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Postoperative neurocognitive dysfunction (PND) is a common postoperative complication. Autophagy is correlated with the pathogenesis of PND. This study investigated the potential role of autophagy in the neuroprotection of dexmedetomidine (Dex) pretreatment in PND. The PND rat model was established by abdominal surgery. The cognitive function of rats was evaluated by Y-maze 3 days after surgery. Nissl staining assessed postoperative hippocampal damage. Immunofluorescence detected the expression of microglial activation (Iba-1) and autophagy-related protein (LC3B) in hippocampal tissues. Western blot detected the autophagy-related protein expression (Beclin 1, LC3B, and p62), proinflammatory cytokines, and the protein activation of the autophagy-related LKB1/AMPK/ULK-1 signaling pathway. RT-PCR quantified the expression of IL-1ß, TNF-α, and IL6. In this study, we found that Dex pretreatment improved spatial memory function impairment and reduced abdominal surgery-induced hippocampal tissue damage. Dex pretreatment significantly increased the expression of Beclin 1 and LC3 II/I and decreased the expression of p62 in the hippocampus after surgery. Furthermore, Dex effectively inhibited microglial activation and proinflammatory cytokines by enhancing autophagy in the hippocampus. Pretreatment with 3-MA, an autophagy inhibitor, significantly weakened the inhibitory effect of Dex on postoperative neuroinflammation. We further demonstrated that Dex suppressed surgery-induced neuroinflammation by activating the LKB1/AMPK/ULK-1 signaling pathway. In conclusion, our study indicated that Dex inhibited hippocampal neuroinflammation and ameliorated PND by enhancing autophagy after surgery in rats, which was related to the LKB1/AMPK/ULK-1 signaling pathway. These findings provide a potential therapeutic prospect for PND.NEW & NOTEWORTHY Dex inhibits hippocampal neuroinflammation and attenuates early cognitive impairment by enhancing autophagy following surgery in rats. Dex may protect postoperative cognitive function by activating the LKB1/AMPK/ULK-1 signaling pathway.
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Disfunção Cognitiva , Dexmedetomidina , Complicações Cognitivas Pós-Operatórias , Ratos , Animais , Dexmedetomidina/metabolismo , Dexmedetomidina/farmacologia , Dexmedetomidina/uso terapêutico , Ratos Sprague-Dawley , Doenças Neuroinflamatórias , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Complicações Cognitivas Pós-Operatórias/tratamento farmacológico , Citocinas , Hipocampo/metabolismo , AutofagiaRESUMO
OBJECTIVE: To evaluate the analgesic efficacy of quadratus lumborum block (QLB) in adults undergoing nephrectomy. DESIGN: Systematic review and meta-analysis. PATIENTS: Adult patients (≥18 years of age) received nephrectomy under general anesthesia. METHODS: We searched PubMed, Embase, the Cochrane Library, and Web of Science on January 10, 2022, including randomized controlled trials that evaluated the analgesic efficacy of QLB for patients undergoing nephrectomy. RESULTS: A total of 12 randomized controlled trials (N = 821 patients) were included in the study. Compared with the non-block, single-shot QLB reduced postoperative opioid consumption (mean difference [MD], -8.37 mg intravenous morphine equivalent; 95% confidence interval [CI], -12.19 to -4.54 mg) and pain scores at 2 hours, 6 hours, 12 hours, and 24 hours at rest and during movement after nephrectomy. Single-shot QLB also prolonged the time to first analgesic request (MD, 6.44 hours; 95% CI, 2.23 to 10.65 hours), shortened the length of hospital stay (MD, -0.32 day; 95% CI, -0.55 to -0.09 day), and decreased the incidence of postoperative nausea and vomiting (risk ratio, 0.48; 95% CI, 0.36 to 0.65). Compared with continuous epidural anesthesia, repeated QLB could provide comparable postoperative analgesic benefits. CONCLUSIONS: Single-shot QLB provided a statistically significant but clinically small improvement in postoperative analgesia and recovery for patients undergoing nephrectomy. The QLB would be beneficial as part of multimodal analgesia. Future research might need to determine which approach of QLB is superior for postoperative analgesia after nephrectomy.
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Anestésicos Locais , Bloqueio Nervoso , Adulto , Humanos , Dor Pós-Operatória/etiologia , Bloqueio Nervoso/efeitos adversos , Analgésicos Opioides , Nefrectomia/efeitos adversos , Ultrassonografia de Intervenção/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Hypokalemia is a common form of electrolyte disorder, which has a higher incidence in hospitalized patients and is closely related to perioperative complications and prognosis. Due to decreased skeletal muscle mass which causes total body potassium reduction, and increased comorbidities, the elderly are more susceptible to hypokalemia. OBJECTIVE: To investigate preoperative hypokalemia in elderly patients and its effect on postoperative complications. METHODS: Data were retrospectively collected from the elderly patients who underwent elective surgery from April 2018 to March 2019 and had preoperative blood gas data available. Patients, with age 60 to 100 years, were divided into hypokalemia group (potassium level < 3.5 mmol/L) and normokalemia group (potassium level between 3.5 and 5.5 mmol/L) according to preoperative blood gas analysis. Hypokalemia can be divided into mild (potassium level 3.0 to 3.5 mmol/L), moderate (potassium level 2.5 to 3.0 mmol/L) and severe (potassium level < 2.5 mmol/L), respectively. The risk factors of preoperative hypokalemia and its impact on postoperative complications and prognosis were primary outcomes. Secondary outcomes included postanesthesia care unit (PACU) stay time and hospital length of stay (LOS). RESULTS: Of 987 participants, 436 (44.17%) developed preoperative hypokalemia, among them 357 (81.88%) mild, 87 (16.74%) moderate and 6 (1.38%) severe. Multivariate logistic regression showed that female gender (OR, 1.851; 95% CI, 1.415-2.421), pre-existing hypokalemia at admission (OR, 4.498; 95% CI, 2.506-8.071), and oral laxative twice or more (OR, 1.823; 95% CI, 1.266-2.624) are risk factors of preoperative hypokalemia. Gynecological and biliopancreatic surgery were more common in hypokalemia group than normokalemia group (P < 0.001, P < 0.05). There was no significant difference in postoperative complications, PACU stay time, LOS, and 30-day mortality between the two groups (all P > 0.05). CONCLUSIONS: Female gender, pre-existing hypokalemia at admission, and oral laxative twice or more are independent risk factors for preoperative hypokalemia in elderly patients. However, postoperative complications and 30-day mortality were not increased, which may be related to monitoring blood gas analysis and prompt correction of potassium levels during surgery.
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Hipopotassemia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipopotassemia/diagnóstico , Hipopotassemia/epidemiologia , Laxantes , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Potássio , Estudos RetrospectivosRESUMO
BACKGROUND: Remimazolam is a newer benzodiazepine with properties of rapid onset, short duration of action, and fast recovery. Our study was to evaluate the effects of different doses of remimazolam combined with alfentanil in colonoscopic polypectomy. METHODS: One hundred twenty patients were randomly divided into four groups: alfentanil and propofol (AP) group, alfentanil and remimazolam 0.1 mg/kg (AR1 group), 0.15 mg/kg (AR2 group), or 0.2 mg/kg (AR3 group). Patients in the four groups received alfentanil 10 µg/kg, followed by propofol 2 mg/kg and three dosages of remimazolam. Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scale, heart rate (HR), oxygen saturation (SpO2), respiratory rate (RR), bispectral index (BIS) values and mean arterial pressure (MAP) were collected at intervals of 5 min and analyzed at different time points: before anesthesia (T0), 5 min (T1), 10 min (T2), 15 min after anesthesia (T3) and at the end of surgery (T4). The average MAP was calculated utilizing the average of all MAP values. The primary outcome was the success rate of sedation. Secondary outcomes included time to full alert and adverse events. RESULTS: The success rate of sedation was 100% among the four groups. The incidence of hypotension was significantly decreased (all P < 0.05) and the average MAP was higher in AR1-AR3 groups than AP group (all P < 0.001). None of the patients developed bradycardia or hypertension during surgery in all study groups. BIS values were higher (all P < 0.001) and the time to full alert was statistically shorter in AR1-AR3 groups (all P < 0.05) compared with the AP group. The MOAA/S score in AR1 was higher than AR2 (P < 0.05) and the AR3 group (P < 0.05) at T1 and BIS values in the AR1 group were significantly higher than AR3 group (P < 0.05) at T4. CONCLUSIONS: Remimazolam combined with alfentanil have a non-inferior sedative effect than propofol during the colonoscopic polypectomy. Moreover, this combination of two short-acting drugs might be a safer alternative. TRIAL REGISTRATION: The clinical trial was registered on (16/05/2021, ChiCTR2100046492).
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Alfentanil , Propofol , Benzodiazepinas , Humanos , Hipnóticos e Sedativos , Estudos ProspectivosRESUMO
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that contributes a crucial role in protection against ischemia (ISC)-reperfusion (REP) injury by driving expression of anti-apoptotic and anti-oxidant genes. STAT3 is also present in the mitochondria, where it modulates the activity of the electron transport chain (ETC) and the permeability transition pore. Transgenic mice that overexpress a mitochondrial-targeted, transcriptionally inactive STAT3 in cardiomyocytes (MLS-STAT3E mice) exhibit a persistent, partial blockade of electron transfer through complex I that uniquely did not lead to tissue dysfunction at baseline, yet increased mitochondrial ischemic tolerance. The direct contribution of non-transcriptional, mitochondria-localized STAT3 to protection during ISC-REP remains to be established. We hypothesized that the enhanced mitochondrial tolerance to ischemia present in MLS-STAT3E mice would decrease cardiac injury during ISC-REP. In the isolated buffer-perfused heart model, MLS-STAT3E hearts exhibit a decreased infarct size compared to non-transgenic littermate hearts. Contractile recovery, expressed as a percent of LV developed pressure before ISC, is improved in MLS-STAT3E mice. Mitochondria isolated at the end of 60 min. of REP from MLS-STAT3E hearts show attenuated ROS release. The partial and persistent blockade of complex I present in MLS-STAT3E mice decreases cardiac injury during REP, in part via a persistent decrease in ROS production and attenuation of mitochondrial permeability transition pore opening at the onset of REP. In vivo, MLS-STAT3E hearts exhibit substantially higher postoperative survival rate and a substantial decrease in myocardial infarct size. STAT3 mediates cardioprotection not only via canonical action as a transcription factor, but also as a modulator of ETC activity directly in the mitochondria.
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Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Técnicas In Vitro , Camundongos , Camundongos Transgênicos , Traumatismo por Reperfusão Miocárdica/mortalidade , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Espécies Reativas de Oxigênio/metabolismoRESUMO
A reversible inhibition of mitochondrial respiration by complex I inhibition at the onset of reperfusion decreases injury in buffer-perfused hearts. Administration of acidic reperfusate for a brief period at reperfusion decreases cardiac injury. We asked if acidification treatment decreased cardiac injury during reperfusion by inhibiting complex I. Exposure of isolated mouse heart mitochondria to acidic buffer decreased the complex I substrate-stimulated respiration, whereas respiration with complex II substrates was unaltered. Evidence of the rapid and reversible inhibition of complex I by an acidic environment was obtained at the level of isolated complex, intact mitochondria and in situ mitochondria in digitonin-permeabilized cardiac myocytes. Moreover, ischemia-damaged complex I was also reversibly inhibited by an acidic environment. In the buffer-perfused mouse heart, reperfusion with pH 6.6 buffer for the initial 5 min decreased infarction. Compared with untreated hearts, acidification treatment markedly decreased the mitochondrial generation of reactive oxygen species and improved mitochondrial calcium retention capacity and inner mitochondrial membrane integrity. The decrease in infarct size achieved by acidic reperfusion approximates the reduction obtained by a reversible, partial blockade of complex I at reperfusion. Extracellular acidification decreases cardiac injury during reperfusion in part via the transient and reversible inhibition of complex I, leading to a reduction of oxyradical generation accompanied by a decreased susceptibility to mitochondrial permeability transition during early reperfusion.
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Cálcio/metabolismo , Respiração Celular/fisiologia , Complexo I de Transporte de Elétrons/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Ácidos/administração & dosagem , Animais , Complexo I de Transporte de Elétrons/fisiologia , Complexo II de Transporte de Elétrons/antagonistas & inibidores , Complexo II de Transporte de Elétrons/metabolismo , Camundongos , Mitocôndrias Cardíacas/metabolismo , Membranas Mitocondriais/metabolismo , Membranas Mitocondriais/fisiologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/metabolismo , Técnicas de Cultura de Órgãos , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To observe the changes of apoptosis and protein kinase B/the mammalian target of Rapamycin (Akt/mTOR) signal pathway in hippocampal neurons of rat with post-straumatic stress disorder (PTSD), and to investigate the mechanism of PTSD. METHODS: Sixty male adult SD rats were divided into control group (n = 10) and PTSD (n = 50) model group. The PTSD animal model was established by giving the rats single-prolonged stress followed a single inescapable electric foot shock (SPS & S). The neuronal apoptosis of hiappocampus of PTSD rats at 1 d, 4 d, 7 d, 14 d and 28 d after model established was detected by flow cytometry (FCM). The expressions of phosphatase and tensin homology deleted on chromosome Ten (PTEN), phosphorylation of ARt and mTOR (p-Akt and p-mTOR) protein were detected by Western blotting. RESULTS: The apoptotic cell rate in PTSD 1 d, 4 d, 7 d and 14 d rats were higher than that in control rats (P < 0.05). The PTEN expression level was higher since PTSD 1 d than that in control group, and peaked in PTSD 4 d (P < 0.05). The p-Akt expression level was lower in PTSD 1 d than that in control group, and then increased in various time points after PTSD, but it was still lower in PTSD 28 d (P < 0.05). The p-mTOR expression level was lower than that in control group since PTSD 4 d, and then increased in various time points after PTSD 4 d, but it was still lower in PTSD 28 d (P < 0.05). CONCLUSION: The Akt/mTOR signal pathway was actived in hippocampal neurons of PTSD rats, and which was involved in neuronal apoptosis regulation.
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Apoptose , Neurônios/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Modelos Animais de Doenças , Hipocampo/citologia , Masculino , Neurônios/patologia , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação , Ratos , Ratos Sprague-DawleyRESUMO
Many neurological diseases can lead to cognitive impairment in patients, which includes dementia and mild cognitive impairment and thus create a heavy burden both to their families and public health. Due to the limited effectiveness of medications in treating cognitive impairment, it is imperative to develop alternative treatments. Electroacupuncture (EA), a required method for Traditional Chinese Medicine, has the potential treatment of cognitive impairment. However, the molecular mechanisms involved have not been fully elucidated. Considering the current research status, preclinical literature published within the ten years until October 2022 was systematically searched through PubMed, Web of Science, MEDLINE, Ovid, and Embase. By reading the titles and abstracts, a total of 56 studies were initially included. It is concluded that EA can effectively ameliorate cognitive impairment in preclinical research of neurological diseases and induce potentially beneficial changes in molecular pathways, including Alzheimer's disease, vascular cognitive impairment, chronic pain, and Parkinson's disease. Moreover, EA exerts beneficial effects through the same or diverse mechanisms for different disease types, including but not limited to neuroinflammation, neuronal apoptosis, neurogenesis, synaptic plasticity, and autophagy. However, these findings raise further questions that need to be elucidated. Overall, EA therapy for cognitive impairment is an area with great promise, even though more research regarding its detailed mechanisms is warranted.
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Objective: This study aims to investigate the impact of social isolation on the utilization of primary health services among older adults in China. Methods: Data from the China Longitudinal Aging Social Survey (CLASS) conducted in 2018 were utilized. A binary logistic regression model was established, and propensity score matching (PSM) was employed for analysis. Results: The results of the binary logistic regression showed that family isolation within social isolation had a significant negative impact on the utilization of primary health services for older adults. In contrast, there was no significant association between friend isolation, community isolation, and the utilization of primary health services. Furthermore, the PSM results, using three matching methods (nearest neighbor matching, radius matching, and kernel matching), confirmed that family isolation significantly reduced older adults' utilization of primary health services, consistent with the baseline regression findings. Conclusion: Reducing the occurrence of family isolation among older adults may be a cost-effective intervention measure. Efforts should be directed toward improving family support for older adults, promoting the utilization of primary health services, and strengthening disease prevention.
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Serviços de Saúde , Isolamento Social , China , Estudos LongitudinaisRESUMO
Continuous movement monitoring helps quickly identify pig abnormalities, enabling immediate action to enhance pig welfare. However, continuous and precise monitoring of daily pig movement on farms remains challenging. We present an approach to automatically and precisely monitor the movement of group-housed pigs. The instance segmentation model YOLOv8m-seg was applied to detect the presence of pigs. We then applied a spatial moment algorithm to quantitatively summarize each detected pig's contour as a corresponding center point. The agglomerative clustering (AC) algorithm was subsequently used to gather the pig center points of a single frame into one point representing the group-housed pigs' position, and the movement volume was obtained by calculating the displacements of the clustered group-housed pigs' center points of consecutive frames. We employed the method to monitor the movement of group-housed pigs from April to July 2023; more than 1500 h of top-down pig videos were recorded by a surveillance camera. The F1 scores of the trained YOLOv8m-seg model during training were greater than 90% across most confidence levels, and the model achieved an mAP50-95 of 0.96. The AC algorithm performs with an average extraction time of less than 1 millisecond; this method can run efficiently on commodity hardware.
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Objective: This study aims to elucidate the heterogeneous cognitive trajectories among older adults in China through a comprehensive, nationally representative longitudinal study. Furthermore, it seeks to investigate the impact of multidimensional social isolation on heterogeneous cognitive trajectories among older adults in China. Methods: Utilizing data from three successive waves of the Chinese Longitudinal Aging Social Survey (CLASS) spanning 2016 to 2020, this investigation quantified baseline social isolation across three dimensions-family isolation, friend isolation, and subjective isolation-alongside cognitive function scores of older adults, measured across all three waves. Through latent class growth models, heterogeneous cognitive trajectories were delineated. The influence of family isolation, friend isolation, and subjective isolation on these cognitive trajectories was examined employing multinomial logistic regression analysis. Results: The study included 6,378 participants aged 60 and above, revealing three primary cognitive trajectories: High baseline stable group (68.8%), High baseline but declining group (21.7%), and Low baseline deteriorating group (9.5%). Adjusting for variables such as personal physical characteristics, social networks, living and working conditions, and the surrounding policy environment, the findings indicated that family isolation did not significantly affect cognitive function's high-level decline or low-level deterioration. Conversely, friend isolation markedly increased the risk of high-level cognitive decline (OR = 1.289) and low-level cognitive deterioration (OR = 1.592). Similarly, subjective isolation significantly heightened the risk for both high-level decline (OR = 1.254) and low-level deterioration (OR = 1.29) in cognitive function. Conclusion: Mitigating friend and subjective isolation among older adults appears to be a more effective strategy in preventing or delaying cognitive decline, potentially reducing the strain on healthcare and social welfare systems.
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Isolamento Social , Humanos , Isolamento Social/psicologia , China , Masculino , Idoso , Feminino , Estudos Longitudinais , Pessoa de Meia-Idade , Cognição , Idoso de 80 Anos ou mais , Disfunção Cognitiva , Inquéritos e QuestionáriosRESUMO
Background: Remimazolam has shown similar or even superior properties to propofol in procedural sedation in adults, but few studies have been conducted in pediatric populations. Thus, we aimed to compare the effect and safety of remimazolam and propofol combined with low dose esketamine for pediatric same-day bidirectional endoscopy (BDE). Methods: Pediatrics <18 years scheduled for elective BDE under sedation were included and randomly assigned to remimazolam group (R group) or propofol group (P group). The primary outcome was the success rate of sedation. Secondary outcomes include sedation-related information and adverse events. Mean arterial pressure (MAP), heart rate (HR), and perfusion index (PI) were recorded during sedation. Results: A total of 106 patients were enrolled and analyzed. The success rate of sedation was 100% in both groups. Compared with the P group, the induction time of the R group was significantly prolonged (p < 0.001), and the incidence of injection pain, intraoperative respiratory depression, hypotension and bradycardia was significantly lower (p < 0.001). The changes in MAP, HR and PI were relatively stable in the R group compared with the P group. Additionally, awake time significantly decreased with age by approximately 1.12 index points for each increase in age in the P group (p = 0.002) but not in the R group (p > 0.05). Furthermore, the decline in PI and PI ratio during BDE was related to body movement in the P group. Conclusion: Remimazolam combined with low dose esketamine has a non-inferior sedative effect than propofol for pediatric BDE, with no injection pain, less respiratory depression, more stable hemodynamics. Moreover, early detection of the decline in PI may avoid harmful stimulation under light anesthesia. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT05686863?id=NCT05686863&rank=1, NCT05686863.
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BACKGROUND: With the increasing prevalence of chronic diseases, the demand for medical services from chronic disease patients has become diversified and personalized. The advantages and role of traditional Chinese medicine in the prevention and treatment of chronic diseases gradually emerging. The preferences and willingness to pay for traditional Chinese medicine services (TCMS) among patients with chronic diseases, as well as any disparities between urban and rural patients, have not been examined in past studies. OBJECTIVE: This study aimed to investigate the preferences of chronic disease patients for TCMS, explore the value/importance that patients place on different treatment attributes, and evaluate whether there are urban-rural differences in their preferences and willingness to pay for TCMS. METHODS: A total of 317 patients from Jiangsu Province, China participated in a discrete choice experiment that elicited the preferences for TCMS. The choice questions were constructed by six attributes: out-of-pocket (OOP) cost, institution, medical provider, treatment method, treatment duration, treatment efficacy. Mixed logit models were used to estimate the stated preference and marginal willingness to pay for each attribute. RESULTS: The choice preferences of chronic disease patients for TCMS in this study were influenced by the four attributes: institution, treatment method, and treatment efficacy, and OOP cost. Improvements in treatment efficacy were the most concerning, followed by being treated in traditional Chinese medicine (TCM) hospital. Patients were willing to pay more to get better treatment outcomes. Compared with primary care institutions, patients were willing to pay more for treatment in TCM hospitals. The preferences for economic attribute (OOP cost) varied between urban and rural areas, and rural patients tended to favor scenarios that imposed a lower economic burden on them. CONCLUSION: The chronic disease patients' preferences for TCMS were determined mainly by treatment efficacy but also by institution, treatment method and OOP cost. The urban-rural difference in preference identified in this study highlights that effective policy interventions should consider the characteristics of patients' demand in different regions.
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Comportamento de Escolha , Medicina Tradicional Chinesa , Preferência do Paciente , População Rural , População Urbana , Humanos , Masculino , Feminino , Doença Crônica/terapia , Pessoa de Meia-Idade , China , Adulto , Idoso , Inquéritos e QuestionáriosRESUMO
The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia-reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia-reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in reducing cell injury during reperfusion, the protection derived from the BET is not fully dependent on AIF-driven mechanisms.
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Fator de Indução de Apoptose/metabolismo , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Animais , Respiração Celular , Transporte de Elétrons , Masculino , Camundongos , Ratos , Ratos Endogâmicos F344RESUMO
Oxidative stress results in myocardial cell apoptosis and even life-threatening heart failure in myocardial ischemia-reperfusion injury. Specific blocking of the complex I could reduce cell apoptosis. Ndufs4 is a nuclear-encoded subunit of the mitochondrial complex I and participates in the electron transport chain. In this study, we designed and synthesized siRNA sequences knocking down the rat Ndufs4 gene, constructed recombinant adenovirus Ndufs4 siRNA (Ad-Ndufs4 siRNA), and primarily verified the role of Ndufs4 in oxidative stress injury. The results showed that the adenovirus infection rate was about 90%, and Ndufs4 mRNA and protein were decreased by 76.7% and 64.9%, respectively. Furthermore, the flow cytometry assay indicated that the cell apoptosis rate of the Ndufs4 siRNA group was significantly decreased as compared with the H2O2-treated group. In conclusion, we successfully constructed Ndufs4 siRNA recombinant adenovirus; furthermore, the downexpression of the Ndufs4 gene may alleviate H2O2-induced H9c2 cell apoptosis.
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Background: Wellbeing of healthcare workers is crucial for the effective functioning of primary health systems. This study aimed to examine the association between occupational stress and subclinical depression among primary healthcare workers, and to establish the foundation for future preventive strategies. Methods: A cross-sectional study was conducted in Tai'an City, Shandong Province, China. Data were collected from 832 medical staff in primary health institutions using a structured self-administered questionnaire. The participants completed the Challenge and Hindrance-Related Self-Reported Stress (C-HSS) Scale and Patient Health Questionnaire-9. Multivariable logistic regression analysis was conducted to explore the relationship between occupational stress and subclinical depression among primary healthcare workers. Results: The prevalence of subclinical depression among primary healthcare workers was 11.66%. Participants with subclinical depression have a significant higher level of occupational stress (including challenge-stress and hindrance-stress). Regression analysis result indicated that higher level of occupational stress was significantly associated with more severe subclinical depression, and the risk of subclinical depression remained after adjusting other covariates (OR = 4.57, 95%CI, 3.14-6.63). The association between challenge-stress and subclinical depression was not statistically significant when controlling for hindrance-stress. Subgroup analysis showed that male healthcare workers who perceived higher level of challenge stress were more likely to develop subclinical depression than female healthcare workers. Conclusion: The level of subclinical depression among Chinese primary healthcare workers was high, and occupational stress especially hindrance stress may contribute to subclinical depression. Findings were also robust in subgroup analysis after adjusting for other covariates. These findings emphasize the importance of occupational stress psychosocial interventions to decrease the risk of developing depression among the primary healthcare workers.
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Regional anesthesia (RA) is a common and irreplaceable technique in clinical, which can be used in different surgery sites and control of acute and chronic pain, especially for outpatients, pediatrics and the elderly. RA demands are increasing during COVID-19 pandemic because many surgeries could be performed under RA to reduce the risk of cross-infection between patients and health care workers. Early and accurate identification of the effects of RA can help physicians make timely decisions about whether to supplement analgesics or switch to general anesthesia, which will save time and improve patient satisfaction in a busy operating room. Perfusion index (PI) is a parameter derived from photoplethysmography (PPG) and represents the ratio of pulsatile and non-pulsatile blood flow at monitoring sites. It reflects local perfusion and is mainly affected by stroke volume and vascular tone. With characteristics of non-invasive, rapid, simple, and objective, PI is widely used in clinical practice, such as fluid responsiveness prediction, nociceptive assessment, etc. Recently, many studies have assessed the accuracy of PI in early prediction of RA success, including brachial plexus block, sciatic nerve block, neuraxial anesthesia, paravertebral block, caudal block and stellate ganglion block. Successful RA often parallels increased PI. In this narrative review, we describe the principles and influencing factors of PI, and introduce the effects of PI on early identification of RA effectiveness.
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Anestesia por Condução , Bloqueio do Plexo Braquial , COVID-19 , Humanos , Criança , Idoso , Índice de Perfusão , Pandemias , Dor Pós-Operatória/epidemiologia , COVID-19/complicações , Anestesia por Condução/métodos , Bloqueio do Plexo Braquial/métodosRESUMO
Perioperative neurocognitive disorders (PND) are a common complication in elderly patients following surgery, which not only prolongs the recovery period but also affects their future quality of life and imposes a significant burden on their family and society. Multiple factors, including aging, vulnerability, anesthetic drugs, cerebral oxygen desaturation, and severe pain, have been associated with PND. Unfortunately, no effective drug is currently available to prevent PND. α5 γ-aminobutyric acid subtype A (α5GABAA) receptors have been implicated in cognitive function modulation. Positive or negative allosteric modulators of α5GABAA receptors have been found to improve cognitive impairment under different conditions. Therefore, targeting α5GABAA receptors may represent a promising treatment strategy for PND. This review focuses on preclinical studies of α5GABAA receptors and the risk factors associated with PND, primarily including aging, anesthetics, and neuroinflammation. Specifically, positive allosteric modulators of α5GABAA receptors have improved cognitive function in aged experimental animals. In contrast, negative allosteric modulators of α5GABAA receptors have been found to facilitate cognitive recovery in aged or adult experimental animals undergoing anesthesia and surgery but not in aged experimental animals under anesthesia alone. The reasons for the discordant findings have yet to be elucidated. In preclinical studies, different strategies of drug administration, as well as various behavioral tests, may influence the stability of the results. These issues need to be carefully considered in future studies.
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Disfunção Cognitiva , Qualidade de Vida , Idoso , Animais , Humanos , Cognição , EnvelhecimentoRESUMO
Methods: We selected 5,172 microdata on individuals from the China Health and Retirement Longitudinal Study (CHARLS) 2018. The binary logit model, the ordered logit model, and the stepwise regression were employed to compare the effects of air pollution on self-rated health (SRH) and activities of daily living (ADL) in an elderly population. The effects on health shocks were explored in different age groups, different gender groups, different regions and different sources of pollutants, respectively. Results: We found that air pollution significantly increased the risk of health shocks in the elderly population, especially in the 60-69 year age group, and the eastern/central region, where NO2 and O3 were important pollutant sources. Conclusion: Targeted management of the environment is necessary to improve the health status of China's elderly population. In addition, paying attention to the health status of vulnerable populations is needed to achieve social equity.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Idoso , Poluentes Atmosféricos/análise , Estudos Transversais , Estudos Retrospectivos , Atividades Cotidianas , Estudos Longitudinais , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologiaRESUMO
Accurate plant leaf image segmentation provides an effective basis for automatic leaf area estimation, species identification, and plant disease and pest monitoring. In this paper, based on our previous publicly available leaf dataset, an approach that fuses YOLOv8 and improved DeepLabv3+ is proposed for precise image segmentation of individual leaves. First, the leaf object detection algorithm-based YOLOv8 was introduced to reduce the interference of backgrounds on the second stage leaf segmentation task. Then, an improved DeepLabv3+ leaf segmentation method was proposed to more efficiently capture bar leaves and slender petioles. Densely connected atrous spatial pyramid pooling (DenseASPP) was used to replace the ASPP module, and the strip pooling (SP) strategy was simultaneously inserted, which enabled the backbone network to effectively capture long distance dependencies. The experimental results show that our proposed method, which combines YOLOv8 and the improved DeepLabv3+, achieves a 90.8% mean intersection over the union (mIoU) value for leaf segmentation on our public leaf dataset. When compared with the fully convolutional neural network (FCN), lite-reduced atrous spatial pyramid pooling (LR-ASPP), pyramid scene parsing network (PSPnet), U-Net, DeepLabv3, and DeepLabv3+, the proposed method improves the mIoU of leaves by 8.2, 8.4, 3.7, 4.6, 4.4, and 2.5 percentage points, respectively. Experimental results show that the performance of our method is significantly improved compared with the classical segmentation methods. The proposed method can thus effectively support the development of smart agroforestry.