Publications by authors named "Lize Xiong"

196 Publications

Transcutaneous electrical acupoint stimulation before surgery reduces chronic pain after mastectomy: A randomized clinical trial.

J Clin Anesth 2021 Jul 13;74:110453. Epub 2021 Jul 13.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Department of Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200434, China. Electronic address:

Study Objective: Despite multiple interventions, the incidence of chronic pain after mastectomy could be as high as 50% after surgery. This study aimed to determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) before anesthesia induction in reducing chronic pain and to compare the effect of combined acupoint TEAS with that of single acupoint TEAS.

Design: A multicenter randomized clinical trial.

Setting: The study was conducted at six medical centers in China from May 2016 to April 2018. Final follow-up was on October 26, 2018.

Participants: Eligible patients were women scheduled for radical mastectomy under general anesthesia.

Interventions: Patients were randomly and equally grouped into sham control (n = 188), single acupoint (PC6, n = 198), or combined acupoints (PC6 and CV17, n = 190) TEAS groups using a centralized computer-generated randomization system. TEAS was applied for 30 min before anesthesia induction. The sham-operated control group received electrode attachment but without stimulation. Anesthesiologists, surgeons, and outcome assessors were blinded to the interventions.

Measures: The primary endpoint was the incidence of chronic pain 6 months after surgery. Incidences were compared among the groups using the unadjusted χ test.

Results: Of the 576 randomized patients, 568 completed the trial. In the intention-to-treat analysis, post-mastectomy pain at 6 months was reported in 42 of 190 patients (22.1%) in the combined acupoints group, 65 of 188 patients (34.6%) in the sham-operated group (P = 0.007; relative risk [RR], 95% confidence interval [CI]: 0.68, 0.52-0.89), and 72 of 198 patients (36.4%) in the single acupoint group (P = 0.002; RR, 95% CI: 0.72, 0.55-0.93). Remifentanil consumption during surgery and postoperative nausea and vomiting at 24 h after surgery were lower in the combined acupoint group than that in the sham-operated group.

Conclusion: TEAS at combined acupoints before surgery was associated with reduced chronic pain 6 months after surgery.

Trial Registration: Clinicaltrials.gov identifier: NCT02741726. Registered on April 13, 2016.
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http://dx.doi.org/10.1016/j.jclinane.2021.110453DOI Listing
July 2021

An MD2-perturbing peptide has therapeutic effects in rodent and rhesus monkey models of stroke.

Sci Transl Med 2021 06;13(597)

Translational Research Institute of Brain and Brain-Like Intelligence and Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai 200434, China.

Studies have failed to translate more than 1000 experimental treatments from bench to bedside, leaving stroke as the second leading cause of death in the world. Thrombolysis within 4.5 hours is the recommended therapy for stroke and cannot be performed until neuroimaging is used to distinguish ischemic stroke from hemorrhagic stroke. Therefore, finding a common and critical therapeutic target for both ischemic and hemorrhagic stroke is appealing. Here, we report that the expression of myeloid differentiation protein 2 (MD2), which is traditionally regarded to be expressed only in microglia in the normal brain, was markedly increased in cortical neurons after stroke. We synthesized a small peptide, Trans-trans-activating (Tat)-cold-inducible RNA binding protein (Tat-CIRP), which perturbed the function of MD2 and strongly protected neurons against excitotoxic injury in vitro. In addition, systemic administration of Tat-CIRP or genetic deletion of MD2 induced robust neuroprotection against ischemic and hemorrhagic stroke in mice. Tat-CIRP reduced the brain infarct volume and preserved neurological function in rhesus monkeys 30 days after ischemic stroke. Tat-CIRP efficiently crossed the blood-brain barrier and showed a wide therapeutic index for stroke because no toxicity was detected when high doses were administered to the mice. Furthermore, we demonstrated that MD2 elicited neuronal apoptosis and necroptosis via a TLR4-independent, Sam68-related cascade. In summary, Tat-CIRP provides robust neuroprotection against stroke in rodents and gyrencephalic nonhuman primates. Further efforts should be made to translate these findings to treat both ischemic and hemorrhagic stroke in patients.
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http://dx.doi.org/10.1126/scitranslmed.abb6716DOI Listing
June 2021

Location matters: Overlooked ethnic-geographic effect in China and Austria on propofol/cisatracurium sex differences among a population pharmacokinetic/pharmacodynamic (PopPK/PD) covariate analysis in men, women, and one transgender subject.

Fundam Clin Pharmacol 2021 May 29. Epub 2021 May 29.

Otto-Loewi Research Center for Physiological Chemistry, Medical University of Graz, Graz, Austria.

A quick literature search using "sex/gender" vs. the commonly used hypnotic propofol or neuromuscular-blocking agent cisatracurium will reveal numerous contradictory sex difference publications depending on the ethnic-geographic location of where these studies were conducted. We induced anesthesia with cisatracurium besylate (GlaxoSmithKline) 100 μg kg administered exactly 1 minute following propofol (AstraZeneca) 2 mg kg . In 20 male and 20 female ethnic Han-Chinese test set patients (Xi'an China), and in similar ethnic white Austrian validation set patients (Graz Austria), we quantified propofol/cisatracurium pharmacodynamic parameters namely propofol onset time, lag time, plasma concentrations (C ) at loss-of-behavioral response (LOBR) using bispectral index (BIS); cisatracurium onset time, lag time, and C at T % (first twitch of train-of-four) complete twitch suppression using mechanomyography (MMG). Serial arterial blood samples were collected for population pharmacokinetic (PopPK) analysis of all demographic and biological covariates (region, sex, age, weight, and height) versus volumes of distribution and clearances pharmacokinetic parameters. In Chinese women (but not in white women), propofol C at LOBR was 33.60% lower than men and cisatracurium C at T % complete twitch suppression was 21.49% lower than men, a clear pharmacodynamic assertion. Region and weight were significant PopPK covariates. We demonstrated that sex differences are influenced by ethnic-geographic location as only in Chinese women (but not in white women) propofol C at LOBR and cisatracurium C at T % complete twitch suppression were lower than in men. When defining sex differences, ethnic-geographic location should be taken into consideration as a predictive factor for optimizing propofol/cisatracurium initial loading recommended dosages.
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http://dx.doi.org/10.1111/fcp.12704DOI Listing
May 2021

Retina-Inspired Organic Heterojunction-Based Optoelectronic Synapses for Artificial Visual Systems.

Research (Wash D C) 2021 22;2021:7131895. Epub 2021 Feb 22.

Interdisciplinary Materials Research Center, School of Materials Science and Engineering, Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai 201804, China.

For the realization of retina-inspired neuromorphic visual systems which simulate basic functions of human visual systems, optoelectronic synapses capable of combining perceiving, processing, and memorizing in a single device have attracted immense interests. Here, optoelectronic synaptic transistors based on tris(2-phenylpyridine) iridium (Ir(ppy)) and poly(3,3-didodecylquarterthiophene) (PQT-12) heterojunction structure are presented. The organic heterojunction serves as a basis for distinctive synaptic characteristics under different wavelengths of light. Furthermore, synaptic transistor arrays are fabricated to demonstrate their optical perception efficiency and color recognition capability under multiple illuminating conditions. The wavelength-tunability of synaptic behaviors further enables the mimicry of mood-modulated visual learning and memorizing processes of humans. More significantly, the computational dynamics of neurons of synaptic outputs including associated learning and optical logic functions can be successfully demonstrated on the presented devices. This work may locate the stage for future studies on optoelectronic synaptic devices toward the implementation of artificial visual systems.
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http://dx.doi.org/10.34133/2021/7131895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926506PMC
February 2021

Activation of astroglial CB1R mediates cerebral ischemic tolerance induced by electroacupuncture.

J Cereb Blood Flow Metab 2021 Mar 4:271678X21994395. Epub 2021 Mar 4.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi Province, China.

There are no effective treatments for stroke. The activation of endogenous protective mechanisms is a promising therapeutic approach, which evokes the intrinsic ability of the brain to protect itself. Accumulated evidence strongly suggests that electroacupuncture (EA) pretreatment induces rapid tolerance to cerebral ischemia. With regard to mechanisms underlying ischemic tolerance induced by EA, many molecules and signaling pathways are involved, such as the endocannabinoid system, although the exact mechanisms have not been fully elucidated. In the current study, we employed mutant mice, neuropharmacology, microdialysis, and virus transfection techniques in a middle cerebral artery occlusion (MCAO) model to explore the cell-specific and brain region-specific mechanisms of EA-induced neuroprotection. EA pretreatment resulted in increased ambient endocannabinoid (eCB) levels and subsequent activation of ischemic penumbral astroglial cannabinoid type 1 receptors (CBR) which led to moderate upregulation of extracellular glutamate that protected neurons from cerebral ischemic injury. These findings provide a novel cellular mechanism of EA and a potential therapeutic target for ischemic stroke.
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http://dx.doi.org/10.1177/0271678X21994395DOI Listing
March 2021

Organic synaptic devices based on ionic gel with reduced leakage current.

Chem Commun (Camb) 2021 Feb;57(15):1907-1910

Interdisciplinary Materials Research Center, School of Materials Science and Engineering, Shanghai Institute of Intelligent Science and Technology, Tongji University, Shanghai, 201804, P. R. China. and Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University, Shanghai, 200434, P. R. China.

In this work, we presented a solid-state hybrid electrolyte dielectric film fabricated by a facile solution process, composed of ionic liquid and high-k polymers for leakage current reduction. With ions involved in the dielectric, the organic transistor can be operated under low voltage, and some essential synaptic behaviors were successfully simulated by the electrostatic coupling effect for building neuromorphic computing systems.
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http://dx.doi.org/10.1039/d0cc07488hDOI Listing
February 2021

Acupoint Catgut Embedding for Insomnia: A Meta-Analysis of Randomized Controlled Trials.

Evid Based Complement Alternat Med 2020 6;2020:5450824. Epub 2020 Nov 6.

Department of Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200434, China.

Objectives: A Meta-analysis was carried out to evaluate the efficacy and safety of acupoint catgut embedding (ACE), a procedure of embedding sutures made of absorbable materials into the skin tissue of acupoints, on insomnia.

Methods: Relevant clinical randomized controlled trials (RCTs) were comprehensively searched from eleven electronic databases (up to 1 March 2020). Two authors independently screened literature, extracted data, and assessed the risk of bias of included studies. Stata 12 and RevMan 5.3.0 software were used for meta-analysis. PyCharm 2019 and Gephi software (version 0.9.2) were used for complex network analysis.

Results: Thirty-four RCTs involving 2,655 patients were included. The meta-analysis suggested that ACE induced a better clinical efficacy compared with that in the estazolam tablets (EZ) group (RR = 1.22, 95% CI: 1.13, 1.31) or in the acupuncture (ACU) group (RR = 1.21, 95% CI: 1.14, 1.28) and could significantly reduce the score of Pittsburgh Sleep Quality Index ( < 0.05). ACE resulted in better long-term efficacy compared to that in the EZ group (RR = 1.87, 95% CI: 1.58, 2.22) and ACU group (RR = 1.30, 95% CI: 1.14, 1.48). ACE could significantly reduce the incidence of adverse events (RR = 0.30, 95% CI: 0.15, 0.60) compared with that in the EZ group. Complex network analysis indicated that acupoints of BL23, SP6, PC6, BL15, BL20, BL18, and HT7 were the core acupoints selected in ACE for insomnia.

Conclusion: The clinical efficacy of ACE for insomnia is better than that of other interventions (EZ and ACU) in both short-term and long-term observations. Considering the efficacy and reduced visits to the clinic by ACE, the present study provides a practical and convenient complementary and alternative therapy for insomnia. This trial is registered with PROSPERO CRD 42020169866.
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http://dx.doi.org/10.1155/2020/5450824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665919PMC
November 2020

Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice.

Neurosci Bull 2020 Dec 13;36(12):1513-1523. Epub 2020 Oct 13.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.

General anesthesia severely affects the metabolites in the brain. Glycogen, principally stored in astrocytes and providing the short-term delivery of substrates to neurons, has been implicated as an affected molecule. However, whether glycogen plays a pivotal role in modulating anesthesia-arousal remains unclear. Here, we demonstrated that isoflurane-anesthetized mice exhibited dynamic changes in the glycogen levels in various brain regions. Glycogen synthase (GS) and glycogen phosphorylase (GP), key enzymes of glycogen metabolism, showed increased activity after isoflurane exposure. Upon blocking glycogenolysis with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), a GP antagonist, we found a prolonged time of emergence from anesthesia and an enhanced δ frequency in the EEG (electroencephalogram). In addition, augmented expression of glycogenolysis genes in glycogen phosphorylase, brain (Pygb) knock-in (Pygb) mice resulted in delayed induction of anesthesia, a shortened emergence time, and a lower ratio of EEG-δ. Our findings revealed a role of brain glycogen in regulating anesthesia-arousal, providing a potential target for modulating anesthesia.
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http://dx.doi.org/10.1007/s12264-020-00587-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719152PMC
December 2020

Astroglial N-myc downstream-regulated gene 2 protects the brain from cerebral edema induced by stroke.

Glia 2021 02 11;69(2):281-295. Epub 2020 Jul 11.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Air Force Military Medical University, Xi'an, China.

Brain edema is a grave complication of brain ischemia and is the main cause of herniation and death. Although astrocytic swelling is the main contributor to cytotoxic edema, the molecular mechanism involved in this process remains elusive. N-myc downstream-regulated gene 2 (NDRG2), a well-studied tumor suppressor gene, is mainly expressed in astrocytes in mammalian brains. Here, we found that NDRG2 deficiency leads to worsened cerebral edema, imbalanced Na transfer, and astrocyte swelling after ischemia. We also found that NDRG2 deletion in astrocytes dramatically changed the expression and distribution of aquaporin-4 and Na -K -ATPase β1, which are strongly associated with cell polarity, in the ischemic brain. Brain edema and astrocyte swelling were significantly alleviated by rescuing the expression of astrocytic Na -K -ATPase β1 in NDRG2-knockout mouse brains. In addition, the upregulation of astrocytic NDRG2 by lentiviral constructs notably attenuated brain edema, astrocytic swelling, and blood-brain barrier destruction. Our results indicate a particular role of NDRG2 in maintaining astrocytic polarization to facilitate Na and water transfer balance and to protect the brain from ischemic edema. These findings provide insight into NDRG2 as a therapeutic target in cerebral edema.
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http://dx.doi.org/10.1002/glia.23888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754347PMC
February 2021

Glycogenolysis Is Crucial for Astrocytic Glycogen Accumulation and Brain Damage after Reperfusion in Ischemic Stroke.

iScience 2020 May 6;23(5):101136. Epub 2020 May 6.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China; Translational Research Institute of Brain and Brain-Like Intelligence & Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200081, China. Electronic address:

Astrocytic glycogen is an important energy reserve in the brain and is believed to supply fuel during energy crisis. However, the pattern of glycogen metabolism in ischemic stroke and its potential therapeutic impact on neurological outcomes are still unknown. Here, we found extensive brain glycogen accumulation after reperfusion in ischemic stroke patients and primates. Glycogenolytic dysfunction in astrocytes is responsible for glycogen accumulation, caused by inactivation of the protein kinase A (PKA)-glycogen phosphorylase kinase (PhK)-glycogen phosphorylase (GP) cascade accompanied by the activation of glycogen synthase kinase-3β (GSK3β). Genetic or pharmacological augmentation of astrocytic GP could promote astrocyte and neuron survival and improve neurological behaviors. In addition, we found that insulin exerted a neuroprotective effect, at least in part by rescuing the PKA-PhK-GP cascade to maintain homeostasis of glycogen metabolism during reperfusion. Together, our findings suggest a promising intervention for undesirable outcomes in ischemic stroke.
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http://dx.doi.org/10.1016/j.isci.2020.101136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240195PMC
May 2020

Intubation and Ventilation amid COVID-19: Reply.

Anesthesiology 2020 08;133(2):465-466

Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China (L.X.).

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http://dx.doi.org/10.1097/ALN.0000000000003375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223572PMC
August 2020

Intubation and Ventilation amid the COVID-19 Outbreak: Wuhan's Experience.

Anesthesiology 2020 06;132(6):1317-1332

From the Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut (L.M., R.D.) the Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China (H.Q.) the Department of Anesthesiology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology, Wuhan, Hubei, China (L.W.) the Departments of Critical Care Medicine (Y.A., L.Z.) Anesthesiology (Q.G.) Respiratory Medicine (J.M.), Xiangya Hospital, Central South University, Changsha, Hunan Province, China the Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China (Z.X.) the Department of Anesthesiology, Wake Forest University, Winston-Salem, North Carolina (C.T.) the Department of Anesthesiology and Pain Medicine, University of California Davis, Sacramento, California (H.L.) the Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China (L.X.).

The COVID-19 outbreak has led to 80,409 diagnosed cases and 3,012 deaths in mainland China based on the data released on March 4, 2020. Approximately 3.2% of patients with COVID-19 required intubation and invasive ventilation at some point in the disease course. Providing best practices regarding intubation and ventilation for an overwhelming number of patients with COVID-19 amid an enhanced risk of cross-infection is a daunting undertaking. The authors presented the experience of caring for the critically ill patients with COVID-19 in Wuhan. It is extremely important to follow strict self-protection precautions. Timely, but not premature, intubation is crucial to counter a progressively enlarging oxygen debt despite high-flow oxygen therapy and bilevel positive airway pressure ventilation. Thorough preparation, satisfactory preoxygenation, modified rapid sequence induction, and rapid intubation using a video laryngoscope are widely used intubation strategies in Wuhan. Lung-protective ventilation, prone position ventilation, and adequate sedation and analgesia are essential components of ventilation management.
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http://dx.doi.org/10.1097/ALN.0000000000003296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155908PMC
June 2020

Age progression from vicenarians (20-29 year) to nonagenarians (90-99 year) among a population pharmacokinetic/pharmacodynamic (PopPk-PD) covariate analysis of propofol-bispectral index (BIS) electroencephalography.

J Pharmacokinet Pharmacodyn 2020 04 25;47(2):145-161. Epub 2020 Feb 25.

Institute of Physiological Chemistry, Medical University of Graz, Graz, Austria.

Background: Pharmacokinetic/pharmacodynamic (PK/PD) modeling has made an enormous contribution to intravenous anesthesia. Because of their altered physiological, pharmacological and pathological aspects, titrating general anesthesia in the elderly is a challenging task.

Methods: Eighty patients were consecutively enrolled divided by decades from vicenarians (20-29 year) to nonagenarians (90-99 year) into eight groups. Using target controlled infusion (TCI) and electroencephalographic (EEG)-derived bispectral index (BIS) we set propofol plasma concentration (C) to gradually reach 3.5 μg mL over 3.5-min. In each patient, we constructed a PK/PD model and conducted a population PK/PD (PopPK-PD) covariate analysis.

Results: Age was significant covariate for baseline BIS effect (E), inhibitory propofol concentration at 50% BIS decline (IC) and maximum BIS decline (E). First-order rate constant K of 0.47 min in vicenarians (20-29 year) gradually increased with age-progression to 1.85 min in nonagenarians (90-99 year). Simulation modelling showed that clinically recommended C of 3.5 μg mL for 20-29 year BIS 50 should be reduced to 3.0 for 30-49 year, 2.5 for 50-69 year and 2.0 for 80-89 year.

Conclusion: We quantified and graded EEG-BIS age-progression among different age groups divided by decades. We demonstrated deeper BIS values with decades' age progression. Our data has important implications for propofol dosing. The practical information for physicians in their daily clinical practice is using propofol C of 3.5 μg mL might not yield BIS value of 50 in elderly patients. Our simulations showed that the recommended regimen of C 3.5 μg mL for 20-29 year should be gradually decreased to 2.0 μg mL for 80-89 year.

Clinical Trial Registry Numbers: European Community Clinical Trials Database EudraCT (http://eudract.emea.eu) initial trial registration number: 2011-002847-81, and subsequently registered at www.clinicaltrials.gov; trial registration number: NCT02585284. Xijing Hospital of Fourth Military Medical University ethics committee approval number 20110707-4.
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http://dx.doi.org/10.1007/s10928-020-09678-0DOI Listing
April 2020

Astrocyte-specific NDRG2 gene: functions in the brain and neurological diseases.

Cell Mol Life Sci 2020 Jul 13;77(13):2461-2472. Epub 2019 Dec 13.

Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, 127 Changle Xi Road, Xi'an, 710032, China.

In recent years, the roles of astrocytes of the central nervous system in brain function and neurological disease have drawn increasing attention. As a member of the N-myc downstream-regulated gene (NDRG) family, NDRG2 is principally expressed in astrocytes of the central nervous system. NDRG2, which is involved in cell proliferation and differentiation, is commonly regarded as a tumor suppressor. In astrocytes, NDRG2 affects the regulation of apoptosis, astrogliosis, blood-brain barrier integrity, and glutamate clearance. Several preclinical studies have revealed that NDRG2 is implicated in the pathogenesis of many neurological diseases not limited to tumors (mostly glioma in the nervous system), such as stroke, neurodegeneration (Alzheimer's disease and Parkinson's disease), and psychiatric disorders (depression and attention deficit hyperactivity disorder). This review summarizes the biological functions of NDRG2 under physiological and pathological conditions, and further discusses the roles of NDRG2 during the occurrence and development of neurological diseases.
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http://dx.doi.org/10.1007/s00018-019-03406-9DOI Listing
July 2020

Inhibition of chemokine CX3CL1 in spinal cord mediates the electroacupuncture-induced suppression of inflammatory pain.

J Pain Res 2019 4;12:2663-2672. Epub 2019 Sep 4.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.

Purpose: Chemokine CX3CL1 and its receptor CX3CR1 in the lumbar spinal cord play crucial roles in pain processing. Electroacupuncture (EA) is recognized as an alternative therapy in pain treatment due to its efficacy and safety. However, the analgesic mechanism of EA remains unclear. The aim of this study was to investigate whether EA suppressed complete Freund's adjuvant (CFA)-induced pain via modulating CX3CL1-CX3CR1 pathway.

Materials And Methods: Inflammatory pain was induced by intraplantar injection of CFA to the left hind paw of Sprague-Dawley rats. EA with 2 Hz for 30 mins was given to bilateral Zusanli acupoints (ST36) on the first and third day after CFA injection. Mechanical allodynia and thermal hyperalgesia were tested with von Frey tests and Hargreaves tests, respectively. The expressions of CX3CL1, CX3CR1 and p38 mitogen-activated protein kinase (MAPK) were quantified with Western blots. The release of IL-1β, IL-6 and TNF-α were evaluated with ELISA. Recombinant CX3CL1 or control IgG were then injected through intrathecal catheters in the EA-treated CFA model rats. The behavioral tests, p38 MAPK activation and cytokine release were then evaluated.

Results: EA significantly inhibited inflammatory pain induced by CFA for 3 days. Meanwhile, EA downregulated the expression of CX3CL1 but not CX3CR1 in the lumbar spinal cord of the CFA rats. Besides, activation of p38 MAPK and the release of pain-related cytokines (IL-1β, IL-6 and TNF-α) were inhibited by EA. Intrathecal injection of CX3CL1 largely reversed the analgesic effect of EA treatment and re-activated p38 MAPK signaling, and resulted in pro-inflammatory cytokines increase in acupuncture-treated rats.

Conclusion: Our findings indicate that EA alleviates inflammatory pain via modulating CX3CL1 signaling in lumbar spinal cord, revealing a potential mechanism of anti-nociception of EA in inflammatory pain.
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http://dx.doi.org/10.2147/JPR.S205987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732508PMC
September 2019

Surgery Under General Anesthesia Alleviated the Hyperactivity but Had No Effect on the Susceptibility to PND in ADHD Rats.

Front Psychiatry 2019 3;10:642. Epub 2019 Sep 3.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, Xi'an, China.

Attention-deficit hyperactivity disorder (ADHD) is a typical neuropsychiatric disorder characterized by inattention, impulsivity, and hyperactivity, particularly in children. Recent studies demonstrated a close relationship between the development of ADHD and surgery under general anesthesia. However, few studies illustrated if ADHD symptoms changed after surgery. Meanwhile, whether these individuals with natural neural impairment were sensitive to postoperative neurocognitive disorder (PND) still remain unclear. Spontaneously hypertensive rats (SHR) were utilized as spontaneous ADHD animal model and Wistar-Kyoto (WKY) rats as non-ADHD animal model. We evaluated the variation of neurocognitive function and locomotor activity of the rats undergoing experimental laparotomy with general anesthesia by isoflurane. Neurocognitive function was assessed by fear conditioning test for contextual memory and Morris water maze (MWM) for spatial memory. Depressive-like behavior after surgery was detected by forced swim test, and open-field test and elevated plus maze test were utilized to evaluate locomotor activities and anxiety. Furthermore, we compared electroencephalogram (EEG) signal in ADHD and WKY rats under free-moving conditions. Afterward, staining was also utilized to detect the excitatory activity of neurons in these rats to explore the neural mechanism. Locomotor activity of SHR assessed by average speed and number of line crossings in the open-field test decreased 1 week after surgery under general anesthesia, but there was no difference concerning anxiety levels between SHR and WKY rats after surgery. This phenomenon was also paralleled with the change in EEG signal (delta band 0∼3 Hz). Surgery under general anesthesia had no effect on spatial and contextual memory, while it improved spontaneous depression in SHR. The expression of was downregulated for at least 1 week in the nucleus accumbens (NAc) area of ADHD rats' brain after surgery. ADHD rats were not sensitive to PND. Surgery with general anesthesia could partly improve the hyperactivity symptom of ADHD rats. This mechanism was related to the suppression of neural activity in the cerebral NAc of ADHD rats induced by general anesthetics.
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http://dx.doi.org/10.3389/fpsyt.2019.00642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733975PMC
September 2019

Anaesthesiology in China: present and future.

Br J Anaesth 2019 11 19;123(5):559-564. Epub 2019 Sep 19.

Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Department of Anaesthesiology and Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

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http://dx.doi.org/10.1016/j.bja.2019.08.004DOI Listing
November 2019

Road to Perioperative Medicine: A Perspective From China.

Anesth Analg 2019 09;129(3):905-907

Department of Anesthesiology and Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.

With the development of anesthesiology, patient safety has been remarkably improved, but the postoperative mortality rate at 30 days is still as high as 0.56%-4%, and the morbidity is even higher. Three years ago, the Chinese Society of Anesthesiology proposed that the direction of the anesthesiology development should be changed to perioperative medicine in China. Anesthesiologists should pay more attention to the long-term outcome. In this article, we introduced what we have done, what the challenges are, and what we should do in the future with regard to the practice of perioperative medicine in China.
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http://dx.doi.org/10.1213/ANE.0000000000004074DOI Listing
September 2019

Hyperhomocysteinemia is key for increased susceptibility to PND in aged mice.

Ann Clin Transl Neurol 2019 08 29;6(8):1435-1444. Epub 2019 Jul 29.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, 127th West Changle Road, Xi'an, 710032, Shaanxi, China.

Background: Postoperative neurocognitive disorder (PND) is a severe postoperative complication with no effective therapy that affects up to 19-52% of senior patients. Age and surgery type have been identified as risk factors. However, what caused the increased risk in the elderly is poorly understood.

Methods: We utilized a PND model in aged mice undergoing experimental laparotomy with general anesthesia to evaluate the causal relationship between hyperhomocysteinemia and increased PND susceptibility. PND was assessed by Novel Object Tasks, Fear Conditioning Tests, and Barnes Maze Tests. Serum homocysteine (Hcy) as well as vitamin B12 and folate acid levels were tested before, immediately after surgery and from day 1 to day 29 after surgery by ELISA. The effectiveness of preventative strategy including diet supplementation of vitamin B12 + folic acid (Vit B12 + FA) and S-adenosylmethionine (SAM) injection targeting hyperhomocysteinemia were also tested.

Results: PND in aged mice lasted for at least 2 weeks after experimental laparotomy, which was not observed in young adult mice. Serum Hcy results indicated a significant correlation between postoperative cognitive performance and perioperative Hcy level. Preoperative supplementation with VB12 and folic acid (FA) in the diet or S-adenosylmethionine (SAM) injection reduced perioperative serum Hcy level and inhibited the development of PND in aged mice.

Conclusions: Serum homocysteine accumulation is a fundamental cause for increased susceptibility of PND in aged mice. Preoperative diet supplementation of VitB12 + FA can effectively reduce PND in aged mice, which may be a promising prophylaxis treatment in clinical settings.
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http://dx.doi.org/10.1002/acn3.50838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689684PMC
August 2019

NDRG2 Protects the Brain from Excitotoxicity by Facilitating Interstitial Glutamate Uptake.

Transl Stroke Res 2020 04 27;11(2):214-227. Epub 2019 Jun 27.

Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.

Glutamate is a prominent neurotransmitter responsible for excitatory synaptic transmission and is taken up by sodium-dependent excitatory amino acid transporters (EAATs) on astrocytes to maintain synaptic homeostasis. Here, we report that N-myc downstream regulated gene 2 (NDRG2), a known tumor suppressor, is required to facilitate astroglial glutamate uptake and protect the brain from glutamate excitotoxicity after ischemia. NDRG2 knockout (Ndrg2) mice exhibited an increase in cerebral interstitial glutamate and a reduction in glutamate uptake into astrocytes. The ability of NDRG2 to control EAAT-mediated glutamate uptake into astrocytes required NDRG2 to interact with and promote the function of Na/K-ATPase β1, which could be disrupted by a Na/K-ATPase β1 peptide. The deletion of NDRG2 or treatment with the Na/K-ATPase β1 peptide significantly increased neuronal death upon a glutamate challenge and aggravated brain damage after ischemia. Our findings demonstrate that NDRG2 plays a pivotal role in promoting astroglial glutamate uptake from the interstitial space and protecting the brain from glutamate excitotoxicity.
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http://dx.doi.org/10.1007/s12975-019-00708-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067740PMC
April 2020

Cardiac-specific overexpression of metallothionein attenuates L-NAME-induced myocardial contractile anomalies and apoptosis.

J Cell Mol Med 2019 07 18;23(7):4640-4652. Epub 2019 May 18.

Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming.

Hypertension contributes to the high cardiac morbidity and mortality. Although oxidative stress plays an essential role in hypertensive heart diseases, the mechanism remains elusive. Transgenic mice with cardiac overexpression of metallothionein, a heavy metal-binding scavenger, were challenged with N -nitro-L-arginine methyl ester (L-NAME) for 14 days prior to measurement of myocardial contractile and intracellular Ca anomalies as well as cell signalling mechanisms using Western blot and immunofluorescence analysis. L-NAME challenge elicited hypertension, macrophage infiltration, oxidative stress, inflammation and cardiac dysfunction manifested as increased proinflammatory macrophage marker F4/80, interleukin-1β (IL-1β), intracellular production, LV end systolic and diastolic diameters as well as depressed fractional shortening. L-NAME treatment reduced mitochondrial membrane potential (MMP), impaired cardiomyocyte contractile and intracellular Ca properties as evidenced by suppressed peak shortening, maximal velocity of shortening/relengthening, rise in intracellular Ca , along with elevated baseline and peak intracellular Ca . These unfavourable mechanical changes and decreased MMP (except blood pressure and macrophage infiltration) were alleviated by overexpression of metallothionein. Furthermore, the apoptosis markers including BAD, Bax, Caspase 9, Caspase 12 and cleaved Caspase 3 were up-regulated while the anti-apoptotic marker Bcl-2 was decreased by L-NAME treatment. Metallothionein transgene reversed L-NAME-induced changes in Bax, Bcl-2, BAD phosphorylation, Caspase 9, Caspase 12 and cleaved Caspase 3. Our results suggest that metallothionein protects against L-NAME-induced myocardial contractile anomalies in part through inhibition of apoptosis.
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http://dx.doi.org/10.1111/jcmm.14375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584723PMC
July 2019

Spinal Cord Glycine Transporter 2 Mediates Bilateral ST35 Acupoints Sensitization in Rats with Knee Osteoarthritis.

Evid Based Complement Alternat Med 2019 7;2019:7493286. Epub 2019 Feb 7.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, Shaanxi, China.

The concept of "acupoint sensitization" refers to the functional status of acupoint switches from silent to active under pathological conditions. In clinic, acupoint sensitization provides important guidance for acupoints selection in different diseases. However, the mechanism behind this phenomenon remains unclear. We generated a model of knee osteoarthritis (KOA) by intra-articular injection of monosodium iodoacetate (MIA) into the left knee of rats. The paw withdrawal mechanical threshold (PWMT) and the total number of mast cells as well as mast cell degranulation rate (MCDR) of acupoint tissue were used to test whether the acupoints were sensitized. The results showed that KOA resulted in a reduced mechanical threshold and elevated total number of mast cell as well as mast cell degranulation rate at bilateral ST35 (Dubi) but not GB37 (Guangming) or nonacupoint area. The acupoint sensitization was accompanied by upregulation of glycine transporter 2 (GlyT2) and reduction of extracellular glycine levels in the bilateral dorsal horns of the spinal cord at L3-5. Selective inhibition of GlyT2 or intrathecal administration of glycine attenuated ST35 acupoint sensitization. The sensitization of bilateral ST35 was blocked after intraspinal GlyT2 short hairpin (sh) RNA (GlyT2-shRNA) microinjection to specifically downregulate GlyT2 expression in the left side (ipsilateral) L3-5 spinal cord dorsal horn before MIA injection. Moreover, electroacupuncture (EA) stimulation at ST35 ameliorated articular pathological lesions and improved KOA-related pain behaviors. GlyT2-shRNA injection reversed EA-induced pain relief but not EA-induced reduction of joint lesions. Overall, this study demonstrated that spinal GlyT2, especially elevated GlyT2 expression in the ipsilateral dorsal horn of the spinal cord, is a crucial mediator of ST35 acupoint sensitization in KOA rats.
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http://dx.doi.org/10.1155/2019/7493286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383421PMC
February 2019

Reply to Coutrot : Is Nitric Oxide Nephro- or Cardioprotective?

Am J Respir Crit Care Med 2019 06;199(11):1442-1443

2 Harvard Medical School Boston, Massachusetts.

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http://dx.doi.org/10.1164/rccm.201901-0089LEDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543716PMC
June 2019

Acupoint Sensitization is Associated with Increased Excitability and Hyperpolarization-Activated Current (I) in C- But Not Aδ-Type Neurons.

Neuroscience 2019 04 1;404:499-509. Epub 2019 Mar 1.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, the 127(th) West Changle Road, Xi'an, 710032, Shaanxi, China. Electronic address:

Under pathological conditions, acupoint sensitization is the phenomenon of acupoints transforming from the stable state to the dynamic state. Evidences suggest that hyperpolarization-activated current (I), conducted by the hyperpolarization-activated/cyclic nucleotide-gated (HCN) channel, greatly contributes to the peripheral and central sensitization. However, the role of the I current in acupoint sensitization has not been explained. In the present study, changes in excitability, I density and the HCN channel of dorsal root ganglion (DRG) nociceptive neurons were examined in the later phase of knee osteoarthritis (KOA) rats. To investigate the neuronal specificity of acupoint sensitization, retrograde dyes were injected into the acupoints ST35 and GB37. The results showed that acupoint sensitization occurred in bilateral ST35 but not GB37 acupoints. The excitability and I density of C- but not A-type neurons innervating ST35 acupoint increased in bilateral L5 DRG of acupoint sensitized rats than that of sham rats. No obvious changes were found in the excitability or I density of C- and A-type neurons innervating the GB37 acupoint in the bilateral L5 DRG. HCN channel subtype 2 (HCN2) expression levels significantly increased after acupoint sensitization. Furthermore, ZD7288, an HCN current (I) blocker, attenuated the acupoint sensitization of the ST35 acupoint. Taken together, our findings suggest that the increased excitability of C- but not A-type neurons and the upregulation of I/HCN2 channels contribute to the formation of acupoint sensitization.
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http://dx.doi.org/10.1016/j.neuroscience.2019.02.028DOI Listing
April 2019

Neuroprotective Autophagic Flux Induced by Hyperbaric Oxygen Preconditioning is Mediated by Cystatin C.

Neurosci Bull 2019 Apr 5;35(2):336-346. Epub 2018 Dec 5.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.

We have previously reported that Cystatin C (CysC) is a pivotal mediator in the neuroprotection induced by hyperbaric oxygen (HBO) preconditioning; however, the underlying mechanism and how CysC changes after stroke are not clear. In the present study, we demonstrated that CysC expression was elevated as early as 3 h after reperfusion, and this was further enhanced by HBO preconditioning. Concurrently, LC3-II and Beclin-1, two positive-markers for autophagy induction, exhibited increases similar to CysC, while knockdown of CysC blocked these elevations. As a marker of autophagy inhibition, p62 was downregulated by HBO preconditioning and this was blocked by CysC knockdown. Besides, the beneficial effects of preserving lysosomal membrane integrity and enhancing autolysosome formation induced by HBO preconditioning were abolished in CysC rats. Furthermore, we demonstrated that exogenous CysC reduced the neurological deficits and infarct volume after brain ischemic injury, while 3-methyladenine partially reversed this neuroprotection. In the present study, we showed that CysC is biochemically and morphologically essential for promoting autophagic flux, and highlighted the translational potential of HBO preconditioning and CysC for stroke treatment.
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http://dx.doi.org/10.1007/s12264-018-0313-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426805PMC
April 2019

TREK-2 Mediates the Neuroprotective Effect of Isoflurane Preconditioning Against Acute Cerebral Ischemia in the Rat.

Rejuvenation Res 2019 Aug 28;22(4):325-334. Epub 2018 Dec 28.

1Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

It is known that preconditional treatment with volatile anesthetics can induce tolerance of the brain to stroke. A previous study demonstrated that the involvement of TREK-1, a two-pore domain K+ channel, in sevoflurane preconditioning induced neuroprotection against focal cerebral ischemia in rats. The present study testified whether TREK-2, another anesthetic-target K+ channel, is also associated with volatile anesthetic-induced neuroprotection, and further explored its potential mechanism. Rats preconditioned with isoflurane were subjected to 1.4vol% isoflurane plus 98% O (1.5 L/min) inhalation for 1 hour daily and continuing for 5 consecutive days. Then, these rats were subjected to middle cerebral artery occlusion (MCAO) as focal cerebral ischemia model. The expression of TWIK-related K+ channel 2 (TREK-2) was analyzed by western blotting and quantitative real-time RT-PCR, and its downstream signaling molecules, protein kinase C (PKC) alpha, extracellular signal-regulated kinase 1/2 (ERK1/2), and pERK1/2 were detected by western blotting also. Subsequently, the expression of TREK-2 was regulated by siRNA transfection in the brain to clarify its role in the neuroprotection of isoflurane preconditioning. Neurological scores, infarction volume, and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining were examined to evaluate the outcomes. The impact of TREK-2 on the expression of its downstream signaling molecules was also examined for preliminary analysis of the possible mechanisms. Isoflurane preconditioning reduced the infarct volume, inhibited the cell apoptosis, and improved the neurological outcome in rats subjected to MCAO. These effects were parallel with the increase in TREK-2 protein and inhibition of the ERK1/2 phosphorylation. The downregulation of TREK-2 through siRNA could significantly attenuate the isoflurane preconditioning-induced neuroprotective effects. Isoflurane preconditioning-induced neuroprotective effects against ischemia-reperfusion injury are associated with the increase in TREK-2 channel activation. These effects depend on the attenuation of PKC alpha and inhibition of ERK1/2 phosphorylation. Results enrich our understanding on the mechanism of two-pore domain K+ channel in preconditioning-induced tolerance to focal cerebral ischemia.
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http://dx.doi.org/10.1089/rej.2017.2039DOI Listing
August 2019

Percutaneous Intramyocardial Septal Radiofrequency Ablation for Hypertrophic Obstructive Cardiomyopathy.

J Am Coll Cardiol 2018 10;72(16):1898-1909

Xijing Hypertrophic Cardiomyopathy Center, Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address:

Background: In patients with disabling symptoms caused by hypertrophic obstructive cardiomyopathy (HOCM), echocardiography-guided percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) could be a less invasive treatment option.

Objectives: This study aimed to investigate the safety and efficacy of the PIMSRA for left ventricular outflow tract (LVOT) gradient reduction in HOCM.

Methods: The study enrolled 15 patients with HOCM. These patients underwent electrocardiography, imaging, and blood biochemistry examination over 6 months of follow-up.

Results: At 6 months of follow-up, patients showed significant reductions in peak LVOT gradients (resting gradient: from 88.00 [66.00] mm Hg to 11.00 [6.00] mm Hg; p = 0.001; stress-induced gradient: from 117.00 [81.00] mm Hg to 25.00 [20.00] mm Hg; p = 0.005) and interventricular septum (IVS) thickness (anterior IVS: from 25.00 [21.00] mm to 14.00 [12.00] mm; p = 0.001; posterior IVS: from 24.00 [21.00] mm to 14.00 [11.50] mm; p = 0.001). The reductions in IVS thickness and LVOT gradients were associated with improvement in New York Heart Association functional classification (from 3.00 [2.00] to 1.00 [1.00]; p < 0.001), total exercise time (from 6.00 [5.50] min to 9.00 [8.00] min; p = 0.007), and pro B-type natriuretic peptide levels (from 924.00 [370.45] pg/ml to 137.45 [75.73] pg/ml; p = 0.028). No patient had bundle branch block or complete heart block.

Conclusions: PIMSRA is a safe and effective treatment approach for severe, symptomatic HOCM and results in sustained improvement in exercise capacity, persistent reduction in LVOT gradient, and sustained improvement in cardiac function.
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http://dx.doi.org/10.1016/j.jacc.2018.07.080DOI Listing
October 2018

Nitric Oxide Decreases Acute Kidney Injury and Stage 3 Chronic Kidney Disease after Cardiac Surgery.

Am J Respir Crit Care Med 2018 11;198(10):1279-1287

2 Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

Rationale: No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery.

Objectives: To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass.

Methods: Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively.

Measurements And Main Results: The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62-0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41-0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36-0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18-0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17-0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20-1.10; P = 0.041).

Conclusions: In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year. Clinical trial registered with ClinicalTrials.gov (NCT01802619).
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http://dx.doi.org/10.1164/rccm.201710-2150OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290943PMC
November 2018

Spinal Cord Injury: How Could Acupuncture Help?

J Acupunct Meridian Stud 2018 Aug 30;11(4):124-132. Epub 2018 May 30.

Department of Anesthesiology, The Ohio State University Wexner Medical Center, Columbus, OH, United States.

Spinal cord injury (SCI) is one of the most common causes of death and disability worldwide, and it can result in both permanent disability and serial complications in patients. Research shows that patients with SCI complications are often interested in acupuncture for symptomatic relief. Therefore, the issue of physicians advising their patients regarding the use of acupuncture to alleviate SCI complications becomes pertinent. We review and summarize two types of relevant publications: (1) literature concerning acupuncture for SCI and its complications and (2) underlying mechanisms of acupuncture therapy for SCI. Clinical trials and reviews have suggested that acupuncture effectively manages a range of post-SCI complications, including motor and sensory dysfunction, pain, neurogenic bowel and bladder, pressure ulcers, spasticity, and osteoporosis. The effect of acupuncture on post-SCI orthostatic hypotension and sexual dysfunction remains unclear. Decreased oxidative stress, inhibition of inflammation and neuronal apoptosis, regulation of the expression and activity of endogenous biological mediators, and increased regenerative stem cell production are the possible mechanisms of acupuncture therapy for SCI. Although many limitations have been reported in previous studies, given the evidence for the efficacy of acupuncture, we recommend that physicians should support the use of acupuncture therapy for SCI complications.
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http://dx.doi.org/10.1016/j.jams.2018.05.002DOI Listing
August 2018

Long-term depression induced by endogenous cannabinoids produces neuroprotection via astroglial CBR after stroke in rodents.

J Cereb Blood Flow Metab 2019 06 12;39(6):1122-1137. Epub 2018 Feb 12.

1 Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xian, Shaanxi Province, China.

Ischemia not only activates cell death pathways but also triggers endogenous protective mechanisms. However, it is largely unknown what is the essence of the endogenous neuroprotective mechanisms induced by preconditioning. In this study we demonstrated that systemic injection of JZL195, a selective inhibitor of eCB clearance enzymes, induces in vivo long-term depression at CA3-CA1 synapses and at PrL-NAc synapses produces neuroprotection. JZL195-elicited long-term depression is blocked by AM281, the antagonist of cannabinoid 1 receptor (CBR) and is abolished in mice lacking cannabinoid CB receptor (CBR) in astroglial cells, but is conserved in mice lacking CBR in glutamatergic or GABAergic neurons. Blocking the glutamate NMDA receptor and the synaptic trafficking of glutamate AMPA receptor abolishes both long-term depression and neuroprotection induced by JZL195. Mice lacking CBR in astroglia show decreased neuronal death following cerebral ischemia. Thus, an acute elevation of extracellular eCB following eCB clearance inhibition results in neuroprotection through long-term depression induction after sequential activation of astroglial CBR and postsynaptic glutamate receptors.
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http://dx.doi.org/10.1177/0271678X18755661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547184PMC
June 2019
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