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

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：//www.chictr.org. cn/） （registration number： ChiCTR-IPR- 16008113）.

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

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.

Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury

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.

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

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.

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

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.

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

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.

Clinical features and prognosis of patients with novel coronavirus pneumonia complicated with diabetes

Objective:To analyze the clinical characteristics and laboratory examinations of patients with new coronavirus(COVID-19)and compare the effect and prognosis of patients with diabetes mellitus(DM)on COVID-19.Methods:56 cases of COVID-19 with DM and 85 age-matched admitted patients without DM who were admitted to the People's Hospital of Wuhan University from January 31,2020 to March 15,2020 were analyzed through a retrospective cohort study.Patients data were collected through electronic cases,and used SPSS 26.0 and Graphpad Prism 8.0 statistical software to compare changes in various indicators of patients in DM and non-DM groups and to draw the survival curves.Results:Compared with the non-DM group,the DM group has a higher percentage of mechanical ventilation,higher mortality and severe patients,with a higher proportion of initial symptoms of nausea and hypertension(P<0.05).There were no significant differences in the gender,initial symptoms(except nausea),the combined underlying diseases(except hypertension)between the two groups(P<0.05);The white blood cell,centroblast count,CRP,PCT,PT,D-dimer,total bilirubin,Urea,LDH,CK,MB,hs-TnI,CK-MB,NT-proBNP were higher in the DM group(P<0.05),and lymphocytes,single Nuclear cell,CD3,CD4,and CD8 counts were low(P<0.05).There was no statistically significant difference in platelet,IL-6,APTT,ALT,AST,Cr and CD19 counts between the two groups.Conclusion:Compared with COVID-19 patients with non-DM,COVID-19 patients with DM have a higher proportion of mortality and severe cases.Heart function,liver and kidney function,immune function damage and coagulation dysfunction are more obvious.Therefore,the monitoring of such patients should be strengthened,and active treatment should be performed to improve the prognosis.

Gastrointestinal symptoms and liver injury of COVID-19

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.

Screening and bioinformatics analysis of diabetic peripheral neuropathy-related genes in women

Objective: To obtain the key genes and signal pathways of diabetic peripheral neuropathy (DPN) through bioinformatics analysis of related gene chips in the GEO database. Methods: The DPN-related gene chip was downloaded from the GEO database, and the differential genes (DEGs) between DPN female patients and the normal control group were analyzed and visualized using R language. According to the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), DEGs were annotated, their functions and related pathways were predicted, and a protein interaction network was constructed using the STRING database to screen for core genes. Results: The analysis chip GSE95849 obtained 4746 DEGs of which 2218 genes were up-regulated and 2528 genes were down-regulated. Among them, TFAP2C, ESR1, CX3CR1, and FGL2 are at the core site of protein interaction. Conclusions: Differential genes are mainly involved in the MAPK pathway. They participate in the pathogenesis of DPN through blood glucose homeostasis, inflammatory effects, and neuronal development, providing new ideas for the diagnosis and treatment of DPN.

Endothelial glycocalyx as a potential theriapeutic target in organ injuries

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.