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Endothelial glycocalyx as a potential theriapeutic target in organ injuries

Chinese Medical Journal 2019年第8期132卷 963-975页

作者： Rui-Na Cao Li Tang zhong-yuan xia Rui xia Department of Anesthesiology The First Affiliated Hospital of Yangtze UniversityJingzhouHubei 434000China Department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei 430061China

Objective:The endothelial glycocalyx(eGC)is a dynamic and multicomponent layer of macromolecules found at the surface of vascular endothelium,which is largely underappreciated.It has recently been recognized that eGC is a major regulator of endothelial function and may have therapeutic value in organ injuries.This study aimed to explore the role of the eGC in various pathologic and physiologic conditions,by reviewing the basic research findings pertaining to the detection of the eGC and its clinical significance.We also explored different pharmacologic agents used to protect and rebuild the eGC.Data sources:An in-depth search was performed in the PubMed database,focusing on research published after 2003 with keywords including eGC,permeability,glycocalyx and injuries,and glycocalyx protection.Study selection:Several authoritative reviews and original studies were identified and reviewed to summarize the characteristics of the eGC under physiologic and pathologic conditions as well as the detection and protection of the eGC.Results:The eGC degradation is closely associated with pathophysiologic changes such as vascular permeability,edema formation,mechanotransduction,and clotting cascade,together with neutrophil and platelet adhesion in diverse injury and disease states including inflammation(sepsis and trauma),ischemia-reperfusion injury,shock,hypervolemia,hypertension,hyperglycemia,and high Na+as well as diabetes and atherosclerosis.Therapeutic strategies for protecting and rebuilding the eGC should be explored through experimental test and clinical verifications.Conclusions:Disturbance of the eGC usually occurs at early stages of various clinical pathophysiologies which can be partly prevented and reversed by protecting and restoring the eGC.The eGC seems to be a promising diagnostic biomarker and therapeutic target in clinical settings.

关键词： Endothelial glycocalyx Permeability Injuries Glycocalyx protection

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Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury

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Neural Regeneration Research 2018年第7期13卷 1263-1268页

作者： Heng-Tao Xie zhong-yuan xia xia Pan Bo Zhao Zhi-Gang Liu Department of Anesthesiology Renmin Hospital of Wuhan University

Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pain are still unclear.In this study,a neuropathic pain animal model was created by partial sciatic nerve ligation.Puerarin（30 or 60 mg/kg） was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment.Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats,especially at 7 days after model establishment.At 7 days after model establishment,quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed m RNA expression of transient receptor potential vanilloid 1（Trpv1） and transient receptor potential ankyrin 1（Trpa1） in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury.These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.

关键词： nerve regeneration puerarin Radix Puerariae traditional Chinese medicine Trpv1 Trpa1 dorsal root ganglion peripheral nerve injury neuropathic pain mechanical allodynia thermal hyperalgesia neural regeneration

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Exendin-4 attenuates pain-induced cognitive impairment by alleviating hippocampal neuroinflammation in a rat model of spinal nerve ligation

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Neural Regeneration Research 2020年第7期15卷 1333-1339页

作者： Shan-Shan Cui xiao-Bo Feng Bing-Hong Zhang zhong-yuan xia Li-Ying Zhan Department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Anesthesiology Zhongnan Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Glucagon-like peptide-1 receptor has anti-apoptotic,anti-inflammatory,and neuroprotective effects.It is now recognized that the occurrence and development of chronic pain are strongly associated with anti-inflammatory responses;however,it is not clear whether glucagon-like peptide-1 receptor regulates chronic pain via anti-inflammatory mechanisms.We explored the effects of glucagon-like peptide-1 receptor on nociception,cognition,and neuroinflammation in chronic pain.A rat model of chronic pain was established using left L5 spinal nerve ligation.The glucagon-like peptide-1 receptor agonist exendin-4 was intrathecally injected into rats from 10 to 21 days after spinal nerve ligation.Electrophysiological examinations showed that,after treatment with exendin-4,paw withdrawal frequency of the left limb was significantly reduced,and pain was relieved.In addition,in the Morris water maze test,escape latency increased and the time to reach the platform decreased following exendin-4 treatment.Immunohistochemical staining and western blot assays revealed an increase in the numbers of activated microglia and astrocytes in the dentate gyrus of rat hippocampus,as well as an increase in the expression of tumor necrosis factor alpha,interleukin 1 beta,and interleukin 6.All of these effects could be reversed by exendin-4 treatment.These findings suggest that exendin-4 can alleviate pain-induced neuroinflammatory responses and promote the recovery of cognitive function via the glucagon-like peptide-1 receptor pathway.All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Renmin Hospital of Wuhan University of China(approval No.WDRM 20171214)on September 22,2017.

关键词： astrocyte chronic pain cognitive impairment exendin-4 hippocampal dentate gyrus microglia Morris water maze neuroinflammation spinal nerve ligation

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The role of glycogen synthase kinase 3 beta in brain injury induced by myocardial ischemia/reperfusion injury in a rat model of diabetes mellitus

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Neural Regeneration Research 2017年第10期12卷 1632-1639页

作者： Bo Zhao Wen-wei Gao Ya-jing Liu Meng Jiang Lian Liu Quan yuan Jia-bao Hou zhong-yuan xia Department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Critical Care Medicine Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Myocardial ischemia/reperfusion injury can lead to severe brain injury.Glycogen synthase kinase 3 beta is known to be involved in myocardial ischemia/reperfusion injury and diabetes mellitus.However,the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear.In this study,we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats.Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin.Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery.Post-conditioning comprised three cycles of ischemia/reperfusion.Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion,the structure of the brain was seriously damaged in the experimental rats compared with normal controls.Expression of Bax,interleukin-6,interleukin-8,terminal deoxynucleotidyl transferase d UTP nick end labeling,and cleaved caspase-3 in the brain was significantly increased,while expression of Bcl-2,interleukin-10,and phospho-glycogen synthase kinase 3 beta was decreased.Diabetes mellitus can aggravate inflammatory reactions and apoptosis.Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes.Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glycogen synthase kinase 3 beta.According to these results,glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.

关键词： nerve regeneration myocardial ischemia/reperfusion injury brain injury glycogen synthase kinase 3 beta ischemic post-conditioning diabetes mellitus neural regeneration

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Polyurethane/poly(vinyl alcohol) hydrogel coating improves the cytocompatibility of neural electrodes

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Neural Regeneration Research 2015年第12期10卷 2048-2053页

作者： Mei Li Hai-han Zhou Tao Li Cheng-yan Li zhong-yuan xia Yanwen Y.Duan Department of Anesthesiology Renmin Hospital of Wuhan University Institute of Molecular Science Shanxi University Department of Neurology Renmin Hospital of Wuhan University College of Chemistry and Molecular Sciences Wuhan University

Neural electrodes,the core component of neural prostheses,are usually encapsulated in polydimethylsiloxane（PDMS）.However,PDMS can generate a tissue response after implantation.Based on the physicochemical properties and excellent biocompatibility of polyurethane（PU）and poly（vinyl alcohol）（PVA）when used as coating materials,we synthesized PU/PVA hydrogel coatings and coated the surface of PDMS using plasma treatment,and the cytocompatibility to rat pheochromocytoma（PC12）cells was assessed.Protein adsorption tests indicated that the amount of protein adsorption onto the PDMS substrate was reduced by 92%after coating with the hydrogel.Moreover,the PC12 cells on the PU/PVA-coated PDMS showed higher cell density and longer and more numerous neurites than those on the uncoated PDMS.These results indicate that the PU/PVA hydrogel is cytocompatible and a promising coating material for neural electrodes to improve their biocompatibility.

关键词： nerve regeneration cerebral injury neural electrodes hydrogel coatings polyurethane polydimethylsiloxane poly（vinyl alcohol） cytocompatibility protein adsorption nerve growth factor mt pheochromocytoma cells synaptic differentiation neural regeneration

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Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization

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Neural Regeneration Research 2018年第2期13卷 280-288页

作者： Chao-liang Tang Juan Li Zhe-tao Zhang Bo Zhao Shu-dong Wang Hua-ming Zhang Si Shi Yang Zhang zhong-yuan xia Department of Anesthesiology Renmin Hospital of Wuhan University Department of Anesthesiology Anhui Provincial Hospital of Anhui Medical University Department of Pharmacy Anhui Provincial Hospital of Anhui Medical University Department of Neurosurgery Anhui Provincial Hospital of Anhui Medical University

Dexmedetomidine has sedative, anxiolytic, analgesic, anti-sympathetic, and anti-shivering effects. Dexmedetomidine might be effective in combination with sevoflurane for anesthesia, but prospective randomized controlled clinical trials with which to verify this hypothesis are lacking. In total, 120 patients who underwent embolization of an intracranial aneurysm were recruited from Anhui Provincial Hospital and Renmin Hospital of Wuhan University of China and randomly allocated to two groups. After intraoperative administration of 2% to 3% sevoflurane inhalation, one group of patients received pump-controlled intravenous injection of 1.0 ~tg/kg dexmedetomidine for 15 minutes followed by maintenance with 0.3 ~tg/kg/h until the end of surgery; the other group of patients only underwent pump-controlled infusion of saline. Bispectral index monitoring revealed that dexmedetomidine-assisted anesthesia can shorten the recovery time of spon- taneous breathing, time to eye opening, and time to laryngeal mask removal. Before anesthetic induction and immediately after laryngeal mask airway removal, the glucose and lactate levels were low, the S100~ and neuron-specific enolase levels were low, the perioperative blood pressure and heart rate were stable, and postoperative delirium was minimal. These findings indicate that dexmedetomidine can effectively assist sevoflurane for anesthesia during surgical embolization of intracranial aneurysms, shorten the time to consciousness and extubation, reduce the stress response and energy metabolism, stabilize hemodynamic parameters, and reduce adverse reactions, thereby reducing the damage to the central nervous system. This trial was registered at the Chinese Clinical Trial Registry （http：//***. cn/）（registration number： ChiCTR-IPR- 16008113）.

关键词： nerve regeneration dexmedetomidine sevoflurane bispectral index fast-track anesthesia embolization of intracranial aneurysm stress response neuroprotection neural regeneration

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Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Cells via Regulation of Ca^2+-STIM1/Orail Signaling

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Current Medical Science 2020年第4期40卷 699-707页

作者： Yi-da HU Chao-liang TANG Jia-zhen JIANG Hai-yan LV yuan-bo WU Xiu-de QIN Si SHI Bo ZHAO xiao-nan ZHU zhong-yuan xia Department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhan 430060China Deparment of Anesihesiology the Firsi Affiliated Hospital of University of Science and Technology of ChinaDivision of LifeSciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Emergency Huashan Hospital NorthFudan UniversiryShanghai 201907China Department of Neurology Shanghai General HospitalShanghai Jiao Tong UniversityShanghai 201620China Department of Neurology the First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Neurology Shenzhen Traditional Chinese Medicine Hospitalthe Fourth Clinical Medical College of GuangzhouUniversity of Chinese MedicineShenzhen 518033.China Department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhan 430060China

Summary:Dexmedetomidine(DEX),a potent and highly selective agonist for a2-adrenergic receptors(a2AR),exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca^2+influx.However,the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation(OGD/R)injury in vitro are unknown.We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells,as evidenced by decreased oxidative stress,autophagy,and neuronal apoptosis.Specifically,DEX pretreatment decreased the expression levels of stromal interaction molecule 1(STIM1)and calcium release-activated calcium channel protein 1(Orail),and reduced the concentration of intracellular calcium pools.In addition,variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions,which were modulated through STIM 1/Orail signaling.Moreover,DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3(LC3),hallmark markers of autophagy,and the formation of autophagosomes.In conclusion,these results suggested that DEX exerts neuroprotective effects against oxidative stress,autophagy,and neuronal apoptosis afier OGD/R injury via modulation of Caf-STIM1/Orai1 signaling.Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.

关键词： dexmedetomidine neuroprotection Ca^2+ STIM1/Orai 1 autophagy PC12 cells neuronal apoptosis

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Gastrointestinal symptoms and liver injury of COVID-19

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Journal of Hainan Medical University 2020年第21期26卷 1-5页

作者： Ai-Ning Zhang Yi Zhang Ye-Long Ji Ke-Fan Wu Yan Leng zhong-yuan xia Department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei 430060

COVID-19 is caused by the SARS-COV-2,which characterized with typical respiratory symptoms.In addition to the respiratory system injury,SARS-COV-2 may also invade other organs that express the cell surface receptor ACE2.Digestive system is a susceptible target of SARS-COV-2.Most patients show clinical symptoms of impaired digestive system during the course of the disease.Gastrointestinal symptoms of COVID-19 include anorexia,nausea,vomiting,diarrhea,abdominal pain,and liver damage.Patients with abnormal symptoms of the digestive system have a greater chance of progressing to severe or critical illness,a worse prognosis,and a higher risk of death.This paper aims to discuss the digestive symptoms of COVID-19 infection,so as to improve the attention to the digestive system abnormalities and gastrointestinal symptoms of COVID-19 patients during clinical diagnosis,treatment and prevention and control.

关键词： COVID-19 SARS-CoV-2 Digestive system Clinical features

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Market Equilibrium Based on Cloud-edge Collaboration

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CSEE Journal of Power and Energy Systems 2024年第1期10卷 96-104页

作者： Tong Cheng Haiwang zhong Qing xia the State Key Laboratory of Power Systems the Department of Electrical EngineeringTsinghua UniversityBeijing 100084China

Market participants can only bid with lagged information disclosure under the existing market mechanism,which can lead to information asymmetry and irrational market behavior,thus influencing market efficiency.To promote rational bidding behavior of market participants and improve market efficiency,a novel electricity market mechanism based on cloudedge collaboration is proposed in this paper.Critical market information,called residual demand curve,is published to market participants in real-time on the cloud side,while participants on the edge side are allowed to adjust their bids according to the information disclosure prior to closure gate.The proposed mechanism can encourage rational bids in an incentive-compatible way through the process of dynamic equilibrium while protecting participants’privacy.This paper further formulates the mathematical model of market equilibrium to simulate the process of each market participant’s strategic bidding behavior towards equilibrium.A case study based on the IEEE 30-bus system shows the proposed market mechanism can effectively guide bidding behavior of market participants,while condensing exchanged information and protecting privacy of participants.

关键词： Cloud-edge collaboration market mechanism residual demand curve strategic bidding

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Visible-frequency nonvolatile reconfigurable Janus metasurfaces for dual-wavelength-switched and spin-asymmetric holograms

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Photonics Research 2024年第2期12卷 356-368页

作者： HUAN yuan ZHEQIANG zhong BIN ZHANG College of Electronics and Information Engineering Sichuan UniversityChengdu 610064China Big Data Analysis and Fusion Application Technology Engineering Laboratory of Sichuan Province Chengdu 610065China

Janus metasurface holography with asymmetric transmission characteristics provides new degrees of freedom for multiplexing technologies.However,earlier metasurfaces with asymmetrical transmission faced limitations in terms of tunability and multifunctionality.In this study,we propose a metasurface color holographic encryption scheme with dynamic switching and asymmetric transmission at visible frequencies using a low-loss nonvolatile optical phase-change material,Sb_(2)S_(3).Using a modified holographic optimization strategy,we achieved highfidelity asymmetric holographic imaging of a nanostructured metasurface.By controlling the incident direction and wavelength of visible light,as well as the level of crystallization of Sb_(2)S_(3),this reconfigurable metasurface enables the precise manipulation of tunable color holographic image displays.In particular,in the semi-crystalline state of Sb_(2)S_(3),the encoded information can be securely encrypted using a two-channel color-holographic image,whereas only a preset camouflaged image is displayed in the crystalline or amorphous state of Sb_(2)S_(3).The proposed multiencrypted Janus metasurface provides a potential approach for dynamic holographic displays with ultrahigh capacity,holographic encryption,and information storage.

关键词： holographic asymmetric visible

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