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Diagnostic and monitoring for drug-induced liver injury (DILI) predominantly rely on serum aminotransferases. However, owing to their widespread expression across multiple organs, a significant challenge emerges from the absence of reliable biomarkers for DILI diagnosis. Herein, we introduce a concept for DILI detection, circumventing the nonspecific elevation and delayed release of aminotransferases and then straightforwardly focusing on the core feature of DILI, abnormal gene expression caused by drug overdose. The developed full-scale platform integrates the properties of spherical nucleic acids with elaborately designed fluorescence in situ hybridization sequences, enabling the sensitive and specific profiling of drug-overdosed miR-122 expression alterations across molecular, cellular, organismal, and clinical scales and effectively bypassing the phenotypic features of disease. Furthermore, the diagnostic efficacies of serum and total RNA extracted from both mouse and human blood samples for DILI diagnosis were analyzed using the receiver operating characteristic curve and principal component analysis. We anticipate that this universal platform holds potential in facilitating DILI diagnosis, therapeutic evaluation, and prognosis.
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A precisely designed dual-color biosensor has realized a visual assessment of thymidine kinase 1 (TK1) mRNA in both living cells and cell lysates. The oligonucleotide probe is constructed by hybridizing the antisense strand of the target and two recognition sequences, in which FAM serves as the donor and TAMRA as the acceptor. Once interacting with the target, two recognition strands are replaced, and then the antisense complementary sequence forms a more stable double-stranded structure. Due to the increasing spatial distance between two dyes, the FRET is attenuated, leading to a rapid recovery of FAM fluorescence and a reduction of TAMRA fluorescence. A discernible color response from orange to green could be observed by the naked eye, with a limit of detection (LOD) of 0.38 nM and 5.22 nM for spectrometer- and smartphone-based assays, respectively. The proposed ratiometric method transcends previous reports in its capacities in visualizing TK1 expression toward reliable nucleic acid biomarker analysis, which might establish a general strategy for ratiometric biosensing via strand displacement.
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Transferencia Resonante de Energía de Fluorescencia , Colorantes Fluorescentes , Límite de Detección , ARN Mensajero , Timidina Quinasa , Timidina Quinasa/genética , Humanos , Transferencia Resonante de Energía de Fluorescencia/métodos , ARN Mensajero/análisis , ARN Mensajero/genética , Colorantes Fluorescentes/química , Técnicas Biosensibles/métodos , Hibridación de Ácido Nucleico , Fluorometría/métodos , Biomarcadores/análisisRESUMEN
BACKGROUND: Rheum palmatum, R. tanguticum, and R. officinale, integral species of the genus Rheum, are widely used across global temperate and subtropical regions. These species are incorporated in functional foods, medicines, and cosmetics, recognized for their substantial bioactive components. PURPOSE: This review aims to synthesize developments from 2014 to 2023 concerning the botanical characteristics, ethnopharmacology, nutritional values, chemical compositions, pharmacological activities, mechanisms of action, and toxicity of these species. METHODS: Data on the three Rheum species were gathered from a comprehensive review of peer-reviewed articles, patents, and clinical trials accessed through PubMed, Google Scholar, Web of Science, and CNKI. RESULTS: The aerial parts are nutritionally rich, providing essential amino acids, fatty acids, and minerals, suitable for use as health foods or supplements. Studies have identified 143 chemical compounds, including anthraquinones, anthrones, flavonoids, and chromones, which contribute to their broad pharmacological properties such as laxative, anti-diarrheal, neuroprotective, hepatoprotective, cardiovascular, antidiabetic, antitumor, anti-inflammatory, antiviral, and antibacterial effects. Notably, the materials science approach has enhanced understanding of their medicinal capabilities through the evaluation of bioactive compounds in different therapeutic contexts. CONCLUSION: As medicinal and economically significant herb species, Rheum species provide both edible aerial parts and medicinal underground components that offer substantial health benefits. These characteristics present new opportunities for developing nutritional ingredients and therapeutic products, bolstering the food and pharmaceutical industries.
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Fitoquímicos , Rheum , Etnofarmacología , Fitoquímicos/farmacología , Fitoquímicos/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Rheum/químicaRESUMEN
Rhubarb contains an abundance of compounds and nutrients that promote health through various activities; however, these activities are affected by the harvest season. In this paper, the changes in nutrients, phytochemical profiles and antioxidant activity of Rheum officinale leaf blades (LRO) during different growth periods were investigated. The results showed that LRO is a good source of protein, fiber, and minerals and contains abundant fatty acids; however, as the harvest time increased from March to July, the levels of protein and amino acid decreased, and the levels of other nutrients reached a maximum in May or June. LRO also contains flavonoids, terpenoids, and quinones. As the harvest time increased, the quinone content decreased, possibly due to the unstable chemical properties of quinones at high temperatures. The flavonoid contents reached a maximum in May or June. This study indicated that LRO is a source of nutrients and chemical components and can be used for functional food production. In addition, the nutrients and chemical components related to the antioxidant activity of LRO changed according to the harvest season.
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BACKGROUND: Rhubarb is widely distributed and cultivated worldwide, and its leaves presented antioxidant activity and could be used as food additive. However, the chemical ingredients, and protective effect of Rheum officinale leaf juice (JROL) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) are still unclear. PURPOSE: This paper sought to the characterization and functional properties of JROL, and explore the underlying mechanism on UC mice. METHODS: UPLC-ESI-Q-TOF/MS and other analytical instruments were employed to determine the chemical ingredients of JROL. After inducing UC model using 3% DSS, multiple biological methods were used to evaluate its protective effect and the potential mechanism. RESULTS: JROL is rich in proximate compositions and minerals and has high nutritional value, and contains reducing sugars, polysaccharides and pectin. Fifteen compounds were identified using UPLC-ESI-Q-TOF/MS. Among them, rutin has the highest content (2.22 %) in UPLC analysis. JROL presented protective effect on DSS-induced UC, and alleviated morphological alterations and ultra-structural feature of tissue, and the polysaccharides and flavonoids may contribute to its protective effect. JROL inhibited NF-κB/NLRP3 signaling pathway to alleviate inflammatory response, oxidative stress and intestinal injury by decreasing the expression of p-p65, p-IκBα, NLRP3, ASC, etc.. Moreover, it up-regulated the expression of tight junction proteins, and re-balanced the disturbance of gut microbiota to regulate the inflammatory response. Finally, a correlation among the inflammatory response, NF-κB/NLRP3 pathway and gut microbiota was established. Moreover, JROL presented the safety in the acute toxicity test. CONCLUSION: JROL could be used as a potential new source for treating UC.
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Colitis Ulcerosa , Sulfato de Dextran , Hojas de la Planta , Rheum , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Animales , Rheum/química , Hojas de la Planta/química , Ratones , Masculino , Extractos Vegetales/farmacología , Extractos Vegetales/química , Modelos Animales de Enfermedad , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , FN-kappa B/metabolismo , Ratones Endogámicos C57BLRESUMEN
Pure spin current, exhibiting no Joule heat and self-powered characteristics, has recently attracted intensive attention. Here, through first-principles calculations and symmetry analysis, we propose a new method to generate photoelectric pure spin current in carbon hexagonal connected three zigzag graphene nanoribbons (ZGNRs) via magnetic field modulation. Specifically, a device with centro-symmetry is designed, which consists of three ZGNRs using two carbon hexagons as connectors ('2-C6'). When the edge spin states of the three ZGNRs from left to right are modulated to AFM-AFM-AFM or FM-AFM-FM by magnetic fields, excellent pure spin currents are obtained which are independent of the photon energy and the angle of the linearly polarized light. However, when the edge spin states are FM-FM-FM orderly, the photocurrent is nearly zero and can be neglected. Analysis show that the first two spin magnetic structures own the spatial inversion antisymmetric spin density which is the origin of stable pure spin currents, while the FM-FM-FM structure owns Cs symmetric spin density, leading to the nearly zero photocurrent. Our findings provide a scheme for obtaining pure spin currents by changing the spin states of the graphene nanoribbons via magnetic field modulation, which is of great importance for the design of spintronic devices.
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Hepatic fibrosis is an early stage of liver cirrhosis, and there are no better non-invasive and convenient methods for the detection and evaluation of the disease. Despite the good progress made with the liver stiffness map (LSM) based on magnetic resonance elastography (MRE), there are still some limitations that need to be overcome, including manual focus determination, manual selection of regions of interest (ROIs), and discontinuous LSM data without structural information, which makes it impossible to evaluate the liver as a whole. In this study, we propose a novel three-dimensional (3D) digital model for the early diagnosis of hepatic fibrosis based on MRE. MRE is a non-invasive imaging technique that employs magnetic resonance imaging (MRI) to measure the liver stiffness at the scanning site through human-computer interaction. Studies have indicated a significant positive correlation between the LSM obtained through MRE and the degree of hepatic fibrosis. However, for clinical purposes, a comprehensive and precise quantification of the degree of hepatic fibrosis is necessary. To address this, the concept of Liver Stiffness Distribution (LSD) was proposed in this study, which refers to the 3D stiffness volume of each liver voxel obtained by the alignment of 3D liver tissue images and MRE indicators. This provides a more effective clinical tool for the diagnosis and treatment of hepatic fibrosis.
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Diagnóstico por Imagen de Elasticidad , Humanos , Cirrosis Hepática/diagnóstico por imagen , Diagnóstico PrecozRESUMEN
In this work, we study the photogalvanic effect of a zigzag graphene nanoribbon junction with a centro-symmetrical structure which consists of 8 zigzag chains by density functional calculations. Specifically, we focus on the cases where the irradiated region is just part of the central region and located at different positions, with an aim to see how the spin dependent photocurrents will change and whether pure spin current can be obtained. It is found that the magnitude of the spin-dependent photocurrents increases with a gradual increase of the irradiated region and pure spin current is achieved when and only when the entire central region is irradiated. In addition, we studied the additive effect in this device to see that if we divide the central region into two parts, whether the sum of the spin current generated by irradiating the two parts individually is equal to that produced when the entire central region is irradiated. It is found that the sum of the spin currents produced by irradiating the two parts individually is smaller than that obtained by irradiating the whole central region, which means that the rule of "1 + 2 = 3" does not hold and the coupling effect between the two parts is important in photocurrent generation.
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BACKGROUND: In a previous study, we found that traditional Chinese medicine (TCM) alleviated the clinical symptoms and improved the quality of life (QoL) in patients with hepatocellular carcinoma (HCC). OBJECTIVES: A cohort was continuously followed up to determine the impact of the TCM adjuvant therapies on the prognosis of HCC after conventional treatments. METHODS: We did a retrospective monocentric cohort study including 175 eligible patients. The participants who received TCM adjuvant therapies were termed as TCM group. For the purpose of stratification analysis, the patients who received TCM adjuvant therapies over 3 months per year were further classified into the high frequency group, while the rest of the TCM users were classified into the low frequency group. Non-users were recorded as the control group. The primary outcome was overall survival (OS) and the secondary outcome was the mean progression-free survival (mPFS) primarily introduced in this study, referring to the time from initial diagnosis to the latest progression over the number of disease progressions. Analyses used Cox proportional hazards and Kaplan-Meier (K-M) methods, adjusted for stratification factors. RESULTS: Until June 30, 2021, 56 patients survived, 21 patients were lost to follow-up, and 98 patients died from the disease. Each disease progression of every individual was recorded, and most of the PFS was within 1 year. The baseline data of the allocated groups were balanced, the result revealed that TCM adjuvant therapies might have little influence on OS (P = .129). However, the 1, 3, and 5-year progression-free survival rates of the patients in TCM and control group were 68.75%, 37.50%; 25.00%, 8.33% and 8.33%, 2.08%, respectively, indicating TCM use significantly extended the mPFS, and decreased the risk of disease progression by a factor of 0.676 (P = .006). In the patients with BCLC stage B HCC, compared with controls, a 37-month median OS advantage in the high frequency group was noted (P = .045); and the high frequency of TCM use significantly suppressed disease progression (P = .001). CONCLUSIONS: The present study revealed that TCM adjuvant therapies could postpone disease progression in HCC. Furthermore, using TCM over 3 months per year might extend OS in patients with intermediate HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Medicina Tradicional China , Estudios Retrospectivos , Calidad de Vida , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Estudios de Cohortes , Pronóstico , Progresión de la EnfermedadRESUMEN
Environmental pollution caused by tetracycline antibiotics (TCs) is a major concern for public health worldwide. Trace detection and reliable discrimination of tetracycline and its analogs are consequently essential to determine the distribution characteristics of various tetracycline family members. Here, a dual-response sensor was constructed by integrating the fluorescence emission of fluorescein isothiocyanate (FITC) doped SiO2 and Eu3+. A portable Lab-on-Paper device is further fabricated through probe immobilization, which allows convenient visual detection of tetracycline using a smartphone. In addition, for the coexistence of multiple tetracycline analogs, dimensionality reduction via principal component analysis is applied to the spectra, realizing accurate differentiation of the four most widely used tetracycline analogs (tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC), and doxycycline (DOX)). The dual-response nanoplatform enabled a wide-gamut color variation crossing from green to red, with limit of detection (LOD) of 2.9 nM and 89.8 nM for spectrometer- and paper-based sensors, respectively. Analytical performance was examined in multiple real samples, including food, environmental, and biological settings, confirming robust environmental adaptability and resistance. Compared to previous TC sensors, this method has several notable improvements, including improved ecological safety, accessibility, reproducibility, practicality, and anti-cross-interference capacity. These results highlight the potential of the proposed "two birds with one stone" strategy, providing an integrated methodology for synchronous quantitative detection and derivative identification toward environmental contaminants.
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Clortetraciclina , Dióxido de Silicio , Reproducibilidad de los Resultados , Antibacterianos/análisis , Tetraciclina/análisis , Colorantes Fluorescentes , Espectrometría de Fluorescencia/métodosRESUMEN
The greatest barrier to the further development and clinical application of tumor image-guided photodynamic therapy (PDT), is the inconsistency between the fluorescence intensity and singlet oxygen generation yield of the photosensitizer under light excitation. Herein, a novel donor-acceptor (D-A) system is designed from the point of molecular selection by wrapping a classical porphyrin molecule (5,10,15,20-tetraphenylphorphyrin, H2 TPP) as an acceptor into conjugated polymer (Poly[N,N'-bis(4-butylpheny)-N,N'-bis(phenyl)benzidine], ADS254BE) as a donor through fluorescence resonance energy transfer (FRET) mechanism, which exhibits bright red emission centered at 650 nm (quantum yield, 0.12), relatively large Stoke shift of 276 nm, enhanced singlet oxygen generation rate of 0.73, and excellent photostability. The investigations on distribution and killing effect of nanomaterials in cancer cells reveal that ADS254BE/H2 TPP NPs can accumulate in the cytoplasm for imaging while simultaneously producing a large amount of singlet oxygen to remarkably kill cancer cells, which can be used for real-time image-guided PDT. In the xenograft tumor model, real-time imaging and long-term tracing in tumor tissue with ADS254BE/H2 TPP NPs disclose that the growth of lung cancer in mice can be effectively inhibited during in situ imaging. From the standpoint of molecular engineering design, this work provides a feasible strategy for novel D-A systems to improve the development of image-guided PDT.
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Neoplasias , Fotoquimioterapia , Humanos , Animales , Ratones , Fotoquimioterapia/métodos , Oxígeno Singlete , Indicadores y Reactivos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias/terapia , Modelos Animales de EnfermedadRESUMEN
We propose nano-constriction engineering of armchair graphene nanoribbons (AGNRs) to construct photoelectric nanodevices aiming to generate pure spin currents through the photogalvanic effect (PGE) using first-principles calculations. Two devices with different symmetries were designed, one by introducing only one isosceles zigzag triangle defect on the lower edge of the central region ('D1') and the other by two symmetrically distributed isosceles zigzag triangle defects on the two edges ('D2'). The results show that pure spin current without accompanying charge current can be generated in both junctions, but with a big difference that pure spin current can be generated only at special polarization angles θ = 0°, 90° and 180° in device D1, while it can be generated at any polarization angle in D2. The robustness in D2 is attributed to the spatial inversion symmetry in geometry and the inversion antisymmetry of spin density. These findings suggest that local magnetism engineering provides a reliable method for generating robust pure spin currents with the PGE in nonmagnetic systems, especially opening up new possibilities for the application of AGNRs in spintronics.
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As a burgeoning non-invasive indicator for reproducible cancer diagnosis, tumor-related biomarkers have a wide range of applications in early cancer screening, efficacy monitoring, and prognosis predicting. Accurate and efficient biomarker determination, therefore, is of great importance to prevent cancer progression at an early stage, thus reducing the disease burden on the entire population, and facilitating advanced therapies for cancer. During the last few years, various DNA structure-based fluorescent probes have established a versatile platform for biological measurements, due to their inherent biocompatibility, excellent capacity to recognize nucleic and non-nucleic acid targets, obvious accessibility to synthesis as well as chemical modification, and the ease of interfacing with signal amplification protocols. After decades of research, DNA fluorescent probe technology for detecting tumor-related mRNAs has gradually grown to maturity, especially the advent of fluorescent nanoprobes has taken the process to a new level. Here, a systematic introduction to recent trends and advances focusing on various nanomaterials-related DNA fluorescent probes and the physicochemical properties of various involved nanomaterials (such as AuNP, GO, MnO2, SiO2, AuNR, etc.) are also presented in detail. Further, the strengths and weaknesses of existing probes were described and their progress in the detection of tumor-related mRNAs was illustrated. Also, the salient challenges were discussed later, with a few potential solutions.
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Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world. Although the current treatment methods for HCC are gradually increasing, its efficacy still cannot meet the medical needs of patients with liver cancer, and new and effective treatment strategies are urgently needed. The total flavonoids of Oldenlandia diffusa (FOD) are the main active components in Oldenlandia diffusa, which have anti-inflammatory, antioxidant and anti-tumor effects, but their mechanism of action in liver cancer is unclear. In this study, we examined the effect of FOD on HCC. Using both in vitro and in vivo models, we confirmed that FOD inhibited HCC proliferation and induced apoptosis and autophagy. Mechanistic studies have shown that FOD induces apoptosis and activates autophagy in HCC cells by inducing endoplasmic reticulum stress (ER stress) and activating the PERK-eIF2α-ATF4 signaling pathway. Taken together, our results suggest that FOD is a potential anticancer drug targeting ER stress for the treatment of HCC.
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Swainsonine (SW) is a substance with both animal neurotoxicity and natural anticancer activity produced by the metabolism of endophytic fungus Alternaria section Undifilum oxytropis of locoweed. This paper produced SW by fermentation of the endophytic fungus A. oxytropis of locoweed and obtained the optimal ultrasonic-assisted extraction process of SW by the response surface methodology. Meanwhile, four mutant strains with significant and stable SW-producing properties were screened out after the mutagenesis of A. oxytropis by heavy-ion irradiation. Of these, three were high-yielding stains and one was a low-yielding strain. In addition, through the analysis of metabolomics studies, it was speculated that the different SW production performance of the mutant might be related to the biosynthesis and utilization of L-lysine, L-2-aminoadipate-6-semialdehyde, etc. These results laid the foundation for the expansion of SW production, artificial construction of low-toxic locoweed and clarification of the SW biosynthesis pathway in A. oxytropis.
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As the ornamental plants and traditional medicines, Rhododendron przewalskii, R. anthopogonoides, R. thymifolium, and R. capitatum are widely distributed in western China. In this paper, the essential oils from these four species were extracted by supercritical extraction and the components were analyzed using headspace solid phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS), the antibacterial, acaricidal and anti-inflammatory activities were investigated. Results showed that R. thymifolium (RTEO) contained the highest yield of 0.99% with 246 compounds, followed by R. capitatum (RCEO, 0.81%) with 290 chemicals, R. anthopogonoides (RAEO, 0.57%) with 302 compounds and R. przewalskii (RPEO, 0.30%) with 294 components. They also exhibited the safety at given doses and have the anti-inflammatory in vitro and in vivo tests via inhibiting the cytokines productions, the acaricidal and antibacterial activities also were found. 4-Hydroxy-3-methylacetophenone from RPEO, α-pinene and ß-pinene from RAEO, ß-farnesene and germacrone from RTEO, and benzylacetone from RCEO, as main and active components, inhibited the NO content in RAW 264.7 cells induced by LPS. These results indicated that four essential oils have certain medicinal value and laid the foundation for the development of these species as raw materials for the pharmaceutical and perfume industries.
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Sarcoptic and psoroptic mange threaten the health of both animals and humans worldwide and result in enormous socioeconomic loss. Discovery of new lead compounds is a major goal for controlling this kind of disease. However, the methodological shortcomings of acaricidal tests against Sarcoptes and Psoroptes mites for screening active compounds in vitro troubles colleagues and should be given more attention.
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Acaricidas , Productos Biológicos , Infestaciones por Ácaros , Ácaros , Psoroptidae , Sarcoptidae , Escabiosis , Acaricidas/farmacología , Animales , Productos Biológicos/farmacología , Humanos , Infestaciones por Ácaros/tratamiento farmacológico , Infestaciones por Ácaros/veterinaria , Sarcoptes scabiei , Escabiosis/diagnóstico , Escabiosis/tratamiento farmacológico , Escabiosis/veterinariaRESUMEN
Background: Previous observational studies and meta-analysis suggested a possible association between metformin use and reduced mortality in women with ovarian cancer (OC). However, clinical factors that may influence the relationship remain poorly evaluated. We performed an updated meta-analysis to systematically evaluate the above association and to observe the potential influences of study characteristics on the association. Methods: Relevant studies reporting the association between metformin use and mortality in women with OC in the multivariate adjusted model were identified by search of electronic databases that included PubMed, Embase, and Web of Science. The random-effects model was adopted to combine the results. Results: Nine studies including 10030 women with OC were included. Overall, metformin use was independently associated with reduced overall mortality (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55-0.93, P=0.01; I 2 = 62%). Consistent results were observed for studies comparing metformin users with nondiabetic women and studies comparing metformin users with diabetic women who did not use metformin (P for subgroup analysis = 0.70). Further subgroup analyses showed consistent results in studies with metformin use before or after the diagnosis of OC, with or without adjustment of body mass index (BMI) and with or without adjustment of concurrent medications (P for subgroup analyses all >0.10). Conclusion: Metformin use is associated with reduced mortality in women with OC, which may be independent of the diabetic status of the controls, timing of metformin use, or adjustment of BMI and concurrent medications. Clinical trials are needed to validate the potential benefits of metformin on survival of OC.