Perioperative neurocognitive disorders (NCDs) refer to neurocognitive abnormalities detected during the perioperative periods, including preexisting cognitive impairment, preoperative delirium, ...delirium occurring up to 7 days after surgery, delayed neurocognitive recovery, and postoperative NCD. The Diagnostic and Statistical Manual of Mental Disorders‐5th edition (DSM‐5) is the golden standard for diagnosing perioperative NCDs. Given the impracticality of using the DSM‐5 by non‐psychiatric practitioners, many diagnostic tools have been developed and validated for different clinical scenarios. The etiology of perioperative NCDs is multifactorial and includes predisposing and precipitating factors. Identifying these risk factors is conducive to preoperative risk stratification and perioperative risk reduction. Prevention for perioperative NCDs should include avoiding possible contributors and implementing nonpharmacologic and pharmacological interventions. The former generally includes avoiding benzodiazepines, anticholinergics, prolonged liquid fasting, deep anesthesia, cerebral oxygen desaturation, and intraoperative hypothermia. Nonpharmacologic measures include preoperative cognitive prehabilitation, comprehensive geriatric assessment, implementing fast‐track surgery, combined use of regional block, and sleep promotion. Pharmacological measures including dexmedetomidine, nonsteroidal anti‐inflammatory drugs, and acetaminophen are found to have beneficial effects. Nonpharmacological treatments are the first‐line measures for established perioperative NCDs. Pharmacological treatments are still limited to severely agitated or distressed patients.
Perioperative neurocognitive disorders constitute a great challenge for older patients scheduled for surgery because their occurrence is associated with increased morbidity and mortality as well as enormous medical costs. Preoperative risk stratification and perioperative risk reduction should be adopted for perioperative NCDs prevention and treatment.
Summary Background Delirium is a postoperative complication that occurs frequently in patients older than 65 years, and presages adverse outcomes. We investigated whether prophylactic low-dose ...dexmedetomidine, a highly selective α2 adrenoceptor agonist, could safely decrease the incidence of delirium in elderly patients after non-cardiac surgery. Methods We did this randomised, double-blind, placebo-controlled trial in two tertiary-care hospitals in Beijing, China. We enrolled patients aged 65 years or older, who were admitted to intensive care units after non-cardiac surgery, with informed consent. We used a computer-generated randomisation sequence (in a 1:1 ratio) to randomly assign patients to receive either intravenous dexmedetomidine (0·1 μg/kg per h, from intensive care unit admission on the day of surgery until 0800 h on postoperative day 1), or placebo (intravenous normal saline). Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method for intensive care units during the first 7 postoperative days. Analyses were done by intention-to-treat and safety populations. This study is registered with Chinese Clinical Trial Registry, www.chictr.org.cn , number ChiCTR-TRC-10000802. Findings Between Aug 17, 2011, and Nov 20, 2013, of 2016 patients assessed, 700 were randomly assigned to receive either placebo (n=350) or dexmedetomidine (n=350). The incidence of postoperative delirium was significantly lower in the dexmedetomidine group (32 9% of 350 patients) than in the placebo group (79 23% of 350 patients; odds ratio OR 0·35, 95% CI 0·22–0·54; p<0·0001). Regarding safety, the incidence of hypertension was higher with placebo (62 18% of 350 patients) than with dexmedetomidine (34 10% of 350 patients; 0·50, 0·32–0·78; p=0·002). Tachycardia was also higher in patients given placebo (48 14% of 350 patients) than in patients given dexmedetomidine (23 7% of 350 patients; 0·44, 0·26–0·75; p=0·002). Occurrence of hypotension and bradycardia did not differ between groups. Interpretation For patients aged over 65 years who are admitted to the intensive care unit after non-cardiac surgery, prophylactic low-dose dexmedetomidine significantly decreases the occurrence of delirium during the first 7 days after surgery. The therapy is safe. Funding Braun Anaesthesia Scientific Research Fund and Wu Jieping Medical Foundation, Beijing, China. Study drugs were manufactured and supplied by Jiangsu Hengrui Medicine Co, Ltd, Jiangsu, China.
Flexible hydroelectric generators (HEGs) are promising self‐powered devices that spontaneously derive electrical power from moisture. However, achieving the desired compatibility between a continuous ...operating voltage and superior current density remains a significant challenge. Herein, a textile‐based van der Waals heterostructure is rationally designed between conductive 1T phase tungsten disulfide@carbonized silk (1T‐WS2@CSilk) and carbon black@cotton (CB@Cotton) fabrics with an asymmetric distribution of oxygen‐containing functional groups, which enhances the proton concentration gradients toward high‐performance wearable HEGs. The vertically staggered 1T‐WS2 nanosheet arrays on the CSilk fabric provide abundant hydrophilic nanochannels for rapid carrier transport. Furthermore, the moisture‐induced primary battery formed between the active aluminum (Al) electrode and the conductive textiles introduces the desired electric field to facilitate charge separation and compensate for the decreased streaming potential. These devices exhibit a power density of 21.6 µW cm−2, an open‐circuit voltage (Voc) of 0.65 V sustained for over 10 000 s, and a current density of 0.17 mA cm−2. This performance makes them capable of supplying power to commercial electronics and human respiratory monitoring. This study presents a promising strategy for the refined design of wearable electronics.
Through constructing 2D nanosheet arrays and moisture‐induced primary battery system, a high‐performance and flexible hydroelectric generator is developed with a sustained open‐circuit voltage of 0.65 V, and an excellent short‐circuitcurrent of 0.51 mA. Moreover, these prepared flexible hydroelectric generators can be used in the wearable self‐powered field.
Textile‐based generators that can convert low‐grade energy from the human body or environment into sustainable electricity have generated immense scientific interest in self‐powered wearable ...applications. However, their low power density and environmental suitability have extremely restricted their portable applications in complex and mutable environments. Herein, an asymmetric sandwich structure between molybdenum disulfide (MoS2)‐carbonized silks (MCs) and MoS2/MXene–Cottons (MMCs) to construct efficient thermo–hydroelectric generators (THEGs) that synergistically harvest heat‐moisture energy to generate considerable electricity is rationally designed. Notably, the large surface area of MoS2/MXene van der Waals heterojunctions (vdWhs) enables efficient charge collection, and the vertical MoS2 nanosheet arrays supply abundant nanochannels for a highly efficient hydration effect, generating an output power density of 32.26 µW cm−2 after wetting with deionized water. Combined with the sensitive temperature recognition ability with a Seebeck coefficient of 23.5 µV K−1, the application possibilities of these prepared THEGs in the mutual conversion of fingertip temperature/language, and the monitoring of the human physiological state is foresee.
Thermo–hydroelectric generators (THEGs) are successfully constructed based on a sandwich structure between p‐type MoS2‐carbonized silks (MCs) with vertical MoS2 nanosheet arrays and n‐type MoS2/MXene–Cottons (MMCs) with van der Waals heterojunctions, demonstrating a Seebeck coefficient of 23.5 µV K−1 and a high output power density of 32.26 µW cm−2, which are favorable acting as self‐powered sensors for health monitoring.
Sepsis is life-threatening and often leads to acute brain damage. Dexmedetomidine, an α
-adrenoceptor agonist, has been reported to possess neuroprotective effects against various brain injury but ...underlying mechanisms remain elusive. In this study, in vitro and in vivo models of sepsis were used to explore the effects of dexmedetomidine on the inflammasome activity and its associated glia pyroptosis and neuronal death. In vitro, inflammasome activation and pyroptosis were found in astrocytes following lipopolysaccharide (LPS) exposure. Dexmedetomidine significantly alleviated astrocyte pyroptosis and inhibited histone release induced by LPS. In vivo, LPS treatment in rats promoted caspase-1 immunoreactivity in astrocytes and caused an increase in the release of pro-inflammatory cytokines of IL-1β and IL-18, resulting in neuronal injury, which was attenuated by dexmedetomidine; this neuroprotective effect was abolished by α
-adrenoceptor antagonist atipamezole. Dexmedetomidine significantly reduced the high mortality rate caused by LPS challenge. Our data demonstrated that dexmedetomidine may protect glia cells via reducing pyroptosis and subsequently protect neurons, all of which may preserve brain function and ultimately improve the outcome in sepsis.
Delirium is a frequent complication after cardiac surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the impact of perioperative dexmedetomidine ...administration on the incidence of delirium in elderly patients after cardiac surgery.
This randomized, double-blinded, and placebo-controlled trial was conducted in two tertiary hospitals in Beijing between December 1, 2014 and July 19, 2015. Eligible patients were randomized into two groups. Dexmedetomidine (DEX) was administered during anesthesia and early postoperative period for patients in the DEX group, whereas normal saline was administered in the same rate for the same duration for patients in the control (CTRL) group. The primary endpoint was the incidence of delirium during the first five days after surgery. Secondary endpoints included the cognitive function assessed on postoperative days 6 and 30, the overall incidence of non-delirium complications within 30 days after surgery, and the all-cause 30-day mortality.
Two hundred eighty-five patients were enrolled and randomized. Dexmedetomidine did not decrease the incidence of delirium (4.9% 7/142 in the DEX group vs 7.7% 11/143 in the CTRL group; OR 0.62, 95% CI 0.23 to 1.65, p = 0.341). Secondary endpoints were similar between the two groups; however, the incidence of pulmonary complications was slightly decreased (OR 0.51, 95% CI 0.26 to 1.00, p = 0.050) and the percentage of early extubation was significantly increased (OR 3.32, 95% CI 1.36 to 8.08, p = 0.008) in the DEX group. Dexmedetomidine decreased the required treatment for intraoperative tachycardia (21.1% 30/142 in the DEX group vs 33.6% 48/143 in the CTRL group, p = 0.019), but increased the required treatment for postoperative hypotension (84.5% 120/142 in the DEX group vs 69.9% 100/143 in the CTRL group, p = 0.003).
Dexmedetomidine administered during anesthesia and early postoperative period did not decrease the incidence of postoperative delirium in elderly patients undergoing elective cardiac surgery. However, considering the low delirium incidence, the trial might have been underpowered.
ClinicalTrials.gov NCT02267538.
As an alternative to hypodermic needles, coated polymer microneedles (MNs) are able to deliver drugs to subcutaneous tissues after being inserted into the skin. The dip-coating process is a ...versatile, rapid fabricating method that can form coated MNs in a short time. However, it is still a challenge to fabricate coated MNs with homogeneous and precise drug doses in the dip-coating process. In this study, to fabricate coated polymer microneedles with controlled drug loading, an adjustable apparatus that can be lifted and lowered was designed to immerse a polylactic acid (PLA) MN patch in the coating solutions. Using the coating solution containing 0.5% (w/w) sulforhodamine B, the drug loadings were up to 12ng, 14ng, and 18ng per needle for the MNs with heights of 550μm, 650μm, and 750μm, respectively. Moreover, for the MNs with a 650-μm height, when increasing the viscosity of the coating solutions from 150mPa·s to 1360mPa·s, 2850mPa·s, and 8200mPa·s, the drug loading increased from 2.5ng to 5ng, 14ng, and 22ng per needle, respectively. Meanwhile, the drug delivery efficiencies of these MNs were approximately 90%. In the insertion experiments, the MNs could successfully penetrate the skin and deliver the coated drug with approximately 90% efficiency when the MN tips were exposed to the outer environment. In vivo studies in mice indicated that the coated polymer MNs continuously delivered drugs, and the skin recovered without any injuries. These results demonstrated that the coated polymer MN was a safe and effective method for transdermal drug delivery.
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The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for ...the Kras
Tp53
(KP) and the Kras
Lkb1
(KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8
and CD4
T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC.
Quantum teleportation provides a 'disembodied' way to transfer quantum states from one object to another at a distant location, assisted by previously shared entangled states and a classical ...communication channel. As well as being of fundamental interest, teleportation has been recognized as an important element in long-distance quantum communication, distributed quantum networks and measurement-based quantum computation. There have been numerous demonstrations of teleportation in different physical systems such as photons, atoms, ions, electrons and superconducting circuits. All the previous experiments were limited to the teleportation of one degree of freedom only. However, a single quantum particle can naturally possess various degrees of freedom--internal and external--and with coherent coupling among them. A fundamental open challenge is to teleport multiple degrees of freedom simultaneously, which is necessary to describe a quantum particle fully and, therefore, to teleport it intact. Here we demonstrate quantum teleportation of the composite quantum states of a single photon encoded in both spin and orbital angular momentum. We use photon pairs entangled in both degrees of freedom (that is, hyper-entangled) as the quantum channel for teleportation, and develop a method to project and discriminate hyper-entangled Bell states by exploiting probabilistic quantum non-demolition measurement, which can be extended to more degrees of freedom. We verify the teleportation for both spin-orbit product states and hybrid entangled states, and achieve a teleportation fidelity ranging from 0.57 to 0.68, above the classical limit. Our work is a step towards the teleportation of more complex quantum systems, and demonstrates an increase in our technical control of scalable quantum technologies.
Efficient acetaminophen (APAP) degradation in the natural pyrite/peroxymonosulfate (PMS) system under acidic conditions was observed. Approximately 88.8% of APAP degradation was attributed to sulfate ...radical and the remaining 11.2% of APAP degradation was attributed to singlet oxygen. Sequential experiments and XPS analysis showed that the rapid Fe(III)/Fe(II) cycle was attributed to the sulfur species at the surface of pyrite. Pyrite showed an excellent stability and reusability, which was successfully applied to long-term APAP removal. This study provides a new understanding of the mechanism in pyrite/PMS system and suggests a simply operative and cost-effective method to treat organic contaminants.
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•Acetaminophen is efficiently degraded in pyrite/PMS system under acidic conditions.•Sulfate radical was identified as the dominant oxidant for acetaminophen degradation.•Sequential activation of PMS by pyrite allowed long-term removal of acetaminophen.
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