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Arnold-Chiari malformations (ACM) is a rare congenital hindbrain maldevelopment, leading to downward herniation of the cerebellar tonsils. Clinical features relates to cerebrospinal fluid disturbances, manifesting as symptoms of headaches, pseudotumour-like episodes, cranial nerve palsies and cerebellar dysfunction. Ocular manifestations includes varying ophthalmoloplegia and accommodation abnormalities. Papilloedema has been rarely implicated and remains an uncommon feature of ACM. We report a case of ACM who developed papilloedema and visual disturbance, that was successfully treated with suboccipital decompression. The presentation of patients with ACM-I and papilloedema unaccompanied by localising signs may resemble that of IIH. Neuroimaging with special attention to the craniocervical junction in saggital and transverse planes is crucial. Surgical decompression of the posterior fossa seems to improve headache symptoms and clinical signs of papilloedema.

Background Competitive Endogenous RNA (ceRNA) may be closely associated with tumor progression. However, studies on ceRNAs and immune cells in LUAD are scarce. Method The profiles of gene expression and clinical data of LUAD patients were extracted from the TCGA database. Bioinformatics methods were used to evaluate differentially-expressed genes (DEGs) and to form a ceRNA network. Preliminary verification of clinical specimens was utilized to detect the expressions of key biomarkers at the tissues. Cox and Lasso regressions were used to identify key genes, and prognosis prediction nomograms were formed. The mRNA levels of 9 genes in the risk score model in independent clinical LUAD samples were detected by qRT-PCR. The interconnection between the risk of cancer and immune cells was evaluated using the CIBERSORT algorithm, while the conformation of notable tumor-infiltrating immune cells (TIICs) in the LUAD tissues of the high and low risk groups was assessed using the RNA transcript subgroup in order to identify tissue types. Finally, co-expression study was used to examine the interconnection between the key genes in the ceRNA networks and the immune cells. Result A ceRNA network of 115 RNAs was established, and nine key genes were identified to construct a Cox proportional-hazard model and create a prognostic nomogram. This risk-assessment model might serve as an independent factor to forecast the prognosis of LUAD, and it was consistent with the preliminary verification of clinical specimens. Survival analysis of clinical samples further validated the potential value of high risk groups in predicting LUAD prognosis. Five immune cells were identified with significant differences in the LUAD tissues of the high and low risk groups. Besides, two pairs of biomarkers associated with the growth of LUAD were found, i.e., E2F7 and macrophage M1 (R = 0.419, p = 1.4e− 08) and DBF4 and macrophage M1 (R = 0.282, p − 16). Conclusion This study identified several important ceRNAs, i.e. (E2F7 and BNF4) and TIICs (macrophage M1), which might be related to the development and prognosis of LUAD. The established risk-assessment model might be a potential tool in predicting LUAD of prognosis.

Background Cognitive deficits are common in patients with sepsis. Previous studies in sepsis-associated encephalopathy (SAE) implicated the C-X-C chemokine receptor type (CXCR) 5. The present study used a mouse model of SAE to examine whether CXCR5 down-regulation could attenuate cognitive deficits. Methods Sepsis was induced in adult male C57BL/6 J and CXCR5−/− mice by cecal ligation and puncture (CLP). At 14–18 days after surgery, animals were tested in a Morris water maze, followed by a fear conditioning test. Transmission electron microscopy of hippocampal sections was used to assess levels of autophagy. Primary microglial cultures challenged with lipopolysaccharide (LPS) were used to examine the effects of short interfering RNA targeting CXCR5, and to investigate the possible involvement of the p38MAPK/NF-κB/STAT3 signaling pathway. Results CLP impaired learning and memory and up-regulated CXCR5 in hippocampal microglia. CLP activated hippocampal autophagy, as reflected by increases in numbers of autophagic vacuoles, conversion of microtubule-associated protein 1 light chain 3 (LC3) from form I to form II, accumulation of beclin-1 and autophagy-related gene-5, and a decrease in p62 expression. CLP also shifted microglial polarization to the M1 phenotype, and increased levels of IL-1β, IL-6 and phosphorylated p38MAPK. CXCR5 knockout further enhanced autophagy but partially reversed all the other CLP-induced effects, including cognitive deficits. Similar effects on autophagy and cytokine expression were observed after knocking down CXCR5 in LPS-challenged primary microglial cultures; this knockdown also partially reversed LPS-induced up-regulation of phosphorylated NF-κB and STAT3. The p38MAPK agonist P79350 partially reversed the effects of CXCR5 knockdown in microglial cultures. Conclusions CXCR5 may act via p38MAPK/NF-κB/STAT3 signaling to inhibit hippocampal autophagy during sepsis and thereby contribute to cognitive dysfunction. Down-regulating CXCR5 can restore autophagy and mitigate the proinflammatory microenvironment in the hippocampus.

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a crucial regulator of neuronal development, neuronal survival, axonal regeneration, and synaptic plasticity. In this study we examined the potential role of PTEN in cognitive function in a mouse model of perioperative neurocognitive disorder (PND). Adult male C57BL/6J mice received intracerebroventricular injections of small interfering RNA (siRNA) against PTEN or control siRNA 3 days prior to exploratory laparotomy (n = 8 per group). A group of healthy mice not undergoing surgery included as additional control. Barnes maze and fear conditioning tests were conducted 7 days after surgery. Mice were then sacrificed to examine the expression of PTEN, AMP-activated protein kinase (AMPK), ionized calcium binding adaptor molecule (Iba)-1, B-cell lymphoma (Bcl)-2, Bcl2-associated X protein (Bax), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α in the hippocampus. The microglial activation was examined by immunohistochemistry using Iba-1 as a microglia maker. Nissl and terminal transferase deoxyuridine triphosphate nick-end labeling (TUNEL) staining were used to measure cell death and apoptosis. In comparison to the healthy controls, surgically treated mice had longer latency to identify the target box in both training and testing sessions in the Barnes maze test and shorter freezing time in the fear conditioning test. Surgically treated mice had increased expression of PTEN, AMPK, Bax, IL-1β, and TNF-α, as well as increasing number of activated microglia and apoptosis neurons in the hippocampus. PTEN knockdown significantly attenuated the behavioral deficits in Barnes maze and fear conditioning tests, as well as over-expression of PTEN, AMPK, Bax, IL-1β, and TNF-α induced by surgery. PTEN knockdown could attenuate cognitive deficits induced by trauma, likely through inhibiting the activation of microglia.

Background Aberrant hippocampal neurogenesis is an important pathological feature of sepsis-associated encephalopathy. In the current study, we examined the potential role of the long noncoding RNA (lncRNA) sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2OT), a known regulator of adult neurogenesis in sepsis-induced deficits in hippocampal neurogenesis and cognitive function. Methods Sepsis was induced in adult C57BL/6 J male mice by cecal ligation and perforation (CLP) surgery. Randomly selected CLP mice were transfected with short interfering RNAs (siRNAs) against SOX2OT or SOX2, or with scrambled control siRNA. Cognitive behavior was tested 8–12 days post-surgery using a Morris water maze. Western blotting and RT-qPCR were used to determine expression of SOX2, Ki67, doublecortin (DCX), nestin, brain lipid-binding protein, and glial fibrillary acidic protein (GFAP) in the hippocampus. The number of bromodeoxyuridine (BrdU)+/DCX+ cells, BrdU+/neuronal nuclei (NeuN)+ neurons, and BrdU+/GFAP+ glial cells in the dentate gyrus were assessed by immunofluorescence. Results CLP mice showed progressive increases in SOX2OT and SOX2 mRNA levels on days 3, 7, and 14 after CLP surgery, accompanied by impaired cognitive function. Sepsis led to decrease in all neuronal markers in the hippocampus, except GFAP. Immunofluorescence confirmed the decreased numbers of BrdU+/DCX+ cells and BrdU+/NeuN+ neurons, and increased numbers of BrdU+/GFAP+ cells. SOX2OT knockdown partially inhibited the effects of CLP on levels of SOX2 and neuronal markers, neuronal populations in the hippocampus, and cognitive function. SOX2 deficiency recapitulated the effects of SOX2OT knockdown. Conclusion SOX2OT knockdown improves sepsis-induced deficits in hippocampal neurogenesis and cognitive function by downregulating SOX2 in mice. Inhibiting SOX2OT/SOX2 signaling may be effective for treating or preventing neurodegeneration in sepsis-associated encephalopathy.

Aberrant ERα signaling and altered circadian rhythms are both features of ER-positive breast cancer, however, the molecular interaction between them is still not fully understood. Herein, we analyzed the interplay between the circadian rhythm molecule DEC1 and ERα and its effect on the proliferation of ER-positive breast cancer cells, providing a new clue for clarifying the pathogenesis of breast cancer. In this study, we revealed that DEC1 negatively regulates the proliferation of ER-positive breast cancer MCF-7 cells through interaction with ERα protein. DEC1 co-localized with ERα in the nucleus of MCF7 cells, stabilized ERα protein independently of its transcriptional activity and without affecting by estrogen stimulation and inhibited the degradation of ERα mediated by CHX in a time-dependent manner. Moreover, results from luciferase reporter assay showed that overexpression of DEC1 significantly inhibits ERα-mediated transcriptional activity in a dose-dependent manner. These results together suggested that DEC1 may serve as a co-repressor of ERα in ER-positive breast cancer. Although DEC1 improved the stability of ERα and alleviated protein degradation, DEC1 inhibited the proliferation of MCF7 cells by decreasing ERα-mediated signal transduction.

Sepsis associated encephalopathy (SAE) is a severe disease secondary to sepsis, which is associated with increased mortality and causes long-term cognitive deficits in survivors. Recently, an increasing body of evidence has shown that gut microbiota is closely related to the central nervous system, and could influence brain function via microbiota-gut-brain axis. Therefore, in the occurrence and development of SAE, cholinergic anti-inflammatory pathway is one of the mechanisms by which gut microbiota could improve cognitive function. Efferocytosis, a process of eliminating apoptotic cells in the body, has anti-inflammatory effects and provides organ protection in sepsis. On the other hand, it could be enhanced by some metabolites of gut microbiota, making it another potential mechanism for gut microbiota regulating SAE. This review summarizes the mutual regulation of gut microbiota, efferocytosis and SAE, to explore potential mechanisms and therapeutic targets of SAE.

Background: Sepsis-associated encephalopathy (SAE) is one of the most serious complications of sepsis, along with brain function and cognitive behavioral changes. The process of efferocytosis with microglia was restrained in SAE rats’ hippocampus. We have previously shown that milk fat globule EGF factor 8 protein (MFG-E8) evoked efferocytosis in SAE rats’ brain, and alleviated the inflammnation in hippocampus. The present study investigated the the contribution of MFG-E8 to the brain functional connectivity (FC) of hippocampus and lateral entorhinal cortex in SAE rats by resting-state functional MRI scan.Methods: Sixty adult male Sprague Dawley rats were divided randomly into Sham operation group, cecal ligation and puncture (CLP) group, CLP+MFGE8 group, and CLP+MFGE8+Cilengitide group. After cecal ligation and puncture (CLP) surgery, MFGE8 (3.3ug) was injected intracerebroventricularly (i.c.v.) and cilengitide (10 mg/kg) was injected intraperitoneal. The Morris water maze (MWM) and open filed test (OFT) were performed continuously for five days. Rats were detected by T2-MRI and rs-fMRI scan 8 days post-surgery, then brain tissues were taken for western blotting and pathological observation by HE stained. One-way ANOVA with Tukey’s post-test of all pair of columns was employed statistical analyses.Results: MFGE8 improved performance of neurobehavioral tests in MWM test and OFT. Expression of IL-1β and the proteins of MFGE8, Rac1, and LC3 were up regulated in CLP+MFGE8 group. On the contrary, expression of IL-6, Rac1, and LC3 were down regulated in CLP+MFGE8+cilengitide group. MFGE8 significantly decreased the hyperintense region in hippocampus detected by T2-MRI, and increased ALFF value in SAE rats’ bilateral sensory cortex, motor cortex and visual cortex by rs-fMRI. In addition, MFGE8 increased FC of CA1 and LEnt in same side of cerebral hemisphere, and the FC of CA1 and LEnt was consistent with the behavior result in Morris water maze test.Conclusions: MFGE8 activated efferocytosis with microglia and improved brain function and functional connectivity between CA1 and LEnt which were reflected in behavior tests and fMRI.

BackgroundCognitive deficits are common in patients with sepsis. Previous studies in sepsis-associated encephalopathy (SAE) implicated the C-X-C chemokine receptor type (CXCR) 5. The present study used a mouse model of SAE to examine whether CXCR5 down-regulation could attenuate cognitive deficits.MethodsSepsis was induced in adult male C57BL/6J and CXCR5-/- mice by cecal ligation and puncture (CLP). At 14-18 days after surgery, animals were tested in a Morris water maze, followed by a fear conditioning test. Transmission electron microscopy of hippocampal sections was used to assess levels of autophagy. Primary microglial cultures challenged with lipopolysaccharide (LPS) were used to examine the effects of short interfering RNA targeting CXCR5, and to investigate the possible involvement of the p38MAPK/NF-κB/STAT3 signaling pathway.ResultsCLP impaired learning and memory and up-regulated CXCR5 in hippocampal microglia. CLP activated hippocampal autophagy, as reflected by increases in numbers of autophagic vacuoles, conversion of microtubule-associated protein 1 light chain 3 (LC3) from form I to form II, accumulation of beclin-1 and autophagy related gene-5, and a decrease in p62 expression. CLP also shifted microglial polarization to the M1 phenotype, and increased levels of IL-1β, IL-6 and phosphorylated p38MAPK. CXCR5 knockout further enhanced autophagy but partially reversed all the other CLP-induced effects, including cognitive deficits. Similar effects on autophagy and cytokine expression were observed after knocking down CXCR5 in LPS-challenged primary microglial cultures; this knockdown also partially reversed LPS-induced up-regulation of phosphorylated NF-κB and STAT3. The p38MAPK agonist P79350 partially reversed the effects of CXCR5 knockdown in microglial cultures.ConclusionsCXCR5 may act via p38MAPK/NF-κB/STAT3 signaling to inhibit hippocampal autophagy during sepsis and thereby contribute to cognitive dysfunction. Down-regulating CXCR5 can restore autophagy and mitigate the proinflammatory microenvironment in the hippocampus.

Sepsis-associated encephalopathy (SAE) is a serious and diffuse cerebral dysregulation with a high morbidity and mortality caused by sepsis. Mitophagy plays an important role in SAE, and microglial phagocytosis of apoptotic cells (efferocytosis) is the core of the brain regenerative response. Voltage dependent anion channel (VDAC1) is an important regulator of mitophagy. However, it remains unknown whether VDAC1 influences SAE progression by regulating mitophagy and efferocytosis. Herein, we explored the mechanism where knockdown of VDAC1 alleviated the cognitive dysfunction caused by sepsis-associated encephalopathy and further elucidated the underlying molecular mechanisms. SAE model in mice was established through caecal ligation and puncture (CLP). The increased mitophagy and decreased efferocytosis were observed by the transmission electron microscope (TEM) in the SAE model. Besides, immunoblot tests showed an interaction between autophagy and efferocytosis. Further behavior tests and TEM results indicated that knockdown of VDAC1 alleviated the cognitive dysfunction by decreasing the autophagy and increasing the efferocytosis in a PINK1/Parkin-dependent manner. Based on these results, we conclude that knockdown of VDAC1 alleviates the cognitive dysfunction in the CLP-induced SAE mouse model.

OBJECTIVE: To assess the effect of transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) on gastric insufflation during general anesthesia induction in obese patients. METHODS: Ninety obese patients (BMI 30-39.9 kg/m(2)) undergoing laparoscopic cholecystectomy under general anesthesia were randomized into 3 groups (n=30) to receive facemask pre- oxygenation followed by face mask ventilation (FMV) after administration of anesthetics (Group M), oxygenation with THRIVE (Group T), or pre-oxygenation with facemask combined with THRIVE followed continuous oxygenation with both FMV and THRIVE after administration of anesthetics (Group M+T). The patients in the latter two groups received continuous oxygen via THRIVE during tracheal intubation. All the patients received real-time ultrasound monitoring of the gastric antrum, and positive gastric insufflation (GI(+)) was defined by the presence of comet-tail artifacts. The cross-sectional area of the gastic antrum (CSA-GA) was measured by ultrasound before and after pre-oxygenation and after intubation. The patients' SpO(2), PaO(2), and PaCO(2) at admission (T(1)), 5 min after pre-oxygenation (T(2)), 5 min after medication (T(3)), and immediately after intubation (T(4)) were recorded, and the incidence of postoperative adverse events was assessed. RESULTS: The incidence of gastric insufflation was significantly higher in Group M and Group M+T than in Group T (P < 0.05). The CSA-GA was significantly greater at T(4) than at T(1) in Group M and Group M+T and in their GI(+)s ubgroups. The GI(+) subgroups in Group M and Group M+ T had significantly larger CSA-GA at T(4) than the GI(-) subgroups (P < 0.05). CSA-GA did not vary significantly during anesthesia induction in Group T (P>0.05). The incidence of grade Ⅰ gastric distension was lower but grade Ⅱ gastric distention was higher in Group M and Group M+T than in Group T (P < 0.05). Group M showed significantly greater variations of PaO(2) at T(3) and T(4) than Group T and Group M+T (P < 0.05). CONCLUSION: Ultrasound monitoring of the comet tail sign and the changes of CSA-GA in the gastric antrum is feasible and reliable for detecting gastrointestinal airflow, and in obese patients, the application of THRIVE for induction of anesthesia can ensure the oxygenation level without further increasing gastric insufflation.

Background Perioperative neurocognitive disorders (PNDs) occur frequently after surgery and worsen patient outcome. How C-X-C motif chemokine (CXCL) 13 and its sole receptor CXCR5 contribute to PNDs remains poorly understood. Methods A PND model was created in adult male C57BL/6J and CXCR5−/− mice by exploratory laparotomy. Mice were pretreated via intracerebroventricular injection with recombinant CXCL13, short hairpin RNA against CXCL13 or a scrambled control RNA, or ERK inhibitor PD98059. Then surgery was performed to induce PNDs, and animals were assessed in the Barnes maze trial followed by a fear-conditioning test. Expression of CXCL13, CXCR5, and ERK in hippocampus was examined using Western blot, quantitative PCR, and immunohistochemistry. Levels of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in hippocampus were assessed by Western blot. Results Surgery impaired learning and memory, and it increased expression of CXCL13 and CXCR5 in the hippocampus. CXCL13 knockdown partially reversed the effects of surgery on CXCR5 and cognitive dysfunction. CXCR5 knockout led to similar cognitive outcomes as CXCL13 knockdown, and it repressed surgery-induced activation of ERK and production of IL-1β and TNF-α in hippocampus. Recombinant CXCL13 induced cognitive deficits and increased the expression of phospho-ERK as well as IL-1β and TNF-α in hippocampus of wild-type mice, but not CXCR5−/− mice. PD98059 partially blocked CXCL13-induced cognitive dysfunction as well as production of IL-1β and TNF-α. Conclusions CXCL13-induced activation of CXCR5 may contribute to PNDs by triggering ERK-mediated production of pro-inflammatory cytokines in hippocampus.

Perioperative neurocognitive disorder (PND) is a common complication of elderly patients after surgery and lacks effective prevention and treatment measures. We investigated the effect and mechanism of gastrodin (GAS), a natural plant ingredient, on postoperative cognition induced by laparotomy in aged mice. Male aged (18 months) mice were subjected to laparotomy and orally treated with GAS (25, 50, and 100 mg/kg) 3 weeks before surgery and 1 week after surgery. In addition, some male aged (18 months) mice were subjected to viral vector or GSK-3β expression virus injection followed by laparotomy with or without 100 mg/kg GAS treatment. GAS improved learning and memory in aged mice after surgery. Surgery increased the levels of pro-inflammatory factors (TNF-α, IL-1β and IL-6) and decreased the level of an anti-inflammatory factor (IL-10) in the mouse hippocampus, and these changes were reversed by GAS treatment. GAS also suppressed the activation of microglia. GAS inhibited the phosphorylation of GSK-3β and Tau. Furthermore, surgery induced more serious cognitive dysfunction, inflammatory factors, activation of microglia, and phosphorylation of GSK-3β and Tau in GSK-3β overexpressing aged mice. The improvement of learning and memory, the reduction of inflammation and microglia activation, and the suppression of GSK-3β and Tau phosphorylation by GAS were prevented when GSK-3β was overexpressed in aged mice subjected to surgery. Our finding suggested that GAS exerts neuroprotective effects in aged mice subjected to laparotomy by suppressing neuroinflammation and GSK-3β and Tau phosphorylation. Thus, these findings suggest that GAS may be a promising agent for PND.

Abnormal protein acetylation and succinylation in lysine residues can cause the initiation and development of numerous different types of tumors. However, to the best of our knowledge, there is currently a lack of systematic investigation in breast cancer. Using proteomic techniques, the present study systematically investigated the two modifications of all proteins in invasive ductal carcinoma tissues to identify potential targets. The results revealed significantly higher modification levels for the majority of proteins in breast cancer tissue when compared with para-carcinomous normal tissue. The bioinformatic analysis demonstrated that either highly acetylated or succinylated proteins were significantly enriched in histone H2A.X (H2A.X) complexes and nucleophosmin (NPM1) may be the key member among them. The results of further analyses revealed that H2A.X complexes were associated with DNA damage response (DDR), and the proteomic results for protein quantification provided further evidence for the abnormal DDR condition in breast cancer tissues. Later, the western blotting results validated the high acetylation and succinylation levels of the majority of proteins, including the modification of NPM1 and its correlation with cell viability. Finally, the upregulation of H2A.X in breast cancer tissues further demonstrated the association between H2A.X complex modification and DDR in breast cancer. Overall, the present study systematically investigated the protein acetylation and succinylation in breast cancer and provided evidence to support H2A.X complexes as potential targets. These results broaden the horizon for breast cancer investigation and link it with epigenetics.

Mitochondrial dysfunction is involved in the process of sepsis and leads to the accumulation of reactive oxygen species (ROS), which breaks cellular homeostasis and activates the downstream inflammatory cascade. The autophagic removal of ROS is a well-established cellular adaptive mechanism. Adiponectin is an adipocytokine that plays an important role in metabolic and inflammatory regulation. In this study, we investigated the anti-inflammatory effect of adiponectin in a sepsis model and its potential association with autophagy. We induced RAW 264.7 macrophages with lipopolysaccharide (LPS) to set up the sepsis model and treated them with adiponectin, an inhibitor of the nucleotide-binding domain and leucine-rich repeat containing family pyrin domain–containing 3 (NLRP3), ROS, Complex I, and an autophagy inhibitor. Flow cytometry and western blot analysis were performed to detect the expression levels of ROS, NLRP3, interleukin-1 beta (IL-1β), microtubule-associated protein 1A/1B-light chain 3II/I (LC3II/I), and adenosine monophosphate–activated protein kinase (AMPK). Expression levels of NLRP3, IL-1β, and ROS were significantly increased following LPS induction, and adiponectin reversed this up-regulation. Meanwhile, adiponectin also enhanced the expression of LC3II/I, an autophagosome marker, but an autophagy inhibitor and AMPK inhibitor depleted (reversed) the anti-inflammatory and antioxidant effect of adiponectin. Taken together, in the LPS-induced sepsis model, adiponectin alleviated the inflammatory reaction by reducing ROS production, possibly by enhancing autophagy via the AMPK pathway. The activation of autophagy may therefore be a key mechanism by which adiponectin ameliorates the inflammatory reactions of sepsis.

Parasthesia free stimulation, such as high frequency and burst have been demonstrated as effective therapies for neuropathic pain. The aim of this meta-analysis was to evaluate the efficacy and safety of conventional spinal cord stimulation (SCS) in the treatment of refractory angina pectoris (RAP). Relevant randomized controlled trial (RCT) studies that investigated SCS for patients with RAP were comprehensively searched in Medline, Pubmed, Embase, and Cochrane Library. Five meta-analyses were performed examining the changes in CCS (Canadian Cardiovascular Society) classes, exercise time, Visual Analogue Scale score, Seattle Angina Questionnaire, and nitroglycerin-use in RAP patients after SCS therapy. We analyzed standardized mean differences (MD) and 95% confidence intervals (CI) for each outcome by Review Manager 5.0 and STATA 12.0. A total of 12 RCTs involving 476 RAP patients were identified. A trend of reduction in the angina frequency (MD=-9.03, 95% CI: -15.70 to -2.36) and nitroglycerin consumption (MD=-0.64, 95%CI: -0.84 to -0.45) could be observed in the SCS group. Compared to the control group, SCS showed benefit on increasing exercise time (MD=0.49, 95% CI: 0.13 to 0.85) and treatment satisfaction (MD=6.87, 95% CI: 2.07 to 11.66) with decreased VAS score (MD=-0.50, 95% CI: -0.81 to -0.20) and disease perception (MD=-8.34, 95% CI: -14.45 to -2.23). However, the result did not reach the significance level in terms of physical limitation (95% CI: -8.75-3.38; P=0.39) or angina stability (95% CI: -7.55-3.67; P=0.50). The current meta-analysis suggested that SCS was a potential alternative in the treatment of PAP patients. Further investigation for finding the appropriate intensity of stimulation is required before this treatment should be widely recommended and applied.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0.

The present study aimed to investigate cognitive dysfunction in the hippocampus induced by sepsis-associated encephalopathy (SAE) via acetylation of cyclophilin D (CypD) and opening of mitochondrial permeability transition pore. It also explored whether activating sirtuin 3 (SIRT3) can mediate deacetylation of CypD and prevent the development of SAE. Male mice were randomly assigned to six groups: sham group, cecal ligation puncture group, CypD siRNA transfection (CypD-si) group, CypD control siRNA transfection (CypD-c) group, SIRT3 overexpression vector pcDNA3.1 (SIRT3-p) group, and SIRT3 empty vector pcDNA3.1 (SIRT3-v) group (n = 18). The CypD-si and CypD-c groups were transfected with CypD siRNA and CypD control siRNA, respectively. The SIRT3-p and SIRT3-v groups were injected with SIRT3 pcDNA3.1 and vector pcDNA3.1, respectively. The learning and memory function was assessed using the learning version of the Morris water maze test. Then, cell apoptosis and the levels of CypD, acetylated CypD, SIRT-3, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and caspase-3 in the hippocampus were determined. The levels of CypD and acetylation of CypD increased in the hippocampus induced by SAE. Increasing SIRT3 and decreasing CypD can attenuate cognitive impairment and neuroapoptosis, and protect the integrity of mitochondrial membrane from damage and restore the protein expressions of IL-6, TNF-α, and caspase-3. Activating SIRT3-mediated deacetylation of CypD attenuated learning and memory dysfunction induced by SAE.

Sepsis is considered to be the most common contributing factor in the development of acute kidney injury (AKI). However, the mechanisms by which sepsis leads to AKI remain unclear. Autophagy is important for a number of fundamental biological activities and plays a key role in numerous different diseases. The present study demonstrated that autophagy is involved in sepsis-induced kidney injury and upregulates ATG7, LC3 and Beclin I. In addition, it was revealed that miR-526b is decreased in sepsis-induced kidney injury, and miR-526b was identified as a direct regulator of ATG7. Furthermore, the present study investigated the biological effects of ATG7 inhibited by miR-526b and demonstrated that miR-526b could promote cell viability by inhibiting autophagy, potentially through targeting ATG7. In conclusion, the present study highlights the role of autophagy in sepsis-induced AKI, and miR-526b in regulating autophagy through targeting ATG7, which suggested that miR-526b may be a molecular therapeutic target for sepsis-induced AKI.

In this study, we investigated the potential role of C-X-C chemokine receptor type (CXCR) 5 in neurocognitive function in a mouse model of sepsis-associated encephalopathy (SAE). Adult male C57BL/6J mice received intracerebroventricular injections of small interfering RNAs (siRNAs) against CXCR5 or scrambled control siRNA. After 3 days, SAE was induced by cecal ligation and puncture (CLP, n = 16 per group). Memory and learning ability were tested using the Morris water maze (MWM) on days 5–9 after CLP. Hippocampal expression of CXCR5, interleukin (IL)-1β and IL-6 were measured by western blot. Cell proliferation and the numbers of immature and mature neurons in the dentate gyrus were assessed by immunohistochemistry. CLP mice had deficits in memory and learning, as shown by increased latency in the MWM training sessions and decreased time spent in and crossing the target quadrant on day 9. CLP also increased the number of proliferating and immature neurons and decreased the number of mature neurons. This was accompanied by increased expression of CXCR5, IL-1β and IL-6 in the hippocampus. CXCR5 knockdown attenuated the memory and learning deficits induced by CLP and partially reversed the effects of CLP on numbers of proliferating, immature and mature neurons, and on expression of IL-1β and IL-6 in the hippocampus. These results suggest that CXCR5 knockdown can attenuate sepsis-induced deficits in hippocampal neurogenesis and cognitive function in mice with SAE.

Perioperative neurocognitive disorder (PND) is a common complication that lacks effective prevention and treatment measures. Neuroinflammation is considered to be one of the important mechanisms of PND. In this study, we investigated the effect and mechanism of anthocyanins (ANT), a natural plant ingredient, on postoperative cognition and neuroinflammation. Mice were subjected to laparotomy and treated with ANT (50–100 mg/kg, orally) 4 weeks before surgery and then once per day for 7 days after surgery. Morris water maze and fear conditioning tests were used to evaluate learning and memory function. Western blotting, RT-PCR and immunofluorescence were used to test the neuroprotective effects and mechanism of ANT. The results showed that ANT improved learning and memory in mice after surgery. ANT also inhibited MLK3 activation and its downstream JNK and p38 MAPK signaling cascades. Moreover, the inhibitor of MLK3 could mimic the effects of ANT. In addition, treatment with ANT significantly reduced neuroinflammation and microglia activation. In conclusion, MLK3 represents a novel target in surgery-induced neuroinflammation and cognitive dysfunction. ANT could inhibit the activation of MLK3 and be a promising agent for the prevention and treatment of PND.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies. Studies have shown that engulfment and cell motility 3 (ELMO3) is highly expressed in NSCLC and can be used as a novel biomarker, but its underlying mechanism remains to be explored. The aim of this study was to investigate the mechanism by which ELMO3 may be down-regulated by COX-2 inhibitors to inhibit NSCLC. NSCLC tissue and adjacent normal lung tissue from 24 patients were used to detect the mRNA and protein expression of ELMO3, COX-2, and other related proteins by Western blot, RT-PCR, and Immunohistochemical analysis. Lewis Lung carcinoma (LLC) cells were used to investigate the effects and the mechanism of siELMO3 and COX-2 inhibitor. C57BL/6 mice inoculated with LLC cells by subcutaneous (s.c.) injection were used to detect the in vivo effects of cox-2 inhibitor. The expression of ELMO3 and cyclooxygenase-2 (COX-2) in human NSCLC tissues was significantly increased compared with that in the adjacent normal tissues. ELMO3 exhibited a positive correlation with COX-2 expression. Moreover, knockdown of ELMO3 suppressed the epithelial-mesenchymal transition (EMT), adhesion, and metastasis of Lewis lung carcinoma (LLC) cells. Importantly, Parecoxib, a selective inhibitor of COX-2, significantly reduced the expression of ELMO3 and EMT in LLC cells and LLC-bearing mice. Furthermore, it could inhibit the growth, adhesion and metastasis of LLC cells in vitro. Our results demonstrate that down regulation of ELMO3 suppressed growth and metastasis of lung cancer by inhibiting EMT. Parecoxib could reduce ELMO3 expression and suppress growth and metastasis of lung cancer, which might be a useful chemotherapeutic agent for inhibiting metastasis and recurrence of NSCLC.

It is still difficult to treat sepsis-associated encephalopathy (SAE) which is a diffuse brain dysfunction caused by sepsis, with excessive activation of microglia as one of the main mechanisms. Ras-related C3 botulinum toxin substrate 1 (RAC1) is proven to be a key molecule in the inflammatory signaling network. By using microglial cell line BV-2 and a mouse model of cecal ligation puncture (CLP), we herein evaluated the effects of β-elemene, an extract of Curcuma zedoaria Rosc., on RAC1 signaling in microglia, as well as the mechanism. β-Elemene decreased the expressions of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6) and attenuated translocation of nuclear factor-κB (NF-κB) p65 from the cytosol to the nucleus of BV-2 cells after lipopolysaccharide (LPS) treatment. It also inhibited the activation of RAC1, mixed-lineage protein kinase 3 (MLK3) and p38 mitogen-activated protein kinase (MAPK). The phosphorylation of the RAC1 Ser71 site was increased by β-elemene. Moreover, the learning and memory abilities of CLP mice in the water maze test and fear conditioning test were improved after β-elemene treatment. It reduced the expression of the microglial marker IBA1, significantly increased RAC1 Ser71 phosphorylation, and suppressed RAC1/MLK3/p38 signaling activation and inflammatory response in the hippocampus. In conclusion, β-elemene effectively alleviated SAE in mice and inhibited the RAC1/MLK3/p38 signaling pathway in microglia, probably as a safe and eligible potential candidate for clinical SAE treatment.

Background: The purpose of this study was to evaluate the effects of adding ketamine to propofol on cognitive functions in patients undergoing sedation for colonoscopy. Methods: In this randomized, double-blinded, and controlled study, 200 patients were randomly allocated to ketamine/propofol admixture group (Group KP, n = 100), and propofol group (Group P, n = 100). Patients in Group KP received 0.25 mg/kg of ketamine and 0.5 mg/kg of propofol. Patients in Group P received 0.5 mg/kg propofol. Cognitive functions were measured using CogState battery before and after the colonoscopy procedure. Ninety five patients in Group KP and 92 patients in Group P had completed the CogStates tests and were included in the data analysis. Results: Compared with before procedure baseline, the performance on detection and identification tasks were significantly impaired after the procedure in both Group KP (P = .004, P = .001) and Group P patients (P = .005, P

Caffeic acid phenethyl ester attenuates neuropathic pain by suppressing the p38/NF-kappaB signal pathway in microglia Hao Cheng, Yong Zhang, Weiping Lu, Xianzhong Gao, Chenjie Xu, Hongguang Bao Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China Background: Management of neuropathic pain is still a clinical challenge. Evidence has accumulated indicating that propolis is effective in attenuating neuropathic pain; however, the mechanism is not fully understood. Our present study investigated the effects and the possible mechanism of caffeic acid phenethyl ester (CAPE), the main ingredient of propolis, in improving neuropathic pain via its inhibition on p38/NF-κB signal pathway in microglia. Materials and methods: Chronic constriction injury (CCI) mice model and the microglial cell line BV-2 were used to investigate the effects and the mechanism of CAPE. Cell signaling was measured by real-time PCR, Western blotting and immunofluorescence assay. Results: CAPE relieved neuropathic pain behaviors induced by CCI in mice. CAPE also inhibited CCI-induced activation of microglia. Furthermore, CAPE suppressed the phosphorylation of p38 mitogen-activated protein kinase, inhibited the translocation of NF-κB and decreased the expression of proinflammatory cytokines tumor necrosis factor-α, IL-1β and IL-6. Conclusion: CAPE was found to be an effective and safe drug candidate for alleviating neuropathic pain by its powerful inhibition on the P38/NF-κB signal pathway. Keywords: caffeic acid phenethyl ester, NF-κB, neuropathic pain, microglia

MicroRNA-485-5p (miR-485-5p) has been reported to be involved in the development and progression of human cancers; however, its role in glioma remains unclear. In the present study, we found that miR-485-5p was significantly down-regulated in both glioma tissues and cell lines. Functional experiments indicated that enhanced expression of miR-485-5p attenuated glioma cell proliferation in vitro and in vivo, and induced glioma cells cycle arrest in G1. MiR-485-5p was found to directly bind to the 3'-UTR of paired box 3 (PAX3) and decrease its expression of protein level, which further inhibits the proliferation of glioma. The decreasing of PAX3 was found to lead to the accumulation of p-JNK. Mechanistic studies revealed that restoring the expression of PAX3 alleviated miR-485-5p-induced inhibition of proliferation of glioma cells. Taken together, these findings suggest that PAX3 modulation by miR-485-5p has an important role in regulating glioma proliferation, and miR-485-5p might be a novel therapeutic target for glioma.

Coal gangue is regarded as a potential source of aluminum and silica. In this work, acid leaching behaviors of aluminum, iron, and silica in coal gangue were investigated using hydrochloric acid as leaching agent. Chemical and mineralogical compositions of coal gangue and the leached residue were determined by X-ray diffraction (XRD), X-ray fluorescence, and Fourier transform infrared spectroscopy. XRD results indicated that kaolinite and boehmite were the predominant minerals in coal gangue. During elevated temperature acid leaching, mineral phases gradually decomposed, and aluminum and iron ions were dissolved in the acid leaching solution. However, the carbonaceous material and the product of silica were not dissolved in acid and were abundant in leached residue. The extraction efficiency of Al and Fe from coal gangue depended on coal gangue size, liquid–solid ratio, temperature and leaching time. Extraction efficiency of Al and Fe increased with increased liquid–solid ratio, temperature, and leaching time. Under the same conditions, SiO 2 content in the ash of leached residue also increased. The optimum technological conditions for aluminum and iron extraction were obtained with a coal gangue size of 74 μm at a liquid–solid ratio of 3:1 to react at 180 °C for 4 h. After evaporation and crystallization, selective precipitation by adding sodium hydroxide solution, carbon decomposition, and calcination, alumina with a purity of 98.70% was prepared from acid leaching solution. Finally, a suitable amount of low ash anthracite was introduced to the leached residue, and the product of SiC was produced by carbon thermal reduction method. The product had a yield and purity of 72.72% and 76.01%, respectively.

Background It has been reported that postoperative cognitive dysfunction (POCD) is correlated with the degeneration of the central nervous system, oxidative stress, inflammation, and endocrine and immune dysfunction. Increased age, predisposed comorbidity, long surgery time, and prolonged stay in the intensive care unit have been reported to be risk factors for developing POCD for cardiac surgery. In the present study, the risk factors of early POCD after colorectal surgery were investigated. Methods Eighty patients, who provided informed consents for their participation in this study, were enrolled and received colorectal surgery under general anesthesia. Neuropsychological tests were performed preoperatively and on postoperative day seven. The risk factors for POCD were analyzed using a multivariate logistic regression model. Results Nineteen patients were diagnosed with POCD (24.7%). Diabetes history (OR = 8.391 [2.208–31.882], P = 0.012), fasting over 3 days after surgery (OR = 5.236 [1.998–13.721], P = 0.001) and an SIRS score of > 3 on the second day after surgery (OR = 6.995 [1.948–25.111], P = 0.003) were risk factors for early POCD in colorectal cancer patients. Conclusion The risk factors for early POCD after colorectal surgery included diabetes history, fasting over 3 days, and an SIRS score of > 3 on the second day.

To explore the effect of prostaglandin E2 (PGE2) on the expression of high mobility group box-1 protein (HMGB1) in peritoneal macrophages of septic mice and its possible mechanisms. Methods: The mouse peritoneal macrophages were isolated and cultured by conventional methods.The model of inflammation was established by using lipopolysaccharide (LPS) to incubate with mouse peritoneal macrophages. The PGE2, prostaglandin E receptor (EP) 4 agonist, EP4 RNAi, and DN.CREB inhibitory plasmid were used to interfere with the LPS-treated mouse peritoneal macrophage. The levels of HMGB1 was determined by Western blot. Results: Compared with LPS alone treatment, the expression of HMGB1 in peritoneal macrophages was increased obviously after 24 h by treatment with PGE2 and LPS, and it was also increased after the combined treatment of EP4 receptor agonist with LPS for 24 h (both P0.05); compared with the PGE2+LPS treatment, the level of HMGB1 was decreased after knockdown of EP4 receptor expression (P0.05); compared with EP4 receptor agonist +LPS treatment, there was no difference in HMGB1 levels in mice after the treatment with DN.CREB plasmid to suppress CREB function (P0.05); compared with LPS alone treatment, the combined treatment of EP4 receptor agonist with LPS for 24 h could up-regulate the phosphorylation of epidermal growth factor receptor (EGFR) and protein kinase B (Akt) thr308 (P0.05), which were blocked by EGFR inhibitor. Once Akt specific inhibitor was used before EP4 and LPS treatment, the expression of HMGB1 was declined (P0.05). Conclusion: PGE2 can up-regulate the expression of HMGB1 in sepsis of peritoneal macrophages through EP4 receptor, which may be related to the activation of EGFR/PI3K/Akt signaling pathway.目的：探讨前列腺素E2(prostaglandin E2，PGE2)对脂多糖(lipopolysaccharide，LPS)诱导的小鼠腹腔巨噬细胞高迁移率族蛋白1(high mobility group box-1 protein，HMGB1)表达的影响及其可能的机制。 方法：运用常规方法提取、培养小鼠腹腔巨噬细胞；采用LPS诱导小鼠腹腔巨噬细胞构建炎症模型；使用PGE2和前列腺素E受体(prostaglandin E receptor，EP)激动剂 、RNAi技术下调巨噬细胞EP4受体表达、抑制性表达DN.CREB质粒处理LPS诱导的小鼠腹腔巨噬细胞，并通过Western印迹测定HMGB1表达水平。结果：与单纯应用LPS处理巨噬细胞比较，PGE2联合LPS共孵育小鼠腹腔巨噬细胞24 h后，HMGB1蛋白的表达水平明显上升，且EP4受体激动剂联合LPS处理小鼠腹腔巨噬细胞24 h后HMGB1蛋白的表达亦增加(均P0.05)；与PGE2+LPS联合处理比较，应用RNAi技术可下调小鼠腹腔巨噬细胞EP4受体表达，再给予外源性PGE2加LPS处理，HMGB1水平下降(P0.05)；使用DN.CREB质粒抑制cAMP结合元件结合蛋白(cAMP respondse element bound protein，CREB)后再加上EP4受体激动剂联合LPS处理，与EP4受体激动剂+LPS处理比较，HMGB1水平差异无统计学意义(P0.05)；与单纯应用LPS 比较，EP4受体激动剂联合LPS处理小鼠腹腔巨噬细胞可上调表皮生长因子受体(epidermal growth factor receptor，EGFR)及蛋白激酶B(protein kinase B，PKB，亦称Akt)thr308磷酸化水平(均P0.05)；使用EGFR抑制剂预处理细胞后，Akt thr308磷酸化水平及HMGB1表达均降低(均P0.05)；采用Akt特异性抑制剂预处理细胞后，HMGB1表达降低(P0.05)。结论：PGE2可以通过EP4受体上调LPS诱导的小鼠腹腔巨噬细胞HMGB1的表达，且这一作用与激活EGFR/磷脂酰肌醇3激酶(PI3K)/Akt信号通路有关。.

Dexmedetomidine attenuates renal ischaemia and reperfusion (I/R) injury, but its mechanism of action is unclear. As sirtuin 3 (SIRT3) activation can alleviate acute kidney injury, we investigated whether dexmedetomidine acts through SIRT3 to reduce renal I/R injury.The potential involvement of SIRT3 in dexmedetomidine attenuation of renal I/R injury was tested in HK2 cells subjected to hypoxia/reoxygenation and C57BL/6J mice subjected to renal I/R. A short interfering RNA targeting SIRT3 was used in some experiments to examine the potential role of SIRT3. Cell death and mitochondrial membrane potential (Δψm) were analysed in cultured cells. Mitochondrial damage in mice was assessed using electron microscopy and markers for renal function. Expression of cyclophilin D, cytochrome c, and SIRT3, and the level of cyclophilin D acetylation were determined.Hypoxia/reoxygenation of HK2 cells increased cell death, cytochrome C expression, and cyclophilin D acetylation, and decreased Δψm and SIRT3 expression (P0.05). Dexmedetomidine attenuated these changes. The dexmedetomidine effects were enhanced by SIRT3 overexpression and eliminated by SIRT3 knockdown. I/R in mice damaged renal function, and increased histological lesions, mitochondrial damage, cytochrome c expression, and cyclophilin D acetylation, while SIRT3 activity was decreased by 51% (P0.05). Dexmedetomidine inhibited these changes in mice expressing normal levels of SIRT3, but not in SIRT3-knockdown mice.Dexmedetomidine appears to act, at least in part, by up-regulating SIRT3 to inhibit mitochondrial damage and cell apoptosis and thereby protect against renal I/R injury.

MicroRNA (miRNA) are emerging as critical regulators of neuropathic pain development. Neuroinflammation contributes to the development of neuropathic pain. miR‑142‑3p has been characterized as an inflammation‑related miRNA in various pathological processes. However, little is known about the role of miR‑142‑3p in neuroinflammation and neuropathic pain. The present study aimed to investigate the function of miR‑142‑3p in neuropathic pain by creating a murine model using spinal nerve ligation (SNL). A significant reduction in miR‑142‑3p expression was observed in the dorsal root ganglion of mice with SNL (P

Currently, advanced glycation end product (RAGE) is receiving much attention in carcinogenesis research due to its involvement in cancer progression and metastasis. We therefore sought to examine the association of circulating soluble RAGE (sRAGE) with all types of cancer by a meta-analysis. The PubMed and EMBASE databases were searched before March 1, 2014. Data and study quality were assessed in duplicate. Effect estimates were expressed as weighted mean difference (WMD) and its 95 % confidence interval (CI). Altogether, nine eligible articles including 1,337 cancer patients and 1,839 controls were analyzed. The overall analysis indicated that circulating sRAGE was remarkably reduced by 222.07 pg/ml in cancer patients compared with controls (95 % CI: −373.77 to −70.37; P = 0.004), with heterogeneity and without publication bias. In subgroup analyses, this reduction was weakened yet still significant in prospective studies (WMD = −87.62; 95 % CI: −138.60 to −36.63; P = 0.001) with improved heterogeneity (I 2 = 56.5 %; P = 0.056). Restricting analyses to the large studies (total number of subjects ≥200) identified significant reduction of circulating sRAGE in cancer patients relative to controls (WMD = −231.34; 95 % CI: −450.10 to −12.58; P = 0.038). Further meta-regression analysis showed that smoking status explained some part of heterogeneity for the association of circulating sRAGE with cancer risk (regression coefficient: −67.02; P = 0.046). Our findings demonstrate a protective role of circulating sRAGE in the development of cancer, especially in patients without diabetes mellitus or with normal renal function.

Background Although photoplethysmography and cerebral state index (CSI) have been used as indices in monitoring vital signs perioperatively, there are only a few reports comparing the performance of photoplethysmography with CSI in monitoring anaesthesia depth. The aim of the present study was to clarify features of photoplethysmography in monitoring balanced general anesthesia compared with CSI. Material/Methods Forty-five patients undergoing elective operation under general anaesthesia were enrolled in this study. Anaesthesia was induced with target-controlled infusion propofol. The photoplethysmogram, CSI, Modified Observer’s Assessment of Alertness/Sedation Scale (MOAAS), and mean arterial pressure (MAP) were continuously monitored and recorded. Finger photoplethysmogram amplitude (PPGA) and pulse beat interval (PBI) were calculated off-line. Results For the period of time from pre-induction to pre-intubation, the coefficient of correlation between MOAAS and CSI was higher than those between MOAAS and PPGA, PBI, and MAP. CSI showed higher prediction probabilities (Pk) to differentiate the levels of MOAAS than did PPGA, PBI, and MAP. PPGA, PBI, and MAP values showed significant differences between before and after intubation, as well as pre- and post-incision (P0.05). Conclusions The present study shows that photoplethysmography-derived parameters appear to be more suitable in monitoring the nociceptive component of balanced general anesthesia, while CSI performs well in detecting the sedation or hypnotic component of balanced general anesthesia.

Background Pain on injection is an acknowledged adverse effect (AE) of propofol administration for the induction of general anesthesia. Flurbiprofen axetil has been reported to reduce the pain of injection. However, results of published papers on the efficacy of flurbiprofen axetil in managing pain on injection of propofol are inconsistent. Material/Methods We conducted a comprehensive meta-analysis of studies to appraise the efficacy and safety of flurbiprofen axetil for controlling pain induced by propofol injection. The pooled risk ratio (RR) with corresponding 95% confidence intervals (CI) was calculated employing fixed- or random-effects models, depending upon the heterogeneity of the included trials. Results Compared with the placebo group, flurbiprofen axetil allows more patients to have no pain (RR 3.51, 95% CI 2.22–5.55, p=0.000), and decreases the cumulative number of patients with mild, moderate, and severe pain on injecting propofol (RR 0.70, 95% CI 0.58–0.86, p=0.000; RR 0.59, 95% CI 0.46–0.75, p=0.000; RR 0.25, 95% CI 0.16–0.38, p=0.000, respectively). In the stratified analysis by the doses, flurbiprofen axetil at a dose of over 50 mg was found to be effective in reducing propofol-induced pain on injection; however, there were no significant differences in relieving pain between treatment and placebo groups with flurbiprofen axetil at a dose of 25 mg. In terms of drug safety, there were no adverse effects (AEs) reported between flurbiprofen axetil-based regimens and placebo regimens. Conclusions Flurbiprofen axetil, an injectable prodrug of flurbiprofen, can significantly prevent or relieve the pain induced by propofol injection. More studies are required to assess its adverse effects.