Publications by authors named "Hai Chen"

252 Publications

The Association between TREM2 Gene and Late-Onset Alzheimer's Disease in Chinese Han Population.

Gerontology 2021 Aug 2:1-7. Epub 2021 Aug 2.

Institute of Literature in Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Objective: The objective of this study was to evaluate the impact of single nucleotide polymorphisms (SNPs) in triggering receptor expressed on the myeloid cells 2 protein (TREM2) gene and their interaction with environmental factors and haplotypes on late-onset Alzheimer's disease (LOAD).

Methods: DNA was extracted from the whole blood of the participants and genotyped using PCR and followed by restriction fragment length polymorphism. The Hardy-Weinberg equilibrium test was used in the control group. Multivariate logistic regression analysis was used to determine the relationship between the 4 SNPs of the TREM2 gene and the risk of LOAD. Generalized multifactor dimensionality reduction was used to test the best interaction combination between SNPs and environmental factors.

Results: Logistic regression analysis showed that the T allele of rs75932628 and the T allele of rs2234253 were independently associated with increased risk of LOAD, and adjusted odds ratios (ORs) were 1.81 (1.271-2.35) and 1.59 (1.15-2.03), respectively. However, there was no significant association with LOAD for rs142232675 and rs143332484. We found a best model significantly associated with LOAD risk that consisted of rs75932628 and smoking, which scored 10/10 for both the sign test and cross-validation consistency (p = 0.012). Stratified analysis indicated that current smokers with rs75932628-CT/TT genotype have the highest LOAD risk compared to never smokers with rs75932628 - CC genotype, OR (95% confidence interval) = 2.73 (1.72-3.79). Haplotypes of rs75932628 and rs2234253 were analyzed using the SHEsis online software. However, no haplotype was found to be significantly associated with the risk of LOAD.

Conclusions: The T allele of rs75932628 and the T allele of rs2234253 and interaction between rs75932628 and smoking were all correlated with increased risk of LOAD.
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http://dx.doi.org/10.1159/000517284DOI Listing
August 2021

The synthesis and bioactivity of pyrrolo[2,3-d]pyrimidine derivatives as tyrosine kinase inhibitors for NSCLC cells with EGFR mutations.

Eur J Med Chem 2021 Jul 21;224:113711. Epub 2021 Jul 21.

Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610093, PR China; Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, PR China; Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610044, PR China. Electronic address:

EGFR mutations are an ongoing challenge in the treatment of NSCLC, and demand continuous updating of EGFR TKI drug candidates. Pyrrolopyrimidines are one group of versatile scaffolds suitable for tailored drug development. However not many precedents of this type of pharmacophore have been investigated in the realm of third generation of covalent EGFR-TKIs. Herein, a series of pyrrolo[2,3-d]pyrimidine derivatives able to block mutant EGFR activity in a covalent manner were synthesized, through optimized Buchwald-Hartwig C-N cross coupling reactions. Their preliminary bioactivity and corresponding inhibitory mechanistic pathways were investigated at molecular and cellular levels. Several compounds exhibited increased biological activity and enhanced selectivity compared to the control compound. Notably, compound 12i selectively inhibits HCC827 cells harboring the EGFR activating mutation with up to 493-fold increased efficacy compared to in normal HBE cells. Augmented selectivity was also confirmed by kinase enzymatic assay, with the test compound selectively inhibiting the T790 M activating mutant EGFRs (IC values of 0.21 nM) with up to 104-fold potency compared to the wild-type EGFR (IC values of 22 nM). Theoretical simulations provide structural evidence of selective kinase inhibitory activity. Thus, this series of pyrrolo[2,3-d]pyrimidine derivatives could serve as a starting point for the development of new EGFR-TKIs.
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http://dx.doi.org/10.1016/j.ejmech.2021.113711DOI Listing
July 2021

Advancement in research on the role of the transient receptor potential vanilloid channel in cerebral ischemic injury (Review).

Exp Ther Med 2021 Aug 15;22(2):881. Epub 2021 Jun 15.

School of Pharmacy and State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.

Stroke is a common critical disease occurring in middle-aged and elderly individuals, and is characterized by high morbidity, lethality and mortality. As such, it is of great concern to medical professionals. The aim of the present review was to investigate the effects of transient receptor potential vanilloid (TRPV) subtypes during cerebral ischemia in ischemia-reperfusion animal models, oxygen glucose deprivation and in other administration cell models to explore new avenues for stroke research and clinical treatments. TRPV1, TRPV2 and TRPV4 employ different methodologies by which they confer protection against cerebral ischemic injury. TRPV1 and TRPV4 are likely related to the inhibition of inflammatory reactions, neurotoxicity and cell apoptosis, thus promoting nerve growth and regulation of intracellular calcium ions (Ca). The mechanisms of neuroprotection of TRPV1 are the JNK pathway, N-methyl-D-aspartate (NMDA) receptor and therapeutic hypothermia. The mechanisms of neuroprotection of TRPV4 are the PI3K/Akt pathways, NMDA receptor and p38 MAPK pathway, amongst others. The mechanisms by which TRPV2 confers its protective effects are predominantly connected with the regulation of nerve growth factor, MAPK and JNK pathways, as well as JNK-dependent pathways. Thus, TRPVs have the potential for improving outcomes associated with cerebral ischemic or reperfusion injuries. The protection conferred by TRPV1 and TRPV4 is closely related to cellular Ca influx, while TRPV2 has a different target and mode of action, possibly due to its expression sites. However, in light of certain contradictory research conclusions, further experimentation is required to clarify the mechanisms and specific pathways by which TRPVs act to alleviate nerve injuries.
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http://dx.doi.org/10.3892/etm.2021.10313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237269PMC
August 2021

Guanosine and uridine alleviate airway inflammation via inhibition of the MAPK and NF-κB signals in OVA-induced asthmatic mice.

Pulm Pharmacol Ther 2021 Jun 5;69:102049. Epub 2021 Jun 5.

Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Frontiers Science Center for Disease-related Molecular Network, Sichuan University, Chengdu, Sichuan, PR China. Electronic address:

Asthma is one of the most common respiratory diseases. Lack of response or poor adherence to corticosteroids demands the development of new drug candidates for asthma. Endogenous nucleosides could be potential options since uridine has been reported to have an anti-inflammatory effect in asthma model. However, its molecular pathways and whether other nucleosides have similar therapeutic effects remain untouched. Thus, we herein report our investigation into the anti-inflammatory effects of guanosine and uridine, and the related inner signaling pathways in asthma model. Present study shows that administration of guanosine or uridine can reduce lung inflammation in OVA-challenged mice. Total cell counts in BALF, cytokines such as IL-4, IL-6, IL-13, OVA-specific IgE and mRNA level of Cxcl1, Cxlc3, IL-17 and Muc5ac were decreased in asthmatic mice after treatment. Besides, the production of IL-6 in LPS/IFN-γ induced THP-1 cells was also decreased by both nucleosides. In vivo and in vitro expressions of key molecules in the MAPK and NF-κB pathways were reduced after the treatment of both compounds. These findings suggest that guanosine has a similar potential therapeutic value in asthma as uridine and they exert anti-inflammatory effects through suppression of the MAPK and NF-κB pathways.
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http://dx.doi.org/10.1016/j.pupt.2021.102049DOI Listing
June 2021

Rehabilitation training inhibits neuronal apoptosis by down-regulation of TLR4/MyD88 signaling pathway in mice with cerebral ischemic stroke.

Am J Transl Res 2021 15;13(4):2213-2223. Epub 2021 Apr 15.

Shaoxing Institute of Traditional Chinese Medicine Culture, Shaoxing Hospital of Traditional Chinese Medicine Shaoxing, Zhejiang Province, China.

Objective: To investigate the role of rehabilitation training and TLR4/MyD88 signaling pathway on neuronal apoptosis in mice with cerebral ischemic stroke.

Methods: Mice were randomized into six groups, which were normal group (healthy mice, n=20), control group (sham surgery, n=20), model group (middle cerebral artery occlusion (MCAO) model, n=20), training (MCAO model, continuous rehabilitation training for 4 weeks, n=20), TAK-242 group (MCAO model, TL R4 inhibitor TAK-242, n=20), and TAK-242 + Training group (MCAO model, TLR4 inhibitor TAK-242 + rehabilitation training, n=20).

Results: Neurobehavioral assessment was performed, and cerebral infarction area of mice was detected by triphenyl tetrazolium chloride staining. Compared with the normal group, no significant differences in all indicators were found in the control group (all P>0.05), while the other groups had higher neurological function scores, cerebral infarction area, neuronal apoptosis rate, increased expressions of TLR4, MyD88, Bax, NF-κB, TNF-α, Caspase-3, IL-1βA and decreased mRNA and protein expressions of Bcl-2 (all P<0.05).

Conclusion: Rehabilitation training can effectively reduce the apoptosis of hippocampal neurons in mice with ischemic stroke by inhibiting the TLR4/MyD88 signaling pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129365PMC
April 2021

Progress in Borneol Intervention for Ischemic Stroke: A Systematic Review.

Front Pharmacol 2021 4;12:606682. Epub 2021 May 4.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Borneol is a terpene and bicyclic organic compound that can be extracted from plants or chemically synthesized. As an important component of proprietary Chinese medicine for the treatment of stroke, its neuroprotective effects have been confirmed in many experiments. Unfortunately, there is no systematic review of these studies. This study aimed to systematically examine the neuroprotective effects of borneol in the cascade reaction of experimental ischemic stroke at different periods. Articles on animal experiments and cell-based research on the actions of borneol against ischemic stroke in the past 20°years were collected from Google Scholar, Web of Science, PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), and other biomedical databases. Meta-analysis was performed on key indicators experiments. After sorting the articles, we focused on the neuroprotective effects and mechanism of action of borneol at different stages of cerebral ischemia. Borneol is effective in the prevention and treatment of nerve injury in ischemic stroke. Its mechanisms of action include improvement of cerebral blood flow, inhibition of neuronal excitotoxicity, blocking of Ca overload, and resistance to reactive oxygen species injury in the acute ischemic stage. In the subacute ischemic stage, borneol may antagonize blood-brain barrier injury, intervene in inflammatory reactions, and prevent neuron excessive death. In the late stage, borneol promotes neurogenesis and angiogenesis in the treatment of ischemic stroke. Borneol prevents neuronal injury after cerebral ischemia via multiple action mechanisms, and it can mobilize endogenous nutritional factors to hasten repair and regeneration of brain tissue. Because the neuroprotective effects of borneol are mediated by various therapeutic factors, deficiency caused by a single-target drug is avoided. Besides, borneol promotes other drugs to pass through the blood-brain barrier to exert synergistic therapeutic effects.
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http://dx.doi.org/10.3389/fphar.2021.606682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129537PMC
May 2021

Neuroprotective Effect for Cerebral Ischemia by Natural Products: A Review.

Front Pharmacol 2021 22;12:607412. Epub 2021 Apr 22.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. Stroke is a disease with high prevalence and incidence, the pathogenesis is a complex cascade reaction. In recent years, it's reported that a vast number of natural products have demonstrated beneficial effects on stroke worldwide. Natural products have been discovered to modulate activities with multiple targets and signaling pathways to exert neuroprotection via direct or indirect effects on enzymes, such as kinases, regulatory receptors, and proteins. This review provides a comprehensive summary of the established pharmacological effects and multiple target mechanisms of natural products for cerebral ischemic injury and preclinical models, and their potential neuro-therapeutic applications. In addition, the biological activity of natural products is closely related to their structure, and the structure-activity relationship of most natural products in neuroprotection is lacking, which should be further explored in future. Overall, we stress on natural products for their role in neuroprotection, and this wide band of pharmacological or biological activities has made them suitable candidates for the treatment of stroke.
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http://dx.doi.org/10.3389/fphar.2021.607412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102015PMC
April 2021

Dynamic Change of Lymphocyte-to-Monocyte Is Associated With the Occurrence of POCD After Cardiovascular Surgery: A Prospective Observational Study.

Front Behav Neurosci 2021 13;15:646528. Epub 2021 Apr 13.

Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.

Postoperative cognitive dysfunction (POCD) is a common and severe complication of cardiovascular surgery. Lymphocyte-to-monocyte ratio (LMR) has been reported to be an independent predictor of lots of diseases associated with inflammation, but the association between the LMR and POCD is not clear. The present study aimed to investigate the potential value of LMR level to predict POCD in patients undergoing cardiovascular surgery. A prospective observational study was performed on the patients diagnosed with heart diseases undergoing cardiovascular surgeries with cardiopulmonary bypass. The leukocyte counts were measured by blood routine examination preoperatively. Then we calculated the LMR by dividing the lymphocyte count by the monocyte count. Neurocognitive functions were assessed 1 day before and 7 days after surgery. Perioperative factors were recorded to explore the relationship between LMR and POCD. In total, 75 patients finished the whole study, while 34 patients developed POCD. The preoperative LMR level in the POCD group was higher than that in the non-POCD group. A cutoff value of 4.855 was identified to predict POCD occurrence according to ROC curve. The perioperative dynamic change of LMR level in the POCD group was higher than those in the non-POCD group. A cutoff value of 2.255 was identified to predict POCD occurrence according to ROC curve and the dynamic LMR change had similar varying trend with preoperative LMR level. The dynamic change of LMR level in the peripheral blood is associated with occurrence of POCD, and preoperative LMR level seems to be a prognostic biomarker of postoperative cognitive dysfunction in patients after cardiovascular surgery.
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http://dx.doi.org/10.3389/fnbeh.2021.646528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076514PMC
April 2021

Predicting mortality in acute ischaemic stroke treated with mechanical thrombectomy: analysis of a multicentre prospective registry.

BMJ Open 2021 04 1;11(4):e043415. Epub 2021 Apr 1.

Department of Neurology, Jinan University First Affiliated Hospital, Guangzhou, China

Objectives: We aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT).

Design: Analysis of a multicentre prospective registry.

Setting: In six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively.

Participants: 224 patients with AIS were treated by MT.

Results: Of 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality.

Conclusions: We developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated.

Trial Registration Number: Chinese Clinical Trial Registry (ChiCTR-OOC-17013052).
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http://dx.doi.org/10.1136/bmjopen-2020-043415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021751PMC
April 2021

Laryngopharyngeal reflux disease management for recurrent laryngeal contact granuloma: A case report.

World J Clin Cases 2021 Mar;9(8):1989-1995

Department of Otorhinolaryngology, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510000, Guangdong Province, China.

Background: Laryngeal contact granuloma (LCG) is difficult to treat and frequently associated with high persistence and recurrence, despite the availability of both surgical and pharmacological treatment options. An appropriate strategy is therefore needed to help patients with multiple recurrences of LCG to potentially avoid unnecess-ary surgery.

Case Summary: We describe the case of a 34-year-old male patient with recurrent LCG in which a good response was achieved through successful management of laryngophar-yngeal reflux disease using a combination pharmacotherapeutic regimen consisting of anti-reflux therapy, pepsin secretion inhibition, bile acid neutralization, and lifestyle modifications. This patient underwent surgery to excise the granuloma, then relapsed, underwent a second surgery, which was followed by a second recurrence. The granuloma then disappeared after 9 mo of combined treatment with ilaprazole enteric-coated capsules (10 mg qd), mosapride tablets (5 mg tid) and compound digestive enzyme capsules (2 tablets). The drug regimen was discontinued after one year, and no recurrence of the lesion has been reported during the one-year follow-up period.

Conclusion: We report a combination of pharmacotherapeutics and lifestyle modifications for the management of laryngopharyngeal reflux disease to address recurring LCG.
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http://dx.doi.org/10.12998/wjcc.v9.i8.1989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953387PMC
March 2021

Hemorrhagic abdominal pseudocyst following ventriculoperitoneal shunt: a case report.

BMC Surg 2021 Mar 21;21(1):154. Epub 2021 Mar 21.

Department of Neurosurgery, Li Hui Li Hospital of Medical Centre of Ningbo, No. 1111 Jiangnan Road, Yinzhou District, Ningbo, 315041, China.

Background: Abdominal cerebrospinal fluid (CSF) pseudocyst is an uncommon but important complication of ventriculoperitoneal (VP) shunts. While individual articles have reported many cases of abdominal CSF pseudocyst following VP shunts, no case of a hemorrhagic abdominal pseudocyst after VP shunts has been reported so far.

Case Presentation: This article reports a 68-year-old woman with a 4-month history of progressive abdominal pain and distention. She denied any additional symptoms. A VP shunt was performed 15 years earlier to treat idiopathic normal pressure hydrocephalus and no other abdominal surgery was performed. Physical examination revealed an elastic palpable mass in her right lower abdomen, which was dull to percussion. Abdominal computed tomography (CT) scan indicated a large cystic collection of homogenous iso-density fluid in the right lower abdominal region with clear margins. The distal segment of the peritoneal shunt catheter was located within the cystic mass. Abdominal CSF pseudocyst was highly suspected as a diagnosis. Laparoscopic cyst drainage with removal of the whole cystic mass was performed, 15-cm cyst which found with thick walls and organized chronic hematic content. No responsible vessel for the cyst hemorrhage was identified. No further shunt revision was placed. Histological examination showed that the cyst wall consisted of outer fibrous tissue and inner granulation tissue without epithelial lining, and the cystic content was chronic hematoma. The patient had an uneventful postoperative course and remained asymptomatic for 8-mo follow-up.

Conclusion: To the best of our knowledge, this is the first report of hemorrhagic onset in the abdominal pseudocyst following VP shunt. Such special condition can accelerate the appearance of clinical signs of the abdominal pseudocyst after VP shunts, and its mechanisms may be similar to the evolution of subdural effusion into chronic subdural hematoma (CSDH).
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http://dx.doi.org/10.1186/s12893-021-01161-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981930PMC
March 2021

Effects of Low-Frequency Repetitive Transcranial Magnetic Stimulation of the Bilateral Parietal Cortex in Patients With Tourette Syndrome.

Front Neurol 2021 12;12:602830. Epub 2021 Feb 12.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Traditional medical treatments are not effective for some patients with Tourette syndrome (TS). According to the literature, repetitive transcranial magnetic stimulation (rTMS) may be effective for the treatment of TS; however, different targets show different results. To assess the efficacy and safety of low-frequency rTMS in patients with TS, with the bilateral parietal cortex as the target. Thirty patients with TS were divided into two groups: active and sham groups. The active group was subjected to 0.5-Hz rTMS at 90% of resting motor threshold (RMT) with 1,200 stimuli/day/side, whereas the sham group was subjected to 0.5-Hz rTMS at 10% of RMT with 1,200 stimuli/day/side with changes in the coil direction. Both groups were bilaterally stimulated over the parietal cortex (P3 and P4 electrode sites) for 10 consecutive days. The symptoms of tics and premonitory urges were evaluated using the Yale Global Tic Severity Scale (YGTSS), Modified Scoring Method for the Rush Video-based Tic Rating Scale (MRVBTS), and Premonitory Urge for Tics Scale (PUTS) scores at baseline, the end of the 10-day treatment, 1 week after treatment, and 1 month after treatment. At the end of the 10-day treatment, the YGTSS total, YGTSS motor tic, YGTSS phonic tic, MRVBTS, and PUTS scores in the active group significantly improved and improvements were maintained for at least 1 month. Low-frequency bilateral rTMS of the parietal cortex can markedly alleviate motor tics, phonic tics, and premonitory urges in patients with TS.
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http://dx.doi.org/10.3389/fneur.2021.602830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907167PMC
February 2021

Redesign of protein nanocages: the way from 0D, 1D, 2D to 3D assembly.

Chem Soc Rev 2021 Mar 15;50(6):3957-3989. Epub 2021 Feb 15.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing Key Laboratory of Functional Food from Plant Resources, Beijing 100083, China.

Compartmentalization is a hallmark of living systems. Through compartmentalization, ubiquitous protein nanocages such as viral capsids, ferritin, small heat shock proteins, and DNA-binding proteins from starved cells fulfill a variety of functions, while their shell-like structures hold great promise for various applications in the field of nanomedicine and nanotechnology. However, the number and structure of natural protein nanocages are limited, and these natural protein nanocages may not be suited for a given application, which might impede their further application as nanovehicles, biotemplates or building blocks. To overcome these shortcomings, different strategies have been developed by scientists to construct artificial protein nanocages, and 1D, 2D and 3D protein arrays with protein nanocages as building blocks through genetic and chemical modification to rival the size and functionality of natural protein nanocages. This review outlines the recent advances in the field of the design and construction of artificial protein nanocages and their assemblies with higher order, summarizes the strategies for creating the assembly of protein nanocages from zero-dimension to three dimensions, and introduces their corresponding applications in the preparation of nanomaterials, electrochemistry, and drug delivery. The review will highlight the roles of both the inter-subunit/intermolecular interactions at the key interface and the protein symmetry in constructing and controlling protein nanocage assemblies with different dimensions.
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http://dx.doi.org/10.1039/d0cs01349hDOI Listing
March 2021

VNTR2/VNTR3 genotype in the gene is associated with reduced effectiveness of intravenous immunoglobulin in patients with myasthenia gravis.

Ther Adv Neurol Disord 2021 27;14:1756286420986747. Epub 2021 Jan 27.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Chang Chun Street, Beijing 100053, China.

Background: Intravenous immunoglobulin (IVIG) has been commonly used to treat myasthenia gravis exacerbation, but is still ineffective in nearly 30% of patients. A variable number of tandem repeat (VNTR) polymorphism in the gene has been found to reduce the efficiency of IgG biologics. However, whether the polymorphism influences the efficacy of IVIG in generalized myasthenia gravis (MG) patients with exacerbations remains unknown.

Methods: The distribution of VNTR genotypes was analyzed in 334 patients with MG. Varied VNTR alleles were determined by capillary electrophoresis and confirmed by Sanger sequencing. Information of endogenous IgG levels were collected in patients without previous immunotherapy ( = 26). Medical records of patients who received IVIG therapy were retrospectively analyzed for therapeutic outcomes of IVIG treatment ( = 61). Patients whose Activities of Daily Living scores decreased by 2 or more points on day 14 were considered responders to the treatment.

Results: The VNTR3/3 and VNTR2/3 genotypes were detected in 96.7% (323/334) and 3.4% (11/334) patients, respectively. Patients with VNTR2/3 heterozygosity had lower endogenous IgG levels than those with VNTR3/3 homozygosity (9.81 ± 2.61 g/L 12.41 ± 2.45g/L,  = 0.016). The response rate of IVIG therapy was 78.7% (48/61). All responders and nine non-responders were VNTR3/3 homozygotes, whereas all the patients with VNTR2/3 genotypes were non-responders ( = 4). In patients who took IVIG treatments, endogenous IgG levels were significantly lower in non-responders compared with responders (12.93 ± 2.24 g/L 8.85 ± 2.69 g/L,  = 0.006), especially in VNTR2/3 heterozygotes (7.86 ± 1.78 g/L,  = 0.001).

Conclusion: The VNTR2/3 genotype could influence endogenous IgG levels and serve as a predictive marker for poor responses to IVIG in MG patients.
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http://dx.doi.org/10.1177/1756286420986747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844454PMC
January 2021

Construction of thermally robust and porous shrimp ferritin crystalline for molecular encapsulation through intermolecular arginine-arginine attractions.

Food Chem 2021 Jul 19;349:129089. Epub 2021 Jan 19.

College of Food Science and Nutritional Engineering, China Agricultural University, Beijing Key Laboratory of Functional Food from Plant Resources, Beijing 100083, China. Electronic address:

Protein colloid crystals are considered as high porous soft materials, presenting great potentials in nutrients and drug encapsulation, but protein crystal fabrication usually needs precipitant and high protein concentration. Herein, an easy implemented approach was reported for the construction of protein colloid crystals in diluted solution with shimp ferritin as building blocks by taking advantage of the strength of multiple intermolecular arginine-arginine interactions. The X-ray single-crystal structure reveals that a group of exquisite arginine-arginine interactions between two neighboring ferritin enable them self-assembly into long-range ordered protein soft materials. The arginine-arginine interactions mediate crystal generation favored at pH 9.5 with 200 mM NaCl, and the resulting colloid crystals exhibit high thermal stability (90 °C for 30 min). Importantly, the interglobular cavity in colloid crystals is three times larger in volume than that of intrinsic ferritin cavity in each unit cell, which can be used for molecular encapsulation.
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http://dx.doi.org/10.1016/j.foodchem.2021.129089DOI Listing
July 2021

Propofol ameliorates endotoxin‑induced myocardial cell injury by inhibiting inflammation and apoptosis via the PPARγ/HMGB1/NLRP3 axis.

Mol Med Rep 2021 03 5;23(3). Epub 2021 Jan 5.

Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi 710032, P.R. China.

Endotoxin lipopolysaccharide (LPS) is one of the primary causes of myocardial injury. Propofol confers protective effects against LPS‑induced myocardial damage; however, the biological functions and mechanisms underlying propofol are not completely understood. The present study aimed to investigate the effects of propofol on LPS‑induced myocardial injury. Primary neonatal rat cardiomyocytes were treated with LPS to establish a myocardial injury model. LDH release in the culture media was measured using a LDH assay kit. The interactions between NLR family pyrin domain containing 3 (NLRP3), apoptosis‑associated speck‑like protein containing A CARD (ASC) and pro‑caspase‑1 were determined using a co‑immunoprecipitation assay. Cell viability was measured using an MTT assay, and the levels of cell apoptosis were determined using flow cytometry, JC‑1 staining (mitochondrial membrane potential) and caspase‑3 activity assays. The mRNA expression levels of TNF‑α, IL‑6, IL‑1β and IL‑18, and the protein expression levels of NLRP3, ASC, pro‑caspase‑1, caspase‑1 p10, pro‑IL‑1β, IL‑1β, pro‑IL‑18, IL‑18, high mobility group box‑1 (HMGB1) and peroxisome proliferator‑activated receptor γ (PPARγ) were analyzed using reverse transcription‑quantitative PCR and western blotting analyses, respectively. ELISAs were performed to measure the production of inflammatory mediators, including TNF‑α, IL‑6, IL‑1β and IL‑18. The present results demonstrated that pretreatment with propofol significantly attenuated LPS‑induced neonatal rat cardiomyocyte injury in a concentration‑ and time‑dependent manner. Propofol pretreatment also significantly inhibited LPS‑induced cardiomyocyte inflammation and apoptosis. The results suggested that propofol pretreatment inactivated HMGB1‑dependent NLRP3 inflammasome signaling, which involved PPARγ activation. Therefore, the results indicated that propofol reduced endotoxin‑induced cardiomyocyte injury by inhibiting inflammation and apoptosis via the PPARγ/HMGB1/NLRP3 axis, suggesting that propofol may serve as a potential therapeutic agent for septic myocardial damage.
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http://dx.doi.org/10.3892/mmr.2020.11815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821353PMC
March 2021

Degradation of norfloxacin by hydroxylamine enhanced fenton system: Kinetics, mechanism and degradation pathway.

Chemosphere 2021 May 23;270:129408. Epub 2020 Dec 23.

Laboratory of Environmental Technology, INET, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory of Radioactive Waste Treatment, Tsinghua University, Beijing, 100084, China. Electronic address:

This study demonstrated a fast and efficient degradation of a typical antibiotic norfloxacin (NOR) in a hydroxylamine enhanced Fenton (HA-Fenton) system, which showed a higher catalytic activity over a wider pH range (3.0-9.0). The removal efficiency of NOR was 96% at following conditions: 10 mg/L NOR, 10 μM Fe, 1.0 mM HO, 0.4 mM HA and pH 5.0. The degradation rate of NOR in the HA-Fenton system (0.23 min) was 10.9 times of that (0.021 min) in Fenton system. The addition of HA to Fenton system accelerated the conversion of Fe to Fe, leading to the high concentration of ·OH in the HA-Fenton system. Ten degradation transformation products were detected by ultra-performance liquid chromatography tandem quadrupole time of flight mass spectrometer (UPLC-QTOF-MS), consequently, three main degradation steps were proposed, including defluorination, quinolone group transformation, and defluorination and piperazinyl ring opening. Further analyses of NO, NO and F after the reaction indicated that defluorination process was the crucial degradation step. The HA-Fenton system might offer an efficient alternative for degradation of antibiotics in wastewater.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129408DOI Listing
May 2021

Seizure symptoms and ambulatory EEG findings: incidence of epileptiform discharges.

Epileptic Disord 2020 Dec;22(6):752-758

Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

Aims: Ambulatory video-EEG monitoring has been utilized as a cost-effective alternative to inpatient video-EEG monitoring for non-surgical diagnostic evaluation of symptoms suggestive of epileptic seizures. We aimed to assess incidence of epileptiform discharges in ambulatory video-EEG recordings according to seizure symptom history obtained during clinical evaluation.

Methods: This was a retrospective cohort study. We queried seizure symptoms from 9,221 consecutive ambulatory video-EEG studies in 35 states over one calendar year. We assessed incidence of epileptiform discharges for each symptom, including symptoms that conformed to a category heading, even if not included in the ILAE 2017 symptom list. We report incidences, odds ratios, and corresponding p values using Fisher's exact test and univariate logistic regression. We applied multivariable logistic regression to generate odds ratios for the six symptom categories that are controlled for the presence of other symptoms.

Results: History that included motor symptoms (OR=1.53) or automatisms (OR=1.42) was associated with increased occurrence of epileptiform discharges, whereas history of sensory symptoms (OR=0.76) predicted lack of epileptiform discharges. Patient-reported symptoms that were associated with increased occurrence of epileptiform discharges included lip-smacking, moaning, verbal automatism, aggression, eye-blinking, déjà vu, muscle pain, urinary incontinence, choking and jerking. On the other hand, auditory hallucination memory deficits, lightheadedness, syncope, giddiness, fibromyalgia and chronic pain predicted absence of epileptiform discharges. The majority of epileptiform discharges consisted only of interictal sharp waves or spikes.

Conclusions: Our study shows that the use of ILAE 2017 symptom categories may help guide ambulatory video-EEG studies.
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http://dx.doi.org/10.1684/epd.2020.1220DOI Listing
December 2020

MOF-derived [email protected] as an efficient catalyst for catalytic ozonation of norfloxacin.

J Hazard Mater 2021 02 15;403:123697. Epub 2020 Aug 15.

Collaborative Innovation Center for Advanced Nuclear Energy Technology, INET, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory of Radioactive Waste Treatment, Tsinghua University, Beijing 100084, China. Electronic address:

Metal-organic frameworks (MOFs) ZIF-67-derived [email protected] composite was prepared, characterized and used as an efficinet catalyst for ozonation of norfloxacin (NOF). Results showed that ZIF-67-derived CoO-C composite maintained the polyhedral structure of ZIF-67. After modification, abundant amorphous FeOOH nanowire attached on the surface of CoO-C composite, resulting in [email protected] interwoven polyhedrons. Furthermore, the specific surface area of the formed composite was about 2.5 times that of CoO-C composite, which might provide more active sites for catalytic reaction. Compared with single ozonation system, the catalytic ozonation process ([email protected]/O) had better performance in NOF mineralization under the same operating conditions. Moreover, in the presence of [email protected], faster O decomposition and higher •OH concentration were observed, which could explain the significant enhancement of TOC removal. The co-existence of Fe and Co in various valence states in catalyst might improve the conversion of Co(III)/Co(II) and Fe(III)/Fe(II), which would increase the catalytic activity in catalytic ozonation process. Besides, several main intermediate products were detected and possible NOF degradation pathway was proposed.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123697DOI Listing
February 2021

Catalytic ozonation of norfloxacin using CoO/C composite derived from ZIF-67 as catalyst.

Chemosphere 2021 Feb 20;265:129047. Epub 2020 Nov 20.

Laboratory of Environmental Technology, INET, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory of Radioactive Waste Treatment, Tsinghua University, Beijing, 100084, China. Electronic address:

In this study, CoO-carbon composite was synthesized by calcined metal organic framework (MOF) ZIF-67 and used as efficient catalysts for ozonation of norfloxacin (NOF). The MOF-derived CoO-C composite remained similar polyhedrons structure of ZIF-67, suggesting that CoO was well-dispersed in CoO-C composite. Furthermore, a larger amount of surface carbon-oxygen functional groups were distributed on CoO-C composite, which resulted in the diversification of active sites for catalytic ozonation reaction. NOF degradation and mineralization could be effectively enhanced in CoO-C/O process. Moreover, NOF mineralization by catalytic ozonation strongly depended on the solution pH, while other operational conditions, such as O concentration and catalyst dosage had not obvious influence on it. CoO-C composite could significantly accelerate O decomposition to produce active free radicals (such as •OH), which enhanced the mineralization of NOF. The possible catalytic mechanism of CoO-C composite was proposed. Additionally, after five consecutive use of CoO-C composite in catalytic ozonation process, there was no obvious decrease in TOC removal efficiency, indicating a stable performance of CoO-C composite, which was suitable for the catalytic ozonation for wastewater treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2020.129047DOI Listing
February 2021

[The role of miRNA in kidney development].

Yi Chuan 2020 Nov;42(11):1062-1072

Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China.

MicroRNAs (miRNAs) are endogenous small non-coding RNAs (19-25 nucleotides) that negatively regulate gene expression at the post transcriptional level by binding to complementary target sequences in the target mRNA. miRNAs play an important role in a wide range of biological processes, including organ development. Recent studies have shown that some miRNAs are highly expressed in the kidney and are closely related to kidney development and diseases, suggesting that miRNAs are important regulators in kidney physiology and pathology. This review will focus on the research progress of miRNA in kidney development, and discuss the role of miRNAs in the occurrence and development of renal dysplasia, which will provide a reference for the diagnosis and research of diseases related to kidney development.
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http://dx.doi.org/10.16288/j.yczz.20-112DOI Listing
November 2020

The high-resolution X-ray structure of vinca-domain inhibitors of microtubules provides a rational approach for drug design.

FEBS Lett 2021 01 10;595(2):195-205. Epub 2021 Jan 10.

Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

Tubulin vinca-domain ligands can inhibit microtubule polymerization, causing cell death in mitosis, and their potential against multiple cancer types has been demonstrated. However, due to drug resistance and toxicities, development of novel vinca-domain ligands is still needed. In this study, we determined the high-resolution crystal structures of vinorelbine, YXD, and Phomopsin A in complex with tubulin at 2.5 Å. Additionally, we recapitulated all previously published high-resolution crystal structures of the vinca binding site to reveal critical residues and the molecular mechanism of vinca-domain ligands interacting with tubulin. Furthermore, we designed putatively novel triazolopyrimidine derivatives by introducing secondary amine groups to establish salt-bridge and H-bond interactions with Asp179 and Asn329 . Our studies provided the structural basis for designing novel tubulin vinca-domain ligands.
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http://dx.doi.org/10.1002/1873-3468.14003DOI Listing
January 2021

Analysis of the interaction effect of 48 SNPs and obesity on type 2 diabetes in Chinese Hans.

BMJ Open Diabetes Res Care 2020 11;8(2)

Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.

Introduction: Both environmental and genetic factors contribute to type 2 diabetes (T2D) risk. Dozens of T2D susceptibility loci have been identified by genome-wide association study. However, these loci account for only a small fraction of the familial T2D risk. We hypothesized that the gene-obesity interaction may contribute to the missing heritability.

Research Design And Method: Forty-eight T2D-associated variants were genotyped using the TaqMan OpenArray Genotyping System and iPLEX Sequenom MassARRAY platform in two separate studies. Obesity was defined according to multiple indexes (body mass index (BMI), waist circumference and waist-hip ratio). Multiplicative interactions were tested using general logistic regression to assess the gene-obesity interaction effect on T2D risk among a total of 6206 Chinese Hans.

Results: After adjusting for the main effects of genes and obesity, as well as covariates (age, sex, smoking and alcohol consumption status), robust multiplicative interaction effects were observed between rs10811661 in and multiple obesity indices (p ranged from 0.001 to 0.043 for BMI, waist circumference and waist-hip ratio). Obese individuals with the TT genotype had a drastically higher risk of T2D than normal weight individuals without the risk allele (OR=17.58, p<0.001). There were no significant differences between subgroups in the stratification analysis. Plausible biological explanations were established using a public database. However, there were no significant interaction effects between the other 47 single nucleotide polymorphism (SNPs) and obesity.

Conclusion: Our findings indicated that the gene-obesity interaction significantly increases T2D risk in Chinese Hans. The interaction effect identified in our study may help to explain some of the missing heritability in the context of T2D susceptibility. In addition, the interaction effect may play a role in the precise prevention of T2D in Chinese individuals.
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http://dx.doi.org/10.1136/bmjdrc-2020-001638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674088PMC
November 2020

Degradation of sulfamethoxazole by ozonation combined with ionizing radiation.

J Hazard Mater 2021 04 27;407:124377. Epub 2020 Oct 27.

Laboratory of Environmental Technology, INET, Tsinghua University, Beijing 100084, China; Beijing Key Laboratory of Radioactive Waste Treatment, Tsinghua University, Beijing 100084, China. Electronic address:

In this study, the degradation and mineralization of sulfamethoxazole (SMX) by ozonation and ionizing radiation were investigated respectively, and the performance of the combined process of ozonation and ionizing radiation was evaluated. Results showed that complete degradation of SMX could be obtained by ozonation in 12 min or by ionizing radiation with the absorbed dose of 1.5 kGy. However, the mineralization of SMX was very limited in ozonation and ionizing radiation system, TOC removal efficiency was less than 15% and 27% in single-ozonation and single-radiation process, respectively. The combination of ozonation and radiation process obviously enhanced the mineralization of SMX, TOC removal efficiency increased to 65.7%. Moreover, the ozonation-radiation process also exhibited good performance in the mineralization of sulfamethazine (SMT) and sulfanilamide (SM), suggesting a good application prospect of the combined process in treating wastewater contaminated with antibiotics. In addition, some different intermediate products were identified during SMX degradation in ozonation process and ionizing radiation process by a high-performance liquid chromatography-mass spectrometry (LC-MS), and possible pathways of SMX degradation by ozonation and radiation were proposed.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124377DOI Listing
April 2021

Degradation and mineralization of ofloxacin by ozonation and peroxone (O/HO) process.

Chemosphere 2021 Apr 3;269:128775. Epub 2020 Nov 3.

Laboratory of Environmental Technology, INET, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory of Radioactive Waste Treatment, Tsinghua University, Beijing, 100084, China. Electronic address:

The degradation and mineralization of ofloxacin (OFX) by ozonation and peroxone process (O/HO) was investigated. The influence of operational conditions and inorganic anions on the mineralization of OFX were also studied. Results showed that OFX could be rapidly oxidized by both O alone and O/HO process. The mineralization of OFX was significantly enhanced (55%) in peroxone process, compared with that in ozonation alone (30%). The direct oxidation of OFX by ozone molecules might account for the degradation of OFX in both ozonation and peroxone process, whereas, in the presence of HO, the improvement of the ozone decomposition and the formation of OH radicals were responsible for enhancing OFX mineralization. The applied dosage of HO and O was important for the performance of peroxone process in OFX mineralization. The addition of HCO and PO enhanced OFX mineralization, while the presence of Cl and NO had negative effect on OFX mineralization in both ozonation and peroxone processes. Ozonation process might be a promising technology for the degradation of OFX, while the combination process of O/HO could be an effective method for the improvement of the mineralization of refractory organic pollutants.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128775DOI Listing
April 2021

Catalytic ozonation for degradation of sulfamethazine using NiCoO as catalyst.

Chemosphere 2021 Apr 2;268:128840. Epub 2020 Nov 2.

Collaborative Innovation Center for Advanced Nuclear Energy Technology, INET, Tsinghua University, Beijing, 100084, China; Beijing Key Laboratory of Radioactive Waste Treatment, Tsinghua University, Beijing, 100084, China. Electronic address:

In this study, spinel NiCoO was prepared, characterized, and used for catalytic ozonation of SMT. The performance of NiCoO in SMT mineralization was systematically evaluated. The results showed that NiCoO could significantly enhance the mineralization of SMT over a wide initial pH range of 3.0-9.0. The mineralization rate of SMT increased with the increase in the dosage of NiCoO and O concentration, while the initial concentration of SMT (from 10 mg/L to 40 mg/L) had no obvious influence on the removal efficiency of TOC, indicating that the SMT mineralization was mainly affected by the mass transfer. Furthermore, according to the result of the determination of OH, NiCoO could undoubtedly improve the generation of OH, the quenching test confirmed that OH played an important role in TOC removal in ozonation process. Moreover, the XPS spectra of as-prepared and used NiCoO catalyst showed that Co ions might indirectly promote the catalytic ozonation process as the Lewis acid sites, while the Ni/Ni cycle in the catalyst played a vital role in catalyzing ozone to generate free radicals and enhancing the mineralization capacity of NiCoO/O system.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128840DOI Listing
April 2021

Poly(I:C) preconditioning protects the heart against myocardial ischemia/reperfusion injury through TLR3/PI3K/Akt-dependent pathway.

Signal Transduct Target Ther 2020 11 6;5(1):216. Epub 2020 Nov 6.

Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Emerging evidence suggests that Toll-like receptors (TLRs) ligands pretreatment may play a vital role in the progress of myocardial ischemia/reperfusion (I/R) injury. As the ligand of TLR3, polyinosinic-polycytidylic acid (poly(I:C)), a synthetic double-stranded RNA, whether its preconditioning can exhibit a cardioprotective phenotype remains unknown. Here, we report the protective effect of poly(I:C) pretreatment in acute myocardial I/R injury by activating TLR3/PI3K/Akt signaling pathway. Poly(I:C) pretreatment leads to a significant reduction of infarct size, improvement of cardiac function, and downregulation of inflammatory cytokines and apoptotic molecules compared with controls. Subsequently, our data demonstrate that phosphorylation of TLR3 tyrosine residue and its interaction with PI3K is enhanced, and protein levels of phospho-PI3K and phospho-Akt are both increased after poly(I:C) pretreatment, while knock out of TLR3 suppresses the cardioprotection of poly(I:C) preconditioning through a decreased activation of PI3K/Akt signaling. Moreover, inhibition of p85 PI3K by the administration of LY294002 in vivo and knockdown of Akt by siRNA in vitro significantly abolish poly(I:C) preconditioning-induced cardioprotective effect. In conclusion, our results reveal that poly(I:C) preconditioning exhibits essential protection in myocardial I/R injury via its modulation of TLR3, and the downstream PI3K/Akt signaling, which may provide a potential pharmacologic target for perioperative cardioprotection.
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http://dx.doi.org/10.1038/s41392-020-00257-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644758PMC
November 2020

Characteristics and evaluation of the effectiveness of monitoring and control measures for the first 69 Patients with COVID-19 from 18 January 2020 to 2 March in Wuxi, China.

Sustain Cities Soc 2021 Jan 17;64:102559. Epub 2020 Oct 17.

Department of Disease Control, Wuxi Center for Disease Control and Prevention, No. 499 Jin Cheng Road, Wuxi 214023, Jiangsu Province, China.

Background: The Coronavirus disease (COVID-19) has caused 91,305 confirmed cases and 4746 deaths in China by 13:50 on October 11, 2020. We analyzed data on 69 infections in Wuxi to describe the disease's characteristics, to analyze factors of cases clinical outcome and to evaluate the prevention and control measures.

Methods: The demographic characteristics, exposure history, time indicators and propagation dynamics in Wuxi were collected.

Results: The clinical severity of cases was mostly mild and normal (75.36 %). Aging (relative risk [RR] = 1.04, 95 % confidence interval [CI]: 1.001-1.08) and fever (RR = 10.33, 95 %CI: 2.75-38.78) were risk factors for disease severity. The mean incubation period was estimated to be 4.77 days (95 % CI: 3.61-5.94), with a mean serial interval of 6.31 days (95 % CI: 5.12-7.50). The controlled reproduction number was estimated to be 1.12 (95 %CI: 0.71-1.69).

Conclusions: The incidence of COVID-19 in Wuxi has turned into a lower level, suggesting the early prevention and control measures have achieved effectiveness. Aging and fever of initial symptom were risk factors for severe clinical outcome. The family clusters provided further clues of the risk factors for COVID-19 transmission.
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http://dx.doi.org/10.1016/j.scs.2020.102559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568471PMC
January 2021

Immunity and coagulation and fibrinolytic processes may reduce the risk of severe illness in pregnant women with coronavirus disease 2019.

Am J Obstet Gynecol 2021 04 22;224(4):393.e1-393.e25. Epub 2020 Oct 22.

Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: There are specific physiological features regarding the immunity and coagulation among pregnant women, which may play important roles in the development of coronavirus disease 2019.

Objective: This study aimed to determine the key factors associated with the deterioration of patients with coronavirus disease 2019 and the differentiating clinical characteristics of pregnant women with coronavirus disease 2019 to interfere with the progression of coronavirus disease 2019.

Study Design: A retrospective study of 539 Chinese Han adult patients with coronavirus disease 2019 was conducted, of which 36 cases were pregnant women. In addition, 36 pregnant women without coronavirus disease 2019 were recruited as the control. The characteristics of severe and critical illnesses, which were differentiated from mild and moderate illnesses in patients with coronavirus disease 2019, were analyzed using a machine learning algorithm. In addition, major differences between pregnant women with coronavirus disease 2019 and age-matched nonpregnant women with severe or critical coronavirus disease 2019, paired with pregnant women without coronavirus disease 2019, were explored to identify specific physiological features of pregnant women with coronavirus disease 2019.

Results: For the total patient population, the lymphocyte, CD3, CD4, CD8, CD19, and CD16CD56 cell counts were significantly lower, and white blood cell count, neutrophil count, and neutrophil-to-lymphocyte ratio were higher in those with severe or critical illness than those with mild or moderate illness (P<.001). The plasma levels of interleukin-6, interleukin-10, and interleukin-6-to-interleukin-10 ratio were significantly increased in patients with critical illness compared with patients with mild, moderate, and severe illnesses (P<.001). The above immunologic coclusters achieved an area under the receiver operating characteristic curve of 0.801 (95% confidence interval, 0.764-0.838), and its combined model with the coagulation and fibrinolysis indices (prothrombin time, D-dimer) achieved an area under the receiver operating characteristic curve of 0.815 (95% confidence interval, 0.779-0.851) using the random forest regression model to predict severe or critical illness. For pregnant women with coronavirus disease 2019, none had preexisting diseases. Compared with nonpregnant women with mild or moderate coronavirus disease 2019, pregnant women with coronavirus disease 2019 displayed increased white blood cell count, neutrophil count, neutrophil-to-lymphocyte ratio, and levels of D-dimer and fibrinogen, along with decreased lymphocyte and interleukin-4 levels (P<.05). Although they presented similar changes of immunologic markers of lymphocyte; white blood cell count; neutrophil-to-lymphocyte ratio; CD3, CD4, CD8, and CD16CD56 cell counts; and interleukin-6-to-interleukin-10 ratio, compared with nonpregnant women with severe or critical coronavirus disease 2019, none of the pregnant women with coronavirus disease 2019 deteriorated into severe or critical illness. There was no significant difference in white blood cell count, lymphocyte count, neutrophil count, neutrophil-to-lymphocyte ratio, immunologic markers, or coagulation and fibrinolysis markers between pregnant women with coronavirus disease 2019 and pregnant women without coronavirus disease 2019. As for the discrepancy of pathophysiological features between pregnant women with coronavirus disease 2019 and nonpregnant women with severe or critical coronavirus disease 2019, the immunologic markers achieved an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.773-0.977), and its combined model with coagulation and fibrinolysis indices achieved an area under the receiver operating characteristic curve of 0.931 (95% confidence interval, 0.850-1.000).

Conclusion: Immune dysregulation was identified as a crucial feature of patients with coronavirus disease 2019, which developed severe or critical illness, and pregnant women with coronavirus disease 2019 presented with similar immune responses but rarer incidences of severe or critical illness. Immune dysregulation is related to the risks of deterioration into severe or critical illness. The specific coagulation and fibrinolysis systems of pregnancy may reduce the risk of pregnant women with coronavirus disease 2019 without preexisting disease from developing severe illness.
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http://dx.doi.org/10.1016/j.ajog.2020.10.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578241PMC
April 2021

Unusual electrophysiological findings in a Chinese ALS 4 family with SETX-L389S mutation: a three-year follow-up.

J Neurol 2021 Mar 30;268(3):1050-1058. Epub 2020 Sep 30.

Department of NEUROLOGY, Xuanwu Hospital, Capital Medical University, Changchun Street, Beijing, 100053, China.

Amyotrophic lateral sclerosis type 4 (ALS4) is a familial form of ALS caused by mutations in the SETX gene. To date, there are seven unrelated ALS4 families with four missense mutations (L389S, T31I, R2136H, and M386T) in SETX. ALS4 is characterized by early onset, distal muscle weakness and atrophy, pyramidal signs, and the absence of sensory deficits. Motor conduction studies often present normality or reduced amplitudes of compound muscle action potential (CMAP). The conduction blocks (CBs) are rare and only observed in one male of an Italian ALS4 family. Our study showed that seven symptomatic patients presented the classical ALS4 phenotype with two asymptomatic females in a Chinese family spanning three generations. Sequencing analysis revealed a heterozygous c.1166T > C/p.L389S mutation in SETX that co-segregated with disease phenotype in the family. The same mutation has been identified previously in three ALS4 families from the United States and Italy, respectively. Specifically, three young males presented multiple CBs and abnormal temporal dispersions (TD) in the median, ulnar and tibial nerves over the three-year follow-up period. Moreover, for the first time, we found that senataxin was also expressed in the myelin sheath of peripheral nerves besides axons. The study indicates that CBs and abnormal TD are the characteristics in the ALS4 family, providing pivotal familial evidence of CBs and TD of motor nerves in ALS4. The unusual electrophysiological features may be associated with the expression of senataxin in peripheral nerves.
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http://dx.doi.org/10.1007/s00415-020-10246-2DOI Listing
March 2021
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