Computational fluid dynamics simulation of hemodynamic changes in a hemodialysis patient with central venous stenosis treated with stent.

BACKGROUND: It has not been demonstrated that computational fluid dynamics (CFD) can be used to model central venous stenosis (CVS), nor that hemodynamic changes in CVS treated with stent placement can be anticipated. The purpose of this study was to demonstrate the hemodynamic performance of CVS patients treated with stent placement. METHODS: Patient-specific geometric models were constructed using computed tomography images of veins from hemodialysis patients treated with stent placement. CFD simulation based on geometry was performed using ANSYS-15 to compare pressure quantitatively, wall shear stress (WSS), and flow velocity in the brachial vein before and after stent placement. RESULTS: Following a covered stent placement, the swelling of the left upper extremity was relieved. Prior to stent implantation, the maximum and mean brachial vein wall pressures were 465.2 Pa and 224.609 Pa, respectively. It was determined that the maximum WSS value was 8.449 Pa and that the mean WSS value was 0.743 Pa. The maximum and mean flow velocities were 1.16 and 0.173 m/s, respectively. After stent placement, the maximum wall pressure, maximum WSS, and maximum flow velocity dropped by 59.4%, 71.2%, and 57.8%, respectively. The mean wall pressure, mean WSS, and mean flow rate decreased by 43.5%, 52.7%, and 17.6%, respectively. CONCLUSION: Hemodynamics of CVS in hemodialysis patients exhibited turbulent, imbalances and disorders, which can be improved by stent placement.

Tau knockout exacerbates degeneration of parvalbumin-positive neurons in substantia nigra pars reticulata in Parkinson's disease-related α-synuclein A53T mice.

α-Synuclein (α-syn)-induced neurotoxicity has been generally accepted as a key step in the pathogenesis of Parkinson's disease (PD). Microtubule-associated protein tau, which is considered second only to α-syn, has been repeatedly linked with PD in association studies. However, the underlying interaction between these two PD-related proteins in vivo remains unclear. To investigate how the expression of tau affects α-syn-induced neurodegeneration in vivo, we generated triple transgenic mice that overexpressed α-syn A53T mutation in the midbrain dopaminergic neurons (mDANs) with different expression levels of tau. Here, we found that tau had no significant effect on the A53T α-syn-mediated mDANs degeneration. However, tau knockout could modestly promote the formation of α-syn aggregates, accelerate the severe and progressive degeneration of parvalbumin-positive (PV+) neurons in substantia nigra pars reticulata (SNR), accompanied with anxiety-like behavior in aged PD-related α-syn A53T mice. The mechanisms may be associated with A53T α-syn-mediated specifically successive impairment of N-methyl-d-aspartate receptor subunit 2B (NR2B), postsynaptic density-95 (PSD-95) and microtubule-associated protein 1A (MAP1A) in PV+ neurons. Our study indicates that MAP1A may play a beneficial role in preserving the survival of PV+ neurons, and that inhibition of the impairment of NR2B/PSD-95/MAP1A pathway, may be a novel and preferential option to ameliorate α-syn-induced neurodegeneration.

Three-dimensional nanostructured substrates enable dynamic detection of ALK-rearrangement in circulating tumor cells from treatment-naive patients with stage III/IV lung adenocarcinoma.

BACKGROUND: Circulating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients. METHODS: We developed the NanoVelcro Chip integrating three functional mechanisms. NanoVelcro CTC capture efficiency was tested in stage III or IV lung adenocarcinoma. Further, ALK-rearrangement status was examined through fluorescent in situ hybridization in CTCs enriched by NanoVelcro. RESULTS: NanoVelcro system showed higher CTC-capture efficiency than CellSearch in stage III or IV lung adenocarcinoma. CTC counts obtained by both methods were positively correlated (r = 0.45, p < 0.05). Further, Correlation between CTC counts and pTNM stage determined by NanoVelcro was more significant than that determined by CellSearch (p < 0.001 VS p = 0.029). All ALK-positive patients had 3 or more ALK-rearranged CTC per ml of blood. Less than 3 ALK-rearranged CTC was detected in ALK-negative patients. NanoVelcro can detect the ALK-rearranged status with consistent sensitivity and specificity compared to biopsy test. Furthermore, the ALK-rearranged CTC ratio correlated to the pTNM stage in ALK-positive patients. Following up showed that CTCs counting by NanoVelcro was more stable and reliable in evaluating the efficacy of Clozotinib both in the short and long run compared with CellSearch. Changing of NanoVlecro CTC counts could accurately reflect disease progression. CONCLUSION: NanoVelcro provides a sensitive method for CTC counts and characterization in advanced NSCLC. ALK-rearrangement can be detected in CTCs collected from advanced NSCLC patients by NanoVelcro, facilitating diagnostic test and prognosis analysis, most importantly offering one noninvasive method for real-time monitoring of treatment reaction.

Degradation of antibiotics and antibiotic resistance genes in fermentation residues by ionizing radiation: A new insight into a sustainable management of antibiotic fermentative residuals.

Antibiotic fermentative residues are categorized into hazardous wastes in China due to the existence of antibiotic resistance genes (ARGs) and residual antibiotics How to treat and manage these wastes is a new challenge. This paper investigated the treatment of erythromycin thiocyanate fermentation (EryTcF) residues using ionizing radiation technology for removing ARGs and antibiotics from the fermentation residues. The results showed that as exposed the EryTcF residues to gamma radiation, the abundance of four macrolide resistance genes (ereA, ermB, mefA and mpfB) decreased 1.0-1.3 log with 90-95% removal, and around 56% of erythromycin was removed at absorbed dose of 30 kGy and room temperature (19-22 °C). Direct action of γ-ray radiation contributed to 42-53% of ARGs removal and indirect action (radicals' reaction) was mainly responsible for erythromycin removal (84%). The positive correlation between total ARGs and Shannon index was observed. The potential ARGs-linked hosts were assigned to genera Aeromonas and Enterobacteriaceae and their abundance decreased by 36-43% at 30 kGy. Radiation has not obvious influence on the nutrient components of residues, such as protein content, suggesting that the radiation treated fermentative residues can be used as fertilizer, which is favorable for the development of recycling economy in antibiotic pharmaceutical factory. The results could provide a new insight into a sustainable management of antibiotic fermentative residuals.

Apoptotic PET Imaging of Rat Pulmonary Fibrosis With [18F]ML-8.

OBJECTIVE: To investigate the value of 2-(3-[18F]fluoropropyl)-2-methyl-malonic acid ([18F]ML-8) positron emission tomography (PET) imaging of rat pulmonary fibrosis. METHODS: Male Sprague-Dawley rats were divided into 2 groups, including pulmonary fibrosis model group and control group. The rat model was established by an intratracheal instillation of bleomycin (BLM). Control rats were treated with saline. Positron emission tomography/computed tomography (CT) with [18F]ML-8 or 18F-fluorodeoxyglucose ([18F]FDG) was performed on 2 groups. After PET/CT imaging, lung tissues were collected for histologic examination. Data were analyzed and comparisons between 2 groups were performed using Student t test. RESULTS: Bleomycin-treated rats showed a higher lung uptake of [18F]ML-8 than control rats ( P < .05). In BLM-treated rats, the lung to muscle relative uptake ratio of [18F]ML-8 was also higher than that of [18F]FDG ( P < .05). Pathological examination showed overproliferation of fibroblasts and deposition of collagen in lungs from BLM-treated rats. Compared to control rats, BLM-treated rats had higher lung hydroxyproline content ( P < .05). Immunofluorescence staining indicated more apoptotic cells in BLM-treated rats than those in control rats. Moreover, the apoptosis rate of lung tissues obtained from BLM-treated rats was higher than that from control rats ( P < .05). CONCLUSIONS: 2-(3-[18F]fluoropropyl)-2-methyl-malonic acid PET/CT could be used for noninvasive diagnosis of pulmonary fibrosis in a rat model.

Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression.

Homozygous tau knockout (Mapt-/-) mice develop age-dependent dopaminergic (DA) neuronal loss in the substantia nigra (SN) and ventral tegmental area (VTA), supporting an important function of tau in maintaining the survival of midbrain dopaminergic neurons (mDANs) during aging. However, it remains to be determined whether the microtubule-associated protein tau regulates the differentiation and survival of mDANs during embryonic developmental stages. Here, we show that tau haploinsufficiency in postnatal day 0 (P0) heterozygous (Mapt+/-) pups, but not a complete loss of tau in the Mapt-/- littermates, led to a significant reduction of DA neurons in the VTA. This selective loss of DA neurons correlated with a similar reduction in orthodenticle homeobox 2 (Otx2), which is restricted to VTA neurons at the postmitotic stage and selectively controls the neurogenesis and survival of specific neuronal subtypes of VTA. Moreover, the prenatal developmental cell death in the Mapt+/- VTA specifically increased, and the expression of microtubule-associated protein (MAP)-1A was significantly up-regulated in the P0 Mapt-/- , but not the Mapt+/- , pups. These results suggest that tau haploinsufficiency, without the compensation effect of MAP1A, induces reduction of Otx2 expression, increases prenatal cell death, and accordingly leads to selective loss of VTA DA neurons in the early postnatal stage. Our findings highlight the impact of tau haploinsufficiency on the survival of mDANs and indicate that tau may participate in midbrain development in a dose-dependent way.-Zheng, M., Jiao, L., Tang, X., Xiang, X., Wan, X., Yan, Y., Li, X., Zhang, G., Li, Y., Jiang, B., Cai, H., Lin, X. Tau haploinsufficiency causes prenatal loss of dopaminergic neurons in the ventral tegmental area and reduction of transcription factor orthodenticle homeobox 2 expression.

Intravenous leiomyomatosis with intracardiac involvement.

Intravenous leiomyomatosis with intracardiac involvement is rare. This is a case report of a 52-year-old female with intravenous leiomyomatosis with intracardiac involvement. She was successfully treated with myomatectomy (left renal vein and inferior vena cava), hysterectomy, and bilateral salpingo-oophorectomy under the cardiopulmonary bypass.

Multi-matrices factorization with application to missing sensor data imputation.

We formulate a multi-matrices factorization model (MMF) for the missing sensor data estimation problem. The estimation problem is adequately transformed into a matrix completion one. With MMF, an n-by-t real matrix, R, is adopted to represent the data collected by mobile sensors from n areas at the time, T1, T2, ..., Tt, where the entry, Rij, is the aggregate value of the data collected in the ith area at Tj. We propose to approximate R by seeking a family of d-by-n probabilistic spatial feature matrices, U(1), U(2), ..., U(t), and a probabilistic temporal feature matrix, [formula in text]. We also present a solution algorithm to the proposed model. We evaluate MMF with synthetic data and a real-world sensor dataset extensively. Experimental results demonstrate that our approach outperforms the state-of-the-art comparison algorithms.

Outline of occupational chromium poisoning in China.

The present study analyzed the feature of occupational chromium poisoning in China since the 1980s. The collected data were acquired from 18 previous surveys of chromium poisoning in 14 cities of China. The method of risk assessment was applied to calculate the relative risk and 95% CI, p < 0.05 was considered as a significant risk. The results showed that nasal disease was the most common sign of occupational chromium poisoning, and the prevalence rate of nasal disease was 17.83% in total population of 6,998. Further, the risk analysis showed that occupational chromium poisoning led to an increased risk of lung or liver cancer in male workers due to the definite carcinogenicity of hexavalent chromium. Significantly, an increased risk of spontaneous or threatened abortion was also found in female workers. In conclusion, these studies suggest that early detection of impaired reproductive function or impaired lung or liver function in female or male workers is essential for controlling occupational chromium poisoning in China.

Towards high-quality development: how does digital economy impact low-carbon inclusive development?: mechanism and path.

High-quality development is the primary task of building a modern socialist country in an all-around way. Innovation, coordination, green development, openness, and sharing are the main connotations of high-quality development. Based on panel data from 286 cities in China, this paper empirically analyzes the impact of the digital economy on low-carbon inclusive development (hereinafter referred to as LIG). The results show that the digital economy has a salient promoting effect on LIG, and with the increase of quantile level, the promoting effect shows a marginal decreasing trend. Heterogeneity analysis found that the cities with low resource dependence and marketization of the digital economy and high environmental concern and competition have more salient promoting effects on LIG. The dimensionality reduction analysis shows that the impact of digital economy on economic growth, social inclusion, and low-carbon ecology gradually increases in turn. The mechanism test shows that R&D investment, green innovation, and market integration play a partial mediating role, while entrepreneurial activity, industrial upgrading, and development imbalance play a fully mediating role. Digital economy promotes urban economic growth and low-carbon ecological development through R&D investment and market integration and mainly promotes low-carbon ecological development through green innovation. The digital economy will promote low-carbon and inclusive urban development by stimulating entrepreneurship, promoting industrial upgrading, and alleviating development imbalances.

Impact of Digital Transformation on Enterprise Carbon Intensity: The Moderating Role of Digital Information Resources.

In the context of China's "digital power" strategy, the realization of a green and low-carbon shift in manufacturing has become a necessary condition to promote the economy, and the digital factor has increasingly become a new driving force. The text mining and IPCC methods were used to measure manufacturing enterprise digitalization and the level of enterprise carbon emission intensity from 2011 to 2021, respectively. This study then explored the impact of digitalization on manufacturing enterprise carbon emission intensity based on the least squares method model and instrumental variable method model. This research comes to three conclusions. (1) Digitalization can significantly reduce the enterprise carbon emission intensity of China's manufacturing industry, and the influence shows a "marginal increase." (2) Notably, a mechanism analysis indicates the intermediary effect sizes of four crucial intermediaries: green technology innovation > financing constraint > information asymmetry > energy use efficiency. Interestingly, digital information resources positively moderate the positive effect of digitalization on carbon emission intensity through three paths: financing constraints, green technology innovation, and information asymmetry. (3) The influence shows evident signs of heterogeneity-as environmental regulation, financial development, executive education, and R&D quality advance, the inhibiting effect of digitalization on enterprise carbon emission intensity becomes more pronounced. Finally, corresponding policy suggestions are proposed.

Silencing of peroxiredoxin 2 suppresses proliferation and Wnt/ß-catenin pathway, and induces senescence in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a common malignancy worldwide, still lacks effective clinical treatment. The study aimed to investigate the oncogenes that affect the progression of HCC and their possible mechanisms. In our study, we initially confirmed a higher level of PRDX2 in the bile of HCC patients compared to those with choledocholithiasis by 2-DE, LC-MS, and ELISA. Subsequently, we demonstrated the high expression of peroxiredoxin 2 (PRDX2) in HCC based on the TCGA database and clinical sample analysis. Furthermore, PRDX2 overexpression enhanced the viability of HCC cells. And PRDX2 silencing induced senescence of HCC cells. In vivo, knockdown of PRDX2 significantly reduced the weight of xenograft tumors. PRDX2 also was found to activate the Wnt/ß-catenin pathway by inducing ß-catenin nuclear translocation. Consequently, we proved that silencing PRDX2 could inhibit proliferation and Wnt/ß-catenin pathway while promoting senescence in HCC cells.

XperCT facilitates sharp recanalization for the treatment of chronic thoracic venous occlusive disease in hemodialysis patients.

OBJECTIVE: Our objective was to evaluate the feasibility of XperCT combined fluoroscopy to guide sharp recanalization for the treatment of chronic thoracic venous occlusive disease in hemodialysis patients. METHODS: The records of hemodialysis patients with chronic thoracic venous occlusive disease who received endovascular sharp recanalization after conventional techniques failed were retrospectively reviewed. The sharp devices used for recanalization included the stiff end of a guidewire, Chiba biopsy needle, RUPS-100 set, and transseptal needle. The needle was advanced toward a target placed at the opposite end of the occlusion and was guided by fluoroscopy and/or XperCT. While the guidewire crossed the occlusion, endovascular procedures such as percutaneous angioplasty were performed for the treatment of the occlusion. RESULTS: The analysis included 32 sharp thoracic vein recanalization procedures in 29 patients. Two attempts in one patient failed, and in one patient the first attempt failed but the second attempt was successful. In one patient, two separate successful procedures were performed, and the other 26 procedures in 26 patients were successful. The overall technical success rate of sharp recanalization was 90%. The mean number of puncture attempts in the combined group was less than that of the fluoroscopy-guided alone group (2 vs 5, p < 0.05). The success rate of sharp recanalization in the combined group was higher (100% vs 86%), and the recanalization time (28.5 min vs 36 min, p > 0.05) was no different. There was no statistical difference in procedure-related complications between the groups. CONCLUSION: XperCT can facilitate sharp recanalization for the treatment of chronic thoracic venous occlusive disease in hemodialysis patients.

Transarterial Chemoembolization Followed by Hepatic Arterial Infusion Chemotherapy Combined a Tyrosine Kinase Inhibitor for Treatment of Large Hepatocellular Carcinoma.

OBJECTIVE: Evaluate the efficacy and safety of transarterial chemoembolization (TACE) sequential with hepatic arterial infusion chemotherapy (HAIC) and a tyrosine kinase inhibitor (TKI) for unresectable large hepatocellular carcinoma (HCC). METHODS: Patients with HCC size > 70 mm were included. They received 1-3 cycles of TACE and sequential HAIC every 3-6 weeks for 2-6 cycles, with each cycle given over a period of 48 hours (oxaliplatin plus fluorouracil/leucovorin). Patients also received sorafenib or lenvatinib beginning at the first TACE cycle and continuing until disease progression. Objective response rate (ORR) at 3 months was the primary endpoint. Progression-free survival (PFS) and safety were the secondary endpoints. RESULTS: From January 2020 to December 2020, 41 patients were included, who were divided into the drug-eluting bead TACE (DEB-TACE) group (n=13) and conventional TACE (cTACE) group (n=28). The overall ORR was 56.1% (23/41) using mRECIST criteria and 34.1% (14/41) using RECIST1.1 criteria. The median PFS of the cohort was 8 months. The ORR of the DEB-TACE group was 76.9% (10/13) vs. 46.4% (13/28) for the cTACE group (p = 0.06). The median PFS of the DEBTACE group was 12 months, and 6 months in the cTACE group (p = 0.09). Conversion hepatectomy was performed in 2 patients in the DEB-TACE group (15.4%), and in 3 patients in the cTACE group (10.7%). ALT/AST elevated, hypertension, nausea, and vomiting were the common treatment related adverse events. There was no treatment related death. CONCLUSION: TACE sequential with HAIC combined a TKI is a well-tolerated and promising tripletherapy for large, unresectable HCC.

Mediastinal Hepatoid Adenocarcinoma Treated With Arterial Interventional Therapy: A Case Report and Review of Literature.

Hepatoid adenocarcinoma (HAC) is an extremely rare extrahepatic carcinoma, which is pathologically featured by hepatocellular carcinoma (HCC) and marked by producing alpha-fetoprotein (AFP). HAC of mediastinum is extremely rare. For inoperable patients, the curative treatment options have not been established, and the outcome of HAC is usually poor. Here, we present a case of mediastinal HAC with normal serum AFP level who achieved well-controlled and good response after local-regional interventional approach combined with systemic PD-1 inhibitor. A 53-year-old male who complained of chest pain was admitted to our hospital in February 2021. A chest CT scan revealed several tumors in his mediastinum. The laboratory data showed normal serum AFP level. HAC was diagnosed through pathological assessment of biopsy. Surgery was not available due to the infiltration of sternum. Local regional FOLFOX chemotherapy was given by transarterial infusion, followed by transcatheter arterial chemoembolization, and thereafter combined with systemic anti-PD-1 treatment. The patient achieved favorable disease control and apparent symptom relief. So transarterial interventional therapy combined immunotherapy may be a possible and promising treatment for mediastinal HAC.

Quantitative synthetic MRI reveals grey matter abnormalities in children with drug-naïve attention-deficit/hyperactivity disorder.

To investigate the quantitative profiles of brain grey matter (GM) in pediatric drug-naïve ADHD patients using synthetic magnetic resonance imaging (SyMRI). A total of 37 drug-naïve pediatric ADHD and 27 age- and gender-matched healthy controls (HC) were enrolled in this study. Each subject underwent both SyMRI and conventional 3D T1-FSPGR scans. Quantitative parameters, T1 and T2 maps, were extracted from the SyMRI data. Between-group quantitative maps were compared using a general linear model analysis. Pearson correlation analysis was conducted to assess the association between significantly altered MR indices and clinical measurements in ADHD. Compared with the HC group, altered T1 and T2 relaxometry times in the ADHD group were mainly distributed in GM regions of the cerebellum, attention and execution control network, default mode network, and limbic areas. Moreover, the T1 value of the right cerebellum 8 was negatively correlated with the attention concentration level in ADHD (R = 0.140, P = 0.0225). With regards to T2 map, the associations were observed between the attention level of ADHD patients and left fusiform gyrus (R = 0.251, P = 0.0016), and right cerebellum crus2 (R = 0.142, P = 0.0214). Altered T1, T2 values found in specific regions of GM, including cerebellum, attention and execution control network, default mode network, and limbic areas, may reveal widespread micromorphology changes, i.e., brain iron deficiency, low myelin content, and enlarged vascular interstitial space in ADHD patients. Thus, T1, T2 values might be promising imaging markers for future ADHD studies.

Clinical Implications of Phenotypes of Hemodialysis Patients With Central Venous Occlusion or Central Venous Stenosis Defined by Cluster Analysis.

Objective: This study aims to investigate the association between clinical factors of patients with central (superior vena cava, brachiocephalic, or subclavian) venous occlusion or central venous stenosis (CVO/CVS) and the difficulty of interventional recanalization as well as the duration of postoperative patency. Methods: A total of 103 hemodialysis patients with CVO/CVS treated with endovascular treatment were enrolled. The two-step cluster analysis was selected to differentiate the cases into distinct phenotypes automatically. Differences in characteristics, the difficulty of interventional recanalization, and the duration of postoperative primary patency time between the two clusters were statistically compared. Results: The 103 cases were divided into distinct two clusters by the two-step cluster analysis with 48 (46.6%) in cluster 1 and 55 (53.4%) in cluster 2. Compared to cluster 2, patients in cluster 1 have a higher proportion of blunt stump, side branches, occlusion lesions >2 cm, calcification, or organization. Moreover, the above four factors were, in turn, the most critical four predictors distinguishing 103 patients into two clusters. The remaining six factors were, in turn, occlusion located in the superior vena cava (SVC), duration of central venous catheterization (CVC), lesion location, vessel diameter, number of CVC, and previously failed lesion. Of the four most important factors, with the exception of occlusion lesions exceeding 2 cm, there were significant differences in the length of procedure time between the groups grouped by the remaining three factors. And there was a significant difference in the primary patency rate between the group with blunt stump and the group without blunt stump and also between the group with occlusion lesions ≥ 2 cm and the group with occlusion lesions <2 cm. The operation time of cluster 1 was longer than that of cluster 2. In terms of postoperative patency time, the primary patency time was significantly longer in the patients of cluster 2 compared with cluster 1 (P = 0.025). Conclusion: Patients were divided into distinct two clusters. CVO/CVS of patients in cluster 1 was more challenging to be recanalized than that in cluster 2, and the primary patency time was significantly longer in the patients of cluster 2 compared with cluster 1. Blunt stump, side branches, occlusion lesions exceeding 2 cm, and calcification or organization are the four most critical predictors distinguishing 103 patients into two clusters.

Propionic Acid-Based PET Imaging of Prostate Cancer.

PURPOSE: This study aimed to evaluate the potential value of 2-[18F]fluoropropionic acid ([18F]FPA) for PET imaging of prostate cancer (PCa) and to explore the relationship between [18F]FPA accumulation and fatty acid synthase (FASN) levels in PCa models. The results of the first [18F]FPA PET study of a PCa patient are reported. PROCEDURES: The LNCaP, PC-3 cell lines with high FASN expression, and DU145 cell lines with low FASN expression were selected for cell culture. A PET imaging comparison of [18F]FDG and [18F]FPA was performed in LNCaP, PC-3, and DU145 tumors. Additionally, in vivo inhibition experiments in those models were conducted with orlistat. In a human PET study, a patient with PCa before surgery was examined with [18F]FPA PET and [18F]FDG PET. RESULTS: The uptake of [18F]FPA in the LNCaP and PC-3 tumors was higher than that of [18F]FDG (P<0.05 and P<0.05), but was lower in DU145 tumors (P<0.05). The accumulation (% ID/g) of [18F]FPA in the LNCaP, PC-3, and DU145 tumors decreased by 27.6, 40.5, and 11.7 %, respectively, after treatment with orlistat. The [18F]FPA showed higher radioactive uptake than [18F]FDG in the first PCa patient. CONCLUSIONS: The [18F]FPA uptake in PCa models may be varies with fatty acid synthase activity and could be reduced after administration of a single FASN inhibitor, albeit the activity that is not measured directly. The [18F]FPA seems to be a potential broad-spectrum PET imaging agent and may serve as a valuable tool in the diagnosis of PCa in humans.

A prognostic score model for predicting the survival benefits of patients undergoing sorafenib plus transarterial chemoembolization for hepatocellular carcinoma with portal vein invasion.

PURPOSE: The survival benefits and which patients with advanced hepatocellular carcinoma (HCC) would benefit from sorafenib plus transarterial chemoembolization (TACE) therapy remain controversial. We aimed to develop a prognostic score model for predicting different prognoses of patients with HCC and portal vein invasion who received sorafenib plus TACE. METHODS: This observational study included 167 patients with HCC and portal vein invasion undergoing sorafenib combined with TACE from January 2013 to June 2018 at two hospitals. Multivariate Cox regression analysis was performed using a training cohort (n = 83) to identify critical factors associated with survival. Then, a prognostic score model was established to classify different outcomes and confirmed using a validation cohort (n = 84). RESULTS: Three factors were determined to critically impact survival in the training cohort: portal vein invasion extent, sorafenib-related dermatologic response, and initial radiological response. Using the ß-coefficients of these factors, a prognostic score was calculated, and the survival time decreased as the score increased. Based on the prognostic score model, three different prognoses of patients with 0 points, 2-3 points, and > 3 points were stratified with a median survival of 38.0 months, 20.0 months, and 7.0 months, respectively (P < 0.001). Time to progression was also significantly different using the same prognostic index. The prognostic score model was confirmed by the validation cohort. CONCLUSION: Sorafenib plus TACE is a potential therapy for selected HCC patients with portal vein invasion. This prognostic score model can predict the survival benefits for these patients.

Biological Evaluation of [18F]AlF-NOTA-NSC-GLU as a Positron Emission Tomography Tracer for Hepatocellular Carcinoma.

Purpose: N-(2-[18F]fluoropropionyl)-L-glutamate ([18F]FPGLU) for hepatocellular carcinoma (HCC) imaging has been performed in our previous studies, but its radiosynthesis method and stability in vivo need to be improved. Hence, we evaluated the synthesis and biological properties of a simple [18F]-labeled glutamate analog, [18F]AlF-1,4,7-triazacyclononane-1,4,7-triacetic-acid-2-S-(4-isothiocyanatobenzyl)-l-glutamate ([18F]AlF-NOTA-NSC-GLU), for HCC imaging. Procedures: [18F]AlF-NOTA-NSC-GLU was synthesized via a one-step reaction sequence from NOTA-NSC-GLU. In order to investigate the imaging value of [18F]AlF-NOTA-NSC-GLU in HCC, we conducted positron emission tomography/computed tomography (PET/CT) imaging and competitive binding of [18F]AlF-NOTA-NSC-GLU in human Hep3B tumor-bearing mice. The transport mechanism of [18F]AlF-NOTA-NSC-GLU was determined by competitive inhibition and protein incorporation experiments in vitro. Results: [18F]AlF-NOTA-NSC-GLU was prepared with an overall radiochemical yield of 29.3 ± 5.6% (n = 10) without decay correction within 20 min. In vitro competitive inhibition experiments demonstrated that the Na+-dependent systems X AG - , B0+, ASC, and minor X C - were involved in the uptake of [18F]AlF-NOTA-NSC-GLU, with the Na+-dependent system X AG - possibly playing a more dominant role. Protein incorporation studies of the Hep3B human hepatoma cell line showed almost no protein incorporation. Micro-PET/CT imaging with [18F]AlF-NOTA-NSC-GLU showed good tumor-to-background contrast in Hep3B human hepatoma-bearing mouse models. After [18F]AlF-NOTA-NSC-GLU injection, the tumor-to-liver uptake ratio of [18F]AlF-NOTA-NSC-GLU was 2.06 ± 0.17 at 30 min post-injection. In vivo competitive binding experiments showed that the tumor-to-liver uptake ratio decreased with the addition of inhibitors to block the XAG system. Conclusions: We have successfully synthesized [18F]AlF-NOTA-NSC-GLU as a novel PET tracer with good radiochemical yield and high radiochemical purity. Our findings indicate that [18F]AlF-NOTA-NSC-GLU may be a potential candidate for HCC imaging. Also, a further biological evaluation is underway.