Imaging, pathology, and diagnosis of solitary fibrous tumor of the pancreas: A case report and review of literature.

BACKGROUND: A solitary fibrous tumor (SFT) is often located in the pleura, while SFT of the pancreas is extremely rare. Here, we report a case of SFT of the pancreas and discuss imaging, histopathology, and immunohistochemistry for accurate diagnosis and treatment. CASE SUMMARY: A 54-year-old man presented to our hospital with pancreatic occupancy for over a month. There were no previous complaints of discomfort. His blood pressure was normal. Blood glucose, tumor markers, and enhanced computed tomography (CT) suggested a malignant tumor. Because the CT appearance of pancreatic cancer varies, we could not confirm the diagnosis; therefore, we performed endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Pathology and immunohistochemistry were consistent with SFT of the pancreas. The postoperative pathology and immunohistochemistry were consistent with the puncture results. The patient presented for a follow-up examination one month after discharge with no adverse effects. CONCLUSION: Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed. CT and pathological histology have diagnostic value for pancreatic tumors. Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively. Surgery is an effective treatment for SFT of the pancreas; however, long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

Hippocampal estrogens rescued the decline of synaptic plasticity after surgery and anesthesia by inhibiting microglia overactivation.

BACKGROUND: Elderly patients experience postoperative cognitive impairment frequently; therefore, effective interventions are urgently needed. Central nervous inflammation characterized by microglia may promote the progression of POCD by reducing synaptic plasticity. Notably, clinical studies revealed that the incidence of female patients was significantly lower than that of male patients. Besides, the brain estrogens have an anti-inflammatory effect and regulate the microglia at the same times. This study aimed to determine whether suppressing microglia overactivation by hippocampal estrogens can rescue the decrease of synaptic plasticity after surgery and anesthesia. METHODS: Exploratory laparotomy was used to establish the POCD model in 15-month-old male or female C57BL/6 J mice and animal behavioral tests were performed to test hippocampal-dependent memory capacity. Western blot and immunofluorescence were used to detect the microglial activation and plasticity related protein expressions. Elisa was used to detect the content of estrogens in the hippocampus. Estrogens and estrogen receptor inhibitor were used to replenish the estrogens in the brain and inhibit the effect of estrogens. RESULTS: Surgery and anesthesia did not cause POCD in female mice (P > 0.05), while the cognitive function decreased significantly after estrogen receptor inhibitor was given(P < 0.05). Male mice experienced cognitive dysfunction after surgery and anesthesia, and their cognitive function improved after estrogens supplementation (P < 0.05). Given estrogens and estrogen receptor inhibitors at the same time, the cognitive function of male mice could not be saved (P < 0.05). By correlation analysis, there was a negative correlation between the content of hippocampal estrogens and microglia (P < 0.05). The number or degree of activation of microglia affected the synaptic plasticity, which ultimately regulated the cognitive function of mice. CONCLUSION: Hippocampal estrogens rescued the decline of synaptic plasticity after surgery and anesthesia by inhibiting microglia overactivation.

Lactate Improves Long-term Cognitive Impairment Induced By Repeated Neonatal Sevoflurane Exposures Through SIRT1-mediated Regulation of Adult Hippocampal Neurogenesis and Synaptic Plasticity in Male Mice.

Repeated neonatal exposures to sevoflurane induce long-term cognitive impairment that has been reported to have sex-dependent differences. Exercise promotes learning and memory by releasing lactate from the muscle. The study tested the hypothesis that lactate may improve long-term cognitive impairment induced by repeated neonatal exposures to sevoflurane through SIRT1-mediated regulation of adult hippocampal neurogenesis and synaptic plasticity. C57BL/6 mice of both genders were exposed to 3% sevoflurane for 2 h daily from postnatal day 6 (P6) to P8. In the intervention experiments, mice received lactate at 1 g/kg intraperitoneally once daily from P21 to P41. Behavioral tests including open field (OF), object location (OL), novel object recognition (NOR), and fear conditioning (FC) tests were performed to assess cognitive function. The number of 5-Bromo-2'- deoxyuridine positive (BrdU+) cells and BrdU+/DCX+ (doublecortin) co-labeled cells, expressions of brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeletal-associated protein (Arc), early growth response 1 (Egr-1), SIRT1, PGC-1α and FNDC5, and long-term potentiation (LTP) were evaluated in the hippocampus. Repeated exposures to sevoflurane induced deficits in OL, NOR and contextual FC tests in male but not female mice. Similarly, adult hippocampal neurogenesis, synaptic plasticity-related proteins and hippocampal LTP were impaired after repeated exposures to sevoflurane in male but not female mice, which could rescue by lactate treatment. Our study suggests that repeated neonatal exposures to sevoflurane inhibit adult hippocampal neurogenesis and induce defects of synaptic plasticity in male but not female mice, which may contribute to long-term cognitive impairment. Lactate treatment rescues these abnormalities through activation of SIRT1.

Strong External Electric Fields Reduce Explosive Sensitivity: A Theoretical Investigation into the Reaction Selectivity in NH2NO2∙∙∙NH3.

Controlling the selectivity of a detonation initiation reaction of explosive is essential to reduce sensitivity, and it seems impossible to reduce it by strengthening the external electric field. To verify this, the effects of external electric fields on the initiation reactions in NH2NO2∙∙∙NH3, a model system of the nitroamine explosive with alkaline additive, were investigated at the MP2/6-311++G(2d,p) and CCSD(T)/6-311++G(2d,p) levels. The concerted effect in the intermolecular hydrogen exchange is characterized by an index of the imaginary vibrations. Due to the weakened concerted effects by the electric field along the -x-direction opposite to the "reaction axis", the dominant reaction changes from the intermolecular hydrogen exchange to 1,3-intramolecular hydrogen transference with the increase in the field strengths. Furthermore, the stronger the field strengths, the higher the barrier heights become, indicating the lower sensitivities. Therefore, by increasing the field strength and adjusting the orientation between the field and "reaction axis", not only can the reaction selectivity be controlled, but the sensitivity can also be reduced, in particular under a super-strong field. Thus, a traditional concept, in which the explosive is dangerous under the super-strong external electric field, is theoretically broken. Compared to the neutral medium, a low sensitivity of the explosive with alkaline can be achieved under the stronger field. Employing atoms in molecules, reduced density gradient, and surface electrostatic potentials, the origin of the reaction selectivity and sensitivity change is revealed. This work provides a new idea for the technical improvement regarding adding the external electric field into the explosive system.

Experimental and theoretical investigation into the response to shock wave for booster explosives JO9C, JH14, JH6, and insensitive RDX.

In order to reduce the vulnerability, the responses to shock waves for booster explosives JO9C, JH14, JH6, and insensitive RDX were evaluated using shock wave partition loading test. To explain the experimental results, molecular dynamics simulation, intermolecular interaction and bond dissociation energy (BDE), and shock initiation pressures were evaluated using the B3LYP, MP2 (full), and M06-2X methods with the 6-311 + + G(2df,2p) basis set. The order of the responsivity is JO9C > JH14 > JH6 > insensitive RDX. The binding energies follow the order of JH14* ≈ JO9C* < insensitive RDX* < JH6*. The interaction energies and BDEs are in RDX∙∙∙(CH3COOCa)+ > RDX∙∙∙CH3COOH > RDX∙∙∙CH2FCH2F. Thus, it can be inferred that for the RDX-based explosives, the stronger the binding energy, intermolecular interaction, and BDE are, the more insensitive the booster is, and thus, the larger energy has to be consumed to overcome the above three kinds of energies during the initiation process, leading to the smaller energy output and weaker response. However, it should be noted that it is mainly the density and the type of explosive that influence the depth of the dent produced on the steel witness block. The essence of the responses to shock waves is revealed by the reduced density gradient, atoms in molecules, and surface electrostatic potentials. HIGHLIGHTS: • Response of booster to shock wave was evaluated by shock wave partition loading test. • Responsivity to shock wave is explained by binding energy, intermolecular interaction, and BDE. • Shock initiation pressures were evaluated. • Essence of responses to shock wave is revealed by RDG, AIM and ESP.

Glycochenodeoxycholate Affects Iron Homeostasis via Up-Regulating Hepcidin Expression.

Increasing hepcidin expression is a vital factor in iron homeostasis imbalance among patients with chronic kidney disease (CKD). Recent studies have elucidated that abnormal serum steroid levels might cause the elevation of hepcidin. Glycochenodeoxycholate (GCDCA), a steroid, is significantly elevated in patients with CKD. However, the correlation between GCDCA and hepcidin has not been elucidated. Decreased serum iron levels and increased hepcidin levels were both detected in patients with CKD in this study. Additionally, the concentrations of GCDCA in nephropathy patients were found to be higher than those in healthy subjects. HepG2 cells were used to investigate the effect of GCDCA on hepcidin in vitro. The results showed that hepcidin expression increased by nearly two-fold against control under 200 µM GCDCA treatment. The phosphorylation of SMAD1/5/8 increased remarkably, while STAT3 and CREBH remained unchanged. GCDCA triggered the expression of farnesoid X receptor (FXR), followed with the transcription and expression of both BMP6 and ALK3 (upward regulators of SMAD1/5/8). Thus, GCDCA is a potential regulator for hepcidin, which possibly acts by triggering FXR and the BMP6/ALK3-SMAD signaling pathway. Furthermore, 40 C57/BL6 mice were treated with 100 mg/kg/d, 200 mg/kg/d, and 300 mg/kg/d GCDCA to investigate its effect on hepcidin in vivo. The serum level of hepcidin increased in mice treated with 200 mg/kg/d and 300 mg/kg/d GCDCA, while hemoglobin and serum iron levels decreased. Similarly, the FXR-mediated SMAD signaling pathway was also responsible for activating hepcidin in liver. Overall, it was concluded that GCDCA could induce the expression of hepcidin and reduce serum iron level, in which FXR activation-related SMAD signaling was the main target for GCDCA. Thus, abnormal GCDCA level indicates a potential risk of iron homeostasis imbalance.

Predictors and predictive effects of acute pain trajectories after gastrointestinal surgery.

Few studies have investigated factors associated with acute postsurgical pain (APSP) trajectories, and whether the APSP trajectory can predict chronic postsurgical pain (CPSP) remains unclear. We aimed to identify the predictors of APSP trajectories in patients undergoing gastrointestinal surgery. Moreover, we hypothesised that APSP trajectories were independently associated with CPSP. We conducted a prospective cohort study of 282 patients undergoing gastrointestinal surgery to describe APSP trajectories. Psychological questionnaires were administered 1 day before surgery. Meanwhile, demographic characteristics and perioperative data were collected. Average pain intensity during the first 7 days after surgery was assessed by a numeric rating scale (NRS). Persistent pain intensity was evaluated at 3 and 6 months postoperatively by phone call interview. CPSP was defined as pain at the incision site or surrounding areas of surgery with a pain NRS score ≥ 1 at rest. The intercept and slope were calculated by linear regression using the least squares method. The predictors for the APSP trajectory and CPSP were determined using multiple linear regression and multivariate logistic regression, respectively. Body mass index, morphine milligram equivalent (MME) consumption, preoperative chronic pain and anxiety were predictors of the APSP trajectory intercept. Moreover, MME consumption and preoperative anxiety could independently predict the APSP trajectory slope. The incidence of CPSP at 3 and 6 months was 30.58% and 16.42% respectively. APSP trajectory and age were predictors of CPSP 3 months postoperatively, while female sex and preoperative anxiety were predictive factors of CPSP 6 months postoperatively. Preoperative anxiety and postoperative analgesic consumption can predict APSP trajectory. In addition, pain trajectory was associated with CPSP. Clinicians need to stay alert for these predictors and pay close attention to pain resolution.

Research Progress on the Role of Inflammatory Mechanisms in the Development of Postoperative Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD), as one of the common postoperative complications, mainly occurs after surgery and anesthesia, especially in the elderly. It refers to cognitive function changes such as decreased learning and memory ability and inability to concentrate. In severe cases, there could be personality changes and a decline in social behavior. At present, a great deal of research had been carried out on POCD, but its specific mechanism remains unclear. The release of peripheral inflammation-related factors, the degradation and destruction of the blood-brain barrier, the occurrence of central inflammation, and the neuronal apoptosis and synaptic loss could be promoted by neuroinflammation indicating that inflammatory mechanisms may play key roles in the occurrence of POCD.

Ethnobotanical survey of medicinal plants in Gaomi, China.

ETHNOPHARMACOLOGICAL RELEVANCE: The uses of medicinal plants have a long history and become one of the important sources of the health cares in Gaomi City, Shandong Province, China. However, limited studies have been done to identify these medicinal plant species and to scientifically document their associated traditional knowledge. Many species used by indigenous people could potentially represent a novel resource of medicine. The study can aid in further investigations of modern pharmacology and planning of the wild species conservation. AIM OF THE STUDY: The study aimed to investigate and record the medicinal plant taxa and their associated traditional knowledge in Gaomi City, China. MATERIALS AND METHODS: Field study was conducted from March 2018 to May 2019 with 184 residents of Gaomi City. Traditional medicinal plant specimens were collected from the field with the help of these residents and were identified and authenticated in the Herbarium of the School of Pharmacy, Binzhou Medical University. Ethnobotanical knowledge was collected by semi-structured face-to-face interviews. The quantitative data were analyzed by using the informant consensus factor (ICF) method and the number of citations. RESULTS: A total of 181 species belonging to 137 genera and 65 families were collected in Gaomi City. Asteraceae was the predominant family and Fabaceae took the second place. River basins and the southern hills in Gaomi were rich in vegetation. However, the cultivated area of medicinal plants only accounted for 10% of agricultural acreage. The main preparation method was decocting (170, 94.48%) and the most frequent mode of administration was oral (177, 97.97%). The highest numerical ICF value was recorded for treating endocrine, metabolic, and nutritional (ICF: 0.85) conditions. Seven of the medicinal plant species used by the people in Gaomi have not been reported previously in China. Verbena officinalis L. was found in Gaomi City, which is a new distribution record for this species. CONCLUSIONS: People in Gaomi hold valuable knowledge about the use of medicinal plants; however, their knowledge has not been comprehensively documented. The therapeutic uses of the documented medicinal plants will provide a basis for further pharmacological and phytochemical investigations. Additionally, the result of this study indicated that the elder people in Gaomi have more traditional knowledge of plant medicines than the younger ones.

[Study on pain control of continuous adductor block analgesia after primary knee replacement].

OBJECTIVE: To investigate the effect of continuous adductor block on pain control after bilateral knee joint Ⅰ stage replacement. METHODS: A retrospective analysis was made of the data of 24 patients with bilateral knee joint I stage replacement who were treated in our hospital from January 2018 to January 2019, and who underwent continuous adductor block analgesia. There were 6 males and 18 females, aged 60 to 72 (65.05±5.82) years old. The patients underwent continuous block of adductor canal with patient-controlled analgesia system. At 4, 6, 12, 24, 36 and 48 hours after operation, visual analogue score(VAS) of resting state and passive motion state was performed;the knee joint activity was followed up for 1 week, 1, 3 and 6 months after operation;the knee joint function was scored at 6 months after operation, using the knee joint scoring standard of American Special Surgery Hospital(HSS);adverse reactions and complications were recorded. RESULTS: The VAS scores under resting state and passive motion state at each time point were less than 3 points in patients with continuous adductor block. The patients had better postoperative exercise of knee joint activity. The score of HSS was excellent in 20 cases, good in 2 cases, fair in 1 case and poor in 1 case. There were only 4 cases of nausea and vomiting, none of them had serious adverse reactions and complications such as bradycardia and deep vein thrombosis. CONCLUSION: Continuous adductor block has a significant effect on pain control and less adverse reactions after bilateral knee jointⅠ -stage replacement.

Hippocampal complement C3 might contribute to cognitive impairment induced by anesthesia and surgery.

Postoperative cognitive dysfunction is a well-recognized complication after major surgery in the elderly, but its pathophysiological mechanism is not fully understood. In the present study, we used liquid chromatography-tandem mass spectrometry combined with tandem mass tags to identify differentially expressed proteins and perform further functional studies on protein of interest. Here, we showed that hippocampal complement C3 was significantly upregulated after surgery, which was accompanied by marked decreases in synaptic related proteins and density. In aged patients undergoing gastrointestinal surgery, we also found significantly increased plasma level of C3b postoperatively and were negatively associated with cognitive performance. Notably, selective inhibition of complement C3 by compstatin was able to rescue synaptic and cognitive impairments induced by surgery in aged mice. Collectively, our study confirms that surgery can induce cognitive impairments, and the possible mechanisms might be related to abnormal complement signaling and synaptic disruption.

Overinhibition mediated by parvalbumin interneurons might contribute to depression-like behavior and working memory impairment induced by lipopolysaccharide challenge.

Systemic inflammation induces cognitive impairments via unclear mechanisms. Accumulating evidence has demonstrated that a subset of neurons that express parvalbumin (PV) play a critical role in regulation of cognitive and emotional behavior. Thus, the aim of the present study was to test whether disruption of PV interneuron mediates systemic inflammation-induced depression-like behavior and working memory impairment by lipopolysaccharide (LPS) challenge. Here we showed that LPS induces depression-like behavior and working memory impairment, coinciding with increased PV expression, enhanced GABAergic transmission, and impaired long-term potentiation (LTP) in the hippocampus. Notably, systemic administration of NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was able to interfere with PV expression and reverse depression-like behavior and working memory impairment, which is probably mediated by reversing impaired LTP. In addition, flumazenil, a competitive antagonist acting at the benzodiazepine binding site of the GABAA receptor, also ameliorated these abnormal behaviors. Collectively, our study added growing evidence to the limited studies that overinhibition mediated by PV interneurons might play a critical role in LPS-induced depression-like behavior and working memory impairment.

Dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca2+/calpain might contribute to postoperative cognitive dysfunction in aging mice.

BACKGROUND: Postoperative cognitive decline (POCD) is a recognized clinical phenomenon characterized by cognitive impairments in patients following anesthesia and surgery, yet its underlying mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, learning, and memory via activation of TrkB-full length (TrkB-FL) receptors. It has been reported that an abnormal truncation of TrkB mediated by calpain results in dysregulation of BDNF/TrkB signaling and is associated with cognitive impairments in several neurodegenerative disorders. Calpains are Ca2+-dependent proteases, and overactivation of calpain is linked to neuronal death. Since one source of intracellular Ca2+ is N-methyl-d-aspartate receptors (NMDARs) related and the function of NMDARs can be regulated by neuroinflammation, we therefore hypothesized that dysregulation of BDNF/TrkB signaling mediated by NMDAR/Ca2+/calpain might be involved in the pathogenesis of POCD. METHODS: In the present study, 16-month-old C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to establish the POCD animal model. For the interventional study, mice were treated with either NMDAR antagonist memantine or calpain inhibitor MDL-28170. Behavioral tests were performed by open field, Y maze, and fear conditioning tests from 5 to 8 days post-surgery. The levels of Iba-1, GFAP, interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), NMDARs, calpain, BDNF, TrkB, bax, bcl-2, caspase-3, and dendritic spine density were determined in the hippocampus. RESULTS: Anesthesia and surgery-induced neuroinflammation overactivated NMDARs and then triggered overactivation of calpain, which subsequently led to the truncation of TrkB-FL, BDNF/TrkB signaling dysregulation, dendritic spine loss, and cell apoptosis, contributing to cognitive impairments in aging mice. These abnormities were prevented by memantine or MDL-28170 treatment. CONCLUSION: Collectively, our study supports the notion that NMDAR/Ca2+/calpain is mechanistically involved in anesthesia and surgery-induced BDNF/TrkB signaling disruption and cognitive impairments in aging mice, which provides one possible therapeutic target for POCD.

Effects of dezocine for the prevention of postoperative catheter-related bladder discomfort: a prospective randomized trial.

Purpose: To evaluate the effects of dezocine on the prevention of postoperative catheter-related bladder discomfort (CRBD). Patients and methods: Ninety-six adult patients undergoing abdominal surgery with urinary catheterization under general anesthesia were randomized into dezocine and control (flurbiprofen) groups. The postoperative CRBD, pain score, sedation score and adverse effects were evaluated at 0, 1, 2 and 6 hrs after tracheal extubation. Results: The primary outcome showed a lower incidence of CRBD at 1 hr post-extubation in the dezocine group (29.17%) than the control group (58.33%, P<0.01). The incidences at 0 and 2 hrs post-extubation and the overall incidence were also lower in the dezocine group than the control group (all P<0.05). The severity of CRBD at 0, 1, 2 and 6 hrs and the pain, sedation score and other adverse effects were comparable between the two groups (P>0.05); however, the overall severity of CRBD was decreased in the dezocine group compared with the control group (P<0.05). Conclusion: Intraoperative dezocine reduces the incidence and severity of postoperative CRBD without clinically relevant adverse effects.

[Effects of different decocting methods on quality of Mahuang Xixin Fuzi decoction].

To compare the quality difference between Mahuang Xixin Fuzi decoction(MXF) prepared by traditional decocting method and that prepared by two commonly used decocting methods, and explore the scientific nature of the traditional decocting method. By taking effect-toxic components in MXF as the research object, this article investigated these three different decocting methods from the quantitative determination of effect-toxic components in MXF. By using multivariate statistical analysis methods, three characteristic constituents were identified as kakoul, mesaconitine (MA) and hypaconitine (HA) respectively. As compared with two commonly used decocting methods, MXF decoction prepared by traditional decocting method had the shortest boiling time, but with the lowest dissolution rates of MA and AC and the higher dissolution rates of mono-ester aconitum alkaloids. In addition, the traditional decocting method increased the dissolution of ephedra alkaloid and accelerated the hydrolysis of diester diterpenoid alkaloids. There were differences in the content of effect-toxic components in MXF decoctions prepared by three different decocting methods, which can provide a reference for use of the classical prescriptions.

Environmental conditions differentially affect neurobehavioral outcomes in a mouse model of sepsis-associated encephalopathy.

Brain dysfunction remains a common complication after sepsis development and is an independent risk factor for a poorer prognosis and an increased mortality. Here we tested the hypothesis that the behavioral outcomes after lipopolysaccharides (LPS) administration are exacerbated by an impoverished environment (IE) and alleviated by an enriched environment (EE), respectively. Mice were randomly allocated in a standard environment (SE), an EE, or an IE for 4 weeks after LPS or normal saline (NS) administration. Neurobehavioral alternations were assessed by the open field, novel objective recognition, and fear conditioning tests. The expressions of proinflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-10), ionized calcium-binding adaptor molecule-1 (IBA1)-positive cells as well as glial fibrillary acidic protein (GFAP)-positive cells, brain derived neurotrophic factor (BDNF), 5-bromo-2-deoxyuridine-labeled cells in the dentate gyrus of the hippocampus, and the number of dendritic spines in the hippocampal CA1 were determined. Our results showed that the some of the neurocognitive abnormalities induced by LPS administration can be aggravated by stressful conditions such as IE but alleviated by EE. These neurocognitive alternations were accompanied by significant changes in biomarkers of immune response and hippocampal synaptic plasticity. In summary, our study confirmed the negative impact of IE and the positive effects of EE on the cognitive function after LPS administration, with potential implications to the basis of sepsis-related cognitive impairments in the critically ill patients.

Repeated Neonatal Sevoflurane Exposure-Induced Developmental Delays of Parvalbumin Interneurons and Cognitive Impairments Are Reversed by Environmental Enrichment.

Parvalbumin (PV) interneurons are critically involved in the cognitive processes. Based on prior investigations that environmental enrichment reverses impaired cognition after anesthetic exposure, we proposed that environmental enrichment protects PV interneurons and thereby improves sevoflurane-induced cognitive impairments. Six-day-old C57BL/6 male mice were exposed to 3 % sevoflurane or 30 % oxygen/air 2 h daily for 3 days from postnatal day 6 (P6) to P8. The mice were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or a standard environment. Western blotting and immunofluorescence were used for determining PV expression in the prefrontal cortex and hippocampus. In another set of experiments, cognitive tests were assessed by the open field test (P41), Morris water maze test (P54-60), and fear conditioning tests (P42-43 and P89-90). Exposure of neonatal mice to sevoflurane resulted in a reduced freezing response in the contextual test at P43 but not P90. The PV expression in these mice was decreased at P9, P14, P28, and P42, but not at ≥P60. No colocalization of caspase-3 and 5-bromo-2-deoxyuridine or caspase-3 and PV was observed, suggesting that caspase-independent pathways may be involved in the mediation of sevoflurane-induced down-regulation of PV. The sevoflurane-exposed mice that were placed in an enriched environment exhibited normal behavior and had PV interneurons that did not differ from those in the control mice at P42-43. Neonatal sevoflurane exposure induces a reduced freezing response in the contextual test at P43 and developmental delays in PV interneurons in the prefrontal cortex and hippocampus. Placement of the sevoflurane-exposed mice in an enriched environment can prevent these abnormalities.

Separation of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane and 1,3,5-trinitro-1,3,5- triazacyclohexane by molecularly imprinted solid-phase extraction.

Synthesis of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane and 1,3,5-trinitro-1,3,5-triazacyclohexane by the Bachmann process leads to a mixture of both. The separation of 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane and 1,3,5-trinitro-1,3,5-triazacyclohexane from their mixture is difficult because the sizes and physical properties of these homologous compounds are similar. For this purpose, seven molecularly imprinted polymers have been synthesized for each explosive, and a selective solid-phase extraction procedure has been developed. A molecularly imprinted polymer, synthesized with 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane as the template, methacrylic acid as the monomer and trimethylolpropane trimethacrylate as the cross-linking agent in a molar ratio of 1:8:8 showed the best separation capability. A packed cartridge containing this polymer can be reused for 23 solid-phase extraction cycles without repacking, and the total separation capability toward 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane reached 6.81 mg per gram of polymer. 1,3,5-Trinitro-1,3,5-triazacyclohexane was not detected in the separated 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane by high-performance liquid chromatography and vice versa. This newly developed method had the advantages of high recovery (100%) and purity, environmental friendliness, and room temperature operability. This study showed that some molecularly imprinted polymers that cannot absorb target analytes well in the solvent in which the polymers were polymerized might have high-binding capacity for the analytes and show imprinting effects in other solvents.

Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice.

Postoperative cognitive decline (POCD) is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated-abnormalities in parvalbumin (PV) interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in 16-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO). Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide (LPS) in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1ß (IL-1ß), markers of oxidative stress and NADPH oxidase 2 (Nox2) in the hippocampus. In addition, LPS exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived reactive oxygen species (ROS) production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice.

GluA1 signal peptide determines the spatial assembly of heteromeric AMPA receptors.

AMPA-type glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and predominantly assemble as heterotetramers in the brain. Recently, the crystal structures of homotetrameric GluA2 demonstrated that AMPARs are assembled with two pairs of conformationally distinct subunits, in a dimer of dimers formation. However, the structure of heteromeric AMPARs remains unclear. Guided by the GluA2 structure, we performed cysteine mutant cross-linking experiments in full-length GluA1/A2, aiming to draw the heteromeric AMPAR architecture. We found that the amino-terminal domains determine the first level of heterodimer formation. When the dimers further assemble into tetramers, GluA1 and GluA2 subunits have preferred positions, possessing a 1-2-1-2 spatial assembly. By swapping the critical sequences, we surprisingly found that the spatial assembly pattern is controlled by the excisable signal peptides. Replacements with an unrelated GluK2 signal peptide demonstrated that GluA1 signal peptide plays a critical role in determining the spatial priority. Our study thus uncovers the spatial assembly of an important type of glutamate receptors in the brain and reveals a novel function of signal peptides.