A Neural Integrity Monitor Electromyography Endotracheal Tube Causes More Severe Postoperative Sore Throat Than a Standard Endotracheal Tube in Adults: A Prospective Cohort Study.

BACKGROUND: This study aimed at figuring out the different effects of a neural integrity monitor electromyography endotracheal tube (NIM-EMG-ETT) and a standard endotracheal tube (ETT) on postoperative sore throat (POST). METHODS: This prospective cohort study enrolled 143 patients scheduled to undergo general anesthesia with endotracheal intubation. Patients were allocated into three groups: Group A, non-thyroid surgery with a standard ETT; Group B, thyroid surgery with a standard ETT; Group C, thyroid surgery with a NIM-EMG-ETT. The incidence, the severity and visual analog scale (VAS) of POST were recorded. The incidence and the severity of POST were tested by χ2 test or Fisher's exact test. And VAS of POST was tested by Kruskal-Wallis test. RESULTS: The incidences of POST in Group B and Group C were significantly higher than that of Group A at all the time points after extubation (P < 0.001). The incidences of POST in Group C was significantly higher than that in Group B at 8 h, 24 h and 48 h after extubation (89.4% vs. 68.8%, P = 0.014, relative risk (RR) 1.30, 95% confidence interval (CI) 1.05-1.61; 89.4% vs. 58.3%, P = 0.001, RR 1.53, 95% CI 1.18-1.98; 76.6% vs. 45.8%, P = 0.002, RR 1.67, 95% CI 1.18-2.36). Moreover, there was a significant higher VAS of POST and more serious POST with Group C than with Group B. CONCLUSIONS: A NIM-EMG-ETT may induce higher incidence of POST and more serious POST than a standard ETT. TRAIL REGISTRATION: Chinese Clinical Trail Registry ( http://www.chictr.org.cn/index.aspx , ChiCTR2200058896, 2022-4-18).

Propofol Suppresses LPS-induced BBB Damage by Regulating miR-130a-5p/ZO-1 Axis.

The blood-brain barrier (BBB) is a highly selective semi-permeable barrier that separates circulating blood from the extracellular fluid of the brain and central nervous system, which is crucial for maintaining brain homeostasis. This study aimed to explore the role of propofol in BBB damage and further evaluate the underlying molecular mechanism. Lipopolysaccharide (LPS) was administered to mice to create an in vivo BBB damage mice model. Additionally, hCMEC/D3 cells as brain microvascular endothelial cells (BMECs) were treated with LPS to establish the in vitro BBB damage cell model. Subsequently, propofol was used for the BBB damage model. Evans blue staining and fluorescein sodium were utilized in the in vivo experiments to demonstrate BBB leakage and BBB permeability. Cell counting kit-8 (CCK-8) assay was used to assess cell viability and the trans-endothelial electrical resistance (TEER) value was measured using an epithelial voltmeter. Furthermore, enzyme-linked immunosorbent assay was performed to measure the levels of the inflammatory cytokines such as interleukin-1ß (IL-1ß) and tumor necrosis factor-alpha (TNF-α). The levels of miR-130a-5p and zonula occludens-1 (ZO-1) in brain tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction, western blot, or immunofluorescence staining. Furthermore, a dual-luciferase reporter assay was used to demonstrate the association between miR-130a-5p and ZO-1. Propofol treatment suppressed BBB leakage, the amount of fluorescein sodium, and the levels of IL-1ß and TNF-α in the LPS-induced BBB damage mice model. Meanwhile, propofol treatment increased the TEER value in the LPS-induced hCMEC/D3 cells. Additionally, propofol treatment significantly down-regulated miR-130a-5p and up-regulated ZO-1. More importantly, miR-130a-5p directly targeted ZO-1 and negatively regulated ZO-1 expression in hCMEC/D3 cells. Furthermore, miR-130a-5p mimic partially reversed the effect of propofol on the TEER value and the levels of inflammatory cytokines such as IL-1ß and TNF-α in the LPS-induced hCMEC/D3 cells. Propofol suppressed LPS-induced BBB damage by regulating miR-130a-5p/ZO-1 axis. These findings suggested a potentially effective treatment approach for BBB damage.

PKD2/polycystin-2 inhibits LPS-induced acute lung injury in vitro and in vivo by activating autophagy.

Polycystin-2 (PC2), which is a transmembrane protein encoded by the PKD2 gene, plays an important role in kidney disease, but its role in lipopolysaccharide (LPS)-induced acute lung injury (ALI) is unclear. We overexpressed PKD2 in lung epithelial cells in vitro and in vivo and examined the role of PKD2 in the inflammatory response induced by LPS in vitro and in vivo. Overexpression of PKD2 significantly decreased production of the inflammatory factors TNF-α, IL-1ß, and IL-6 in LPS-treated lung epithelial cells. Moreover, pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, reversed the inhibitory effect of PKD2 overexpression on the secretion of inflammatory factors in LPS-treated lung epithelial cells. We further demonstrated that overexpression of PKD2 could inhibit LPS-induced downregulation of the LC3BII protein levels and upregulation of SQSTM1/P62 protein levels in lung epithelial cells. Moreover, we found that LPS-induced changes in the lung wet/dry (W/D) weight ratio and levels of the inflammatory cytokines TNF-α, IL-6 and IL-1ß in the lung tissue were significantly decreased in mice whose alveolar epithelial cells overexpressed PKD2. However, the protective effects of PKD2 overexpression against LPS-induced ALI were reversed by 3-MA pretreatment. Our study suggests that overexpression of PKD2 in the epithelium may alleviate LPS-induced ALI by activating autophagy.

Could C3, 4, and 5 Nerve Root Block be a Better Alternative to Interscalene Block Plus Intermediate Cervical Plexus Block for Patients Undergoing Surgery for Midshaft and Medial Clavicle Fractures? A Randomized Controlled Trial.

BACKGROUND: Variable innervation of the clavicle is a major challenge in surgery of clavicle fractures with patients under regional anesthesia. An interscalene block (ISB) combined with an intermediate cervical plexus block (ICPB) provides analgesia in clavicle fracture surgery, but this combination does not completely block sensation in the midshaft or medial clavicle. Cervical nerve root block is an alternative to deep cervical plexus block and has recently been used as an analgesic method in the neck and shoulder. Whether it should be used as an alternative for midshaft and medial clavicle fractures is unknown. QUESTIONS/PURPOSES: In this randomized controlled trial, we compared a C3, 4, and 5 nerve root block to ISB combined with ICPB in surgery of midshaft and medial clavicle fractures in terms of the (1) proportion of patients achieving a sensory block that is sufficient for surgery, (2) onset time and duration of the block, and (3) effectiveness of postoperative analgesia, as measured by pain scores and consumption of analgesics. METHODS: Between November 2021 and December 2021, we treated 154 patients for clavicle fractures. A total of 122 were potentially eligible, 91 of whom agreed to participate in this study. Twenty-nine patients were excluded because the patients chose general anesthesia or declined to undergo surgery. Ultimately, 62 patients were randomly allocated into the C3, 4, and 5 group or ISB + ICPB group, with 31 patients in each group; there were no dropouts. All patients were analyzed in the group they were randomized to under intention-to-treat principles. The assessor and patients were blinded to randomization throughout the trial. The two groups did not differ in any important ways, including age, gender, BMI, American Society of Anesthesiologists classification, and type of clavicle fracture. The two groups received either an ultrasound-guided C3, 4, and 5 nerve root block with 2, 3, and 5 mL of 0.5% ropivacaine or ultrasound-guided ISB with ICPB with 20 mL of 0.5% ropivacaine. The primary outcome was the proportion of patients in each group with a successful nerveba block who did not receive general anesthesia; this was defined as nerve block success. Secondary outcomes included the onset time and duration of the sensory block, defined as the onset to the moment when the patients felt pain and sought rescue analgesia; pain assessment in terms of the numeric rating scale (NRS) score (range 0 to 10) for pain after nerve block before and during surgery; and the median amount of sufentanil consumed intraoperatively and postoperatively in the recovery room. The dosing of sufentanil was determined by the assessor when the NRS score was 1 to 3 points. If the NRS score was more than 3 points, general anesthesia was administered as a rescue method. Complications after the two inventions such as toxic reaction, dyspnea, hoarseness, pneumothorax, and Horner syndrome were also recorded in this study. RESULTS: A higher proportion of patients in the C3, 4, and 5 group had a successful nerve block than in the ISB + ICPB group (97% [30 of 31] versus 68% [21 of 31], risk ratio 6 [95% CI 1.5 to 37]; p < 0.01). The median onset time was 2.5 minutes (range 2.0 to 3.0 minutes) in the C3, 4, and 5 group and 12 minutes (range 9 to 16 minutes) in the ISB + ICPB group (difference of medians 10 minutes; p < 0.001). The sensory block duration was 10 ± 2 hours in the C3, 4, and 5 group and 8 ± 2 hours in the ISB + ICPB group (mean difference 2 hours [95% CI 1 to 3 hours]; p < 0.001). The median sufentanil consumption was lower in the C3, 4, 5 group than in the ISB + ICPB (median 5 µg [range 0.0 to 5.0 µg] versus median 0 µg [range 0.0 to 0.0 µg]; difference of medians 5.0 µg; p < 0.001). There were no differences between the two groups regarding NRS scores after nerve blocks and NRS score for incision and periosteum separation, with the minimum clinically important difference set at a 2-point difference (of 10). There were no severe complications in this study. CONCLUSION: Based on our analysis of the data, a C3, 4, and 5 nerve root block was better than ISB combined with ICPB for surgery to treat medial shaft and medial clavicle fractures. When choosing the anesthesia method, however, the patient's basic physiologic condition and possible complications should be considered. LEVEL OF EVIDENCE: Level I, therapeutic study.

An injectable mesoporous silica-based analgesic delivery system prolongs the duration of sciatic nerve block in mice with minimal toxicity.

The major limitation of traditional local anesthetics is the finite duration of a single injection. The present study developed two kinds of novel injectable anesthetic nanocomposites based on mesoporous silica, and evaluated their long-lasting analgesic effect and biosafety. The nanoparticulate carriers, mesoporous silica nanoparticles (MSNs) and mesoporous silica-coated gold nanorods (GNR@MSN), were firstly constructed using the oil-water biphase reaction approach and then ropivacaine (RPC), a local anesthetic, was loaded into the mesoporous carriers by vacuum suction. Transmission electron microscopic images showed the well-ordered mesoporous structure for drug loading. RPC-loaded MSNs and RPC-loaded GNR@MSN exhibited a sustained-release pattern in vitro, and the latter also showed a controlled-release manner triggered by near-infrared (NIR) irradiation. RPC-loaded MSNs and RPC-loaded GNR@MSN caused an initial sensory blockade in mice that lasted for 6 h, almost 2.5 folds of that from free RPC solution. Furthermore, upon NIR irradiation, the latter induced three additional periods of the blockade. Neither of them showed motor nerve block, which may be due to the sustained release manner. The low myotoxicity and low neurotoxicity of the two nanocomposites were presented both in vitro and in vivo. These results demonstrate the potential of the mesoporous silica-based analgesic nanocomposites in effectively controlling postoperative pain, maybe RPC-loaded MSNs for moderate pain and RPC-loaded GNR@MSN for severe pain. STATEMENT OF SIGNIFICANCE: Adequate postoperative analgesia helps early functional exercise after surgery and accelerates rapid recovery, while uncontrolled postoperative pain probably develops chronic post-surgical pain that impacts the life quality of patients for a long time. However, postoperative pain management is still a challenge. The current treatment drugs are always accompanied by some side effects due to their systemic effect. Opioids have risks of addiction and respiratory depression, and nonsteroidal anti-inflammatory drugs can lead to gastrointestinal reaction. Therefore, the long-lasting local anesthetic formulation with good biocompatibility is the most promising solution to manage post-surgical pain. The present study developed novel injectable anesthetic nanocomposites based on mesoporous silica, providing long-lasting pain relief in mice with minimal toxicity.

Butorphanol Promotes Macrophage Phenotypic Transition to Inhibit Inflammatory Lung Injury via κ Receptors.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by diffuse inflammation of the lung parenchyma and refractory hypoxemia. Butorphanol is commonly used clinically for perioperative pain relief, but whether butorphanol can regulate LPS-induced alveolar macrophage polarization is unclear. In this study, we observed that butorphanol markedly attenuated sepsis-induced lung tissue injury and mortality in mice. Moreover, butorphanol also decreased the expression of M1 phenotype markers (TNF-α, IL-6, IL-1ß and iNOS) and enhanced the expression of M2 marker (CD206) in alveolar macrophages in the bronchoalveolar lavage fluid (BALF) of LPS-stimulated mice. Butorphanol administration reduced LPS-induced numbers of proinflammatory (M1) macrophages and increased numbers of anti-inflammatory (M2) macrophages in the lungs of mice. Furthermore, we found that butorphanol-mediated suppression of the LPS-induced increases in M1 phenotype marker expression (TNF-α, IL-6, IL-1ß and iNOS) in bone marrow-derived macrophages (BMDMs), and this effect was reversed by κ-opioid receptor (KOR) antagonists. Moreover, butorphanol inhibited the interaction of TLR4 with MyD88 and further suppressed NF-κB and MAPKs activation. In addition, butorphanol prevented the Toll/IL-1 receptor domain-containing adaptor inducing IFN-ß (TRIF)-mediated IFN signaling pathway. These effects were ameliorated by KOR antagonists. Thus, butorphanol may promote macrophage polarization from a proinflammatory to an anti-inflammatory phenotype secondary to the inhibition of NF-κB, MAPKs, and the TRIF-mediated IFN signaling pathway through κ receptors.

DOCK2 contributes to endotoxemia-induced acute lung injury in mice by activating proinflammatory macrophages.

Dedicator of cytokinesis 2 (DOCK2), an atypical Rac activator, has important anti-inflammatory properties in blepharitis, enteric bacterial infection and colitis. However, the roles of DOCK2 in macrophage activation and acute lung injury (ALI) are still poorly elucidated. In vitro studies demonstrated that DOCK2 was essential for the nucleotide-sensing Toll-like receptor (TLR) 4-mediated inflammatory response in macrophages. We also confirmed that exposure of macrophages to LPS induced Rac activation through a TLR4-independent, DOCK2-dependent mechanism. Phosphorylation of IκB kinase (IKK) ß and nuclear translocation of transcription factor nuclear factor kappa B (NF-κB) were impaired in Ad-shDOCK2-expressing macrophages, resulting in a decreased inflammatory response. Similar results were obtained when EHop-016 (a Rac inhibitor) was used to treat uninfected macrophages. In summary, these data indicate that the DOCK2-Rac signaling pathway acts in parallel with TLR4 engagement to control IKKß activation for inflammatory cytokine release. Next, we investigated whether pharmacological inhibition of DOCK2 protects against endotoxemia-induced lung injury in mice. Treatment with 4-[3'-(2″-chlorophenyl)-2'-propen-1'-ylidene]-1-phenyl-3,5-pyrazolidinedione (CPYPP), a small-molecule inhibitor of DOCK2, reduced the severity of lung injury, as indicated by decreases in the lung injury score and myeloperoxidase (MPO) activity. Moreover, CPYPP attenuated LPS-induced proinflammatory cytokine release in mice. Our studies suggest that inhibition of DOCK2 may suppress LPS-induced macrophage activation and that DOCK2 may be a novel target for treating endotoxemia-related ALI.

Ketamine and Propofol Protect Neuron Cells from Oxygen-Glucose Deprivation-Induced Injury through SAPK/JNK Signalling Pathway.

Ketamine and propofol are commonly used anaesthetic reagents. Recent research revealed that ketamine and propofol have an important role in cell survival. However, it remains unknown whether they affect the outcome of hypoxic-ischemic brain injury. To address this issue, we in this study investigated the effects of ketamine and propofol on the survival and proliferation of neuronal PC12 cells after exposure to oxygen-glucose deprivation- (OGD-) induced injury. PC12 cells were maintained under a 3-dimensional (3D) culture system to mimic a real physiological microenvironment. The cell injury was induced by 5% CO2 and 95% N2 for a different time point. MTT assay was used for the cell proliferation assay. The cell apoptosis was evaluated by annexin V and propidium iodide (PI) labeling, immunofluorescence staining, transmission electron microscopy (TEM), flow cytometry, and Western blot, respectively. Our results showed that PC12 cell apoptosis was significantly increased for up to 70% after the cells were treated with OGD for 24 hours and reduced to baseline at the 72-hour time point. However, pretreatment with ketamine and propofol significantly protected the cells from OGD-induced cell apoptosis, as evidenced by more expression of antiapoptotic Bcl-2 and lower expression of proapoptotic cleaved caspase-3, phosphor-SAPK/JNK, and phosphor-c-Jun than those of untreated control cells. Thus, we conclude that ketamine and propofol protected PC12 cells from OGD-induced cell apoptosis, at least partially through the SAPK/JNK signalling pathway.

Neurofilament degradation is involved in laparotomy-induced cognitive dysfunction in aged rats.

Excessive neuroinflammatory responses play important roles in the development of postoperative cognitive dysfunction (POCD). Neurofilaments (NFs) were essential to the structure of axon and nerve conduction; and the abnormal degradation of NFs were always accompanied with degenerative diseases, which were also characterized by excessive neuroinflammatory responses in brain. However, it is still unclear whether the NFs were involved in the POCD. In this study, the LC-MS/MS method was used to explore the neuroinflammatory response and NFs of POCD in aged rats. Moreover, trichostatin A (TSA), an inflammation-related drug, was selected to test whether it could improve the surgery-induced cognitive dysfunction, inflammatory responses and NFs. Evident cognitive dysfunction, excessive microglia activation, neuroinflammatory responses and upregulated NFs in hippocampus were observed in the POCD group. TSA pretreatment could significantly mitigate these changes. The KEGG analysis revealed that nine pathways were enriched in the TSA + surgery group (versus the surgery group). Among them, two signaling pathways were closely related with the changes of NFs proteins. In conclusion, surgery could impair the cognitive function and aggravate neuroinflammation and NFs. The TSA could significantly improve these changes which might be related to the activation of the "focal adhesion" and "ECM-receptor interaction" pathways.

Ursodeoxycholic acid protects against lung injury induced by fat embolism syndrome.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life-threatening disease with a high mortality rate, which was a common complication of fat embolism syndrome (FES). Ursodeoxycholic acid (UDCA) has been reported to exert potent anti-inflammatory effects under various conditions. In vivo, perinephric fat was injected via tail vein to establish a rat FES model, the anti-inflammatory effects of UDCA on FES-induced lung injury were investigated through histological examination, ELISA, qRT-PCR, Western blot and immunofluorescence. In vitro, human lung microvascular endothelial cells (HPMECs) were employed to understand the protective effects of UDCA. The extent of ALI/ARDS was evaluated and validated by reduced PaO2 /FiO2 ratios, increased lung wet/dry (W/D) ratios and impaired alveolar-capillary barrier, up-regulation of ALI-related proteins in lung tissues (including myeloperoxidase [MPO], vascular cell adhesion molecule 1 [VCAM-1], intercellular cell adhesion molecule-1 [ICAM-1]), elevated protein concentration and increased proinflammatory cytokines levels (TNF-α and IL-1ß) in bronchoalveolar lavage fluid (BALF). Pre-treatment with UDCA remarkably alleviated these pathologic and biochemical changes of FES-induced ALI/ARDS; our data demonstrated that pre-treatment with UDCA attenuated the pathologic and biochemical changes of FES-induced ARDS, which provided a possible preventive therapy for lung injury caused by FES.

The TGF-ß1 Induces the Endothelial-to-Mesenchymal Transition via the UCA1/miR-455/ZEB1 Regulatory Axis in Human Umbilical Vein Endothelial Cells.

Transforming growth factor-beta 1 (TGF-ß1) plays important roles in the endothelial-to-mesenchymal transition (EndMT). Recently, long noncoding RNAs (lncRNAs) have been identified to be involved in the physiological and pathological processes of human diseases. However, the role of endothelial lncRNAs in the TGF-ß1-mediated control of angiogenesis and its underlying mechanism remains largely unclear. In this study, we first demonstrated that TGF-ß1 induced EndMT; promoted cell viability, proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). Second, our study displayed that TGF-ß1 upregulated the lncRNA UCA1 expression in HUVECs, knocked down UCA1 with small interfering RNAs, and inhibited the function of TGF-ß1 in HUVECs. Third, our study showed that UCA1 was located in the cytoplasm and absorbed miR-455 in TGF-ß1-treated HUVECs. Further, the miR-455 inhibitor restored the role of the inhibited UCA1 in HUVECs treated with TGF-ß1. Fourth, our study revealed that miR-455 inhibited ZEB1 expression, and overexpression of ZEB1 restored the role of miR-455 in HUVECs treated with TGF-ß1. Finally, our study revealed that UCA1 exerted its role via regulating the UCA1/miR-455/ZEB1 regulatory axis in HUVECs treated with TGF-ß1. Collectively, our study identified the role of the UCA1/miR-455/ZEB1 pathway in HUVECs treated with TGF-ß1 and indicated the potential therapeutic role of this regulatory axis in angiogenesis.

DJ-1 plays a neuroprotective role in SH-SY5Y cells by modulating Nrf2 signaling in response to lidocaine-mediated oxidative stress and apoptosis.

To investigate the effects of DJ-1 on lidocaine-induced cytotoxicity in neurons and the link with Nrf2 signaling, SH-SY5Y cells were treated with 1, 4, 8, and 16 mM lidocaine. Cell viability was measured by MTT assay, and apoptosis was measured by flow cytometry analysis. The mitochondrial membrane potential, reactive oxygen species (ROS) levels, lipid peroxidation (MDA), and GSH/GSSG ratio were determined with specific kits. Expression of DJ-1, Nrf2, and Nrf2 downstream signaling proteins (glutathione peroxidase [GPx], heme oxygenase-1 [HO-1], catalase [CAT], and glutathione reductase [GR]), was determined by western blot and qRT-PCR. The cell viability was dramatically decreased, while levels of apoptosis, ROS and Cys106-oxidized DJ-1 were significantly enhanced following treatment with lidocaine (concentration 4-16 mM), and increases were observed in a dose-dependent manner. After treatment with 8 mM lidocaine, DJ-1, and nuclear Nrf2, as well as antioxidative stress-related proteins, GPx, GR, HO-1, and CAT, were all significantly inhibited. Overexpression of DJ-1 suppressed lidocaine-induced apoptosis and oxidative stress in SH-SY5Y cells and activated Nrf2 signalling at the same time, and these effects were reversed by the inhibition of Nrf2. DJ-1 could protect SH-SY5Y cells from lidocaine-induced apoptosis through inhibition of oxidative stress via Nrf2 signaling.

Ursodeoxycholic acid stimulates alveolar fluid clearance in LPS-induced pulmonary edema via ALX/cAMP/PI3K pathway.

This study aims to examine the impact of ursodeoxycholic acid (UDCA) on pulmonary edema and explore the underlying molecular mechanisms. The effects of UDCA on pulmonary edema were assessed through hematoxylin and eosin (H&E) staining, lung dry/wet (W/D) ratio, TNF-α/IL-1ß levels of bronchoalveolar lavage fluid (BALF), protein expression of epithelial sodium channel (ENaC), and Na+ /K+ -ATPase. Besides, the detailed mechanisms were explored in primary rat alveolar type (AT) II epithelial cells by determining the effects of BOC-2 (ALX [lipoxin A4 receptor] inhibitor), Rp-cAMP (cAMP inhibitor), LY294002 (PI3K inhibitor), and H89 (PKA inhibitor) on the therapeutic effects of UDCA against lipopolysaccharide (LPS)-induced changes. Histological examination suggested that LPS-induced lung injury was obviously attenuated by UDCA. BALF TNF-α/IL-1ß levels and lung W/D ratios were decreased by UDCA in LPS model rats. UDCA stimulated alveolar fluid clearance (AFC) though the upregulation of ENaC and Na+ /K+ -ATPase. BOC-2, Rp-cAMP, and LY294002 largely suppressed the therapeutic effects of UDCA. Significant attenuation of pulmonary edema and lung inflammation was revealed in LPS-challenged rats after the UDCA treatment. The therapeutic efficacy of UDCA against LPS was mainly achieved through the ALX/cAMP/PI3K pathway. Our results suggested that UDCA might be a potential drug for the treatment of pulmonary edema induced by LPS.

Effects of the ALX/FPR2 receptors of lipoxin A4 on lung injury induced by fat embolism syndrome in rats.

This study was designed to investigate the inflammatory responses in fat embolism syndrome (FES) and the relationship of ALX/FPR2 receptors and lipoxin A4 (LXA4) in FES models. In this model, lung injury score, lung tissue wet-to-dry (W/D) ratio and total protein concentration in bronchoalveolar lavage fluid (BALF) were increased compared with those of the control group. Meanwhile, the number of leukocytes and neutrophils was significantly increased in the FES group, as was the myeloperoxidase (MPO) activity and mRNA expression. In addition, the release of TNF-α and IL-1ß was increased. Then, we explored whether LXA4 and ALX/FPR2 were involved in the pathological process of FES. The LXA4 concentration in the experimental groups was markedly higher than that in the control group. At the same time, the protein and mRNA levels of ALX/FPR2 were upregulated in the rat model of FES. Moreover, rats treated with BML-111, an agonist for the ALX/FPR2 receptor of LXA4, showed a lower inflammatory response than mice treated with fat alone. However, the role of BML-111 in fat emboli (FE)-induced acute lung injury (ALI) was attenuated by BOC-2, an antagonist of the ALX/FPR2 receptor of LXA4. Our results demonstrated that the inflammatory response may play an important role in the pathogenesis of FES and that the activation of the ALX/FPR2 receptor for LXA4 can decrease the inflammatory response and may be a therapeutic target for FE-induced ALI.

Effect of ultrasound-guided lumbar plexus block on emergence agitation in children undergoing hip surgery: study protocol for a randomized controlled trial.

BACKGROUND: Emergence agitation (EA) is a common postoperative issue in children that causes self-injury, increases stress on healthcare team members, and even leads to postoperative maladaptive behavioral changes in children. Clear answers regarding a 'gold standard' for prevention of EA are not available. Pain is regarded as an important causative factor of EA, and ultrasound-guided lumbar plexus block is a safe and efficient anesthetic method that can provide satisfactory pain relief in pediatric hip surgery. The purpose of our study is to determine whether ultrasound-guided lumbar plexus block can reduce the incidence of EA in children undergoing hip surgery. METHODS/DESIGN: We designed a prospective, randomized, controlled, blinded trial to determine the effect of ultrasound-guided lumbar plexus block on EA. A total of 100 American Society of Anesthesiologists class I-II children (1-6 years old) scheduled for elective hip surgery will be recruited for this study. Participants will be randomized at a 1:1 ratio to receive either ultrasound-guided lumbar plexus block or fentanyl after the induction of general anesthesia. The primary outcome is the incidence of EA 30 min after emergence from anesthesia using the Pediatric Anesthesia Emergence Delirium (PAED) score. The secondary outcomes are the severity and duration of EA 30 min after emergence from anesthesia using the PAED score, postoperative pain evaluated by the Children's Hospital of Eastern Ontario Pain Scale, and the incidence of postoperative adverse events. Randomization will be conducted using a computer-generated randomization schedule. Outcome assessors and data collectors will be blinded to the group allocations. Assessments will be performed before surgery, intraoperatively, and postoperatively at every time point. DISCUSSION: Our hypothesis in this trial is that ultrasound-guided lumbar plexus block can decrease the incidence of EA in children undergoing elective hip surgery. This trial will provide clinical answers to verify our hypothesis. If our hypothesis is confirmed, the results could provide a safe method to prevent EA. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-INR-17011525 . Registered on 30 May 2017.

Lidocaine inhibits melanoma cell proliferation by regulating ERK phosphorylation.

The melanoma is responsible for the majority of all skin cancer-related deaths worldwide. Evidence suggests that local anesthetics provide some benefit in the treatment of cancer via inhibition of cellular proliferation, invasion and migration. However, the potential antiproliferative effects of local anesthetics in the treatment of melanoma remain to be elucidated. In this study, we investigated the antiproliferative effects and underlying mechanism of the commonly used local anesthetic (lidocaine) on melanoma cells. A375 melanoma cells were treated by lidocaine or vemurafenib. Cell Counting Kit-8, histological staining, flow cytometric analysis, immunohistochemical staining, and Western blot analyses were carried out to test the effects of lidocaine and vemurafenib on A375 cells. BALB/C-nu/nu mice intraperitoneally injected with A375 cells were treated by lidocaine, and then tumor volume and weight were calculated. Lidocaine exhibited vemurafenib-like effects totally. Lidocaine inhibited A375 melanoma cell proliferation in a dose- and time-dependent manner and colony formation also showed a dose-dependent inhibition. Lidocaine treatment resulted in the arrest of cell-cycle progression in the G1 phase and inhibited Ki-67 expression in a dose-dependent manner. This effect was associated with inhibited extracellular signal-regulated kinase (ERK) phosphorylation. In vivo experiments revealed that intravenous injections of lidocaine suppressed tumor volume and weight. Lidocaine inhibits melanoma cell proliferation in a dose- and time-dependent manner via a mechanism that may involve inhibition of the ERK signaling pathway. Thus, lidocaine may provide some benefit for the treatment of melanoma.

Rapamycin alleviated pulmonary injury induced by fat embolism syndrome in rats.

Fat embolism syndrome (FES) is a serious complication after trauma, surgery and fat emulsion input and can lead to serious pulmonary injury. Autophagy controls the cell survival and homeostasis by removing the mis-folded proteins and damaged organelles as well as intracellular pathogens through a lysosomal degradation pathway. Increasing research documented that autophagy was wildly involved in variety of human diseases and had huge therapeutic potential. However, the role and mechanism of autophagy in FES remains largely unknown. The rat model of FES was established by tail vein injection with fat and was assessed by Wet-to-Dry (W/D) ratio analysis, hematoxylin-eosin (HE) analysis, staining Oil red staining analysis and qPCR analysis. Western blots were employed to detect the expression of autophagy markers. The changes of pulmonary injury were observed after premedication of rapamycin (an autophagy activator). The alveolar structural damage, red free fat substances in the blood vessels of lung, increased the lung ratio, and the up-regulated MPO expression and activity were showed in the FES models. The expressions of autophagy markers were decreased and meanwhile, apoptosis markers were increased in the FES model. Rapamycin restored the expression of autophagy markers and inhibited the apoptosis and further, resulting in the improvement of the pulmonary injury. Thus, our study demonstrated that autophagy was inhibited and apoptosis was promoted in FES and further Rapamycin alleviated the pulmonary damage in FES via restoring the autophagy and inhibiting the apoptosis.