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The flexible actuator has attracted significant interest for its ability to respond flexibly to external stimuli, especially for renewable natural energy sources. However, the flexible actuator faces issues such as inadequate sensitivity and inability to achieve synergistic responses. Therefore, we prepared a highly sensitive flexible actuator by mixing liquid metal (LM) with poly(vinylpyrrolidone) (PVP), graphene oxide (GO), and coating the resulting mixtures onto poly(ethylene terephthalate) (PET) substrate materials using the rod coating process. The flexible actuator responds quickly to near-infrared light and humidity and can be rapidly transformed from flat to curved with a maximum angular change of 540°. By demonstrating the flexible actuator in action, it can be used to create a crawling robot that mimics the movement of an inchworm on a leaf, as well as a gripper capable of lifting objects 5 times its weight, and a crawling robot that moves forward, turns left, and then right. Flexible actuators hold significant promise for applications in emerging fields such as advanced bionics and artificial intelligence.
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STUDY OBJECTIVE: This meta-analysis aimed to assess whether continuous intravenous administration of DEX during surgery can be part of the measures to prevent the onset of postoperative delirium and postoperative cognitive dysfunction in elderly individuals following regional anesthesia. METHODS: We searched the databases of PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (by June 1, 2023) for all available randomized controlled trials assessing whether intravenous application of dexmedetomidine can help with postoperative delirium and postoperative cognitive dysfunction in the elderly with regional anesthesia. Subsequently, we carried out statistical analysis and graphing using Review Manager software (RevMan version 5.4.1) and STATA software (Version 12.0). MAIN RESULTS: Within the scope of this meta-analysis, a total of 18 randomized controlled trials were included. Among them, 10 trials aimed to assess the incidence of postoperative delirium as the primary outcome, while the primary focus of the other 8 trials was on the incidence of postoperative cognitive dysfunction. The collective evidence from these 10 studies consistently supports a positive relationship between the intravenous administration of dexmedetomidine and a decreased risk of postoperative delirium (RR: 0.48; 95%CI: 0.37 to 0.63, p < 0.00001, I2 = 0%). The 8 literature articles and experiments evaluating postoperative cognitive dysfunction showed that continuous intravenous infusion of dexmedetomidine during the entire surgical procedure exhibited a positive preventive effect on cognitive dysfunction among the elderly population with no obvious heterogeneity (RR: 0.35; 95%CI: 0.25 to 0.49,p < 0.00001, I2 = 0%). CONCLUSION: Administering dexmedetomidine intravenously during surgery can potentially play a significant role in preventing postoperative delirium and postoperative cognitive dysfunction in patients older than 60 years with regional anesthesia according to this meta-analysis.
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Anestesia por Condução , Dexmedetomidina , Complicações Cognitivas Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Dexmedetomidina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Anestesia por Condução/métodos , Idoso , Infusões Intravenosas , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Complicações Cognitivas Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Delírio/prevenção & controle , Delírio/epidemiologia , Hipnóticos e Sedativos/administração & dosagem , Disfunção Cognitiva/prevenção & controle , Delírio do Despertar/prevenção & controle , Delírio do Despertar/epidemiologiaRESUMO
BACKGROUND: In the global aging population, the incidence of postoperative delirium (POD) is increasing. Therefore, finding its effective predictive tools becomes crucial. We aimed to identify potential Cerebrospinal fluid (CSF)biomarkers for POD. METHODS: A total of 825 patients undergoing knee/hip arthroplasty under combined spinal-epidural anesthesia were selected. The patients were aged 40 to 90 years with American Society of Anesthesiologists physical status I~II. The Mini-Mental State Examination was completed 1 day before the operation. CSF was extracted after successful spinal-epidural combined puncture, and α-synuclein (α-syn), amyloid beta40 (Aß40), amyloid beta42 (Aß42), t-Tau, phosphorylated Tau (p-Tau), progranulin (PGRN) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in the CSF were measured by enzyme-linked immunosorbent assays (ELISA). The patient's operation time, anesthesia time, intraoperative blood loss and fluid input were also recorded. After the operation, the occurrence rate and severity of POD were determined by the Confusion Assessment Method and the Memorial Delirium Assessment Scale (MDAS), respectively. Patients were categorized into POD group and non-POD group. Logistic regression analysis was performed on the indicators with statistically significant differences, and the area under the ROC curve (AUC) was used to estimate the predictive accuracy of the biomarkers for POD. RESULTS: A total of 92 patients developed POD and the incidence of POD was 11.15%. The results of the multivariable logistic regression showed that CSF t-Tau (P = 0.004, OR = 1.006, 95%CI 1.002~1.009) and α-syn (P = 0.004, OR = 1.001, 95%CI 1.000~1.001) were positively associated with the occurrence rate of POD, while Aß42 (P < 0.001, OR = 0.989, 95%CI 0.986~0.993), CSF PGRN (P = 0.002, OR = 0.999, 95%CI 0.999~1.000), Aß42/ t-Tau (P < 0.001, OR = 0.181, 95%CI 0.102~0.319) and Aß42/p-Tau (P < 0.001, OR = 0.617, 95%CI 0.526~0.725) were inversely proportional to the occurrence of POD. ROC curve analysis indicated that Aß42/t-Tau (AUC = 0.823), CSF Aß42 (AUC = 0.813), Aß42/p-Tau (AUC = 0.810), α-syn (AUC = 0.644) and PGRN (AUC = 0.638) could predict the occurrence rate of POD. The combination of all these biomarkers showed a greater AUC(0.896) than using any of them alone. CONCLUSIONS: CSF Aß42, PGRN, α-syn, Aß42/t-Tau and Aß42/p-Tau might be associated with the occurrence rate of POD in patients undergoing knee/hip arthroplasty. TRIAL REGISTRATION: Clinical Registration No. ChiCTR2000033439.
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Doença de Alzheimer , Artroplastia de Quadril , Delírio do Despertar , Humanos , Idoso , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Artroplastia de Quadril/efeitos adversos , Envelhecimento , Biomarcadores/líquido cefalorraquidiano , Fragmentos de Peptídeos , Doença de Alzheimer/diagnósticoRESUMO
Cherenkov radiation (CR) is the characteristic blue glow that is generated during radiotherapy or radioisotope decay. Its distribution and intensity naturally reflect the actual dose and field of radiotherapy and the location of radioisotope imaging agents in vivo. Therefore, CR can represent a potential in situ light source for radiotherapy monitoring and radioisotope-based tumor imaging. When used in combination with new imaging techniques, molecular probes or nanomedicine, CR imaging exhibits unique advantages (accuracy, low cost, convenience and fast) in tumor radiotherapy monitoring and imaging. Furthermore, photosensitive nanomaterials can be used for CR photodynamic therapy, providing new approaches for integrating tumor imaging and treatment. Here the authors review the latest developments in the use of CR in tumor research and discuss current challenges and new directions for future studies.
Cherenkov radiation (CR) is the characteristic blue glow that is generated during radiotherapy (a common treatment that uses radiation to kill cancer cells) or radioisotope decay (the process that emits radiation from radioisotopes). CR can be used for monitoring the dose and dose distribution of radiotherapy to prevent radiotherapy-related adverse events. In addition, radioisotope-induced CR can be used as a light source for locating the tumor region for tumor imaging. With a combination of imaging techniques, molecular probes and nanomedicine, CR exhibits huge potential and unique advantages (accuracy, low cost, convenience and fast) in tumor radiotherapy monitoring and imaging. Furthermore, some photosensitive nanomaterials have been developed to absorb CR to generate reactive oxygen species, which can result in cell death. This therapeutic strategy is known as CR photodynamic therapy. CR photodynamic therapy is available to integrate with radiotherapy or tumor imaging, providing new approaches for tumor diagnosis and treatment. Here the authors review the latest developments in the use of CR in tumor research and discuss current challenges and new directions for future studies.
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Neoplasias , Planejamento da Radioterapia Assistida por Computador , Diagnóstico por Imagem , Humanos , Sondas Moleculares , Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
BACKGROUND: Although the incidence of postoperative delirium (POD) in the elderly after surgery are rising as individuals are living longer, the pathogenesis of POD remains poorly understood. It has been suggested that miRNA-320 may play a role in POD based on animal study and human study. METHODS: We first carried out an animal study, and designed and conducted a human study based on the result of animal study. The aged rats were randomly assigned to five groups: the control (C), anesthesia and surgery (AS), saline (NS), agomir-320 (AG), and antagomir-320 (AT) groups. Postoperative spatial learning and memory in rats were analyzed by the Morris water maze and the open field tests. The plasma levels of insulin-like growth factor-1 (IGF-1), amyloid precursor protein (APP) proteins, miRNA320 and IGF-1mRNA were measured by ELISA and qRT-PCR, respectively. A total of 240 Chinese Han patients over 65 years who underwent tibial fracture internal fixation were included in the PNDABLE study. POD cases and non-POD controls (1:1 matched) were selected by an anesthesiologist using Confusion Assessment Method. RESULTS: For Group AS, the escape latency was significantly longer and the ratio of time spent in the target quadrant was significantly reduced, APP and miR-320 were upregulated and IGF-1mRNA was downregulated compared with Group C. For Group AG, the escape latency was significantly longer and the ratio of time spent in the target quadrant was significantly reduced, APP and miR-320 were upregulated and IGF-1mRNA was downregulated compared with Group AS. For Group AT, the escape latency was significantly reduced and the ratio of time spent in the target quadrant was significantly longer, APP and miR-320 were downregulated and IGF-1mRNAwas upregulated compared with Group AS. Compared with NPOD patients, the expressions of plasma miR-320 and APP protein were increased and the expression of plasma IGF-1 mRNA was decreased in POD patients after surgery. CONCLUSIONS: MiRNA-320 might play a role in up-regulating the levels of IGF-1mRNA and APP protein, which offered a new target for POD treatment. TRIAL REGISTRATION: Correlation of perioperative neurocognitive disorders with lifestyle and biomarkers. ChiCTR2000033439 . Registered 1 June 2020.
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Delírio , MicroRNAs , Fraturas da Tíbia , Idoso , Precursor de Proteína beta-Amiloide , Animais , Delírio/epidemiologia , Fixação Interna de Fraturas/efeitos adversos , Humanos , Fator de Crescimento Insulin-Like I/genética , MicroRNAs/genética , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/genética , Ratos , Fraturas da Tíbia/cirurgiaRESUMO
BACKGROUND: This study aims to assess the learning curve of robotic distal gastrectomy (RDG) and robotic total gastrectomy (RTG) for gastric cancer. METHODS: Data on consecutive patients who underwent robotic gastrectomy for gastric cancer by five surgeons between March 2010 and August 2019 at two high-volume institutions were collected. The learning curve was determined based on the analyses of operation time and postoperative complications within 30 days. Cumulative sum analysis (CUSUM) and risk-adjusted-CUSUM (RA-CUSUM) were applied to identify the turning points (TPs). RESULTS: A total of 899 consecutive patients were included. The mean number of patients needed to overcome the learning curve for operation time of RDG and RTG were 22 and 20, respectively. The number of patients needed to overcome the learning curve for postoperative complications after RDG and RTG were 23 and 18, respectively. The surgical outcomes in the post-TP group were better than in the pre-TP group and improved as surgeons' experience increased. Also, increased case numbers in RDG promoted the RTG learning process. CONCLUSION: The present study demonstrated a substantial influence of surgical cumulative volume on improved surgical outcomes in robotic gastrectomy. Increased experience in RDG may help surgeons to achieve proficiency faster in RTG.
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Gastrectomia/métodos , Laparoscopia/métodos , Curva de Aprendizado , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Gástricas/cirurgia , Humanos , Duração da Cirurgia , Estudos RetrospectivosRESUMO
Chrysotile, which is classified as a class I carcinogen by the International Agency for Research on Cancer (IARC), has extensive application in the industry and can lead to lung or other cancers. However, whether chrysotile causes malignant mesothelioma and its molecular mechanism remain debatable. Thus, this study aimed to demonstrate the mesothelioma-inducing potential of chrysotile at the mesothelial cellular level and the function of microRNA-28 in malignantly transformed mesothelial MeT-5A cells. MeT-5A cells malignantly transformed by a nontoxic dose of chrysotile were named Asb-T, and miR-28 expression was downregulated in Asb-T cells. Restoration of miR-28 expression inhibited the proliferation, migration and invasion of Asb-T cells. We verified that IMPDH is a putative target of miR-28. The expression of IMPDH was significantly higher in Asb-T MeT-5A cells than in control cells, whereas the opposite trend was observed with miR-28 overexpression. Additionally, inhibition of IMPDH had similar effects as miR-28 overexpression. After miR-28 was elevated or IMPDH was inhibited, Ras activation was reduced, and its downstream pathways (the Erk and Akt signalling pathways) were inhibited. Surprisingly, the content of miR-28 in the blood of mesothelioma patients was higher than that in control subjects. Overall, nontoxic doses of chrysotile can cause malignant transformation of MeT-5A cells. Moreover, miR-28 inhibits the proliferation, migration and invasion of Asb-T MeT-5A cells, negatively regulates the expression of IMPDH through the Ras signalling pathway and may be an important therapeutic target.
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Asbestos Serpentinas/toxicidade , MicroRNAs/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , HumanosRESUMO
We evaluated the occurrence and distribution of 12 antibiotics from the sulfonamide (SAs), fluoroquinolone (FQs) and tetracycline (TCs) groups in the Weihe River, North China. The total antibiotic concentrations in surface water, pore water, and sediment samples ranged from 11.1 to 173.1 ng/L, 5.8 to 103.9 ng/L, and 9.5 to 153.4 µg/kg, respectively. The values of the sediment-water partitioning coefficient in the Weihe River varied widely, from not detected to 943, 2213, and 2405 L/kg for SAs, FQs, and TCs, respectively. The values of the partitioning coefficients between sediment and surface water were generally lower than those between sediment and pore water, which indicated ongoing inputs to the water. The risk assessment showed that there were relatively high ecological risks to aquatic algae in this area from sulfamethoxazole, norfloxacin, tetracycline, ofloxacin, and ciprofloxacin.
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Fluoroquinolonas/análise , Sedimentos Geológicos/química , Rios/química , Sulfonamidas/análise , Tetraciclinas/análise , Antibacterianos/análise , China , Monitoramento Ambiental , Medição de Risco , Água , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction. METHODS: A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler. MAIN RESULTS: This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64, p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96, p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86, p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26, p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81-2.24, p = 0.25, I2 = 0%). CONCLUSION: Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.
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Dexmedetomidina , Delírio do Despertar , Hipotensão , Complicações Cognitivas Pós-Operatórias , Humanos , Bradicardia/epidemiologia , Dexmedetomidina/uso terapêutico , Delírio do Despertar/epidemiologia , Delírio do Despertar/prevenção & controle , Hipotensão/epidemiologia , Infusões Intravenosas , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Fluorescence quenching induced by photoinduced electron transfer (PET) stands as an effective strategy for identifying water pollutants. Herein, a novel (4, 8)-connected three-dimensional framework Cu(I)-MOF ([Cu2I(tpt)]n) with unique 8-connected [Cu4I2]2+ cationic clusters is designed by employing the nitrogen-rich ligand (Htpt = 5-[4(1H-1,2,4-triazol-1-yl)]phenyl-2H-tetrazole). Water-stabilized Cu(I)-MOF exhibits outstanding fluorescence properties, facilitating its application in detecting organic pollutants in water. Benefiting from the fact that the Cu(I)-MOF possesses a higher lowest unoccupied molecular orbitals (LUMO) energy level than that of the analyte, the rapid d-PET can occur, entitling Cu(I)-MOF to a sensitive fluorescence quenching response to roxarsone (ROX), nitrofurazone (NFZ) and nitrofurantoin (NFT) (with detection limits as low as 0.13 µM, 0.15 µM, and 0.13 µM, respectively). The nitrogen-containing sites of melamine foam (MF) are utilized to facilitate the anchoring and growth of Cu-MOF crystals, which enables the preparation of hierarchical microporous - macroporous Cu(I)-MOF/MF composites. The ordered porous structure of Cu(I)-MOF/MF provides cavities and open sites for the efficient removal of ROX (qmax = 210.6 mgâg-1), NFZ (qmax = 111.5 mgâg-1) and NFT (qmax = 238.9 mgâg-1) from water. This characteristic endows the Cu(I)-MOF/MF with rapid and recyclable adsorption capacity. Therefore, this work provides valuable insights to address the problem of detection and removal of pollutants in the aquatic environment.
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Excessive use of pesticides has brought about serious environmental risks worldwide that pose significant harm for human health. Herein, a series of metal-organic framework (MOF)-based gel capsules with a pitaya-like core-shell structure are constructed through a green polymerization strategy for pesticide detection and removal, namely ZIF-8/M-dbia/SA (M = Zn, Cd). Significantly, the ZIF-8/Zn-dbia/SA capsule exhibits sensitive detection of alachlor, a representative pre-emergence acetanilide pesticide, with a satisfactory detection limit of 0.23 µM. In addition, the MOF-based gel capsules can be extended to a universal visual platform for the noninvasive detection of pesticide residues with various MOFs, such as Eu-MOF, Tb-MOF, and Cu-MOF, and participating dye. Similar to pitaya, the ordered porous structure of MOF in ZIF-8/Zn-dbia/SA capsules offers cavity and open sites for removing pesticide from water with the maximum adsorption amount qmax of 61.1 mg·g-1 toward alachlor in a Langmuir model. Thereby, this work presents the universality of gel capsule self-assembly technologies, including the well-preserved visible fluorescence area and porosity of the different structurally diverse MOFs, offering an ideal strategy for water decontamination and food safety control fields.
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PURPOSE: We aimed to investigate the relevance of body mass index (BMI) to postoperative delirium (POD), and to test whether the influences of BMI on POD were mediated by cerebrospinal fluid (CSF) biomarkers. PATIENTS AND METHODS: Our study recruited 682 and 761 cognitively intact individuals from the perioperative neurocognitive disorder risk factor and prognosis (PNDRFAP) study and the perioperative neurocognitive disorder and biomarker lifestyle (PNDABLE) study, respectively. The incidence of POD was evaluated by using Confusion Assessment Method (CAM), and POD severity was measured by using the Memorial Delirium Assessment Scale (MDAS). Logistic regression was used to analyze the relationship between BMI and POD. The levels of Aß40, Aß42, T-tau, and P-tau in preoperative CSF were measured by enzyme-linked immune-sorbent assay (ELISA) in the PNDABLE study. Mediation analysis with 5000 bootstrapped iterations was used to explore the mediation effects. RESULTS: In the PNDRFAP study, the incidence of POD was 16.3%, with logistic regression analysis showing that BMI (odds ratio [OR] = 0.900, 95% confidence interval [CI] 0.823-0.985, p = .022) is a protective factor of POD. In the PNDABLE study, the incidence of POD was 18.7%, and regression analysis confirmed that BMI (OR = 0.832, 95% CI 0.761-0.910, p < .001) is a protective factor of POD, while T-tau (OR = 1.005, 95% CI 1.003-1.006, p < .001) and P-tau (OR = 1.037, 95% CI 1.024-1.050, p < .001) were risk factors of POD. Mediation analyses revealed that the association between BMI and POD was partially mediated by T-tau (proportion: 36%) and P-tau (proportion: 24%). CONCLUSION: Higher BMI mediated protective effects on POD through CSF biomarkers (T-tau and P-tau).
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Delírio , Biomarcadores/líquido cefalorraquidiano , Índice de Massa Corporal , Delírio/epidemiologia , Delírio/etiologia , Humanos , Incidência , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de RiscoRESUMO
Objective: We aimed to investigate the relationship between preoperative lipid level and postoperative delirium (POD) and explore whether lipid's effect on POD is mediated by POD core protein. Methods: A total of 635 patients who were planned to undergo knee/hip arthroplasty under combined spinal-epidural anesthesia, regardless of gender, were selected. The patients were aged 40-90 years with American Society of Anesthesiologists physical status I II. The Mini-Mental State Examination (MMSE) was completed 1 day before the operation. Five milliliter elbow venous blood was taken from the patients before anesthesia, and serum levels of total cholesterol (TG), triglyceride (TC), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) were detected. Cerebrospinal fluid (CSF) was extracted after successful spinal-epidural combined puncture, and amyloid beta40 (Aß40), amyloid beta42 (Aß42), total Tau (t-Tau), and phosphorylated Tau (p-Tau) in the CSF were measured by enzyme-linked immunosorbent assays (ELISA). After the operation, the occurrence and severity of POD were assessed using the Confusion Assessment Method and the Memorial Delirium Assessment Scale (MDAS), respectively. Patients were categorized into POD group and NPOD group. Logistic regression was used to analyze the relationship between POD and TC, TG, LDL-C, and HDL-C, and the mediating effect was used to analyze the role of POD core proteins in the relationship between lipid and MDAS. We used the receiver operating characteristic (ROC) and the precision-recall curve (PRC) analysis to assess the ability of TC, TG, LDL-C, and HDL-C ability to predict POD. Finally, we performed a sensitivity analysis to assess the stability of the results. Results: A total of 562 patients were finally enrolled in this study, and 66 patients developed POD, with an incidence of 11.7%. Logistic regression analysis showed that high concentration of TC (OR = 3.148, 95%CI 1.858â¼5.333, P < 0.001), TG (OR = 2.483, 95%CI 1.573â¼3.918, P < 0.001), and LDL-C (OR = 2.469, 95%CI 1.310â¼4.656, P = 0.005) in serum were risk factors for POD. A high concentration of HDL-C (OR = 0.258, 95%CI 0.112â¼0.594, P = 0.001) was a protective factor for POD after adjusted for age, sex, education, and MMSE score. ROC curves showed that HDL-C have the highest sensitivity and specificity in predicting POD. For these four lipid markers, the PRC range from 0.602 to 0.731, respectively. The mediating analysis showed that POD core proteins could partially mediate the relationship between lipid and POD (effect value: 16.19â¼91.04%). The results were barely changed in the sensitivity analysis, and the sensitivity analysis has shown that the results were stable. Conclusion: The increase of serum TG, TC, and LDL-C concentration is a risk factor for POD development, while high HDL-C concentration is a protective factor for POD, and the occurrence of POD is caused by hyperlipidemia may be caused by POD core proteins. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [Chictr200033439].
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OBJECTIVES: To compare differential expression protein in hippocampal tissues from mice of perioperative neurocognitive disorder (PND) and normal control mice and to explore the possible mechanism of PND. METHODS: Mice were randomly divided into a PND group (n = 9) and a control group (n = 9).The mice in the PND group were treated with open tibial fracture with intramedullary fixation under isoflurane anesthesia, while the mice in the control group received pure oxygen without surgery. The cognitive functions of the two groups were examined using Morris water maze experiment, Open field test and Fear conditioning test. The protein expression of the hippocampus of mice was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the principal functions of dysregulated proteins. RESULTS: A total of 21 proteins were differentially expressed between PND and control mice on days 1, 3, and 7 after the operation. These proteins were involved in many pathological processes, such as neuroinflammatory responses, mitochondrial oxidative stress, impaired synaptic plasticity, and neuronal cell apoptosis. Also, the dysregulated proteins were involved in MAPK, AMPK, and ErbB signaling pathways. CONCLUSION: The occurrence of PND could be attributed to multiple mechanisms.
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Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/cirurgia , Proteoma/análise , Proteômica/métodos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cognição/fisiologia , Modelos Animais de Doenças , Reação de Fuga/fisiologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Camundongos Endogâmicos C57BL , Transtornos Neurocognitivos/fisiopatologia , Período Perioperatório , Proteoma/metabolismo , Espectrometria de Massas em Tandem/métodosRESUMO
To assess all available data to compare the efficacy of glucocorticoids treatment and orbital decompression for dysthyroid optic neuropathy (DON). PubMed, EMBASE, the Cochrane Library databases as well as other sources were searched by two independent reviewers followed by extensive hand-searching for the identification of relevant studies. The primary outcomes were the improvement in visual acuity and responder rate. Secondary outcomes were the proptosis reduction, change in diplopia, and clinical activity score (CAS). One randomized controlled trial, three retrospective case series and one prospective case series met the inclusion criteria. They were divided into intravenous high-dose glucocorticoids (ivGC) group and orbital decompression (OD) group. Both groups demonstrated improvement in visual acuity. In addition, the proportion of patients with improved vision in OD group was higher than that in ivGC group (P<0.001). Post-treatment proptosis reduction was also reported in both groups. Overall, weighted mean in proptosis reduction estimated at 1.64 and 5.45 mm in patients treated with ivGC and OD respectively. This study also presented results regarding pre-existing and new-onset diplopia. Apart from diplopia, a wide variety of minor and major complications were noted in 5 included studies. The most common complication in ivGC group and OD group was Cushing's syndrome and epistaxis respectively. The present systematic review shows that both glucocorticoids treatment and OD are effective in treating DON and OD may work better in improving visual acuity and reducing proptosis. However, high-quality, large-sample, controlled studies need to be performed in the future.
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Injectable implants with the ability to form in situ are one of the most promising carriers for the delivery of chemotherapeutic drugs to tumor sites. We have reported a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA), ethyl oleate, along with the sol-gel phase transition. The chemotherapeutic drug-loaded injectable NBCA ethyl oleate implant (INEI) exhibited excellent therapeutic efficacy for local chemotherapy. Herein, we utilize this INEI to carry N, N'-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide) (TE-C-5003), which is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor, to treat the lung cancer mice model. The in vitro experiment shows that TE-C-5003 has a good anti-tumor effect on lung cancer (IC50 = 0.7022 µM for A549; IC50 = 0.6844 µM for NCL-H1299) and breast cancer (IC50 = 0.4128 µM for MCF-7; IC50 = 0.5965 µM for MDA-MB-231). Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human lung cancer cells by the TE-C-5003-loaded INEI (40% NBCA) was 68.23%, which is far more than TC-E-5003 alone (31.76%). Our study further confirms that INEI is an effective technique to improve the anti-tumor effect. The druggability of small molecule compounds can be improved with the help of the mentioned technology. Also, TC-E-5003 may be developed as a broad spectrum anti-tumor drug.
Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Embucrilato/química , Feminino , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Ácidos Oleicos/química , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Proteínas Repressoras/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Myosin heavy chain 11 (MYH11), encoded by the MYH11 gene, is a protein that participates in muscle contraction through the hydrolysis of adenosine triphosphate. Although previous studies have demonstrated that MYH11 gene expression levels are downregulated in several types of cancer, its expression levels have rarely been investigated in lung cancer. The present study aimed to explore the clinical significance and prognostic value of MYH11 expression levels in lung cancer and to further study the underlying molecular mechanisms of the function of this gene. The Oncomine database showed that the MYH11 expression levels were decreased in lung cancer compared with those noted in the normal lung tissue (P<0.05). Kaplan-Meier plotter results revealed that the decreased MYH11 expression levels were correlated with poor prognosis in lung cancer patients. Among the lung cancer cases with gene alteration of MYH11, mutation was the most common of all alteration types. Coexpedia and Metascape analyses revealed that the target genes were primarily enriched in 'muscle contraction', 'contractile fiber part', 'actin cytoskeleton' and the 'adherens junction'. These results indicated that MYH11 is a potential novel drug target and prognostic indicator of lung cancer.
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Glaucoma is one of the leading causes of vision loss worldwide. More and more studies have suggested that glaucoma is a complicated retinal neurovascular disease. The homeostasis imbalance of retinal neurovascular unit(RNVU)composed of neurons, glial cells and microvascular cells not only induces changes in microvascular structure and glial cells, but also affects the nerve tissue of the retina, resulting in vision loss, which there is no effective treatment to reverse, currently. Exploring the cellular composition and molecular structure of RNVU and investigating the destruction mechanism of normal cellular environment and intercellular connections in glaucoma are of great significance in exploring the pathogenesis and the treatment of glaucoma. The research progress on structural changes and dysfunction of RNVU in glaucoma are reviewed, hoping to provide new ideas for the treatment of glaucoma.
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Objective:To investigate the role and mechanism of long non-coding RNA (lncRNA) gastric cancer associated transcript 3 (GACAT3) in glioma radioresistance.Methods:Real-time reverse transcription PCR (RT-qPCR) was used to detect the expression of lncRNA GACAT3 and miR-497 in human astrocyte NHA cells and glioma cells U251. NC-siRNA and GACAT3-siRNA were transfected into U251 cells, and the cells were treated with X-ray irradiation. Colony formation assay was used to detect the survival fraction of U251 cells. The apoptosis of U251 cells was detected by flow cytometry. Western blot was used to detect the expression of cysteine containing aspartate specific protease 3 (Caspase-3) in U251 cells. Bioinformatics software and dual luciferase reporter gene assay were used to predict and verify the targeting relationship between lncRNA GACAT3 and miR-497, and between miR-497 and Yes-associated protein 1 (YAP1), respectively. NC mimic, miR-497 mimic, GACAT3-siRNA and NC inhibitor, GACAT3-siRNA and miR-497 inhibitor were co-transfected into U251 cells. Colony formation assay, flow cytometry and Western blot were adopted to evaluate the effect of miR-497 overexpression and lncRNA GACAT3 on the radiosensitivity of U251 cells by regulating miR-497.Results:Compared with NHA cells, the expression of lncRNA GACAT3 in U251 cells was significantly up-regulated, and the expression of miR-497 in U251 cells was significantly down-regulated (both P<0.05). After knockdown of GACAT3, the survival fraction of irradiated U251 cells was significantly decreased, while the apoptosis rate and Caspase-3 protein expression were significantly increased (all P<0.05). lncRNA GACAT3 targeted and negatively regulated the expression of miR-497. Overexpression of miR-497 significantly reduced the survival fraction of U251 cells after irradiation, and increased the apoptosis rate and Caspase-3 protein expression. Inhibition of miR-497 significantly reversed the promoting effect of lncRNA GACAT3 knockdown on the radiosensitivity of U251 cells. miR-497 targeted and negatively regulated the expression of YAP1. Conclusion:Knockdown of lncRNA GACAT3 can enhance the radiosensitivity of glioma cells by regulating the miR-497/YAP1 axis.
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【Objective】 To analyze the independent influencing factors of repeated extracorporeal shock wave lithotripsy (ESWL) in the treatment of upper urinary calculi (UUC), based on which a nomogram model was established to predict the efficacy. 【Methods】 Clinical and imaging data of 203 patients receiving repeated ESWL during Jan.2020 and Dec.2022 were collected, including 117 cases in the successful group and 86 cases in the unsuccessful group.The patients’ age and sex, stone volume (SV), surface area (SA), skin-to-site distance (SSD), maximum CT value, mean stone density (MSD), and stone heterogeneity index (SHI) were compared between the two groups.The independent predictors were analyzed with logistic regression and the meaningful variables (P<0.05) were used to establish a nomogram.The efficacy of the model was evaluated using receiver operating characteristic (ROC) curve and decreasing curve analysis (DCA).Internal validation was also performed. 【Results】 Stepwise regression showed that SV, SSD, MSD and SHI were independent influencing factors (P<0.05).The area under the ROC curve (AUC), optimal threshold, sensitivity and specificity were 0.793 (95%CI: 0.674-0.911), 0.619, 77.1% and 74.0%, respectively.The DCA curve was above two extreme curves.Hosmer-Lemeshow test and calibration curve showed that the nomogram had a good fitting degree (χ2=5.526, P=0.489), and the correction C-index was 0.746. 【Conclusion】 SV, SSD, MSD and SHI are independent predictors of the efficacy of repeated ESWL in the treatment of UUC.The nomogram established based on the above indicators has good predictive efficiency and clinical applicability.