RESUMEN
OBJECTIVES: The prevention of mother-to-child transmission of HIV has been a global success. But little is known about the growth parameters of infants delivered by mothers with HIV or the drug resistance of infants with HIV in China. The study aimed to assess growth parameters and drug resistance in Chinese infants exposed to HIV. METHODS: We conducted an 18-month longitudinal follow-up study of 3283 infants (3222 without HIV; 61 with HIV) born to mothers with HIV in the Guangxi Zhuang Autonomous Region between January 2015 and December 2021. The weight and length of all participants was recorded. In addition, genetic subtypes and drug resistance analysis were performed for infants with HIV. RESULTS: Compared with infants without HIV, those with HIV had significantly lower weight/length Z-scores, except at 18 months of age. The length/age Z-scores of infants with HIV was significantly reduced, except at 1 month of age. The weight/age Z-scores of infants with HIV were significantly lower at all follow-up time points. The weight/length Z-scores of male infants without HIV were significantly lower than for female infants without HIV at all follow-up time points. Male infants without HIV had lower length/age and weight/age Z-scores than female infants at the remaining follow-up points, except at 1 month of age. Of a total of 61 infants with HIV, subtype and drug-resistance data were obtained from 37 (60.66%) samples. Infants with HIV were dominated by the CRF01_AE genotype and showed a diversity of mutation sites dominated by non-nucleoside reverse transcriptase inhibitor resistance. CONCLUSION: Our study demonstrates the growth of infants exposed to HIV in southwest China and provides detailed information on subtype distribution and drug resistance of those with HIV. Nutritional support and drug-resistance surveillance for infants exposed to HIV need to be strengthened.
Asunto(s)
Farmacorresistencia Viral , Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , China/epidemiología , Lactante , Masculino , Estudios Longitudinales , Estudios de Seguimiento , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Farmacorresistencia Viral/genética , Embarazo , Recién Nacido , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Peso Corporal , GenotipoRESUMEN
Trinitromethyl and N-amino groups were innovatively incorporated into the framework of 1,2,4-triazole, resulting in 1-amino-5-nitro-3-(trinitromethyl)-1,2,4-triazole (2). Ammonium and hydrazinium salts of 1-amino-5-nitro-3-(dinitromethyl)-1,2,4-triazole were synthesized by acidification, extraction, and neutralization with bases from the potassium salt. All of the newly prepared energetic compounds were comprehensively characterized by using infrared spectroscopy, elemental analysis, nuclear magnetic resonance spectroscopy, and single crystal X-ray diffraction. Compound 2 exhibits favorable properties such as positive oxygen balance (OBCO2 = 5.8%), high density (1.88 g cm-1), good detonation performances (vD = 8937 m s-1, P = 35.5 GPa), and appropriate friction sensitivity (FS = 144 N). The potassium salt 3 demonstrates good thermal decomposition temperature (181 °C) and high density (1.98 g cm-1), while the ammonium salt and hydrazinium salt also display good thermal decomposition temperatures of 183 and 176 °C, respectively. Among these compounds, the ammonium salt exhibits the lowest mechanical sensitivities (FS = 144 N, IS = 6 J).
RESUMEN
Extracellular matrix metalloproteinase inducer CD147 is a glycoprotein on the cell surface. There is minimal expression of CD147 in normal epithelial and fetal tissues, but it is highly expressed in a number of aggressive tumors. CD147 has been implicated in pan-cancer immunity and progression. With the development of CD147-targeting therapeutic strategy, accurate detection of CD147 expression in tumors and its changes during the therapy is necessary. In this study we constructed a novel radiotracer by labeling the anti-CD147 mAb with radionuclide 124/125I (124/125I-anti-CD147) for noninvasive detection of CD147 expression in pan-cancers, and characterized its physicochemical properties, affinity, metabolic characteristics, biodistribution and immunoPET imaging with 124I-IgG and 18F-FDG as controls. By examining the expression of CD147 in cancer cell lines, we found high CD147 expression in colon cancer cells LS174T, FADU human pharyngeal squamous cancer cells and 22RV1 human prostate cancer cells, and low expression of CD147 in human pancreatic cancer cells ASPC1 and human gastric cancer cells BGC823. 124/125I-anti-CD147 was prepared using N-bromine succinimide (NBS) as oxidant and purified by PD-10 column. Its radiochemical purity (RCP) was over 99% and maintained over 85% in saline or 5% human serum albumin (HSA) for more than 7 d; the RCP of 125I-anti-CD147 in blood was over 90% at 3 h post injection (p.i.) in healthy mice. The Kd value of 125I-anti-CD147 to CD147 protein was 6.344 nM, while that of 125I-IgG was over 100 nM. 125I-anti-CD147 showed much greater uptake in CD147 high-expression cancer cells compared to CD147 low-expression cancer cells. After intravenous injection in healthy mice, 125I-anti-CD147 showed high initial uptake in blood pool and liver, the uptake was decreased with time. The biological half-life of distribution and clearance phases in healthy mice were 0.63 h and 19.60 h, respectively. The effective dose of 124I-anti-CD147 was estimated as 0.104 mSv/MBq. We conducted immunoPET imaging in tumor-bearing mice, and demonstrated a significantly higher tumor-to-muscle ratio of 124I-anti-CD147 compared to that of 124I-IgG and 18F-FDG in CD147 (+) tumors. The expression levels of CD147 in cells and tumors were positively correlated with the maximum standardized uptake value (SUVmax) (P < 0.01). In conclusion, 124/125I-anti-CD147 displays high affinity to CD147, and represents potential for the imaging of CD147-positive tumors. The development of 124I-anti-CD147 may provide new insights into the regulation of tumor microenvironment and formulation of precision diagnosis and treatment programs for tumors.
Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias de la Próstata , Masculino , Humanos , Ratones , Animales , Distribución Tisular , Radiofármacos , Radioisótopos de Yodo , Inmunoglobulina G , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Ambient ultraviolet radiation (UVB) from solar and artificial light presents serious environmental risks to aquatic ecosystems. The Pacific oyster, Crassostrea gigas, perceives changes in the external environment primarily through its mantle tissue, which contains many nerve fibers and tentacles. Changes within the mantles can typically illustrate the injury of ambient UVB. In this study, a comprehensive analysis of phenotypic, behavioral, and physiological changes demonstrated that extreme UVB radiation (10â¯W/m²) directly suppressed the behavioral activities of C. gigas. Conversely, under ambient UVB radiation (5â¯W/m²), various physiological processes exhibited significant alterations in C. gigas, despite the behavior remaining relatively unaffected. Using mathematical model analysis, the integrated analysis of the full-length transcriptome, proteome, and metabolome showed that ambient UVB significantly affected the metabolic processes (saccharide, lipid, and protein metabolism) and cellular biology processes (autophagy, apoptosis, oxidative stress) of the C. gigas mantle. Subsequently, using Procrustes analysis and Pearson correlation analysis, the association between multi-omics data and physiological changes, as well as their biomarkers, revealed the effect of UVB on three crucial biological processes: activation of autophagy signaling (key factors: Ca2+, LC3B, BECN1, caspase-7), response to oxidative stress (reactive oxygen species, heat shock 70, cytochrome c oxidase), and recalibration of energy metabolism (saccharide, succinic acid, translation initiation factor IF-2). These findings offer a fresh perspective on the integration of multi-data from non-model animals in ambient UVB risk assessment.
Asunto(s)
Crassostrea , Animales , Crassostrea/metabolismo , Rayos Ultravioleta/efectos adversos , Ecosistema , Respuesta al Choque Térmico , TranscriptomaRESUMEN
This paper introduces a method for quantifying the three-dimensional deformation of ground targets and outlines the associated process. Initially, ground-based synthetic aperture radar was employed to monitor the radial deformation of targets, and optical equipment monitored pixel-level deformation in the vertical plane of the line of sight. Subsequently, a regression model was established to transform pixel-level deformation into two-dimensional deformation based on a fundamental length unit, and the radar deformation monitoring data were merged with the optical deformation monitoring data. Finally, the fused data underwent deformation, resulting in a comprehensive three-dimensional deformation profile of the target. Through physical data acquisition experiments, the comprehensive three-dimensional deformation of targets was obtained and compared with the actual deformations. The experimental results show that the method has a relative error of less than 10%, and monitoring accuracy is achieved at the millimeter level.
RESUMEN
OBJECTIVE: Early detection of a tumour remains an unmet medical need, and approaches with high sensitivity and specificity are urgently required. Mass cytometry time-of-flight (CyTOF) is a powerful technique to profile immune cells and could be applied to tumour detection. We attempted to establish diagnostic models for hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). DESIGN: We performed CyTOF analysis for 2348 participants from 15 centres, including 1131 participants with hepatic diseases, 584 participants with pancreatic diseases and 633 healthy volunteers. Diagnostic models were constructed through random forest algorithm and validated in subgroups. RESULTS: We determined the disturbance of systemic immunity caused by HCC and PDAC, and calculated a peripheral blood immune score (PBIScore) based on the constructed model. The PBIScore exhibited good performance in detecting HCC and PDAC, with both sensitivity and specificity being around 80% in the validation cohorts. We further established an integrated PBIScore (iPBIScore) by combining PBIScore and alpha-fetoprotein or carbohydrate antigen 19-9. The iPBIScore for HCC had an area under the curve (AUC) of 0.99, 0.97 and 0.96 in training, internal validation and external validation cohorts, respectively. Similarly, the iPBIScore for PDAC showed an AUC of 0.99, 0.98 and 0.97 in the training, internal validation and external validation cohorts, respectively. In early-stage and tumour-marker-negative patients, our iPBIScore-based models also showed an AUC of 0.95-0.96 and 0.81-0.92, respectively. CONCLUSION: Our study proved that the alterations of peripheral immune cell subsets could assist tumour detection, and provide a ready-to-use detection model for HCC and PDAC.
Asunto(s)
Carcinoma Hepatocelular , Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Biomarcadores de Tumor , Neoplasias PancreáticasRESUMEN
Improved chondrogenic differentiation of mesenchymal stem cells (MSCs) by genetic regulation is a potential method for regenerating articular cartilage. LncRNA MIR22HG has been proven to accelerate osteogenic differentiation, but the regulation mechanism of chondrogenic differentiation is still unclear. Human adipose-derived stem cells (hADSCs) have been widely utilised for bone tissue engineering applications. The present study aimed to examine the effect of MIR22HG on the chondrogenic differentiation of hADSCs. The results confirmed that MIR22HG was downregulated in the process of chondrogenic differentiation. Subsequently, gain- and loss-of-function of MIR22HG experiments showed that the overexpression of MIR22HG suppressed the deposition of cartilage matrix proteoglycans and decreased the expression of cartilage-related markers (e.g. Sox9, ACAN and Col2A1), whereas the knockdown of MIR22HG had the opposite effect. MIR22HG could bind to CTCF (CCCTC-binding factor), and CTCF could bind to the CRLF1 (cytokine receptor-like factor 1) promoter and upregulate CRLF1 gene expression. Besides, inhibition of CRLF1 can reverse the effect of MIR22HG on cell chondrogenic differentiation of hADSCs. Taken together, our outcomes reveal that MIR22HG suppressed chondrogenic differentiation by interaction with CTCF to stabilise CRLF1.
Asunto(s)
Células Madre Mesenquimatosas , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Osteogénesis , Factor de Unión a CCCTC/genética , Factor de Unión a CCCTC/metabolismo , Factor de Unión a CCCTC/farmacología , Diferenciación Celular/genética , Células Madre Mesenquimatosas/metabolismo , Células CultivadasRESUMEN
PURPOSE: Transperineal mpMRI-targeted fusion prostate biopsies (TPFBx) are recommended for prostate cancer diagnosis, but little is known about their learning curve (LC), especially when performed under local anaesthesia (LA). We investigated how operators' and institutions' experience might affect biopsy results. METHODS: Baseline, procedure and pathology data of consecutive TPFBx under LA were prospectively collected at two academic Institutions, from Sep 2016 to May 2019. Main inclusion criterion was a positive MRI. Endpoints were biopsy duration, clinically significant prostate cancer detection rate on targeted cores (csCDR-T), complications, pain and urinary function. Data were analysed per-centre and per-operator (with ≥ 50 procedures), comparing groups of consecutive patient, and subsequently through regression and CUSUM analyses. Learning curves were plotted using an adjusted lowess smoothing function. RESULTS: We included 1014 patients, with 27.3% csCDR-T and a median duration was 15 min (IQR 12-18). A LC for biopsy duration was detected, with the steeper phase ending after around 50 procedures, in most operators. No reproducible evidence in favour of an impact of experience on csPCa detection was found at operator's level, whilst a possible gentle LC of limited clinical relevance emerged at Institutional level; complications, pain and IPSS variations were not related to operator experience. CONCLUSION: The implementation of TPFBx under LA was feasible, safe and efficient since early phases with a relatively short learning curve for procedure time.
Asunto(s)
Imagen por Resonancia Magnética Intervencional , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Próstata/patología , Curva de Aprendizaje , Anestesia Local , Estudios Prospectivos , Imagen por Resonancia Magnética Intervencional/métodos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , DolorRESUMEN
Here, we report the nitration of NH on the 1,2,3-triazole ring and the synthesis of several nitrogen-rich energetic compounds based on key intermediate 4-azido-5-(chlorodinitromethyl)-2-nitro-2H-1,2,3-triazole (5). Starting from 4-amino-1H-1,2,3-triazole-5-carbonitrile (1), we successfully constructed compound 5 through four steps. Subsequently, the dechlorination of compound 5 gave potassium 4-azido-5-(dinitromethyl)-2H-1,2,3-triazole (6) (IS = 1 J, vD = 8802 m s-1). Additionally, diammonium (8) and dihydrazinium (9) salts based on 4-azido-5-(dinitromethyl)-2H-1,2,3-triazole were also successfully synthesized and characterized. A novel fused nitrogen-rich heterocycle, namely, 6H-[1,2,3]triazolo[4,5-d][1,2,3] triazine-6,7-diamine (10), was surprisingly obtained, which has a high nitrogen content of 73.66% and shows good thermal stability (Tdec = 203 °C) and insensitivity to mechanical stimuli, while the detonation velocity (vD) and detonation pressure (P) reach 8421 m s-1 and 26.0 GPa, respectively.
RESUMEN
Halobacteriovorax are predatory bacteria that have a significant ecological role in marine environments. However, understanding of dynamics of populations, driving forces, and community composition of Halobacteriovorax groups in natural marine environments is still limited. Here, we used high-throughput sequencing to study the underlying mechanisms governing the diversity and assembly of the Halobacteriovorax community at spatiotemporal scales in a subtropical estuary. Phylogenetic analysis showed that 10 of 15 known Halobacteriovorax clusters were found in the studied estuary. Halobacteriovorax α-diversity and ß-diversity exhibited significant seasonal variation. Variation partitioning analysis showed that the effect of nutrients was greater than that of other measured water properties on Halobacteriovorax community distribution. The results of Spearman's and Mantel's tests indicated that the trophic pollutants dissolved inorganic phosphorus (DIP) and NH4+-N in the estuary were the key factors that significantly affected Halobacteriovorax species and community diversity. In addition, this work indicated that the biological stoichiometry (especially N/P) of nutrients exerted a significant influence on the Halobacteriovorax community. Furthermore, we found that both deterministic and stochastic processes contributed to the turnover of Halobacteriovorax communities, and environmental filtering dominated the assembly of estuarine Halobacteriovorax communities. Overall, we provide new insights into the mechanisms in the generation and maintenance of the Halobacteriovorax community in marine environments.
Asunto(s)
Ecosistema , Estuarios , Estaciones del Año , Filogenia , ProteobacteriaRESUMEN
Polymer nanocomposites (PNCs) have been attracting myriad scientific and technological attention due to their promising mechanical and functional properties. However, there remains a need for an efficient method that can further strengthen the mechanical performance of PNCs. Here, we propose a strategy to design and fabricate novel PNCs by incorporating porous fillers (PFs) such as metal-organic frameworks with ultrahigh specific surface areas and tunable nanospaces to polymer matrices via coarse-grained molecular dynamics simulations. Three important parametersâthe polymer chain stiffness (k), the interaction strength between the PF center and the end functional groups of polymer chains (εcenter end), and the PF weight fraction (w)âare systematically examined. First, attributed to the penetration of polymer chains into PFs at a strong εcenter end, the dimension of polymer chains such as the radius of gyration and the end-to-end distance increases greatly as a function of k compared to the case of the neat polymer system. The penetration of polymer chains is validated by characterizing the radial distribution function between end functional groups and filler centers, as well as the visualization of the snapshots. Also, the dispersion state of PFs tends to be good because of the chain penetration. Then, the glass transition temperature ratio of PNCs to that of the neat systems exhibits a maximum in the case of k = 5ε, indicating that the strongest interlocking between polymer chains and PFs occurs at intermediate chain stiffness. The polymer chain dynamics of PNCs decreases to a plateau at k = 5ε and then becomes stable, and the relative mobility to that of the neat system as well presents the same variation trend. Furthermore, the mechanical property under uniaxial deformation is thoroughly studied, and intermediates k, εcenter end, and w can bring about the best mechanical property. This is because of the robust penetration and interaction, which is confirmed by calculating the stress of every component of PNCs with and without end functional groups and PF centers as well as the nonbonded interaction energy change between different components. Finally, the optimal condition (k = 5.36ε, εcenter end = 5.29ε, and w = 6.54%) to design the PNC with superior mechanical behavior is predicted by Gaussian process regression, an active machine learning (ML) method. Overall, incorporating PFs greatly enhances the entanglements and interactions between polymer chains and nanofillers and brings effective mechanical reinforcements with lower filler weight fractions. We anticipate that this will provide new routes to the design of mechanically reinforced PNCs.
RESUMEN
BACKGROUND: Situs inversus totalis (SIT) is a rare congenital anomaly characterized by a complete transposition of all the viscera. SIT cases were usually reported because of the presence of tumors, leading to false association between them. Therefore, any research that advances our understanding on SIT is highly required. This study firstly describes a very rare case of SIT with "jumping" metastasis to pancreas of gallbladder carcinoma. CASE PRESENTATION: A 69-year-old female patient presented at our hospital with complaints of one month of epigastric pain was studied. She had not sought for treatment prior the visit. Imaging examinations of this patient revealed SIT and a variation of the common hepatic artery with concomitant tumors of gallbladder and pancreas. However, there was no evidence of distant metastases beyond the abdominal cavity. She underwent a combination of radical cholecystectomy, total pancreatectomy, splenectomy and hepatic artery-splenic artery reconstruction. Histological analyses revealed metastasis of the gallbladder carcinoma in to the pancreas. Although the patient opted against chemotherapy, she survived without tumor for 16 months following the surgery. A review of the current literature on association with SIT and tumor occurrence was presented. CONCLUSIONS: It is a great surgical challenge for the resection of multicenter hepatobiliary and pancreatic tumors in such rare SIT anatomical abnormalities with vascular variants. A reliable surgical plan based on detailed preoperative imaging and intraoperative anatomical exploration is crucial to achieving radical resection.
Asunto(s)
Neoplasias de la Vesícula Biliar , Situs Inversus , Anciano , Femenino , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/cirugía , Arteria Hepática/diagnóstico por imagen , Humanos , Estudios Multicéntricos como Asunto , Pancreatectomía , Situs Inversus/complicaciones , Situs Inversus/diagnóstico por imagen , Situs Inversus/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To investigate the causes of missed diagnosis in mpMRI/TRUS fusion-guided targeted prostate biopsy. METHODS: The clinical data of 759 patients who underwent transperineal prostate biopsy from March 2021 to June 2021 at Nanjing DrumTower Hospital were retrospectively analyzed. Twenty-one patients had MRI contraindications. Ultimately, 738 patients completed mpMRI/TRUS fusion-guided targeted prostate biopsy + 12-core transperineal systematic biopsy after mpMRI and PI-RADS scoring. The pathological diagnoses from targeted and systematic biopsy were compared to evaluate and analyze the reasons for missed diagnoses in targeted biopsy. RESULTS: A total of 388 prostate cancer patients were identified, including 37 (9%) missed diagnoses with targeted biopsy and 44 (11.34%) with systematic biopsy. Between the target biopsy missed diagnosis group and not missed diagnosis group, there was no significant difference in age (71.08 ± 7.11 vs. 71.80 ± 7.94), but PSA (13.63 ± 12.41 vs. 54.54 ± 177.25 ng/ml), prostate volume (61.82 ± 40.64 vs. 44.34 ± 25.07 cm3), PSAD (0.27 ± 0.28 vs. 1.07 ± 2.91), and ISUP grade [1(1) vs. 3(2)] were significantly different. The pathological results of the 37 targeted biopsy missed diagnoses were recompared with MRI: 21 prostate cancers were normal on MRI; 9 cancer areas were abnormal on MRI; and 7 cancer areas on MRI were PI-RADS 3. CONCLUSIONS: Early prostate cancer, large prostate, effect of local anesthesia, doctor-patient cooperation, MRI diagnosis, and operator technology were possible factors for missed diagnosis in targeted biopsy. Improvements imaging technology, greater experience, and personalized biopsy may lead to an accurate pathological diagnosis.
Asunto(s)
Imagen por Resonancia Magnética Intervencional , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Humanos , Biopsia Guiada por Imagen/métodos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética Intervencional/métodos , Masculino , Diagnóstico Erróneo , Estudios Prospectivos , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Ultrasonografía Intervencional/métodosRESUMEN
OBJECTIVES: To investigate the sonographic features in Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) using both conventional ultrasound (US) and contrast-enhanced US (CEUS) and evaluate the usefulness of sonographic imaging characteristics to differentiate between Xp11.2 tRCC and the three common RCC subtypes. METHODS: Thirty-four adult Xp11.2 tRCC patients who preoperatively underwent both conventional US and CEUS and had solitary renal lesions and pathological confirmation after surgery were enrolled. Control matched patients included 131 with clear cell RCC (ccRCC), 48 with papillary RCC (pRCC), and 35 with chromophobe RCC (chRCC). Conventional US and CEUS data of all patients were retrospectively analyzed and compared. RESULTS: Xp11.2 tRCC was more common in young women. The echogenicity of Xp11.2 tRCC lesions was hypo- and isoechoic relative to the adjacent renal cortex. A higher frequency of calcification within tumors was detected in Xp11.2 tRCC, but the presence of color flow signal (26.5%, 9/34) was much lower. Regarding CEUS features relative to the adjacent renal cortex, synchronous wash-in (61.8%, 21/34), iso-enhancement at peak (55.9%, 19/34), and fast wash-out (50.0%, 17/34) were more common in Xp11.2 tRCC. Moreover, an integrated variables model based on these features could differentiate Xp11.2 tRCC from ccRCC, pRCC, and chRCC (area under the curve, sensitivity, and specificity: 0.934, 92.0%, and 86.0%; 0.907, 88.0%, and 87.0%; and 0.808, 65.0%, and 99.0%, respectively). CONCLUSIONS: Combining conventional US and CEUS lesion features with clinical information may provide a feasible and effective method to differentiate Xp11.2 tRCC from ccRCC, pRCC, and chRCC.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Adulto , Humanos , Femenino , Carcinoma de Células Renales/diagnóstico por imagen , Carcinoma de Células Renales/genética , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/genética , Diagnóstico Diferencial , Estudios Retrospectivos , Translocación Genética , Ultrasonografía/métodosRESUMEN
SCOPE: The dysbiosis of intestinal microecology plays an important pathogenic role in the development of inflammatory bowel disease. METHODS AND RESULTS: A polysaccharide named Fuc-S, with a molecular weight of 156 kDa, was prepared by the ultrasonic degradation of fucoidan. Monosaccharide composition, FTIR, methylation, and NMR spectral analysis indicated that Fuc-S may have a backbone consisting of â3)-α-L-Fucp-(1â, â4)-α-L-Fucp-(1â and â3, 4)-α-D-Glcp-(1â. Moreover, male C57BL/6 mice were fed three cycles of 1.8% dextran sulfate sodium (DSS) for 5 days and then water for 7 days to induce colitis. The longitudinal microbiome alterations were evaluated using 16S amplicon sequencing. In vivo assays showed that Fuc-S significantly improved clinical manifestations, colon shortening, colon injury, and colonic inflammatory cell infiltration associated with DSS-induced chronic colitis in mice. Further studies revealed that these beneficial effects were associated with the inhibition of Akt, p-38, ERK, and JNK phosphorylation in the colon tissues, regulating the structure and abundance of the gut microbiota, and modulating the host-microbe tryptophan metabolism of the mice with chronic colitis. CONCLUSION: Our data confirmed the presence of glucose in the backbone of fucoidan and provided useful information that Fuc-S can be applied as an effective functional food and pharmaceutical candidate for IBD treatment.
Asunto(s)
Colitis , Microbioma Gastrointestinal , Animales , Masculino , Ratones , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colon/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Sulfatos/farmacología , Triptófano/farmacología , Ultrasonido , OligosacáridosRESUMEN
A growing body of research suggests that inflammatory insult contributes to the etiology of central nervous system diseases, such as depression, Alzheimer's disease, and so forth. However, the effect of prenatal systemic inflammation exposure on offspring brain development and cerebral susceptibility to inflammatory insult remains unknown. In this study, we utilized the prenatal inflammatory insult model in vivo and the neuronal damage model in vitro. The results obtained show that prenatal maternal inflammation exacerbates LPS-induced memory impairment, neuronal necrosis, brain inflammatory response, and significantly increases protein expressions of COX-2, DP2, APP, and Aß, while obviously decreasing that of DP1 and the exploratory behaviors of offspring rats. Meloxicam significantly inhibited memory impairment, neuronal necrosis, oxidative stress, and inflammatory response, and down-regulated the expressions of APP, Aß, COX-2, and DP2, whereas significantly increased exploring behaviors and the expression of DP1 in vivo. Collectively, these findings suggested that maternal inflammation could cause offspring suffering from inflammatory and behavioral disorders and increase the susceptibility of offspring to cerebral pathological factors, accompanied by COX-2/PGD-2/DPs pathway activation, which could be ameliorated significantly by COX-2 inhibitor meloxicam treatment.
Asunto(s)
Lesiones Encefálicas , Diagnóstico Preimplantación , Efectos Tardíos de la Exposición Prenatal , Animales , Encéfalo/metabolismo , Lesiones Encefálicas/metabolismo , Ciclooxigenasa 2/metabolismo , Femenino , Humanos , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Meloxicam , Trastornos de la Memoria/metabolismo , Necrosis/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Factores de Transcripción/metabolismoRESUMEN
Objective: To investigate the detection rate of clinically significant PCa (CSPCa) in lesions of prostate imaging-reporting and data system (version 2) (PI-RADS v2) score 3 in different histological zones of the prostate, the value range of clinical parameters, and the possibility of improving the detection rate by MRI/TRUS fusion prostate biopsy. METHODS: This retrospective study included 297 patients with prostatic lesions of PI-RADS v2 score 3 undergoing transperineal prostate biopsy in Nanjing Drum Tower Hospital from January to December 2019. We analyzed their clinical data, the detection rate of CSPCa in the four histological zones of the prostate and the value range of the clinical parameters. RESULTS: The detection rates of CSPCa in the peripheral zone, transitional zone, central zone and anterior fibromuscular stroma were 23.8%, 11.2%, 40.0% and 50.0%, respectively. In comparison with conventional biopsy, additional MRI/TRUS image fusion biopsy improved the detection rate of CSPCa in the four zones, though with no statistically significant difference. The patients with CSPCa, compared with those in the non-CSPCa group, showed a lower value of free PSA/total PSA (fPSA/tPSA) (0.12 ± 0.05 vs 0.18 ± 0.07) but a higher tPSA level (ï¼»13.06 ± 10.07ï¼½ vs ï¼»8.61 ± 5.86ï¼½ µg/L) and PSA density (PSAD) (ï¼»0.35 ± 0.34ï¼½ vs ï¼»0.16 ± 0.11ï¼½ µg/L2). CONCLUSIONS: In prostate lesions of PI-RADS v2 score 3, the detection rate of CSPCa was higher in the peripheral zone, even higher in the central zone and anterior fibromuscular stroma, than in the transitional zone. Prostatic biopsy is strongly recommended for patients with fPSA/tPSA < 0.12 or PSAD > 0.35 µg/L2, and additional MRI/TRUS image fusion biopsy is preferable for the lesions in the transitional or central zone.
RESUMEN
OBJECTIVE: To compare the accuracy of different methods of measuring the prostate volume (PV) based on the manifestations of prostatic ultrasonography and MRI. METHODS: Using the drainage method, we measured the volumes of 101 prostatic specimens collected from radical prostatectomy. And with the measures obtained as reference standards, we calculated the PV of the patients with the maximum width (W), height (H) and length (L) of the prostates obtained preoperatively by transabdominal ultrasonography (TAUS), transrectal ultrasonography (TRUS) and MRI using the ellipsoidal formula (PV = W × H × L × 0.52), bullet formula (PV = W × H × L × 0.65) and 3D reconstruction technology. We evaluated the accuracy of the above methods using the Mann-Whitney U test, intraclass correlation coefficient (ICC), and Bland-Altman scatterplot. RESULTS: No statistically significant differences were observed between the specimen and preoperative PVs. The ICCs of the specimen PVs obtained by MRI 3D reconstruction, TRUS bullet formula, MRI ellipsoidal formula and TAUS ellipsoidal formula were 0.978, 0.862, 0.857 and 0.745, respectively. The Bland-Altman scatterplot exhibited that the preoperative PV calculated by MRI 3D reconstruction had the highest consistency with that of the specimen PV, followed by that measured by TRUS bullet formula and that obtained by MRI ellipsoidal formula, while that determined by TAUS ellipsoidal formula had a low consistency. CONCLUSION: The MRI 3D reconstruction technology is the most reliable method for the measurement of PV, followed by TRUS bullet formula, but the latter is recommended for its high applicability in clinical practice.
Asunto(s)
Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/cirugía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Ultrasonografía , Prostatectomía , Imagen por Resonancia Magnética/métodosRESUMEN
PURPOSE: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) is an ideal tool for staging and restaging of prostate cancer (PCa). This study was designed to investigate the prognostic role of preoperative 68Ga-PSMA-11 PET/CT in predicting pathological upgrading from multiparametric magnetic resonance imaging-targeted biopsy (mpMRI-TB) to final radical prostatectomy (RP) specimens in patients with localized PCa. METHODS: A total of 67 biopsy-confirmed localized PCa patients with mpMRI and 68Ga-PSMA-11 PET/CT prior to RP were included. Clinical and imaging characteristics derived from mpMRI and PET/CT were compared in patients with or without pathological upgrading. Predictors for pathological upgrading were evaluated by using univariate and multivariable analyses. A prediction model was developed based on the identified parameters and validated using internal validation. RESULTS: Pathological upgrading from mpMRI-TB to final RP specimens occurred in 38.8% (26/67) of the patients. Multivariable logistic regression analysis showed SUVmax (OR: 1.223, 95% CI 1.068-1.399, p = 0.003); highest tumor grade at mpMRI-TB, ISUP grade group (ISUP GG) 1 vs. 4 (OR: 0.11, 95% CI 0.000-0.452, p = 0.018) and ISUP GG 2 vs. 4 (OR: 0.16, 95% CI 0.001-0.252, p = 0.003); and multifocality on PET/CT (OR: 9.821, 95% CI 1.438-67.085, p = 0.02) were independent risk factors for pathological upgrading. Our developed prediction model based on the identified parameter showed good calibration at internal validation (mean absolute error = 0.033). CONCLUSION: 68Ga-PSMA-11 PET/CT was found to be an ideal biomarker for the prediction of pathological upgrading from mpMRI-TB to RP, especially for patients with lower tumor grade at mpMRI-TB.
Asunto(s)
Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Biopsia , Ácido Edético , Isótopos de Galio , Radioisótopos de Galio , Humanos , Imagen por Resonancia Magnética , Masculino , Prostatectomía , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To assess the outcomes of multiparametric magnetic resonance imaging (mpMRI) transperineal targeted fusion biopsy (TPFBx) under local anaesthesia. PATIENTS AND METHODS: We prospectively screened 1327 patients with a positive mpMRI undergoing TPFBx (targeted cores and systematic cores) under local anaesthesia, at two tertiary referral institutions, between September 2016 and May 2019, for inclusion in the present study. Primary outcomes were detection of clinically significant prostate cancer (csPCa) defined as (1) International Society of Urological Pathologists (ISUP) grade >1 or ISUP grade 1 with >50% involvement of prostate cancer (PCa) in a single core or in >2 cores (D1) and (2) ISUP grade >1 PCa (D2). Secondary outcomes were: assessment of peri-procedural pain (numerical rating scale [NRS]) and procedure timings; erectile (International Index of Erectile Function) and urinary (International Prostate Symptom Score) function changes; and complications. We also investigated the value of systematic sampling and concordance with radical prostatectomy (RP). RESULTS: A total of 1014 patients were included, of whom csPCa was diagnosed in 39.4% (n = 400). The procedure was tolerable (NRS pain score 3.1 ± 2.3), with no impact on erectile (P = 0.45) or urinary (P = 0.58) function, and a low rate of complications (Clavien-Dindo grades 1 or 2, n = 8; grade >2, n = 0). No post-biopsy sepsis was recorded. Twenty-two men (95% confidence interval [CI] 17-29) needed to undergo additional systematic biopsy to diagnose one csPCa missed by targeted biopsies (D1). ISUP grade concordance of biopsies with RP was as follows: k = 0.40 (95% CI 0.31-0.49) for targeted cores alone and k = 0.65 (95% CI 0.57-0.72; P < 0.05) overall. CONCLUSIONS: The use of TPFBx under local anaesthesia yielded good csPCa detection and was feasible, quick, well tolerated and safe. Infectious risk was negligible. Addition of systematic to targeted cores may not be needed in all men, although it improves csPCa detection and concordance with RP.