Research hotspots and new trends in the impact of resistance training on aging, bibliometric and visual analysis based on CiteSpace and VOSviewer.

Purpose: Resistance training (RT) can intervene in aging, which can effectively improve trainees' life. However, unhealthy living habits such as irregular life, obesity and hyperlipidemia, and chronic diseases lead to a significant decline in the energy level of the population, seriously affecting the health of the population. Our research identifies the research hotspots of RT to intervene in aging from the perspective of bibliometrics, predicts research frontiers and development trends, and provides more perspectives for research on aging populations. Methods: In this study, we used CiteSpace and VOSviewer visualization software to draw the scientific knowledge map of countries/regions, institutions, authors, co-occurrence keywords, and co-cited references of published articles, and explore the Web of Science core collection database all about the RT intervention aging research status, hotspots, frontiers, and development trends of articles on aging. Results: Among the 760 articles that meet the inclusion criteria, the number of articles published and the frequency of citations have increased steadily in the past 5 years. Judging from the countries/regions, institutions, scholars, and journals that published articles, the ones with the largest numbers are the USA, Univ Estadual Londrina, Cyrino ES, and Exp Gerontol. The ones with the highest influence are England, Univ Arkansas Med Sci, Frontera WR, and Biochem Biophys Rep Co. The top five co-occurrence keywords of include exercise, strength, resistance training, skeletal muscle, and muscle strength. The research frontier is physical function. Conclusion: In the field of RT intervention aging research, relevant scholars deserve further in-depth research and exploration. The United States, Brazil, Canada, and other economically developed countries/regions, institutions, and authors have greater influence and productivity. These quantitative research results can provide references for relevant scholars' follow-up research and government departments to formulate and modify health policies or measures.

Investigation of the relationship between red blood cell distribution width and mortality in patients with hemophagocytic lymphohistiocytosis: a retrospective study.

BACKGROUND: Red blood cell distribution width (RDW) is related to sepsis-related mortality. Hemophagocytic lymphohistiocytosis (HLH) is a syndrome caused by severe infection, tumors, or autoimmunity without a specific diagnosis. OBJECTIVE: To explore the correlation between RDW and mortality in patients with HLH. DESIGN AND SETTING: A retrospective study conducted in a hospital in China. METHODS: A total of 101 inpatients with HLH from January 1, 2017 to December 31, 2021 were divided into non-survivor (n = 52) and survivor (n = 49) groups. A non-parametric test was used to analyze demographic, clinical, and laboratory data between groups. Independent variables with P < 0.05 were analyzed using binary logistic regression to screen out mortality-related variables. Selected variables were subjected to multivariate logistic regression analysis, and those with strong correlations were screened. Receiver operating characteristic (ROC) curves of strongly correlated variables and area under curve (AUC) values were obtained. RESULTS: The APACHE II score, RDW, and platelet (PLT) and fibrinogen (FIB) levels (P < 0.05) different significantly. RDW, PLT, FIB were correlated with mortality. The AUC values of RDW, PLT, and FIB were 0.857, 0.797, and 0.726, respectively. RDW was associated with mortality in patients with HLH (P < 0.01, cut-off value: 16.9). The sensitivity and specificity of predicting mortality were 97.96% and 96.1%, respectively. CONCLUSION: Logistic regression analysis showed a correlation between RDW and patients' mortality. Therefore, RDW can be used to predict mortality in patients with HLH.

The B-box transcription factor IbBBX29 regulates leaf development and flavonoid biosynthesis in sweet potato.

Plant flavonoids are valuable natural antioxidants. Sweet potato (Ipomoea batatas) leaves are rich in flavonoids, regenerate rapidly, and can adapt to harsh environments, making them an ideal material for flavonoid biofortification. Here, we demonstrate that the B-box (BBX) family transcription factor IbBBX29 regulates the flavonoid contents and development of sweet potato leaves. IbBBX29 was highly expressed in sweet potato leaves and significantly induced by auxin (IAA). Overexpression of IbBBX29 contributed to a 21.37%-70.94% increase in leaf biomass, a 12.08%-21.85% increase in IAA levels, and a 31.33%-63.03% increase in flavonoid accumulation in sweet potato, whereas silencing this gene produced opposite effects. Heterologous expression of IbBBX29 in Arabidopsis (Arabidopsis thaliana) led to a dwarfed phenotype, along with enhanced IAA and flavonoid accumulation. RNA-seq analysis revealed that IbBBX29 modulates the expression of genes involved in the IAA signaling and flavonoid biosynthesis pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assay indicated that IbBBX29 targets key genes of IAA signaling and flavonoid biosynthesis to activate their expression by binding to specific T/G-boxes in their promoters, especially those adjacent to the transcription start site. Moreover, IbBBX29 physically interacted with developmental and phenylpropanoid biosynthesis-related proteins, such as AGAMOUS-LIKE 21 protein IbAGL21 and MYB308-like protein IbMYB308L. Finally, overexpressing IbBBX29 also increased flavonoid contents in sweet potato storage roots. These findings indicate that IbBBX29 plays a pivotal role in regulating IAA-mediated leaf development and flavonoid biosynthesis in sweet potato and Arabidopsis, providing a candidate gene for flavonoid biofortification in plants.

Investigation of the relationship between red blood cell distribution width and mortality in patients with hemophagocytic lymphohistiocytosis: a retrospective study

ABSTRACT BACKGROUND: Red blood cell distribution width (RDW) is related to sepsis-related mortality. Hemophagocytic lymphohistiocytosis (HLH) is a syndrome caused by severe infection, tumors, or autoimmunity without a specific diagnosis. OBJECTIVE: To explore the correlation between RDW and mortality in patients with HLH. DESIGN AND SETTING: A retrospective study conducted in a hospital in China. METHODS: A total of 101 inpatients with HLH from January 1, 2017 to December 31, 2021 were divided into non-survivor (n = 52) and survivor (n = 49) groups. A non-parametric test was used to analyze demographic, clinical, and laboratory data between groups. Independent variables with P < 0.05 were analyzed using binary logistic regression to screen out mortality-related variables. Selected variables were subjected to multivariate logistic regression analysis, and those with strong correlations were screened. Receiver operating characteristic (ROC) curves of strongly correlated variables and area under curve (AUC) values were obtained. RESULTS: The APACHE II score, RDW, and platelet (PLT) and fibrinogen (FIB) levels (P < 0.05) different significantly. RDW, PLT, FIB were correlated with mortality. The AUC values of RDW, PLT, and FIB were 0.857, 0.797, and 0.726, respectively. RDW was associated with mortality in patients with HLH (P < 0.01, cut-off value: 16.9). The sensitivity and specificity of predicting mortality were 97.96% and 96.1%, respectively. CONCLUSION: Logistic regression analysis showed a correlation between RDW and patients' mortality. Therefore, RDW can be used to predict mortality in patients with HLH.

Identification and characterization of nontuberculous mycobacteria isolated from suspected pulmonary tuberculosis patients in eastern china from 2009 to 2019 using an identification array system.

OBJECTIVE: Nontuberculous mycobacteria (NTM) species are increasingly being isolated and have become a key factor affecting public health by causing pulmonary diseases. Most NTM species do not respond to conventional tuberculosis (TB) drugs. This study aimed to identify NTM isolated from suspected pulmonary TB patients from the Zhejiang province and analyze their distribution in the region. METHODS: A total of 1,113 NTM isolates from patients suspected to be suffering from acid-fast bacilli-positive tuberculosis were identified at the species level, using the CapitalBio Mycobacterium identification array and polymerase chain reaction amplification and sequencing of 16S-23S gene internal transcribed spacer (ITS), 16S rRNA, and hsp65. RESULTS: Of the 23,138 isolates, we identified 1,102 NTM (4.8%), mainly including Mycobacterium intracellulare (54.81%, 604/1,102), M. chelonae-M. abscessus (16.52%, 182/1,102), M. avium (13.16%, 145/1,102), M. kansasii (8.17%, 90/1,102), and M. gordonae (3.27%, 36/1,102). CONCLUSION: The distribution of NTM species observed in patients with suspected pulmonary tuberculosis provides guidance for the diagnosis and treatment of NTM pulmonary diseases.

Assessment of standing passenger traumatic brain injury caused by ground impact in subway collisions.

Human head is the most vulnerable region in subway collisions. To design a safer subway, the head impact biomechanical response should be studied first. This paper aims to investigate the standing passenger head-ground impact dynamic response and traumatic brain injury (TBI) in subway collisions. A standing passenger-subway interior dynamic model was numerically developed by using our previous validated finite element (FE)-multibody (MB) coupled human body model, which was integrated by the Total Human Model for Safety (THUMS) head-neck FE model and the extracted remaining body segments pedestrian MB model of TNO. A parametric study considering the handrail type, standing angle, and friction coefficient between the shoes and ground was performed. Results show that the passenger dynamic response could be divided into two categories according to whether the passenger hit handrails. Passenger TBIs severity could be efficiently alleviated by the passenger body (excluding the head) hitting the handrail first before head-ground impact. The probabilities of DAI in the cerebellum and brain stem were low. A statistical analysis of TBIs demonstrated that the risks of TBIs were sensitive to the handrail type in subway collisions, but did not to the standing angle and friction coefficient. This study provides practical help for improving the interior crashworthiness performance of subways.

Unusual polymethylene-interrupted, Δ5 monounsaturated and omega-3 fatty acids in sea urchin (Arbacia punctulata) from the Gulf of Mexico identified by solvent mediated covalent adduct chemical ionization mass spectrometry.

Sea urchin (class Echinoidea) gonads are a prized delicacy in Japan and many other world cultures. The complexity of its fatty acid (FA) profile, particularly minor FA, presents a formidable analytical challenge. We applied solvent mediated (SM) covalent adduct chemical ionization (CACI) tandem mass spectrometry to comprehensive de novo structural and quantitative characterization of the FA profile of Gulf of Mexico Atlantic sea urchin (Arbacia punctulata). >100 FA were detected including many with unusual double bond structure. Gulf sea urchin gonad lipids are rich in Δ5 monounsaturated FA 20:1(5Z) at 2.7% and the polymethylene-interrupted (PMI) diene 20:2(5Z,11Z) at 4.9%, as well as common omega-3 eicosapentaenoic acid (EPA; 5Z, 8Z, 11Z, 14Z, 17Z) at 9.8%±3.1% and arachidonic acid (AA; 5Z, 8Z, 11Z, 14Z) at 6.1%±2.1%. We propose plausible desaturation/elongation-based biochemical pathways for the endogenous production of unusual unsaturates. Unusual unsaturates may modify mammalian signaling and present novel bioactivities.

Identification and characterization of nontuberculous mycobacteria isolated from suspected pulmonary tuberculosis patients in eastern china from 2009 to 2019 using an identification array system

Abstract Objective Nontuberculous mycobacteria (NTM) species are increasingly being isolated and have become a key factor affecting public health by causing pulmonary diseases. Most NTM species do not respond to conventional tuberculosis (TB) drugs. This study aimed to identify NTM isolated from suspected pulmonary TB patients from the Zhejiang province and analyze their distribution in the region. Methods A total of 1,113 NTM isolates from patients suspected to be suffering from acid-fast bacilli-positive tuberculosis were identified at the species level, using the CapitalBio Mycobacterium identification array and polymerase chain reaction amplification and sequencing of 16S-23S gene internal transcribed spacer (ITS), 16S rRNA, and hsp65. Results Of the 23,138 isolates, we identified 1,102 NTM (4.8%), mainly including Mycobacterium intracellulare (54.81%, 604/1,102), M. chelonae-M. abscessus (16.52%, 182/1,102), M. avium (13.16%, 145/1,102), M. kansasii (8.17%, 90/1,102), and M. gordonae (3.27%, 36/1,102). Conclusion The distribution of NTM species observed in patients with suspected pulmonary tuberculosis provides guidance for the diagnosis and treatment of NTM pulmonary diseases.

Challenging Diagnosis and Endoscopic Management of Dieulafoy's Lesion-Induced Small-Bowel Bleeding: A Case Report.

Small-bowel bleeding is a relatively uncommon event of gastrointestinal bleeding. Some causes of small-bowel bleeding, such as vascular lesions, are still challenging to confirm, despite the use of various diagnostic modalities (e.g., capsule endoscopy, deep enteroscopy, and radiographic imaging). Vascular lesion-induced bleeding tends to be insidious and intermittent, but sometimes it can be massive and fatal, so that the timing of an endoscopy is critical. We describe herein the case of an elderly female patient with Dieulafoy's lesion-induced small-bowel bleeding presenting with recurrent melena. In this article, we describe how the cause of her bleeding was found and how the bleeding was stopped endoscopically. Finally, we discuss the characteristics of a small-bowel Dieulafoy's lesion and its endoscopic treatment.

Serum uric acid levels and hyperuricemia in patients with psoriasis: a hospital-based cross-sectional study

Abstract: A hospital-based cross-sectional study was performed, including 117 psoriatic patients and 117 controls matched for age, gender, and body mass index. Psoriatic patients had higher levels of serum uric acid (6.25 ± 1.62 vs 5.71 ± 1.35 mg/dl; P=0.019) and significantly greater prevalence of hyperuricemia (31.6% vs 16.2%; P=0.009) than individuals without psoriasis. Psoriatic patients had significantly higher serum uric acid than controls in subjects without metabolic syndrome. Multivariate logistic regression analysis showed that psoriasis can be a strong predictor of hyperuricemia (odds ratio 2.61; 95% confidence interval 1.34-5.00; P=0.004).

Serum uric acid levels and hyperuricemia in patients with psoriasis: a hospital-based cross-sectional study.

A hospital-based cross-sectional study was performed, including 117 psoriatic patients and 117 controls matched for age, gender, and body mass index. Psoriatic patients had higher levels of serum uric acid (6.25 ± 1.62 vs 5.71 ± 1.35 mg/dl; P=0.019) and significantly greater prevalence of hyperuricemia (31.6% vs 16.2%; P=0.009) than individuals without psoriasis. Psoriatic patients had significantly higher serum uric acid than controls in subjects without metabolic syndrome. Multivariate logistic regression analysis showed that psoriasis can be a strong predictor of hyperuricemia (odds ratio 2.61; 95% confidence interval 1.34-5.00; P=0.004).

The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi

Aspergillus sp., Fusarium sp., and Ramularia sp. were endophytic fungi isolated from Rumex gmelini Turcz (RGT), all of these three strains could produce some similar bioactive secondary metabolites of their host. However the ability to produce active components degraded significantly after cultured these fungi alone for a long time, and were difficult to recover. In order to obtain more bioactive secondary metabolites, the co-culture of tissue culture seedlings of RGT and its endophytic fungi were established respectively, and RGT seedling was selected as producer. Among these fungi, Aspergillus sp. showed the most significant enhancement on bioactive components accumulation in RGT seedlings. When inoculated Aspergillus sp. spores into media of RGT seedlings that had taken root for 20 d, and made spore concentration in co-culture medium was 1 × 104 mL-1, after co-cultured for 12 d, the yield of chrysophaein, resveratrol, chrysophanol, emodin and physcion were 3.52-, 3.70-, 3.60-, 4.25-, 3.85-fold of the control group. The extreme value of musizin yield was 0.289 mg, which was not detected in the control groups. The results indicated that co-culture with endophytic fungi could significantly enhance bioactive secondary metabolites production of RGT seedlings.(AU)

The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi

Abstract Aspergillus sp., Fusarium sp., and Ramularia sp. were endophytic fungi isolated from Rumex gmelini Turcz (RGT), all of these three strains could produce some similar bioactive secondary metabolites of their host. However the ability to produce active components degraded significantly after cultured these fungi alone for a long time, and were difficult to recover. In order to obtain more bioactive secondary metabolites, the co-culture of tissue culture seedlings of RGT and its endophytic fungi were established respectively, and RGT seedling was selected as producer. Among these fungi, Aspergillus sp. showed the most significant enhancement on bioactive components accumulation in RGT seedlings. When inoculated Aspergillus sp. spores into media of RGT seedlings that had taken root for 20 d, and made spore concentration in co-culture medium was 1 × 104 mL-1, after co-cultured for 12 d, the yield of chrysophaein, resveratrol, chrysophanol, emodin and physcion were 3.52-, 3.70-, 3.60-, 4.25-, 3.85-fold of the control group. The extreme value of musizin yield was 0.289 mg, which was not detected in the control groups. The results indicated that co-culture with endophytic fungi could significantly enhance bioactive secondary metabolites production of RGT seedlings.

The clinical efficacy and safety of paclitaxel combined with avastin for NSCLC patients diagnosed with malignant pleural effusion.

OBJECTIVE: The current study aimed to investigate the clinical efficacy of paclitaxel combined with avastin for non-small cell lung cancer (NSCLC) patients diagnosed with malignant pleural effusion (MPE). METHOD: Total of 33 patients diagnosed with NSCLC as well as malignant pleural effusion were included. All of them received paclitaxel (175 mg/m2) and avastin (5 mg/kg). Clinical efficacy was evaluated using the total response rate, overall survival, progression-free survival and changes in MPE volume. Adverse events and rates of toxicities were examined as well. RESULTS: The total response rate reached 77% while the overall survival and the median progression-free survival were respectively 22.2 months and 8.4 months. Toxicities of grade 3-4 consisted of neutropenia in 57% of patients, anemia in 17% of them, febrile neutropenia in 11%, as well as anorexia in 7%. No treatment-correlated deaths were found. CONCLUSION: Paclitaxel combined with avastin decreased MPE volume and increased survival rate of NSCLC patients via inhibiting vascular endothelial growth factor expression.

The clinical efficacy and safety of paclitaxel combined with avastin for NSCLC patients diagnosed with malignant pleural effusion

Summary Objective: The current study aimed to investigate the clinical efficacy of paclitaxel combined with avastin for non-small cell lung cancer (NSCLC) patients diagnosed with malignant pleural effusion (MPE). Method: Total of 33 patients diagnosed with NSCLC as well as malignant pleural effusion were included. All of them received paclitaxel (175 mg/m2) and avastin (5 mg/kg). Clinical efficacy was evaluated using the total response rate, overall survival, progression-free survival and changes in MPE volume. Adverse events and rates of toxicities were examined as well. Results: The total response rate reached 77% while the overall survival and the median progression-free survival were respectively 22.2 months and 8.4 months. Toxicities of grade 3-4 consisted of neutropenia in 57% of patients, anemia in 17% of them, febrile neutropenia in 11%, as well as anorexia in 7%. No treatment-correlated deaths were found. Conclusion: Paclitaxel combined with avastin decreased MPE volume and increased survival rate of NSCLC patients via inhibiting vascular endothelial growth factor expression.

The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi.

Aspergillus sp., Fusarium sp., and Ramularia sp. were endophytic fungi isolated from Rumex gmelini Turcz (RGT), all of these three strains could produce some similar bioactive secondary metabolites of their host. However the ability to produce active components degraded significantly after cultured these fungi alone for a long time, and were difficult to recover. In order to obtain more bioactive secondary metabolites, the co-culture of tissue culture seedlings of RGT and its endophytic fungi were established respectively, and RGT seedling was selected as producer. Among these fungi, Aspergillus sp. showed the most significant enhancement on bioactive components accumulation in RGT seedlings. When inoculated Aspergillus sp. spores into media of RGT seedlings that had taken root for 20d, and made spore concentration in co-culture medium was 1×104mL-1, after co-cultured for 12d, the yield of chrysophaein, resveratrol, chrysophanol, emodin and physcion were 3.52-, 3.70-, 3.60-, 4.25-, 3.85-fold of the control group. The extreme value of musizin yield was 0.289mg, which was not detected in the control groups. The results indicated that co-culture with endophytic fungi could significantly enhance bioactive secondary metabolites production of RGT seedlings.

The improvement of bioactive secondary metabolites accumulation in Rumex gmelini Turcz through co-culture with endophytic fungi

Abstract Aspergillus sp., Fusarium sp., and Ramularia sp. were endophytic fungi isolated from Rumex gmelini Turcz (RGT), all of these three strains could produce some similar bioactive secondary metabolites of their host. However the ability to produce active components degraded significantly after cultured these fungi alone for a long time, and were difficult to recover. In order to obtain more bioactive secondary metabolites, the co-culture of tissue culture seedlings of RGT and its endophytic fungi were established respectively, and RGT seedling was selected as producer. Among these fungi, Aspergillus sp. showed the most significant enhancement on bioactive components accumulation in RGT seedlings. When inoculated Aspergillus sp. spores into media of RGT seedlings that had taken root for 20 d, and made spore concentration in co-culture medium was 1 × 104 mL-1, after co-cultured for 12 d, the yield of chrysophaein, resveratrol, chrysophanol, emodin and physcion were 3.52-, 3.70-, 3.60-, 4.25-, 3.85-fold of the control group. The extreme value of musizin yield was 0.289 mg, which was not detected in the control groups. The results indicated that co-culture with endophytic fungi could significantly enhance bioactive secondary metabolites production of RGT seedlings.

Impact of the integration of proton magnetic resonance imaging spectroscopy to PI-RADS 2 for prediction of high grade and high stage prostate cancer.

OBJECTIVE: To compare the predictions of dominant Gleason pattern ≥ 4 or non-organ confined disease with Prostate Imaging Reporting and Data System (PI-RADS v2) with or without proton magnetic resonance spectroscopic imaging (1H-MRSI). MATERIALS AND METHODS: Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including 1H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and 1H-MRSI scores to index lesions. Statistical analyses used logistic regressions, receiver operating characteristic (ROC) curves, and 2x2 tables for diagnostic accuracies. RESULTS: The sensitivity and specificity of 1H-MRSI and PI-RADS v2 for high-grade prostate cancer (PCa) were 85.7% (57.1%) and 92.9% (100%), and 56% (68.0%) and 24.0% (24.0%). The sensitivity and specificity of 1H-MRSI and PI-RADS v2 for extra-prostatic extension (EPE) were 64.0% (40%) and 20.0% (48%), and 50.0% (57.1%) and 71.4% (64.3%). The area under the ROC curves (AUC) for prediction of high-grade prostate cancer were 0.65 and 0.61 for PI-RADS v2 and 0.72 and 0.70 when combined with 1H-MRSI (readers 1 and 2, p = 0.04 and 0.21). For prediction of EPE the AUC were 0.54 and 0.60 for PI-RADS v2 and 0.55 and 0.61 when combined with 1H-MRSI (p > 0.05). CONCLUSION: 1H-MRSI might improve the discrimination of high-grade prostate cancer when combined to PI-RADS v2, particularly for PI-RADS v2 score 4 lesions, but it does not affect the prediction of EPE.

OBJETIVO: Comparar as predições de tumor com padrão 4 de Gleason dominante ou de tumor com extensão extraprostática utilizando o sistema Prostate Imaging Reporting and Data System (PI-RADS v2), combinado ou não a espectroscopia por ressonância magnética (1H-ERM). MATERIAIS E MÉTODOS: Trinta e nove pacientes submeteram-se a RM de 3 tesla com bobina endorretal, incluindo 1H-ERM, e prostatectomia. Dois radiologistas classificaram as principais lesões identificadas em cada caso utilizando PI-RADS v2 e escores de 1H-ERM. As análises estatísticas incluíram regressões logísticas, curvas receiver operating characteristic (ROC) e tabelas 2x2 para acurácia diagnóstica. RESULTADOS: A sensibilidade e a especificidade da 1H-ERM e do PI-RADS v2 para a detecção de câncer de próstata de alto grau foram 85,7% (57,1%) e 92,9% (100%), e 56% (68%) e 24% (24%). A sensibilidade e a especificidade da 1H-ERM e do PI-RADS v2 para a detecção de extensão extraprostática (EEP) foram 64,0% (40%) e 20% (48%), e 50% (57,1%) e 71,4% (64,3%). As áreas das curvas ROC para a predição de câncer de alto grau foram 0,65 e 0,61 para PI-RADS v2 e 0,72 e 0,70 quando combinado com 1H-ERM (radiologistas 1 e 2, p = 0.04 e 0.21). Para a predição de EEP, as áreas das curvas ROC foram 0,54 e 0,60 para PI-RADS v2 e 0,55 e 0,61 quando combinado com 1H-ERM (p > 0.05). CONCLUSÃO: É possível que a 1H-ERM melhore a predição de câncer de alto grau quando combinada ao PI-RADS v2, em particular para lesões que recebem um escore PI-RADS v2 4; entretanto, ela não afeta a predição de EEP.

Impact of the integration of proton magnetic resonance imaging spectroscopy to PI-RADS 2 for prediction of high grade and high stage prostate cancer / Impacto da incorporação da espectroscopia por ressonância magnética ao PI-RADS 2 para a predição de câncer de próstata de alto grau e de estágio avançado

Abstract Objective: To compare the predictions of dominant Gleason pattern ≥ 4 or non-organ confined disease with Prostate Imaging Reporting and Data System (PI-RADS v2) with or without proton magnetic resonance spectroscopic imaging (1H-MRSI). Materials and Methods: Thirty-nine men underwent 3-tesla endorectal multiparametric MRI including 1H-MRSI and prostatectomy. Two radiologists assigned PI-RADS v2 and 1H-MRSI scores to index lesions. Statistical analyses used logistic regressions, receiver operating characteristic (ROC) curves, and 2x2 tables for diagnostic accuracies. Results: The sensitivity and specificity of 1H-MRSI and PI-RADS v2 for high-grade prostate cancer (PCa) were 85.7% (57.1%) and 92.9% (100%), and 56% (68.0%) and 24.0% (24.0%). The sensitivity and specificity of 1H-MRSI and PI-RADS v2 for extra-prostatic extension (EPE) were 64.0% (40%) and 20.0% (48%), and 50.0% (57.1%) and 71.4% (64.3%). The area under the ROC curves (AUC) for prediction of high-grade prostate cancer were 0.65 and 0.61 for PI-RADS v2 and 0.72 and 0.70 when combined with 1H-MRSI (readers 1 and 2, p = 0.04 and 0.21). For prediction of EPE the AUC were 0.54 and 0.60 for PI-RADS v2 and 0.55 and 0.61 when combined with 1H-MRSI (p > 0.05). Conclusion: 1H-MRSI might improve the discrimination of high-grade prostate cancer when combined to PI-RADS v2, particularly for PI-RADS v2 score 4 lesions, but it does not affect the prediction of EPE.

Resumo Objetivo: Comparar as predições de tumor com padrão 4 de Gleason dominante ou de tumor com extensão extraprostática utilizando o sistema Prostate Imaging Reporting and Data System (PI-RADS v2), combinado ou não a espectroscopia por ressonância magnética (1H-ERM). Materiais e Métodos: Trinta e nove pacientes submeteram-se a RM de 3 tesla com bobina endorretal, incluindo 1H-ERM, e prostatectomia. Dois radiologistas classificaram as principais lesões identificadas em cada caso utilizando PI-RADS v2 e escores de 1H-ERM. As análises estatísticas incluíram regressões logísticas, curvas receiver operating characteristic (ROC) e tabelas 2x2 para acurácia diagnóstica. Resultados: A sensibilidade e a especificidade da 1H-ERM e do PI-RADS v2 para a detecção de câncer de próstata de alto grau foram 85,7% (57,1%) e 92,9% (100%), e 56% (68%) e 24% (24%). A sensibilidade e a especificidade da 1H-ERM e do PI-RADS v2 para a detecção de extensão extraprostática (EEP) foram 64,0% (40%) e 20% (48%), e 50% (57,1%) e 71,4% (64,3%). As áreas das curvas ROC para a predição de câncer de alto grau foram 0,65 e 0,61 para PI-RADS v2 e 0,72 e 0,70 quando combinado com 1H-ERM (radiologistas 1 e 2, p = 0.04 e 0.21). Para a predição de EEP, as áreas das curvas ROC foram 0,54 e 0,60 para PI-RADS v2 e 0,55 e 0,61 quando combinado com 1H-ERM (p > 0.05). Conclusão: É possível que a 1H-ERM melhore a predição de câncer de alto grau quando combinada ao PI-RADS v2, em particular para lesões que recebem um escore PI-RADS v2 4; entretanto, ela não afeta a predição de EEP.

The anti-hepatocellular carcinoma cell activity by a novel mTOR kinase inhibitor CZ415.

Dysregulation of mammalian target of rapamycin (mTOR) in hepatocellular carcinoma (HCC) represents a valuable treatment target. Recent studies have developed a highly-selective and potent mTOR kinase inhibitor, CZ415. Here, we showed that nM concentrations of CZ415 efficiently inhibited survival and induced apoptosis in HCC cell lines (HepG2 and Huh-7) and primary-cultured human HCC cells. Meanwhile, CZ415 inhibited proliferation of HCC cells, more potently than mTORC1 inhibitors (rapamycin and RAD001). CZ415 was yet non-cytotoxic to the L02 human hepatocytes. Mechanistic studies showed that CZ415 disrupted assembly of mTOR complex 1 (mTORC1) and mTORC2 in HepG2 cells. Meanwhile, activation of mTORC1 (p-S6K1) and mTORC2 (p-AKT, Ser-473) was almost blocked by CZ415. In vivo studies revealed that oral administration of CZ415 significantly suppressed HepG2 xenograft tumor growth in severe combined immuno-deficient (SCID) mice. Activation of mTORC1/2 was also largely inhibited in CZ415-treated HepG2 tumor tissue. Together, these results show that CZ415 blocks mTORC1/2 activation and efficiently inhibits HCC cell growth in vitro and in vivo.