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.

Lactated Ringer's solution versus normal saline in pediatric living-donor liver transplantation: A matched retrospective cohort study.

BACKGROUND: In pediatric living-donor liver transplantation, lactated Ringer's solution and normal saline are commonly used for intraoperative fluid management, but the comparative clinical outcomes remain uncertain. AIMS: To compare the effect between lactated Ringer's solution and normal saline for intraoperative volume replacement on clinical outcomes among pediatric living-donor liver transplantation patients. METHODS: This single-center, retrospective trial study enrolled children who received either lactated Ringer's solution or normal saline during living-donor liver transplantation between January 2010 and August 2016. The groups with comparable clinical characteristics were balanced by propensity score matching. The primary outcome was 90-day all-cause mortality, and the secondary outcomes included early allograft dysfunction, primary nonfunction, acute renal injury, and hospital-free days (days alive postdischarge within 30 days of liver transplantation). RESULTS: We included 333 pediatric patients who met the entry criteria for analysis. Propensity score matching identified 61 patients in each group. After matching, the lactated Ringer's solution group had a higher 90-day mortality rate than the normal saline group (11.5% vs. 0.0%). Early allograft dysfunction and primary nonfunction incidences were also more frequent in the lactated Ringer's solution group (19.7% and 11.5%, respectively) than in the normal saline group (3.3% and 0.0%, respectively). In the lactated Ringer's solution group, four (6.6%) recipients developed acute renal injury within 7 days postoperatively compared with three (4.9%) recipients in the normal saline group. Hospital-free days did not differ between groups (9 days [1-13] vs. 9 days [0-12]). CONCLUSIONS: For intraoperative fluid management in pediatric living-donor liver transplantation patients, lactated Ringer's solution administration was associated with a higher 90-day mortality rate than normal saline. This finding has important implications for selecting crystalloid in pediatric living-donor liver transplantation. Further randomized clinical trials in larger cohort are necessary to confirm this finding.

MiR-574-5p promotes the differentiation of human cardiac fibroblasts via regulating ARID3A.

Cardiac fibrosis after myocardial infarction (MI) is mainly associated with cardiac fibroblasts and its differentiation is the key pathological process. However, the cellular mechanism of fibroblast-to-myofibroblast conversion has not been clarified and a deeper mechanistic understanding is needed. We found that miR-574-5p was up-regulated in TGF-ß-induced myofibroblast differentiation. Silencing transiently miR-574-5p in HCFs, we found that suppression of miR-574-5p decreased myofibroblasts differentiation as validated by expression levels of fibrosis related genes, EDU imaging assay, wound healing assay and transwell assays. Conversely, overexpression of miR-574-5p displayed opposite results. ARID3A was verified as a direct target gene of miR-574-5p and decreased level of ARID3A forced fibroblast-to-myofibroblast differentiation of TGF-ß-induced HCFs. Our data suggests that miR-574-5p plays a pivotal role in human cardiac fibroblasts (HCFs) myofibroblast differentiation and demonstrates that miR-574-5p and arid3a may be a novel therapeutic target for cardiac fibrosis.

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.

SPI1-mediated macrophage polarization aggravates age-related macular degeneration.

Objective: This study revealed a core regulator and common upstream mechanisms for the multifaceted pathological processes of age-related macular degeneration (AMD) and provided proof-of-concept for this new therapeutic target. Methods: Comprehensive gene expression analysis was performed using RNA sequencing of eye cup from old mice as well as laser-induced choroidal neovascularization (CNV) mouse model. Through integrative analysis and protein-protein interaction (PPI) analysis, common pathways and key transcription factor was identified simultaneously engaged in age-related retinal degeneration and CNV, the two typical pathological process of AMD. Subsequently, the expression changes of Spi1, the key regulator, as well as the alternation of the downstream mechanisms were validated in both models through qRT-PCR, Elisa, flow cytometry and immunofluorescence. Further, we assessed the impact of Spi1 knockdown in vitro and in vivo using gene intervention vectors carried by adeno-associated virus or lentivirus to test its potential as a therapeutic target. Results: Compared to corresponding controls, we found 1,939 and 1,319 genes differentially expressed in eye cups of old and CNV mice respectively. The integrative analysis identified a total of 275 overlapping DEGs, of which 150 genes were co-upregulated. PPI analysis verified a central transcription factor, SPI1. The significant upregulation of Spi1 expression was then validated in both models, accompanied by macrophage polarization towards the M1 phenotype. Finally, SPI1 suppression significantly inhibited M1 polarization of BMDMs and attenuated neovascularization in CNV mice. Conclusion: This study demonstrates that SPI1 exerts a pivotal role in AMD by regulation of macrophage polarization and innate immune response, offering promise as an innovative target for treating AMD.

Transfer RNA derived fragment, tRF-Glu-CTC, aggravates the development of neovascular age-related macular degeneration.

Rationale: Angiogenesis expedites tissue impairment in many diseases, including age-related macular degeneration (AMD), a leading cause of irreversible blindness in elderly. A substantial proportion of neovascular AMD patients, characterized by aberrant choroidal neovascularization (CNV), exhibit poor responses or adverse reactions to anti-VEGF therapy. Herein, we aimed to unveil the function of newly identified transfer RNA-derived small RNA, tRF-Glu-CTC, in the pathology of CNV and determine its potential in inhibiting angiogenesis. Methods: Small non-coding RNA sequencing and quantitative polymerase chain reaction were conducted to detect expression pattern of tRF-Glu-CTC in CNV development. Immunofluorescence staining, fundus fluorescein angiography and ex vivo choroidal sprouting assays were employed for the evaluation of tRF-Glu-CTC's function in CNV development. The role of tRF-Glu-CTC in endothelial cells were determined by in vitro endothelial cell proliferation, migration and tube formation assays. Transcriptome sequencing, dual-luciferase reporter assay and in vitro experiments were conducted to investigate downstream mechanism of tRF-Glu-CTC mediated pathology. Results: tRF-Glu-CTC exhibited substantial up-regulation in AMD patients, laser-induced CNV model, and endothelial cells under hypoxia condition, which is a hallmark of CNV. Inhibiting tRF-Glu-CTC reduced angiogenesis and hypoxia stress in the neovascular region without neuroretina toxicity in laser-induced CNV model, showing an anti-angiogenic effect comparable to bevacizumab, while overexpression of tRF-Glu-CTC significantly augmented CNV. Mechanically, under hypoxia condition, angiogenin was involved in the production of tRF-Glu-CTC, which in turn triggered endothelial cell tubulogenesis, migration and promoted the secretion of inflammatory factors via the suppression of vasohibin 1 (VASH1). When downregulating VASH1 expression, the inhibition of tRF-Glu-CTC showed minimal suppression on angiogenesis. Conclusions: This study demonstrated the important role of tRF-Glu-CTC in the progression of angiogenesis. Targeting of tRF-Glu-CTC may be an alternative to current anti-VEGF therapy for CNV in AMD and other conditions with angiogenesis.

Proteotranscriptomic analyses reveal distinct interferon-beta signaling pathways and therapeutic targets in choroidal neovascularization.

Aim: To investigate the molecular mechanism underlying the onset of choroidal neovascularization (CNV). Methods: Integrated transcriptomic and proteomic analyses of retinas in mice with laser-induced CNV were performed using RNA sequencing and tandem mass tag. In addition, the laser-treated mice received systemic interferon-ß (IFN-ß) therapy. Measurements of CNV lesions were acquired by the confocal analysis of stained choroidal flat mounts. The proportions of T helper 17 (Th17) cells were determined by flow cytometric analysis. Results: A total of differentially expressed 186 genes (120 up-regulated and 66 down-regulated) and 104 proteins (73 up-regulated and 31 down-regulated) were identified. The gene ontology and KEGG pathway analyses indicated that CNV was mainly associated with immune and inflammatory responses, such as cellular response to IFN-ß and Th17 cell differentiation. Moreover, the key nodes of the protein-protein interaction network mainly involved up-regulated proteins, including alpha A crystallin and fibroblast growth factor 2, and were verified by Western blotting. To confirm the changes in gene expression, real-time quantitative PCR was performed. Furthermore, levels of IFN-ß in both the retina and plasma, as measured by enzyme-linked immunosorbent assay (ELISA), were significantly lower in the CNV group than in the control group. IFN-ß treatment significantly reduced CNV lesion size and promoted the proliferation of Th17 cells in laser-treated mice. Conclusions: This study demonstrates that the occurrence of CNV might be associated with the dysfunction of immune and inflammatory processes and that IFN-ß could serve as a potential therapeutic target.

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.

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.