Differential hippocampal protein expression between normal mice and mice with the perioperative neurocognitive disorder: a proteomic analysis.

OBJECTIVES: To compare differential expression protein in hippocampal tissues from mice of perioperative neurocognitive disorder (PND) and normal control mice and to explore the possible mechanism of PND. METHODS: Mice were randomly divided into a PND group (n = 9) and a control group (n = 9).The mice in the PND group were treated with open tibial fracture with intramedullary fixation under isoflurane anesthesia, while the mice in the control group received pure oxygen without surgery. The cognitive functions of the two groups were examined using Morris water maze experiment, Open field test and Fear conditioning test. The protein expression of the hippocampus of mice was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the principal functions of dysregulated proteins. RESULTS: A total of 21 proteins were differentially expressed between PND and control mice on days 1, 3, and 7 after the operation. These proteins were involved in many pathological processes, such as neuroinflammatory responses, mitochondrial oxidative stress, impaired synaptic plasticity, and neuronal cell apoptosis. Also, the dysregulated proteins were involved in MAPK, AMPK, and ErbB signaling pathways. CONCLUSION: The occurrence of PND could be attributed to multiple mechanisms.

Bimetallic composite induced ultra-stable solid electrolyte interphase for dendrite-free lithium metal anode.

Lithium metal is the most promising anode materials for the next generation lithium ion battery. However, the electrode polarization leads to the formation of dendrites and "dead lithium", which degrades the performance of lithium metal batteries and induce a variety of security risk. The electrode polarization and lithium dendrites can be suppressed by lithium metal composite electrode. Herein, a simple and effective strategy is adopted to construct nickel and lithium bimetallic composite (NiLi-BC) electrode by a double roll process. The Ni framework inside the electrode can optimize the electric field and Li+ distribution at the electrode/electrolyte interface and induce the uniform lithium deposition. As a result, the NiLi-BC exhibits a lithium dendrite-free feature and stable cycling performance under a low overpotential (<15 mV throughout 2180 h at 1 mA cm-2 with a deposition capacity of 1 mAh cm-2). Moreover, the assembled NiLi-BC||LiFePO4 coin cell and pouch cell exhibit improved capability and stable cycling performance. Finally, the in-situ optical microscopy and in-situ Raman spectroscopy are employed to obtain a better understanding of the interfacial structure and chemical component during the Li plating and striping processes. The scheme of this study of the NiLi electrode has great practical application value.

Selective-cerebral-hypothermia-induced neuroprotection against-focal cerebral ischemia/reperfusion injury is associated with an increase in SUMO2/3 conjugation.

Selective cerebral hypothermia is considered an effective treatment for neuronal injury after stroke and avoids the complications of general hypothermia. Several recent studies hanve suggested that SUMO2/3 conjugation occurs following cerebral ischemia/reperfusion (I/R) injury. However, the relationship between the cerebral protective effect of selective cerebral hypothermia and SUMO2/3 conjugation remains unclear. In this study, we investigated the effect of selective cerebral hypothermia on SUMO2/3 conjugation during focal cerebral I/R injury. A total of 140 Sprague-Dawley rats were divided into four groups. In the sham group, only the carotid artery was exposed. The endoluminal filament technique was used to induce middle cerebral artery occlusion in the other three groups. After 2 h of occlusion, the filaments were slowly removed to allow blood reperfusion in the I/R group. In the hypothermia (HT) group and normothermia (NT) group, normal saline at 4 °C and 37 °C, respectively , was perfused through the carotid artery, followed by the restoration of blood flow. The results of the modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining demonstrated that selective cerebral hypothermia significantly decreased I/R-induced neuronal injury (mNSS, n = 8, 24 h, HT (5.88 ± 2.36) vs. I/R (8.63 ± 3.38), P < 0.05. 48 h, HT (5.75 ± 2.25) vs. I/R (8.5 ± 2.88), P < 0.05. Cerebral infarct volume percentages, n = 5, HT (18.71 ± 2.13) vs. I/R (41.52 ± 2.90), P < 0.01. Cell apoptosis rate, n = 5, 24 h, HT (21.28 ± 2.61) vs. I/R (43.72 ± 4.30), P < 0.05. 48 h, HT (20.50 ± 2.53) vs. I/R (38.94 ± 2.93), P < 0.05). The expression of Ubc9 and conjugated SUMO2/3 proteins was increased at 24 and 48 h after reperfusion in the 3 non-sham groups, and hypothermia further upregulated the expression of Ubc9 and conjugated SUMO2/3 proteins in the HT group. The expression of SENP3 was increased in the NT group and I/R group, while it was decreased in the HT group at 24 and 48 h after reperfusion (Relative quantities, n = 5, Ubc9, 24 h, HT (2.44 ± 0.22) vs. I/R (1.55 ± 0.39), P < 0.05. 48 h, HT (2.69 ± 0.16) vs. I/R (2.25 ± 0.33), P < 0.05. SENP3, 24 h, HT (0.47 ± 0.15) vs. I/R (2.18 ± 0.43), P < 0.05. 48 h, HT (0.72 ± 0.06) vs. I/R (1.51 ± 0.19), P < 0.05. conjugated SUMO2/3 proteins, 24 h, HT (2.84 ± 0.24) vs. I/R (2.51 ± 0.20), P < 0.05. 48 h, HT (2.73 ± 0.13) vs. I/R (2.44 ± 0.13), P < 0.05). Further analysis showed that the variation in SENP3 expression was more obvious than that in Ubc9 under hypothermia intervention in the HT group. These findings suggest that selective cerebral hypothermia could increase SUMO2/3 modification mainly via down-regulating the expression of SENP3, and then exert neuroprotective effects in rats with cerebral I/R injury.

Blood-brain Barrier Disruption Leads to Postoperative Cognitive Dysfunction.

BACKGROUND: Postoperative Cognitive Dysfunction (POCD) has received considerable attention as one of the main postoperative complications. The underlying mechanism of POCD in elderly subjects has not been fully elucidated to date. The Central Nervous System (CNS) is isolated from the bloodstream by the Blood Brain Barrier (BBB) that consists of endothelial cells, capillary blood vessels and tight junctions. The tight junctions carry out significant biological functions that are associated with the CNS and blood circulation. METHODS: In this review, I present a hypothesis that blood-brain barrier disruption leads to postoperative cognitive dysfunction. A total of 81 healthy male Wistar rats were used for the present study. All the experimental animals were randomly divided into 3 groups: normal control group, isoflurane group and splenectomy group. The control group was not subjected to any form of treatment. The rats in isoflurane group were given 1.5-2% isoflurane under intubation and mechanical ventilation. The rats in splenectomy group underwent splenectomy under the same anesthesia as the isoflurane group. The Morris water maze was used to examine the learning and memory ability of the animals. The expression of the Tight Junctions Proteins (TJPs) in the hippocampus was analyzed using Western blotting. The concentration of Evans Blue (EB) in the supernatant was analyzed using UV spectroscopy. Ultrastructure changes in the basal laminas, the Tight Junctions (TJs), mitochondria and the endoplasmic reticulum surrounding the capillaries were assessed by Transmission Electron Microscopy (TEM). RESULTS: Following splenectomy, the rats displayed concomitant significant cognitive deficits in the Morris water maze test. Taken together, the results indicate that the expression levels of occludin (65KD) following splenectomy were reduced on days one and three in aged rats. No significant difference was noted in the expression levels of claudin-5, except for a reduction after surgery on day one. The leakage of EB was higher following splenectomy than control group and isoflurane group. The ultrastructure of the neurovascular unit was monitored on the day prior to surgery and on the 1st, 3rd and 7th day following surgery using a transmission electronmicroscope. CONCLUSION: The alterations in the levels of tight junction proteins following splenectomy may contribute to the BBB permeability increase, which in turn will induce postoperative cognitive dysfunction.

[Impacts of electroacupucnture at Zusanli (ST 36) and Feishu (BL 13) on the postoperative inflammatory reaction and pulmonary complications in senile patients after radical resection of pulmonary carcinoma].

OBJECTIVE: To observe the impacts of electroacupuncture (EA) at Zusanli (ST 36) and Feishu (BL 13) applied 30 min before the operation till the end of the operation on the postoperative inflammatory reaction and pulmonary complications in the senile patients after radical resection of pulmonary carcinoma. METHODS: Eighty senile patients of pulmonary carcinoma were selected and randomized into an observation group and a control group, 40 cases in each one. In the observation group, EA stimulation at Zusanli (ST 36) and Feishu (BL 13) was used 30 min before the operation till the end of the operation. In the control group, electric stimulation was not used. Separately, before operation (T1, basic state), 12 h after operation (T2) and 24 h after operation (T3), blood sample was collected from the central vein. The concentrations of plasma tumor necrosis factor-ɑ (TNF-ɑ) and interleukin-10 (IL-10) were detected. Additionally, the radial arterial blood sample was collected at the above time points; oxygen partial pressure (PaO2) was determined; pulmonary alveoli-arterial partial pressure of oxygen (PA-aDO2) and oxygenation index (OI) were calculated. The pulmonary complication in the two days after operation was recorded. RESULTS: Compared with the control group, in the observation group, at T2 and T3, TNF-ɑ concentration and PA-aDO2 were lower (all P<0.05); plasma IL-10 concentration and OI were higher (all P<0.05). In the observation group, the incidences of postoperative pneumonia and acute pulmonary injury were lower than those in the control group (both P<0.05). CONCLUSIONS: EA reduces the postoperative inflammatory reaction in the senile patients with radical resection of pulmonary carcinoma and decreases the postoperative pulmonary complicattizen.

[Impacts of transcutaneous acupoint electric stimulation on the postoperative nausea and vomiting and plasma 5-HT concentration after cesarean section].

OBJECTIVE: To observe the effect of transcutaneous acupoint electric stimulation on the postoperative nausea and vomiting (PONV) and explore its mechanism. METHODS: Ninety cases of elective cesarean section of I to II grade in American Society of Anesthesiologists (ASA) were collected and randomized into a transcutaneous acupoint electric stimulation group (group A), a sham-acupoint group (group B) and a blank control group (group C), 30 cases in each one. In the group A, 30 min before operation, the transcutaneous electric stimulation was applied to bilateral Neiguan (PC 6) and Zusanli (ST 36). The stimulation lasted during operation and 1 h after operation. In the group B, the same electric stimulation was given at the sites 3 cm lateral to the medial sides of Neiguan (PC 6) and Zusanli (ST 36). In the group C, the electric plaster was attached to bilateral Neiguan (PC 6) and Zusanli (ST 36), without any electric stimulation. The lumbar epidural combined anesthesia and the postoperative analgesia were same in each group. The mean arterial pressure (MAP), heart rate (HR) , oxygen saturation of blood (SpO2) and the VAS (visual analogue scale) score of nausea and vomiting were recorded before acupoint stimulation (T0), at skin incision (T1), fetal delivery (T2), abdominal exploration (T3) and 1 h after operation (T4) as well as bleeding and application of oxytocin, ephedrine and atropine during operation separately. The changes of plasma 5-hydroxytryptamine (5-HT) concentration were observed at T0 and 30 min after electric stimulation. RESULTS: The differences were not significant in MAP, HP and SpO2 at each time point of the three groups (all P> 0.05). The differences were not significant in bleeding and application of oxytocin, ephedrine and atropine during operation (all P > 0.05). The scores of nausea and vomiting in the group A during T1 to T4 were lower than those in the group B and group C (all P < 0.05). In the group A, 30 min after transcutaneous acupoint electric stimulation, plasma 5-HT concentration was lower than those in the group B and group C (both P < 0.01). CONCLUSION: The transcutaneous acupoint electric stimulation apparently relieves nausea and vomiting during and after cesarean section and the mechanism is relevant with the decrease of plasma 5-HT concentration.

[Effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase and S-100ß and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head].

OBJECTIVE: To explore the effects of parecoxib sodium analgesia on serum concentrations of neuron-specific enolase (NSE) and S-100ß and postoperative cognitive function of elderly patients undergoing acute replacement of femoral head. METHODS: After the approval of institutional review board and the provision of informed consent, 80 patients over 70 years old, undergoing acute replacement of femoral head under combined spinal and epidural anesthesia and midazolam sedation at Qingdao Municipal Hospital and Qingdao Hiser Medical Center from January 2011 to May 2012, were randomly assigned into control group (group C, n = 40) and parecoxib group (group P, n = 40). In group P, parecoxib sodium 20/40 mg (based on weight 50 kg) was administered via an intravenous injection after admission with 12 hours intervals for six times. In group C, morphine 2/4 mg was given initially. Additional morphine 2 mg was given to maintain the pain visual analog scale (VAS) of 3 points or less in both groups. Primary observation indices: (1) postoperative time and additional amount of morphine; (2) rate of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) at 3 days, 1 week, 3 months and 6 months postoperation (T1-T4); (3) se rum levels of NSE and S-100ß were measured at the timepoints of before analgesia (t0), before anesthesia (t1), end of surgery (t2) and 6 hours, 24 hours, 48 hours postoperation (t3-t5); (4) other serious complications. RESULTS: Compared with group C, the additional amount of morphine, postoperative time, rate of POD and POCD at T1-T4, the level of NSE at t2-t5 and S-100ß at t1-t5 were lower in group P (P < 0.05). No other serious complications were observed. CONCLUSIONS: Parecoxib sodium analgesia reduces the rate of POD and POCD in elderly patients with neuroprotective effects.

[Influence of auricular point sticking on incidence of nausea and vomiting and analgesia effect after gynecological laparoscopy].

OBJECTIVE: To observe the influence of auricular point sticking on incidence of nausea and vomiting and analgesia effect after gynecological laparoscopy, and provide evidence for clinical application of auricular point sticking. METHODS: One hundred and twenty cases of selective gynecological laparoscopy under general anesthesia were randomly divided into an auricular point sticking group and a placebo group, 60 cases in each group. In the auricular point sticking group, the auricular point sticking with vaccaria seeds was applied at Shenmen (TF 4), Wei (CO 4) and Jiaogan (AH 6a) before the operation and 1, 5, 9, 23 h after the operation, which were pressed 5 min each point each time. The two ears were proceeded at the same time. In the placebo group, the same point selection, sticking paste was used as the auricular point sticking group, but no sticking or pressing with vaccaria seeds was adopted. The incidence of nausea and vomiting, the usage rate of tropisetron and morphine within 24 hours of the operation, as well as the score of visual analogue scale (VAS) and other adverse reactions at 2, 6, 10, 24 h after the operation were observed respectively. RESULTS: Compared with the placebo group, the incidence of nausea and vomiting [31.7% (19/60), 16.7% (10/60) vs 58.3% (35/60), 35.0% (21/60)], the usage rate of tropisetron [21.7% (13/60) vs 48.3% (29/60)] and morphine [18.3% (11/60) vs 38.3% (23/60)], the VAS scores at all different time points in the auricular point sticking group were all decreased (all P < 0.05), and no adverse reaction was observed. CONCLUSION: The auricular point sticking could significantly decrease the incidence of nausea and vomiting in patients of gynecological laparoscopy and has positive analgesic effect.

[Effects of transcutaneous electrical stimulation of auricular Shenmen point on postoperative nausea and vomiting and patient-controlled epidural analgesia in cesarean section].

OBJECTIVE: To investigate the effects of transcutaneous electrical stimulation of auricular Shenmen point on postoperative nausea and vomiting and patient-controlled epidural analgesia in cesarean section. METHODS: After IRB approval and informed consent, one hundred and eighty singleton primiparas undergoing elective cesarean section, in Qingdao Municipal Hospital, and Qingdao Hiser Medical Center, from November 2011 to March 2012, were randomly assigned to three groups: transcutaneous electrical stimulation of auricular Shenmen point group (group A, n = 60), transcutaneous electrical stimulation of auricular Eye point group (group B, n = 60) and control group (group C, n = 60). Women of group A received transcutaneous electrical stimulation of auricular Shenmen point (frequency 1.5 HZ) at the time of preoperation, 4, 10 and 22 hours of postoperation for 30 minutes. The strength was controlled by themselves. Women of group B received stimulation of auricular Eye point as group A. Women of group C received pressurization and connected line were the same with group A, but without electrical stimulation. The following indexes was observed: the incidence of postoperative nausea and vomiting (PONV) for 48 hours; the rate of metoclopramide; the visual analogue scale (VAS) score of rest pain, uterine contration pain and dynamic pain at the time of postoperation for 6, 12, 24 and 48 hours (T(1)-T(4)); the total number and effective compressions number of patient-controlled epidural analgesia(PCEA);the dose of analgesia mixture; the anal exhaust time; the volume of postoperative bleeding for 6 hours of postoperation and the other side effects. RESULTS: Compared with group B and group C, the incidence of PONV, the rate of metoclopramide, the VAS score at the time T(1)-T(4), the total number and effective compressions number of PCEA, the ratio of the total number with effective compressions number and the dose of analgesia mixture were decreased in group A (P < 0.05), but no difference compared group B with group C (P > 0.05). The anal exhaust time and the volume of postoperative bleeding for 6 hours of postoperation were no difference in the three groups (P > 0.05). No other side effects were observed. CONCLUSION: Transcutaneous electrical stimulation of auricular Shenmen point can reduce the incidence of PONV and improves analgesia effect of PCEA in postoperation of cesarean section.

[Efficacy and safety of patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section].

OBJECTIVE: To study the efficacy and safety of patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section. METHODS: A randomized controlled clinical trail was conducted on 180 singleton primiparas (SAS > 30) undergoing selective cesarean section. They were randomly assigned to three groups, i. e., the patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) group (Group A, 60 cases), the patient-controlled sedation with transcutaneous electrical stimulation of auricular eye point group (Group B, 60 cases), and the control group (Group C, 60 cases). Patients in Group A received patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in the operating room. The strength was controlled by patients themselves. The stimulation lasted for 30 min before the epidural puncture till ending the surgery. Patients in Group B received stimulation of auricular eye point. Patients in Group C received pressurization with the same connected line as Group A, but without electric stimulation. The following indices were observed: (1) the bispectral index (BIS), heart rate (HR), mean arterial pressure (MAP), Ramsay sedation score when the women entered the operating room (T0), 30 min after stimulation (T1), at the time after removing the fetus (T2), and by the end of surgery (T3); (2) the concentrations of plasma angiotensin II (AngII) and cortisone (Cor) at the aforesaid time points; (3) the use rates of oxytocin, atropine, and ephedrine; the hemorrhage amount, and the neonatal Apgar score. RESULTS: Compared with Group A, the BIS, the plasma concentrations of AngII and Cor increased at T1, T2, and T3 (P < 0.05), and the Ramsay sedation score decreased (P < 0.05). The HR and MAP increased at T1 (P < 0.05) in Group B and Group C. Compared with T0, the BIS, HR, MAP, and Ramsay sedation score, the plasma concentrations of AnglI and Cor were lowered in Group A at T1 (P < 0.05). There was no statistical difference in the use rates of oxytocin, atropine, and ephedrine; the hemorrhage amount, and the neonatal Apgar score (P > 0.05). CONCLUSIONS: Patient-controlled sedation with transcutaneous electrical stimulation of auricular Shenmen (TF4) in cesarean section had obvious sedative effects. It had no adverse effects on puerperal or neonates.

[Efficacy and delivery outcomes of women underwent double-catheter epidural block during labor].

OBJECTIVE: To investigate the efficacy and pregnancy outcomes of women receiving double-catheter epidural block in labor analgesia, and compare the results with single-catheter epidural block. METHODS: A double-blind clinical trial was conducted on 206 full-term singleton primiparas, aged 25 - 35 and at the 37 - 42 weeks of gestation who delivered at the Department of Obstetrics, Qingdao Municipal Hospital from August 2006 to December 2008, which were randomly divided into two groups: double-catheter epidural block (group D, n = 103) and single-catheter epidural-block (group S, n = 103). Women in group D were given mixture of 0.1% repivacaine hydrochloride and 0.5 mg/L sufentinil 4 - 6 ml as initial dose. Patient control epidural analgesia pump (PCEA) was connected with the upper catheter after 45 minutes. A bolus dose of 4 - 6 ml analgesia mixture was infused according to the condition through the lower catheter. Women in group S received analgesia mixture 10 - 15 ml as initial dose and PCEA pump was connected after 45 minutes. Oxytocin was infused in both groups according to uterine contraction after 30 minutes. The following indexes was observed: (1) visual analogue scales (VAS); (2)modified Bromage Scores; (3) the total dose of analgesia mixture, the percentage of oxytocin infusion, duration of labor and duration of the second stage of labor; (4) fetal birth weight and Apgar scores (1, 5 minutes); (5) mode of delivery; (6) the concentration of plasma cortisol and angiotension II at the beginning of regular uterine contraction and at the time when cervical dilated to 4 cm and 10 cm and fetal disengagement; (7) anesthesia-related complications. RESULTS: (1) The neonatal birth weight and Apgar scores (1, 5 minutes) of group D were (3456 ± 468) g, 9.8 ± 0.6 and 9.9 ± 0.7, respectively, while (3399 ± 569) g, 9.8 ± 0.5 and 9.9 ± 0.7 in group S (P > 0.05). No motor function block was reported in any group and the modified Bromage score was zero. (2) The total dose of analgesia mixture in group D was similar to that in group S [(57 ± 9) ml vs. (58 ± 11) ml, P > 0.05]. However, the percentage of women received oxytocin in group D was smaller [59.2% (61/103) vs. 81.6% (84/103), P < 0.01], and the total time of labor and the duration of second stage of labor in group D were shorter [(532 ± 140) minutes vs. (608 ± 150) minutes; (46 ± 31) minutes vs. (60 ± 34) minutes, P < 0.05]. (3) There were no significant differences in VAS at 30 minutes after initial dose and in the first stage of labor between group D and S (1.2 ± 1.1 vs 1.2 ± 1.1, 1.1 ± 1.1 vs. 1.2 ± 1.0, P > 0.05). VAS at the second stage of labor stage was lower in group D than in group S (1.2 ± 1.1 vs. 4.5 ± 2.2, P < 0.01). (4) The rate of cesarean section, instrumental delivery and episiotomy in group D were lower than in group S (7.8% vs. 17.5%, 7.8% vs. 15.5%, 10.7% vs. 18.4%, P < 0.05). The incidence of fetal distress and meconium-stained amniotic fluid as the indication of cesarean section were similar between the two groups (P > 0.05). Lower incidence of fetal malpresentation and arrested second stage of labor were shown in group D than in group S (2.9% vs. 9.7%, 1.0% vs. 5.8%, P < 0.05). (5) The concentration of plasma cortisol and angiotension II were lower in group D than in group S [(86 ± 25) ng/L vs. (100 ± 20) ng/L, (278 ± 53) nmol/L vs. (311 ± 53) nmol/L, P < 0.05] only at the end of second stage of labor, but not at any other times (P > 0.05). (6) No serious anesthesia-related complications were reported in any groups. Some light backache around the puncture point were complained by 29.1% (30/103) of the women in group D and 31.1% (32/103) in group S (P > 0.05). CONCLUSION: Double-catheter epidural block can provide better analgesia effect during labor than single-catheter epidural block, without any adverse influence on delivery outcomes.