Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

The modulatory effects of gut microbes and metabolites on blood-brain barrier integrity and brain function in sepsis-associated encephalopathy.

Background: Intestinal microbiota homeostasis and the gut-brain axis are key players associated with host health and alterations in metabolic, inflammatory, and neurodegenerative disorders. Sepsis-associated encephalopathy (SAE), which is closely associated with bacterial translocation, is a common secondary organ dysfunction and an urgent, unsolved problem affecting patient quality of life. Our study examined the neuroprotective effects of the gut microbiome and short-chain fatty acid (SCFA) metabolites on SAE. Methods: Male C57BL/6 mice were administered SCFAs in drinking water, then subjected to cecal ligation and puncture (CLP) surgery to induce SAE. 16S rRNA sequencing was used to investigate gut microbiome changes. The open field test (OFT) and Y-maze were performed to evaluate brain function. The permeability of the blood-brain barrier (BBB) was assessed by Evans blue (EB) staining. Hematoxylin and eosin (HE) staining was used to examine intestinal tissue morphology. The expression levels of tight junction (TJ) proteins and inflammatory cytokines was assessed by western blots and immunohistochemistry. In vitro, bEND.3 cells were incubated with SCFAs and then with lipopolysaccharide (LPS). Immunofluorescence was used to examine the expression of TJ proteins. Results: The composition of the gut microbiota was altered in SAE mice; this change may be related to SCFA metabolism. SCFA treatment significantly alleviated behavioral dysfunction and neuroinflammation in SAE mice. SCFAs upregulated occludin and ZO-1 expression in the intestine and brain in SAE mice and LPS-treated cerebromicrovascular cells. Conclusions: These findings suggested that disturbances in the gut microbiota and SCFA metabolites play key roles in SAE. SCFA supplementation could exert neuroprotective effects against SAE by preserving BBB integrity.

Electroacupuncture alleviates cognitive dysfunction and neuronal pyroptosis in septic mice.

BACKGROUND: Sepsis is defined as organ dysfunction caused by an uncontrolled response to infection and is followed by a high incidence of cognitive dysfunction, which can severely affect patients' quality of life. Previous studies have suggested that electroacupuncture (EA) is protective against sepsis-associated cognitive dysfunction and that pyroptosis plays a vital role in cognitive function. The aim of this study was to investigate the effect of EA on cognition and neuronal pyroptosis in a mouse model of sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP) surgery. Mice were randomly divided into three groups (control, CLP and CLP + EA). EA was performed at bilateral ST36 for three consecutive days after the surgery. The 7-day survival rate of each group was observed on the seventh day after the surgery. The Morris water maze (MWM) was used to test cognitive function from the 8th to 12th day after the surgery. We used transmission electron microscopy (TEM) and transferase dUTP nick-end labeling (TUNEL) staining to determine the structural integrity of hippocampal neuronal membranes and the number of surviving neurons in the hippocampal tissues, respectively. Expression of nucleotide-binding domain-like receptor protein 1 (NLRP1), caspase-1 and gasdermin-D (GSDM D) in hippocampal CA1 neurons was detected by Western blotting and real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and caspase-1 concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the CLP group, 7-day survival rates and cognitive function were significantly improved in the CLP + EA group. After EA treatment, the integrity of the hippocampal CA1 neuronal membrane and mortality of hippocampal neurons were significantly decreased, and expression of NLRP1, caspase-1 and GSDM D was downregulated. CONCLUSION: EA can alleviate cognitive dysfunction and neuronal pyroptosis in septic mice.

Effect of nimotuzumab and PF induction chemotherapy combined with concurrent chemoradiotherapy in treating locally advanced nasopharyngeal carcinoma.

PURPOSE: To investigate the efficacy and safety of nimotuzumab + cisplatin and 5-fluorouracil (PF) induction chemotherapy combined with concurrent chemoradiotherapy in treating locally advanced nasopharyngeal carcinoma. METHODS: The clinical data of 126 patients with stage III-IVa nasopharyngeal carcinoma who were admitted to and treated in our department from September 2013 to May 2016 were collected, and the patients were randomly divided into two groups and treated with nimotuzumab combined with PF induction therapy (NPF group, n=65) and induction therapy of docetaxel, cisplatin and fluorouracil (TPF) regimen (TPF group, n=65). After 2 cycles of induction therapy, all the patients received cisplatin combined with concurrent intensity-modulated radiation therapy (IMRT). Moreover, the clinical efficacy, changes in patients' quality of life and incidence of adverse reactions were observed and compared between the two groups, and the survival of the patients was followed up and recorded. RESULTS: The objective response rate (ORR) and disease control rate (DCR) were remarkably higher in NPF group than those in TPF group [78.5% (51/65) vs. 58.5% (38/65), 93.8% (61/65) vs. 80.0% (52/65)] (p=0.014, p=0.019). During induction therapy, the patients in NPF group had notably ameliorated leukopenia compared with those in TPF group (p=0.018). Only 8 cases of skin rash (grade I) occurred in NPF group (p=0.004), which subsided spontaneously after treatment with nimotuzumab. In the stage of concurrent chemoradiotherapy, NPF group exhibited better tolerance to treatment, but there were no statistically significant differences in adverse reactions between the two groups (p>0.05). Besides, according to the scores of functional assessment of cancer therapy-head and neck (FACT-H&N) scale for measuring the quality of life of patients with head and neck neoplasms in the two groups after treatment, the quality-of-life scores were improved to different extents in both groups. Besides, the functional status score [(19.85±4.74) points vs. (18.14±4.49) points, p=0.037], head and neck additional items score [(23.95±5.20) points vs. (22.21±4.84) points, p=0.040] and total scale score [(108.55±14.65) points vs. (104.65±13.23) points, p=0.023] in NPF group were markedly superior to those in TPF group. It was shown in the results of follow-up that the median overall survival (OS) was (18.9±3.6) months and (16.3±3.8) months in NPF group and TPF group, respectively. Through log-rank test, it was found that the OS was distinctly longer in NPF group than that in TPF group (p=0.017). CONCLUSIONS: Compared with TPF induction chemotherapy, nimotuzumab and PF induction chemotherapy combined with concurrent chemoradiotherapy results in better short-term clinical efficacy in treating locally advanced nasopharyngeal carcinoma, higher quality of life and long-term survival rate as well as tolerable adverse reactions.

Long Noncoding RNA H19 Overexpression Protects against Hypoxic-Ischemic Brain Damage by Inhibiting miR-107 and Up-Regulating Vascular Endothelial Growth Factor.

Long noncoding RNAs play critical roles in cellular homeostasis, and long noncoding RNA H19 (H19) is implicated in several pathologic conditions. The putative role of H19 in the pathogenesis and progression of hypoxic-ischemic brain damage (HIBD) is not yet understood. Therefore, a series of in vivo and in vitro experiments were designed to investigate the potential roles of H19 in neuronal apoptosis and cognitive dysfunction in HIBD. H19 expression was decreased in HIBD rat models established by partial occlusion of carotid artery. H19 bound to and decreased the expression of miR-107, which also increased VEGF expression. H19 overexpression reduced neuronal apoptosis and alleviated cognitive dysfunction in HIBD rats. The up-regulation of miR-107 reversed the protective effects conferred by H19. In addition, the cell model of HIBD was established by oxygen-glucose deprivation in neuronal cells used. H19 overexpression in oxygen-glucose deprivation neurons increased B-cell lymphoma-2 and decreased B-cell lymphoma-2-associated X, total and cleaved caspase-3 expressions. Taken together, the results showed that H19 expresses at a low level in HIBD. H19 overexpression decreased miR-107 and increased VEGF expression, which resulted in repressed neuronal apoptosis and alleviated cognitive dysfunction. Thus, H19 may serve as a molecular target for translational research for HIBD therapy.

Repeated isoflurane exposures of neonatal rats contribute to cognitive dysfunction in juvenile animals: the role of miR-497 in isoflurane-induced neurotoxicity.

INTRODUCTION: Isoflurane anesthesia at the period of brain development can lead to neurotoxicity and long-term cognitive impairment. This study aimed to investigate the role of miR-497 on isoflurane-induced neurotoxicity. MATERIAL AND METHODS: Neonatal rats (P7) were subject to isoflurane for 2 h at P7, P9, and P11. MiR-497 and neuron apoptosis were evaluated in hippocampal tissue by qRT-PCR and western blot. Fear conditioning test and Morris water maze were performed to determine cognitive function. The cell viability of isolated hippocampal neuronal cells exposed to isoflurane was measured using MTT test. The regulation of phospholipase D1 (PLD1) by miR-497 in isolated hippocampal neuronal cells was evaluated by luciferase reporter assays and western blot. Immunohistochemistry and TUNEL staining were employed to examine the PLD1 expression and neuronal cell apoptosis in hippocampus of neonatal rats, respectively. RESULTS: Repeated isoflurane anesthesia led to neurons' apoptosis and long-term cognitive impairment. Isoflurane exposure led to apoptosis and viability reduction in hippocampal neuronal cells. MiR-497 was observed to be upregulated after isoflurane exposure both in vivo and in vitro. Knockdown of miR-497 attenuated isoflurane-induced neuronal cells apoptosis and viability reduction. Furthermore, PLD1 was predicted and then validated as a novel target of miR-497. miR-497 could negatively regulate PLD1 by binding to its 3'-untranslated region. Downregulation of PLD1 was also observed after isoflurane exposure in neonatal rat hippocampus and hippocampal primary neuronal cell cultures. CONCLUSIONS: Induction of miR-497 was involved in isoflurane anesthesia-induced cognitive impairment and neuronal cell apoptosis by targeting PLD1. miR-497 may be a novel potential mechanism in isoflurane-induced neurotoxicity so that our findings provide new insight into a better and understanding of the clinical application of isoflurane.

Propofol affects the growth and metastasis of pancreatic cancer via ADAM8.

BACKGROUND: Anesthesia is a major component of surgery and recently considered an important regulator of cell phenotypes. Here we aimed to investigate propofol, an anesthesia drug, in suppressing pancreatic cancer (PDAC), focusing on A disintegrin and metalloprotease 8, (ADAM8) as a molecular mediator. METHODS: Quantitative real-time PCR and western blot were used to assess the change of ADAM8 expression in Panc1 PDAC cells treated with 5 or 10 µg/mL propofol, using cells treated with BB-94 inhibitor as controls. ADAM8 activity was measured through quantifying fluorescence release induced by PEPDAB013 decomposition. MTT assay, scratch wound assay and Matrigel invasion assay were used to investigate the proliferation, migration and invasion of the cells. Western blot and immunohistochemical analysis were used to quantify integrin ß1, ERK1/2, MMP2 and MMP9 expression. RESULTS: Propofol and BB-94 reduced ADAM8 expression, cell proliferation and migration of Panc1 cells. Tumor growth was inhibited by propofol and BB-94, concomitant with downregulation of integrin ß1, ERK1/2, MMP2 and MMP9. ADAM8 is downregulated by propofol, leading to inhibition of pancreatic cancer proliferation and migration. CONCLUSION: Pancreatic tumor growth is also inhibited by propofol and BB-94, which is attributed to suppression of ERK/MMPs signaling.

The effect of TEAS on the quality of early recovery in patients undergoing gynecological laparoscopic surgery: a prospective, randomized, placebo-controlled trial.

INTRODUCTION: In current study we assessed the effect of transcutaneous electrical acupoint stimulation (TEAS) on the quality of early recovery in patients undergoing gynecological laparoscopic surgery. METHODS: Sixty patients undergoing gynecological laparoscopic surgery were randomly assigned to TEAS (TEAS group) or control group (Con group). TEAS consisted of 30 min of stimulation (12-15 mA, 2/100 Hz) at the acupoints of Baihui (GV20), Yingtang (EX-HN-3), Zusanli (ST36) and Neiguan (PC6) before anesthesia. The patients in the Con group had the electrodes applied, but received no stimulation. Quality of recovery was assessed using a 40-item questionnaire as a measure of quality of recovery (QoR-40; maximum score 200) scoring system performed on preoperative day 1 (T0), postoperative day 1 (T1) and postoperative day 2 (T2); 100-mm visual analogue scale (VAS) scores at rest, mini-mental state examination (MMSE) scores, the incidence of nausea and vomiting, postoperative pain medications, and antiemetics were also recorded. RESULTS: QoR-40 and MMSE scores of T0 showed no difference between two groups (QoR-40: 197.50 ± 2.57 vs. 195.83 ± 5.17), (MMSE: 26.83 ± 2.74 vs. 27.53 ± 2.88). Compared with the Con group, QoR-40 and MMSE scores of T1 and T2 were higher in the TEAS group (P < 0.05) (QoR-40: T1, 166.07 ± 8.44 vs. 175.33 ± 9.66; T2, 187.73 ± 5.47 vs. 191.40 ± 5.74), (MMSE: T1, 24.60 ± 2.35 vs. 26.10 ± 2.78; T2, 26.53 ± 2.94 vs. 27.83 ± 2.73). VAS scores of T1 and T2 were lower (P < 0.05) in the TEAS group (T1, 4.73 ± 1.53 vs. 3.70 ± 1.41; T2, 2.30 ± 0.95 vs. 1.83 ± 0.88); the incidence of postoperative nausea and vomiting (PONV), remedial antiemetics and remedial analgesia was lower in the TEAS group (P < 0.05) (PONV: 56.7% vs. 23.3%; incidence of remedial antiemetics: 53.3% vs. 23.3%; incidence of remedial analgesia: 80% vs. 43.3%). CONCLUSION: The use of TEAS significantly promoted the quality of early recovery, improved MMSE scores and reduced the incidence of pain, nausea and vomiting in patients undergoing gynecological laparoscopic surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02619578. Registered on 2 December 2015. Trial registry name: https://clinicaltrials.gov.

PRR34-AS1 overexpression promotes protection of propofol pretreatment against ischemia/reperfusion injury in a mouse model after total knee arthroplasty via blockade of the JAK1-dependent JAK-STAT signaling pathway.

Long noncoding RNAs have been documented to be protective against ischemia/reperfusion (I/R) injury. However, few research works have focused on the protective effects of PRR34-AS1 on I/R injury after total knee arthroplasty (TKA). The objective of the present study was to investigate the possible effect of PRR34-AS1 on I/R injury after TKA. A mouse model with I/R injury after TKA was established. The interaction between PRR34-AS1 and Janus kinase 1 (JAK1) was examined and thoroughly investigated. Next, the effects of PRR34-AS1 on the expression of apoptosis-related proteins, JAS-signal transducer and activator of transcription (STAT) signaling pathways, and inflammation-related genes, chondrocyte proliferation, and apoptosis were analyzed after gain- and loss-of-function experiments. Attenuated symptoms were observed in mice pretreated with propofol, which was evidenced by decreased positive expression rate of JAK1 protein and superoxide dismutase content along with increased malondialdehyde content and IL-10 levels. PRR34-AS1 was poorly expressed in mice with I/R injury after TKA. JAK1 was a target of PRR34-AS1. Upregulated PRR34-AS1 diminished expression of JAK1, STAT1, JAK2, and STAT3 as well as cell apoptosis, while enhancing cell proliferation in vitro. Furthermore, JAK1 silencing could reverse the suppressed cell proliferation and enhanced cell apoptosis of chondrocytes imposed by silencing PRR34-AS1. Upregulation of PRR34-AS1 can potentially relieve I/R injury after TKA in mice pretreated with propofol through inhibition of the JAS-STAT signaling pathway by targeting JAK1.

Effect of ketamine combined with lidocaine in pediatric anesthesia.

BACKGROUND: We conducted a randomized clinical trial to determine whether adjunctive lidocaine diminishes the incidence of adverse effects in pediatric patients sedated with ketamine. METHODS: This case-control study involved 586 consecutive pediatric patients necessitating anesthesia. Then systolic blood pressure, heart rate, respiratory rate, and blood oxygen saturation were observed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) levels were tested. General dose of ketamine, the time of onset and duration of anesthesia and postoperative recovery, anesthesia effect, and adverse reaction were subsequently compared. High-performance liquid chromatography was employed to detect ketamine concentration at different time points after administration, and the postoperative cognition function was further evaluated. RESULTS: Intra- and post-operation, the rising degree of ALT, AST, BUN, and Cr in patients treated with ketamine was higher than those in patients treated with the ketamine-lidocaine complex. General dose of ketamine, the time of onset and duration of anesthesia, postoperative recovery time, and the incidence rate of adverse reaction in patients treated with ketamine-lidocaine complex were lower, but the concentration of ketamine was higher compared to the patients treated with ketamine. In patients treated with the ketamine-lidocaine complex, elimination half-life of ketamine was prolonged, the area under curve was increased, and the plasma clearance rate was decreased relative to those with ketamine alone. CONCLUSIONS: Ketamine combined with lidocaine may be beneficial in shortening the onset of anesthesia, promoting postoperative awake, prolonging elimination half-life, increasing area under curve, and decreasing plasma clearance rate and incidence of adverse reactions.

Effect of sevoflurane treatment on microglia activation, NF-kB and MAPK activities.

Microglia activation has been implicated in neurodegenerative disease. Sevoflurane is fluorinated methyl isopropyl ether with anti-inflammatory activity. In this study, we evaluated the potential effects of sevoflurane on lipopolysaccharides (LPS)-induced microglia activation. We treated primary microglia cells with sevoflurane prior to LPS treatment and tested the microglia migration, the productions of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-6 and interleukin-8. We also explored the effects of sevoflurane on NF-κB and p38 MAPK activation. Finally, we examined the effect of sevoflurane on cytokines production in rat brain. Sevoflurane significantly reduced LPS-induced microglial migration. Sevoflurane significantly decreased the production of pro-inflammatory cytokines both in vitro and in vivo. Sevoflurane attenuated activations of NF-κB and MAPK signaling pathways. Sevoflurane treatment decreased microglia activation by suppressing NF-kB and MAPK signaling pathways.

Efficacy of chemoradiotherapy combined with bevacizumab in patients with nasopharyngeal carcinoma: A comparative study.

PURPOSE: To investigate the efficacy of chemoradiotherapy combined with bevacizumab in patients with nasopharyngeal carcinoma and its clinical value in the cognitive function and radiation-induced brain injury. METHODS: A total of 80 patients with nasopharyngeal carcinoma treated in our hospital from March 2013 to October 2015 were selected and randomly divided into the control group (n=40) and the observation group (n=40). Patients in the control group were treated with three-dimensional conformal radiotherapy and regular chemotherapy, while patients in the observation group were treated with bevacizumab. Progression-free survival (PFS) and median survival (MS), the therapeutic effect, the levels of vascular endothelium-related indexes, S-100B protein and neuron-specific enolase (NSE), the changes in subjective evaluation criteria for cognitive function, the changes in auditory event-related potential P300 amplitude and latency, and the changes in neurological score during treatments were compared. RESULTS: In the observation group, both PFS and MS were longer than those in the control group (p<0.05); meanwhile, the overall effective rate of treatment was significantly higher (p<0.05). In addition, S-100B protein and NSE levels in the observation group 6 months after treatments were obviously lower than those in control group. At 3 and 6 months after treatments, the cognitive function score in the observation group was obviously higher compared to the control group. The auditory event-related potential P300 amplitude in observation group was lower than that in control group, while the latency was longer compared to the control group. At 3 and 6 months after treatments, the neurological score in observation group was remarkably higher than that in control group (p<0.05). CONCLUSIONS: The combined application of bevacizumab for patients with nasopharyngeal carcinoma after chemoradiotherapy can significantly prolong the survival time of patients, improve the clinical therapeutic effect and the cognitive function of patients, and reduce the incidence rate of radiation-induced brain injury.

Analysis of postoperative cognitive dysfunction and influencing factors of dexmedetomidine anesthesia in elderly patients with colorectal cancer.

Effect of dexmedetomidine-assisted general anesthesia on early postoperative cognitive dysfunctions in elderly patients with colorectal cancer was explored. In total, 140 patients with radical colorectal cancer under general anesthesia from March 2012 to June 2015 were enrolled in the Guizhou Provincial People's Hospital, including 80 patients in the dexmedetomidine group and 60 patients in the saline group. Surgery conditions were recorded, and the incidence of postoperative cognitive dysfunction (POCD) and cognitive function score (MMSE score) were compared between the two groups. Serum levels of S-100ß protein (S-100ß) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. The anesthesia time and intraoperative blood loss in the experiment group were significantly lower than those in the control group (P<0.05). The MMSE scores of the two groups on the 1st and 3rd day after surgery were lower than those before surgery (P<0.05). The incidence rates of the experiment group were significantly lower than that of the control group (P<0.05). The levels of serum IL-6 and S-100ß were increased on the 1st and 3rd day after surgery compared with those before surgery (P<0.05). The levels of serum IL-6 and S-100ß in the control group were significantly higher than those in the experiment group on the 1st and 3rd day after surgery (P<0.05). Age, duration of anesthesia, intraoperative blood loss, expression of IL-6 and S-100ß were the influencing factors of POCD. Age ≥70 years, anesthesia duration ≥3 h, intraoperative blood loss ≥350 ml, and high expression of IL-6 and S-100ß was an important factor related to the occurrence (P<0.05). Dexmedetomidine can significantly improve postoperative cognitive dysfunction in elderly patients with colorectal cancer, and the occurrence of cognitive dysfunction can be affected by age, duration of anesthesia, intraoperative blood loss and the high expression of IL-6 and S-100ß.

Effect of transcutaneous electrical acupuncture point stimulation on expression of p-JNK in the dorsal root ganglion in a rat model of myofascial pain syndrome.

BACKGROUND: Acupuncture has been used to treat myofascial pain syndrome (MPS) for 2000 years in China, but its mechanisms are still not entirely clear. In the present study, we explored the effects of transcutaneous electrical acupuncture point stimulation (TEAS) at an Ashi acupuncture point on expression of phosphorylated c-Jun N-terminal kinase (p-JNK) in the dorsal root ganglion (DRG) using a rat model of MPS. METHODS: 32 rats were divided into four groups: normal, MPS, MPS+TEAS and MPS+sham- TEAS. MPS was produced by a blunt strike to the left vastus medialis combined with eccentric exercise for 8 weeks. Rats in the MPS+TEAS group received TEAS (6-9 mA, 2 Hz, 30 min) treatment at the Ashi acupuncture point for 2 weeks; rats in the MPS+sham -TEAS group had the same electrodes applied but received no stimulation. Paw withdrawal thermal latency (PWTL) was studied at baseline and on days 3, 7, 11 and 15 after treatment. Haematoxylin and eosin staining was used to examine for morphological changes in the left vastus medialis muscles; expression of p-JNK in the L3-L5 DRG was determined by immunofluorescence staining and western blotting after treatment. RESULTS: Compared with the normal group, PWTL decreased significantly (P<0.01) and the expression of p-JNK in the DRG increased in the MPS and MPS-sham-TEAS groups (P<0.01); compared with the MPS group, PWTL was increased significantly (P<0.01) and expression of p-JNK in the DRG was decreased in the MPS+TEAS group. However, when compared with the normal group, PWTL did not recover to baseline and expression of p-JNK was still higher. CONCLUSION: TEAS treatment may produce an analgesic effect, probably by inhibiting the expression of p-JNK in the DRG of rats with MPS.

Long non-coding RNA MALAT1 sponges microRNA-429 to regulate apoptosis of hippocampal neurons in hypoxic-ischemic brain damage by regulating WNT1.

Hypoxic-ischemic brain damage (HIBD) is a common neurological disorder. Emerging reports reveal that long non-coding RNAs and microRNAs (miRs) are implicated in the progress of HIBD. In this study we tried to ascertain whether lncRNA MALAT1, with the involvement of miR-429 and WNT1, affects HIBD. Initially, a HIBD mouse model was established. Then, we treated HIBD mice with dexmedetomidine (DEX) and then up- or down-regulated the expression of MALAT1, miR-429 and WNT1 in HIBD mice and neurons. Meanwhile, brain injury and hippocampal neuronal apoptosis were evaluated. Moreover, the interaction among MALAT1, miR-429 and WNT1 in HIBD was investigated. MALAT1 and WNT1 were high-expressed in brain tissues of HIBD mice while miR-429 was low-expressed in brain tissues from HIBD mice. Interestingly, MALAT1 silencing was observed to enhance the cerebral protection of DEX against HIBD. In addition, it was confirmed that MALAT1 sponged miR-429 downregulating expression of miR-429, thereby promoting apoptosis of hippocampal neurons. This effect was achieved through up-regulating the level of WNT1. Taken together, this study demonstrates that silencing of MALAT1 enhances the cerebral protection of DEX against HIBD by suppressing WNT1 expression through miR-429.

Propofol inhibits pancreatic cancer progress under hypoxia via ADAM8.

BACKGROUND: To investigate the potential anti-tumoral properties of propofol in pancreatic cancer and elucidate the underlying mechanisms. METHODS: The relative expression of ADAM metallopeptidase domain 8 (ADAM8) in response to hypoxia in Panc1 cells was analyzed by western blotting. The enzymatic activity was determined by fluorescence release from PEPDAB013 decomposition. Cell growth was measured via cell counting and cell viability was measured using CCK-8 kit. Cell migrative capacity was evaluated by transwell and adhesion assay. The relative abundance of angiogenesis-related markers including platelet-derived growth factor AA, angiogenin, endothelin-1 and vascular endothelial growth factor were determined by real-time polymerase chain reaction and western blotting. The anti-tumoral activity of propofol was investigated with Panc1-derived xenograft mice model. RESULTS: ADAM8 was significantly induced by hypoxia and efficiently inhibited by co-treatment with propofol. Propofol suppressed proliferation and compromised viability of Panc1 cells. In addition, the migrative capacity was greatly inhibited by propofol dosage. Comprehensive profiling of angiogenesis-related markers demonstrated that propofol remarkably suppressed neovascularization response in Panc1 cells under hypoxia. We further uncovered that propofol administration via subcutaneous injection delayed xenograft tumor progression. CONCLUSION: Propofol specifically inhibited ADAM8 expression and activation in response to hypoxia in pancreatic cancer, and held great value for therapeutic effects.

NF-κB signaling pathway inhibition suppresses hippocampal neuronal apoptosis and cognitive impairment via RCAN1 in neonatal rats with hypoxic-ischemic brain damage.

NF-κB is a core transcription factor, the activation of which can lead to hypoxic-ischemic brain damage (HIBD), while RCAN1 plays a protective role in HIBD. However, the relationship between NF-κB and RCAN1 in HIBD remains unclear. This study aimed to explore the mechanism of NF-κB signaling pathway in hippocampal neuron apoptosis and cognitive impairment of neonatal rats with HIBD in relation to RCAN1. Initially, microarray analysis was used to determine the differentially expressed genes related to HIBD. After the establishment of HIBD rat models, gain- or loss-of-function assay was performed to explore the functional role of NF-κB signaling pathway in HIBD. Then, the learning and memory ability of rats was evaluated. Expression of RCAN1, NF-κB signaling pathway-related genes and glial fibrillary acidic protein (GFAP), S-100ß and acetylcholine (Ach) level, and acetylcholinesterase (AchE) activity were determined with neuron apoptosis detected to further explore the function of NF-κB signaling pathway. RCAN1 could influence the development of HIBD. In the HIBD model, the expression of RCAN1 and NF-κB-related genes increased, and NF-κB p65 showed a significant nuclear shift. By activation of NF-κB or overexpression of RCAN1, the number of neuronal apoptosis, S-100ß protein level, and AchE level increased significantly, Ach activity decreased significantly, and GFAP positive cells increased. In addition, after the activation of NF-κB or overexpression of RCAN1, the learning and memory ability of HIBD rats was inhibited. All the results show that activation of NF-κB signaling pathway promotes RCAN1 expression, thus increasing neuronal apoptosis and aggravating cognitive impairment in HIBD rats.