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With the development of technology, more infants receive general anesthesia for surgery, other interventions, or clinical examination at an early stage after birth. However, whether general anesthetics can affect the function and structure of the developing infant brain remains an important, complex, and controversial issue. Sevoflurane is the most-used anesthetic in infants, but this drug is potentially neurotoxic. Short or single exposure to sevoflurane has a weak effect on cognitive function, while long or repeated exposure to general anesthetics may cause cognitive dysfunction. This review focuses on the mechanisms by which sevoflurane exposure during development may induce long-lasting undesirable effects on the brain. We review neural cell death, neural cell damage, impaired assembly and plasticity of neural circuits, tau phosphorylation, and neuroendocrine effects as important mechanisms for sevoflurane-induced developmental neurotoxicity. More advanced technologies and methods should be applied to determine the underlying mechanism(s) and guide prevention and treatment of sevoflurane-induced neurotoxicity. 1. We discuss the mechanisms underlying sevoflurane-induced developmental neurotoxicity from five perspectives: neural cell death, neural cell damage, assembly and plasticity of neural circuits, tau phosphorylation, and neuroendocrine effects. 2. Tau phosphorylation, IL-6, and mitochondrial dysfunction could interact with each other to cause a nerve damage loop. 3. miRNAs and lncRNAs are associated with sevoflurane-induced neurotoxicity.

Abstract: Intestinal ischemia-reperfusion injury is a relatively common clinical condition that seriously threatens the prognosis of patients; however, the exact mechanism of intestinal ischemia-reperfusion injury has not been clarified. Recent studies have found that noncoding RNAs, including but not limited to lncRNA, circRNA, and miRNA, play an important role in the pathogenesis of intestinal ischemia-reperfusion. The findings cited in this paper reveal the expression, function, and mechanism of ncRNAs during intestinal ischemia-reperfusion. The mechanistic roles of noncoding RNAs in the occurrence and development of intestinal ischemia-reperfusion are discussed, including cell proliferation, autophagy, oxidative stress, apoptosis, oxidative stress, iron death, and many other aspects. However, many unknown mechanisms of association between ncRNAs and intestinal ischemia-reperfusion remain to be investigated.

Hypoxia-inducible factor 1-α (HIF-1α) mediates the occurrence and development of renal diseases and fibrosis. In the process, dysregulated cellular metabolism was suggested to be involved in several pathological processes. Here, we found that HIF-1α expression was increased in the early stage of renal fibrosis, and significant metabolic remodeling was triggered. Epigenetic events that drive diseases were characterized previously. Our study showed that ten-eleven translocation-2 (TET2) was upregulated in both renal fibrosis models and metabolite-treated samples. Furthermore, we found that the promoter of α-SMA was hypomethylated at CpG sites, which promoted the expression of α-SMA and the occurrence of renal fibrosis. HIF-1α inhibition alleviated renal fibrosis development by improving metabolic remodeling and TET2 activation. Our studies provide novel insight into HIF-1α-mediated metabolic remodeling in the pathogenesis of renal fibrosis and propose a concept that targets this pathway to treat fibrotic disorders.

Intestinal ischemia-reperfusion (I/R) injury is a condition in which tissue injury is aggravated after ischemia due to recovery of blood supply. Bone marrow mesenchymal stem cell-derived exosome (BMSC-exo) showed a positive effect on I/R injury. This study aimed to investigate the effects and possible mechanism of BMSC-exo on intestinal I/R injury based on pyroptosis. BMSC-exos were isolated by super-centrifugation methods. Cell proliferation and apoptosis in the cell model, and intestinal barrier injury in the mouse model were analyzed to explore the effects of BMSC-exo on intestinal I/R, and inflammatory cytokines and pyroptosis-related proteins were analyzed to explore the effects of BMSC-exo on pyroptosis. In addition, miRNA microarray sequencing was used to analyze the differentially expressed miRNA in the regulation of BMSC-exo in intestinal I/R to further elucidate the mechanism. The results showed that BMSC-exo effectively reduced cell apoptosis, alleviated intestinal barrier injury, and regulated the expression of inflammatory cytokines and pyroptosis-related protein, suggesting that BMSC-exo may alleviate intestinal I/R injury by regulating pyroptosis in vitro and in vivo. In addition, the differentially expressed miRNA screened by miRNA microarray sequencing was miR-143-3p. Bioinformatics analysis predicted that there was a binding site between miR-143-3p and MyD88, and dual-luciferase reporter assay confirmed that miR-143-3p could directly target MyD88 and regulate its expression. Further studies verified that miR-143-3p may regulate pyroptosis by regulating NLRP3 through the TLR4/MyD88/NF-кB pathway and participate in BMSC-exo to alleviat intestinal I/R. In conclusion, this study found that BMSC-exo alleviated intestinal I/R by regulating pyroptosis through the miR-143-3p/MyD88/NF-кB/NLRP3 axis.

Resumo Introducao e objetivos Os mecanismos de neurotoxicidade dos anestesicos locais sao complexos. A apoptose e a autofagia sao mecanismos altamente organizados que mantem a homeostase celular durante o estresse. Estudos revelam que a ativacao da autofagia atua como mecanismo de protecao in vitro. Nao esta claro se a autofagia tambem desempenha essa funcao in vivo. O objetivo deste estudo foi analisar o papel da autofagia na neurotoxicidade induzida por anestesico local e esclarecer o mecanismo dessa neurotoxicidade utilizando um modelo de injecao intratecal em ratos. Metodos Dezoito ratos Sprague‐Dawley machos adultos saudaveis foram divididos aleatoriamente em tres grupos. Antes de receber a injecao intratecal de bupivacaina a 1%, cada rato recebeu injecao intraperitoneal de veiculo ou rapamicina (1 mg.kg‐1) uma vez ao dia durante 3 dias. As alteracoes patologicas foram examinadas por coloracao com Hematoxilina e Eosina (HE). A apoptose foi analisada por coloracao com o metodo dUTP Nick‐End Labeling (TUNEL) mediado por TdT. A expressao de caspase‐3, Beclin1 e LC3 foram examinadas por coloracao Imunohistoquimica (IHQ). A expressao de Beclin1 e LC3 e a razao LC3‐II/LC3‐I foram detectadas por analise de western blot. Resultados Apos a injecao intratecal de bupivacaina, ocorreu lesao patologica nos neuronios da medula espinhal e os niveis de apoptose e caspase‐3 aumentaram. A ativacao da autofagia causada pela rapamicina mitigou de forma expressiva as alteracoes patologicas e diminuiu os niveis de apoptose e caspase‐3, aumentando a expressao de LC3 e Beclin1 e a razao LC3‐II/LC3‐I. Conclusoes O aumento da autofagia diminui a apoptose dependente da caspase‐3 e melhora a sobrevivencia neuronal in vivo. A ativacao da autofagia pode ser uma estrategia terapeutica potencial para a neurotoxicidade induzida por anestesicos locais.

Cadmium (Cd) is one of the toxic heavy metals which is confirmed to be related to male sterile. Here, confocal Raman spectroscopy was employed to detect biomolecular composition and changes in testis under acute and chronic Cd treatment. Specific Raman shifts associated with mitochondria, nucleic acids, proteins, lipids, and cholesterol were identified which were distinguishing among groups undergoing different Cd treatment times. Supporting evidences were provided by conventional experimental detections. The relevant biochemical parameters, pathological changes, and protein expression related to testosterone synthesis were all changed and consistent with Raman spectrum information. In conclusion, confocal Raman spectroscopy presents a reliable data and provides a novel method which is expected to be a promising strategy in reproduction toxicity research.

Background Intestinal ischemia–reperfusion injury (IRI) causes localized and distant tissue lesions. Multiple organ failure is a common complication of severe intestinal IRI, leading to its high rates of morbidity and mortality. Thus far, this is poorly treated, and there is an urgent need for new more efficacious treatments. This study evaluated the beneficial effects of mesenchymal stem cells (MSCs) therapy on intestinal IRI using many animal experiments. Methods We conducted a comprehensive literature search from 4 databases: Pubmed, Embase, Cochrane library, and Web of science. Primary outcomes included the survival rate, Chiu’s score, intestinal levels of IL-6, TNF-α and MDA, as well as serum levels of DAO, D-Lactate, and TNF-α. Statistical analysis was carried out using Review Manager 5.3. Results It included Eighteen eligible researches in the final analysis. We demonstrated that survival rates in animals following intestinal IRI were higher with MSCs treatment compared to vehicle treatment. Besides, MSCs treatment attenuated intestinal injury caused by IRI, characterized by lower Chiu’s score (− 1.96, 95% CI − 2.72 to − 1.19, P P = 0.0002), TNF-α (− 3.00, 95% CI − 4.74 to − 1.26, P = 0.0007)) and oxidative stress (MDA (− 2.18, 95% CI − 3.17 to − 1.19, P P P P Conclusions Taken together, these studies revealed that MSCs as a promising new treatment for intestinal IRI, and the mechanism of which may be associated with inflammation, oxidative stress, apoptosis, and pyroptosis. However, further studies will be required to confirm these findings.

Dexmedetomidine (Dex) can protect the intestine against ischemia/reperfusion (I/R)-induced injury. Sirtuin 1 (SIRT1) pathway, which could be activated by Dex, was reported to inhibit I/R injury. Pyroptosis plays an important role in intestinal diseases. We aimed to investigate whether Dex could attenuate pyroptosis of hypoxia/reoxygenation (H/R)-induced intestinal epithelial cells via activating SIRT1. The intestinal epithelial cell line IEC-6 with or without SIRT1 knockdown after H/R treatment was exposed to Dex, then cell viability, endoplasmic reticulum stress (ERS), apoptosis, pyroptosis, inflammatory cytokines production and SIRT1 expression were detected. Results showed that Dex treatment had no significant effect on IEC-6 cell viability but rescued the H/R-reduced cell viability. The expression of proteins involved in ERS including Grp78, Gadd153 and caspase 12 was enhanced upon H/R stimulation, but was reversely reduced by Dex. The cell apoptosis increased by H/R was also decreased by Dex. Additionally, Dex inhibited pyroptosis and inflammation, which were markedly promoted upon H/R stimulation. The expression of SIRT1, which was reduced after H/R treatment was also partially rescued by Dex. Finally, the above effects of Dex were all blocked by SIRT1 knockdown. In conclusion, Dex could inhibit H/R-induced intestinal epithelial cells ERS, apoptosis and pyroptosis via activating SIRT1 expression.

Introduction: Intestinal ischemia-reperfusion (I/R) injury is a common clinical event. Mesenchymal stem cells (MSCs) have been widely used to repair intestinal injury in animal models. However, the effects of MSCs on intestinal I/R injury therapy remain unclear. Thus, we will perform a systematic review and meta-analysis of controlled trials to evaluate the efficacy of MSCs in animal models of intestinal I/R injury.Methods and analysis: We will search PubMed, Web of Science, Embase, Cochrane Library, Science Citation Index, China National Knowledge Information database, Wanfang Database, and the Chinese Scientific and Technological Journal Database in May 2021. We will include studies that evaluate the two different interventions for target MSCs to be maintained for the degree of histopathologic changes, mortality rate of rats, tumour necrosis factor α, and diamine oxidase. Two reviewers will independently screen titles and abstracts, perform a full article review, and extract study data. We will also use the SYRCLE tool to assess the risk of bias in the included studies. Furthermore, a random-effects meta-analysis will be conducted. Dichotomous and continuous outcomes will be analysed using risk ratios with 95% confidence intervals (CIs) and weighted mean difference with 95% CIs, respectively. For outcomes where different scales or different measurement methods have been used, the standardised mean difference will be applied. Subgroup and sensitivity analyses will be performed to explore the heterogeneity. Stata (version 12.0, Stata Corp, College Station, Texas, USA) will be used to analyse and pool the individual research results.Ethics and dissemination: This systematic review and meta-analysis does not require an ethical approval because no human beings are involved. We aim to publish this systematic review in a peer-reviewed journal.PROSPERO registration number: CRD42021231826

Cognitive impairments following the use of general anesthetics are well documented but the underlying mechanisms are unclear. Here, long-lasting cognitive deficits were observed in aged mice following administration of etomidate at a clinically relevant concentration (20 mg/kg); these deficits were closely related to hippocampal synaptic inhibition and astrocyte dysfunction. Using microdialysis and magnetic-activated cell-sorting techniques, we found that astrocyte secretion of glutamate, d -serine, and ATP, as well as astrocyte function, were depressed in the hippocampus following treatment with etomidate. Interestingly, hippocampal astrocyte inhibition (designer receptors exclusively activated by designer drugs; DREADDs) had no effect on the initial synaptic inhibition, but reversed synaptic and cognitive depression in the long term. Furthermore, continual activation of hippocampal astrocytes following administration of a sedative dose (8 mg/kg) of etomidate induced synaptic inhibition and cognitive dysfunction. Our results indicate that general anesthetic-induced hippocampal astrocyte dysfunction plays a role in maintaining synaptic inhibition, which eventually induces long-lasting cognitive deficits.

The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).

Background Gastric cancer(GC) treated with fluorouracil and cisplatin can cause chemotherapy resistance, which is one of the most common postoperative clinical complications and leads to in poor prognosis. Methods The purpose of this study is to investigate the susceptibility of patients with GC after postoperative chemotherapy based on autophagy-related genes (ATGs). Under the background of TCGA database, for patients with GC undergoing and during chemotherapy,gene expression data was integrated and analyzed. Prognostic genes were screened based on univariate and various analysis regression models. Subjects were divided into two groups: high-risk group and low-risk group. Univariate and various analytical regression models were used to screen for prognostic genes. Median risk score was used for analysis. OS and DFS were evaluated by the product limit estimation method. Subject curve analysis is used to determine the accuracy of the forecast. We also have performed appropriate analysis and conducted some detailed assessments in our work. The differential expression of ATGs was mainly associated with chemotherapy resistance.Results After chemotherapy administration, we have screened 9 ATGs outcomes in the subjects and DFS and OS were precisely predicted by the model of GEO and TCGA databases.Conclusions 9 genes were established as prognostic markers to predict the relationship between ATGs and GC chemotherapy susceptibility, suggesting a better individualized treatment in clinical practice.

Dexmedetomidine, used as an adjuvant to local anesthetics (LAs), may prolong the duration of peripheral nerve block. However, the effect of dexmedetomidine on the neurotoxicity of LAs is not completely understood. The present study was designed to investigate the efficacy of two doses of dexmedetomidine as an adjuvant to ropivacaine and its protective effect against the neurotoxicity of LAs. Paw withdrawal thermal latency testing was used to detect the sensory blockade. Extensor postural thrust testing was used to detect the motor blockade. The results demonstrated that the addition of dexmedetomidine to ropivacaine prolonged the duration of sensory and motor blockade in a dose-dependent manner compared with ropivacaine alone. TUNEL staining was performed to examine apoptosis. Western blotting was used to detect the Cleaved caspase-3 expression levels. The results showed that the addition of dexmedetomidine to ropivacaine decreased the rate of apoptosis and caspase-3 expression levels in a dose-dependent manner compared with ropivacaine alone (P

Brain ischemia reperfusion injury (BIRI) is defined as a series of brain injury accompanied by inflammation and oxidative stress. Astrocyte-derived extracellular vesicles (EVs) are importantly participated in BIRI with involvement of microRNAs (miRs). Our study aimed to discuss the functions of miR-29a from astrocyte-derived EVs in BIRI treatment. Thus, astrocyte-derived EVs were extracted. Oxygen and glucose deprivation (OGD) cell models and BIR rat models were established. Then, cell and rat activities and pyroptosis-related protein levels in these two kinds of models were detected. Functional assays were performed to verify inflammation and oxidative stress. miR-29a expression in OGD cells and BIR rats was measured, and target relation between miR-29a and tumor protein 53-induced nuclear protein 1 (TP53INP1) was certified. Rat neural function was tested. Astrocyte-derived EVs improved miR-29a expression in N9 microglia and rat brains. Astrocyte-derived EVs inhibited OGD-induced injury and inflammation in vitro, reduced brain infarction, and improved BIR rat neural functions in vivo. miR-29a in EVs protected OGD-treated cells and targeted TP53INP1, whose overexpression suppressed the protective function of EVs on OGD-treated cells. miR-29a alleviated OGD and BIRI via downregulating TP53INP1 and the NF-κB/NLRP3 pathway. Briefly, our study demonstrated that miR-29a in astrocyte-derived EVs inhibits BIRI by downregulating TP53INP1 and the NF-κB/NLRP3 axis.

The objective of study was to investigate the inhibitory effect of sinomenine on neuropathic pain on dorsal root ganglia (DRG). The DRG cell line and spinal nerve ligation (SNL) model were used in this study. The effect of sinomenine on the cell viability was examined by MTT assay. The expression of p38 MAPK, NF-κB, c-fos, SP and TNF-α was detected by using immunofluorescence and immunohistochemistry assay. We also assessed the level of p-CaMKII, COX-2, p-CREB, IL-17A, TLR4 and IL-1β via western blotting and RT-qPCR. Compared to the controls, sinomenine showed a protective effect on TNF-α-induced apoptosis on DRG cells in a dose-dependent manner, with an increase of cell viability and a decrease of reactive oxygen species level as well as LDH release. Parallelly, sinomenine treatment significantly reduced the expression of various factors related to stress and inflammation, including p38 MAPK, NF-κB, c-fos, p-CAMKII, COX-2, p-CREB, TLR4 and IL-17A in DRG cells in vitro. Furthermore, we found that administration of sinomenine significantly reduced mechanical withdrawal threshold and thermal withdrawal latency and inhibited the inflammation and activation of p38 signaling in SNL rats. It is noting that combined therapy of sinomenine and pulsed radiofrequency exhibited higher efficacy of dorsal root ganglia inflammation than single treatment as well as the combination of oxycodone and pulsed radiofrequency. Sinomenine inhibited the apoptosis of DRG cell by regulating p38 MAPK/CREB signalling pathway, which provides evidence to alleviate neuropathic pain in clinic.

Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we aimed to characterize the antinociceptive effects of DEX in acute inflammatory visceral pain (AIVP) induced by acetic acid in rats and to evaluate whether antinociception was regulated by the extracellular signal-regulated protein kinase (ERK) pathway, Toll-like receptor (TLR) signaling, and transient receptor potential (TRP) channel. Acetic acid was administered to 30 male rats with or without DEX. Rats were divided into six groups, as follows: control, disease (received no treatment before acetic acid administration), vehicle-treated, low-dose DEX (lDEX), medium-dose DEX (mDEX), and high-dose DEX (hDEX)-treated groups. Thermal withdrawal latency (TWL), mechanical withdrawal threshold (MWT), and abdominal withdrawal reflex (AWR) were measured to assess pain. We detected electromyographic (EGM) responses in the rectus abdominis muscle and measured the average arterial blood pressure. Levels of interleukin 1 (IL-1), IL-2, and IL-6 in the serum, as well as tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2) in the peritoneal fluid, were measured by ELISA. The expression levels of phospho(p)CREB, pERK1/2, pMEK1, and TRP cation channel subfamily V member 1 (TRPV1), as well as the activation state of TLR4, were determined in the spinal cord of rats by real-time polymerase chain reaction and western blot analysis. TWL and MWT scores were elevated (P

Objective:To investigate the effect of combination of dexmedetomidine and sufentanil on patient-controlled intravenous analgesia (PCIA) in patients after abdominal operation and to assess the safety and validity of this treatment.Methods:This is a prospective, randomized controlled, blinded, multice

// Xinghua Lyu 1 , Wenhui Qiao 1 , Debang Li 1 and Yufang Leng 1 1 Department of Anaesthesiology, The First Hospital of Lanzhou University, Lanzhou, China Correspondence to: Yufang Leng, email: // Keywords : colorectal, liver, oncology, outcomes Received : November 07, 2016 Accepted : March 09, 2017 Published : March 31, 2017 Abstract BACKGROUND: Perioperative blood transfusion may be associated with negative clinical outcomes in oncological surgery. A meta-analysis of published studies was conducted to evaluate the impact of blood transfusion on short- and long-term outcomes following liver resection of colorectal liver metastasis (CLM). MATERIALS AND METHODS: A systematic search was performed to identify relevant articles. Data were pooled for meta-analysis using Review Manager version 5.3. RESULTS: Twenty-five observational studies containing 10621 patients were subjected to the analysis. Compared with non-transfused patients, transfused patients experienced higher overall morbidity (odds ratio [OR], 1.98; 95% confidence intervals [CI] =1.49-2.33), more major complications (OR, 2.12; 95% CI =1.26-3.58), higher mortality (OR, 4.13; 95% CI =1.96-8.72), and longer length of hospital stay (weighted mean difference, 4.43; 95% CI =1.15-7.69). Transfusion was associated with reduced overall survival (risk ratio [RR], 1.24, 95% CI =1.11-1.38) and disease-free survival (RR, 1.38, 95% CI=1.23-1.56). CONCLUSION: Perioperative blood transfusion has a detrimental impact on the clinical outcomes of patients undergoing CLM resection.

Lung ischemia-reperfusion injury remains a problem in thoracic surgery, as minimal progress has been made concerning its prevention and control. In the present study, the protective effects and the underlying mechanism of Shenfu injection preconditioning on a rat lung ischemia-reperfusion model was investigated. Shenfu injection is a well-known Chinese traditional medicine, which is composed of Red Radix Ginseng and Radix Aconitum carmichaelii, with ginseng saponin and aconitum alkaloids as the active ingredients. A total of 72 specific pathogen-free, healthy male Wistar rats were randomly divided into control, model and Shenfu injection (10 ml/kg injection prior to injury) groups and were assessed at the following points: Ischemia 45 min; reperfusion 60 min; and reperfusion 120 min. Blood collected from the aorta abdominalis was cryopreserved at −70°C for the analysis of malondialdehyde (MDA) and superoxide dismutase (SOD) activity. Lung tissues were divided into three equal sections in order to assess the wet-to-dry (W/D) lung ratio, tumor necrosis factor (TNF)-α expression levels, myeloperoxidase (MPO) activity, alveolar damage, total protein and hematoxylin and eosin staining. The results demonstrated that the lung W/D weight ratio, TNF-α expression levels and SOD activity in the Shenfu group were significantly lower at 120 min reperfusion (P

The neurotoxicity of local anesthetics has received an increasing amount of attention and more effective therapeutic agents are required. Extracellular polymeric substances from Aphanizomenon flos-aquae (EPS-A) are high molecular weight polysaccharides. The present study aimed to elucidate the protective effects of EPS-A on neurotoxicity induced by local anesthetics in an intraperitoneal injection bupivacaine rat model. The results of immunohistochemical staining inicated that following intraperitoneal injection of EPS-A the levels of apoptosis and caspase-3 decreased, and the expression levels of microtubule-associated protein 1A light chain 3 (LC3) and beclin1 increased. In order to further clarify the mechanism of the EPS-A-mediated protection, the expression of key proteins associated with autophagy was investigated by western blotting. The results suggested that the ratio of LC3-II/LC3-I and the expression level of beclin1 increased. Taken together, the results indicated that EPS-A induced neuroprotective effects on bupivacaine-induced neurotoxicity. The underlying mechanism may be associated with the inhibition of apoptosis, upregulation of autophagy and improvement of cell survival. The results suggested that EPS-A may be a candidate neuroprotective agent against neurotoxicity caused by local anesthetics.

The neurotoxicity of local anesthetics has received an increasing amount of attention and more effective therapeutic agents are required. Extracellular polymeric substances from Aphanizomenon flos-aquae (EPS-A) are high molecular weight polysaccharides. The present study aimed to elucidate the protective effects of EPS-A on neurotoxicity induced by local anesthetics in an intraperitoneal injection bupivacaine rat model. The results of immunohistochemical staining inicated that following intraperitoneal injection of EPS-A the levels of apoptosis and caspase-3 decreased, and the expression levels of microtubule-associated protein 1A light chain 3 (LC3) and beclin1 increased. In order to further clarify the mechanism of the EPS-A-mediated protection, the expression of key proteins associated with autophagy was investigated by western blotting. The results suggested that the ratio of LC3-II/LC3-I and the expression level of beclin1 increased. Taken together, the results indicated that EPS-A induced neuroprotective effects on bupivacaine-induced neurotoxicity. The underlying mechanism may be associated with the inhibition of apoptosis, upregulation of autophagy and improvement of cell survival. The results suggested that EPS-A may be a candidate neuroprotective agent against neurotoxicity caused by local anesthetics.

Background and objective Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its impact on postoperative outcomes and long-term survival after cancer resection remains controversial. A meta-analysis of published studies was conducted to address this issue. Methods An extensive electronic search of four databases was performed for relevant articles. Data were processed for meta-analysis using Review Manager version 5.1. Results Seventeen observational studies involving 5407 patients were subjected to the analysis. Overall morbidity or any type of complications and mortality were comparable between diabetic and non-diabetic subjects. Overall DM has a significant negative impact on survival (risk ratio [RR], 1.24, 95% confidence interval [CI], 1.05–1.45; P = 0.01). Stratification by the type of DM revealed that new-onset DM (

Dexmedetomidine (DEX) is a highly selective α2 adrenergic receptor agonist. In this study, we investigated the analgesic effect and the underlying mechanisms of DEX on inflammatory visceral pain in rats. Twenty-five male Sprague Dawley (SD) rats were randomly divided into 5 groups, including control, sham, low dose DEX, medium dose DEX and high dose DEX group. Pain was induced with 10% formalin and scored every 15min till 2 h-post the induction. Hematoxylin-eosin (HE) staining was used to evaluate the toxicity of DEX on spinal cord neurons. Acetycholine (Ach) and noradrenaline (NA) levels were determined by using ELISA method. The expressions of natural nitric oxide synthase (nNOS), protein kinase γ (PKCγ) and protease-activated receptor 2 (PAR2) were determined by using western blot. DEX treatment relieved formaldehyde-induced pain in rats in a dose-dependent manner. Furthermore, DEX showed little neuro-toxicity on the spinal cord neurons, even at the highest dosage used in our study. Ach level was significantly increased in Sham group compared with control group. DEX treatment decreased NA levels and increased Ach levels in the incubation medium of spinal cord sections. Western blot analysis showed that the expression of nNOS, PKCγ and PAR2 was significantly decreased in DEX group compared with Sham group, whereas these effects of DEX on nNOS, PKCγ and PAR2 were blocked by both yohimbine and idazoxan, indicating that the analgesic effect of DEX is mediated by both α2 adrenergic receptor and imidazoline receptor. Yohimbine and idazoxan treatment significantly enhanced pain scores compared to DEX group, and which antagonizes the effects DEX. In conclusion, our study demonstrated that DEX could inhibit formaldehyde-induced pain by inhibiting nNOS, PKCγ and PAR2 expression through α2 adrenergic receptor and imidazoline receptor.

The Bennett and Xie (1988) model of chronic constriction injury (CCI) investigated the effects of tetramethylpyrazine (TMP) on neuropathic pain-associated behaviors and neuronal apoptosis in the spinal dorsal horn. Fifty-four male rats were randomly divided into sham (group S), CCI (group C) and TMP groups (group T). Each group was divided into subgroups (n = 6 in each group) according the time of sacrifice: 3 d, 7 d and 14 d. Rat sciatic nerves were unligated (group S), or the right sciatic nerve was loosely ligated (groups C and T) to produce CCI. Mechanical withdrawal thresholds (MWTs) and thermal withdrawal latencies (TWLs) were measured, and the rats were sacrificed at different time points post-operation. The L4-L6 sections of the spinal cord were removed. Apoptotic changes were evaluated using the TUNEL method. Immunohistochemistry assessed Bcl-2 and caspase-3 expression. TMP treatment increased MWT and TWL values and Bcl-2 expression, but it reduced neuronal apoptosis and caspase-3 expression in laminae I–II of the spinal dorsal horn. These results suggested that the inhibition of neuronal apoptosis via the modulation of Bcl-2 and caspase-3 proteins in the rat spinal dorsal horn contributed to TMP-induced analgesia.