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Background: Patients who undergo video-assisted thoracic surgery (VATS) that impair the integrity of the chest wall frequently experience moderate to severe postoperative pain. Serratus anterior plane block (SAPB) is a relatively novel technique that can block the lateral cutaneous branches of the intercostal nerves as well as the long thoracic nerve. Methods: Our study aimed to evaluate the analgesic efficiency of deep serratus plane block (DSPB) and superficial serratus anterior plane block (SSPB) as well as paravertebral nerve block (PVB) in the patients undergoing VATS. A total of 74 patients aged from 20-80 undergoing VATS were randomized to receive either DSPB or SSPB as well as PVB. Ultrasound (US) guided DSPB or SSPB as well as PVB with 20ml 0.5% ropivacaine was performed preoperatively to the patients according to their groups. All patients were provided with patient-controlled intravenous analgesia (PCIA) for postoperative analgesia. The primary outcomes were the levels of postoperative pain at rest and on coughing evaluated by visual analog scale (VAS), intraoperative and postoperative opioids consumption. The secondary outcomes included PCIA pressed times, side effects and satisfaction of analgesia, duration of nerve block, intraoperative hemodynamic changes and vasoactive drug dosage. Results: No significant differences of VAS score were found in the three groups at each time points. During operation, PVB reduced consumption of opioids (27.23±5.10mg) compared to DSPB (31.20±3.80mg) and SSPB (32.61±5.28mg) (pp=0.009) at postoperative 12h. Accordingly, SSPB group reduced the dosage of PCIA (26.55±4.72ml) than PVB group (31.45±7.60ml) (p=0.046). Time consuming of PVB procedure was longer (11.14±1.66min) than DSPB (5.68±1.10min) and SSPB (4.77±1.04min) (pP=0.043). Conclusion: DSPB and SSPB are easy to perform and can serve as a promising alternative technique to PVB that may offer comparable analgesic effectiveness and a better side-effect profile for patients who undergoing VATS. Trial registration: This study was registered to Chinese Clinical Trials Registry on July 20, 2019. (Registration No: ChiCTR1900024678)

Purpose Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) concentration is increased in cerebrospinal fluid (CSF) in early symptomatic phase of Alzheimer’s disease (AD). This study investigated whether CSF sTREM2 has a relationship with postoperative cognitive dysfunction (POCD) in cardiac surgery patients. Methods A total of 82 patients undergoing thoracoabdominal aortic replacement were recruited in this study. Neuropsychological testing battery was conducted before and after surgery. POCD was defined as a Z-score > 1.96 on at least 2 different tests or Telephone Interviews for Cognitive Status-Modified (TICS-M) score 42, T-tau and P-tau were collected and measured by ELISA on day before surgery and postoperative day 3. Results Patients were classified into POCD (n = 34) and non-POCD (n = 48) groups according to Z-score. Compared to non-POCD group, the levels of CSF sTREM2 (p p = 0.001) were significantly higher in POCD group on postoperative day 3, the levels of Aβ42 (p = 0.005) and Aβ42/T-tau ratio (p = 0.036) were significantly lower in POCD group on postoperative day 3. Multivariate logistic regression analysis revealed that higher value of postoperative CSF sTREM2 (odds ratio: 1.06, 95% confidence interval: 1.02–1.11, p = 0.009), age (OR: 1.15, 95%CI: 1.03–1.28, p = 0.014) and POD duration (OR: 2.47, 95%CI: 1.15–5.29, p = 0.02) were the influencing factors of POCD. Conclusion This study indicates that elevated CSF sTREM2 is associated with an increased risk of early POCD.

Postoperative cognitive dysfunction (POCD) is a major postoperative complication. Triggering receptor expressed on myeloid cells 2 (TREM2) exerts a neuroprotective function against neuro-inflammatory responses. The present study investigated the role of TREM2 in anesthesia and surgery-induced cognitive impairment and the potential related mechanism. Our results revealed that TREM2 was downregulated, coupled with activation of the NLRP3 inflammasome and subsequent IL-1β expression on postoperative day 3. A corresponding decline in PSD-95 and BDNF was found at the same time point. The key regulator of mitophagy PINK1 and Parkin protein levels were significantly decreased following surgery and anesthesia. TREM2 overexpression partially reversed postoperative cognitive impairment and enhanced PSD-95 and BDNF expression. TREM2 overexpression also improved mitophagy function and inhibited activation of the NLRP3 inflammasome and associated production of IL-1β. Our findings demonstrate that TREM2 rescues anesthesia and surgery-induced spatial learning and memory impairment and neuro-inflammation in aged C57/BL6 mice, which may be at least partially mediated through the activation of mitophagy and subsequent inhibition of the NLRP3 inflammasome.

Autophagy is crucial for cell survival, development, division, and homeostasis. The mammalian target of rapamycin (mTOR), which is the foremost negative controller of autophagy, plays a key role in many endogenous processes. The present study investigated whether rapamycin can ameliorate surgery-induced cognitive deficits by inhibiting mTOR and activating autophagy in the hippocampus. Both adult and aged C57BL/6J mice received an intraperitoneal injection of rapamycin (10 mg/kg/day) for 5 days per week for one and a half months. Mice were then subjected to partial hepatectomy under general anesthesia. Behavioral performance was assessed on postoperative days 3, 7, and 14. Hippocampal autophagy-related (Atg)-5, phosphorylated mTOR, and phosphorylated p70S6K were examined at each time point. Brain derived neurotrophic factor (BDNF), synaptophysin, and tau hyperphosphorylation (T396) in the hippocampus were also examined. Surgical trauma and anesthesia exacerbated spatial learning and memory impairment in aged mice on postoperative days 3 and 7. Following partial hepatectomy, the levels of phosphorylated mTOR, phosphorylated 70S6K, and phosphorylated tau were all increased in the hippocampus. A corresponding decline in BDNF and synaptophysin were observed. Rapamycin treatment restored autophagy function, attenuated phosphorylation of tau protein, and increased BDNF and synaptophysin expression in the hippocampus of surgical mice. Furthermore, surgery and anesthesia induced spatial learning and memory impairments were also reversed by rapamycin treatment. Autophagy impairments and mTOR hyperactivation were detected along with surgery-induced behavioral deficits. Inhibiting the mTOR signaling pathway with rapamycin successfully ameliorated surgery-related cognitive impairments by sustaining autophagic degradation, inhibiting tau hyperphosphorylation, and increasing synaptophysin and BDNF expression.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a crucial role in modulating microglial-mediated neuroinflammation. The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) regulates mitochondrial oxidative stress response and neuroinflammation. TREM2 deficiency impairs the denovo synthesis pathway of NAD

Accumulating evidence has demonstrated that damages of gut microbiota are strongly associated with central nervous system (CNS) diseases, such as perioperative neurocognitive disorders (PND). The present study investigated the role of gut microbial metabolite short-chain fatty acids (SCFAs) in surgery-induced cognitive deficits and neuroinflammation in the hippocampus. Adult male C57BL/6J mice received either SCFA mixture or saline orally for 4 weeks, and then partial hepatectomy was performed. The fecal supernatant of surgical mice was transplanted to normal mice for 3 weeks. The Morris water maze (MWM) and open-field tests were used to evaluate behavioral performance on postoperative or post-transplantation days 3 and 7. In the MWM test, pretreatment with exogenous SCFAs partially reversed surgery-induced impairments in crossing times and the time spent in the target quadrant on postoperative day 3 (p < 0.05, p < 0.05, respectively). In the open-field test, compared with the surgical mice, exogenous SCFA administration prior to surgery partially improved the locomotor activity (p < 0.05) and anxiety-like behavior (p < 0.05) on postoperative day 3. Surgical trauma and anesthesia enhanced ionized calcium-binding adapter molecule 1 (Iba-1) expression (p < 0.001), increased the levels of interleukin (IL)-1β (p < 0.001) and IL-6 (p < 0.001), and inhibited SCFA production (p < 0.001) on postoperative day 3. The expression of the brain-derived neurotrophic factor (BDNF) was also decreased (p < 0.001). Overall, surgical trauma and anesthesia exacerbated cognitive impairment, enhanced neuroinflammatory responses, and inhibited SCFA production. Pretreatment with SCFAs attenuated these effects partially by reversing microglial overactivation, inhibiting neuroinflammatory responses, and enhancing BDNF expression.

Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists exhibit neurotrophic and neuroprotective effects. The aim of this study was to explore whether the GLP-1R agonist exendin-4 can alter surgery-induced behavioral deficits and exert neuroprotective effects via the activation of the hippocampal GLP-1/GLP-1R pathway. 120 male Sprague-Dawley rats (aged 18–20 months old) were randomly divided into four groups: control group, exendin-4 group, surgery group, and surgery + exendin-4 group. The animals received either exendin-4 (5 µg/kg/day) or saline intra-peritoneally for 14 days, and then were subjected to partial hepatectomy 24 h after the last injection. Behavioral changes were evaluated with Morris Water Maze and Open field testing on postoperative days 7 and 14. The levels of IL-1β, NF-κB, Iba-1, Synaptophysin, GLP-1/GLP-1R, GSK-3β, p-GSK-3β (Ser9), p-Tau (Ser396), and p-Tau (Ser202/199) in the hippocampus were measured at the same time point. Surgical trauma induced an exacerbated spatial learning and memory impairment, increased the levels of depressive performance, and enhanced hippocampal NF-κB and IL-1β expression in the aged rats on postoperative day 7. A corresponding decline in GLP-1R was also found following surgical challenge on postoperative day 7. Exendin-4 treatment partly reversed surgery-induced postoperative behavioral impairment, downregulated the levels of NF-κB and IL-1β, ameliorated tau hyperphosphorylation and enhanced the activity of p-GSK-3β (Ser9). Together, the downregulation of GLP-1R exacerbated surgery-induced behavior deficits. Exendin-4 treatment attenuated these effects by inhibiting neuroinflammation and tau hyperphosphorylation. These findings suggest that pretreatment with exendin-4 is a potential adjuvant for preventing surgery-induced behavioral deficits.

Toll-like receptor 4 (TLR4) and TLR4 interactor with leucine-rich repeats (TRIL) play a crucial role in the inflammatory response. This study investigated the role of long noncoding RNA taurine-upregulated gene 1 (lncRNA TUG1) in TRIL/TLR4 signaling in spinal cord ischemia reperfusion (IR) injury. IR injury was induced in experimental rats; knockdown of TUG1 and TRIL was induced by intrathecal injection of siRNAs and overexpression of TRIL was induced by pcDNA3.3-TRIL. The results showed that the mRNA levels of TUG1 were increased at 12 hours after IR; this was accompanied by increased expression of the TRIL- and TLR4-mediated NF-κB/IL-1β signaling pathway. Activated microglia, detected with increased ionized calcium-binding adapter molecule 1 as a marker, exacerbated the hind-limb neurological impairment and blood-spinal cord barrier (BSCB) leakage after IR. TUG1 knockdown inhibited expression of TRIL and TLR4 signaling proinflammatory cytokines and microglial activation, and attenuated neurological deficit and BSCB leakage. TRIL knockdown inhibited the TLR4-mediated inflammatory response, while TRIL expression reversed the inhibited inflammatory effect caused by TUG1 knockdown. These data suggest that TUG1 knockdown inhibited inflammatory damage of the TLR4-mediated NF-κB/IL-1β signaling pathway after IR via suppressing TRIL expression.

Background This study was to determine the analgesic effect of ultrasound-guided erector spinae plane block (ESPB) and paravertebral block (PVB) as well as the combination of PVB and ESPB (P + E) after video-assisted thoracoscopic surgery (VATS). Patients and Methods Patients were randomly assigned to receive ESPB, PVB or PVB combined with ESPB with 0.5% ropivacaine (20 ml). The primary outcomes were cumulative hydromorphone consumption and Visual Analogue Scale (VAS) scores at rest and while coughing at 0 h, 12 h, 24 h, 48 h and 72 h postoperatively. The secondary outcomes were effective PCA usage count and rescue analgesia requirement at the same time points. Results The median (interquartile range) hydromorphone consumption, including converted oxycodone, was significantly different at 48 h postoperatively among the three groups (ESPB, 10.24 [9.53-11.71] mg; PVB, 9.94 [9.19-10.75] mg; P + E, 9.44 [8.96-9.97] mg; P = 0.011). Hydromorphone consumption in P + E group was lower compared with that in ESPB group at 12 h, 24 h and 48 h (P < 0.001, P = 0.004 and P = 0.003, respectively). VAS scores at rest were significantly higher for ESPB group compared to P + E group at 0 h postoperatively (P = 0.009). VAS scores while coughing were significantly higher for ESPB group compared to P + E group at 0 h and 12 h postoperatively (P = 0.015 and P < 0.001) and to the PVB group at 12 h postoperatively (P = 0.002). The effective PCA usage count in P + E group was lower than in ESPB group in 0-12 h (P < 0.001). More patients needed rescue analgesia in ESPB group compared to those in P + E group in 0-12 h, 0-24 h and 0-48 h (P = 0.022, 0.035 and 0.035, respectively). Conclusions Ultrasound-guided PVB combined with ESPB provided superior analgesia to ESPB for VATS. The combination of PVB and ESPB had a similar analgesic effect compared with PVB alone.

Background/Aims: TREM2 plays a crucial role in modulating microglial function through interaction with DAP12, the adapter for TREM2. Emerging evidence has demonstrated that TREM2 could suppress neuroinflammatory responses by repression of microglia-mediated cytokine production. This study investigated the potential role of TREM2 in surgery-induced cognitive deficits and neuroinflammatory responses in wild-type (WT) and APPswe/PS1dE9 mice. Methods: Adult APPswe/PS1dE9 transgenic male mice (a classic transgenic model of Alzheimer’s disease, 3 months old) and their age-matched WT mice received intracerebral lentiviral particles encoding the mouse TREM2 gene and then were subjected to partial hepatectomy at 1 month after the lentiviral particle injection. The behavioral changes were evaluated with an open-field test and Morris water maze test on postoperative days 3, 7, and 14. Hippocampal TREM2, DAP12, and interleukin (IL)-1β were measured at each time point. Ionized calcium-binding adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, synaptophysin, tau hyperphosphorylation (T396), and glycogen synthase kinase-3β (GSK-3β) were also examined in the hippocampus. Results: Surgical trauma induced an exacerbated cognitive impairment and enhanced hippocampal IL-1β expression in the transgenic mice on postoperative days 3 and 7. A corresponding decline in the levels of TREM2 was also found on postoperative days 3, 7, and 14. Overexpression of TREM2 downregulated the levels of IL-1β, ameliorated T396 expression, inhibited the activity of GSK-3β, and improved sickness behavior. Increased Arg1 expression and a high level of synaptophysin were also observed in the transgenic mice following TREM2 overexpression. Conclusion: The downregulation of TREM2 exacerbated surgery-induced cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Overexpression of TREM2 potentially attenuated these effects by decreasing the associated production of proinflammatory cytokines, inhibiting tau hyperphosphorylation, and enhancing synaptophysin expression.

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) remain common and distressing complications following surgery. PONV and PDNV can delay discharge and recovery and increase medical costs. The high incidence of PONV has persisted in part because of the tremendous growth in ambulatory surgery and the increased emphasis on earlier mobilization and discharge after both minor and major operations. Pharmacological management of PONV should be tailored to the patients' risk level using the PONV and PDNV scoring systems to minimize the potential for these adverse side effects in the postoperative period. A combination of prophylactic antiemetic drugs should be administered to patients with moderate-to-high risk of developing PONV in order to facilitate the recovery process. Optimal management of perioperative pain using opioid-sparing multimodal analgesic techniques and preventing PONV using prophylactic antiemetics are key elements for achieving an enhanced recovery after surgery. Strategies that include reductions of the baseline risk (e.g., adequate hydration, use of opioid-sparing analgesic techniques) as well as a multimodal antiemetic regimen will improve the likelihood of preventing both PONV and PDNV.

Increasing evidence indicates that stress potentiates pro-inflammatory response to a subsequent peripheral immune challenge. The present study investigated if prior exposure to inescapable tailshock (IS) delayed the recovery of surgery-induced spatial learning and memory impairment and prolonged hippocampus interleukin (IL)-1β and IL-6 expression. Methods A total of 192 aged rats were trained with Morris water-maze (MWM) for 6 consecutive days. A single session of inescapable tailshock was performed on day 6 after training. Then, the rats subjected to partial hepatectomy. Hippocampal-dependent spatial learning and memory were assessed on postoperative days 1, 3 and 7. The cytokines IL-1β and IL-6 and ionized calcium binding adaptor protein (Iba)-1 were measured at each time point. Cluster of differentiation 200 (CD200) was also measured to explore potential mechanisms of glial cell activation. Results Exposure of IS alone failed to affect the latency to platform and increase hippocampal cytokine levels at each time point. However, IS alone significantly increased the expression levels of Iba-1. A prolonged latency and additional significant increase in hippocampal levels of IL-1β and IL-6 were observed when partial hepatectomy was performed in aged rats exposed to IS 24 h later. The combination of IS and surgical trauma dramatically upregulated the levels of Iba-1 and significantly decreased the expression of CD200. Conclusion IS alone failed to induce cognitive deficits and increase pro-inflammatory cytokines expression. However, IS delayed the recovery of surgery-induced spatial learning and memory impairment and prolonged pro-inflammatory response to the subsequent surgery challenge.

Age is the most prominent risk factor for the development of postoperative cognitive dysfunction. The present study investigated the role of CX3CL1-CX3CR1 signaling in age-related differences in surgery-induced cognitive deficits and neuroinflammation. Adult and aged male Sprague-Dawley rats were subjected to partial hepatectomy or partial hepatectomy with intracerebroventricular infusion of CX3CL1. On postoperative days 3, 7, and 14, the rats were subjected to an open field test and the Morris water maze test. Hippocampal interleukin-1β, CX3CL1, CX3CR1, brain derived neurotrophic factor (BDNF), ionized calcium-binding adapter molecule 1 (Iba-1), and Arginase-1 (Arg1) levels were measured. Age exacerbated cognitive impairment and increased neuroinflammation following surgery. Surgery-induced decreases in CX3CL1 and CX3CR1 proteins were accompanied by increased microglial activation, as indicated by increased Iba-1 expression. Corresponding decline in Arg1 and BDNF levels were observed. Treatment with CX3CL1 decreased proinflammatory cytokines expression, increased BDNF and Arg1 levels in the brain, and enhanced behavioral recovery. The surgery-induced decreases in CX3CL1 and CX3CR1 expression exacerbated postoperative cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Treatment with CX3CL1 attenuated these effects, at least partly by inhibiting microglial activation, decreasing the associated production of proinflammatory cytokines, and enhancing BDNF expression.

Background: We evaluated the use of a new higher intensity 42 Watt cold laser for treating chronic pain related to osteoarthritis (OA) in former NFL football players. Methods: 39 consenting former NFL football players with OA underwent 1-3 treatment sessions lasting 10-20 min with a 42 Watt FDA-approved high-intensity cold laser (Phoenix thera-lase, Dallas, TX) at a wavelength of 1275 nm. We recorded their pain verbal rating scale (VRS) score at rest and with activity before and after each treatment using an 11-point VRS with 0=no pain to 10=worst pain imaginable. In addition, we assessed the duration of the painrelieving effect produced by each laser treatment, as well as its effects on other OA-related symptoms. Results: The chronic pain scores were significantly reduced both at rest and with activity after each treatment. Baseline VRS pain scores were 3.5 ± 2.9 at rest and 6.0 ± 2.6 with activity. After the initial treatment, the pain scores were reduced to 1.2 ± 1.8 (p

Accumulated evidence indicates that stress sensitizes neuroinflammatory responses to a subsequent peripheral immune challenge. The present study investigated whether chronic unpredictable stress (CUS) aggravated surgery-induced sickness behavior and neuroinflammatory processes via glucocorticoids secretion in the adult brain. Methods Sprague-Dawley adult male rats (12–14 weeks old) were exposed to 14-day CUS and then subjected to partial hepatectomy 24 h after the last stress session. The rats were pretreated with an antagonist of the glucocorticoids (GCs) receptor RU486 (30 mg/kg, i.p.) 1 h prior to stress exposure. The behavioral changes were evaluated with open field test and elevated plus-maze test. The hippocampal cytokines interleukin (IL)-1β and IL-6 were measured on postoperative days 1, 3 and 7. Ionized calcium binding adaptor protein (Iba)-1, microglial M2 phenotype marker Arg1, brain derived neurotrophic factor (BDNF) and CD200 were also examined at each time point. Results CUS exacerbated surgery-induced sickness behavior. Exposure to CUS alone failed to alter the levels of pro-inflammatory cytokines in the brain. However, CUS exaggerated surgery-induced pro-inflammatory cytokines expression (e.g. IL-1β and IL-6) and upregulated the levels of Iba-1 on postoperative days 1 and 3. An additional significant decreased BDNF, CD200 and a lower level of Arg1 were also observed in the stressed rats following surgical procedure. Pretreatment with RU486 blunted the potentiating effects of CUS on surgery-induced sickness behavior and neuroinflammatory responses. Conclusion Chronic unpredictable stress enhanced surgery-induced sickness behavior and neuroinflammatory responses. Stress-induced GCs played a pivotal role in enhancing surgery-induced neuroinflammatory processes by modulation of microglia functions.

Age is the most prominent risk factor for the development of postoperative cognitive dysfunction. This study investigated the potential role of anti-inflammatory interleukin (IL)-4 in age-related differences of surgery-induced cognitive deficits and neuroinflammatory responses. Both adult and aged Sprague-Dawley male rats were subjected to partial hepatectomy or partial hepatectomy with a cisterna magna infusion of IL-4. On postoperative days 1, 3, and 7, the rats were subjected to a reversed Morris water maze test. Hippocampal IL-1β, IL-6, IL-4, and IL-4 receptor (IL-4R) were measured at each time point. Brain derived neurotrophic factor (BDNF), synaptophysin, Ionized calcium-binding adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, and CD200 were also examined in the hippocampus. Age induced an exacerbated cognitive impairment and an amplified neuroinflammatory response triggered by surgical stress on postoperative days 1 and 3. A corresponding decline in the anti-inflammatory cytokine IL-4 and BDNF were also found in the aged rats at the same time point. Treatment with IL-4 downregulated the expression of proinflammatory cytokines (e.g., IL-1β and IL-6), increased the levels of BDNF and synaptophysin in the brain and improved the behavioral performance. An increased Arg1 expression and a high level of CD200 were also observed after a cisterna magna infusion of IL-4. An age-related decrease in IL-4 expression exacerbated surgery-induced cognitive deficits and exaggerated the neuroinflammatory responses. Treatment with IL-4 potentially attenuated these effects by enhancing BDNF and synaptophysin expression, inhibiting microglia activation and decreasing the associated production of proinflammatory cytokines.

The aim of this review is to provide an overview of the drugs and techniques used for multimodal postoperative pain management in the older population undergoing surgery in the ambulatory setting.Interest has grown in the possibility of adding adjuncts to a single shot nerve block in order to prolong the local anesthetic effect. The rapid and short-acting local anesthetics for spinal anesthesia are potentially beneficial for day-case surgery in the older population because of shorter duration of the motor block, faster recovery, and less transient neurologic symptoms. Another recent advance is the introduction of intravenous acetaminophen, which can rapidly achieve rapid peak plasma concentration (15 min) following infusion and analgesic effect in ∼5 min with a duration of action up to 4 h.The nonopioid analgesic therapies will likely assume an increasingly important role in facilitating the recovery process and improving the satisfaction for elderly ambulatory surgery patients. Strategies to avoid the use of opioids and minimize opioid-related side-effects is an important advance as we expand on the use of ambulatory surgery for the aging population.

It has been previously reported that subhypnotic doses of propofol could offer an advantage over midazolam for premedication. This study was designed to test the hypothesis that a 20 mg IV dose of propofol would be more effective than a standard 2 mg IV dose of midazolam for reducing acute anxiety prior to induction of anesthesia.One hundred twenty outpatients scheduled to undergo orthopedic surgery were randomly assigned to one of three study groups: control (saline); propofol (20 mg); or midazolam (2 mg). Immediately before administering the study medication, each patient evaluated their level of acute anxiety and sedation on 11‑point verbal rating scales (VRSs) 0=none- 10=highest, and they were also shown a picture. Upon arrival in the OR ~5 min after administering the study medication, anxiety and sedation levels were reassessed and a second picture was shown. At discharge from the recovery area, anxiety and sedation levels and their ability to recall the two pictures were reassessed.Compared to the saline group, both propofol and midazolam produced significant increases in the patient's level of sedation upon entering the OR (+2.5±2.4 vs. +4.6±2.5 and +5.2±2.3, respectively [p0.001]). Propofol was effective as midazolam compared to saline in reducing the patient's level of preinduction anxiety (from 3.2±2.2 to1.8±1.8 vs. 3.1±2.2 to 2.3±2.1 and 2.7±1.8 to 2.8±2.1, respectively). Propofol produced more pain on injection and midazolam significantly reduced recall of the second picture.When administered ~5 min prior to entering the OR, propofol, 20mg IV, was as effective as midazolam 2mg IV in reducing anxiety.

The aim is to investigate the clinical implications of the Oct-4 and Nestin protein in human breast cancers. A total of 346 cases including 26 fresh and 320 paraffin-embedded tumor tissues were selected for characterizing the frequency of CD44(+)CD24(-) tumor cells by flow cytometry and the differential expression of the stem cell-related genes between CD44(+)CD24(-) and non-CD44(+)CD24(-) tumor cells was analyzed by PCR Array and immunofluorescence. In comparison with the non-CD44(+)CD24(-) tumor cells, the CD44(+)CD24(-), particularly for those with high percentage of Oct-4(+) and Nestin(+), tumor cells had higher tumorigenicity by forming mammospheres in vitro. More importantly, 42 (13.125%) out of 320 tumor tissues were positive for Oct-4 and Nestin staining. Universal analysis and multivariate analysis revealed that the expression of Oct-4 and Nestin was associated significantly with younger age, pathogenic degrees, lymph node metastasis and triple-negative breast cancer independently (P

There is increasing interest in studying the role of tau hyperphosphorylation associated with memory impairment. We examined the involvement of tau hyperphosphorylation in memory impairment after hypothermia following isoflurane anaesthesia in rats.Adult rats were randomly divided into three groups: the control group received no treatment and others were subjected to 1.5% isoflurane anaesthesia with or without temperature control for 2 h. On the day before anaesthesia and on postanaesthetic days 1, 3 and 7, cognitive functions were assessed in a Y-maze test paradigm. To find the relationship between memory results and tau, we measured the site-specific phosphorylation of tau at Thr-205 and Ser-396 and the activity of protein phosphatase 2A within the hippocampus.The spatial learning and memory of animals with hypothermia were impaired at day 1 after anaesthesia, compared with nonanaesthetized rats. Anaesthesia and hypothermia led to tau hyperphosphorylation at the Thr-205 and Ser-396 epitopes in the hippocampus. There was no significant difference in the protein phosphatase 2A activity between the control and the postanaesthetic rat hippocampal samples, whereas nearly 45% protein phosphatase 2A inhibition was detected in the anaesthetized without temperature maintenance rat samples.Our results indicate that tau phosphorylation is not a direct result of anaesthesia per se, but it is due to anaesthesia-induced hypothermia and this leads to the inhibition of phosphatase activity as well as tau hyperphosphorylation. Tau hyperphosphorylation is associated with the observed deficits in spatial learning and memory following anaesthesia in hypothermic rats.

1. Postoperative cognitive dysfunction has become more prevalent in recent years. We used a splenectomized rat model with postoperative spatial learning and memory deficits to investigate the role of tau hyperphosphorylation and glycogen synthase kinase-3β (GSK-3β) within the hippocampus. 2. Cognitive function was assessed in a Y-maze 1 day before and 1, 3 and 7 days after surgery. We measured site-specific phosphorylation of hippocampal tau (Thr-205 and Ser-396), GSK-3β activity and expression of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) mRNA and protein as markers of inflammation. We also tested the effects of treatment with lithium chloride (LiCl), a GSK-3β inhibitor. 3. Splenectomy was associated with learning and memory impairment 3 days later, as well as a rapid and massive hyperphosphorylation of hippocampal tau at Thr-205 and Ser-396, activated GSK-3β, and increased IL-1β and TNF-α expression. LiCl completely restored tau hyperphosphorylation to control levels. 4. These data from the splenectomized rat model suggest that inflammatory factors affect tau pathology through the GSK-3β signalling pathway and that LiCl is a promising treatment for postoperative cognitive deficits.

• A case of electrocautery-induced ventricular fibrillation in a patient undergoing elective thoracotomy was presented.

Background There is currently no widely accepted instrument for measuring preoperative anxiety. The objective of this study was to develop a simple visual facial anxiety scale (VFAS) for assessing acute preoperative anxiety. Methods The initial VFAS was comprised of 11 similarly styled stick-figure reflecting different types of facial expressions (Fig 1). After obtaining IRB approval, a total of 265 participant-healthcare providers (e.g., anesthesiologists, anesthesiology residents, and perioperative nurses) were recruited to participate in this study. The participants were asked to: (1) rank the 11 faces from 0-10 (0 = no anxiety, while 10 = highest anxiety) and then to (2) match one of the 11 facial expression with a numeric verbal rating scale (NVRS) (0 = no anxiety and 10 = highest level of anxiety) and a specific categorical level of anxiety, namely no anxiety, mild, mild-moderate, moderate, moderate-high or highest anxiety. Based on these data, the Spearman correlation and frequencies of the 11 faces in relation to the 11-point numerical anxiety scale and 6 categorical anxiety levels were calculated. The highest frequency of a face assigned to a level of the numerical anxiety scale resulted in a finalized order of faces corresponding to the 11-point numeric rating scale. Results The highest frequency for each of the NVRS anxiety scores were as follow: A0, A1, A2, A3, A4, A5, A7, A6, A8, A9 and A10 (Fig 2). For the six categorical anxiety levels, a total of 260 (98.1%) participants chose the face A0 as representing 'no' anxiety, 250 (94.3%) participants chose the face A10 as representing 'highest' anxiety and 147 (55.5%) participants chose the face A8 as representing 'moderate-high' anxiety. Spearman analysis showed a significant correlation between the faces A3 and A5 assigned to the mild-moderate anxiety category (r = 0.58), but A5 was ultimately chosen due to its higher frequency compared to the frequency of A3 (30.6% vs 24.9%)(Fig 3). Similarly, the correlation of the faces A7 and A6 was significantly correlated with moderate anxiety (r = 0.87), but A7 remained because of its higher frequency (35.9% vs 22.6%). Using frequency and Spearman correlations, the final order of the faces assigned to the categories none, mild, mild-moderate, moderate, moderate-high and highest anxiety levels was A0, A1, A5, A7, A8 and A10, respectively (Fig 4). Conclusion The proposed VFAS was a valid tool for assessing the severity of acute [state] anxiety, and could be easy to administer in routine clinical practice.

Background Microglia are the primary immune cells of the spinal cord that are activated in response to ischemia/reperfusion (IR) injury and release various neurotrophic and/or neurotoxic factors to determine neuronal survival. Among them, matrix metalloproteinase-9 (MMP-9), which cleaves various components of the extracellular matrix in the basal lamina and functions as part of the blood spinal cord barrier (BSCB), is considered important for regulating inflammatory responses and microenvironmental homeostasis of the BSCB in the pathology of ischemia. Sevoflurane has been reported to protect against neuronal apoptosis during cerebral IR. However, the effects of sevoflurane preconditioning on spinal cord IR injury remain unclear. In this study, we investigated the role of sevoflurane on potential genetic roles of microglial MMP-9 in tight junction protein breakdown, opening of the BSCB, and subsequent recruitment of microglia to apoptotic spinal cord neurons. Results The results showed significant upregulation of MMP-9 in rats with IR-induced inflammation of the BSCB compared to that of the sham group, manifested as dysfunctional BSCB with increased Evans blue extravasation and reduced expression of occludin protein. Increased MMP-9 expression was also observed to facilitate invasion and migration of activated microglia, imaging as high Iba-1 expression, clustered to neurons in the injured spinal cord, as shown by double immunofluorescence, and increased proinflammatory chemokine production (CXCL10, CCL2). Further, sevoflurane preconditioning markedly improved motor function by ameliorating neuronal apoptosis, as shown by reduced TUNEL-positive cell counts and expression of cleaved caspase-3. These protective effects were probably responsible for downregulation of MMP-9 and maintenance of normal expression of occludin protein indicating BSCB integrity from inflammatory damage, which was confirmed by decreased protein levels of Iba-1 and MMP-9, as well as reduced production of proinflammatory chemokines (CXCL10, CCL2) and proinflammatory cytokines (IL-1β). Intrathecal injection of specific siRNAs targeting MMP-9 had similar protective effects to those of sevoflurane preconditioning. Conclusions Preconditioning with 2.4% sevoflurane attenuated spinal cord IR injury by inhibiting recruitment of microglia and secretion of MMP-9; thus inhibiting downstream effects on inflammatory damage to BSCB integrity and neuronal apoptosis. Electronic supplementary material The online version of this article (doi:10.1186/s13041-014-0069-7) contains supplementary material, which is available to authorized users.

It is known that surgery-induced tissue damage activates the peripheral immune system resulting in the release of inflammatory mediators and cognitive impairment in aged mice. Vitamin D has been shown to have immunomodulatory function, but the molecular basis for it has not been well understood. In this study, we mainly investigated the efficacy and mechanism of vitamin D against postoperative cognitive dysfunction (POCD). The treatment of C57BL mice with vitamin D significantly preserves postoperative cognitive function, markedly inhibits surgery-induced interleukin (IL)-17, IL-6, transforming growth factor beta (TGF-β), and retinoic acid-related orphan receptor (RORγt) production, and obviously induces IL-10 and forkhead box p3 (Foxp3) expression. These findings indicate that vitamin D amelioration of POCD is, to a large extent, due to inhibit inflammatory CD4_T cell lineage, T helper 17 (Th17) cells, accompanied with expansion in regulatory T cells (Treg cells), a subset of CD4_T cells that are important in inhibiting inflammation. Our results suggest that Th17 and Treg cell imbalance may play a role in the development of POCD. Vitamin D is useful in the control of inflammatory diseases.

Postoperative cognitive dysfunction (POCD) is characterized by the progressive deterioration of intellectual/cognitive function following surgery. It has been suggested that the senile brain, which characteristically expresses higher levels of central proinflammatory cytokines, interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α, is more susceptible to additional insult following surgery. The authors of this study investigated the expression of central cytokines IL-1β, IL-6 and TNF-α and hippocampal glial cell activation in aged and adult rats following partial hepatectomy. Cognitive function was assessed in a reversal-learning version of the Morris water maze (MWM) before and after surgery. Hippocampal pro-inflammatory cytokines IL-1β, IL-6 and TNF-α and glial cell activation markers glial fibrillary acidic protein (GFAP) and S100β were measured at each time point; CD200 and CD200R were also measured to explore potential mechanisms of glial cell activation. Surgical trauma resulted in impairments in distance and latency only on postoperative day 1 (p