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Natural polyphenolic compound rosmarinic acid (RA) has good antitumor activity. However, the distinctive tumor microenvironment, characterized by low pH and elevated levels of glutathione (GSH), enhances the tolerance of tumors to the singular anti-tumor treatment mode using RA, resulting in unsatisfactory therapeutic efficacy. Targeting nonapoptotic programmed cell death processes may provide another impetus to inhibit tumor growth. RA possesses the capability to coordinate with metal elements. To solve the effect restriction of the above single treatment mode, it is proposed to construct a self-assembled nanocomposite, Fe-RA. Under tumor microenvironment, Fe-RA nanocomposite exerts the characteristics of POD-like enzyme activity and depletion of GSH, producing a large amount of hydroxyl radical (·OH) while disrupting the antioxidant defense system of tumor cells. Moreover, due to the enhanced permeability and retention effect (EPR), Fe-RA can transport Fe2+ to a greater extent to tumor cells and increase intracellular iron content. Causing an imbalance in iron metabolism in tumor cells and promoting cell ferroptosis. The results of the synchrotron X-ray absorption spectroscopy (XAS) and high-resolution mass spectrometry (HRMS) prove the successful complexation of Fe-RA nanocomposite. Density functional theory (DFT) explains the efficient catalytic mechanism of its peroxide-like enzyme activity and the reaction principle with GSH.
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BACKGROUND: Iron plays a pivotal role in various physiological processes, including intestinal inflammation, ferroptosis, and the modulation of the gut microbiome. However, the way these factors interact with each other is unclear. METHODS: Mice models were fed with low, normal and high iron diets to assess their impacts on colitis, ferroptosis and gut microbiota. Untargeted fecal metabolomics analysis, 16S rRNA sequencing, histopathology analysis, real-time quantitative PCR and western blot were performed to analyze the differences in the intestinal inflammatory response and understanding its regulatory mechanisms between low, normal and high iron groups. RESULTS: The iron overload changed the serum iron, colon iron and fecal iron. In addition, the iron overload induced the colitis, induced the ferroptosis and altered the microbiome composition in the fecal of mice. By using untargeted fecal metabolomics analysis to screen of metabolites in the fecal, we found that different metabolomics profiles in the fecal samples between iron deficiency, normal iron and iron overload groups. The correlation analysis showed that both of iron deficiency and overload were closely related to Dubosiella. The relationship between microbial communities (e.g., Akkermansia, Alistipes, and Dubosiella) and colitis-related parameters was highly significant. Additionally, Alistipes and Bacteroides microbial communities displayed a close association with ferroptosis-related parameters. Iron overload reduced the concentration of metabolites, which exert the anti-inflammatory effects (e.g., (+)-.alpha.-tocopherol) in mice. The nucleotide metabolism, enzyme metabolism and metabolic diseases were decreased and the lipid metabolism was increased in iron deficiency and iron overload groups compared with normal iron group. CONCLUSION: Iron overload exacerbated colitis in mice by modulating ferroptosis and perturbing the gut microbiota. Iron overload-induced ferroptosis was associated with NRF2/GPX-4 signaling pathway. Specific microbial taxa and their associated metabolites were closely intertwined with both colitis and ferroptosis markers.
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Colite , Ferroptose , Microbioma Gastrointestinal , Deficiências de Ferro , Sobrecarga de Ferro , Animais , Camundongos , RNA Ribossômico 16S , Colite/induzido quimicamente , Ferro , Bacteroidetes , Firmicutes , Camundongos Endogâmicos C57BLRESUMO
Nasopharyngeal carcinoma (NPC) is known for high curability during early stage of the disease, and early diagnosis relies on nasopharyngeal endoscopy and subsequent pathological biopsy. To enhance the early diagnosis rate by aiding physicians in the real-time identification of NPC and directing biopsy site selection during endoscopy, we assembled a dataset comprising 2,429 nasopharyngeal endoscopy video frames from 690 patients across three medical centers. With these data, we developed a deep learning-based NPC detection model using the you only look once (YOLO) network. Our model demonstrated high performance, with precision, recall, mean average precision, and F1-score values of 0.977, 0.943, 0.977, and 0.960, respectively, for internal test set and 0.825, 0.743, 0.814, and 0.780 for external test set at 0.5 intersection over union. Remarkably, our model demonstrated a high inference speed (52.9 FPS), surpassing the average frame rate (25.0 FPS) of endoscopy videos, thus making real-time detection in endoscopy feasible.
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Large-scale, high-strength aluminum alloy forgings are essential components in the aerospace industry, with benefits including increasing strength and decreasing weight. Accurate shape-property control is the secret to forging quality. This study uses the alloy 7050 to experimentally evaluate the parametric influence of cold compression on residual stress and mechanical characteristics. The evolutions of mechanical properties, microstructure and residual stress are theoretically studied using various cold compression strains from 1% to 5% on an equivalent part, of which the results are further applied on a complicated rib-structured die forging. It is demonstrated that increasing the compression strain reduces the tensile strength of the material, but has little impact on conductivity and fracture toughness. According to the TEM results, compression also encourages the precipitation and growth of precipitated phases, particularly in positions with high dislocation densities after aging. Cold compression significantly reduces residual stress; nevertheless, as compression strain increases, residual stress first decreases and then increases. With the use of rib-structured forging, it is observed that the compression strain for 7050 aluminum alloy ranges from 2% to 4%, and the combined pressing method of the rib and web improves the uniformity of residual stress.
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Ferroptosis, a form of regulated cell death, has been widely explored as a novel target for the treatment of diseases. The failure of the antioxidant system can induce ferroptosis. Epigallocatechin-3-Gallate (EGCG) is a natural antioxidant in tea; however, whether EGCG can regulate ferroptosis in the treatment of liver oxidative damage, as well as the exact molecular mechanism, is unknown. Here, we discovered that iron overload disturbed iron homeostasis in mice, leading to oxidative stress and damage in the liver by activating ferroptosis. However, EGCG supplementation alleviated the liver oxidative damage caused by iron overload by inhibiting ferroptosis. EGCG addition increased NRF2 and GPX4 expression and elevated antioxidant capacity in iron overload mice. EGCG administration attenuates iron metabolism disorders by upregulating FTH/L expression. Through these two mechanisms, EGCG can effectively inhibit iron overload-induced ferroptosis. Taken together, these findings suggest that EGCG is a potential ferroptosis suppressor, and may be a promising therapeutic agent for iron overload-induced liver disease.
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Catequina , Ferroptose , Sobrecarga de Ferro , Hepatopatias , Camundongos , Animais , Antioxidantes/farmacologia , Estresse Oxidativo , Sobrecarga de Ferro/tratamento farmacológico , Catequina/farmacologia , Catequina/uso terapêutico , Hepatopatias/tratamento farmacológicoRESUMO
Objective.To develop and test the feasibility of a novel Single ProjectIon DrivEn Real-time Multi-contrast (SPIDERM) MR imaging technique that can generate real-time 3D images on-the-fly with flexible contrast weightings and a low latency.Approach.In SPIDERM, a 'prep' scan is first performed, with sparse k-space sampling periodically interleaved with the central k-space line (navigator data), to learn a subject-specific model, incorporating a spatial subspace and a linear transformation between navigator data and subspace coordinates. A 'live' scan is then performed by repeatedly acquiring the central k-space line only to dynamically determine subspace coordinates. With the 'prep'-learned subspace and 'live' coordinates, real-time 3D images are generated on-the-fly with computationally efficient matrix multiplication. When implemented based on a multi-contrast pulse sequence, SPIDERM further allows for data-driven image contrast regeneration to convert real-time contrast-varying images into contrast-frozen images at user's discretion while maintaining motion states. Both digital phantom andin-vivoexperiments were performed to evaluate the technical feasibility of SPIDERM.Main results.The elapsed time from the input of the central k-space line to the generation of real-time contrast-frozen 3D images was approximately 45 ms, permitting a latency of 55 ms or less. Motion displacement measured from SPIDERM and reference images showed excellent correlation (R2≥0.983). Geometric variation from the ground truth in the digital phantom was acceptable as demonstrated by pancreas contour analysis (Dice ≥ 0.84, mean surface distance ≤ 0.95 mm). Quantitative image quality metrics showed good consistency between reference images and contrast-varying SPIDREM images inin-vivostudies (meanNMRSE=0.141,PSNR=30.12,SSIM=0.88).Significance.SPIDERM is capable of generating real-time multi-contrast 3D images with a low latency. An imaging framework based on SPIDERM has the potential to serve as a standalone package for MR-guided radiation therapy by offering adaptive simulation through a 'prep' scan and real-time image guidance through a 'live' scan.
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Imageamento Tridimensional , Imageamento por Ressonância Magnética , Abdome , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Movimento (Física) , Imagens de FantasmasRESUMO
OBJECTIVE: To explore and find a new method to treat hilar cholangiocarcinoma with deep jaundice assisted by Da Vinci robot. METHODS: A hilar cholangiocarcinoma patient of type Bismuch-Corlette IIIa was found with deep jaundice (total bilirubin: 635 µmol/L). On the first admission, we performed Da Vinci robotic surgery including drainage of left hepatic duct, dissection of right hepatic vessels (right portal vein and right hepatic artery), and placement of right-hepatic vascular control device. Three weeks later on the second admission when the jaundice disappeared we occluded right-hepatic vascular discontinuously for 6 days and then sustained later. On the third admission after 3 weeks of right-hepatic vascular control, the right hemihepatectomy was performed by Da Vinci robot for the second time. RESULTS: The future liver remnant after the right-hepatic vascular control increased from 35% to 47%. The volume of left lobe increased by 368 mL. When the total bilirubin and liver function were all normal, right hemihepatectomy was performed by Da Vinci robot 10 weeks after the first operation. The removal of atrophic right hepatic lobe with tumor in bile duct was found with no pathologic cancer remaining in the margin. The patient was followed up at our outpatient clinic every 3 months and no tumor recurrence occurs by now (1 y). CONCLUSIONS: Under the Da Vinci robotic surgical system, a programmed treatment can be achieved: first, the hepatic vessels were controlled gradually together with biliary drainage, which results in liver's partial atrophy and compensatory hypertrophy in the other part. Then a radical hepatectomy could be achieved. Such programmed hepatectomy provides a new treatment for patients of hilar cholangiocarcinoma with deep jaundice who have the possibility of radical heptolobectomy.
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Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia/métodos , Icterícia/complicações , Fígado/irrigação sanguínea , Procedimentos Cirúrgicos Robóticos , Adulto , Humanos , Masculino , ReoperaçãoRESUMO
BACKGROUND: Since the introduction of Da Vinci robotic surgery, more and more complicated surgeries can now be performed robotically, yet there have been very few on robotic hepatectomy, especially when billiary reconstruction is involved. The video shows our initial experience with an anatomic hepatectomy using Da Vinci surgical robot. In this case, we also conducted billiary reconstruction due to the anatomic abnormality of bile duct, while applying the choledochoscopy. The preoperative diagnosis is primary liver carcinoma, tumor thrombi in bile duct, and hepatitis B. METHODS: First, the gallbladder was resected, and cystic artery and duct were identified. After opening of the common bile duct above the junction, the choledochoscopy was performed. Tumor thrombi were found in common bile duct and left hepatic duct, and they were all removed. Left branches hepatic artery and portal vein were dissected, ligated, and divided. Thrombi in the left hepatic duct were removed also. After marking the cutting line along the ischemic boarder, liver parenchyma was transected using robotic harmonic scalpel. Branches of ducts were encountered and managed by either direct coagulating or dividing after clipping. The left hepatic vein was visualized, exposed, and divided during hepatectomy. Two T tubes were placed into common hepatic duct and the proximal cutting end of right anterior bile duct which was found to join the left hepatic duct, respectively. RESULTS: The operation went on successfully. The operation time was 410 minutes, the blood loss was 200 mL. The pathologic diagnosis was introductal papillary adenocarcinoma of left hepatic duct. The patient went on well postoperatively and was followed up for 22 months till now. Postoperative computed tomography examination showed no recurrence. CONCLUSIONS: Da Vinci-assisted robotic hepatectomy can be performed safely in the hands of experienced hepatobilliary surgeons, and choledochoscopy can be combined for bile duct exploration. With the advantages of Da Vinci robot system, complicated billiary reconstruction can be performed (http://links.lww.com/SLE/A74).
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Ductos Biliares/cirurgia , Hepatectomia/métodos , Hepatopatias/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Robótica , Humanos , Laparoscopia , Resultado do TratamentoRESUMO
AIM: To investigate the incidence of clinically detected port-site metastasis (PSM) in patients who underwent robotic surgery for biliary malignancies. METHODS: Using a prospective database, the patients undergoing fully robotic surgery for biliary malignancies between January 2009 and January 2011 were included. Records of patients with confirmed malignancy were reviewed for clinicopathological data and information about PSM. RESULTS: Sixty-four patients with biliary tract cancers underwent robotic surgery, and sixty patients met the inclusion criteria. The median age was 67 year (range: 40-85 year). During a median 15-mo follow-up period, two female patients were detected solitary PSM after robotic surgery. The incidence of PSM was 3.3%. Patient 1 underwent robotic anatomatic left hemihepatectomy and extraction of biliary tumor thrombi for an Klatskin tumor. She had a subcutaneous mass located at the right lateral abdominal wall near a trocar scar. Patient 2 underwent robotic pancreaticoduodenectomy for distal biliary cancer. She had two metachronous subcutaneous mass situated at the right lateral abdominal wall under a same trocar scar at 7 and 26 mo. The pathology of the excised PSM masses confirmed metastatic biliary adenocarcinoma. CONCLUSION: The incidence of PSMs after robotic surgery for biliary malignancies is relatively low, and biliary cancer can be an indication of robotic surgery.
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Adenocarcinoma/cirurgia , Neoplasias do Sistema Biliar/cirurgia , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Inoculação de Neoplasia , Robótica , Cirurgia Assistida por Computador/efeitos adversos , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
PURPOSE: Numerous studies have evaluated the association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma risk in the Chinese Han population. However, the results have been inconsistent. We therefore here examined whether the XRCC1 Arg399Gln gene polymorphism confers hepatocellular carcinoma risk by conducting a meta-analysis. METHODS: PubMed, Google scholar and China National Knowledge Infrastructure databases were searched for eligible articles in English and Chinese that were published before April 2012. RESULTS: 6 studies involving 1,246 patients with hepatocellular carcinoma and 1,953 controls were included. The association between XRCC1 Arg399Gln gene polymorphism and hepatocellular carcinoma in the Chinese Han population was significant under GG vs AA (OR = 1.48, 95% CI = 1.13 to 1.94). Limiting the analysis to the studies with controls in the Hardy-Weinberg equilibrium, the results were persistent and robust. CONCLUSIONS: In the Chinese Han population, the XRCC1 Arg399Gln gene polymorphism is associated with an increased hepatocellular carcinoma risk.
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Povo Asiático/genética , Carcinoma Hepatocelular/etiologia , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença , Neoplasias Hepáticas/etiologia , Polimorfismo de Nucleotídeo Único/genética , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Humanos , Neoplasias Hepáticas/epidemiologia , Fatores de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
BACKGROUND: Pancreatoduodenectomy (PD) for pancreatic cancer is very challenging to many surgeons. Information regarding the advantage of using the Da Vinci robotic system over conventional open surgery for PD is rare. Therefore, a comparison of the outcomes of PD performed using the Da Vinci robotic system with outcomes using open surgery was conducted. METHODS: Between January 2009 and December 2009 sixteen patients underwent PD, eight patients receiving robot-assisted surgery using the Da Vinci surgical robotic system (Group I) and eight being treated using conventional open surgery (Group II). RESULTS: There was no significant difference in radical resection (R0) rate between the two groups, 87.5% vs 100%, P = 0.05. The operative time in group I was longer than in group II, 718 ± 186 vs 420 ± 127 min, P = 0.011, while the surgical blood loss in group I was less than in group II, 153 ± 43 vs 210 ± 53 mL, P = 0.045. The length of bed time and hospital stay after surgery in group I were shorter than in group II, 27.5 ± 7.1 vs 96 ± 18.1 h, P = 0.000; 16.4 ± 4.1 vs 24.3 ± 7.1 days, P = 0.04, respectively). Complication rate of group I was lower than that of group II, 25% vs 75%, P = 0.05. CONCLUSION: It is feasible and safe to perform PD using the Da Vinci robot-assisted surgical system; patients recovered faster postoperatively with less blood loss during surgery.
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Pancreaticoduodenectomia/instrumentação , Pancreaticoduodenectomia/métodos , Robótica/instrumentação , Robótica/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Operatórios/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Cholangiocarcinoma (CC) is devastating neoplasm and very few specific biomarkers could be used in clinical diagnosis. A study was taken to find novel serum biomarkers for CC. METHODS: Surface enhanced laser desorption/ionization (SELDI) technology was used to analyze 427 serum samples including 56 CCs, 49 hepatobiliary diseases, 269 other cancer control, and 53 healthy individuals. The candidates were isolated and identified by SDS-PAGE, ESI/MS-MS, Western blot, and immunoprecipitation. Liver functions of CC patients were examined and enzyme-linked immunosorbent assay (ELISA) of transthyretin (TTR) and CA19-9 were further performed in some sets of serum samples. RESULTS: 13.76, 13.88, and 14.04 k m/z peaks in sera were significantly decreased in CC compared with the control groups (P < 0.001). Subsequently, these three peaks were identified as native TTR and its two variants. ELISA assay indicated that TTR levels were consistent with SELDI analysis in CC compared with healthy control and benign diseases of hepatobiliary (P < 0.001). Liver function test levels were obviously elevated for CC patients. TTR combining with CA19-9 to differentiate CC from benign hepatobiliary diseases showed sensitivity and specificity were 98.2% and 100%, respectively. CONCLUSION: The levels of TTR were significantly down-regulated in sera of CC patients and may be complementary markers of CA19-9 in diagnosis for CC.