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Proving mathematical theorems at the olympiad level represents a notable milestone in human-level automated reasoning1-4, owing to their reputed difficulty among the world's best talents in pre-university mathematics. Current machine-learning approaches, however, are not applicable to most mathematical domains owing to the high cost of translating human proofs into machine-verifiable format. The problem is even worse for geometry because of its unique translation challenges1,5, resulting in severe scarcity of training data. We propose AlphaGeometry, a theorem prover for Euclidean plane geometry that sidesteps the need for human demonstrations by synthesizing millions of theorems and proofs across different levels of complexity. AlphaGeometry is a neuro-symbolic system that uses a neural language model, trained from scratch on our large-scale synthetic data, to guide a symbolic deduction engine through infinite branching points in challenging problems. On a test set of 30 latest olympiad-level problems, AlphaGeometry solves 25, outperforming the previous best method that only solves ten problems and approaching the performance of an average International Mathematical Olympiad (IMO) gold medallist. Notably, AlphaGeometry produces human-readable proofs, solves all geometry problems in the IMO 2000 and 2015 under human expert evaluation and discovers a generalized version of a translated IMO theorem in 2004.
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Matemática , Processamento de Linguagem Natural , Resolução de Problemas , Humanos , Matemática/métodos , Matemática/normasRESUMO
Mitochondrial DNA (mtDNA) encodes several key components of respiratory chain complexes that produce cellular energy through oxidative phosphorylation. mtDNA is vulnerable to damage under various physiological stresses, especially oxidative stress. mtDNA damage leads to mitochondrial dysfunction, and dysfunctional mitochondria can be removed by mitophagy, an essential process in cellular homeostasis. However, how damaged mtDNA is selectively cleared from the cell, and how damaged mtDNA triggers mitophagy, remain mostly unknown. Here, we identified a novel mitophagy receptor, ATAD3B, which is specifically expressed in primates. ATAD3B contains a LIR motif that binds to LC3 and promotes oxidative stress-induced mitophagy in a PINK1-independent manner, thus promoting the clearance of damaged mtDNA induced by oxidative stress. Under normal conditions, ATAD3B hetero-oligomerizes with ATAD3A, thus promoting the targeting of the C-terminal region of ATAD3B to the mitochondrial intermembrane space. Oxidative stress-induced mtDNA damage or mtDNA depletion reduces ATAD3B-ATAD3A hetero-oligomerization and leads to exposure of the ATAD3B C-terminus at the mitochondrial outer membrane and subsequent recruitment of LC3 for initiating mitophagy. Furthermore, ATAD3B is little expressed in m.3243A > G mutated cells and MELAS patient fibroblasts showing endogenous oxidative stress, and ATAD3B re-expression promotes the clearance of m.3243A > G mutated mtDNA. Our findings uncover a new pathway to selectively remove damaged mtDNA and reveal that increasing ATAD3B activity is a potential therapeutic approach for mitochondrial diseases.
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ATPases Associadas a Diversas Atividades Celulares/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Mitofagia , Estresse Oxidativo , ATPases Associadas a Diversas Atividades Celulares/química , ATPases Associadas a Diversas Atividades Celulares/genética , Animais , Células Cultivadas , Dano ao DNA , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Células HEK293 , Células HeLa , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mitocondriais/química , Proteínas Mitocondriais/genética , Ligação ProteicaRESUMO
Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) has become the leading cause of chronic liver disease. Liver biopsy, as the diagnostic gold standard, is invasive and has sampling bias, making it particularly important to search for sensitive and specific biomarkers for diagnosis. Cytokeratin 18 (CK18) M30 and M65 are products of liver cell apoptosis and necrosis, respectively, and liver-expressed antimicrobial peptide 2 (LEAP-2) is a related indicator of glucose and lipid metabolism. Correlation studies have found that all three indicators positively correlate with the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Through comparison of diagnostic values, it was found that CK18 M65 can better distinguish between healthy individuals and MAFLD; LEAP-2 can effectively distinguish MAFLD from other liver diseases, especially ALD.
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Peptídeos Catiônicos Antimicrobianos , Biomarcadores , Queratina-18 , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alanina Transaminase/sangue , Peptídeos Catiônicos Antimicrobianos/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biópsia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/patologia , Fígado Gorduroso/sangue , Queratina-18/sangue , Fígado/patologia , Fragmentos de Peptídeos , Sensibilidade e EspecificidadeRESUMO
Rare-earth-doped silica-based composite glasses (Re-SCGs) are widely used as high-quality laser gain media in defense, aerospace, energy, power, and medical applications. The variable regional chemical environments of Re-SCGs can induce new photoluminescence properties of rare-earth ions but can cause the selective aggregation of rare-earth ions, limiting the application of Re-SCGs in the field of high-power lasers. Here, topological engineering is proposed to adjust the degree of cross-linking of phase-separation network chains in Re-SCGs. A combination of experimental and theoretical characterization techniques suggested that the selective aggregation of rare-earth ions originates from the formation of phase-separated structures in glasses. The decomposition of nanoscale phase separation structures to the sub-nanometer scale, enabled by incorporating Al3+ ions, not only maintains the high luminescence efficiency of rare earth ions but also increases light transmittance and reduces light scattering. Furthermore, our investigation encompassed the exploration of the inhibitory mechanism of Al3+ ions on phase-separation structures, as well as their influence on the spectral characteristics of Re-SCGs. This work provides a new design concept for composite glass materials doped with rare-earth ions and could broaden their application in the field of high-power lasers.
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BACKGROUND: Myopia is the most prevalent refractive error and a growing global health concern that significantly affects visual function. Researchers have recently emphasized considerably on the influence of lifestyle on myopia incidence and development. This study investigates the relationship between leisure sedentary behaviors (LSB)/physical activity (PA)/sleep traits and myopia. METHODS: LSB, PA, and sleep trait-associated genetic variants were used as instrument variables in a Mendelian randomization (MR) study to examine their causal effects on myopia. Summary genome-wide association studies (GWASs) statistical data for LSB and PA were obtained from UK Biobank, and the data of sleep traits was obtained from UK Biobank, UK Biobank and 23andMe, and FinnGen. We used summary statistics data for myopia from MRC IEU. The MR analyses was performed using the inverse variance-weighted (IVW), MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier methods. RESULTS: Computer use was genetically predicted to increase the myopia risk [IVW odds ratio (OR) = 1.057; 95% confidence interval (CI), 1.038-1.078; P = 7.04 × 10- 9]. The self-reported moderate-to-vigorous physical activity (MVPA) (IVW OR = 0.962; 95% CI, 0.932-0.993; P = 1.57 × 10- 2) and television watching (IVW OR = 0.973; 95% CI, 0.961-0.985, P = 1.93 × 10- 5) were significantly associated with a lower myopia risk. However, genetically predicted sleep traits or accelerometer-measured physical activity had no significant associations with myopia. CONCLUSION: Our results indicated that computer use is a risk factor for myopia, whereas television watching and MVPA may protect against myopia. These findings shed new light on possible strategies for reducing the prevalence of myopia.
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Miopia , Comportamento Sedentário , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Miopia/epidemiologia , Miopia/genética , Exercício Físico , Sono , Atividades de LazerRESUMO
BACKGROUND: Lung cancer remains a major global health concern due to its high incidence and mortality rates. With advancements in medical treatments, an increasing number of early-stage lung cancer cases are being detected, making surgical treatment the primary option for such cases. However, this presents challenges to the physical and mental recovery of patients. Peplau known as the "mother of psychiatric associations" has formulated a theory of interpersonal relationships in nursing. Through effective communication between nurses and patients over four periods, she has established a good therapeutic nurse-patient relationship. Therefore, this study aimed to explore the effect of perioperative multimodal nursing based on Peplau's interpersonal relationship theory on the rehabilitation of patients with surgical lung cancer. METHODS: We retrospectively analyzed 106 patients with non-small cell lung cancer who underwent thoracoscopic lobectomy at our department between June 2021 and April 2022. Patients were categorized into two groups according to the different nursing intervention techniques. The Peplau's group comprised 53 patients who received targeted nursing interventions, and the control group comprised 53 patients who received conventional nursing care. We observed the patients' illness uncertainty, quality of life, and clinical symptoms in both groups. RESULTS: Patients in the Peplau's group had significantly lower illness uncertainty scores and a significantly higher quality of recovery than those in the control group. However, there were no significant differences in length of post-anesthesia care unit stay, complication rates, and visual analog scores between both groups. CONCLUSION: The multimodal perioperative nursing based on Peplau's interpersonal relationship theory not only reduces the illness uncertainty of patients with lung cancer surgery and improves their QoR but also expands the application of this theory in clinical practice, guiding perioperative nursing of patients with lung cancer. IMPLICATIONS: These findings provide practical information for standardized care in a hectic anesthetic care setting. IMPACT: The assessed anesthesia nursing model helps reduce uncertainty and promote early recovery in patients with cancer at various stages of their disease, which expands the scope of therapeutic practice and existing theories. It also serves as a guide for care in the anesthesia recovery room. REPORTING METHOD: We adhered to the relevant Equator guidelines and the checklist of items in the case-control study report. PATIENT OR PUBLIC CONTRIBUTION: Patients cooperated with medical staff to complete relevant scales.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Teoria de Enfermagem , Estudos Retrospectivos , Estudos de Casos e Controles , Neoplasias Pulmonares/cirurgia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Qualidade de VidaRESUMO
BACKGROUND: Traditional total hip arthroplasty (THA) using the direct anterior approach (DAA) requires a hip extension. This study aimed to compare the clinical outcomes of patients undergoing THA with DAA using either the no hip extension (NHE) or the traditional hip extension (THE) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 123 patients treated between January 2020 and November 2021. The patients were categorised into two groups: NHE (84 patients) and THE (39 patients). RESULTS: The NHE group exhibited shorter operative time and had more male participants with higher ages. Comparable outcomes were observed in the visual analogue scale, Harris Hip, and Oxford Hip scores at the final follow-up. Furthermore, complications were observed in the NHE and THE groups, including two and one greater trochanteric fractures and three and one transfusions, respectively. CONCLUSIONS: Compared to the THE, employing the NHE strategy during THA with DAA in elderly and young female patients resulted in comparable clinical outcomes with several advantages, such as favourable surgical time. The NHE method also exhibited good safety and effectiveness. Therefore, the NHE strategy may be a favourable option for elderly and young female patients.
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Artroplastia de Quadril , Humanos , Masculino , Feminino , Idoso , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Estudos Retrospectivos , Resultado do Tratamento , Radiografia , Duração da CirurgiaRESUMO
Intracranial aneurysm (IA) is a common cerebrovascular disease. Immune system disorders and endothelial dysfunction are essential mechanisms of its pathogenesis. This study aims to explore the therapeutic effect and mechanism of Geniposide (Gen) on IA, which has a protective impact on endothelial cells and cardiovascular and cerebrovascular diseases. IA mouse models were administered intraperitoneal injections of geniposide for 2 weeks following elastase injection into the right basal ganglia of the brain for intervention. The efficacy of Gen in treating IA was evaluated through pathological testing and transcriptome sequencing analysis of Willis ring vascular tissue. The primary mechanism of action was linked to the expression of GSK3ß in Th17 cells. The percentage of splenic Th17 cell differentiation in IA mice was significantly inhibited by Gen. GSK3ß/STAT3, and other pathway protein expression levels were also significantly inhibited by Gen. Additionally, TNF-α and IL-23 cytokine contents were significantly downregulated after Gen treatment. These results indicated that Gen significantly inhibited the percentage of Th17 cell differentiation, an effect that was reversed upon overexpression of the GSK3B gene. Furthermore, Gen-treated, Th17 differentiation-inducing cell-conditioned medium significantly up-regulated the expression of tight junction proteins ZO-1, Occludin, and Claudin-5 in murine aortic endothelial cells. Administering the GSK3ß inhibitor Tideglusib to IA mice alleviated the severity of IA disease pathology and up-regulated aortic tight junction protein expression. In conclusion, Gen inhibits Th17 cell differentiation through GSK3ß, which reduces endothelial cell injury and up-regulates tight junction protein expression.
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Serum protein electrophoresis (SPEP) is a valuable laboratory test that separates proteins from the blood based on their electrical charge and size. The test can detect and analyze various protein abnormalities, and the interpretation of graphic SPEP features plays a crucial role in the diagnosis and monitoring of conditions, such as myeloma. Furthermore, the advancement of artificial intelligence (AI) technology presents an opportunity to enhance the organization and optimization of analytical procedures by streamlining the process and reducing the potential for human error in SPEP analysis, thereby making the process more efficient and reliable. For instance, AI can assist in the identification of protein peaks, the calculation of their relative proportions, and the detection of abnormalities or inconsistencies. This review explores the characteristics and limitations of AI in SPEP, and the role of standardization in improving its clinical utility. It also offers guidance on the rational ordering and interpreting of SPEP results in conjunction with AI. Such integration can effectively reduce the time and resources required for manual analysis while improving the accuracy and consistency of the results.
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The development of biomimetic catalytic systems that can imitate or even surpass natural enzymes remains an ongoing challenge, especially for bioinspired syntheses that can access non-natural reactions. Here, we show how an all-inorganic biomimetic system bearing robust nitrogen-neighbored single-cobalt site/pyridinic-N site (Co-N4/Py-N) pairs can act cooperatively as an oxidase mimic, which renders an engaged coupling of oxygen (O2) reduction with synthetically beneficial chemical transformations. By developing this broadly applicable platform, the scalable synthesis of greater than 100 industrially and pharmaceutically appealing O-silylated compounds including silanols, borasiloxanes, and silyl ethers via the unprecedented aerobic oxidation of hydrosilane under ambient conditions is demonstrated. Moreover, this heterogeneous oxidase mimic also offers the potential for expanding the catalytic scope of enzymatic synthesis. We anticipate that the strategy demonstrated here will pave a new avenue for understanding the underlying nature of redox enzymes and open up a new class of material systems for artificial biomimetics.
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BACKGROUND: Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear. AIMS: In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. METHODS: SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR. RESULTS: In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways. CONCLUSIONS: In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.
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Medicamentos de Ervas Chinesas , Lycium , Traumatismos da Medula Espinal , Animais , Masculino , Ratos , Ácidos Docosa-Hexaenoicos/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Glicopeptídeos , Lycium/química , Lycium/metabolismo , Doenças Neuroinflamatórias , NF-kappa B/metabolismo , Piroptose , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológicoRESUMO
BACKGROUND AND AIMS: Sam50, a key component of the sorting and assembly machinery (SAM) complex, is also involved in bridging mitochondrial outer-membrane and inner-membrane contacts. However, the physiological and pathological functions of Sam50 remain largely unknown. APPROACH AND RESULTS: Here we show that Sam50 interacts with MICOS (mitochondrial contact site and cristae organizing system) and ATAD3 (ATPase family AAA domain-containing protein 3) to form the Sam50-MICOS-ATAD3-mtDNA axis, which maintains mtDNA stability. Loss of Sam50 causes mitochondrial DNA (mtDNA) aggregation. Furthermore, Sam50 cooperates with Mic60 to bind to cardiolipin, maintaining the integrity of mitochondrial membranes. Sam50 depletion leads to cardiolipin externalization, which causes mitochondrial outer-membrane and inner-membrane (including crista membrane) remodeling, triggering Bax mitochondrial recruitment, mtDNA aggregation, and release. Physiologically, acetaminophen (an effective antipyretic and analgesic)-caused Sam50 reduction or Sam50 liver-specific knockout induces mtDNA release, leading to activation of the cGAS-STING pathway and liver inflammation in mice. Moreover, exogenous expression of Sam50 remarkably attenuates APAP-induced liver hepatoxicity. CONCLUSIONS: Our findings uncover the critical role of Sam50 in maintaining mitochondrial membrane integrity and mtDNA stability in hepatocytes and reveal that Sam50 depletion-induced cardiolipin externalization is a signal of mtDNA release and controls mtDNA-dependent innate immunity.
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Antipiréticos , Membranas Mitocondriais , Animais , Humanos , Camundongos , Acetaminofen , Adenosina Trifosfatases/metabolismo , Proteína X Associada a bcl-2/metabolismo , Cardiolipinas/metabolismo , DNA Mitocondrial/genética , Células HeLa , Hepatócitos/metabolismo , Fígado/metabolismo , Proteínas de Membrana/genética , Membranas Mitocondriais/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/metabolismo , Nucleotidiltransferases/metabolismoRESUMO
Seafood tends to be highly vulnerable to spoilage and deterioration due to biochemical reactions and microbial contaminations, which requires appropriate processing technologies to improve or maintain its quality. Flavor, as an indispensable aspect reflecting the quality profile of seafood and influencing the final choice of consumers, is closely related to the processing technologies adopted. This review gives updated information on traditional and emerging processing technologies used in seafood processing and their implications on flavor. Traditional processing technologies, especially thermal treatment, effectively deactivate microorganisms to enhance seafood safety and prolong its shelf life. Nonetheless, these methods come with limitations, including reduced processing efficiency, increased energy consumption, and alterations in flavor, color, and texture due to overheating. Emerging processing technologies like microwave heating, infrared heating, high pressure processing, cold plasma, pulsed electric field, and ultrasound show alternative effects to traditional technologies. In addition to deactivating microorganisms and extending shelf life, these technologies can also safeguard the sensory quality of seafood. This review discusses emerging processing technologies in seafood and covers their principles, applications, developments, advantages, and limitations. In addition, this review examines the potential synergies that can arise from combining certain processing technologies in seafood processing.
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Many cancer cells maintain enhanced aerobic glycolysis due to irreversible defective mitochondrial oxidative phosphorylation (OXPHOS). This phenomenon, known as the Warburg effect, is recently challenged because most cancer cells maintain OXPHOS. However, how cancer cells coordinate glycolysis and OXPHOS remains largely unknown. Here, we demonstrate that OMA1, a stress-activated mitochondrial protease, promotes colorectal cancer development by driving metabolic reprogramming. OMA1 knockout suppresses colorectal cancer development in AOM/DSS and xenograft mice models of colorectal cancer. OMA1-OPA1 axis is activated by hypoxia, increasing mitochondrial ROS to stabilize HIF-1α, thereby promoting glycolysis in colorectal cancer cells. On the other hand, under hypoxia, OMA1 depletion promotes accumulation of NDUFB5, NDUFB6, NDUFA4, and COX4L1, supporting that OMA1 suppresses OXPHOS in colorectal cancer. Therefore, our findings support a role for OMA1 in coordination of glycolysis and OXPHOS to promote colorectal cancer development and highlight OMA1 as a potential target for colorectal cancer therapy.
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Neoplasias Colorretais , Fosforilação Oxidativa , Animais , Ciclo do Ácido Cítrico , Neoplasias Colorretais/genética , Glicólise , Hipóxia/genética , CamundongosRESUMO
BACKGROUND: Non-suicidal self-injury (NSSI) by adolescent patients with depression has become a serious public health problem. This cross-sectional study aims to identify subgroups of adolescents based on NSSI and explore the factors related to these subgroups. METHODS: The study recruited 326 in- and out-patient adolescents (263 girls and 63 boys) aged 12 to 18 years (mean = 14.7, SD = 1.6) who had self-injured in the past year. Latent class indicators included 12 NSSI variables, as well as suicidal ideation. Logistic regression examined associations between identified classes and related factors. RESULTS: In this study, two distinct subgroups were identified: a "high suicidal ideation NSSI group" (n = 129, 39.6%) and a "low suicidal ideation NSSI group" (n = 197, 60.4%). Depression (OR = 1.10; 95% CI, 1.05-1.16), female (OR = 2.01; 95% CI, 1.09-3.69), left-behind experience (OR = 2.08; 95% CI, 1.17-3.71), single-parent family (OR = 1.84; 95% CI, 1.11-3.04) and peer victimization (OR = 1.04; 95% CI, 1.02-1.05) increases the probability of belonging to the "high suicidal ideation NSSI group". A high level of perceived social support (OR = 0.99; 95% CI, 0.97-0.99) was a protective factor towards NSSI. CONCLUSIONS: This study identifies two subgroups of NSSI and the factors associated with each subgroup. The early identification of high-risk groups for major NSSI in adolescents diagnosed with depression is possible due to the identification of correlating factors. Different treatment plans can be developed for different subtypes of NSSI to improve the effectiveness of prevention and intervention, promoting the healthy physical and mental development of adolescents with depression.
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Comportamento Autodestrutivo , Tentativa de Suicídio , Masculino , Humanos , Adolescente , Feminino , Depressão , Estudos Transversais , Análise de Classes Latentes , Fatores de Risco , Comportamento Autodestrutivo/complicações , Ideação SuicidaRESUMO
The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger's test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.
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Anestésicos , Delírio , Adulto , Humanos , Criança , Xenônio/farmacologia , Período Pós-Operatório , Anestesia por Inalação/efeitos adversos , Delírio/induzido quimicamenteRESUMO
Objective: To analyze the risk factors of metabolic dysfunction-associated fatty liver disease (MAFLD) in the physical examination population, to establish a risk prediction model for the occurrence of MAFLD, and to provide management strategies for the prevention and occurrence of the disease. Methods: A total of 14664 people who underwent physical examination at the Physical Examination Center, West China Hospital, Sichuan University between January 2018 and December 2021 were selected as research subjects. The subjects were divided into a MAFLD group ( n=4013) and a non-MAFLD group ( n=10651) according to whether they had MAFLD. The differences in biochemical indices, for example, glycolipid metabolism levels, were compared and logistic regression was conducted to analyze the risk factors for MAFLD, thereby establishing a nomogram prediction model. The prediction effect of the model was validated and evaluated with the consistency index (C-index) and the calibration curve. Results: Among the 14664 subjects who underwent physical examination, 4013 were MAFLD patients, presenting an overall prevalence of 27.37%, with significantly higher prevalence in men than that in women (38.99% vs. 10.06%, P<0.001). Compared with those of the non-MAFLD group, the levels of glucose (GLU), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and uric acid (UA) were increased ( P<0.05), while the high density lipoprotein cholesterol (HDL-C) level was decreased ( P<0.05) in the MAFLD group. The results of logistic regression analysis showed that male sex, age, body mass index, GLU, TG and hypertension were all independent risk factors of MAFLD, while HDL-C was a protective factor of MAFLD. The risk factors were used to establish a nomogram risk prediction model and the C-index and calibration curve showed that the nomogram model produced good predictive performance. The receiver operating characteristic (ROC) curve showed that the nomogram model had good predictive value for the risk of MAFLD. Conclusion: We found a relatively high prevalence of MAFLD in the physical examination population, and the nomogram model established with routine physical examination screening can provide indications for the clinical screening and analysis of high-risk patients, which has an early warning effect on the high-risk population.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Feminino , Fatores de Risco , Triglicerídeos , HDL-Colesterol , Exame Físico , GlucoseRESUMO
Hemoglobin (Hb) variants are common factors that affect the results of glycosylated hemoglobin (A1C) tests. Hemoglobin variants react differently to different testing methods. Herein, we presented the first ever report of the effect of hemoglobin C (Hb C) on the test results of A1C in the Chinese population. High performance liquid chromatography (HPLC) and capillary electrophoresis were performed to measure A1C. Hemoglobin electrophoresis was conducted to identify the hemoglobin variants. Hb sequencing was performed to determine the mutation sites on the ß chain. HPLC showed decreased A1C results, which could be corrected by electrophoresis, but the electrophoresis graph still showed abnormal peaks. The hemoglobin electrophoresis results suggested that there were hemoglobin variants, which hemoglobin sequencing results revealed to be Hb C. Uncommon variations in a specific population tend to be overlooked. To avoid clinical decision-making being affected by the results of a single test, we recommend that an explanatory reporting model be routinely adopted for A1C tests so that all reports always contain explanatory notes for the testing methodology and analysis of the graphs.
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Hemoglobina C , Hemoglobinas Anormais , Humanos , Hemoglobina C/análise , Hemoglobina C/genética , Hemoglobinas Glicadas , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/análise , Mutação , Eletroforese Capilar , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Insect cytochrome P450 plays major roles in detoxification of phytotoxin and insecticides. However, determination of P450 activity in aphids has variable success and there is no reliable method yet. In this study, we found that homogenizing the green peach aphid, Myzus persicae, in the 96-well microplate resulted in significantly higher P450 activities than those in Eppendorf tube. Homogenizing aphids in Eppendorf tube released uncharacterized compounds that inhibited aphids and pig liver P450 activities, whereas aphids homogenized in the microplate may not be completely ground and thus released fewer such inhibitors. Then, the microplate homogenization method was optimized as follows: one or two aphids were placed in one well of the 96 well-microplate and ground in phosphate buffer using pipette tips for 20 cycles, followed by addition of 7-ethoxycoumarin, and then incubated for 1 h at room temperature, after which glycine buffer-ethanol mixture was added to stop the reaction. This method is also suitable for the pea aphid, Acyrthosiphon pisum, and the bird cherry-oat aphid, Rhopalosiphum padi. These results highlight the importance of considering inhibitory effects of endogenous compounds in insects on their P450 activities and provide one possible method to reduce these inhibitory effects.