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This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.
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Medicamentos Herbarios Chinos , Metabolismo Energético , Diana Mecanicista del Complejo 1 de la Rapamicina , Mitocondrias , Panax notoginseng , Proteínas Proto-Oncogénicas c-akt , Ratas Sprague-Dawley , Animales , Masculino , Ratas , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Panax notoginseng/química , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Metabolismo Energético/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Rizoma/química , Humanos , Transducción de Señal/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Insuficiencia Renal/tratamiento farmacológico , Insuficiencia Renal/metabolismoRESUMEN
Invited for this issue's cover is the group of Huilei Yu at the East China University of Science and Technology. The image shows a sustainable biosynthesis route to nylon monomers from bio-based substrate α, ω-dicarboxylic acids. The Research Article itself is available at 10.1002/cssc.202301477.
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Diaminas , Ácidos Grasos , Aminoácidos , ChinaRESUMEN
Aliphatic ω-amino fatty acids (ω-AFAs) and α,ω-diamines (α,ω-DMs) are essential monomers for the production of nylons. Development of a sustainable biosynthesis route for ω-AFAs and α,ω-DMs is crucial in addressing the challenges posed by climate change. Herein, we constructed an unprecedented thermodynamically favorable multi-enzyme cascade (TherFavMEC) for the efficient sustainable biosynthesis of ω-AFAs and α,ω-DMs from cheap α,ω-dicarboxylic acids (α,ω-DAs). This TherFavMEC was developed by incorporating bioretrosynthesis analysis tools, reaction Gibbs free energy calculations, thermodynamic equilibrium shift strategies and cofactor (NADPH&ATP) regeneration systems. The molar yield of 6-aminohexanoic acid (6-ACA) from adipic acid (AA) was 92.3 %, while the molar yield from 6-ACA to 1,6-hexanediamine (1,6-HMD) was 96.1 %, which were significantly higher than those of previously reported routes. Furthermore, the biosynthesis of ω-AFAs and α,ω-DMs from 20.0â mM α,ω-DAs (C6-C9) was also performed, giving 11.2â mM 1,6-HMD (56.0 % yield), 14.8â mM 1,7-heptanediamine (74.0 % yield), 17.4â mM 1,8-octanediamine (87.0 % yield), and 19.7â mM 1,9-nonanediamine (98.5 % yield), respectively. The titers of 1,9-nonanediamine, 1,8-octanediamine, 1,7-heptanediamine and 1,6-HMD were improved by 328-fold, 1740-fold, 87-fold and 3.8-fold compared to previous work. Therefore, this work holds great potential for the bioproduction of ω-AFAs and α,ω-DMs.
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Aminoácidos , Diaminas , Ácidos Dicarboxílicos , Ácidos GrasosRESUMEN
The target gene sequences of the novel coronaviruses obtained by sequencing were compared with the reference sequences to analyze the genetic variation of the two cases of the novel coronaviruses from Inner Mongolia Autonomous Region in 2022 and to explore the sources of infection. The results showed that the two sequences belonged to different evolutionary branches, Delta (AY.122) and Omicron (BA.1.1), respectively. hCoV-19/Inner Mongolia/IVDC-591/2022 had 48 single nucleotide polymorphisms on the genome sequences, sharing 40 nucleotide mutation sites with a Mongolian strain; hCoV-19/Inner Mongolia/IVDC-592/2022 genome shared 57 nucleotide mutation sites with a UK strain, and the nucleotide mutation site identity was 100% (57/57). Phylogenetic analysis showed that the target gene sequences were not directly related to domestic novel coronavirus sequences during the same period, but were related to isolates from Europe and Mongolia.
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Humanos , COVID-19 , SARS-CoV-2/genética , Filogenia , Genoma Viral , Nucleótidos , Análisis de SecuenciaRESUMEN
The target gene sequences of the novel coronaviruses obtained by sequencing were compared with the reference sequences to analyze the genetic variation of the two cases of the novel coronaviruses from Inner Mongolia Autonomous Region in 2022 and to explore the sources of infection. The results showed that the two sequences belonged to different evolutionary branches, Delta (AY.122) and Omicron (BA.1.1), respectively. hCoV-19/Inner Mongolia/IVDC-591/2022 had 48 single nucleotide polymorphisms on the genome sequences, sharing 40 nucleotide mutation sites with a Mongolian strain; hCoV-19/Inner Mongolia/IVDC-592/2022 genome shared 57 nucleotide mutation sites with a UK strain, and the nucleotide mutation site identity was 100% (57/57). Phylogenetic analysis showed that the target gene sequences were not directly related to domestic novel coronavirus sequences during the same period, but were related to isolates from Europe and Mongolia.
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Humanos , COVID-19 , SARS-CoV-2/genética , Filogenia , Genoma Viral , Nucleótidos , Análisis de SecuenciaRESUMEN
The P450-mediated terminal hydroxylation of non-activated C-H bonds is a chemically challenging reaction. CYP153A7 monooxygenase, discovered in Sphingomonas sp. HXN200, belongs to the CYP153A subfamily and shows a pronounced terminal selectivity. Herein, we report the significantly improved terminal hydroxylation activity of CYP153A7 by redesign of the substrate binding pocket based on molecular docking of CYP153A7-C8:0 and sequence alignments. Some of the resultant single mutants were advantageous over the wild-type enzyme with higher reaction rates, achieving a complete conversion of n-octanoic acid (C8:0, 1â mM) in a shorter time period. Especially, a single-mutation variant, D258E, showed 3.8-fold higher catalytic efficiency than the wild type toward the terminal hydroxylation of medium-chain fatty acid C8:0 to the high value-added product 8-hydroxyoctanoic acid.
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Sistema Enzimático del Citocromo P-450 , Ácidos Grasos , Dominio Catalítico , Sistema Enzimático del Citocromo P-450/metabolismo , Ácidos Grasos/química , Hidroxilación , Simulación del Acoplamiento Molecular , Especificidad por SustratoRESUMEN
BACKGROUND: Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. METHODS: Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan-Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. RESULTS: In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan-Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. CONCLUSIONS: In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. HIGHLIGHTS: 1. Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. 2. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. 3. DPYSL2 can independently predict the LUAD outcomes. 4. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Biomarcadores de Tumor/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Linfocitos Infiltrantes de Tumor , Pronóstico , Microambiente TumoralRESUMEN
In order to evaluate the land quality geochemical survey achievement in the service of the accurate management of urban land resources, the initial area of the Xiong'an New District as urbanization pathfinder in China is chosen as the research subject. The sample points were set by differential classification, and the spatial interpolation accuracy of the soil elements at a plot scale and a quantitative assessment of the consistency of the land plot (pattern spot) prediction evaluation were studied under the conditions of different sampling densities. The regional geochemical variation values randomly distributed on the plane can be reflected quantitatively by differential classification sampling, which can meet the basic demand of the quality attribute of a single plot (map spot) by the accurate management of urban land resources. The spatial variability of soil elements is mostly middle to moderate, and Cd, Cu, Pb, Hg, Se, N, P, and other elements of high spatial variability are affected by human industrial and agricultural production activities. Under the same sampling density, the larger the element variation coefficient, the worse the spatial interpolation accuracy. Although the interpolation accuracy of the same element index is affected by the sampling density, the increase in the sampling density could not identify the continuous component on the structure of the soil element content. The soil environment is clean, and the heavy metal content is lower than the GB15618-2018 standard. The interpolation results are basically consistent with the grading results of the measured values, while the contents of N, P, and K of the nutrient indices vary greatly, and the predicted and measured geochemical grades of the plots (map spot) differ substantially under the influence of factors such as human disturbance and spatial variability. The quantitative evaluation of the six different sampling densities indicates that the 16 points·km-2 sampling density adopted in the geochemical survey and evaluation of urban land quality can satisfy the needs of an accurate control of urban land resources in the study area and similar areas. The research can provide key technologies to support and serve the accurate management of urban land resources for geochemical surveys and the evaluation of land quality in land parcel scale cities.
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Terpenoids, formed by cyclization and/or permutation of isoprenes, are the most diverse and abundant class of natural products with a broad range of significant functions. One family of the critical enzymes involved in terpenoid biosynthesis is terpene cyclases (TCs), also known as terpene synthases (TSs), which are responsible for forming the ring structure as a backbone of functionally diverse terpenoids. With the recent advances in biotechnology, the researches on terpene cyclases have gradually shifted from the genomic mining of novel enzyme resources to the analysis of their structures and mechanisms. In this review, we summarize both the new methods for genomic mining and the structural mechanisms of some typical terpene cyclases, which are helpful for the discovery, engineering and application of more and new TCs.
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Background The 2019 Bosniak classification (version 2019) of cystic renal masses (CRMs) provides a systematic update to the currently used 2005 Bosniak classification (version 2005). Further validation is required before widespread application. Purpose To evaluate the interobserver agreement of MRI criteria, the impact of readers' experience, and the diagnostic performance between version 2019 and version 2005. Materials and Methods From January 2009 to December 2018, consecutive patients with CRM who had undergone renal MRI and surgical-pathologic examination were included in this retrospective study. On the basis of version 2019 and version 2005, all CRMs were independently classified by eight radiologists with different levels of experience. By using multirater κ statistics, interobserver agreement was evaluated with comparisons between classifications and between senior and junior radiologists. Diagnostic performance between classifications by dichotomizing classes I-IV into lower (I-IIF) and higher (III-IV) classes was compared by using the McNemar test. P < .05 was considered to indicate a statistically significant difference. Results A total of 207 patients (mean age ± standard deviation, 49 years ± 12; 139 male and 68 female patients) with CRMs were included. Overall, interobserver agreement was higher with version 2019 than version 2005 (weighted κ = 0.64 vs 0.50, respectively; P < .001). Interobserver agreement between senior and junior radiologists did not differ between version 2019 (weighted κ = 0.65 vs 0.64, respectively; P = .71) and version 2005 (weighted κ = 0.54 vs 0.46; P < .001). Diagnostic specificity for malignancy was higher with version 2019 than with version 2005 (83% [92 of 111] vs 68% [75 of 111], respectively; P < .001), without any difference in sensitivity (89% [85 of 96] vs 84% [81 of 96]; P = .34). Conclusion In the updated Bosniak classification, interobserver agreement improved and was unaffected by observers' experience. The diagnostic performance with version 2019 was superior to that with version 2005, with higher specificity. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Choyke in this issue.
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Competencia Clínica , Enfermedades Renales Quísticas/clasificación , Enfermedades Renales Quísticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estudios RetrospectivosRESUMEN
Imaging-guided percutaneous microwave ablation (MWA) with high thermal efficiency comprises rapid, successful management of small renal cell carcinomas (RCCs) in selected patients. Ultrasound Committee of Chinese Medical Association, Interventional Oncology Committee of Chinese Research Hospital Association developed evidence-based guidelines for MWA of RCCs after systematically reviewing the 1969-2019 literature. Systematic reviews, meta-analyses, randomized controlled trials, cohort, and case-control studies reporting MWA of RCCs were included and levels of evidence assessed. Altogether, 146 articles were identified, of which 35 reported percutaneous MWA for T1a RCCs and 5 articles for T1b RCCs. Guidelines were established based on indications, techniques, safety, and effectiveness of MWA for RCCs, with the goal of standardizing imaging-guided percutaneous MWA treatment of RCCs. Key points Microwave ablation is recommended for managing small renal cell carcinoma in selected patients. Imaging protocols are tailored based on the procedural plan, guidance, and evaluation. Patient's selection evaluation, updated technique information, clinical efficacy, and complications are recommended to standardize management. A joint task force (multidisciplinary team) summarized the key elements of the standardized report.
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Carcinoma de Células Renales , Ablación por Catéter , Neoplasias Renales , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/cirugía , China , Hospitales , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Microondas , Resultado del TratamientoRESUMEN
BACKGROUND: Nuclear grade is of importance for treatment selection and prognosis in patients with clear cell renal cell carcinoma (ccRCC). PURPOSE: To develop and validate an MRI-based radiomic model for preoperative predicting WHO/ISUP nuclear grade in ccRCC. STUDY TYPE: Retrospective. POPULATION: In all, 379 patients with histologically confirmed ccRCC. Training cohort (n = 252) and validation cohort (n = 127) were randomly assigned. FIELD STRENGTH/SEQUENCE: Pretreatment 3.0T renal MRI. Imaging sequences were fat-suppressed T2 WI, contrast-enhanced T1 WI, and diffusion weighted imaging. ASSESSMENT: Three prediction models were developed using selected radiomic features, radiomic and clinicoradiologic characteristics, and a model containing only clinicoradiologic characteristics. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to assess the predictive performance of these models in predicting high-grade ccRCC. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) and minimum redundancy maximum relevance (mRMR) method were used for the selection of radiomic features and clinicoradiologic characteristics, respectively. Multivariable logistic regression analysis was used to develop the radiomic signature of radiomic features and clinicoradiologic model of clinicoradiologic characteristics. RESULTS: The radiomic signature showed good performance in discriminating high-grade (grades 3 and 4) from low-grade (grades 1 and 2) ccRCC, with sensitivity, specificity, and AUC of 77.3%, 80.0%, and 0.842, respectively, in the validation cohort. The radiomic model, combining radiomic signature and clinicoradiologic characteristics, displayed good predictive ability for high-grade with sensitivity, specificity, and accuracy of 63.6%, 93.3%, and 88.2%, respectively, in the validation cohort. The radiomic model showed a significantly better performance than the clinicoradiologic model (P < 0.05). DATA CONCLUSION: Multiparametric MRI-based radiomic model can predict WHO/ISUP grade in patients with ccRCC with satisfying performance, and thus could help the physician to improve treatment decisions. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.
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Carcinoma de Células Renales , Neoplasias Renales , Imágenes de Resonancia Magnética Multiparamétrica , Carcinoma de Células Renales/diagnóstico por imagen , Humanos , Neoplasias Renales/diagnóstico por imagen , Estudios Retrospectivos , Organización Mundial de la SaludRESUMEN
Substrate inhibition of enzymes is one of the main obstacles encountered frequently in industrial biocatalysis. Haloketone reductase SsCR was seriously inhibited by substrate 2,2',4'-trichloroacetophenone. In this study, two essential loops were found that have a relationship with substrate binding by conducting X-ray crystal structure analysis. Three key residues were selected from the tips of the loops and substituted with amino acids with lower hydrophobicity to weaken the hydrophobic interactions that bridge the two loops, resulting in a remarkable reduction of substrate inhibition. Among these variants, L211H showed a significant attenuation of substrate inhibition, with a Ki of 16 mM, which was 16 times that of the native enzyme. The kinetic parameter kcat/Km of L211H was 3.1 × 103 s-1 mM-1, showing the comparable catalytic efficiency to that of the wild-type enzyme (WT). At the substrate loading of 100 mM, the space time yield of variant L211H in asymmetric reduction of the haloketone was 3-fold higher than that of the WT.
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Oxidorreductasas de Alcohol/química , Oxidorreductasas de Alcohol/metabolismo , Ingeniería de Proteínas/métodos , Oxidorreductasas de Alcohol/genética , Sitios de Unión , Biocatálisis , Cristalografía por Rayos X , Cinética , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Conformación Proteica , Especificidad por SustratoRESUMEN
BACKGROUND: Vena cava thrombus is one of the main clinical manifestations of locally aggressive renal cell carcinoma (RCC). Inferior vena cava (IVC) wall invasion and presence of bland thrombus could affect the surgical outcome. This study aims to assess the value of contrast-enhanced ultrasound (CEUS) in detecting wall invasion and differentiating bland thrombus from tumor thrombus during robot-assisted IVC thrombectomy for RCC. METHODS: The intraoperative CEUS findings of 60 patients with RCC accompanied by IVC tumor thrombus were retrospectively analyzed. The CEUS features were compared with the intra- and post-operative pathological findings. CEUS in patients with wall invasion showed that the tumor thrombus was enhanced synchronously with the IVC wall, and the continuity of the IVC wall was lost. In contrast, in patients without wall invasion, CEUS showed that the contrast agent could pass between the tumor thrombus and the IVC wall, and the continuity of IVC wall was good. Typically, contrast-enhanced perfusion was seen in tumor thrombus but not in bland thrombus. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CEUS were statistically analyzed. RESULTS: The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the typical enhancement mode of CEUS were 93.1, 93.5, 93.3, 93.1, and 93.5% in identifying wall invasion and 100, 96, 96.7, 83.3, and 100% in differentiating bland thrombus from tumor thrombus, respectively. There were excellent inter-observer agreements for identifying IVC wall invasion and differentiating bland thrombus from tumor thrombus with kappa coefficients of 0.90 and 0.97. CONCLUSIONS: The present study indicates that intraoperative CEUS plays an important role in robot-assisted IVC thrombectomy for RCC. It can detect wall invasion and differentiate bland thrombus from tumor thrombus, thus offering real-time information to the operator during surgery.
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Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Células Neoplásicas Circulantes , Trombectomía/métodos , Trombosis/diagnóstico por imagen , Ultrasonografía/métodos , Vena Cava Inferior/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/patología , Medios de Contraste , Femenino , Humanos , Cuidados Intraoperatorios , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/diagnóstico por imagen , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados , Trombosis/cirugía , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/patología , Trombosis de la Vena/patologíaRESUMEN
Clinical data of 85 patients with breast abscess during lactation treated in our hospital from January 2014 to October 2017 were retrospectively analyzed.Among 85 cases,30 patients received traditional abscess incision drainage,35 received needle aspiration,and 20 received negative pressure drainage with small incision.The pus culture findings,average hospitalization expenses,average treatment time,pain score,postoperative breast appearance were evaluated.The pus culture found 24 cases of staphylococcus aureus infection in 85 cases (28%),including 40 cases of Methicillin resistant Staphylococcus aureus (47%).The proportion of central abscess (14/20) in patients with small incision drainage was significantly higher than that of patients with needle aspiration treatment (4/35) (P<0.05).The average hospitalization expense of the puncture group was significantly lower than that of other two groups (P<0.01).The average treatment time of abscess incision drainage group was significantly higher than that of other two groups (P<0.01),and the recovery time was all longer 1 month.The score of pain in the abscess incision drainage group was significantly higher than that in other two groups (P<0.01),and all patients had moderate to severe pain.The breast shape satisfaction of abscess incision drainage group was significantly lower than that of other two groups (P<0.01).The analysis indicates that treatment of breast abscess during lactation with needle aspiration and negative pressure drainage has short treatment time,no scars and less pain;and it is suggested that central abscess may be treated early with negative pressure drainage.
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Preoperative renal tumor subtype differentiation is important for radiology and urology in clinical practice. Pharmacokinetic data (K trans & V e, etc.) derived from dynamic contrast-enhanced MRI (DCE-MRI) have been used to investigate tumor vessel permeability. In this prospective study on DCE-MRI pharmacokinetic studies, we enrolled patients with five common renal tumor subtypes: clear cell renal cell carcinoma (ccRCC; n = 65), papillary renal cell carcinoma (pRCC; n = 12), chromophobic renal cell carcinoma (cRCC; n = 9), uroepithelial carcinoma (UEC; n = 14), and fat-poor angiomyolipoma (fpAML; n = 10). The results show that K trans of ccRCC, pRCC, cRCC, UEC and fpAML (0.459 ± 0.190 min-1, 0.206 ± 0.127 min-1, 0.311 ± 0.111 min-1, 0.235 ± 0.116 min-1, 0.511 ± 0.159 min-1, respectively) were different, but V e was not. K trans could distinguish ccRCC from non-ccRCC (pRCC & cRCC) with a sensitivity of 76.9% and a specificity of 71.4%, respectively, as well as to differentiate fpAML from non-ccRCC with a sensitivity of 100% and a specificity of 76.2%, respectively. Our findings suggest that DCE-MRI pharmacokinetics are promising for differential diagnosis of renal tumors, especially for RCC subtype characterization and differentiation between fpAML and non-ccRCC, which may facilitate the treatment of renal tumors.
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Aumento de la Imagen , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Imagen por Resonancia Magnética , Adulto , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Femenino , Humanos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/metabolismo , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Curva ROC , Carga TumoralRESUMEN
Pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) have been increasingly used to evaluate the permeability of tumor vessel. Histogram metrics are a recognized promising method of quantitative MR imaging that has been recently introduced in analysis of DCE-MRI pharmacokinetic parameters in oncology due to tumor heterogeneity. In this study, 21 patients with renal cell carcinoma (RCC) underwent paired DCE-MRI studies on a 3.0 T MR system. Extended Tofts model and population-based arterial input function were used to calculate kinetic parameters of RCC tumors. Mean value and histogram metrics (Mode, Skewness and Kurtosis) of each pharmacokinetic parameter were generated automatically using ImageJ software. Intra- and inter-observer reproducibility and scan-rescan reproducibility were evaluated using intra-class correlation coefficients (ICCs) and coefficient of variation (CoV). Our results demonstrated that the histogram method (Mode, Skewness and Kurtosis) was not superior to the conventional Mean value method in reproducibility evaluation on DCE-MRI pharmacokinetic parameters (K( trans) &Ve) in renal cell carcinoma, especially for Skewness and Kurtosis which showed lower intra-, inter-observer and scan-rescan reproducibility than Mean value. Our findings suggest that additional studies are necessary before wide incorporation of histogram metrics in quantitative analysis of DCE-MRI pharmacokinetic parameters.
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Carcinoma de Células Renales/diagnóstico por imagen , Medios de Contraste/farmacocinética , Neoplasias Renales/diagnóstico por imagen , Imagen por Resonancia Magnética , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To investigate the clinic-pathological characteristics and prognosis of 48 female cases with peritoneal pseudomyxoma(PMP). METHODS: The clinicopathologic features and follow-up data of 48 female patients with PMP diagnosed in the General Hospital of People's Liberation Army from Jan.1982 to Dec.2011 were retrospectively reviewed. The relationship between clinic-pathological characteristics and prognosis were analyzed using log-rank test and Cox proportional hazards model. RESULTS: (1) Clinicopathologic features: the mean age of the 48 cases was 58.8 years (range from 24 to 79 years). SYMPTOMS: abdominal distention and abdominal discomfort were the main symptoms. Imaging examinations showed nonspecific abdominal and pelvic lesions in most cases. TREATMENT: all the 48 patients underwent laparotomy and cytoreductive surgery (CRS), in which 15(31%) patients with completeness of the cancer resection (CCR) -1, 24(50%) cases with CCR-2, and CCR-3 in 9(19%) cases. Six (12%) cases were treated by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin, 20(42%) patients were treated with different options postoperative adjuvant chemotherapy. Pathological types:the cases were histologically classified into 3 subcategories:disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and PMCA with intermediate or discordant features (PMCA-I/D), which were 22(46%) cases, 9 (19%)cases and 17 (35%)cases, respectively. Appendiceal tumors: 44(92%) cases underwent appendectomy, in which 38 cases presented appendiceal tumors (including 20 cases of low-grade appendiceal mucinous adenoma and 18 cases of appendiceal mucinous adenocarcinoma), 2 cases were diagnosed as appendicitis, 4 cases with unknown pathologic diagnosis. And the other 4(8%) cases, who didn't undergo appendectomy at the first operation, presented peritoneal tumor recurrence and appendiceal mucinous tumors 1, 11, 32 and 85 months after surgery, respectively. Parenchymal organs involved: ovarian involving was happened in 34 (71%) patients including 15 cases with the right ovary involving, 13 cases in both sides, and 6 cases involving the left side. The other parenchymal organs in 10(21%) cases. (2) Prognostic factors: 11 patients died, 31 survived and 6 cases were lost to follow-up. The mean survival time was 99 months(ranged from 1 to 312 months). The 3-year, 5-year and 10-year survival rates were 73.3%, 68.0% and 46.6%, respectively. Univariate statistical analysis showed that age, pathological type and parenchymal involvement were significantly relationship with the survival time (all P < 0.05). But the operation times, appendiceal tumor type, ovarian involvement, CCR, intraperitoneal HIPEC and post-operative adjuvant chemotherapy were not significantly correlate with survival time (all P > 0.05). Multivariate analysis showed that age and pathologic type were independent prognostic factors(P < 0.05). CONCLUSIONS: No specific clinical features presented in PMP. CRS with HIPEC should the recommended treatment. Both ovaries exploration and appendectomy should be carried out routinely in CRS. The 10-year overall survival of PMP is low. Age, pathological type and parenchymal organs involvement other than ovarian are correlated with the prognosis. And the pathological type and age are independent prognostic factors of PMP.
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Adenocarcinoma Mucinoso/patología , Neoplasias del Apéndice/patología , Neoplasias Peritoneales/patología , Seudomixoma Peritoneal/patología , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/terapia , Adulto , Factores de Edad , Anciano , Apendicectomía , Neoplasias del Apéndice/diagnóstico , Neoplasias del Apéndice/terapia , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/terapia , Pronóstico , Seudomixoma Peritoneal/diagnóstico , Seudomixoma Peritoneal/terapia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To study the clinicopathologic features and histologic differential diagnosis of small cell neuroendocrine carcinoma (SmCC) of kidney. METHODS: The clinicopathologic features of 12 cases of SmCC of kidney encountered during the period from 1999 to 2010 were retrospectively reviewed. RESULTS: Six cases of primary and 6 cases of metastatic SmCC involving kidney were identified. Amongst the primary renal SmCC, 2 were located in renal parenchyma and 4 in renal pelvis. Chest X-ray showed negative findings. Five of them underwent radical nephrectomy. On gross examination, the tumor was located centrally around the renal pelvis in 4 cases and peripherally in renal parenchyma in 1 case. On the other hand, 4 of the 6 cases of metastatic SmCC were discovered during therapy for pulmonary SmCC. Two of these patients presented with abdominal pain and gross hematuria, with lung and renal tumor masses identified simultaneously. The diagnosis of all the 6 cases of metastatic SmCC was confirmed by fine needle aspiration biopsy. Microscopically, pure SmCC was demonstrated in the 2 cases of primary renal parenchymal SmCC and 6 cases of metastatic SmCC. The 4 primary renal pelvic SmCC coexisted with urothelial carcinoma component. On immunohistochemical study, all cases were positive for cytokeratin, synaptophysin and CD56. All metastatic cases and 4 primary cases were also positive for TTF-1. Of six patients with primary SmCC two died 4 and 9 months after operation, and two were alive with a follow-up of 25 and 138 months, respectively. Five of six cases with metastatic SmCC died 3 - 8 months after diagnosis. The other 3 cases were failed to follow-up. CONCLUSIONS: Both primary and metastatic SmCC can be found in the kidney. Although rare, primary SmCC is located either in renal parenchyma or in pelvis. The diagnosis of SmCC relies on morphologic examination and immunohistochemical study. TTF-1 immunostaining cannot reliably distinguish primary from metastatic SmCC in kidney. Correlation with clinicoradiologic findings and demonstration of coexisting urothelial carcinoma component (if any) is helpful in delineation of the tumor origin.
Asunto(s)
Carcinoma Neuroendocrino/patología , Carcinoma de Células Pequeñas/patología , Neoplasias Renales/patología , Neoplasias Pulmonares/secundario , Adulto , Anciano , Antígeno CD56/metabolismo , Carcinoma Neuroendocrino/metabolismo , Carcinoma Neuroendocrino/secundario , Carcinoma Neuroendocrino/cirugía , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Carcinoma de Células Pequeñas/metabolismo , Carcinoma de Células Pequeñas/secundario , Carcinoma de Células Pequeñas/cirugía , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Queratinas/metabolismo , Neoplasias Renales/metabolismo , Neoplasias Renales/secundario , Neoplasias Renales/cirugía , Neoplasias Pulmonares/patología , Linfoma/metabolismo , Linfoma/patología , Masculino , Persona de Mediana Edad , Nefrectomía , Proteínas Nucleares/metabolismo , Estudios Retrospectivos , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/patología , Sinaptofisina/metabolismo , Factor Nuclear Tiroideo 1 , Factores de Transcripción/metabolismo , Resultado del Tratamiento , Tumor de Wilms/metabolismo , Tumor de Wilms/patologíaRESUMEN
OBJECTIVE: To explore prognostic factors and the expression of glypican-3, hepatocyte antigen (HEP), alpha-fetoprotein (AFP), CD34 and CD10 in hepatocellular carcinoma (HCC) and their prognostic value. METHODS: Clinicopathologic data were analyzed in 375 cases of HCC, in which 80 cases with follow-up were examined by immunohistochemical staining to detect the expression of glypican-3, HEP, AFP, CD34 and CD10 proteins. The relationship between the proteins expression and clinicopathologic features was also evaluated. RESULTS: Tumor number (P = 0.000), tumor size (P = 0.025), tumor differentiation (P = 0.001) and vessel invasion (P = 0.000) were closely related to prognosis of HCC patients; the expression of glypican-3 (66/80,82.5%; P = 0.002), HEP (64/80,80.0%; P = 0.021), AFP (38/80,47.5%; P = 0.014) and CD10 (28/80,35.0%; P = 0.002) was significantly related to tumor differentiation; that of glypican-3 was significantly correlated with tumor number and presence of satellite nodules (P = 0.028) and that of AFP and CD10 was significantly correlated with portal vein thrombi (P = 0.000, P = 0.010). On Kaplan-Meier regression analysis, both low expression of HEP and high expression of AFP were closely related to poor prognosis. CONCLUSIONS: Tumor number, size, differentiation and vessel invasion were important factors affecting the prognosis of patients with HCC. HEP and AFP have prognostic significance in HCC.