National survey on sedation for gastrointestinal endoscopy in 2758 Chinese hospitals.

BACKGROUND: Although sedation during gastrointestinal endoscopy is widely used in China, the characteristics of sedation use, including regional distribution, personnel composition, equipment used, and drug selection, remain unclear. The present study aimed to provide insights into the current practice and regional distribution of sedation for gastrointestinal endoscopy in China. METHODS: A questionnaire consisting of 19 items was distributed to directors of anaesthesiology departments and anaesthesiologists in charge of endoscopic sedation units in mainland China through WeChat. RESULTS: The results from 2758 participating hospitals (36.7% of the total) showed that 9 808 182 gastroscopies (69.3%) and 4 353 950 colonoscopies (30.7%), with a gastroscopy-to-colonoscopy ratio of 2.3, were conducted from January to December 2016. Sedation was used with 4 696 648 gastroscopies (47.9%) and 2 148 316 colonoscopies (49.3%), for a ratio of 2.2. The most commonly used sedative was propofol (61.0% for gastroscopies and 60.4% for colonoscopies). Haemoglobin oxygen saturation (SpO2) was monitored in most patients (96.1%). Supplemental oxygen was routinely administered, but the availability of other equipment was variable (anaesthesia machine in 64.9%, physiological monitor in 84.4%, suction device in 72.3%, airway equipment in 75.5%, defibrillator in 32.7%, emergency kit in 57.0%, and difficult airway kit in 20.8% of centres responding). CONCLUSIONS: The sedation rate for gastrointestinal endoscopy is much lower in China than in the USA and in Europe. The most commonly used combination of sedatives was propofol plus an opioid (either fentanyl or sufentanil). Emergency support devices, such as difficult airway devices and defibrillators, were not usually available.

Multiple Anesthesia/Surgery Cannot Impair Reference Memory in Adult Mice.

Postoperative cognitive dysfunction increases mortality and morbidity in perioperative patients. Numerous studies have demonstrated that multiple surgery/anesthesia during the neurodevelopmental period affects cognitive function, whereas a single anesthesia/surgery rarely causes cognitive dysfunction in adults. However, whether adults who undergo multiple anesthesia/surgery over a short period will experience cognitive dysfunction remains unclear. In this study, central nervous system inflammation and changes in cholinergic markers were investigated in adult mice subjected to multiple laparotomy procedures over a short period of time. The results showed that despite the increased expression of IL-6 and TNF-α in the hippocampus after multiple operations and the activation of microglia, multiple anesthesia/surgery did not cause a decline in cognitive function in adult mice. There were no changes in the cholinergic markers after multiple anesthesia/surgery.

Central cholinergic neuronal degeneration promotes the development of postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality. However, its mechanism remains poorly understood. We hypothesized that central cholinergic neuronal degeneration facilitates the development of POCD. The impact of anesthesia/surgery (appendectomy) on learning and memory and the levels of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), and choline transporter (CHT) in adult and aged mice were measured. Separate cohorts were analyzed after pretreatment with donepezil, an AChE inhibitor, in aged mice or with murine-p75-saporin (mu-p75-sap), a cholinergic-specific immunotoxin, in adult mice. Morris Water Maze was used to measure the learning and memory changes after anesthesia/surgery. Western blot was used to measure the changes in the protein levels of the biomarkers of the central cholinergic system. We found that anesthesia/surgery-induced memory decline and attenuation of central cholinergic biomarkers (ChAT and VAChT) in aged mice but not in adult mice. Donepezil pretreatment reduced central cholinergic impairment in the aged mice and prevented learning and memory declines after anesthesia/surgery. In contrast, when central cholinergic neurons were pre-injured with mu-p75-sap, cognitive dysfunction developed in the adult mice after anesthesia/surgery. These data suggest that central cholinergic neuronal degeneration facilitates the development of POCD.

TSG-6 secreted by bone marrow mesenchymal stem cells attenuates intervertebral disc degeneration by inhibiting the TLR2/NF-κB signaling pathway.

Inflammation has been correlated with intervertebral disc degeneration (IDD). Recent evidence suggests that TNF-α-stimulated gene 6 protein (TSG-6) secreted by bone marrow mesenchymal stem cells (BMSCs) displays a remarkable ability to inhibit inflammatory processes in a variety of diseases. However, it is unknown whether BMSCs exert their therapeutic effect against IDD by secreting TSG-6. Here we investigated the effects of BMSCs and TSG-6 on IDD and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs and TSG-6 reduced the expression of MMP-3 and MMP-13, and increased the expression of collagen II and aggrecan in the IL-1ß-treated nucleus pulposus cells (NPCs), but the protective effects of BMSCs and TSG-6 were attenuated when TSG-6 expression was silenced. We also found that the activation of the TLR2/NF-κB pathway was inhibited by BMSCs and TSG-6. The levels of IL-6 and TNF-α in the degenerated NPCs were reduced and the proliferation of IL-1ß-treated NPCs was increased in the presence of BMSCs and TSG-6. Furthermore, in vivo experiments showed that BMSCs and TSG-6 restored the MRI T2-weighted signal intensity and increased collagen II and aggrecan expression in the degenerated nucleus pulposus (NP) tissues. Finally, our results showed that BMSCs and TSG-6 downregulated the TLR2/NF-κB signaling and reduced the expression of MMPs and inflammatory cytokines in the degenerated NP tissues. The present study is the first to demonstrate the involvement of TLR2/NF-κB pathway in the potential anti-IDD therapeutic effect of TSG-6, and the results provide new insight into the beneficial effect of BMSCs in the treatment of IDD.

NLRP3/ASC-mediated alveolar macrophage pyroptosis enhances HMGB1 secretion in acute lung injury induced by cardiopulmonary bypass.

Our previous study showed that high levels of HMGB1 existed in rats following cardiopulmonary bypass (CPB)-induced acute lung injury (ALI) and neutralization of high-mobility group box 1(HMGB1) reduced CPB-induced ALI. However, the mechanism by which CPB increases HMGB1 secretion is unclear. Recent studies have shown that inflammasome-mediated cell pyroptosis promotes HMGB1 secretion. This study aimed to investigate the relationship between inflammasome-mediated pyroptosis and HMGB1 in CPB-related ALI. We employed oxygen-glucose deprivation (OGD)-induced alveolar macrophage (AM) NR8383 pyroptosis to measure HMGB1 secretion. We found that OGD significantly increased the levels of caspase-1 cleaved p10, IL-1ß and ASC expression, caspase-1 activity and the frequency of pyroptotic AM, and promoted the cytoplasm transportation and secretion of HMGB1, which were significantly mitigated by ASC silencing or pre-treatment with glyburide (a Nlrp3 inhibitor) in AM. CPB also increased the expression levels of Nlrp3, ASC, caspase-1 P10, and IL-1ß, and the percentages of AM pyroptosis in the lungs of experimental rats accompanied by increased levels of serum and bronchoalveolar lavage fluid (BALF) HMGB1. Treatment with glyburide significantly mitigated the CPB-increased ASC, caspase-1 p10 and IL-1ß expression, and the percentages of AM pyroptosis in the lungs, as well as the levels of HMGB1 in serum and BALF in rats. Therefore, our data indicated that the Nlrp3/ASC-mediated AM pyroptosis increased HMGB1 secretion in ALI induced by CPB. These findings may provide a therapeutic strategy to reduce lung injury and inflammatory responses during CPB.

Bibliometric analysis of research topics on blood-brain barrier breakdown and cognitive function over the last two decades (2000-2021).

Introduction: Blood-brain barrier (BBB) breakdown is closely associated with cognitive dysfunction. This study aimed to categorize and summarize research topics on the correlation between BBB breakdown and its effects on cognitive function. Methods: Bibliometric analysis methods were used to quantitatively and qualitatively assess research progress and predict future research hotspots. Relevant publications from the Web of the Science Core Collection were extracted on November 5, 2022 and analyzed to predict trends and hotspots in the field. Results: We identified 5518 articles published from 2000 to 2021 about the BBB and cognition. The number of manuscripts on this topic increased steadily during this time period, especially after 2013. We found that the number of articles published in China increased gradually and is in second place behind the United States of America (USA). In the research field of BBB breakdown and cognitive function, the USA is still far ahead. Keyword burst detection suggested that cognitive impairment, neurodegeneration disease and neuroinflammation are emerging research hotspots. Discussion: The mechanisms of BBB integrity breakdown and its effects on the deterioration of cognitive function are complex, and clinical treatment of the affected diseases has been a hot topic in the field over the past 22 years. Looking forward, this body of research is aimed at improving or maintaining patients' cognitive abilities, by finding preventive measures and to provide a basis for finding new treatments of cognitive disorders.

Pre-operative administration of butorphanol mitigates emergence agitation in patients undergoing functional endoscopic sinus surgery: A randomized controlled clinical trial.

Background: This study explored the effectiveness of pre-operative intravenous injection of butorphanol in the alleviation of emergence agitation (EA) in patients undergoing functional endoscopic sinus surgery (FESS). Methods: Patients (n = 708) were randomized into two groups. The butorphanol group (Group B, n = 358) received butorphanol infusion (20 ug/kg) before anesthesia induction, while the control group (Group C, n = 350) received an equal volume of normal saline infusion. General anesthesia was induced with sufentanil, propofol, and rocuronium, and was maintained with sevoflurane and remifentanil. Vasoactive drugs maintained the hemodynamic indices within 20% of the baseline. Results: The incidence of EA was significantly lower in Group B than that in Group C (Group B vs. C: 24.3% vs. 31.4%, respectively; P = 0.034). The times to spontaneous breathing (26.5 min vs. 23.7 min, P = 0.011), verbal response (36.0 min vs. 33.4 min, P = 0.012), and extubation (31.0 min vs. 28.7 min, P = 0.025) were longer in Group B, and the grade of cough (0.33 vs. 0.43, P = 0.024) at extubation in Group B was lower than that in Group C (P = 0.024). The mean arterial pressure at the end of the operation (P = 0.004) and at 5 min after extubation (P = 0.008) was higher and hypotension was less prominent (0.6% vs. 2.6%, P = 0.030) in Group B. Conclusion: Pre-operative intravenous injection of butorphanol decreased the incidence of EA after FESS and provided smooth and hemodynamically stable emergence without extending the stay in post-anesthesia care unit. Clinical trial registration: https://www.clinicaltrials.gov/, identifier NCT03398759.

Emerging Trends and Hot Spots in Sepsis-Associated Encephalopathy Research From 2001 to 2021: A Bibliometric Analysis.

Study Objectives: To evaluate sepsis-associated encephalopathy (SAE) research and to quantitatively and qualitatively predict research hot spots using bibliometric analysis. Methods: We extracted relevant publications from the Web of Science Core Collection on July 28, 2021. We investigated the retrieved data by bibliometric analysis (e.g. co-cited and cluster analysis, keyword co-occurrence) using the software CiteSpace and VOSviewer, the Online Analysis Platform of Literature Metrology (http://bibliometric.com/) and Bibliometrix to analyse and predict the trends and hot spots in this field. Main Results: We identified 1,582 published articles and reviews on SAE from 2001 to 2021. During this period, the number of manuscripts on SAE increased steadily and peaked in 2021. The USA and China were the leading countries that had a critical impact on SAE research. Among all institutions, Vanderbilt University and Pittsburgh University held leading positions and became central in the collaboration network. Among all the journals, Critical Care Medicine published the maximum number of manuscripts in the field of SAE within 20 years. Dal-Pizzol Felipe was the most productive author (61 papers) and received the largest number of citations (930 citations). Co-citation cluster analysis revealed that the most popular terms on SAE in the manner of cluster labels were critical illness, sepsis-associated encephalopathy, polymicrobial sepsis, posterior reversible encephalopathy syndrome, rat brain, intensive care unit, prior sepsis, molecular hydrogen, inflammation drive, metabolic encephalopathies, delirium pathophysiology, and clinical neuroscience. Keyword burst detection indicated that neuroinflammation, blood-brain barrier (BBB) and mitochondria dysfunction were the current research hot spots. Conclusions: Our study revealed that neuroinflammation, blood-brain barrier, and mitochondria dysfunction had been the research foci of SAE over the past 20 years. These have emerged as the basis for transformation from basic research to clinical application in finding effective methods for the prevention and treatment of SAE.

Peripheral Neutrophils-Derived Matrix Metallopeptidase-9 Induces Postoperative Cognitive Dysfunction in Aged Mice.

Background: Aging is one of the most important risk factors of postoperative cognitive dysfunction (POCD); however, the mechanisms are still not completely understood. In this study, we explore the roles of matrix metalloproteinase-9 (MMP-9) in aged mice with POCD. Methods: Appendectomy was performed in 18-month-old C57BL/6 and MMP-9-/- mice under anesthesia to establish the POCD model. Learning and memory were assessed using the Morris water maze (MWM) or Barnes maze. Protein expression of MMP-9 was measured by Western blotting or enzyme-linked immunosorbent assay (ELISA). To explore the role of neutrophils-derived MMP-9 in POCD, we treated mice with anti-Gr-1 monoclonal antibody to deplete peripheral neutrophils. And the percentage of neutrophils and other leukocytes were detected by flow cytometry. We further used sodium fluorescein (NaFlu) to evaluate the blood-brain barrier (BBB) permeability. Results: The spatial learning and memory ability was injured, and expression of MMP-9 increased in both plasma and the hippocampus after anesthesia/surgery. However, cognitive dysfunction was alleviated in both MMP-9-/- and peripheral neutrophils-depleted mice. The permeability of BBB was increased after anesthesia/surgery while recused by anti-Gr-1 antibody administration. Conclusion: These findings suggest that peripheral neutrophils-derived MMP-9 could lead to POCD of aged mice through increasing the BBB permeability.

Electroacupuncture relieves neuropathic pain by inhibiting degradation of the ecto-nucleotidase PAP in the dorsal root ganglions of CCI mice.

BACKGROUND: Although electroacupuncture is widely used in chronic pain management, it is quite controversial due to its unclear mechanism. We hypothesised that EA alleviates pain by inhibiting degradation of the ecto-nucleotidase prostatic acid phosphatase (PAP) and facilitating ATP dephosphorylation in dorsal root ganglions (DRGs). METHODS: We applied EA in male C57 mice subjected to chronic constriction injury (CCI) and assessed extracellular ATP and 5'-nucleotidease expression in DRGs. Specifically, we used a luminescence assay, quantitative reverse transcriptase-polymerase chain reaction, Western blotting, immunohistochemistry and nociceptive-related behavioural changes to gather data, and we tested for effects after PAP expression was inhibited with an adeno-associated virus (AAV). Moreover, membrane PAP degradation was investigated in cultured DRG neurons and the inhibitory effects of EA on this degradation were assessed using immunoprecipitation. RESULTS: EA treatment alleviated CCI surgery-induced mechanical pain hypersensitivity. Furthermore, extracellular ATP decreased significantly in both the DRGs and dorsal horn of EA-treated mice. PAP protein but not mRNA increased in L4-L5 DRGs, and inhibition of PAP expression via AAV microinjection reversed the analgesic effect of EA. Membrane PAP degradation occurred through a clathrin-mediated endocytosis pathway in cultured DRG neurons; EA treatment inhibited the phosphorylation of adaptor protein complex 2, which subsequently reduced the endocytosis of membrane PAP. CONCLUSIONS: EA treatment alleviated peripheral nerve injury-induced mechanical pain hypersensitivity in mice by inhibiting membrane PAP degradation via reduced endocytosis and subsequently promote ATP dephosphorylation in DRGs. SIGNIFICANCE: In a mouse model of chronic pain, electroacupuncture treatment increased levels of prostatic acid phosphatase (PAP: an ecto-nucleotidase known to relieve pain hypersensitivity) by inhibiting PAP degradation in dorsal root ganglions. This promoted extracellular ATP dephosphorylation, inhibited glia activation and eventually alleviated peripheral nerve injury-induced mechanical pain hypersensitivity in mice. Our findings represent an important step forward in clarifying the mechanisms of pain relief afforded by acupuncture treatment.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange With Nasopharyngeal Airway Facilitates Apneic Oxygenation: A Randomized Clinical Noninferiority Trial.

Background: Transnasal humidified rapid insufflation ventilatory exchange (THRIVE) was used to extend the safe apnea time. However, THRIVE is only effective in patients with airway opening. Nasopharyngeal airway (NPA) is a simple device that can help to keep airway opening. This study aimed to investigate the noninferiority of NPA to jaw thrust for airway opening during anesthesia-induced apnea. Methods: This was a prospective randomized single-blinded noninferiority clinical trial on the use of THRIVE in patients with anesthesia-induced apnea. The participants were randomly allocated to receive NPA or jaw thrust. The primary outcomes were PaO2 and PaCO2 at 20 min after apnea, with noninferiority margin criteria of -6.67 and 0.67 kPa, respectively. Results: A total of 123 patients completed the trial: 61 in the NPA group and 62 in the jaw thrust group. PaO2 at 20 min after apnea was 42.9 ± 14.0 kPa in the NPA group and 42.7 ± 13.6 kPa in the jaw thrust group. The difference between these two means was 0.25 kPa (95% CI, -3.87 to 4.37 kPa). Since the lower boundary of the 95% CI was > -6.67 kPa, noninferiority was established because higher PO2 is better. PaCO2 at 20 min after apnea was 10.74 ± 1.09 kPa in the NPA group and 10.54 ± 1.18 kPa in the jaw thrust group. The difference between the two means was 0.19 kPa (95% CI, -0.14 to 0.53 kPa). Since the upper boundary of the 95% CI was <0.67 kPa, noninferiority was established because lower PCO2 is better. No patient had a SpO2 < 90% during apnea. Conclusion: When THRIVE was applied during anesthesia-induced apnea, NPA placement kept airway opening and was noninferior to jaw thrust in terms of its effects on PaO2 and PaCO2 at 20 min after apnea. Clinical Trial Registration: ClinicalTrials.gov (NCT03741998).

Electroacupuncture Pretreatment Attenuates Acute Lung Injury Through α7 Nicotinic Acetylcholine Receptor-Mediated Inhibition of HMGB1 Release in Rats After Cardiopulmonary Bypass.

Acute lung injury is a common complication after cardiopulmonary bypass (CPB). α7 Nicotinic acetylcholine receptors (α7nAChR) and α7nAChR-dependent cholinergic signaling are implicated in suppressing the release of high-mobility group box 1 (HMGB1) and reducing the inflammatory response. A previous study has shown the electroacupuncture (EA) pretreatment induces tolerance against lung injury. However, the role of EA in CPB is poorly understood. This study used EA and a rat model of CPB to determine whether EA was associated with CPB-induced lung injury. Rats were treated with EA at "Zusanli (ST36)" and "Feishu (BL13)" acupoints for 5 days before being subjected to CPB. Two hours post-CPB, samples of blood, bronchoalveolar lavage fluid (BALF), and lung tissues were processed for investigations. Our results showed that the expression of α7nAChR in lung tissue was significantly decreased after CPB. EA pretreatment prevented the reduction in the expression of α7nAChR, EA pretreatment reduced lung edema, inhibited inflammatory cytokines release in serum and lung as well as protein concentrations in BALF and HMGB1 release after CPB, and the beneficial effects were attenuated by α-BGT. Our study demonstrates that EA pretreatment plays a protective role in CPB-induced ALI, and inhibits HMGB1 release through α7nAChR activation in rats.

Central cholinergic system mediates working memory deficit induced by anesthesia/surgery in adult mice.

Background: Postoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality, which has become a major concern of patients and caregivers. Although POCD occurs mainly in aged patients, it happens at any age. Previous studies demonstrated that anesthesia/surgery had no effects on reference memory of adult mice. However, whether it impairs working memory remains unclear. Working memory deficit would result in many deficits of executive function. We hypothesized that anesthesia/surgery impaired the working memory of adult mice and the central cholinergic system was involved. Method: Tibial fracture internal fixation under the anesthesia of isoflurane was performed in two-month-old C57BL/6 mice. Two days later, the spatial reference memory and working memory were measured by a Morris Water Maze (MWM). Donepezil, an inhibitor of acetylcholinesterase (AChE), was administered in another cohort mice for 4 weeks. Then, the working memory was measured by MWM 2 days after anesthesia/surgery. Western blot was used to detect the protein levels of acetylcholine transferase (ChAT), AChE, vesicular acetylcholine transporter (VAChT), and choline transporter (ChT) in the prefrontal cortex (PFC). Results: We found that anesthesia/surgery had no effects on the reference memory, but it impaired the working memory in adult mice. Meanwhile, we also found that the protein level of ChAT in PFC decreased significantly compared with that in control group. Donepezil pretreatment prevented working memory impairment and the decrease of the protein levels of ChAT induced by anesthesia/surgery. Conclusion: These results suggest that anesthesia/surgery leads to working memory deficits in adult mice and central cholinergic system impairment is involved.