Effect of transcutaneous electrical acupoint stimulation on postoperative pain in pediatric orthopedic surgery with the enhanced recovery after surgery protocol: a prospective, randomized controlled trial.

STUDY OBJECTIVE: To evaluate the safety and effectiveness of transcutaneous electrical acupoint stimulation (TEAS) in postoperative analgesia following pediatric orthopedic surgery with the enhanced recovery after surgery (ERAS) protocol. DESIGN: Prospective randomized controlled trial. SETTING: The Seventh Medical Center of the Chinese People's Liberation Army General Hospital. PARTICIPANTS: Eligible participants were children aged 3-15 years who were scheduled to undergo orthopedic surgery of the lower extremities under general anesthesia. INTERVENTIONS: A total of 58 children were randomly allocated into two groups: TEAS (n = 29) and sham-TEAS (n = 29). The ERAS protocol was used in both groups. In the TEAS group, the bilateral Hegu (LI4) and Neiguan (PC6) acupoints were stimulated starting from 10 min before anesthetic induction until the completion of surgery. In the sham-TEAS group, the electric stimulator was also connected to the participants; however, electrical stimulation was not applied. MEASURES: The primary outcome was the severity of pain before leaving the post-anesthesia care unit (PACU) and at postoperative 2 h, 24 h, and 48 h. Pain intensity was measured with the Faces Pain Scale-Revised (FPS-R). RESULTS: None of the participants had any TEAS-related adverse reactions. In comparison with the sham-TEAS group, FPS-R scores in the TEAS group were significantly decreased before leaving the PACU and at postoperative 2 h and 24 h (p < 0.05). The incidence of emergence agitation, intraoperative consumption of remifentanil, and time to extubation were significantly reduced in the TEAS group. Furthermore, the time to first press of the patient-controlled intravenous analgesia (PCIA) pump was significantly longer, the pressing times of the PCIA pump in 48 h after surgery was significantly decreased, and parental satisfaction was significantly improved (all p < 0.05). CONCLUSION: TEAS may safely and effectively relieve postoperative pain and reduce the consumption of perioperative analgesia in children following orthopedic surgery with the ERAS protocol. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200059577), registered on May 4, 2022.

Age-dependent neurovascular coupling characteristics in children and adults during general anesthesia.

General anesthesia is an indispensable procedure in clinical practice. Anesthetic drugs induce dramatic changes in neuronal activity and cerebral metabolism. However, the age-related changes in neurophysiology and hemodynamics during general anesthesia remain unclear. Therefore, the objective of this study was to explore the neurovascular coupling between neurophysiology and hemodynamics in children and adults during general anesthesia. We analyzed frontal electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) signals recorded from children (6-12 years old, n = 17) and adults (18-60 years old, n = 25) during propofol-induced and sevoflurane-maintained general anesthesia. The neurovascular coupling was evaluated in wakefulness, maintenance of a surgical state of anesthesia (MOSSA), and recovery by using correlation, coherence and Granger-causality (GC) between the EEG indices [EEG power in different bands and permutation entropy (PE)], and hemodynamic responses the oxyhemoglobin (Δ[HbO]) and deoxy-hemoglobin (Δ[Hb]) from fNIRS in the frequency band in 0.01-0.1 Hz. The PE and Δ[Hb] performed well in distinguishing the anesthesia state (p > 0.001). The correlation between PE and Δ[Hb] was higher than those of other indices in the two age groups. The coherence significantly increased during MOSSA (p < 0.05) compared with wakefulness, and the coherences between theta, alpha and gamma, and hemodynamic activities of children are significantly stronger than that of adults' bands. The GC from neuronal activities to hemodynamic responses decreased during MOSSA, and can better distinguish anesthesia state in adults. Propofol-induced and sevoflurane-maintained combination exhibited age-dependent neuronal activities, hemodynamics, and neurovascular coupling, which suggests the need for separate rules for children's and adults' brain states monitoring during general anesthesia.

Thermally activated upconversion luminescence and ratiometric temperature sensing under 1064 nm/808 nm excitation.

In this research, a thermally activated upconversion luminescence (UCL) probe with ratiometric temperature sensing under 1064 nm and 808 nm excitation was designed. Especially, Nd3+, Tm3+and Ce3+were doped in rare earth nanoparticles (RENPs) as UCL modulators. By optimizing the elements and ratios, the excitation wavelength is successfully modulated to 1064 nm excitation with UCL intensity enhanced. Additionally, the prepared RENPs have a significant temperature response at 1064 nm excitation and can be used for thermochromic coatings. The intensity ratio of three-photon UCL (1064 nm excitation) to two-photon UCL (808 nm excitation) as an exponential function of temperature can be used as a ratiometric temperature detector. Therefore, this designed thermochromic coatings may enable new applications in optoelectronic device and industrial sensor.

Machine Learning Enhanced Optical Spectroscopy for Disease Detection.

Optical spectroscopy plays an important role in disease detection. Improving the sensitivity and specificity of spectral detection has great importance in the development of accurate diagnosis. The development of artificial intelligence technology provides a great opportunity to improve the detection accuracy through machine learning methods. In this Perspective, we focus on the combination of machine learning methods with the optical spectroscopy methods widely used for disease detection, including absorbance, fluorescence, scattering, FTIR, terahertz, etc. By comparing the spectral analysis with different machine learning methods, we illustrate that the support vector machine and convolutional neural network are most effective, which have potential to further improve the classification accuracy to distinguish disease subtypes if these machine learning methods are used. This Perspective broadens the scope of optical spectroscopy enhanced by machine learning and will be useful for the development of disease detection.

Dual-molecular targeted NIR II probe with enhanced response for head and neck squamous cell carcinoma imaging.

In this research, a fluorescent probe of 7-(diethylamine) coumarin derivatives with multiple binding sites to detect biothiols in tumor cell with strong NIR II luminescencein vivowas synthesized. The biothiols include cysteine (Cys) and glutathione (GSH) in tumor cells, and the tumor-response luminescence was proved by the cell experiment. Importantly, the monolayer functional phospholipid (DSPE-PEG) coating and aggregation induced emission (AIE) dye of TPE modification made the probe have good stability and biocompatibility with little luminescence quenching in aqueous phase, which was proved byin vitroandin vivoexperiments. The final aqueous NIR II probe combined with bevacizumab (for VEGF recognition in the cancer cells) and Capmatinib (for Met protein recognition in the cancer cells) has stronger targeted imaging on head and neck squamous cell carcinoma (HNSCC) cancer with intravenous injection. This GSH/Cys detection in the tumor cell and strong dual-molecular NIR II bioimagingin vivomay provide new strategy to tumor detection.

Exosome-based rare earth nanoparticles for targeted in situ and metastatic tumor imaging with chemo-assisted immunotherapy.

In this research, a tumor exosome system DOX/2DG@E-RENPs with good biocompatibility, low immunogenicity, and a high targeting effect was proposed for theranostics with high chemo-/starvation/immunotherapy efficiency. DOX and 2-deoxy-D-glucose (DOX/2DG) together with rare earth nanoparticles (RENPs) can be simultaneously carried on the exosome by endocytosis of tumor cells and then exocytosis in vitro. This platform has a good monodispersity with an average size of 70 nm, and the system can emit upconversion luminescence and NIR II luminescence under a single NIR laser. In particular, this exosome can target homing cancer cells and kill the origin tumor cells. The strong targeting effect was proved by different cell lines with exosomes from different orthogonal cells (normal/cancer cells and human/mouse sources, respectively), and the in vivo NIR II imaging guided targeted cancer imaging and liver metastases can be realized by intravenous injection of E-RENPs. Furthermore, the good targeted therapeutic effect and in vivo NIR II imaging and metastases of this platform can be proved. The chemotherapy, starvation therapy, and immunotherapy (immune checkpoint inhibitors of an anti-PD-L1 antibody) could achieve effective synergistic therapy for lung adenocarcinoma, and the immunotherapy can be further proved by the clinical data. This will provide a new strategy for the precise targeting and treatment of tumors.

Age-dependent cross frequency coupling features from children to adults during general anesthesia.

BACKGROUND: The frequency coupling characteristics in electroencephalogram (EEG) induced by anesthetics have been well studied in adults, but the investigation of the age-dependent cross frequency coupling features from children to adults is still lacking. METHODS: We analyzed EEG signals recorded from pediatric to adult patients (n = 131), separated into six age groups: <1 year (n = 15), 1-3 years (n = 23), 3-6 years (n = 19), 6-12 years (n = 18), 12-18 years (n = 16), and 18-45 years (n = 40). Age related EEG power and cross frequency coupling analysis (phase amplitude coupling (PAC) and quadratic phase coupling) of data from maintenance of a surgical state of anesthesia (MOSSA) was conducted. Also, for patients of ages less than 6 years, we analyzed the performance of cross frequency coupling derived indices in distinguishing the states of wakefulness, MOSSA, and recovery of consciousness (ROC). RESULTS: (1) During MOSSA, EEG power substantially increased with age from infancy to 3-6 years then decreased with age in the theta-gamma frequency bands. The infant group (<1 year) had the highest slow oscillation (SO) power among all age groups. (2) The distinct PAC pattern is absent in patients less than 1 year of age both in SO-alpha and delta-alpha frequency band coupling during propofol induced unconsciousness. The modulation index between delta and alpha oscillations in MOSSA increased with age. (3) Wavelet bicoherence derived indices reach their peaks in the 3-6 years group and then decrease with age growth. (4) The Diag_En index (normalized entropy of the diagonal bicoherence entries of the bicoherence matrix) performed the best at distinguishing different states for ages less than 6 years (p<0.05). CONCLUSIONS: The combination of propofol induction and sevoflurane maintenance exhibited age-dependent EEG power spectra, PAC, and bicoherence, likely related to brain development. These observations suggest new rules for infant and child brain state monitoring during general anesthesia are needed.

Astroglial N-myc downstream-regulated gene 2 protects the brain from cerebral edema induced by stroke.

Brain edema is a grave complication of brain ischemia and is the main cause of herniation and death. Although astrocytic swelling is the main contributor to cytotoxic edema, the molecular mechanism involved in this process remains elusive. N-myc downstream-regulated gene 2 (NDRG2), a well-studied tumor suppressor gene, is mainly expressed in astrocytes in mammalian brains. Here, we found that NDRG2 deficiency leads to worsened cerebral edema, imbalanced Na+ transfer, and astrocyte swelling after ischemia. We also found that NDRG2 deletion in astrocytes dramatically changed the expression and distribution of aquaporin-4 and Na+ -K+ -ATPase ß1, which are strongly associated with cell polarity, in the ischemic brain. Brain edema and astrocyte swelling were significantly alleviated by rescuing the expression of astrocytic Na+ -K+ -ATPase ß1 in NDRG2-knockout mouse brains. In addition, the upregulation of astrocytic NDRG2 by lentiviral constructs notably attenuated brain edema, astrocytic swelling, and blood-brain barrier destruction. Our results indicate a particular role of NDRG2 in maintaining astrocytic polarization to facilitate Na+ and water transfer balance and to protect the brain from ischemic edema. These findings provide insight into NDRG2 as a therapeutic target in cerebral edema.

TSPO ligand etifoxine attenuates LPS-induced cognitive dysfunction in mice.

The translocator protein (TSPO), once known as peripheral-type benzodiazepine receptor, was reported to be related with several physiological functions. Etifoxine is a clinically available anxiolytic drug, and has recently shown neuroprotective effects as a TSPO ligand. The aim of the present study was to investigate the influence of etifoxine on LPS-induced neuroinflammation and cognitive dysfunction. C57/BL6 male mice were injected with etifoxine (50 mg/kg, i.p.) three days before lipopolysaccharide (LPS, 500 µg/kg, i.p.) administration. Etifoxine pretreatment alleviated hippocampal inflammation, increased brain levels of progesterone, allopregnanolone and attenuated cognitive dysfunction in LPS-injected mice. While LPS increased expression of caspase-3 and decreased p-Akt/Akt, etifoxine returned caspase-3 and p-Akt/Akt to control levels. Finasteride, a 5α-reductase inhibitor that blocked allopregnanolone production, partially reversed the effects of etifoxine. We concluded that etifoxine exerted neuroprotective effects in LPS-induced neuroinflammation and the neuroprotection may be related with increase of neurosteroids synthesis and decrease of apoptosis.

Anxiolytic and Anti-depressive Like Effects of Translocator Protein (18 kDa) Ligand YL-IPA08 in a Rat Model of Postpartum Depression.

Translocator protein 18 kDa (TSPO) is mainly distributed in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. It mediates cholesterol transportation across the phospholipid membrane, which is a prerequisite for neurosteroid synthesis. Though the ligand of TSPO has clinical value in the diagnosis and treatment of neuropsychiatric disorders, the pharmacological study of TSPO for anti-postpartum depression has not been reported. In this study, the classical method of reproductive hormone withdrawal was used to construct a rat model of postpartum depression (PPD). The effect of YL-IPA08, a new ligand compound of TSPO, on PPD was evaluated using multiple behavioral tests at progressive time points. Additionally, real-time quantitative PCR, Western-blotting and an enzyme linked immunosorbent assay were conducted to elucidate the potential molecular mechanism of such effect. We report that the levels of TSPO and neurosteroids in the hippocampus and prefrontal cortex were significantly decreased in PPD rats compared to healthy controls. After 3 weeks of drug treatment, the levels of TSPO and neurosteroids in the hippocampus of PPD rats were increased, and anxiety and depressive like behaviors were alleviated. Meanwhile, compared with sertraline treatment, a positive control in this study, YL-IPA08 treatment had a shorter onset time. Our results suggest that the anxiolytic and anti-depressive activity of YL-IPA08 has significant value in the treatment of PPD and that TSPO may be a potential new target for the treatment of PPD.

The Critical Period for Neuroprotection by Estrogen Replacement Therapy and the Potential Underlying Mechanisms.

17ß-Estradiol (estradiol or E2) is a steroid hormone that has been broadly applied as a neuroprotective therapy for a variety of neurodegenerative and cerebrovascular disorders such as ischemic stroke, Alzheimer's disease, and Parkinson's disease. Several laboratory and clinical studies have reported that Estrogen Replacement Therapy (ERT) had no effect against these diseases in elderly postmenopausal women, and at worst, increased their risk of onset and mortality. This review focuses on the growing body of data from in vitro and animal models characterizing the potential underlying mechanisms and signaling pathways that govern successful neuroprotection by ERT, including the roles of E2 receptors in mediating neuroprotection, E2 genomic regulation of apoptosis- related pathways, membrane-bound receptor-mediated non-genomic signaling pathways, and the antioxidant mechanisms of E2. Also discussed is the current evidence for a critical period of effective treatment with estrogen following natural or surgical menopause and the outcomes of E2 administration within an advantageous time period. The known mechanisms governing the duration of the critical period include depletion of E2 receptors, the switch to a ketogenic metabolic profile by neuronal mitochondria, and a decrease in acetylcholine that accompanies E2 deficiency. Also the major clinical trials and observational studies concerning postmenopausal Hormone Therapy (HT) are summarized to compare their outcomes with respect to neurological disease and discuss their relevance to the critical period hypothesis. Finally, potential controversies and future directions for this field are discussed throughout the review.

Spinal Clear Cell Meningiomas: Clinical Features and Factors Predicting Recurrence.

OBJECTIVE: As a World Health Organization grade II tumor of the nervous system, clear cell meningioma (CCM) is an uncommon histologic variant of meningioma. Spinal CCMs are even rarer, with <100 spinal CCMs reported in the English literature. We present this study to characterize clinical manifestations of spinal CCMs and determine the factors predicting recurrence. METHODS: A literature search was performed for relevant case reports and series in PubMed and Embase until September 1, 2019. These articles were reviewed to identify clinical features, treatment modalities, and prognosis of patients with spinal CCMs. RESULTS: Eighty-four spinal CCMs were analyzed. Of these patients, 36 (42.9%) were young (age ≤18 years), and the mean age at resection was 24 years. Fifty-three patients (63.1%) were female and 31 (36.9%) were male. Most of the tumors (56/84, 66.7%) were located in the lumbar region. In 31 patients (36.9%) >2 segments in the craniocaudal direction were involved (number of involved segments ≥3 levels). Gross tumor resection was performed in 77 patients (91.7%). Twenty patients (23.8%) showed radiographic evidence of recurrence during follow-up. Recurrence-free survival at 1, 5, and 10 years after resection of spinal CCM was 87%, 71%, and 47%, respectively. Multivariate analysis showed that age ≤18 years (hazard ratio [HR], 3.64; P = 0.024), subtotal resection (HR, 3.43; P = 0.031), and segments involving ≥3 levels (HR, 5.66; P = 0.002) were associated with increased recurrence. CONCLUSIONS: Spinal CCMs have their own unique clinical features compared with conventional spinal meningiomas and intracranial CCMs. Spinal CCMs have a predilection to affect younger patients, are prone to appear in the lumbar region, and have a high recurrence rate. Age ≤18 years, subtotal resection, and involvement of long segments (≥3 levels) are positive predictors of recurrence.

High glucose and bupivacaine­induced cytotoxicity is mediated by enhanced apoptosis and impaired autophagy via the PERK­ATF4­CHOP and IRE1­TRAF2 signaling pathways.

Bupivacaine has previously been reported to induce neurotoxicity, which is further enhanced by high glucose levels. In the present study, the underlying molecular mechanisms via which bupivacaine induces cytotoxicity under high glucose conditions were investigated in cultured human SH­SY5Y cells. In order to identify the optimal concentrations of glucose and bupivacaine that induced cytotoxicity, SH­SY5Y cells were treated with 30­100 mM glucose and 0.5­1.0 mM bupivacaine. Based on the dose response experiments, 50 mM glucose and 0.5 mM bupivacaine was used in the present study. The effects that 3­MA (autophagy inhibitor) and rapamycin (RAPA; autophagy inducer) exerted on cell apoptosis, autophagy and the expression of protein kinase R­like endoplasmic reticulum kinase (PERK)­activating transcription factor 4 (ATF4)­C/EBP­homologous protein (CHOP) and inositol­requiring enzyme 1 (IRE1)­tumor necrosis factor receptor associated factor 2 (TRAF2) signaling proteins were measured in high glucose and bupivacaine­treated cells. Cell viability was measured using a Cell Counting Kit­8 assay, cell apoptosis was assessed using flow cytometry, and protein expression was determined using western blot analyses. Compared with the control group, high glucose and bupivacaine significantly increased ATF4, CHOP and caspase­12 expression, increased apoptosis, and decreased p­IRE1, TRAF2, LC3­II/LC3­I and Beclin1 expression. Promoting autophagy with RAPA partly reversed the high glucose and bupivacaine­induced changes in p­PERK, CHOP, TRAF2, Beclin1, caspase­12 and apoptosis, while inhibiting autophagy with 3­MA further enhanced the changes in ATF4, CHOP, p­IRE1, TRAF2 and apoptosis. High glucose and bupivacaine induced cytotoxicity in SH­SY5Y cells, at least in part, through enhancing cell apoptosis and inhibiting autophagy via the PERK­ATF4­CHOP and IRE1­TRAF2 signaling pathways.

The effects of various estrogen doses on the proliferation and differentiation of cultured neural stem cells.

The brain has long been known as a dimorphic organ and as a target of estrogen. Neurogenesis, including proliferation and differentiation of neural stem cells (NSCs), could be stimulated and regulated by estrogen. However, the dose and timing of estrogen treatment is controversial, and the underlying mechanism remains unclear. In this study, we tested the effects of various estrogen doses on the neurogenesis of NSCs derived from Sprague-Dawley rat embryos. First, we identified that the estrogen receptor-ERα, ERß and GPR30 were highly expressed in NSCs. The results from cell cycle and Western blot analyses revealed that 10 nM 17ß-estradiol (E2) treatment for 3 days significantly increased NSCs proliferation of and p-ERK1/2 expression level but that 50 nM E2 exposure markedly decreased NSCs proliferation and p-ERK1/2 expression level. According to immunofluorescence staining and Western blot analyses, 10 nM E2 treatment for 7 days significantly stimulated NSCs to differentiate into neurons and inhibited their differentiation into astrocytes. These results demonstrate that NSCs are a target of estrogen and that an appropriate dose of E2 (10 nM) can significantly increase the proliferation of NSCs and stimulate NSCs to differentiate into neurons, which contributes to knowledge regarding the regulatory effects of estrogens on neurogenesis.

Role of interleukin-6 to differentiate sepsis from non-infectious systemic inflammatory response syndrome.

Differentiating between sepsis and non-infectious systemic inflammatory response syndrome (SIRS) poses a great challenge. Several potential bloodstream biomarkers including Interleukin 6 (IL-6) have been investigated for their ability to diagnose sepsis. We conducted the present meta-analysis to evaluate the diagnostic quality of IL-6 in differentiating sepsis from non-infectious SIRS in adults. We also compared its accuracy with procalcitonin (PCT) and C-reactive protein (CRP). PubMed and EMBASE were systematically searched for studies published up to January 18, 2016. Twenty articles containing 22 studies and 2680 critically ill patients were included, of which, 21 studies also involved PCT and 14 involved CRP. Quantitative synthesis of studies showed that the pooled sensitivity/specificity of IL-6 and PCT were 0.68/0.73 and 0.78/0.67. The area under the curve (AUC) of IL-6, PCT and CPR for diagnosis of sepsis was 0.80, 0.83, and 0.71, respectively. This meta-analysis provides evidence that the IL-6 test has moderate diagnostic performance in differentiating sepsis from non-infectious SIRS in adults. IL-6 and PCT test has similar diagnostic value but higher than CRP. Considering its relatively high specificity, we recommend the use of IL-6 as a diagnostic aid to confirm infection rather than exclude infection in patients with SIRS.

Over-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice.

The translocator protein 18kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future.

TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration.

Translocator protein 18 kDa (TSPO) is now an attractive drug target for controlling neuroinflammation. Studies applying TSPO ligands to neurodegenerative diseases, especially Alzheimer's disease (AD), were rare. Our study was aimed to evaluate the effect of PK11195, a specific TSPO ligand, in an animal model of neuroinflammation caused by systemic LPS administration. C57/BL6 mice were treated with lipopolysaccharide (LPS, 500 µg/kg, i.p.) three days after PK11195 administration (3mg/kg, i.p.). The drugs were not discontinued until the mice were sacrificed. Cognitive function was assessed by Morris water maze (MWM) seven days after LPS injection. Chronic LPS-injection in mice was characterized by cognitive dysfunction, increased expression of cyclooxygenase (COX)-2 and TSPO, elevated Aß content with increased expression of ß-site APP cleaving enzyme-1 (BACE-1) and insulin-degrading enzyme (IDE) as well as decreased brain progesterone and brain-derived neurophic factor (BDNF) level. PK11195 pretreatment protected cognitive function in LPS-injected animals and normalized the inflammatory proteins. Moreover, PK11195 pre-administration decreased elevated hippocampal Aßx-42 levels and increased brain levels of progesterone, allopregnanolone. However, LPS-induced BDNF decrease was not reversed by PK11195 administration. Our data demonstrated that PK11195 could protect cognitive deficits induced by chronic LPS administration. The underling mechanism may involve alleviated neuroinflammation, increased synthesis of neurosteroid and decreased Aß accumulation accompanied by down-regulation of BACE-1.

Dexmedetomidine reduces postoperative delirium after joint replacement in elderly patients with mild cognitive impairment.

BACKGROUND AND AIMS: Postoperative delirium (POD) is a common and serious surgical complication among the elderly, especially in those with amnestic mild cognitive impairment (aMCI). Dexmedetomidine (DEX) is neuroprotective for delirium. In this study, we determined the effect of intravenously administered DEX during general anesthesia on POD in elderly aMCI patients undergoing elective hip joint or knee joint or shoulder joint replacement surgery. METHODS: This was a prospective, randomized parallel-group study of aMCI (n = 80) and normal elderly patients (n = 120). Prior to surgery, all subjects underwent neuropsychological assessment and were assigned to one of four groups: the aMCI DEX group (MD group, n = 40), the aMCI normal saline group (MN group, n = 40), the control DEX group (CD group, n = 60), and the control normal saline group (CN group, n = 60). The confusion assessment method was used to screen POD on postoperative days 1, 3, and 7. RESULTS: We found patients age was positively correlated with POD incidence in the MN group (p < 0.05) but not in the CN group (p < 0.05). DEX treatment significantly decreased POD incidence in both control and aMCI groups relative to their respective placebo groups (all p < 0.05). The fraction of patients whose normal cognitive function was not restored by day 7 after surgery was significantly higher in the MN group than the MD and CN groups (all p < 0.05). CONCLUSIONS: These findings suggested that DEX treatment during surgery significantly reduced POD incidence in both normal and aMCI elderly patients, suggesting that it may be an effective option for the prevention of POD.

Ulinastatin decreases permeability of blood--brain barrier by inhibiting expression of MMP-9 and t-PA in postoperative aged rats.

Tissue-type plasminogen activator (t-PA) and matrix metalloproteinase-9 (MMP-9) have been reported to play important roles in increased permeability of blood-brain barrier (BBB) under many pathological circumstances. We have showed that Ulinastatin, a broad-spectrum serine protease inhibitor, could alleviate inflammation in the hippocampus of aged rats following partial hepatectomy. In this study, we investigate the expression and potential roles of t-PA and MMP-9 in the protective effect of Ulinastatin. We found that partial hepatectomy increased Evans blue leakage in hippocampus at day 1 and 3 postoperatively. Furthermore, surgery decreased the protein levels of claudin-5, ZO-1, and NF-kB p65 while upregulating the mRNA and protein levels of t-PA and MMP-9 in brain capillaries. All these effects caused by surgery were partially reversed by administering Ulinastatin. Our study sheds light on the roles of t-PA and MMP-9 of BBB in post-surgical neuroinflammation and postoperative cognitive dysfunction. Besides, it could also help to understand the mechanism of Ulinastatin alleviating neuroinflammation.

Mammalian target of rapamycin/p70 ribosomal S6 protein kinase signaling is altered by sevoflurane and/or surgery in aged rats.

The mammalian target of rapamycin (mTOR)/p70 ribosomal S6 protein kinase (p70S6k) pathway exerts anti­apoptotic effects that may contribute to disease pathogenesis. The memory impairment in patients with Alzheimer's disease (AD) has been suggested to be contributed to by abnormal mTOR signaling. The aim of the current study was to investigate the association between sevoflurane and/or surgery and AD through the mTOR/p70S6K signaling pathway. Sprague­Dawley rats were randomly assigned to the sevoflurane, surgery or control groups. The animals in the surgery group received a partial hepatectomy under sevoflurane anesthesia. The hippocampal levels of phosphorylated (p)­mTOR, p­p70S6K, caspase­3 and p­tau/total (t)­tau were analyzed. The Morris water maze (MWM) was used to evaluate cognitive function following treatment. The levels of p­mTOR and p­p70S6K were reduced, whereas caspase­3 levels were increased in the surgery group compared with the sevoflurane group. The p­tau/t­tau levels were increased, however, tau mRNA was unaffected by sevoflurane and/or surgery. The rats in the surgery group required a significantly longer time to locate the platform in the MWM test compared with the control and sevoflurane groups. Sevoflurane treatment and/or surgery reduced anti­apoptotic activity, and the postoperative cognitive dysfunction following surgery may be due to mTOR signaling pathway inhibition in aged rats. Increased neuronal apoptosis and tau phosphorylation are suggested to be involved in the association between anesthesia and AD occurrence.