-00748-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077923PMC
April 2021

Diversity of the type I-U CRISPR-Cas system in Bifidobacterium.

Arch Microbiol 2021 Aug 9;203(6):3235-3243. Epub 2021 Apr 9.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, People's Republic of China.

The CRISPR-Cas system is widely distributed in prokaryotes and plays an important role in the adaptive immunity of bacteria and archaea. Bifidobacterium is an important component of the intestinal flora of humans and animals, and some species of this bacterium can be employed as food additives. However, the Bifidobacterium CRISPR-Cas system has not been fully elucidated to date. In this study, the genomes of 110 strains of Bifidobacterium were employed to research the diversity of the type I-U system. The 110 strains were divided into five groups according to the genes adjacent to the CRISPR locus, including group A, B, C, D and E. Strains in the intergroup had unique species classifications and MLST types. An evolutionary tree was constructed based on the conserved cas4/cas1 fusion gene. The results showed that group A had a different evolutionary branch compared with the other groups and had a relatively low spacer number. Notably, group B, C and E had exhibited ABC transporter regulators in the genes adjacent to the CRISPR locus. ABC transporters play important roles in the exocytosis of many antibiotics and are involved in horizontal gene transfer. This mechanism may have promoted the evolution of Bifidobacterium and the horizontal gene transfer of the type I-U system, which may have promoted the generation of system diversity. In summary, our results help to elucidate the role of the type I-U system in the evolution of Bifidobacterium.
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http://dx.doi.org/10.1007/s00203-021-02310-wDOI Listing
August 2021

Heat Treatment-Induced Microstructure and Property Evolution of Mg/Al Intermetallic Compound Coatings Prepared by Al Electrodeposition on Mg Alloy from Molten Salt Electrolytes.

Materials (Basel) 2021 Mar 14;14(6). Epub 2021 Mar 14.

National Engineering Research Center of Light Alloy Net Forming, Shanghai Jiao Tong University, 800 Dongchuan Road, Minhang District, Shanghai 200240, China.

A method of forming an Mg/Al intermetallic compound coating enriched with MgAl and MgAl was developed by heat treatment of electrodeposition Al coatings on Mg alloy at 350 °C. The composition of the Mg/Al intermetallic compounds could be tuned by changing the thickness of the Zn immersion layer. The morphology and composition of the Mg/Al intermetallic compound coatings were characterized using scanning electron microscopy (SEM), X-ray diffraction (XRD), and electron backscattered diffraction (EBSD). Nanomechanical properties were investigated via nano-hardness (nHV) and the elastic modulus (EIT), and the corrosion behavior was studied through hydrogen evolution and potentiodynamic (PD) polarization. The compact and uniform Al coating was electrodeposited on the Zn-immersed AZ91D substrate. After heat treatment, MgAl and MgAl phases formed, and as the thickness of the Zn layer increased from 0.2 to 1.8 μm, the ratio of MgAl and MgAl varied from 1:1 to 4:1. The nano-hardness increased to 2.4 ± 0.5 GPa and further improved to 3.5 ± 0.1 GPa. The Mg/Al intermetallic compound coating exhibited excellent corrosion resistance and had a prominent effect on the protection of the Mg alloy matrix. The control over the ratio of intermetallic compounds by varying the thickness of the Zn immersion layer can be an effective approach to achieve the optimal comprehensive performance. As the Zn immersion time was 4 min, the obtained intermetallic compounds had relatively excellent comprehensive properties.
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http://dx.doi.org/10.3390/ma14061407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000904PMC
March 2021

Long non-coding RNA LINC01137 contributes to oral squamous cell carcinoma development and is negatively regulated by miR-22-3p.

Cell Oncol (Dordr) 2021 Jun 2;44(3):595-609. Epub 2021 Apr 2.

Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Purpose: Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. LINC01137 is a recently identified lncRNA of which the functional role in the development of oral squamous cell carcinoma (OSCC) has not been determined yet.

Methods: We analyzed the expression of LINC01137 using a microarray-based OSCC gene expression dataset (GSE31056), and validated the results obtained using RT-qPCR in 26 pairs of primary OSCC tumor tissues and adjacent non-tumor tissues. The proliferative and invasive effects of LINC01137 on OSCC cells were determined using CCK-8, colony formation and transwell assays, respectively. Targeted binding between miR-22-3p and LINC01137 was verified using a dual luciferase reporter assay.

Results: We found that LINC01137 was significantly upregulated in primary OSCCs. LINC01137 knockdown inhibited OSCC cell proliferation, migration and invasion, whereas LINC01137 overexpression induced opposite effects. LINC01137 upregulation along with p53 inhibition enhanced the malignant transformation of oral cells. In addition, we found that miR-22-3p can directly target LINC01137 through interaction with a putative miR-22-3p-binding site present within the LINC01137 sequence. A significant negative correlation was observed between LINC01137 and miR-22-3p expression in primary OSCC specimens. Exogenous overexpression of miR-22-3p markedly reduced the endogenous expression level of LINC01137 in OSCC cells. Additional functional assays showed that miR-22-3p overexpression enhanced the inhibitory effect of siRNA-mediated LINC01137 silencing on OSCC cell proliferation, migration and invasion, whereas miR-22-3p inhibition had the opposite effect.

Conclusions: Our results indicate that LINC01137 functions as an oncogenic lncRNA in OSCC. miR-22-3p can directly target LINC01137 and negatively regulate its expression and function.
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http://dx.doi.org/10.1007/s13402-021-00586-0DOI Listing
June 2021

Synergistic effect of carboxymethylcellulose and Cryptococcus laurentii on suppressing green mould of postharvest grapefruit and its mechanism.

Int J Biol Macromol 2021 Jun 26;181:253-262. Epub 2021 Mar 26.

Key Laboratory for Forest Resources Conservation and Use in the Southwest Mountains of China, Ministry of Education, Southwest Forestry University, Kunming 650224, China; Key Laboratory of National Forestry and Grassland Administration on Biodiversity Conservation in Southwest China, Southwest Forestry University, Kunming 650224, China. Electronic address:

The synergistic effects of carboxymethylcellulose (CMC) combined with Cryptococcus laurentii FRUC DJ1 were studied on controlling green mould resulting from Penicillium digitatum in grapefruit fruit. The results indicate that both C. laurentii and the CMC treatment suppressed P. digitatum conidia germination. In addition, C. laurentii growth in vitro was not affected by low CMC concentrations, nevertheless, the biofilm of C. laurentii was enhanced. Compared with the control fruit, the grapefruit had a lower green mould in all treatments. Significantly synergistic effects were caused by combining C. laurentii and CMC on minimum decay incidence and lesion diameter. Combined treatment induced defence enzyme activities, including chitinase, β-1,3-glucanase, peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase, together with disease tolerance-associated total phenol. Also, this combination inhibited the pathogen growth by adhered to the hyphae and reduced its infection in fruit wounds. Moreover, the commercial quality parameters in the combined treatment of C. laurentii and CMC, including weight loss, total soluble solids, ascorbic acid, and titratable acidity, were superior to single treatment. The combination of C. laurentii and CMC can not only control postharvest decay but also maintain fruit qualities. Thus, it can be used in grapefruit for commercial purposes.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.03.155DOI Listing
June 2021

If small molecules immunotherapy comes, can the prime be far behind?

Eur J Med Chem 2021 Jun 11;218:113356. Epub 2021 Mar 11.

Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China; Innovation Institute for Artificial Intelligence in Medicine, Zhejiang University, Hangzhou, 310058, PR China; Cancer Center of Zhejiang University, Hangzhou, 310058, PR China. Electronic address:

Anti-cancer immunotherapy, which includes cellular immunotherapy, immune checkpoint inhibitors and cancer vaccines, has transformed the treatment strategies of several malignancies in the past decades. Immune checkpoints blockade (ICB) is the most commonly tested therapy and has the potential to induce a durable immune response in different types of cancers. However, all approved immune checkpoint inhibitors (ICIs) are monoclonal antibodies (mAbs), which are fraught with disadvantages including lack of oral bioavailability, prolonged tissue retention and poor membrane permeability. Therefore, the research focus has shifted to developing small molecule inhibitors to obviate the limitations of mAbs. Given the complexity of the tumor micro-environment (TME), the combination of ICIs with various small molecule agonists/inhibitors are currently being tested in clinical trials to improve treatment outcomes and prevent tumor recurrence. In this review, we have summarized the mechanisms and therapeutic potential of several molecular targets, along with the current status of small molecule inhibitors.
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http://dx.doi.org/10.1016/j.ejmech.2021.113356DOI Listing
June 2021

The interaction of graphene oxide-silver nanoparticles with trypsin: Insights from adsorption behaviors, conformational structure and enzymatic activity investigations.

Colloids Surf B Biointerfaces 2021 Jun 9;202:111688. Epub 2021 Mar 9.

School of Physics and Information Technology, Shaanxi Normal University, Xi'an, 710062, China. Electronic address:

In this work, we synthesized graphene oxide-silver nanoparticles (GO-AgNPs) hybrids by one-pot method. Since there are relatively few reports on whether GO-AgNPs bind and change the structure and function of trypsin, A variety of methods were employed to systematically characterize the molecular interaction between GO-AgNPs and trypsin. Results exhibited that GO-AgNPs bound with trypsin to form a ground state complex. GO-AgNPs had higher adsorption capacity for trypsin compared with single GO. Langmuir-Blodgett assembly method was used to confirm that AgNPs did not interfere with the adsorption of trypsin by GO. The secondary structure and the microenvironment of amino acid residues of trypsin were altered after interacting with GO-AgNPs. In addition, GO-AgNPs can enhance the activity of trypsin and promote the hydrolysis of bovine serum protein (BSA) by trypsin. These findings provide important support for the application of GO-based nanocomposites in the efficient immobilization of enzymes.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111688DOI Listing
June 2021

Prolactin Is Associated With Insulin Resistance and Beta-Cell Dysfunction in Infertile Women With Polycystic Ovary Syndrome.

Front Endocrinol (Lausanne) 2021 25;12:571229. Epub 2021 Feb 25.

Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Our study aimed to investigate if serum prolactin (PRL) levels associated with insulin resistance and beta-cell dysfunction in infertile patients with polycystic ovary syndrome (PCOS).

Methods: This was a retrospective cross-sectional study performed in the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University. From January 2007 to August 2018, a total of 792 PCOS and 700 non-PCOS infertile women were included. All patients' prolactin levels were in the normal range. PCOS was diagnosed according to the Rotterdam Criteria. Anthropometric parameters, blood pressure, serum prolactin levels, sex hormones, fasting lipids, fasting plasma glucose (FPG), fasting insulin (FINS) and hepatic biological parameters were measured in all subjects.

Results: Serum prolactin levels in PCOS women were significantly decreased compared with levels in non-PCOS women after adjusting for age and BMI ( < 0.05). Moreover, we found that prolactin levels were positively associated with high-density lipoprotein cholesterol (HDL-C) and negatively associated with age, BMI, waist circumference (WC), hip circumference (HC), luteinizing hormone/follicle stimulating hormone (LH/FSH), estradiol (E), FINS, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β (HOMA-β), triglyceride (TG) and alanine aminotransferase (ALT) ( < 0.05). After adjusting for age and BMI, multiple linear regression analysis revealed that LH, LH/FSH, E, FINS, HOMA-IR, and HOMA-β were negatively associated with serum PRL ( < 0.05).

Conclusions: Low serum PRL levels within the normal range associates with a higher incidence of insulin resistance and beta-cell dysfunction in infertile women with PCOS.
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http://dx.doi.org/10.3389/fendo.2021.571229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947819PMC
February 2021

Pathogenesis Study of Enterovirus 71 Using a Novel Human SCARB2 Knock-In Mouse Model.

mSphere 2021 03 10;6(2). Epub 2021 Mar 10.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China

Enterovirus 71 (EV71) can cause a severe hand-foot-mouth disease in children. However, the precise mechanism of EV71-associated disease, particularly the neuropathogenesis and pulmonary disorder, is still not fully understood because no suitable animal models are available. The human scavenger receptor class B, member 2 (hSCARB2), is a cellular receptor for EV71. Here, we generated a novel knock-in (KI) mouse model using the CRISPR/Cas9 system to insert the hSCARB2 gene into the mouse locus to study the pathogenesis of EV71. The hSCARB2 KI mice infected with clinical isolates of EV71 showed neurological symptoms, such as ataxia, paralysis, and death. Viral replication was detected in mainly astrocytes and a limited number of neurons and microglia, accompanied by gliosis. Vascular leakage and alveoli filled with erythrocytes were detected, suggesting that edema and hemorrhage, which are observed in human patients, also occurred in EV71-infected KI mice. In addition, proinflammatory cytokines and chemokines were significantly increased in the serum of infected KI mice. These pathological features of the KI mice after infection resembled those of EV71 encephalomyelitis in humans. Therefore, our KI mouse model is suitable to study the pathogenesis of EV71 and is of great significance for development of antiviral drugs and vaccines to treat or prevent EV71 infection. Enterovirus 71 (EV71) is associated with severe hand-foot-mouth disease. Recently, outbreaks of EV71 infection with high mortality have been reported in the Asia-Pacific region, posing a great challenge for global public health. To date, the precise mechanism of EV71-induced disease, particularly the neuropathogenesis and respiratory disorders, is still not fully understood because no suitable animal models are available. Human scavenger receptor class B, member 2 (hSCARB2), has been identified as a cellular receptor for EV71. Here, we introduce a novel CRISPR/Cas9-mediated hSCARB2 knock-in (KI) mouse model for the study of EV71 pathogenesis, which is of great significance for the development of antiviral drugs and vaccines.
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http://dx.doi.org/10.1128/mSphere.01048-20DOI Listing
March 2021
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