miRNA-124 alleviated memory impairment induced by d-galactose rapidly in male rats via microglia polarization.

MiRNA-124 has been considered to play a significant role in the formation of memory and a variety of neurodegenerative diseases. In this study, the aim is to verify whether miRNA-124 is involved in memory impairment induced by d-galactose, and explore the underlying neuroprotective mechanism. The results revealed that rapid administration of d-galactose (1000 mg/kg subcutaneously) in mice caused memory impairments, as determined by Novel Object Recognition test, Morris Water Maze test, and histological assessments. MiRNA-124 agomir is stereotactic injected into hippocampus, thus alleviated memory impairment induced by d-galactose and reversed the neural damage and neuroinflammation. Furthermore, the results of molecular biological analysis and immunohistochemistry revealed that miRNA-124 markedly reduced neuroinflammation induced by d-galactose through polarization of microglia as determined by detection of ionized calcium binding adapter molecule 1 (Iba-1), inducible nitric oxide synthase (iNOS) and arginase-1(Arg-1), which also downregulated inflammatory mediators, including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), and upregulated IL-4 and IL-10. Hence, taken together, the results of the present study suggested that miRNA-124 showed a significant negative correlation with memory impairment and neuroinflammation induced by d-galactose rapidly, possibly via polarization of microglia from M1 to M2. It is possible that miRNA-124 can be used as a new target for the pathogenesis of memory impairment, including age-associated neurodegenerative diseases such as Alzheimer's disease.

CSF-CN contributes to cancer-induced bone pain via the MKP-1-mediated MAPK pathway.

Pain is a major complication of cancer and significantly affects the quality of life. Cerebrospinal fluid-contacting nucleus (CSF-CN) has been reported to be involved in the development of neuropathic pain and inflammatory pain. However, whether CSF-CN contributes to cancer-induced bone pain (CIBP) remains unknown. In this study, we aimed to illustrate the role of CSF-CN in the pathogenesis of CIBP and identify its potential mechanism via the MKP-1-mediated MAPK pathway. The Walker 256 cancer cells were injected into the tibia cavity of female Sprague-Dawley rats to induce CIBP models. Intracerebroventricular injection of cholera toxin subunit B- saporin (CB-SAP) was performed to "knockout" the CSF-CN. Morphine and LV-MKP-1 were applied. Mechanical and thermal hyperalgesia behaviors, double immunofluorescence staining and Western blot were conducted after CIBP induction. The results revealed that CIBP significantly reduced the mechanical withdrawal threshold and the thermal threshold. Double immunofluorescence staining revealed that c-Fos-positive neurons in CSF-CN were significantly higher in the CIBP group than that in the sham group. Targeted ablation of CSF-CN dramatically aggravated pain sensitivity. Moreover, MKP-1 was down-regulated in the CSF-CN after CIBP induction. Pharmacological intervention with morphine significantly ameliorated the mechanical and thermal hyperalgesia through reversing the down-expression of MKP-1 in the CSF-CN on day 14 after CIBP induction. Mechanically, overexpression of MKP-1 by LV-MKP-1 injection significantly relieved CIBP via inhibiting the expression of phosphorylated p38, which subsequently decreased the protein levels of Bax, cleaved caspase-3 and Iba-1, and reduced the mRNA levels of IL-1ß, TNF-α and IL-6 in CSF-CN. In conclusion, CSF-CN contributed to CIBP via regulating the MKP-1-mediated p38-MAPK pathway. Future therapy targeting the expression of MKP-1 in the CSF-CN may be a promising new choice.

Role of Parkin-mediated mitophagy in the protective effect of polydatin in sepsis-induced acute kidney injury.

BACKGROUND: We have reported that polydatin (PD) alleviates mitochondrial dysfunction in rat models of sepsis-induced acute kidney injury (SI-AKI), but the mechanism is not well understood. Here, we investigated the role of Parkin-mediated mitophagy in the protective effects of PD in SI-AKI in mice. METHODS: Sepsis was induced in the mice by caecal ligation and puncture. Mitophagy was determined by mitochondrial mass. NLRP3 inflammasome activation was determined by NLRP3, ASC and caspase-1. Mitophagy was blocked by treatment with mitochondrial division inhibitor-1 and Parkin knockout. KEY RESULTS: PD treatment increased the sepsis-induced loss of mitochondrial mass, indicating the upregulation of mitophagy. Furthermore, PD treatment mediated Parkin translocation from the cytoplasm to the mitochondria. This suggests that Parkin-mediated mitophagy is an underlying mechanism. This was confirmed by the suppression of PD-induced mitophagy in Parkin-/- mice and in mice that were treated with a mitophagy inhibitor. PD-induced Parkin translocation and mitophagy were blocked by inhibiting SIRT1; thus, activation of SIRT1 might be an important molecular mechanism that is triggered by PD. Additionally, PD treatment protected against sepsis-induced kidney injury. These effects were blocked by inhibition of Parkin-dependent mitophagy. Furthermore, PD also protected against mitochondrial dysfunction and mitochondria-dependent apoptosis, and the effect was blocked when Parkin-dependent mitophagy was inhibited. Finally, PD suppressed NLRP3 inflammasome activation that was also dependent on Parkin-mediated mitophagy. CONCLUSIONS: These findings indicate that Parkin-mediated mitophagy is important for the protective effect of PD in SI-AKI, and the underlying mechanisms include the inhibition of mitochondrial dysfunction and NLRP3 inflammasome activation.

Comparison of Remifentanil-Based Fast-Track and Fentanyl-Based Routine Cardiac Anesthesia for Intraoperative Device Closure of Atrial Septal Defect (ASD) in Pediatric Patients.

BACKGROUND The aim of this study was to evaluate the effectiveness and safety of remifentanil-based fast-track anesthesia for intraoperative device closure of atrial septal defects (ASDs). MATERIAL AND METHODS The clinical data of 152 pediatric patients who received intraoperative device closure of ASD in our hospital from January 2015 to December 2017 were retrospectively analyzed. Patients were divided into 2 groups: group F (remifentanil-based fast-track anesthesia group, n=72) and group C (fentanyl-based routine anesthesia group, n=80). The relevant data from 2 groups were collected and analyzed. RESULTS No significant differences were found in the preoperative data or intraoperative hemodynamic index between these 2 groups. Group C was significantly inferior to group F regarding the duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, and hospitalization expenses (P<0.05). In terms of postoperative complications, no death, third-degree atrioventricular block, occluder detachment, or residual leakage was reported in either group. The incidence of lung infections and bronchospasm was significantly higher in group C than in group F. There were no anesthetic-related complications. CONCLUSIONS The application of remifentanil-based fast-track anesthesia for intraoperative device closure of ASD is as effective and safe as fentanyl-based routine anesthesia. Moreover, remifentanil-based fast-track anesthesia has the advantages of shorter duration of mechanical ventilation, shorter length of hospital and ICU stay, fewer postoperative complications, and lower hospitalization expenses, and is therefore worthy of promotion in clinical practice.

Hyperbaric Oxygen Improves Long-Term Learning and Memory Impairment by Attenuating Neuronal Apoptosis in aMCI Rats.

Background: With the aging of the population and the increasing incidence of neurological diseases, amnestic mild cognitive impairment (aMCI) has attracted attention. Hyperbaric oxygen (HBO) has gradually shown the potential in the treatment of aMCI as an emerging treatment method in recent times. This study is to observe the effect of HBO on the long-term learning memory of aMCI rats, and investigate the associated mechanisms. Methods: Seventy-two male rats (4-month-old) were randomly divided into control (CON) group, aMCI group, HBO group, 24 rats in each group. Each group was randomly divided into CON1, CON7, CON28; aMCI1, aMCI7, aMCI28; HBO1, HBO7, HBO28, 8 rats in each group. The aMCI model rats were established in aMCI and HBO groups. HBO group was treated with HBO for 7 days. The ethological and cytopathology which include Morris water maze (MWM) test, HE staining, TUNEL staining and the expression of Fas/FasL on neuron membrane were conducted to evaluate the effects of HBO on day 1, day 7 and day 28 after HBO treatment. Results: MWM test showed that the spatial learning and memory ability of the rats decreased in aMCI group, and recovered in HBO group; Compared with aMCI group, the pathological damage of hippocampal nerve cells was alleviated, the number of apoptotic cells was significantly reduced (P < 0.05), and the expression of Fas/FasL on the surface of nerve cell membrane was significantly weakened in HBO group (P < 0.05). There were no significant changes in the spatial learning and memory ability, pathological damage of hippocampal neurons, the number of apoptotic cells, and the changes of Fas/FasL on the surface of hippocampal neurons in HBO1, HBO7, and HBO28 groups (P > 0.05). However, in aMCI1, aMCI7, and aMCI28 groups gradually aggravated (P < 0.05). Conclusion: 1. HBO can improve the long-term learning and memory impairment by attenuating neuronal apoptosis in aMCI rats. 2. Fas/FasL mediated cell receptor death pathway is involved in the apoptosis of hippocampal neurons.

Effect of lidocaine on cognitively impaired rats: Anti-inflammatory and antioxidant mechanisms in combination with CRMP2 antiphosphorylation.

OBJECTIVE: Studies have shown that lidocaine has antioxidative stress, anti-inflammatory, and nerve-protective effects. The current study investigated the effects of lidocaine on cognitive function in rats with cognitive dysfunction. METHODS: A total of 48 rats were randomly assigned to four groups of 12 rats each: control group; L (lidocaine) + D (d-galactose) group, d-galactose group (D group); and D + L group. We assessed cognitive function using a Morris water maze (MWM) and pathologic changes of hippocampal sections. An enzyme-linked immunosorbent assay (ELIZA) was used to detect serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels in rats, and protein immunoblotting (western blot) was used to detect brain tissue proteins (collapsing response mediator protein-2 [CRMP2], phosphorylated-collapsing response mediator protein-2 [P-CRMP2], and ß-amyloid protein [Aß]). RESULTS: The MWM showed that the d-gal group (284.09 ± 20.46, 5.20 ± 0.793) performed worse than the L + D (265.37 ± 22.34, 4.170 ± 0.577; p = .000) and D + L groups (254.72 ± 27.87, 3.750; p = .000) in escape latency and number of platform crossings, respectively. The L + D group (44.94 ± 2.92 pg/mL, 6.22 ± 0.50 pg/mL, and 460.02 ± 8.26 nmol/mL) and D + L group (46.88 ± 2.63 pg/mL, 5.90 ± 0.38 pg/mL, and 465.6 ± 16.07 nmol/mL) had significantly lower serum inflammatory levels of interleukin-6, tumor necrosis factor-α, and MDA than the d-gal group (57.79 ± 3.96 pg/mL, 11.25 ± 1.70 pg/mL, and 564.9 ± 15.90 nmol/mL), respectively. The L + D group (3.17 ± 0.41 µg/mL) and D + L group (3.08 ± 0.09 µg/mL) had significantly higher serum inflammatory levels of SOD than the d-gal group (2.20 ± 0.13 µg/mL) (all p = .000). The levels of CRMP2, P-CRMP2, and Aß in the brain tissue homogenates of the L + D group (0.87 ± 0.04, 0.57 ± 0.0, and 0.16 ± 0.02) and the D + L group (0.82 ± 0.05, 0.58 ± 0.09, and 0.15 ± 0.02) were significantly different than the d-gal group (0.67 ± 0.03, 0.96 ± 0.040, and 0.29 ± 0.05). CONCLUSIONS: Lidocaine was shown to reduce cognitive impairment in rats with cognitive dysfunction through anti-inflammatory and antioxidative stress mechanisms in combination with CRMP2 antiphosphorylation.

The role of acute normovolemic hemodilution in reducing allogeneic blood transfusion in glioblastoma surgery: a case-control study.

BACKGROUND: Acute normovolemic hemodilution (ANH) was first introduced in glioblastoma surgery, and its role in reducing allogeneic blood transfusion was investigated in this study. METHODS: This study enrolled supratentorial glioblastoma patients who received total resection. In the ANH group, the patients were required to draw blood before the operation, and the blood will be transfused back to the patient during the operation. The association between ANH and clinical features was investigated. RESULTS: Sixty supratentorial glioblastoma patients were enrolled in this study, 25 patients were allocated in the ANH group, and another 35 patients were included in the control group. ANH dramatically reduced the need for allogeneic blood transfusion (3 [12%] vs 12 [34.3%], P = 0.049), and the blood transfusion per total of patients was dramatically decreased by the application of ANH (0.40 ± 1.15 units vs 1.06 ± 1.59 units, P = 0.069). Furthermore, ANH also markedly reduced the requirement of fresh frozen plasma (FFP) transfusion (2 [8%] vs 11 [31.4%], P = 0.030) and the volume of FFP transfusion per total of patients (32.00 ± 114.46 mL vs 115.71 ± 181.00 mL, P = 0.033). The complication rate was similar between the two groups. CONCLUSIONS: ANH was a safe and effective blood conservation technique in glioblastoma surgery.

Ultrasonic evaluation of metoclopramide's effect on gastric motility in emergency trauma patients.

Objective: The present study aimed to use bedside ultrasound to evaluate the effects of metoclopramide on gastric motility in patients being treated for trauma in the emergency department. Methods: Fifty patients underwent an ultrasound immediately after attending the emergency department of Zhang Zhou Hospital due to trauma. The patients were randomly divided into two groups: a metoclopramide group (group M, n = 25) and a normal saline group (group S, n = 25). The cross-sectional area (CSA) of the gastric antrum was measured at 0, 30, 60, 90, and 120 min (T = time). The gastric emptying rate (GER, GER=-AareaTn/AareaTn-30-1×100), GER/min (GER divided by the corresponding interval time), gastric content properties, Perlas grade at different time points, T120 gastric volume (GV), and GV per unit of body weight (GV/W) were evaluated. The risk of vomiting, reflux/aspiration, and type of anesthetic treatment were also evaluated. Results: The differences between the two groups in the CSA of the gastric antrum at each time point were statistically significant (p < 0.001). The CSAs of the gastric antrum in group M were lower than those in group S, and the greatest difference between the two groups occurred at T30 (p < 0.001). The differences between the two groups in GER and GER/min were also statistically significant (p < 0.001); those differences in group M were higher than those in group S, and the greatest differences between the two groups occurred at T30 (p < 0.001). There were no obvious change trends in the properties of the gastric contents and the Perlas grades in either group, and the differences between the two groups were not statistically significant (p = 0.97). The differences between the two groups in the GV and GV/W at T120 were statistically significant (p < 0.001), as was the risk of reflux and aspiration at T120 (p < 0.001). Conclusion: When metoclopramide was used in satiated emergency trauma patients, it accelerated gastric emptying within 30 min and reduced the risk of accidental reflux. However, a normal gastric emptying level was not achieved, which can be attributed to the delaying effect of trauma on gastric emptying.

ADENOSINE MONOPHOSPHATE-ACTIVATED PROTEIN KINASE PHOSPHORYLATION MEDIATED BY SIRTUIN 5 ALLEVIATES SEPTIC ACUTE KIDNEY INJURY.

ABSTRACT: Background : Our previous studies have shown that ameliorating mitochondrial damage in renal tubular epithelial cells (RTECs) can alleviate septic acute kidney injury (SAKI). It is reported that AMPK phosphorylation (p-AMPK) could ameliorate mitochondrial damage in renal tissue and Sirtuin 5 (SIRT5) overexpression significantly enhanced the level of p-AMPK in bovine preadipocytes. However, the role of SIRT5-mediated phosphorylation of AMPK in SAKI needs to be clarified. Methods : WT/SIRT5 gene knockout mouse model of cecal ligation and puncture-induced SAKI and a human kidney 2 cell model of LPS-induced SAKI were constructed. An AMPK chemical activator and SIRT5 overexpression plasmid were used. Indexes of mitochondrial structure and function, level of p-AMPK, and expression of SIRT5 protein in renal tissue and RTECs were measured. Results : After sepsis stimulation, the p-AMPK level was decreased, mitochondrial structure was disrupted, and ATP content was decreased. Notably, an AMPK activator alleviated SAKI. Sirtuin 5 gene knockout significantly aggravated SAKI, while SIRT5 overexpression alleviated mitochondrial dysfunction after LPS stimulation, as manifested by the increase of p-AMPK level, the alleviation of mitochondrial structure damage, the restoration of ATP content, the decrease of proapoptotic protein expression, as well as the reduction of reactive oxygen species generation. Conclusions : Upregulation of SIRT5 expression can attenuate mitochondrial dysfunction in RTECs and alleviate SAKI by enhancing the phosphorylation of AMPK.

Flurbiprofen axetil alleviates the effect of formalin-induced inflammatory pain on the cognitive function of rats with mild cognitive impairment through the AMPKα/NF-κB signaling pathway.

Background: Mild cognitive impairment (MCI) as a prestage of dementia shares the most risk factors with dementia. In the present study, we explored the effect of flurbiprofen axetil on reducing the response of the central nervous system to inflammatory factors and anti-inhibiting apoptosis with the aim of developing a formalin-induced inflammatory pain model using MCI rats. Methods: Rats were subjected to sham operation (Sham group) or formalin-induced inflammatory pain, with or without flurbiprofen axetil (10 mg/kg). MCI rats were administered D-galactose (1,000 mg/kg) for 7 days subcutaneously. Thereafter, formalin was injected subcutaneously into the hind paws of rats, while sham group was injected with only normal saline. In the formalin/flurbiprofen group (F/F group), flurbiprofen axetil was injected into the tail vein 15 min before formalin was given, and the formalin/saline group (F/S group) used normal saline instead of the drug for injection. The pain score was recorded, and the time-score curve was drawn. The escape latency time and the number of times crossing the platform were recorded. The expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), AMP-activated protein kinase-α (AMPKα), and nuclear factor-κB p65 (NF-κB p65) in hippocampal tissue was determined. Varying degrees of pathological changes in the hippocampal CA1 region were observed. Results: The II phase pain score of rats in the F/F group was lower than that of the F/S group rats (P<0.05). The evasion incubation period and the number of platform crossings increased in both the F/F group and the F/S group (P<0.05), and were more significant in the F/S group. The relative content of AMPKα increased sequentially in the 3 groups, and the difference between the two comparisons of each group was statistically significant (P<0.05). The relative content of IL-6, TNF-α and NF-κB in the F/S group was greater than that of the F/F group, and the difference was statistically significant (P<0.001). Pathological morphological observations can be seen that the phenomena of nuclear consolidation, deep staining, and neuronal apoptosis occur, and the F/S group is more obvious. Conclusions: Flurbiprofen axetil can reduce the inflammatory response and cognitive function of an inflammatory pain model using MCI rats through the AMPKα/NF-κB signaling pathway.

The effects of dexmedetomidine on the cognitive function of mild cognitive impairment (MCI) rats.

Background: The study sought to investigate the effects of dexmedetomidine (DEX) on cognitive function after anesthesia and to examine its actual mechanism. Methods: A total of 48 rats were injected with d-galactose (D-gal) 1,000 mg·kg-1·d-1 and normal saline at the neck and back for 1 week to establish rats with mild cognitive impairment (MCI) and conduct behavioral tests. Sevoflurane was inhaled and DEX was pumped into each group respectively. Morris water maze (MWM) test was conducted 24 hours later. The inflammatory factors interleukin (IL)-1, interleukin (IL)-6, and a tumor necrosis factor (TNF)-α in brain homogenate were quantitatively measured by enzyme-linked immunosorbent assay (ELISA) on the next day. The apoptosis of hippocampal cells was observed by hematoxylin-eosin staining (HE staining). Results: In relation to the model establishment, we found that there was no significant difference in body weight and swimming speed before and after modeling. There was no statistically significant difference in the escape latency between Groups A, B, C, and D before modeling. After modeling, there was no statistical difference in the escape latency between Groups A, B, and C, but the difference was statistically significant when compared to Group D (P<0.05). In relation to the DEX intervention, we found that compared to Group C, MWM test performance in Groups A and B was considerably worse longer escape latencies and fewer platform crossings within 90 seconds), and were more significant in Group A. Compared with Group D, the levels of inflammatory cytokines of the brain homogenates were elevated, and this elevation was highest in Group A, followed by Group B; the pathological changes were consistent with changes in behavioral tests. In Group A, there were obvious disorders of glial cell arrangement, apoptosis and deletion. There was no significant change in Group D. And the changes of vertebral cells in Group B and Group C were slight, with orderly arrangement and intact cell structure. Conclusions: DEX inhibits the apoptosis of hippocampal cells and reduces the cognitive dysfunction of rats with MCI induced by D-gal via the inhibition of the release of inflammatory cytokines.

Melatonin suppresses ferroptosis via activation of the Nrf2/HO-1 signaling pathway in the mouse model of sepsis-induced acute kidney injury.

BACKGROUND: Ferroptosis is a regulated form of cell death. At present, the role of ferroptosis in sepsis-induced acute kidney injury (SAKI) has not been studied. Melatonin (MEL) has been reported to be an effective ferroptosis inhibitor, but it is unclear whether Melatonin can regulate ferroptosis in SAKI and whether its downstream mechanism correlates with the Nrf2/HO-1 pathway. METHODS: The cecal ligation and puncture (CLP) method and LPS injection were used to induce SAKI in mouse model. Ferroptosis markers, including malondialdehyde (MDA) and glutathione peroxidase 4 (GPX4), were assessed. The ferroptosis inhibitor ferrostatin-1 (Fer-1) was used to explore the role of ferroptosis in SAKI. The GPX4 inhibitor RSL3, the HO-1 inhibitor zinc protoporphyrin(ZnPP), and the Nrf2 inhibitor ML385 were used to explore the specific mechanism of MEL in alleviation of SAKI. RESULTS: The ferroptosis level was increased in the renal tissue of CLP- and LPS-induced septic mice. Both Fer-1 and MEL administration could suppress ferroptosis and attenuate kidney injury upon sepsis challenge. RSL3 partially blocked MEL's beneficial renal-protective effects. MEL up-regulated Nrf2 and HO-1 in CLP mice, and both ZnPP and ML385 blocked the MEL-mediated effects of ferroptosis inhibition and renal protection. CONCLUSIONS: Ferroptosis aggravates SAKI. Melatonin treatment suppresses ferroptosis and alleviates kidney injury in the context of experimental sepsis by upregulating Nrf2/HO-1 pathway.

The Use of Acute Normovolemic Hemodilution in Clipping Surgery for Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The occurrence of coronavirus disease 2019 (COVID-19) has overwhelmed the blood supply chain worldwide and severely influenced clinical procedures with potential massive blood loss, such as clipping surgery for aneurysmal subarachnoid hemorrhage (aSAH). Whether acute normovolemic hemodilution (ANH) is safe and effective in aneurysm clipping remains largely unknown. METHODS: Patients with aSAH who underwent clipping surgery within 72 hours from bleeding were included. The patients in the ANH group received 400 mL autologous blood collection, and the blood was returned as needed during surgery. The relationships between ANH and perioperative allogeneic blood transfusion, postoperative outcome, and complications were analyzed. RESULTS: Sixty-two patients with aSAH were included between December 2019 and June 2020 (20 in the ANH group and 42 in the non-ANH group). ANH did not reduce the need of perioperative blood transfusion (3 [15%] vs. 5 [11.9%]; P = 0.734). However, ANH significantly increased serum hemoglobin levels on postoperative day 1 (11.5 ± 2.5 g/dL vs. 10.3 ± 2.0 g/dL; P = 0.045) and day 3 (12.1 ± 2.0 g/dL vs. 10.7 ± 1.3 g/dL; P = 0.002). Multivariable analysis indicated that serum hemoglobin level on postoperative day 1 (odds ratio, 0.895; 95% confidence interval, 0.822-0.973; P = 0.010) was an independent risk factor for unfavorable outcome, and receiver operating characteristic curve analysis showed that it had a comparable predictive power to World Federation of Neurosurgical Societies grade (Z = 0.275; P > 0.05). CONCLUSIONS: ANH significantly increased postoperative hemoglobin levels, and it may hold the potential to improve patients' outcomes. Routine use of ANH should be considered in aneurysm clipping surgery.

The protective effect of PK11195 on D-galactose-induced amnestic mild cognitive impairment in rats.

BACKGROUND: This study aimed to investigate the preventive effect of translocator protein 18kDa (TSPO) ligand PK11195 on amnestic mild cognitive impairment (aMCI), as well as its influence on astrocytes, in order to identify effective ways to prevent aMCI. METHODS: Male SD rats were randomly divided into control group (n=10), aMCI group (n=10), PK11195 group (n=10), PK11195 + D-gal group (n=10). The preventive effect of PK11195 on aMCI in rats was evaluated. The cognitive function of rats in four different treatment groups was determined using the Morris water maze (MWM), as well as whole-brain pathology and immunofluorescence of rat brain tissue. RESULTS: The results of the MWM behavioral test showed that rats pre-treated with PK11195 had improved escape latency and a higher number of platform crossings compared with the aMCI model rats. PK11195 was also shown to prevent the D-galactose (D-gal)-induced senescence of pyramidal cells in the hippocampal CA1 region and to inhibit the apoptosis of astrocytes. At the same time, compared with the aMCI model rats, the TSPO in the brain tissue of rats pretreated with PK11195 had a lower distribution density. CONCLUSIONS: Our results prove that PK11195 can effectively prevent D-gal-induced decline of learning and memory function as well as inhibit abnormal changes of related cells.

The method and effect of rapid establishment of a mild cognitive impairment model.

BACKGROUND: To further the exploration of the pathogenesis of mild cognitive impairment (MCI), we aimed to determine the appropriate dose for a rapidly established MCI rat model using D-galactose (D-gal), with lasting cognitive effects. METHODS: In Experiment 1, we evaluated various D-gal concentrations (100-2,000 mg/kg/day), and determined that, compared with saline injections of the same volume. In Experiment 2, we evaluated the duration of the effect of 1,000 mg/kg/day D-gal injections for 1 week, with MWM testing initiated at 1 day, 1 month, and 3 months after completion of the injection regime in three model groups, respectively. RESULTS: In Experiment 1, D-gal injections at a concentration of 1,000 mg/kg/day for 1 week was adequate to induce a significantly worse Morris water maze (MWM) test performance and pathomorphologic changes in the hippocampus, with MWM testing initiated 1 day after completion of the injection regime. In Experiment 2, Before modeling, the overall condition (fur, mental state, foraging behavior, and activity level), body weight, swimming speed, and swimming time did not significantly differ between the control (saline injections) and model groups (D-gal injections). After modeling, MWM test performance was considerably worse (longer escape latencies and fewer platform crossings within 90 seconds) in the model groups than in the control group, without significant differences among model groups. Furthermore, movement trajectories were similar among model groups. CONCLUSIONS: These results demonstrate that subcutaneous injections of D-gal 1,000 mg/kg/day for 1 week produce changes consistent with the characteristics and pathological processes of MCI. Thus, high-dose D-gal injection allows the rapid establishment of an MCI model that is effective and sustainable.

Cannabidiol alleviates hemorrhagic shock-induced neural apoptosis in rats by inducing autophagy through activation of the PI3K/AKT pathway.

Recently, several studies have reported that the pharmacological effects exerted by cannabidiol (CBD) are partially related to the regulation of autophagy. Increasing evidence indicates that autophagy provides protection against ischemia-induced brain injury. However, the protective effect of CBD against mitochondrial-dependent apoptosis in hemorrhagic shock (HS)-induced brain injury has not been studied. In the present study, we observed the protective effects of CBD against neural mitochondrial-dependent apoptosis in a rat model of HS. In addition, CBD increased Beclin-1 and LC3II expression and reduced P62 expression, which were indicative of autophagy. CBD treatment attenuated the neural apoptosis induced by HS, as reflected by restoring mitochondrial dysfunction, downregulation of BAX, neuro-apoptosis ratio and NF-κB signaling activation, and upregulation of BCL2 in the cerebral cortex. Such protective effects were reversed by 3-Methyladenine, a specific autophagy inhibitor, indicating that the protective effects of CBD treatment involved autophagy. LY294002, a PI3K inhibitor, significantly inhibited CBD-induced autophagy, demonstrating that PI3K/AKT signaling is involved in the CBD's regulation of autophagy. Furthermore, we found that CBD treatment upregulated PI3K/AKT signaling via cannabinoid receptor 1. Therefore, these findings suggested that CBD treatment protects against cerebral injury induced by HS-mediated mitochondrial-dependent apoptosis by activating the PI3K/AKT signaling pathway to reinforce autophagy.

Hyperbaric oxygen therapy cognitive function in a rat model of mild cognitive impairment via ERK signaling.

BACKGROUND: The development of novel treatment strategies to reverse or impede cognitive dysfunction associated with mild cognitive impairment (MCI) has gained attention in recent times. Meanwhile, hyperbaric oxygen (HBO) has been widely used as a neuroprotective therapy that can promote recovery of damaged neurons. The aim of this study was to investigate the effects of HBO on cognitive function in rats with MCI and to clarify the associated mechanisms. METHODS: We established a D-galactose-induced MCI rat model and evaluated the role of extracellularregulated kinase (ERK) signaling in HBO therapy for cognitive function using a specific inhibitor, U0126. All Rats were randomly assigned to four groups with 12 rats per group: normal control group; D-gal model group (group MCI); D-gal + HBO group (group HBO); D-gal + HBO + U0126 group (group U0126). We evaluated cognitive function by Morris water maze and pathological changes by hematoxylin and eosin (HE) staining of hippocampal slices. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of caspase 3, while total ERK1/2 and phospho-ERK1/2 were assessed by Western blotting. RESULTS: Shorter escape latency was observed in the HBO group as compared to the MCI group, which was to some extent reversed by U0126. Similarly, the HBO group showed the highest number of platform crossings as compared to the MCI and U0126 groups. Pathological analysis also showed less apoptosis and better hippocampal cell morphology in the HBO group. Caspase 3 levels also differed significantly, with lowest expression in the HBO group as compared to the MCI and U0126 groups. The levels of total ERK1/2 and p-ERK1/2 were more elevated in the HBO group as compared to the MCI group. CONCLUSIONS: This study found that HBO treatment has a protective effect on early cognitive dysfunction in rats with MCI. HBO therapy may act through ERK signaling, which inhibits apoptosis and protects cognitive function.

Flexible video endoscope versus Macintosh laryngoscope for orotracheal tracheal intubation in the lateral position: a study protocol for a randomized controlled trial.

BACKGROUND: Tracheal intubation with the patient in the lateral position is difficult because the laryngeal view is compromised during direct laryngoscopy. Flexible video endoscopes may facilitate intubation even when laryngeal views are poor on direct laryngoscopy because the patients are positioned laterally. Thus, this trial aims to compare the efficacy of flexible video endoscopes to Macintosh laryngoscopes for orotracheal intubation in the lateral position and to investigate their feasibility, i.e., whether the use of the two devices in combination can secure the airway when endotracheal intubation in the lateral position has failed using one device. METHODS: This will be a prospective, randomized, single-center, clinical trial. One hundred and seventy-four patients aged 18-65 years, who have been scheduled to undergo tracheal intubation under uniform general anesthetic techniques for elective kidney surgery in the lateral decubitus position will be randomly divided into the flexible video endoscope and the Macintosh laryngoscope groups. Primary outcomes include intubation time and intubation success rate. Secondary outcomes include overall user satisfaction (graded from 1 to 10 (1 = very poor, 10 = excellent)) and perioperative side effects and complications, such as frequency of esophageal intubation, lip or dental injury, sore throat, and hoarseness. DISCUSSION: The trial will clarify the efficacy of intubation with a Macintosh laryngoscope and a flexible video endoscope in the lateral position, and whether the two devices could be used in combination to secure the airway in cases where endotracheal intubation in the lateral position has failed with one device. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR- IOR-15007175 . Registered on 6 October 2015.

Improvement of Cu2 ZnSn(S,Se)4 Solar Cells by Adding N,N-Dimethylformamide to the Dimethyl Sulfoxide-Based Precursor Ink.

Cu2 ZnSn(S,Se)4 (CZTSSe) solar cells based on dimethyl sulfoxide (DMSO) Cu-Zn-Sn-S precursor ink have seen tremendous progress in recent years. However, the wettability between the ink and Mo substrate is poor, owing to the high viscosity of the highly concentrated Cu-Zn-Sn-S ink. Herein, a solvent engineering process is proposed in which N,N-dimethylformamide (DMF) is added into the DMSO-based Cu-Zn-Sn-S ink for the deposition of CZTSSe thin-film absorbers in air. The addition of DMF significantly improves the wettability between the precursor ink and Mo substrate. The DMF/(DMF+DMSO) ratio also plays a critical role in determining the crystal quality of the resulting CZTSSe absorber and the device performance. The grain size of CZTSSe thin films increases with increasing DMF/(DMF+DMSO) ratio. Particularly, large grains through the whole cross section can be achieved with 20 % DMF addition. Accordingly, the power conversion efficiency of the device increases from 6.5 % to 8.6 % under AM 1.5G illumination. However, the efficiency decreases to 5.4 % when the DMF content is further increased to 30 %. Interface recombination and back contact barrier are found to be the main limitations of these devices.

Optimal concentration of the transversus abdominis plane block in enhanced recovery after surgery protocols for patients of advanced age undergoing laparoscopic rectal cancer surgery.

OBJECTIVE: The transversus abdominis plane (TAP) block ameliorates visual analogue scale scores and decreases morphine requirements, but its role remains unclear. Patients of advanced age are susceptible to local anesthetic intoxication. We aimed to identify an optimal concentration that can be used in enhanced recovery after surgery (ERAS) without compromising analgesic efficacy. METHODS: In total, 120 patients aged ≥65 years undergoing laparoscopic rectal cancer surgery received general anesthesia combined with a TAP block using 0.25% ropivacaine (Group A), 0.50% ropivacaine (Group B), or 0.75% ropivacaine (Group C) in a 40-mL volume. Group D only received general anesthesia. Epinephrine, plasma cortisol, interleukin-6, and tumor necrosis factor-α were measured at baseline, skin incision, celiac exploration, and tracheal extubation. The proportions of CD4+ and CD4+/CD8+ cells were measured at baseline and postoperative days 1 and 3. RESULTS: The TAP block relieved the stress response and accelerated intestinal functional recovery as shown by significant reductions in VAS scores and anesthetic requirements. However, there was no significant difference between Groups B and C. CONCLUSION: The TAP block plays an important role in ERAS in older patients undergoing laparoscopic rectal cancer surgery, and 0.5% ropivacaine is an optimal concentration that can reduce toxicity without undermining analgesia.