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Gut microbiota plays a vital role in host metabolism; however, the influence of gut microbes on polyamine metabolism is unknown. Here, we found germ-free models possess elevated polyamine levels in the colon. Mechanistically, intestinal Lactobacillus murinus-derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition, Lactobacillus murinus delays recovery of dextran sodium sulfate-induced colitis by reducing polyamine levels in mice. Notably, a decline in the abundance of small RNAs was observed in the colon of mice with colorectal cancer (CRC) and human CRC specimens, accompanied by elevated polyamine levels. Collectively, our study identifies a specific underlying mechanism used by intestinal microbiota to modulate host polyamine metabolism, which provides potential intervention for the treatment of polyamine-associated diseases.
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Colitis , Microbioma Gastrointestinal , Lactobacillus , Poliaminas , Animales , Poliaminas/metabolismo , Ratones , Lactobacillus/metabolismo , Lactobacillus/genética , Humanos , Porcinos , Colitis/metabolismo , Colitis/microbiología , Colitis/inducido químicamente , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/microbiología , Sulfato de Dextran , Colon/metabolismo , Colon/microbiología , Vesículas Extracelulares/metabolismoRESUMEN
BACKGROUND: Adverse pregnancy outcomes have reached epidemic proportions in recent years with serious health ramifications, especially for diverse cancers risk. Therefore, we carried out an umbrella review to systematically evaluate the validity and strength of the data and the extent of potential biases of the established association between adverse pregnancy outcomes and cancers risk in both mother and offspring. METHODS: PubMed, Embase, and Web of Science databases were searched from inception until 18 January 2024. Meta-analyses of observational studies investigating the relationship between adverse pregnancy outcomes and multiple cancers risk in both mother and offspring were included. Evidence certainty was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. The protocol for this umbrella review was prospectively registered in PROSPERO (CRD42023470544). RESULTS: The search identified 129 meta-analyses of observational studies and 42 types of cancer. Moderate certainty of evidence, exhibiting statistical significance, has been observed linking per kilogram increase in birth weight to a heightened risk of breast cancer (OR = 1.07, 95% CI = 1.02-1.12), prostate cancer (OR = 1.02, 95% CI = 1.00-1.05), leukemia (OR = 1.18, 95% CI = 1.13-1.23), and acute lymphoblastic leukemia in offspring (OR = 1.18, 95% CI = 1.12-1.23); rubella infection during pregnancy to an increased risk of leukemia in offspring (OR = 2.79, 95% CI = 1.16-6.71); and a linear dose-response association between an increase in the proportion of optimal birth weight and an elevated risk of acute lymphoblastic leukemia in offspring (OR = 1.16, 95% CI = 1.09-1.24), respectively. CONCLUSIONS: Although some adverse pregnancy outcomes have clinically promising associations with risk of several cancers in both mother and offspring, it is essential to conduct additional research to solidify the evidence, evaluate causality, and ascertain clinical utility.
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Neoplasias , Resultado del Embarazo , Femenino , Humanos , Embarazo , Metaanálisis como Asunto , Neoplasias/epidemiología , Estudios Observacionales como Asunto , Complicaciones del Embarazo/epidemiología , Factores de Riesgo , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: The aim of this study is to analyze the trend of acute onset of chronic cor pulmonale at Chenggong Hospital of Kunming Yan'an Hospital between January 2018 and December 2022.Additionally, the study will compare the application of the ARIMA model and Holt-Winters model in predicting the number of chronic cor pulmonale cases. METHODS: The data on chronic cor pulmonale cases from 2018 to 2022 were collected from the electronic medical records system of Chenggong Hospital of Kunming Yan'an Hospital. The ARIMA and Holt-Winters models were constructed using monthly case numbers from January 2018 to December 2022 as training data. The performance of the model was tested using the monthly number of cases from January 2023 to December 2023 as the test set. RESULTS: The number of acute onset of chronic cor pulmonale in Chenggong Hospital of Kunming Yan'an Hospital exhibited a downward trend overall from 2018 to 2022. There were more cases in winter and spring, with peaks observed in November to December and January of the following year. The optimal ARIMA model was determined to be ARIMA (0,1,1) (0,1,1)12, while for the Holt-Winters model, the optimal choice was the Holt-Winters multiplicative model. It was found that the Holt-Winters multiplicative model yielded the lowest error. CONCLUSION: The Holt-Winters multiplicative model predicts better accuracy. The diagnosis of acute onset of chronic cor pulmonale is related to many risk factors, therefore, when using temporal models to fit and predict the data, we must consider such factors' influence and try to incorporate them into the models.
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Modelos Estadísticos , Enfermedad Cardiopulmonar , Humanos , Enfermedad Cardiopulmonar/epidemiología , Enfermedad Cardiopulmonar/diagnóstico , Enfermedad Crónica , Estaciones del Año , China/epidemiología , Masculino , Femenino , Enfermedad Aguda , Registros Electrónicos de Salud/estadística & datos numéricos , Predicción/métodos , Persona de Mediana EdadRESUMEN
Chirality is ubiquitous in nature, and closely related to biological phenomena. Nature-originated nanomaterials such as cellulose nanocrystals (CNCs) are able to self-assemble into hierarchical chiral nematic CNC films and impart handedness to nano and micro scale. However, the effects of the chiral nematic surfaces on cell adhesion are still unknown. Herein, this work presents evidence that the left-handed self-assembled chiral nematic CNC films (L-CNC) significantly improve the adhesion of L929 fibroblasts compared to randomly arranged isotropic CNC films (I-CNC). The fluidic force microscopy-based single-cell force spectroscopy is introduced to assess the cell adhesion forces on the substrates of L-CNC and I-CNC, respectively. With this method, a maximum adhesion force of 133.2 nN is quantified for mature L929 fibroblasts after culturing for 24 h on L-CNC, whereas the L929 fibroblasts exert a maximum adhesion force of 78.4 nN on I-CNC under the same condition. Moreover, the instant SCFS reveals that the integrin pathways are involved in sensing the chirality of substrate surfaces. Overall, this work offers a starting point for the regulation of cell adhesion via the self-assembled nano and micro architecture of chiral nematic CNC films, with potential practical applications in tissue engineering and regenerative medicine.
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Although significant progress has been made in developing preclinical models for metabolic dysfunction-associated steatotic liver disease (MASLD), few have encapsulated the essential biological and clinical outcome elements reflective of the human condition. We conducted a comprehensive literature review of English-language original research articles published from 1990 to 2023, sourced from PubMed, Embase, and Web of Science, aiming to collate studies that provided a comparative analysis of physiological, metabolic, and hepatic histological characteristics between MASLD models and control groups. The establishment of a robust metabolic dysfunction-associated steatotic liver rodent model hinges on various factors, including animal species and strains, sex, induction agents and methodologies, and the duration of induction. Through this review, we aim to guide researchers in selecting suitable induction methods and animal species for constructing preclinical models aligned with their specific research objectives and laboratory conditions. Future studies should strive to develop simple, reliable, and reproducible models, considering the model's sensitivity to factors such as light-dark cycles, housing conditions, and environmental temperature. Additionally, the potential of diverse in vitro models, including 3D models and liver organ technology, warrants further exploration as valuable tools for unraveling the cellular mechanisms underlying fatty liver disease.
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Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.
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OBJECTIVE: This study aimed to evaluate the differences in the accuracy of immediate intraoral, immediate extraoral, and delayed dental implant placement with surgical guides (static computer-aided implant surgery) in patients treated with mandibular reconstruction. METHODS: This was a retrospective study. The patients were divided into three groups: immediate intraoral placement (IIO), immediate extraoral placement (IEO), and delayed placement (DEL). Four variables were used to compare the planned and actual implant positions: angular deviation, three-dimensional (3D) deviation at the entry point of the implant, 3D deviation at the apical point of the implant, and depth deviation. RESULTS: The angular deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. The 3D deviation at the entry point was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .01) groups. The 3D deviation at the apical point was significantly higher in the IIO group than in the IEO (p < .01) and DEL (p < .01) groups. The depth deviation was significantly higher in the IIO group than in the IEO (p < .05) and DEL (p < .05) groups. There was no statistical difference between the IEO and DEL group in angular and 3D deviation. CONCLUSION: With surgical guides, among the different approaches for implant placement, delayed implant placement remains the most accurate approach for patients treated with mandibular reconstruction.
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Implantes Dentales , Reconstrucción Mandibular , Cirugía Asistida por Computador , Humanos , Implantación Dental Endoósea/métodos , Estudios Retrospectivos , Cirugía Asistida por Computador/métodos , Diseño Asistido por Computadora , Imagenología Tridimensional , Tomografía Computarizada de Haz CónicoRESUMEN
OBJECTIVE: The ultrasonic diagnosis of cervical and facial cystic masses, as well as cases of missed diagnosis and misdiagnosis, was examined, to improve the diagnosis of branchial cleft anomalies. METHODS: A retrospective analysis was conducted on 17 patients with branchial cleft cyst anomalies, including 11 males and 6 females, aged 12-53 years, with an average age of 33 ± 2 years, were unilateral single. All patients who underwent an ultrasound examination and image storage for retrospective analysis, and both longitudinal and transverse sections were scanned to observe the shape, size, boundary, peripheral relationship, and blood flow signal of the masses. All cases were examined with an enhanced CT scan, and pathological reports were generated. RESULTS: Among the 17 cases of branchial cleft anomalies, 15 cases were branchial cleft cysts, while one case involved fistula formation and one case involved sinus tract formation. Based on the type of branchial cleft, the first, second, and third cysts were classified in 4, 12, and 1 case, respectively. The sensitivity rate and specificity of ultrasonic diagnosis were 14/17 (82.4%) and 4/6 (66.7%), respectively. Ultrasonic characteristic analysis for the masses can be found in simple cystic masses or hypoechoic masses, most of them are of a regular shape and have a distinct boundary, and almost no blood flow signal. All patients who were misdiagnosed exhibited blood flow signals, including 1 patient with an abundant blood flow signal, 1 patient suspected of having ectopic thyroid with an abnormal function due to the rat-tail sign, 2 patients misdiagnosed as local inflammatory focus, and 1 patient misdiagnosed with tuberculous lymphadenitis. CONCLUSION: Ultrasound has a detection rate of up to 100% for cervical and facial masses, providing a fundamental determination of lesion characteristics and specific guidance for preoperative diagnosis. If the blood flow signals can be identified and carefully considered their peripheral relationship, the diagnostic rate can be improved.
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Branquioma , Fístula , Neoplasias de Cabeza y Cuello , Masculino , Femenino , Humanos , Animales , Ratas , Adulto , Branquioma/diagnóstico por imagen , Branquioma/cirugía , Estudios Retrospectivos , Región Branquial/diagnóstico por imagen , Región Branquial/cirugía , Región Branquial/anomalías , Neoplasias de Cabeza y Cuello/diagnóstico por imagen , Neoplasias de Cabeza y Cuello/cirugía , Fístula/cirugía , UltrasonografíaRESUMEN
Aero engines are the key power source for aerospace vehicles. Cermet turbine blades are the guarantee for the new-generation fighters to improve aero-engine overall performance. X-ray non-destructive reconstruction can obtain the internal structure and morphology of cermet turbine blades. However, the beam hardening effect causes artifacts in objects and affects the reconstruction quality, which is an issue that needs to be solved urgently. This study proposes a hardening-correction framework for industrial computed tomography (ICT) images based on iterative linear fitting. First, an iterative binarization was performed to improve the penetration length accuracy of the forward projection. Then, the proposed linear fitting technology combined with the Hermite function model is derived and analyzed to obtain suitable parameters of blade data. Finally, the fitting curves of the blade data, using the proposed method and the traditional polynomial fitting method, were analyzed and compared and were used to correct the engine turbine blade projection data to reconstruct different groups of tomographic images. Different groups of tomographic images were analyzed using three quantitative image quality evaluation indicators. The results show that the root-mean-square error (RMSE) of the tomographic image obtained by the proposed framework is 0.0133, which is lower than that of the compared method. The peak signal-to-noise ratio (PSNR) is 37.7050 dB and the feature structural similarity (FSIM) is 0.9881, which are both higher than that of the compared method. The proposed method improves the hardening-artifact-correction capability and can obtain higher-quality images, which provides new ideas for the development of imaging and detection of new-generation aero-engine turbine blades.
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Deep fertilization strategy has been proven to be an important fertilizer management method for improving fertilizer utilization efficiency and crop yield. However, the relationship between soil chemical and biochemical characteristics and crop productivity under different fertilization depth patterns still needs comprehensive evaluation. Field tests on spring maize were therefore carried out in the Loess Plateau of China for two successive growing seasons from 2019 to 2020. Four distinct fertilization depths of 5 cm, 15 cm, 25 cm, and 35 cm were used to systematically investigate the effects of fertilization depth on soil physicochemical parameters, enzyme activity, and biochemical properties. The findings demonstrated that although adjusting fertilization depths (D15, D25) did not significantly affect the soil organic carbon content, they did significantly improve the soil chemical and biochemical characteristics in the root zone (10-30 cm), with D25 having a greater influence than D15. Compared with D5, the total nitrogen (TN), total phosphorus (TP), available nitrogen (AN), Olsen-P, dissolved organic carbon, and nitrogen (DOC and DON) in the root zone of D25 significantly increased by 12.02%, 7.83%, 22.21%, 9.56%, 22.29%, and 26.26%, respectively. Similarly, the urease, invertase, phosphatase, and catalase in the root zone of D25 significantly increased by 9.56%, 13.20%, 11.52%, and 18.05%, while microbial biomass carbon, nitrogen, and phosphorus (MBC, MBN, and MBP) significantly increased by 18.91%, 32.01% and 26.50%, respectively, compared to D5. By optimizing the depth of fertilization, the distribution ratio of Ca2-P and Ca8-P in the inorganic phosphorus components of the root zone can also be increased. Therefore, optimizing fertilization depth helps to improve soil chemical and biochemical characteristics and increase crop yield. The results of this study will deepen our understanding of how fertilization depth influence soil properties and crop responses.
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Agricultura , Suelo , Suelo/química , Agricultura/métodos , Zea mays , Fertilizantes/análisis , Estaciones del Año , Carbono/análisis , Nitrógeno/análisis , China , Fósforo/análisis , FertilizaciónRESUMEN
This study employed knowledge graph technology to analyze the research status and hot spots of Realgar and provide guidance for clinical application and further research of this drug. The research articles both in English and Chinese involving Realgar were retrieved from five databases including CNKI, Wanfang, VIP, SinoMed, and Web of Science. And NoteExpress, a literature management software was used to screen literature. CiteSpace was utilized for visualized analysis and presentations of the authors, institutions, and keywords. 2 879 articles in Chinese and 194 articles in English were included. China Journal of Chinese Materia Medica and Journal of Ethnopharmacology were the top Chinese and English journals in terms of publication volume. Realgar is widely used in the treatment of skin diseases, blood diseases, and cancer. JIANG Hong was the author who have published more articles in Chinese and English working with teams. School of Public Health of China Medical University and China Academy of Chinese Medical Sciences published the most articles in Chinese and English. The research on Realgar mainly focuses on clinical application, mechanism of action, reduction of toxicity, and enhancement of efficacy. The authors and institutions of Realgar research are mainly concentrated in China. The study on the mechanism of treating hematological diseases and cancer with Realgar, as well as the research on its effects of reducing toxicity and enhancing efficacy, are the current research hotspots. The mechanism of "same treatment for different diseases" in Realgar needs to be further explored. It is urgent to carry out interdisciplinary research on Realgar. This study can provide a refe-rence for the clinical application of Realgar and provide ideas for further research on Realgar.
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Arsenicales , Sulfuros , Humanos , Arsenicales/química , China , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Investigación BiomédicaRESUMEN
This article explored the mechanism by which ginsenoside Re reduces hypoxia/reoxygenation(H/R) injury in H9c2 cells by regulating mitochondrial biogenesis through nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/peroxisome prolife-rator-activated receptor gamma coactivator-1α(PGC-1α) pathway. In this study, H9c2 cells were cultured in hypoxia for 4 hours and then reoxygenated for 2 hours to construct a cardiomyocyte H/R injury model. After ginsenoside Re pre-administration intervention, cell activity, superoxide dismutase(SOD) activity, malondialdehyde(MDA) content, intracellular reactive oxygen species(Cyto-ROS), and intramitochondrial reactive oxygen species(Mito-ROS) levels were detected to evaluate the protective effect of ginsenoside Re on H/R injury of H9c2 cells by resisting oxidative stress. Secondly, fluorescent probes were used to detect changes in mitochondrial membrane potential(ΔΨ_m) and mitochondrial membrane permeability open pore(mPTP), and immunofluorescence was used to detect the expression level of TOM20 to study the protective effect of ginsenoside Re on mitochondria. Western blot was further used to detect the protein expression levels of caspase-3, cleaved caspase-3, Cyto C, Nrf2, HO-1, and PGC-1α to explore the specific mechanism by which ginsenoside Re protected mitochondria against oxidative stress and reduced H/R injury. Compared with the model group, ginse-noside Re effectively reduced the H/R injury oxidative stress response of H9c2 cells, increased SOD activity, reduced MDA content, and decreased Cyto-ROS and Mito-ROS levels in cells. Ginsenoside Re showed a good protective effect on mitochondria by increasing ΔΨ_m, reducing mPTP, and increasing TOM20 expression. Further studies showed that ginsenoside Re promoted the expression of Nrf2, HO-1, and PGC-1α proteins, and reduced the activation of the apoptosis-related regulatory factor caspase-3 to cleaved caspase-3 and the expression of Cyto C protein. In summary, ginsenoside Re can significantly reduce I/R injury in H9c2 cells. The specific mechanism is related to the promotion of mitochondrial biogenesis through the Nrf2/HO-1/PGC-1α pathway, thereby increasing the number of mitochondria, improving mitochondrial function, enhancing the ability of cells to resist oxidative stress, and alleviating cell apoptosis.
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Ginsenósidos , Factor 2 Relacionado con NF-E2 , Biogénesis de Organelos , Humanos , Especies Reactivas de Oxígeno/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Caspasa 3/metabolismo , Transducción de Señal , Estrés Oxidativo , Hipoxia , Miocitos Cardíacos , Apoptosis , Superóxido Dismutasa/metabolismoRESUMEN
This study explored the specific mechanism by which tetrahydropalmatine(THP) inhibited mitophagy through the UNC-51-like kinase 1(ULK1)/FUN14 domain containing 1(FUNDC1) pathway to reduce hypoxia/reoxygenation(H/R) injury in H9c2 cells. This study used H9c2 cells as the research object to construct a cardiomyocyte H/R injury model. First, a cell viability detection kit was used to detect cell viability, and a micro-method was used to detect lactate dehydrogenase(LDH) leakage to evaluate the protective effect of THP on H/R injury of H9c2 cells. In order to evaluate the protective effect of THP on mitochondria, the chemical fluorescence method was used to detect intracellular reactive oxygen species, intramitochondrial reactive oxygen species, mitochondrial membrane potential, and autophagosomes, and the luciferin method was used to detect intracellular adenosine 5'-triphosphate(ATP) content. Western blot was further used to detect the ratio of microtubule-associated protein 1 light chain 3(LC3) membrane type(LC3-â ¡) and slurry type(LC3-â ) and activated cleaved caspase-3 expression level. In addition, ULK1 expression level and its phosphorylation degree at Ser555 site, as well as the FUNDC1 expression level and its phosphorylation degree of Ser17 site were detected to explore its specific mechanism. The results showed that THP effectively reduced mitochondrial damage in H9c2 cells after H/R. THP protected mitochondria by reducing the level of reactive oxygen species in cells and mitochondria, increasing mitochondrial membrane potential, thereby increasing cellular ATP production, enhancing cellular activity, reducing cellular LDH leakage, and finally alleviating H/R damage in H9c2 cells. Further studies have found that THP could reduce the production of autophagosomes, reduce the LC3-â ¡/LC3-â ratio, and lower the expression of the apoptosis-related protein, namely cleaved caspase-3, indicating that THP could reduce apoptosis by inhibiting autophagy. In-depth studies have found that THP could inhibit the activation of the ULK1/FUNDC1 pathway of mitophagy and the occurrence of mitophagy by reducing the phosphorylation degree of ULK1 at Ser555 and FUNDC1 at Ser17. The application of ULK1 agonist BL-918 reversely verified the effect of THP on reducing the phosphorylation of ULK1 and FUNDC1. In summary, THP inhibited mitophagy through the ULK1/FUNDC1 pathway to reduce H/R injury in H9c2 cells.
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Alcaloides de Berberina , Hipoxia , Mitofagia , Fenilacetatos , Humanos , Mitofagia/fisiología , Caspasa 3 , Especies Reactivas de Oxígeno/metabolismo , Apoptosis , Adenosina Trifosfato/farmacología , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Péptidos y Proteínas de Señalización Intracelular , Proteínas de la Membrana/metabolismo , Proteínas MitocondrialesRESUMEN
BACKGROUND: Our study aimed to compare the short-term outcomes between robot-assisted segmentectomy (RAS) and video-assisted segmentectomy (VAS) for small pulmonary nodules. METHODS: The study included of 299 segmentectomies (132 RAS and 167 VAS procedures) for small pulmonary nodules between June 2018 and November 2021. The patients were divided into two groups: the RAS group and the VAS group. Propensity score-matching (PSM) analysis was performed to minimize bias. A logistic regression model was performed to identify the independent risk factors associated with complications. RESULTS: Before PSM, the following clinical variables were not balanced: age (P = 0.004), tumor size (P < 0.001), forced expiratory volume for 1 s (FEV1), and FEV1 percentage (P < 0.001). The patients with RAS had a shorter operative time (P = 0.014), less blood loss, a shorter postoperative hospital stay, less use of strong opioids, less drainage on postoperative day 1, and less postoperative total drainage, but more cost (all P < 0.001). Conversion to open surgery was performed for two patients in the VAS group but none in the RAS group. After PSM, 53 pairs were successfully matched. The data again suggested that the patients with RAS had less blood loss, a shorter postoperative hospital stay, and less use of strong opioids, but more cost (all P < 0.001). The operation time also was shorter in the RAS group, with a borderline statistically significant P value (0.053). CONCLUSIONS: In our study, RAS had better short-term outcomes than VAS, indicating a safer and more efficient technique than VAS.
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Nódulos Pulmonares Múltiples , Robótica , Humanos , Neumonectomía/métodos , Puntaje de Propensión , Mastectomía Segmentaria , Cirugía Torácica Asistida por Video/efectos adversos , Estudios RetrospectivosRESUMEN
In-depth understanding of the mechanisms underlying the adhesion of myocardial cells holds significant importance for the development of effective therapeutic biomaterials aimed at repairing damaged or pathological myocardial tissues. Herein, we present evidence that myocardial cells (H9C2) exhibit integrin-based mechanosensing during the initial stage of adhesion (within the first 2 h), enabling them to recognize and respond to variations in substrate stiffnesses. Moreover, the bioinformatics analysis of RNA transcriptome sequencing (RNA-seq) reveals that the gene expressions associated with initial stage focal adhesion (Ctgf, Cyr61, Amotl2, Prickle1, Serpine1, Akap12, Hbegf, and Nedd9) are up-regulated on substrates with elevated Young's modulus. The fluorescent immunostaining results also suggest that increased substrate stiffness enhances the expression of Y397-phosphorylated focal adhesion kinase (FAK Y397), talin, and vinculin and the assembly of F-actin in H9C2 cells, thereby facilitating the adhesion of myocardial cells on the substrate. Next, we utilize fluidic force microscopy (FluidFM)-based single-cell force spectroscopy (SCFS) to quantitatively evaluate the impact of substrate stiffness on the cell adhesion force and adhesion work, thus providing novel insights into the biomechanical regulation of initial cell adhesion. Our findings demonstrate that the maximum adhesion forces of myocardial cells exhibit a rise from 23.6 to 248.0 nN when exposed to substrates with different moduli. It is worth noting that once the αvß3 integrins are blocked, the disparities in the adhesion forces of myocardial cells on these substrates become negligible. These results exhibit remarkable sensitivity of myocardial cells to mechanical cues of the substrate, highlighting the role of αvß3 integrin as a biomechanical sensor for the regulation of cell adhesion. Overall, this work offers a prospective approach for the regulation of cell adhesion via integrin mechanosensing with potential practical applications in the areas of tissue engineering and regenerative medicine.
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Señales (Psicología) , Miocitos Cardíacos , Miocitos Cardíacos/metabolismo , Adhesión Celular/fisiología , Integrinas/metabolismo , Adhesiones Focales/metabolismoRESUMEN
OBJECTIVE: To investigate the impact of selective artery clamping (SAC) and main artery clamping (MAC) during robot-assisted partial nephrectomy (RAPN) on renal function and the influence of holographic three-dimensional (3D) reconstruction of renal segments on the selection between SAC and MAC. METHODS: This retrospective observational study included patients who underwent RAPN at First Hospital Affiliated to the Army Medical University between December 2016 and July 2022. According to the clamping methods, the patients were divided into the SAC group and the MAC group. The primary outcome was renal function. RESULTS: A total of 422 patients (194 in the SAC group and 228 in the MAC group) were included. The RAPN procedures were all completed successfully. The patients in SAC group had less glomerular filtration rate (GFR) decline in the affected kidney (8.6 ± 7.0 ml/min vs. 18.7 ± 10.9 ml/min, P < 0.001) and minor estimated glomerular filtration rate (eGFR) decrease (4.3 ± 10.5 ml/min vs. 12.6 ± 12.1 ml/min, P < 0.001) than those in MAC group. Among 37 patients with baseline renal insufficiency, the GFR decline of the affected kidney in the SAC subgroup was significantly lower than in the MAC subgroup (5.5 ± 6.5 ml/min vs. 14.3 ± 9.2 ml/min, P = 0.002). The proportion of patients who underwent 3D reconstruction was significant higher in the SAC group than in the MAC group. (65.46% vs. 28.07%, P < 0.001). CONCLUSION: The SAC technique during RAPN may serve as a protective measure for renal function, while the implementation of holographic 3D renal segment reconstruction technique may facilitate optimal selection of SAC.
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Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Robótica , Humanos , Arteria Renal/cirugía , Constricción , Neoplasias Renales/cirugía , Resultado del Tratamiento , Riñón/cirugía , Riñón/fisiología , Riñón/irrigación sanguínea , Nefrectomía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios RetrospectivosRESUMEN
PURPOSE: To investigate the efficacy, safety, and mid-term outcomes of percutaneous mechanical thrombectomy (PMT) for acute symptomatic iliofemoral deep venous thrombosis (DVT) patients with recent (within 4 weeks) aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: From January 2016 to February 2020, 11 acute symptomatic iliofemoral DVT patients with a recent history of aSAH were enrolled in this study. All patients had a history of aneurysm ligation or clipping previously, computed tomography (CT) scans revealed ventricular hemorrhage had been absorbed obviously and no residual aneurysm. The mean time of DVT onset after aSAH ictus was 19.2±4.5 days, and the mean Glasgow score was 6.8 ± 0.7 (range, 6-8). These patients underwent PMT with an 8 French Aspirex®S device (Straub Medical AG, Wangs, Switzerland), subsequent stenting was performed to relieve the underlying stenosis, followed by anticoagulation alone. The procedure-related complications were assessed after intervention. The follow-ups were conducted up to 1 year, the patency was evaluated via duplex ultrasonography, and the incidence of post-thrombotic syndrome (PTS) was evaluated using the Villalta scale. RESULTS: Grade III (>90%) clearance was achieved in all 11 patients. Stenting was performed in 7 patients (63.6%). There were no cerebral rebleeding events or other severe complications except 1 puncture site bleeding during treatment. A total of 90.9% (10 of 11) of patients were alive at the 12 month follow-up, and 7 patients achieved a good functional outcome. At the 1 year follow-up, there was 1 patient (10%) with mild PTS. The ultrasound showed that the patency of the iliofemoral veins was 100%, and femoral valvular incompetence was observed in 1 patient. CONCLUSION: Percutaneous mechanical thrombectomy seems to be a feasible and safe treatment for acute iliofemoral DVT in selected patients with recent aSAH, and it shows promising results in restoring patency and reducing the risk of PTS.
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Síndrome Postrombótico , Hemorragia Subaracnoidea , Trombosis de la Vena , Humanos , Terapia Trombolítica/efectos adversos , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/terapia , Hemorragia Subaracnoidea/complicaciones , Vena Femoral/diagnóstico por imagen , Resultado del Tratamiento , Factores de Tiempo , Vena Ilíaca/diagnóstico por imagen , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/terapia , Trombosis de la Vena/etiología , Trombectomía/efectos adversos , Síndrome Postrombótico/diagnóstico por imagen , Síndrome Postrombótico/etiología , Enfermedad Aguda , Estudios RetrospectivosRESUMEN
Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the most common malignancy of the female genital tract. MiR-1299 serves as a tumor suppressor, while KCNQ1OT1 acts as an oncogene in multiple malignancies. This research was designed to investigate the impacts of miR-1299 and KCNQ1OT1 on CESC progression. The downstream target of miR-1299 and the underlying regulatory mechanism of KCNQ1OT1 action on miR-1299 were explored. RT-qPCR was applied for RNA expression detection in CESC tissues and cells. RNA immunoprecipitation, RNA pulldown and luciferase reporter assays were applied to evaluate the binding between molecules in CESC cells. Cell Counting Kit-8 and colony formation assays were used for the measurement of CESC cell viability and proliferation. Western blotting was utilized to measure levels of apoptosis-related in CESC cells. MiR-1299 was downregulated in CESC tissues and presented a negative correlation with KCNQ1OT1 expression. KCNQ1OT1 was directly bound to miR-1299 to negatively modulate miR-1299 expression in CESC cells. The proliferative ability of CESC cells was suppressed by miR-1299 overexpression and was facilitated by KCNQ1OT1 overexpression. CESC cells apoptosis was promoted by miR-1299 mimics and inhibited by KCNQ1OT1 overexpression. In addition, in in vivo studies, miR-1299 overexpression rescued the effects of KCNQ1OT1 overexpression on CESC xenograft tumor growth. Finally, KCNQ1OT1 was bound to miR-1299 to upregulate PDPK1 expression in CESC cells. Collectively, miR-1299 was regulated by KCNQ1OT1 and inhibited CESC progression in vivo and in vitro, suggesting the tumor-suppressor role of miR-1299 for CESC.
Asunto(s)
Carcinoma de Células Escamosas , MicroARNs , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Femenino , Humanos , Proteínas Quinasas Dependientes de 3-Fosfoinosítido , Apoptosis/genética , Proliferación Celular/genética , MicroARNs/genética , Oncogenes , Neoplasias del Cuello Uterino/genética , ARN Largo no Codificante/genéticaRESUMEN
BACKGROUND: We compared the early and midterm (31, 3-63 months) outcomes of conservative treatment, bare stent treatment (BST), and bare stent-assisted coiling treatment (BSACT) to determine the most effective treatment for patients with symptomatic isolated superior mesenteric artery dissection (SISMAD). METHODS: Consecutive patients with SISMAD admitted to the study hospital between January 2016 and December 2021 were included in this retrospective study. Their demographic data, clinical findings, treatment options, early outcomes, and follow-up results were analyzed. RESULTS: A total of 121 patients were included in the study (23 with conservative treatment, 42 with BST, and 56 with BSACT). Symptoms were relieved in 91.3% of conservative patients, whereas all patients (100%) with BST or BSACT had symptom relief (P = 0.035). There was no significant difference in the length of hospital stay between the 2 endovascular treatments (P = 0.9051), but hospital stay was significantly shorter compared to conservative treatment (P < 0.0001). The cumulative rate of complete remodeling was 100% for BSACT versus 46.3% for BST (P < 0.0001) versus 42.9% for conservative patients (P < 0.0001). There were no significant differences between the last 2 groups (P = 0.3925). The prevalence of adverse events for abdominal pain recurrence and aneurysm formation was also significantly lower in the BSACT group at follow-up. CONCLUSIONS: BSACT for SISMAD has a preferable early outcome. The cumulative complete remodeling rate and the event-free survival rate are satisfactory at midterm follow-up. BSACT is an effective approach for SISMAD.
Asunto(s)
Tratamiento Conservador , Arteria Mesentérica Superior , Humanos , Arteria Mesentérica Superior/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Tratamiento Conservador/efectos adversos , StentsRESUMEN
Dynamic performance is one of the most important characteristics of a variable focus lens. However, there are few studies investigating the dynamic response of a membrane-based variable focus lens. In this paper, we present a mathematical model to describe spring-damping phenomena in theory. The first order natural frequencies with different scales were confirmed via finite element analysis. We also built a dynamic response experiment platform with changeable optical apertures, which was driven by a high-speed piezo stack actuator. A photodiode module was placed behind the lens to measure the variation of light luminance as the lens changed, and a laser displacement sensor was used to measure the deformation of the membrane. A series of data was collected with different optical apertures (20 mm, 30 mm, 50 mm) and different pre-stretching ratios (200%, 300%) under different driving frequencies (from 5 Hz to 25 Hz in every 5 Hz step). The experimental results were consistent with the mathematical model, which showed that the first order natural frequency increased as the aperture decreased or the membrane stiffness increased. This frequency-dependent characteristic of the variable focus lens provides a basis for further research on its dynamic performance.