Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane-exposed offspring mice.

INTRODUCTION: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO. METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods. RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor. CONCLUSION: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.

Effect of different modes of administration of dexmedetomidine on the quality of recovery in ambulatory thyroidectomy: a randomized, controlled trial.

OBJECTIVE: To compare the effects of two different administration methods of dexmedetomidine (DEX) used as an adjuvant to ropivacaine in ultrasound-guided bilateral intermediate cervical plexus block (CPB) in terms of efficacy and the duration of postoperative analgesia in patients undergoing ambulatory thyroidectomy. METHODS: This double-blind, randomized study enrolled patients who underwent thyroidectomy with ultrasound-guided bilateral intermediate CPB. Patients were randomized to receive either perineural administration of dexmedetomidine (group DP) or intravenous pumping of dexmedetomidine (group DI). The 40-item Quality of Recovery (QoR-40) questionnaire was used to assess the primary endpoint, which was the global QoR-40 score 24 h after the operation. RESULTS: Sixty patients were randomized equally into the two groups. The total QoR-40 score 24 h postoperatively was significantly higher in group DP than group DI (160.6 ± 9.1 versus 152.8 ± 7.9, respectively). Dimensions of physical comfort and pain scores were significantly higher in group DP than group DI. The visual analogue scale pain score scores were significantly lower in group DP than group DI at 12 and 24 h postoperatively. CONCLUSIONS: DEX as an adjuvant to ropivacaine in ultrasound-guided intermediate CPB can improve the QoR-40 score and prolong postoperative analgesia.Trial registration number: ChiCTR2000031264 at www.chictr.org.cn on 26 March 2020.

[Effects of low-dose dexmedetomidine combined with hydromorphone in postoperative analgesia and on the serum IL-6 and CRP levels of prostate cancer patients].

OBJECTIVE: To explore the effects of low-dose dexmedetomidine (DM) combined with hydromorphone (HM) in postoperative analgesia and on levels of serum interleukin-6 (IL-6) and C-reactive protein (CRP) in PCa patients. METHODS: Using the random number table, we divided 102 PCa patients undergoing radical prostatectomy from January 2019 to November 2020 into a trial group (n = 51) and a control group (n = 51), the former given HM and the latter low-dose DM + HM for postoperative analgesia. We recorded the postoperative resuscitation time, extubation time and pain, perioperative cognitive function, IL-6 and CRP levels, and drug-related adverse reactions of the patients, and compared them between the two groups. RESULTS: There was no statistically significant difference in postoperative resuscitation time and extubation time between the two groups of patients (P > 0.05). The frequency of patient-controlled epidural analgesia (PCEA) compressions was lower in the trial than in the control group within 24 hours after surgery (P < 0.05). The Visual Analogue Scale (VAS) scores were higher in both of the groups at 24 hours than at 4, 12, and 48 hours after surgery (P < 0.05), at 12 hours than at 4 and 48 hours (P < 0.05) and at 4 hours than at 48 hours (P < 0.05), but lower in the trial than in the control group at 4, 12 and 24 hours postoperatively (P < 0.05). No statistically significant difference was observed in the scores of the Mini Mental State Evaluation Scale between the two groups of patients (P > 0.05). The levels of IL-6 and CRP were higher in both of the groups at 24 hours after than before and at 4, 12 and 48 hours after surgery (P < 0.05), at 48 hours after than before and at 4 and 12 hours after surgery (P < 0.05), at 12 hours after than before and at 4 hours after surgery (P <0.05), and at 4 hours after than before surgery (P < 0.05), but lower in the trial than in the control group at 4, 12, 24 and 48 hours postoperatively (P < 0.05). There was no statistically significant difference in the total incidence rate of adverse reactions between the two groups (P > 0.05). CONCLUSIONS: Low-dose dexmedetomidine combined with hydromorphone is a safe and effective option for postoperative analgesia in PCa patients, and it can inhibit the expression of inflammatory factors.

G protein-coupled estrogen receptor in the rostral ventromedial medulla contributes to the chronification of postoperative pain.

AIMS: Chronification of postoperative pain is a common clinical phenomenon following surgical operation, and it perplexes a great number of patients. Estrogen and its membrane receptor (G protein-coupled estrogen receptor, GPER) play a crucial role in pain regulation. Here, we explored the role of GPER in the rostral ventromedial medulla (RVM) during chronic postoperative pain and search for the possible mechanism. METHODS AND RESULTS: Postoperative pain was induced in mice or rats via a plantar incision surgery. Behavioral tests were conducted to detect both thermal and mechanical pain, showing a small part (16.2%) of mice developed into pain persisting state with consistent low pain threshold on 14 days after incision surgery compared with the pain recovery mice. Immunofluorescent staining assay revealed that the GPER-positive neurons in the RVM were significantly activated in pain persisting rats. In addition, RT-PCR and immunoblot analyses showed that the levels of GPER and phosphorylated µ-type opioid receptor (p-MOR) in the RVM of pain persisting mice were apparently increased on 14 days after incision surgery. Furthermore, chemogenetic activation of GPER-positive neurons in the RVM of Gper-Cre mice could reverse the pain threshold of pain recovery mice. Conversely, chemogenetic inhibition of GPER-positive neurons in the RVM could prevent mice from being in the pain persistent state. CONCLUSION: Our findings demonstrated that the GPER in the RVM was responsible for the chronification of postoperative pain and the downstream pathway might be involved in MOR phosphorylation.

An appropriate level of autophagy reduces emulsified isoflurane-induced apoptosis in fetal neural stem cells.

Autophagy plays essential roles in cell survival. However, the functions and regulation of the autophagy-related proteins Atg5, LC3B, and Beclin 1 during anesthetic-induced developmental neurotoxicity remain unclear. This study aimed to understand the autophagy pathways and mechanisms that affect neurotoxicity, induced by the anesthetic emulsified isoflurane, in rat fetal neural stem cells. Fetal neural stem cells were cultured, in vitro, and neurotoxicity was induced by emulsified isoflurane treatment. The effects of pretreatment with the autophagy inhibitors 3-methyladenine and bafilomycin and the effects of transfection with small interfering RNA against ATG5 (siRNA-Atg5) were observed. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and apoptosis was assessed using flow cytometry. Ultrastructural changes were analyzed through transmission electron microscopy. The levels of the autophagy-related proteins LC3B, Beclin 1, Atg5, and P62 and the pro-apoptosis-related protein caspase-3 were analyzed using western blot assay. The inhibition of cell proliferation and that of apoptosis rate increased after treatment with emulsified isoflurane. Autophagolysosomes, monolayer membrane formation due to lysosomal degradation, were observed. The autophagy-related proteins LC3B, Beclin 1, Atg5, and P62 and caspase-3 were upregulated. These results confirm that emulsified isoflurane can induce toxicity and autophagy in fetal neural stem cells. Pre-treatment with 3-methyladenine and bafilomycin increased the apoptosis rate in emulsified isoflurane-treated fetal neural stem cells, which indicated that the complete inhibition of autophagy does not alleviate emulsified isoflurane-induced fetal neural stem cell toxicity. Atg5 expression was decreased significantly by siRNA-Atg5 transfection, and cell proliferation was inhibited. These results verify that the Atg5 autophagy pathway can be regulated to maintain appropriate levels of autophagy, which can inhibit the neurotoxicity induced by emulsified isoflurane anesthetic in fetal neural stem cells.

Dexmedetomidine inhibits the invasion, migration, and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by reducing the expression of NLRC5.

Rheumatoid arthritis (RA) is a chronic, autoimmune disease characterized by inflammatory synovitis, but its pathogenesis remains unclear. NLRC5 is a newly discovered member of the NLR family that is effective in regulating autoimmunity, inflammatory responses, and cell death processes. Dexmedetomidine (DEX) has been reported to have a variety of pharmacological effects, including anti-inflammatory and analgesic effects. However, the role of DEX in RA has not been explored. In adjuvant-induced arthritis (AA) rat models, DEX (10 µg/kg and 20 µg/kg) reduced the pathological score, the arthritis score, paw swelling volume, and the serum levels of IL-1ß, IL-6, IL-17A, and TNF-α. Moreover, by using Western blot and real-time quantitative PCR (RT-qPCR), it was demonstrated that DEX can inhibit the expression of IL-1ß, IL-6, MMP-3, MMP-9 and P-P65 in the synovial tissue of AA rats. In human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs), DEX (250 nM and 500 nM) was found to inhibit the expression of IL-1ß, IL-6, MMP-3, MMP-9, and P-P65 following stimulation with TNF-α. Moreover, DEX can inhibit the invasion and migration of RA-FLSs stimulated by TNF-α. Finally, the expression of NLRC5 in RA-FLSs and AA rat models was also reduced by DEX. After silencing NLRC5 in RA-FLSs, the expression of IL-1ß, IL-6, MMP-3, MMP-9, and P-P65, as well as the invasion and migration of cells, were significantly reduced. These results indicate that DEX inhibits the invasion, migration, and inflammation of RA-FLSs by reducing the expression of NLRC5 and inhibiting the NF-κB activation.

Margatoxin mitigates CCl4­induced hepatic fibrosis in mice via macrophage polarization, cytokine secretion and STAT signaling.

A number of macrophage phenotypes have been previously identified as crucial regulators in the progression of hepatic fibrosis (HF). Cytokines from macrophages or Kupffer cells (KCs) have also been identified to be important regulators in HF. Blocking Kv1.3 in models of HF, regulating macrophage polarization and cytokine secretion have not yet been assessed as potential treatments options for this condition. In the current study, a model of carbon tetrachloride (CCl4)­induced HF was established and examined the effects of margatoxin (MgTX; an inhibitor of Kv1.3) on HF. Hematoxylin and eosin, Masson's trichrome and immunohistochemistry staining were performed to determine whether MgTX can alleviate liver fibrosis. To elucidate the mechanisms through which MgTX attenuates liver injury, reverse transcription­quantitative PCR and western blot analysis were used to detect polarized macrophage markers in RAW264.7 cells and cytokines were examined using ELISA. Furthermore, macrophage polarization signal transducer and activator of transcription (STAT) signaling, which is associated with macrophage polarization, was identified in RAW264.7 cells. The results revealed that MgTX protected the mice from CCl4­induced liver fibrosis. Furthermore, MgTX decreased the expression of M1 phenotype biomarkers, and increased the expression of M2 phenotype biomarkers in CCl4­induced HF. Additionally, the production of pro­inflammatory cytokines was decreased and interleukin­10 production was increased in the serum of mice with HF injected with MgTX. Furthermore, MgTX was found to regulate the expression of M1 markers by suppressing p­STAT1 activity and increasing the expression of M2 markers by promoting p­STAT6 activity. On the whole, the findings of this study demonstrate that MgTX is able to alleviate CCl4­induced HF in mice, possibly via macrophage polarization, cytokine secretion and STAT signaling.

Effects of Morphine on Interstitial Cells of Cajal in Rabbit Colon and Small Intestinal Transit: An Experimental Study.

OBJECTIVE: This study aims to investigate the effect of morphine with naloxone on intestinal peristalsis and the number of interstitial cells of Cajal (ICC) in colon tissues of rabbits. METHODS: Thirty rabbits were randomly divided into five groups (n=6, each group): saline control group (NS group), low concentration of morphine group (L group), medium concentration of morphine group (M group), high concentration of morphine group (H group), medium concentration of morphine and naloxone mixed with antagonist group (NM group). Rabbits in these five groups were administered with an epidural puncture tube and dorsal epidural analgesia pump, and were continuously infused for seven days. Fecal characteristics were observed, and the ink propulsion rate was calculated. The expression level of ICC C-kit protein in colon tissues was tested by western blot. RESULTS: The stool characteristics in the L, M and H groups were more severe than those in the NS and NM groups. Furthermore, the intestinal propulsion rate in the L, M and H groups was lower than that in the NS and NM groups. The C-kit mRNA and protein expression in the colon of rabbits were significantly lower in the L, M and H groups, when compared to the NS and NM groups. CONCLUSION: Naloxone blocked the mRNA and protein expression of C-kit, and improved intestinal motor function.

Hyperbaric oxygen preconditioning improves postoperative cognitive dysfunction by reducing oxidant stress and inflammation.

Postoperative cognitive dysfunction is a crucial public health issue that has been increasingly studied in efforts to reduce symptoms or prevent its occurrence. However, effective advances remain lacking. Hyperbaric oxygen preconditioning has proved to protect vital organs, such as the heart, liver, and brain. Recently, it has been introduced and widely studied in the prevention of postoperative cognitive dysfunction, with promising results. However, the neuroprotective mechanisms underlying this phenomenon remain controversial. This review summarizes and highlights the definition and application of hyperbaric oxygen preconditioning, the perniciousness and pathogenetic mechanism underlying postoperative cognitive dysfunction, and the effects that hyperbaric oxygen preconditioning has on postoperative cognitive dysfunction. Finally, we conclude that hyperbaric oxygen preconditioning is an effective and feasible method to prevent, alleviate, and improve postoperative cognitive dysfunction, and that its mechanism of action is very complex, involving the stimulation of endogenous antioxidant and anti-inflammation defense systems.

Effects of intravenous lidocaine, dexmedetomidine and their combination on postoperative pain and bowel function recovery after abdominal hysterectomy.

BACKGROUND: Intravenous (IV) lidocaine and dexmedetomidine have been shown to decrease postoperative pain, reduce analgesic consumption and facilitate return of bowel function. We investigated whether lidocaine combined with dexmedetomidine infusion was superior in controlling pain and recovery of bowel function. METHODS: A total of 240 women undergoing elective abdominal hysterectomy were randomly assigned into four groups: group CON received normal saline infusion, group LIDO received lidocaine infusion (1.5 mg/kg loading, 1.5 mg/kg/h infusion), group DEX received dexmedetomidine infusion (0.5 µg/kg loading, 0.4 µg/kg/h infusion) and group LIDO+DEX received lidocaine (1.5 mg/kg loading, 1.5 mg/kg/h infusion) and dexmedetomidine infusions (0.5 µg/kg loading, 0.4 µg/kg/h infusion). The primary outcome was visual analog pain scale (VAS) scores at 1, 4, 8, 12, 24, and 48 hours after surgery. The secondary outcomes included time to first bowel sounds and flatus, postoperative fentanyl requirement and perioperative propofol and remifentanil consumption. RESULTS: The VAS scores were significantly lower in groups LIDO and DEX at 4, 8, and 12 hours compared to group CON after surgery (P<0.01). The VAS scores were also significantly lower in group LIDO+DEX at 1, 4, 8, 12, and 24 hours compared to other three groups after surgery (P<0.01). Time to first bowel sounds and flatus was significantly shorter in groups LIDO and LIDO+DEX than groups CON and DEX (P<0.01). Postoperative fentanyl requirement was significantly lower in group LIDO at 1 and 4 hours and in group DEX at 1, 4, 8 hours compared to group CON after surgery (P<0.01). Postoperative fentanyl requirement was also significantly lower in group LIDO+DEX at 1, 4, 8, 12, 24 and 48 hours compared to other three groups after surgery (P<0.01). Propofol and remifentanil consumption was significantly lower in groups LIDO, DEX and LIDO+DEX compared to group CON (P<0.01). CONCLUSIONS: Lidocaine combined with dexmedetomidine infusion significantly improved postoperative pain and enhanced recovery of bowel function undergoing abdominal hysterectomy.

A simple blind placement of the left-sided double-lumen tubes.

One-lung ventilation (OLV) has been commonly provided by using a double-lumen tube (DLT). Previous reports have indicated the high incidence of inappropriate DLT positioning in conventional maneuvers.After obtaining approval from the medical ethics committee of First Affiliated Hospital of Anhui Medical University and written consent from patients, 88 adult patients belonging to American society of anesthesiologists (ASA) physical status grade I or II, and undergoing elective thoracic surgery requiring a left-side DLT for OLV were enrolled in this prospective, single-blind, randomized controlled study. Patients were randomly allocated to 1 of 2 groups: simple maneuver group or conventional maneuver group. The simple maneuver is a method that relies on partially inflating the bronchial balloon and recreating the effect of a carinal hook on the DLTs to give an idea of orientation and depth. After the induction of anesthesia the patients were intubated with a left-sided Robertshaw DLT using one of the 2 intubation techniques. After intubation of each DLT, an anesthesiologist used flexible bronchoscopy to evaluate the patient while the patient lay in a supine position. The number of optimal position and the time required to place DLT in correct position were recorded.Time for the intubation of DLT took 100 ±â€Š16.2 seconds (mean ±â€ŠSD) in simple maneuver group and 95.1 ±â€Š20.8 seconds in conventional maneuver group. The difference was not statistically significant (P = 0.221). Time for fiberoptic bronchoscope (FOB) took 22 ±â€Š4.8 seconds in simple maneuver group and was statistically faster than that in conventional maneuver group (43.6 ±â€Š23.7 seconds, P < 0.001). Nearly 98% of the 44 intubations in simple maneuver group were considered as in optimal position while only 52% of the 44 intubations in conventional maneuver group were in optimal position, and the difference was statistically significant (P < 0.001).This simple maneuver is more rapid and more accurate to position left-sided DLTs, it may be substituted for FOB during positioning of a left-sided DLT in condition that FOB is unavailable or inapplicable.

Comparison of the type and severity of early attentional network decline after total intravenous or epidural anesthesia in middle-aged women after gynecological surgery.

Compared with regional anesthesia, general anesthesia may increase the risk of postoperative cognitive decline. This study aimed to investigate the type and severity of attentional network decline and the recovery of attentional networks in middle-aged women after gynecological surgery. A total of 140 consenting women undergoing elective gynecological surgery were enrolled in the study. Patients were assigned randomly to receive either total intravenous anesthesia or epidural anesthesia. To determine the efficacy of the attentional networks, patients were examined for alerting, orienting, and executive networks on the preoperative day and on the first and fifth postoperative days using the attentional network test. Significant differences were observed in the effect scores of the three attentional networks at all time points. These effect scores differed significantly between groups and between 1 and 5 days postoperation (DPO). Participants showed significantly lower effect scores for the alerting and orienting network tasks and had more difficulties in resolving conflict at 1 DPO compared with the baseline. On comparing effect scores between baseline and 5 DPO, no significant differences on the alerting and orienting network tasks were observed in the epidural anesthesia group, a significant difference on the orienting network task was observed in the general anesthesia group, and significant differences on the executive control network were observed in both the groups. Compared with epidural anesthesia, total intravenous anesthesia is more likely to impair and delay the recovery of attentional networks in middle-aged women undergoing elective hysterectomy. The executive control function showed marked damage and there were difficulties in recovery from either type of anesthesia.

Selective impairment of attention networks during propofol anesthesia after gynecological surgery in middle-aged women.

BACKGROUND: Postoperative cognitive dysfunction is a common complication of anesthesia and surgery. Attention networks are essential components of cognitive function and are subject to impairment after anesthesia and surgery. It is not known whether such impairment represents a global attention deficit or relates to a specific attention network. We used an Attention Network Task (ANT) to examine the efficiency of the alerting, orienting, and executive control attention networks in middle-aged women (40-60 years) undergoing gynecologic surgery. A matched group of medical inpatients were recruited as a control. METHODS: Fifty female patients undergoing gynecologic surgery (observation group) and 50 female medical inpatients (control group) participated in this study. Preoperatively patients were administered a mini-mental state examination as a screening method. The preoperative efficiencies of three attention networks in an attention network test were compared to the 1st and 5th post-operative days. RESULTS: The control group did not have any significant attention network impairments. On the 1st postoperative day, significant impairment was shown in the alerting (p=0.003 vs. control group, p=0.015 vs. baseline), orienting (p<0.001 vs. both baseline level and control group), and executive control networks (p=0.007 vs. control group, p=0.002 vs. baseline) of the observation group. By the 5th postoperative day, the alerting network efficiency had recovered to preoperative levels (p=0.464 vs. baseline) and the orienting network efficiency had recovered partially (p=0.031 vs. 1st post-operative day), but not to preoperative levels (p=0.01 vs. baseline). The executive control network did not recover by the 5th postoperative day (p=0.001 vs. baseline, p=0.680 vs. 1st post-operative day). CONCLUSIONS: Attention networks of middle-aged women show a varying degree of significant impairment and differing levels of recovery after surgery and propofol anesthetic.

Subhypnotic doses of propofol impair spatial memory retrieval in rats.

Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3ß (GSK-3ß) activity affects memory. Constitutively active GSK-3ß is required for memory retrieval, and propofol has been shown to inhibit GSK-3ß. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3ß activity. Adult Sprague-Dawley rats were trained on a Morris water maze task (eight acquisition trials in one session) and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol (25 mg/kg) spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3ß in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3ß signaling in the hippocampus.

[Investigation methodology and application on scientific and technological personnel of traditional Chinese medical resources based on data from Chinese scientific research paper].

The aim of this study is to identify the present status of the scientific and technological personnel in the field of traditional Chinese medicine (TCM) resource science. Based on the data from Chinese scientific research paper, an investigation regarding the number of the personnel, the distribution, their output of paper, their scientific research teams, high-yield authors and high-cited authors was conducted. The study covers seven subfields of traditional Chinese medicine identification, quality standard, Chinese medicine cultivation, harvest processing of TCM, market development and resource protection and resource management, as well as 82 widely used Chinese medicine species, such as Ginseng and Radix Astragali. One hundred and fifteen domain authority experts were selected based on the data of high-yield authors and high-cited authors. The database system platform "Skilled Scientific and Technological Personnel in the field of Traditional Chinese Medicine Resource Science-Chinese papers" was established. This platform successfully provided the retrieval result of the personnel, output of paper, and their core research team by input the study field, year, and Chinese medicine species. The investigation provides basic data of scientific and technological personnel in the field of traditional Chinese medicine resource science for administrative agencies and also evidence for the selection of scientific and technological personnel and construction of scientific research teams.

Awakening from anesthesia using propofol or sevoflurane with epidural block in radical surgery for senile gastric cancer.

OBJECTIVE: To study the awakening of the elderly patients from propofol intravenous general anesthesia or sevoflurane inhalation general anesthesia combined with epidural block after radical gastric cancer surgery. METHOD: Eighty cases receiving selective radical surgery for gastric cancer were included. They were aged 65-78 years and classified as ASA grade I-II. Using a random number table, the cases were divided into 4 groups (n = 20): propofol intravenous general anesthesia (P group), sevoflurane inhalation general anesthesia (S group), propofol intravenous general anesthesia combined with epidural block (PE group), and sevoflurane inhalation general anesthesia combined with epidural block (SE group). For P and PE group, target controlled infusion of propofol was performed; for S and SE group, sevoflurane was inhaled to induce and maintain general anesthesia; for PE and SE group, before general anesthesia induction, epidural puncture and catheterization at T7-8 was performed. After surgery, perform patient controlled intravenous analgesia (PCIA) or patient controlled epidural analgesia (PCEA), and maintain VAS ≤ 3. The recorded indicators were as follows: time to recovery of spontaneous respiration, time to awakening, time of endotracheal tube removal, time to orientation, time to achieve modified Aldrete scores ≥ 9, modified OAA/S and Aldrete scores upon endotracheal tube removal (T1), 5 min after removal (T2), 15 min after removal (T3) and 30 min after removal (T4), dose of intraoperative remifentanil, intraoperative hypotension, and emergence agitation. RESULTS: Time to awakening, time of endotracheal tube removal, time to orientation, and time to achieve modified Aldrete scores ≥ 9 in PE and SE group were obviously shortened compared with P and S group (P < 0.05); modified OAA/S and Aldrete scores at T1 and T2 in PE and SE group were significantly higher than those in P and S group (P < 0.05), and the scores of SE group at T1 were much higher compared to PE group (P < 0.05). Dose of intraoperative remifentanil in PE and SE group was significantly lower than that in P and S group. CONCLUSION: Compared to propofol intravenous general anesthesia or sevoflurane inhalation general anesthesia, propofol or sevoflurane general anesthesia combined with epidural block was more conducive to increasing the awakening quality of the senile patients from anesthesia after radical gastric cancer surgery. Moreover, sevofluorane inhalation general anesthesia combined with epidural block achieved a more stable hemodynamics and a shortened time to awakening.

Involvement of GSK3ß/ß-catenin signaling in the impairment effect of ketamine on spatial memory consolidation in rats.

The cellular mechanisms underlying amnesia produced by the analgesic ketamine are not clear. The current study examined the effects of ketamine on memory consolidation in rats trained in a Morris water maze task, and further tested whether the glycogen synthase kinase (GSK)3ß/ß-catenin signaling pathway was involved in mediating the effects of posttraining ketamine on retention. Adult male Sprague-Dawley rats were injected with ketamine (0, 25, 50, or 100mg/kg) immediately after an eight-trial water maze training session. A probe trial was carried out 24 h later to examine the effects of ketamine on memory. Rats hippocampi were subjected to western blot assays to measure levels of native versus phosphorylated (p) GSK3ß and ß-catenin protein. Memory performance was significantly impaired in rats injected with ketamine (100 mg/kg) after training. Western blots showed that p-GSK-3ß(Ser9) levels were reduced and p-ß-catenin(Ser33/37/Thr41) levels were elevated in ketamine treated rats during consolidation. These posttraining changes in hippocampal p-GSK-3ß and p-ß-catenin were blocked by injection of 100mg/kg ketamine immediately after training, indicating that the 100mg/kg dose of ketamine altered activation of GSK3ß/ß-catenin signaling pathway in the hippocampus. Acute injection of the GSK3ß specific inhibitor SB216763 (1 ng/0.5 µl/side) into area CA1 of the hippocampus after water maze training prevented ketamine-induced impairment of memory and blocked ketamine-induced effects on the GSK3ß/ß-catenin signaling pathway in the hippocampus. Our results suggest that an anesthetic dose of ketamine injected immediately after Morris water maze training impaired memory consolidation and support the hypothesis that GSK3ß/ß-catenin signaling may play a role in ketamine-induced retrograde amnesia.

Peroxisome proliferator-activated receptor-α activation protects against endoplasmic reticulum stress-induced HepG2 cell apoptosis.

Live ischemia-reperfusion injury is associated with endoplasmic reticulum (ER) stress-induced apoptosis. Activation of peroxisome proliferator-activated receptor-α (PPARα) may inhibit hepatocyte apoptosis induced by oxidative stress and protect against liver injury. This study aimed to investigate the effects of PPARα activation, through a specific agonist, on ER stress-induced apoptosis in human liver hepatocellular carcinoma (HepG2) cells. HepG2 cells were challenged with H2O2 and treated with WY14643, a selective PPARα agonist, in the presence or absence of the PPARα antagonist of MK886. Cell viable assay (MTT) and immunostaining were used to evaluate cell viability. The level of apoptotic cell death was quantified through Annexin V/PI staining. Alanine aminotransferase, asparatate aminotransferase, and malondialdehyde levels were measured to determine the presence of cellular injury and oxidative stress. RT-PCR and Western blot analysis were used to detect mRNA and protein expression of PPARα, BiP, and CHOP. Immunofluorescence was utilized to determine the intracellular localization of CHOP. H2O2 and MK886 both reduced the viability of HepG2 cells, increased oxidative stress and apoptosis, up-regulated the BiP and CHOP expression, and induced CHOP translocation from the cytoplasm to the nucleus. Compared with cells treated with H2O2 alone, pre-administration of WY14643 increased cell viability, attenuated apoptosis, improved cell function, down-regulated BiP and CHOP expression and inhibited CHOP translocation. The effects of WY14643 were completely abolished using the MK886 antagonist. PPARα activation protects against H2O2-induced HepG2 cell apoptosis. The underlying mechanisms may be associated with its activation to suppress excessive ER stress.

Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China.

AIM: To construct normal values for the tests of the psychometric hepatic encephalopathy score (PHES) and to evaluate its usefulness in the diagnosis of minimal hepatic encephalopathy (MHE) among Chinese individuals with cirrhosis. METHODS: The five tests of PHES, number connection test-A (NCT-A), number connection test-B, serial dotting test, line tracing test and digit symbol test (DST), were administered to all enrolled subjects in a quiet room with sufficient light. Cirrhotic subjects with overt HE were excluded by the West-Haven criteria and a detailed neurological examination. Based on the nomograms of healthy volunteers, the patients were classified as having MHE when their PHES was less than -4. RESULTS: In total, 146 healthy volunteers completed all the PHES tests. Age and education years were confirmed to be predictors of all five tests. In total, 53 patients with liver cirrhosis completed the PHES. Of the patients with liver cirrhosis, 24 (45.3%), 22(41.5%) and 7(13.2%) had Child-Pugh grades A, B and C, respectively. MHE was diagnosed in 26 patients (49.1%). Compared with compensated cirrhotic patients (Child A), decompensated cirrhotic patients (Child B and C) had a higher proportion of MHE (65.5% vs 29.2%). No differences in age and education years were found between the MHE and non-MHE groups. NCT-A and DST were able to diagnose MHE with a sensitivity of 76.9% and a specificity of 96.3% (AUC = 0.866, K = 0.735). CONCLUSION: The proportion of MHE is associated with liver function. NCT-A and DST are simple tools that can be used for the diagnosis of MHE in China.

Antioxidant Stress and Anti-Inflammation of PPARα on Warm Hepatic Ischemia-Reperfusion Injury.

Hepatic ischemia-reperfusion (IR) injury is a serious clinical problem. Minimizing the adverse effect of ischemia-reperfusion injury after liver surgery or trauma is an urgent need. It has been proved that besides the effect of regulating the lipid and lipoprotein metabolism, PPARα also undertakes the task of organ protection. In this paper, related literature has been summarized and we come to the conclusion that administration of PPARα agonists can strengthen the antioxidant and anti-inflammation defense system by the upregulation of the expression of antioxidant enzymes and inhibition of NF-κB activity. This may provide a potential clinical treatment for hepatic ischemia-reperfusion injury.