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BACKGROUND: To define the incidence and independent predictive factors of intraoperative adverse events (IOAEs) after minimally invasive radical nephrectomy and thrombectomy (RNAT) and to determine the impact of intraoperative adverse events on oncological outcomes. PATIENTS AND METHODS: A total of 294 patients underwent minimally invasive RNAT from January 2010 to December 2023 in our center were included. IOAEs are defined as any deviation from the normal surgical procedure during the operation course. Multivariate logistic regression analysis was performed to identify the independent predictive factors of IOAEs. The Kaplan-Meier curves was used to compare overall survival and cancer-specific survival between patients with IOAEs or not. RESULTS: Seventy-four IOAEs occurred in 57 of 294 patients (19.4%) and the most frequent IOAEs were conversion to open surgery (42/74, 56.7%), followed by excessive hemorrhage (20/74, 27.0%). In multivariate logistic analysis, side (OR 0.0929; 95%Cl 0.0367-0.2160; p < 0.001), operation approach (OR 0.1762; 95%Cl 0.06828-0.4109; p < 0.001), and Mayo grade (OR 6.321; 95%Cl 3.846-11.13; p < 0.001) were independent predictive predictors of IOAEs during minimally invasive RNAT. IOAEs (OR 2.713; 95%Cl 1.242-5.897; p = 0.012) was an independent risk factor of the occurrence of postoperative complications. Between the patients with IOAEs or not, neither overall survival (OS) nor cancer-specific survival (CSS) showed statistical differences. Patients with postoperative complications show shorter OS and CSS. CONCLUSION: We found that the independent predictive factors of minimally invasive RNAT were side, operation approach and Mayo grade, and it is a risk factor of the occurrence of postoperative complications. In addition, the occurrence of IOAEs had no effect on long-term oncological outcomes.
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OBJECTIVE: To summarize the clinical characteristics of patients with renal angiomyolipoma (RAML) combined with inferior vena cava (IVC) tumor thrombus, and to explore the feasibility of partial nephrectomy and thrombectomy in this series of patients. METHODS: The clinical data of patients diagnosed with RAML combined with IVC tumor thrombus in the Department of Urology of the Peking University Third Hospital from April 2014 to March 2023 were retrospectively analyzed, and demographic and perioperative data of RAML patients with IVC tumor thrombus were recorded and collected from Electronic Medical Record System, including age, gender, surgical methods, and follow-up time, etc. The clinical characteristics between classic angiomyolipoma (CAML) patients with IVC tumor thrombus and epithelioid angiomyolipoma (EAML) patients with IVC tumor thrombus were compared to determine the clinical characteristics of these patients. RESULTS: A total of 11 patients were included in this study, including 7 patients with CAML with IVC tumor thrombus and 4 patients with EAML with IVC tumor thrombus. There were 9 females (9/11, 81.8%) and 2 males (2/11, 18.2%), with an average age of (44.0±17.1) years. 9 patients (9/11, 81.8%) experienced clinical symptoms, including local symptoms including abdominal pain, hematuria, abdominal masses, and systemic symptoms including weight loss and fever; 2 patients (2/11, 18.2%) with RAML and IVC tumor thrombus did not show clinical symptoms, which were discovered by physical examination. Among the 11 patients, 10 underwent radical nephrectomy with thrombectomy, of whom, 3 underwent open surgery (3/10, 30.0%), 2 underwent laparoscopic surgery (2/10, 20.0%), and 5 underwent robot-assisted laparoscopic surgery (5/10, 50.0%). In addition, 1 patient underwent open partial nephrectomy and thrombectomy. The patients with EAML combined with IVC tumor thrombus had a higher proportion of systemic clinical symptoms (100% vs. 0%, P=0.003), more intraoperative bleeding [400 (240, 3 050) mL vs. 50 (50, 300) mL, P =0.036], and a higher proportion of tumor necrosis (75% vs. 0%, P=0.024) compared to the patients with CAML combined with IVC tumor thrombus. However, there was no statistically significant difference in operation time [(415.8±201.2) min vs. (226.0±87.3) min, P=0.053] between the two groups. CONCLUSION: Compared with the patients with CAML and IVC tumor thrombus, the patients with EAML and IVC tumor thrombus had a higher rate of systemic symptoms and tumor necrosis. In addition, in the selected patients with CAML with IVC tumor thrombus, partial nephrectomy and tumor thrombectomy could be performed to better preserve renal function.
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Angiomiolipoma , Neoplasias Renais , Nefrectomia , Trombectomia , Veia Cava Inferior , Humanos , Angiomiolipoma/cirurgia , Angiomiolipoma/diagnóstico , Angiomiolipoma/patologia , Angiomiolipoma/complicações , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/diagnóstico , Feminino , Masculino , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Estudos Retrospectivos , Nefrectomia/métodos , Trombectomia/métodos , Adulto , Pessoa de Meia-Idade , Trombose Venosa/cirurgia , Trombose Venosa/etiologia , Laparoscopia/métodos , Trombose/cirurgia , Trombose/diagnósticoRESUMO
The aim of this study was to explore how the total flavonoids from Eucommia ulmoides leaves (EULs) regulate ischemia-induced nerve damage, as well as the protective effects mediated by oxidative stress. The cell survival rate was significantly improved compared to the ischemic group (p < 0.05) after treatment with the total flavonoids of EULs. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) decreased, while catalase (CAT) and glutathione (GSH) increased, indicating that the total flavonoids of EULs can significantly alleviate neurological damage caused by ischemic stroke by inhibiting oxidative stress (p < 0.01). The mRNA expression level of VEGF increased (p < 0.01), which was consistent with the protein expression results. Meanwhile, the protein expression of ERK and CCND1 increased (p < 0.01), suggesting that the total flavonoids of EULs could protect PC12 cells from ischemic injury via VEGF-related pathways. MCAO rat models indicated that the total flavonoids of EULs could reduce brain ischemia-reperfusion injury. In conclusion, this study demonstrates the potential mechanisms of the total flavonoids of EULs in treating ischemic stroke and their potential therapeutic effects in reducing ischemic injury, which provides useful information for ischemic stroke drug discovery.
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Eucommiaceae , Flavonoides , AVC Isquêmico , Estresse Oxidativo , Folhas de Planta , Animais , Ratos , Flavonoides/farmacologia , Eucommiaceae/química , Folhas de Planta/química , Células PC12 , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , Estresse Oxidativo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Masculino , Espécies Reativas de Oxigênio/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Sobrevivência Celular/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Ratos Sprague-Dawley , Malondialdeído/metabolismoRESUMO
Some wheat-based foods require different doses of oil to moderate quality of dough during processing and the influence mechanisms remain unclear. Therefore, the effect of rapeseed oil addition on physicochemical characteristics and fine structure of dough and underlying mechanism were elucidated by rheometer, scanning microscope and molecular spectroscopic method. Results showed that compared with native dough (without exogenous rapeseed oil), the addition of rapeseed oil changed the fine structure, improved extensibility, but reduced viscoelasticity of the dough. Moreover, high addition especially 20 wt% oil (based on wheat flour) significantly changed gelatinization and retrogradation behaviors of the dough, whilst disrupted gluten network and increased random coil content (32.1%) of dough except that decreased its α-helix (21.2%), ß-sheet (23.1%), disulfide bond (7.9 µmol/g) compared with native dough which were 16.3%, 29.2%, 33.1%, 11.0 µmol/g, respectively. Results in the study could provide a certain understanding for application of vegetable oils in wheat-based products.
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Chlorophylls and ß-carotene are fat-soluble phytochemicals in daily diets, while their bioaccessibility interaction remains unknown. Eight dietary chlorophylls and their derivatives (chlorophyll a, chlorophyll b, pheophytin a, pheophytin b, chlorophyllide a, chlorophyllide b, pheophorbide a, pheophorbide b) were combined with ß-carotene in six different oil matrices (corn oil, coconut oil, medium-chain triglycerides, peanut oil, olive oil and fish oil) and were subjected to in vitro digestion. Generally, chlorophylls significantly decreased ß-carotene bioaccessibility by competitive incorporation into micelles. Dephytylated chlorophylls had a greater inhibitory effect on the micellarization and bioaccessibility of ß-carotene compared to phytylated chlorophylls. In their co-digestion system, olive oil group exhibited the smallest particle size and biggest zeta potential in both digesta and micelles. For chlorophylls, the phytol group and their levels are key factors, which was also buttressed by the mice model where additional supplementation of pheophorbide a significantly hindered the accumulation of ß-carotene and retinoids compounds.
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Clorofila , beta Caroteno , Clorofila/química , Clorofila/metabolismo , beta Caroteno/química , beta Caroteno/metabolismo , Animais , Camundongos , Disponibilidade Biológica , Digestão , Humanos , Óleos de Plantas/química , Óleos de Plantas/metabolismo , Modelos Biológicos , MicelasRESUMO
This study investigated the ERK pathway of the peripheral nervous system and discovered a gender-specific pattern of ERK activation in the dorsal root ganglion of an acid-induced chronic widespread muscular pain model. We employed a twice acid-induced chronic musculoskeletal pain model in rats to evaluate mechanical pain behavior in both male and female groups. We further conducted protein analysis of dissected dorsal root ganglions from both genders. Both male and female rats exhibited a similar pain behavior trend, with females demonstrating a lower pain threshold. Protein analysis of the dorsal root ganglion (DRG) showed a significant increase in phosphorylated ERK after the second acid injection in all groups. However, phosphorylation of ERK was observed in the dorsal root ganglion, with higher levels in the male ipsilateral group compared to the female group. Moreover, there was a no difference between the left and right sides in males, whereas the significant difference was observed in females. In conclusions, the administration of acid injections induced painful behavior in rats, and concurrent with this, a significant upregulation of pERK was observed in the dorsal root ganglia, with a greater magnitude of increase in males than females, and in the contralateral side compared to the ipsilateral side. Our findings shed light on the peripheral mechanisms underlying chronic pain disorders and offer potential avenues for therapeutic intervention.
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MAP Quinases Reguladas por Sinal Extracelular , Fibromialgia , Gânglios Espinais , Ratos Sprague-Dawley , Caracteres Sexuais , Animais , Masculino , Feminino , Fibromialgia/metabolismo , Gânglios Espinais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Limiar da Dor , Modelos Animais de Doenças , Dor/metabolismo , Dor/fisiopatologiaRESUMO
In this study, a QuEChERS method based on citrate was developed and utilized for the analysis of twelve neonicotinoid pesticides in fresh red chilies, fresh green chilies, and dried chilies, coupled with ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS). In the sample preparation, acetonitrile containing 1% formic acid was used as the extraction solvent. Anhydrous sodium sulfate replaced the traditional anhydrous magnesium sulfate for water removal, effectively eliminating the issues of salt caking. Graphitized carbon black, octadecyl silica, and primary secondary amine were used as cleaning agents. The method showed good sensitivity, with the limits of quantification below 0.03 mg/kg for fresh chilies and below 0.15 mg/kg for dried chilies. Values of matrix effects ranged from -19.5% to 8.4%, and the recovery was 86.9% - 105.2%. The analytical method provided an effective tool for the high throughput detection of neonicotinoid pesticide residues in multiple chili matrices.
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Capsicum , Contaminação de Alimentos , Resíduos de Praguicidas , Cromatografia Líquida de Alta Pressão , Capsicum/química , Contaminação de Alimentos/análise , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/química , Resíduos de Praguicidas/isolamento & purificação , Espectrometria de Massas/métodos , Neonicotinoides/análise , Neonicotinoides/química , Espectrometria de Massas em Tandem/métodosRESUMO
Background: The aging population and high rates of Alzheimer's disease (AD) create significant medical burdens, prompting a need for early prevention. Targeting modifiable risk factors like vascular risk factors (VRFs), closely linked to AD, may provide a promising strategy for intervention. Objective: This study investigates how VRFs influence cognitive performance and brain structures in a community-based cohort. Methods: In this cross-sectional study, 4,667 participants over 50 years old, drawn from the Beijing Ageing Brain Rejuvenation Initiative project, were meticulously examined. Cognitive function and VRFs (diabetes mellitus, hypertension, hyperlipidemia, obesity, and smoking), were comprehensively assessed through one-to-one interviews. Additionally, a subset of participants (nâ=â719) underwent MRI, encompassing T1-weighted and diffusion-weighted scans, to elucidate gray matter volume and white matter structural network organization. Results: The findings unveil diabetes as a potent detriment to memory, manifesting in atrophy within the right supramarginal gyrus and diminished nodal efficiency and degree centrality in the right inferior parietal lobe. Hypertension solely impaired memory without significant structural changes. Intriguingly, individuals with comorbid diabetes and hypertension exhibited the most pronounced deficits in both brain structure and cognitive performance. Remarkably, hyperlipidemia emerged as a factor associated with enhanced cognition, and preservation of brain structure. Conclusions: This study illuminates the intricate associations between VRFs and the varied patterns of cognitive and brain structural damage. Notably, the synergistic effect of diabetes and hypertension emerges as particularly deleterious. These findings underscore the imperative to tailor interventions for patients with distinct VRF comorbidities, especially when addressing cognitive decline and structural brain changes.
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Envelhecimento , Encéfalo , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Envelhecimento/patologia , Envelhecimento/fisiologia , Estudos Transversais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Coortes , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , Cognição/fisiologiaRESUMO
OBJECTIVE: To investigate the effect of different surgical timing on the surgical treatment of renal angiomyolipoma (RAML) with rupture and hemorrhage. METHODS: The demographic data and perioperative data of 31 patients with rupture and hemorrhage of RAML admitted to our medical center from June 2013 to February 2023 were collected. The surgery within 7 days after hemorrhage was defined as a short-term surgery group, the surgery between 7 days and 6 months after hemorrhage was defined as a medium-term surgery group, and the surgery beyond 6 months after hemorrhage was defined as a long-term surgery group. The perioperative related indicators among the three groups were compared. RESULTS: This study collected 31 patients who underwent surgical treatment for RAML rupture and hemorrhage, of whom 13 were males and 18 were females, with an average age of (46.2±11.3) years. The short-term surgery group included 7 patients, the medium-term surgery group included 12 patients and the long-term surgery group included 12 patients. In terms of tumor diameter, the patients in the long-term surgery group were significantly lower than those in the recent surgery group [(6.6±2.4) cm vs. (10.0±3.0) cm, P=0.039]. In terms of operation time, the long-term surgery group was significantly shorter than the mid-term surgery group [(157.5±56.8) min vs. (254.8±80.1) min, P=0.006], and there was no significant difference between other groups. In terms of estimated blood loss during surgery, the long-term surgery group was significantly lower than the mid-term surgery group [35 (10, 100) mL vs. 650 (300, 1 200) mL, P < 0.001], and there was no significant difference between other groups. In terms of intraoperative blood transfusion, the long-term surgery group was significantly lower than the mid-term surgery group [0 (0, 0) mL vs. 200 (0, 700) mL, P=0.014], and there was no significant difference between other groups. In terms of postoperative hospitalization days, the long-term surgery group was significantly lower than the mid-term surgery group [5 (4, 7) d vs. 7 (6, 10) d, P=0.011], and there was no significant difference between other groups. CONCLUSION: We believe that for patients with RAML rupture and hemorrhage, reoperation for more than 6 months is a relatively safe time range, with minimal intraoperative bleeding. Therefore, it is more recommended to undergo surgical treatment after the hematoma is systematized through conservative treatment.
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Angiomiolipoma , Neoplasias Renais , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Neoplasias Renais/complicações , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Angiomiolipoma/complicações , Angiomiolipoma/cirurgia , Angiomiolipoma/patologia , Hemorragia/etiologia , Hemorragia/cirurgia , Ruptura , Hospitalização , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) is developed to concurrently enhance hypoxia-constrained tumor starvation therapy and immunotherapy. The ACG gel is formed in situ following intratumoral injection of a biohybrid fluid composed of alginate, Chlorella sorokiniana, and glucose oxidase, facilitated by the crossing-linking between divalent ions within tumors and alginate. The microalgae Chlorella sorokiniana embedded in ACG gel generate abundant oxygen through photosynthesis, enhancing glucose oxidase-catalyzed glucose consumption and shifting the TME from immunosuppressive to immunopermissive status, thus reducing the tumor cell energy supply and boosting antitumor immunity. In murine 4T1 tumor models, the ACG gel significantly suppresses tumor growth and effectively prevents postoperative tumor recurrence. This study, leveraging microalgae as natural oxygenerators, provides a versatile and universal strategy for the development of oxygen-dependent tumor therapies.
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Chlorella , Microalgas , Neoplasias , Animais , Camundongos , Hidrogéis , Glucose Oxidase , Fotossíntese , Hipóxia , Oxigênio , Imunoterapia , Alginatos , Microambiente TumoralRESUMO
Newborns with intrauterine growth restriction (IUGR) have a higher likelihood of developing pulmonary arterial hypertension (PAH) in adulthood. Although there is increasing evidence suggesting that pericytes play a role in regulating myofibroblast transdifferentiation and angiogenesis in malignant and cardiovascular diseases, their involvement in the pathogenesis of IUGR-related pulmonary hypertension and the underlying mechanisms remain incompletely understood. To address this issue, a study was conducted using a Sprague-Dawley rat model of IUGR-related pulmonary hypertension. Our investigation revealed increased proliferation and migration of pulmonary microvascular pericytes in IUGR-related pulmonary hypertension, accompanied by weakened endothelial-pericyte interactions. Through whole-transcriptome sequencing, Ddx5 (DEAD-box protein 5) was identified as one of the hub genes in pericytes. DDX5, a member of the RNA helicase family, plays a role in the regulation of ATP-dependent RNA helicase activities and cellular function. MicroRNAs have been implicated in the pathogenesis of PAH, and microRNA-205 (miR-205) regulates cell proliferation, migration, and angiogenesis. The results of dual-luciferase reporter assays confirmed the specific binding of miR-205 to Ddx5. Mechanistically, miR-205 negatively regulates Ddx5, leading to the degradation of ß-catenin by inhibiting the phosphorylation of Gsk3ß at serine 9. In vitro experiments showed the addition of miR-205 effectively ameliorated pericyte dysfunction. Furthermore, in vivo experiments demonstrated that miR-205 agomir could ameliorate pulmonary hypertension. Our findings indicated that the downregulation of miR-205 expression mediates pericyte dysfunction through the activation of Ddx5. Therefore, targeting the miR-205/Ddx5/p-Gsk3ß/ß-catenin axis could be a promising therapeutic approach for IUGR-related pulmonary hypertension.
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Proliferação de Células , RNA Helicases DEAD-box , Epigênese Genética , Retardo do Crescimento Fetal , Glicogênio Sintase Quinase 3 beta , Hipertensão Pulmonar , MicroRNAs , Pericitos , Ratos Sprague-Dawley , Animais , Feminino , Humanos , Masculino , Ratos , beta Catenina/metabolismo , beta Catenina/genética , Movimento Celular/genética , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/patologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Pericitos/metabolismo , Pericitos/patologiaRESUMO
PURPOSE: To explore the ability of intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI) and background parenchyma enhancement (BPE) to predict the Nottingham prognostic index (NPI) and molecular subtypes of breast cancer (BC). MATERIALS AND METHODS: In this study, 93 patients with BC were included, and they all underwent DKI, IVIM and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations. The corresponding mean kurtosis value (MK), pure diffusion (MD), perfusion fraction (f), pseudo diffusion coefficient (D*), true diffusion coefficient (D), and BPE were measured. We used logistic regression analysis to investigate the relevance between the NPI, molecular subtypes and variables. The diagnostic efficacy was analyzed using receiver operating characteristic curves (ROC). RESULTS: The MD and D values of the high-level NPI group were significantly lower than those of the low-level NPI group (p < 0.01), and the f value of the high-level NPI group was obviously higher than that of low-level NPI group (p < 0.001). The area under curve (AUC) of the combined model (f + D) was 0.824. Comparing with non-Luminal subtypes, the Luminal subtypes showed obviously lower MK, f and D*, and the AUC of the combined model (MK + f + D*) was 0.785. In comparison to other subtypes, the MK and D* values of triple-negative subtype were higher than other subtypes, and the combined model (MK + D*) represented an AUC of 0.865. CONCLUSION: The quantitative parameters of DKI and IVIM have vital value in predicting the NPI and molecular subtypes of BC, while BPE could not provide additional information. Besides, these combined models can obviously improve the prediction performance.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Prognóstico , Sensibilidade e Especificidade , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética/métodos , Movimento (Física)RESUMO
BACKGROUND: To define the incidence and risk factors of chyle leak (CL) after radical nephrectomy and thrombectomy and to determine the impact of chyle leak on oncological outcomes. PATIENTS AND METHODS: A total of 445 patients who underwent radical nephrectomy and thrombectomy between January 2014 and January 2023 were included. CL is defined as the drainage of chyle with a triglyceride level greater than 110 mg/dL after oral intake or enteral nutrition. Multivariate logistic regression analysis was performed to identify the risk factors of postoperative (CL). The Kaplan-Meier curves were used to compare overall survival and cancer-specific survival. RESULTS: 44 patients (9.9%) were diagnosed as (CL). All patients developed CL within 6 days after the operation with a median time of 3 days. In multivariate logistic regression analysis, Mayo grade and side were independent patient-related risk factors. In addition, operation approach, operation time, and number of lymph nodes harvested were independent surgery-related risk factors. Between the CL group and the non-CL group, neither overall survival nor cancer-specific survival showed statistical differences. CONCLUSION: Based on this retrospective study of renal cell carcinoma and tumor thrombus patients in our center, we found that the risk factors were Mayo grade, side, operation approach, operation time, and number of lymph nodes harvested, and the occurrence of CL significantly prolonged hospital stay, but had no effect on long-term oncological outcomes.
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Carcinoma de Células Renais , Quilo , Neoplasias Renais , Nefrectomia , Trombectomia , Humanos , Masculino , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Incidência , Neoplasias Renais/cirurgia , Trombectomia/métodos , Trombectomia/efeitos adversos , Estudos Retrospectivos , Carcinoma de Células Renais/cirurgia , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controleRESUMO
Imidacloprid (IMI) and cadmium (Cd) are pollutants of concern in the environment. Although investigations about their combined toxicity to organisms such as earthworms, aquatic worms, Daphnia magna, and zebrafish have been carried out, their combined toxicity to mammals remains unknow. In this study, twenty-four 8-week-old mice were arbitrarily separated into 4 groups: CK (control group), IMI (15 mg/kg bw/day, 1/10 LD50), Cd (15 mg/kg bw/day, 1/10 LD50), and IMI + Cd (15 mg/kg bw/day IMI + 15 mg/kg bw/d Cd) and the combined toxic effects of IMI and Cd were examined with biochemical (oxidative stress testing) and omics approaches (metabolomics and lipidomics). The results revealed changes in each treatment group in terms of oxidative stress, abnormalities in lipid metabolism, and disturbances in amino acid metabolism. Co-administration had antagonistic effects on MDA accumulation and lipid metabolism disorders while acting synergistically on changes in SOD and GSH-Px activities. It is worth noting that after analysis, the changes caused by mixed administration in vivo were closer to those caused by IMI administration alone. This study provides new insights into the combined toxicity of neonicotinoids and heavy metals, which is helpful for relevant environmental governance and further investigations about their impacts on human health and the environment.
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Cádmio , Metabolismo dos Lipídeos , Humanos , Camundongos , Animais , Cádmio/farmacologia , Peixe-Zebra , Conservação dos Recursos Naturais , Política Ambiental , Neonicotinoides/toxicidade , Estresse Oxidativo , Nitrocompostos/toxicidade , Aminoácidos , MamíferosRESUMO
BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most challenging chronic lung disease for prematurity, with difficulties in early identification. Given lncRNA emerging as a novel biomarker and the regulator of ferroptosis, this study aims to develop a BPD predictive model based on ferroptosis-related lncRNAs (FRLs). METHODS: Using a rat model, we firstly explored mRNA levels of ferroptosis-related genes and ferrous iron accumulation in BPD rat lungs. Subsequently, a microarray dataset of umbilical cord tissue from 20 preterm infants with BPD and 34 preterm infants without BPD were downloaded from the Gene Expression Omnibus databases. Random forest and LASSO regression were conducted to identify diagnostic FRLs. Nomogram was used to construct a predictive BPD model based on the FRLs. Finally, umbilical cord blood lymphocytes of preterm infants born before 32 weeks gestational age and term infants were collected and determined the expression level of diagnostic FRLs by RT-qPCR. RESULTS: Increased iron accumulation and several dysregulated ferroptosis-associated genes were found in BPD rat lung tissues, indicating that ferroptosis was participating in the development of BPD. By exploring the microarray dataset of preterm infants with BPD, 6 FRLs, namely LINC00348, POT1-AS1, LINC01103, TTTY8, PACRG-AS1, LINC00691, were determined as diagnostic FRLs for modeling. The area under the receiver operator characteristic curve of the model was 0.932, showing good discrimination of BPD. In accordance with our analysis of microarray dataset, the mRNA levels of FRLs were significantly upregulated in umbilical cord blood lymphocytes from preterm infants who had high risk of BPD. CONCLUSION: The incorporation of FRLs into a predictive model offers a non-invasive approach to show promise in improving early detection and management of this challenging chronic lung disease in premature infant, enabling timely intervention and personalized treatment strategies.
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Displasia Broncopulmonar , Ferroptose , RNA Longo não Codificante , Lactente , Recém-Nascido , Humanos , Animais , Ratos , Recém-Nascido Prematuro , Displasia Broncopulmonar/genética , RNA Longo não Codificante/genética , Ferroptose/genética , RNA Mensageiro , FerroRESUMO
BACKGROUND: Targeted therapy combined with immunotherapy is the current first-line treatment for metastatic renal cell carcinoma (mRCC), but patients with tumor thrombus (TT) may suffer from lower limb edema or even sudden cardiac death, so the purpose of this study is to investigate the efficacy and safety of surgical treatment in patients with mRCC and TT and explore worse factors to affect the prognosis in this series of patients. PATIENTS AND METHODS: A total of 85 mRCC patients with TT who received cytoreductive nephrectomy and thrombectomy at our medical center from 2014 to 2023 are included. All patients received postoperative systemic therapy. Overall survival (OS) is defined as the time from surgery to death due to any reason or the last follow-up. Kaplan-Meier analysis was performed to evaluate OS and differences among groups were tested by log-rank. Multivariable Cox proportional hazards analysis was performed to ascertain independent relationships between clinicopathological factors and OS. RESULTS: The median age of patients was 58 years old. Eleven patients (12.9%) had no symptoms, 39 patients (45.9%) had local symptoms, 15 patients (17.6%) had systemic symptoms, and 20 patients (23.5%) had both. Mayo grade of TT was 0, 1, 2, 3, and 4 for 12, 27, 31, 7, and 8 patients respectively. Fifty-five patients had lung metastasis, 23 had bone metastasis, 16 had liver metastasis, 13 had adrenal metastasis, and 9 had lymph node metastasis. Of all patients, 17 patients had multiple metastases. The median operation time is 289 min and the median intraoperative hemorrhage is 800 ml. Twenty-eight patients experienced postoperative complications, 8 of which were serious complications of modified Clavien grade III or higher. The median OS of all patients was 33 months and median follow up time was 26 months. In multivariate analysis, systemic symptom (p = 0.00753), pathological type (p = 0.0166), sarcomatous degeneration (p = 0.0334), and perirenal fat infiltration (p = 0.0202) are independent predictors of OS. CONCLUSION: Cytoreductive nephrectomy and thrombectomy is relatively safe and effective for patients with mRCC accompanied by TT. In this series of patients, the worse prognosis is associated with systemic symptoms, non-clear cell carcinoma, sarcomatous degeneration and perirenal fat infiltration.
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Carcinoma de Células Renais , Neoplasias Renais , Trombose , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Neoplasias Renais/patologia , Procedimentos Cirúrgicos de Citorredução , População do Leste Asiático , Trombose/etiologia , Trombose/cirurgia , Nefrectomia , Prognóstico , TrombectomiaRESUMO
Local lung microbiota is closely associated with lung tumorigenesis and therapeutic response. It is found that lung commensal microbes induce chemoresistance in lung cancer by directly inactivating therapeutic drugs via biotransformation. Accordingly, an inhalable microbial capsular polysaccharide (CP)-camouflaged gallium-polyphenol metal-organic network (MON) is designed to eliminate lung microbiota and thereby abrogate microbe-induced chemoresistance. As a substitute for iron uptake, Ga3+ released from MON acts as a "Trojan horse" to disrupt bacterial iron respiration, effectively inactivating multiple microbes. Moreover, CP cloaks endow MON with reduced immune clearance by masquerading as normal host-tissue molecules, significantly increasing residence time in lung tissue for enhanced antimicrobial efficacy. In multiple lung cancer mice models, microbe-induced drug degradation is remarkably inhibited when drugs are delivered by antimicrobial MON. Tumor growth is sufficiently suppressed and mouse survival is prolonged. The work develops a novel microbiota-depleted nanostrategy to overcome chemoresistance in lung cancer by inhibiting local microbial inactivation of therapeutic drugs.
Assuntos
Anti-Infecciosos , Gálio , Neoplasias Pulmonares , Microbiota , Nanopartículas , Animais , Camundongos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Polifenóis , Pulmão/metabolismo , Ferro , Neoplasias Pulmonares/tratamento farmacológico , PolissacarídeosRESUMO
Purpose: To explore the safety and effectiveness of the Pure Retroperitoneal Laparoscopic Peritoneum Incision Technique (PREP-IT) in laparoscopic radical nephrectomy (LRN) and inferior vena cave (IVC) tumor thrombectomy for right renal-cell carcinoma (RCC) with level Mayo I to III venous tumor thrombus (VTT). Patients and Methods: From May 2015 to September 2020, 92 patients with right RCC and Mayo I to III VTT were retrospectively reviewed, including 57 patients who underwent retroperitoneal LRN and IVC thrombectomy using PREP-IT, and 35 patients who underwent open surgery. PREP-IT refers to dissecting the retroperitoneum and temporarily placing the right kidney into the abdominal cavity to enlarge the retroperitoneal workspace for a safer and faster IVC operation. Results: Compared with the open surgery group, the PREP-IT group had a larger tumor diameter, while a larger proportion of Mayo I tumor thrombus and smaller maximum tumor thrombus width. Two patients (3.5%) in the PREP-IT group had a history of abdominal surgery. No conversion to open surgery or standard laparoscopic surgery occurred in PREP-IT group. Laparoscopic surgery with PREP-IT was characterized by shorter operative time, less surgical blood loss, shorter postoperative hospital stay, and lower postoperative complication rate. With a 33-month (ranges: 2-86) follow-up time period, the estimated mean overall survival time was 57.2 ± 5.3 and 58.1 ± 71.5 months in the PREP-IT group and open surgery group, respectively. Log-rank test indicated no significant difference between the two groups in terms of overall survival and cancer-specific survival. Conclusions: The PREP-IT is relatively safe and feasible for retroperitoneal LRN with right renal tumor and IVC tumor thrombus, allowing for a large workspace and wide exposure for IVC operations.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Laparoscopia , Trombose , Trombose Venosa , Humanos , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Peritônio , Estudos Retrospectivos , Trombectomia/métodos , Trombose/patologia , Veia Cava Inferior/patologia , Trombose Venosa/cirurgiaRESUMO
BACKGROUND: Long-term child-parent relationship quality following hospitalization for pediatric traumatic brain injury (TBI) remains poorly understood. OBJECTIVE: We tested whether current child-parent conflict and closeness were related to the children's history of TBI-related experiences and contemporary child/family characteristics. METHODS: The sample included 202 Chinese children (Boys: 60.4%) with a history of hospitalization for TBI. On average, the children were 11.2 years old (SD = 1.59) and sustained TBI at 8.5 years old (SD = 1.6). TBI-related data were obtained from hospital medical records. Parents provided data on child-parent closeness, child-parent conflict, and parental efficacy 2-4 years (M = 2.7, SD = 0.7) after discharge. RESULTS: Forty-nine children (24.3%) had mild TBI, 139 (68.8%) had moderate TBI, and 14 (6.9%) had severe TBI. Surgical intervention occurred among 128 (63.4%) of the 202 children. Contemporaneous child and family characteristics explained 19% of the variance, history of surgery, length of hospitalization, and recovery status explained another 7%, and the interaction between length of hospitalization and parental efficacy explained another 4% in child-parent conflict. Contemporaneous child and family characteristics explained 29% of the variance, and TBI-related variables explained another 2% in child-parent closeness. CONCLUSION: Post-TBI child-parent relationship was more associated with child/family characteristics than with TBI variables. Practitioners and families should be aware of the long-term challenges to child-parent relationship following hospitalization for pediatric TBI.
Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Masculino , Criança , Humanos , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/terapia , Pais , Relações Pais-Filho , HospitalizaçãoRESUMO
BACKGROUND: As previous studies reported, gadolinium deposits in globus pallidus (GP) and dentate nucleus (DN) after repeated administrations of gadolinium-based contrast agents (GBCAs) and a signal intensity (SI) increase on T1-weighted images were related to linear GBCAs, not macrocyclic GBCAs. PURPOSE: To identify whether quantitative susceptibility mapping (QSM) could measure a subtle increase in magnetic susceptibility in DN and GP in patients after repeated administrations of gadoteric acid meglumine (Gd-DOTA). MATERIAL AND METHODS: In this study, 50 patients with cerebral tumors who had received at least three injections of Gd-DOTA (GBCA group) and 50 individuals without a history of GBCA injections (non-GBCA group) were included. The image data for QSM and T1-weighted images were reviewed. Spearman rank correlation was used to estimate the associations between the values (magnetic susceptibility of QSM and SI ratios of T1-weighted images) and the number of Gd-DOTA injections. RESULTS: The mean magnetic susceptibility of GP in GBCA group was 0.136 ± 0.031 ppm, which was significantly higher than that in control group (0.114 ± 0.030 ppm) (P = 0.001). In the GBCA group (n = 50), we found a substantial positive correlation between magnetic susceptibility of GP and the number of Gd-DOTA injections according to Spearman rank correlation coefficient (ρ = 0.673, P = 0.0001). There was a modest but significant correlation between magnetic susceptibility of DN and the number of Gd-DOTA injections (ρ = 0.311, P = 0.028). CONCLUSION: In comparison to the control group, the magnetic susceptibility of GP in the GBCA group was significantly higher and had a substantial positive association with the number of Gd-DOTA injections.