Remifentanil preconditioning promotes liver regeneration via upregulation of ß-arrestin 2/ERK/cyclin D1 pathway.

Remifentanil is a potent, short-acting opioid analgesic drug that can protect tissues from ischemia and reperfusion injury though anti-inflammatory effects. However, the utility of remifentanil in liver regeneration after hepatectomy is not known. Using a 70% hepatectomy mouse model (PHx), we found that preconditioning animals with 4 µg/kg remifentanil enhanced liver regeneration through supporting hepatocyte proliferation but not through anti-inflammatory effects. These effects were also phenocopied in vitro where 40 mM remifentanil promoted the proliferation of primary mouse hepatocyte cultures. We further identified that remifentanil treatment increased the expression of ß-arrestin 2 in vivo and in vitro. Demonstrating specificity, remifentanil preconditioning failed to promote liver regeneration in liver-specific ß-arrestin 2 knockout (CKO) mice subjected to PHx. While remifentanil increased the expression of activated (phosphorylated)-ERK and cyclin D1 in PHx livers, their levels were not significantly changed in remifentanil-treated CKO mice nor in WT mice pretreated with the ERK inhibitor U0126. Our findings suggest that remifentanil promotes liver regeneration via upregulation of a ß-arrestin 2/ERK/cyclin D1 axis, with implications for improving regeneration process after hepatectomy.

Remifentanil Preconditioning Attenuates Hepatic Ischemia-Reperfusion Injury in Rats via Neuronal Activation in Dorsal Vagal Complex.

Remifentanil, an ultra-short acting opiate, has been reported to protect against hepatic ischemia-reperfusion injury, which is a major cause of postoperative liver dysfunction. The objective of this study was to determine whether a central vagal pathway is involved in this protective procedure. Rat models of hepatic ischemia-reperfusion were used in the experimental procedures. The results revealed that intravenous pretreatment with remifentanil decreased serum aminotransferases and hepatic histologic damage; however, an intraperitoneal injection of µ-opioid receptor antagonist did not abolish the protection of remifentanil preconditioning. c-Fos immunofluorescence of the brain stem showed that dorsal motor nucleus of the vagus was activated after remifentanil preconditioning. Moreover, serum alanine aminotransferase, histopathologic damage, and apoptosis decreased in remifentanil preconditioning group compared to vagotomized animals with remifentanil preconditioning, and there was no statistical difference of TNF-α and IL-6 between NS/Va and RPC/Va groups. In addition, remifentanil microinjection into dorsal vagal complex decreased serum aminotransferases, inflammatory cytokines, and hepatic histologic injury and apoptosis, and these effects were also abolished by a peripheral hepatic vagotomy. In conclusion, remifentanil preconditioning conferred liver protection against ischemia-reperfusion injury, which was mediated by the central vagal pathway.

Emerging trends and hotspots of the itch research: A bibliometric and visualized analysis.

AIMS: Itch, a common uncomfortable sensory experience, occurs frequently in inflammatory or allergic disorders. In recent years, with the discovery of itch-specific pathways in the peripheral and central nervous system, the association between immunology and neural pathways has gradually emerged as the main mechanism of itch. Although many studies have been conducted on itch, no bibliometric analysis study focusing on this topic has been conducted. This study aimed to explore the research hotspots and trends in the itch field from a bibliometric perspective. METHODS: Publications relevant to itch, published from 2003 to 2022, were retrieved from the Science Citation Index-Expanded of Web of Science Core Collection. Publications were critically reviewed and analyzed with CiteSpace software, Vosviewer, and the bibliometric online analysis platform. Visual maps were conducted in terms of annual production, collaborating countries or institutions, productive authors, core journals, co-cited references, and keyword bursts. RESULTS: 2395 articles on itch that met our criteria were identified and the quantity of publications has been increasing rapidly since 2012. The USA was the most influential country. University Hospital Münster was the institution with the most publications. Gil Yosipovitch was the most prolific author. Atopic dermatitis (AD), intradermal serotonin, chronic pruritus, mechanical itch, gastrin-releasing peptide, substance p, interleukin-31 receptor, histamine-induced itch, bile acid, scratching behavior, and h-4 receptor were the top 11 clusters in co-citation cluster analysis. Keyword burst analysis suggested that treatment, inflammation, and AD are current research hotspots. CONCLUSION: Global publications on itch research have increased steadily and rapidly over the past 20 years. Inflammation and AD are current research hotspots. The neuroimmunological and neuroinflammatory mechanisms of itch, as well as clinical assessment methods and therapeutic targets, will be novel research directions in the future. This study provides guidance for further itch research.

Bibliometric and visual analysis of research on the links between the gut microbiota and pain from 2002 to 2021.

Background and aims: The gut microbiota is involved in the regulation of pain, which is proved by plenty of evidence. Although a substantial quantity of research on the link between the gut microbiota and pain has emerged, no study has focused on the bibliometric analysis of this topic. We aim to present a bibliometric review of publications over the past 20 years and predict research hot spots. Methods: Relevant publications between 2002 and 2021 were extracted from the Science Citation Index-Expanded (SCI-EXPANDED) of the Web of Science Core Collection (WoSCC) database on April 22, 2022. CiteSpace (version 5.8 R3c), VOSviewer, the Online Analysis Platform of Literature Metrology, and the R package bibliometrix were used to analyze and visualize. Results: A total of 233 articles have been published between 2002 and 2021. The number of publication outputs increased rapidly since 2016. The collaboration network revealed that the USA, Baylor College of Medicine, and Vassilia Theodorou were the most influential country, institute, and scholar, respectively. Alimentary pharmacology and therapeutics and Gut were the most co-cited journal and Neurogastroenterology and Motility was the most productive journal. Visceral sensitivity, fibromyalgia, gastrointestinal, chronic pain, stress, gut microbiome, LGG, brain-gut axis, SLAB51, and sequencing were the top 10 clusters in co-occurrence cluster analysis. Keyword burst detection indicated that the brain-gut axis and short-chain fatty acid were the current research hot spots. Conclusion: Research on the links between the gut microbiota and pain has increased rapidly since 2016. The current research focused on the brain-gut axis and short-chain fatty acid. Accordingly, the SCFAs-mediated mechanism of pain regulation will be a research direction of great importance on the links between the gut microbiota and pain. This study provided instructive assistance to direct future research efforts on the links between the gut microbiota and pain.

Engineering 2D Silicene-Based Mesoporous Nanomedicine for In Vivo Near-Infrared-Triggered Analgesia.

The utilization of local anesthetics for postoperative analgesia represents an effective approach, but generally suffers from short half-lives and brachychronic local neurotoxicity. A desirable anesthetic with controllable and sustainable drug-releasing performance for adequate analgesia effect is highly required. In this work, the core/shell-structured two-dimenional (2D) silicene nanosheets coated with mesoporous silica layer (abbreviated as Silicene@MSNs) have been rationally constructed as localized drug-delivery system in sciatic nerve block to achieve on-demand release of loaded ropivacaine (RP) in mesoporous silica layer for local analgesia. Based on the specific photothermal performance of 2D silicene core, this local anesthesia system can be triggered by near-infrared laser to release the loaded RP, resulting in on-demand and long-lasting regional anesthesia. The analgesia effect is assessed by pain behavior tests, which demonstrates that the RP-loaded Silicene@MSNs core/shell nanosystem behaves almost five times longer analgesia effect than free RP. Furthermore, the activation of pain-related neurons in nerve conduction pathways is tested to explore the underlying analgesia mechanism, revealing that the designed nanosystem can improve the pain threshold, reduce the activation of neurons in dorsal root ganglion and excitability in spinal substantia gelatinosa neurons. This designed anesthetic nanomedicine provides a facile but effective methodology for long-lasting regional anesthesia.

Emerging Trends and Hot Spots in Hepatic Glycolipid Metabolism Research From 2002 to 2021: A Bibliometric Analysis.

Glycolipid metabolic diseases, including type 2 diabetes, non-alcoholic fatty liver disease, obesity, hypertension, dyslipidemia, and atherosclerosis, which have become a major public health concern worldwide, are mainly triggered by hepatic glycolipid metabolism disorder. Bibliometric analysis has provided a comprehensive review of developments in hepatic glycolipid metabolism research and changes in research hotspots over the past 20 years. The articles regarding hepatic glycolipid metabolism from 2002 to 2021 were identified from the Science Citation Index-Expanded of Web of Science Core Collection. Acquired data were then processed by the CiteSpace software and the Online Analysis Platform of Literature Metrology to analyze trends and predict hot spots in this field. A total of 4,856 articles regarding hepatic glycolipid metabolism published from 2002 to 2021 were selected. The leading country was China. The Chinese Academy of Sciences was the most productive institution. Co-citation cluster labels revealed characteristics of ten main clusters: non-alcoholic fatty liver disease, gut microbiota, adiponectin, fructose, fgf21, fatty acid, liver x receptor, nr4a, obese mice, and bile acids. Keyword bursts analysis indicated that management, non-alcoholic fatty liver disease, and modulation were the newly emerging research hot spots. We described the overall structure of scientific research on hepatic glycolipid metabolism and presented systematic information to other researchers. The current focus on NAFLD and gut microbiota is critical to further study and will help explore effective therapeutic strategy for aberrant glycolipid metabolism in liver.

Emerging trends and hotspots in the links between the gut microbiota and MAFLD from 2002 to 2021: A bibliometric analysis.

Background: The prevalence of metabolic associated fatty liver disease (MAFLD) presented a booming growth over recent years in the whole world. MAFLD was associated with a higher risk of end-stage liver disease, hepatocellular carcinoma and liver transplantation. Accumulating evidence indicated that gut microbiota and MAFLD were interrelated and interacted with each other. However, to the knowledge of the authors, no bibliometric quantitative analysis has been carried out to evaluate the links between the gut microbiota and MAFLD. This study aimed to use bibliometric analysis to evaluate current publication trends and hotspots in the links between the gut microbiota and MAFLD, in order to advance research in this field. Methods: The articles regarding the links between gut microbiota and MAFLD from 2002 to 2021 were identified from the Science Citation Index-Expanded of Web of Science Core Collection. CiteSpace software, Vosviewer, the R package "bibliometrix" and the Online Analysis Platform of Literature Metrology were used to analyze current publication trends and hotspots in this field. Results: A total of 707 articles were retrieved regarding the links between gut microbiota and MAFLD from 2002 to 2021. The USA occupied the leading role until 2015 and the dominance of China started in 2016. The USA was the most frequently involved country in international cooperation. Shanghai Jiao Tong University was the most productive institution. Ina Bergheim was the most productive author, publishing 14 articles. The co-citation keywords cluster label displayed ten main clusters: probiotics, bile acid, immune function, adolescents, nutritional genomics, high fat diet, systems biology, lipopolysaccharides, phosphatidylcholine, and oxidative stress. Keyword bursts analysis indicated that diet induced obesity, metabolic syndrome, ppar alpha, and lactobacillus were the research hotspots with high strength. Conclusion: The number of publications covering the links of gut microbiota and MAFLD increased dramatically in the past decade and especially became exponential growth in the last 3 years. Probiotics and bile acid will be the research direction of great importance in the etiology and novel treatment for MAFLD. This study provided systematic information and instructive assistance for future research work, that helped to discover the mechanisms and new treatments of MAFLD.

G protein-coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain.

AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein-coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism. METHODS AND RESULTS: Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14 days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER-positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT-PCR and immunoblot analyses showed that the levels of GPER and phosphorylated µ-type opioid receptor (p-MOR) in the RVM of pain persisting mice were apparently increased on 14 days after incision surgery. Furthermore, chemogenetic activation of GPER-positive neurons in the RVM of Gper-Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER-positive neurons in the RVM could prevent mice from being in the pain persistent state. CONCLUSION: Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation.

Correction to: Effectiveness and pulmonary complications of perioperative laryngeal mask airway used in elderly patients (POLMA-EP trial): study protocol for a randomized controlled trial.

After publication of our article [1] we have been notified on a mistake in the sample size.

Study design of the DAS-OLT trial: a randomized controlled trial to evaluate the impact of dexmedetomidine on early allograft dysfunction following liver transplantation.

BACKGROUND: Perioperative ischemia/reperfusion (I/R) injury during liver transplantation is strongly associated with early allograft dysfunction (EAD), graft loss, and mortality. Hepatic I/R injury also causes remote damage to other organs including the renal and pulmonary systems. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist which is used as an adjuvant to general anesthesia, has been shown in preclinical studies to provide organ protection by ameliorating the effects of I/R injury in a range of tissues (including the liver). However, prospective clinical evidence of any potential benefits in improving outcomes in liver transplantation is lacking. This study aimed to verify the hypothesis that the application of dexmedetomidine during the perioperative period of liver transplantation can reduce the incidence of EAD and primary graft non-function (PNF). At the same time, the effects of dexmedetomidine application on perioperative renal function and lung function were studied. METHODS: This is a prospective, single-center, randomized, parallel-group study. Two hundred participants (18-65 years) scheduled to undergo liver transplantation under general anesthesia will be included in this study. For participants in the treatment group, a loading dose of DEX will be given after induction of anesthesia (1 µg/kg over 10 min) followed by a continuous infusion (0.5 µg/kg /h) until the end of surgery. For participants in the placebo group, an equal volume loading dose of 0.9% saline will be given after the induction of anesthesia followed by an equal volume continuous infusion until the end of surgery. All other supplements, e.g., opioids, sedatives, and muscle relaxant, will be identical in both arms and administered according to routine clinical practice. DISCUSSION: The present trial will examine whether DEX confers organoprotective effects in the liver, in terms of reducing the incidence of EAD and PNF in orthotopic liver transplantation recipients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03770130. Registered on 10 December 2018. https://clinicaltrials.gov/ct2/show/NCT03770130.

Effectiveness and pulmonary complications of perioperative laryngeal mask airway used in elderly patients (POLMA-EP trial): study protocol for a randomized controlled trial.

BACKGROUND: With the increasing amount of geriatric surgery, it has become a great challenge for anesthesiologists to reduce the incidence of postoperative pulmonary complications (PPCs). The two most popular airway management methods, laryngeal mask airway (LMA) and endotracheal intubation (ETI), both have their unique advantages in specific clinical settings. For the purpose of helping clinicians make better decisions on airway management during geriatric surgery, we designed this multi-center clinical trial to compare the influence of LMA and ETI on PPCs. METHODS/DESIGN: In this multi-center, randomized, parallel clinical trial, a total of 6000 elderly patients, aged ≥ 70 years, with an American Society of Anesthesiologists classification level of 1-2 and a body mass index ≤ 35 kg/m2, undergoing elective surgery will be enrolled and randomized into the LMA or the ETI group. Both groups will receive usual perioperative care except for the adoption of LMA/ETI. Primary outcomes are the occurrence of PPCs and patients' perioperative mortality rates. Ease of intubation, anesthetics consumption, treatment for PPCs, duration of surgery, anesthesia recovery time and performance, time of PPC onset, postanesthesia care unit stay, intensive care unit admission and stay, in-hospital days, re-admission rates, hospitalization cost, and patients' satisfactory scores will be secondary outcomes. Follow-up will be conducted through phone-call visits until 12 weeks after discharge. DISCUSSION: This trial will assess the possible benefits or disadvantages of perioperative LMA use in elderly patients compared with ETI regarding the occurrence of PPCs and clinical prognosis. We expect that this trial will also add to the current understanding of PPCs in geriatric populations and contribute to the international recommendations of geriatric surgery management. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02240901 . Registered on 16 September 2014.