Role of formyl peptide receptor 2 in steatosis of L02 cells exposed to Mono-(2-ethylhexyl) phthalate.

Mono-(2-ethylhexyl) phthalate (MEHP) can accumulate in the liver and then lead to hepatic steatosis, while the underlying mechanism remains unclear. Inflammation plays an important role in the disorder of hepatic lipid metabolism. This study aims to clarify the role of the inflammatory response mediated by formyl peptide receptor 2 (FPR2) in steatosis of L02 cells exposed to MEHP. L02 cells were exposed to MEHP of different concentrations and different time. A steatosis model of L02 cells was induced with oleic acid and the cells were exposed to MEHP simultaneously. In addition, L02 cells were incubated with FPR2 antagonist and then exposed to MEHP. Lipid accumulation was determined by oil red O staining and extraction assay. The indicators related to lipid metabolism and inflammatory response were measured with appropriate kits. The relative expression levels of FPR2 and its ligand were determined by Western blot, and the interaction of them was detected by co-immunoprecipitation. As a result, MEHP exposure could promote the occurrence and progression of steatosis and the secretion of chemokines and inflammatory factors in L02 cells. MEHP could also affect the expression and activation of FPR2 and the secretion of FPR2 ligands. In addition, the promotion effect of MEHP on the secretion of total cholesterol and interleukin 1ß in L02 cells could be significantly inhibited by the FPR2 antagonist. We concluded that FPR2 might affect the promotion effect of MEHP on steatosis of L02 cells by mediating inflammatory response.

TfR1 mediated iron metabolism dysfunction as a potential therapeutic target for osteoarthritis.

OBJECTIVE: Transferrin receptor-1 (TfR1) plays important roles in controlling cellular iron levels, but its role in OA pathology is unknown. Herein we aim to investigate the role of TfR1 in OA progression and its underlying mechanisms. METHODS: TfR1 expression in cartilage during OA development were examined both in vivo and in vitro. Then IL-1ß was used to induce chondrocytes degeneration in vitro and TfR1 siRNA was used for observing the effect of TfR1 in modulating iron homeostasis, mitochondrial function and degrading enzymes expression. Also the inhibitor of TfR1 was exploited to analyze the protective effect of TfR1 inhibition in vivo. RESULTS: TfR1 is elevated in OA cartilage and contributes to OA inflammation condition. Excess iron not only results in oxidative stress damage and sensitizes chondrocytes to ferroptosis, but also triggers c-GAS/STING-mediated inflammation by promoting mitochondrial destruction and the release of mtDNA. Silencing TfR1 using TfR1 siRNA not only reduced iron content in chondrocytes and inhibited oxidative stress, but also facilitated the mitophagy process and suppressed mtDNA/cGAS/STING-mediated inflammation. Importantly, we also found that Ferstatin II, a novel and selective TfR1 inhibitor, could substantially suppress TfR1 activity both in vivo and in vitro and ameliorated cartilage degeneration. CONCLUSION: Our work demonstrates that TfR1 mediated iron influx plays important roles in chondrocytes degeneration and OA pathogenesis, suggesting that maintaining iron homeostasis through the targeting of TfR1 may represent a novel therapeutic strategy for the treatment of OA.

Nrf2 protects against cartilage endplate degeneration through inhibiting NCOA4­mediated ferritinophagy.

Iron overload and ferroptosis are associated with intervertebral disc degeneration (IDD); however, the mechanism underlying the regulation of iron homeostasis remains to be elucidated. Nuclear factor erythroid 2­related factor 2 (Nrf2) has been reported to regulate cellular iron homeostasis; however, its impact on IDD pathology and the underlying mechanism of action requires further investigation. In the present study, immunohistochemistry analysis of Nrf2 expression in the cartilage endplate (CEP) was conducted and it was demonstrated that Nrf2 expression was increased in the CEP at the early stages of the development of IDD, whereas it was decreased at the late stages of the development of IDD. The results of western blot analysis indicated that the inadequate activation of Nrf2 may aggravate mitochondrial dysfunction and oxidative stress, thus promoting CEP chondrocyte degeneration and calcification. It was also revealed that Nrf2 was involved in TNF­α­induced CEP chondrocyte iron metabolism dysfunction and ferroptosis. Inhibition of Nrf2 expression using Nrf2 small interfering RNA could enhance the process of nuclear receptor coactivator 4 (NCOA4)­mediated ferritinophagy and increase ferrous ion content, which may promote CEP chondrocyte ferroptotic cell death and extracellular matrix degradation. Furthermore, a decrease in cellular iron concentration may inhibit CEP chondrocyte ferroptosis, and CEP degeneration and calcification. The present study highlights the role of the Nrf2/NCOA4 axis in chondrocyte ferroptosis and IDD pathogenesis, thus suggesting that activation of Nrf2 may be a promising strategy for IDD treatment.

Prognostic value of pretreatment FDG PET-CT for short-term efficacy of radioactive iodine-125 seed implantation in patients with NSCLC.

PURPOSE: To analyze the short-term clinical response of radioactive iodine-125 seed implantation (I125-SI) in patients of non-small-cell lung cancer (NSCLC) and explore possible correlations of various metabolic parameters of pretreatment FDG PET-CT with the short-term efficacy of this treatment modality. METHODS AND MATERIALS: The present study is a retrospective analysis of treatment records of 46 NSCLC patients who were treated with I125-SI for lung tumors in Tianjin First Central Hospital from January 2016 to December 2018. The correlation among parameters D90, gender, pathological pattern, age, maximum tumor diameter, Metabolic Tumor Volume (MTV), SUVmax, SUVpeak, SUVmean, Total Lesion Glycolysis (TLG), High metabolic tumor cell ratio (HMR) and Carcinoembryonic antigen(CEA)with short-term efficacy of I125-SI was analyzed by two independent-sample t-test, Mann-Whitney U test or Chi-squared test and binary logistic regression. RESULTS: After uneventful completion of treatment, patients were followed up at regular intervals. At the first month followup, none of cases showed complete response (CR), while 4 cases showed partial response (PR). After 3 months, there were 2 cases of CR, and 25 cases of PR; after 6 months, there were 5 cases of CR, and 27 cases of PR. D90 (p= 0.028, OR:1.075, 95% CI:1.008-1.147), MTV (p= 0.026, OR: 0.918, 95% CI: 0.851-0.990), HMR (p= 0.020, OR: 0.003, 95% CI: 0-0.407) were independent predictors for the short-term efficacy. The predictive accuracy of MTV was medium (AUC = 0.781; cutoff value = 44.58). However, the predictive accuracies of D90 and HMR were low, with the values of AUC being 0.650 for both the parameters, and their cutoff values being 127.8 Gy and 0.27 respectively. CONCLUSIONS: I125-SI is an effective therapy with few complications in NSCLC patients. Small MTV, high D90 and low HRM were found to be linked with better local control at 6 months postimplantation.

In vitro spermatogenesis in isolated seminiferous tubules of immature mice.

Mouse spermatogenesis, from spermatogonial stem cell proliferation to sperm formation, can be reproduced in vitro by culturing testis tissue masses of neonatal mice. However, it remains to be determined whether this method is also applicable when testis tissues are further divided into tiny fragments, such as segments of the seminiferous tubule (ST), a minimal anatomical unit for spermatogenesis. In this study, we investigated this issue using the testis of an Acrosin-GFP/Histone H3.3-mCherry (Acr/H3) double-transgenic mouse and monitored the expression of GFP and mCherry as indicators of spermatogenic progression. Initially, we noticed that the cut and isolated stretches of ST shrunk rapidly and conglomerated. We therefore maintained the isolation of STs in two ways: segmental isolation without truncation or embedding in soft agarose. In both cases, GFP expression was observed by fluorescence microscopy. By whole-mount immunochemical staining, meiotic spermatocytes and round and elongating spermatids were identified as Sycp3-, crescent-form GFP-, and mCherry-positive cells, respectively. Although the efficiency was significantly lower than that with tissue mass culture, we clearly showed that spermatogenesis can be induced up to the elongating spermatid stage even when the STs were cut into short segments and cultured in isolation. In addition, we demonstrated that lowered oxygen tension was favorable for spermatogenesis both for meiotic progression and for producing elongating spermatids in isolated STs. Culturing isolated STs rather than tissue masses is advantageous for explicitly assessing the various environmental parameters that influence the progression of spermatogenesis.

Occurrence of perfluoroalkyl substances in the environment compartments near a mega fluorochemical industry: Implication of specific behaviors and emission estimation.

With the stringent restrictions on long-chain per- and polyfluoroalkyl substances (PFASs), ether-PFASs are being widely used as alternatives. We estimated that the mega fluorochemical industrial park (FIP) in Shandong, China, had emitted a maximum of 5040 kg and 1026 kg of hexafluoropropylene oxides (HFPOs), and 7560 kg and 1890 kg of perfluorooctanoic acid (PFOA) to water and air during 2021. In the surface water, groundwater, outdoor dust, soil, tree leaf and bark collected in the vicinity of the FIP, PFOA was predominant, followed by HFPOs. The much higher percentage of HFPO dimer acid (HFPO-DA) in groundwater than in surface water verified that this compound was more mobile in porous media. The strong correlations between the main PFASs in outdoor dust and surface soil suggested that the soil PFASs were mainly derived from air deposition, particularly for HFPO trimer acid (HFPO-TA), which has a stronger binding affinity with particles than PFOA. High percentage of the hydroxylated product of 6:2 polyfluorinated ether sulfonic acid was observed in groundwater, implying reductive dechlorination might occur in groundwater. Strong correlations between PFASs in outdoor dust and those in tree leaf and bark magnified that tree could serve as a sampler to effectively monitor airborne PFASs. This study provides the first line of information about the discharge, transport, and fate of novel ether-PFASs in the multiple environmental media near a point source.

Quantifying Indirect Contribution from Precursors to Human Body Burden of Legacy PFASs Based on Paired Blood and One-Week Duplicate Diet.

The restriction on legacy perfluoroalkyl substances (PFASs) has led to increasing application and contamination of their precursors and novel alternatives. However, the indirect contribution from precursors has not been well characterized. In this study, 24 PFASs were measured in the paired human blood and urine from general volunteers (n = 20), as well as their corresponding exposure matrices (7 day duplicate diet, drinking water and dust). Perfluorooctanoic acid (PFOA) was predominant, followed by 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFESA), contributing 21.6-47.0 and 6.6-20.0% of the total concentrations, respectively. Total oxidable precursor (TOP) assay and isomeric analysis coupled with a toxicokinetic model suggested that around 19% of perfluorooctane sulfonate (PFOS) in human was contributed by its precursors. The strong correlation between the estimated daily intake (EDI) and human blood concentration for 6:2 Cl-PFESA suggested that it was mainly contributed by direct exposure. The bioavailability of 6:2 Cl-PFESA in the food matrices was estimated as 18.6% by comparing the estimated and measured blood concentrations, implying that human exposure might be overestimated if the bioavailability of PFASs in food was not considered. Assuming that they had a similar bioavailability, it was estimated that ca. 20% of PFOS body burden was from indirect exposure to its precursors, which was supported by TOP assay.

Insights into the Competitive Mechanisms of Per- and Polyfluoroalkyl Substances Partition in Liver and Blood.

Some per- and polyfluoroalkyl substances (PFASs) tend to be accumulated in liver and cause hepatotoxicity. However, the difficulty to directly measure liver concentrations of PFASs in humans hampers our understanding of their hepatotoxicity and mechanisms of action. We investigated the partitioning of 11 PFASs between liver and blood in male CD-1 mice. Although accumulation of the perfluoroalkanesulfonic acids (PFSAs) in mice serum was higher than their carboxylic acids (PFCAs) counterparts as expected, the liver-blood partition coefficients (RL/S) of PFSAs were lower than the PFCAs RL/S, implying a competition between liver and blood. The in vitro experiments further indicated that the partitioning was dominantly determined by their competitive binding between human liver fatty acid binding protein (hL-FABP) and serum albumin (HSA). The binding affinities (Kd) of PFASs to both proteins were measured. The correlations between the RL/S and log Kd (hL-FABP)/log Kd (HSA) were stronger than those with log Kd (hL-FABP) alone, magnifying that the partitioning was dominantly controlled by competitive binding between hL-FABP and HSA. Therefore, the liver concentrations of the selected PFASs in humans could be predicted from the available serum concentrations, which is important for assessing their hepatotoxicity.

[Differential Expression of Long Non-coding RNA Cancer Susceptibility Candidate 2 and Imprinted Gene H19 in Extrahepatic Cholangiocarcinoma].

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ 2=6.222,P=0.022)and lymph node metastasis(χ2=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ2=1.174,P=0.029)and tumor size(χ2=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.

A polysaccharide-based bioflocculant BP50-2 from banana peel waste: Purification, structure and flocculation performance.

In this study, the purification and characterization of a polysaccharide-based bioflocculant BP50-2 of banana peel waste were investigated. BP50-2 was purified and identified through HPLC, XPS, TG, SEM, AFM, etc. The results showed that BP50-2 was a heteropolysaccharide composed of Mannose, Rhamnose, Glucuronic acid, Galacturonic acid, Glucose, Galactose, and Fucose at a molar ratio of 8.97:5.36:1.92:1.00:32.52:8.30:2.64, respectively. The MW of BP50-2 was 1.47 × 10 3 KDa. BP50-2 had high pH stability that maintained flocculation activity on kaolin suspension for a pH range from 3 to 11, and high-temperature stability ranged from room temperature to 90 °C. BP50-2 was non-sensitive to cation and affected by HCl, EDTA, little affected by urea, which showed that the BP50-2 was non-cation dependent and its main binding mode with kaolin was ionic bond and contained a small amount of hydrogen bond. And flocculation mechanisms were discussed, which indicated that adsorption bridging was the main mechanism of the flocculation process of BP50-2-Kaolin or BP50-2-Mg2+-Kaolin. Moreover, BP50-2 had decolorization activity on RhB and removal activity of heavy metal ion, of which removal rate of Pb2+ was the highest. In brief, BP50-2 showed good performance on the removal of pigment, adsorption of heavy metals, and flocculation of particles.

External and internal human exposure to PFOA and HFPOs around a mega fluorochemical industrial park, China: Differences and implications.

Hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA) are used as alternatives to legacy perfluorooctanoic acid (PFOA); however, little is known about their human exposure risks. In this study, the concentrations of PFOA and HFPO were measured in major human exposure matrices and human bio-samples of local residents near a mega fluorochemical industrial park in Shandong, China, to characterize their external and internal exposures. Although HFPO-DA was detected in drinking water and indoor dust, it exhibited a considerably low bioaccumulation potential in animal-origin food and human samples (urine, hair, and serum), implying that it might be a benign alternative to PFOA. Although the estimated daily intake (EDI) of HFPO-TA was comparable to that of PFOA, its concentration in urine was higher than that of PFOA, implying that it might be eliminated faster than PFOA. A simple one-compartment pharmacokinetic model was applied to estimate the serum concentrations of the target compounds and subsequently compare them with the measured concentrations. The predicted concentration of PFOA in serum based on its concentration in urine and half-life was close to the measured value, confirming the distinct internal exposure of PFOA in the local residents. However, the measured concentrations of HFPO in serum were considerably lower than those predicted from the external EDI and urine concentrations, implying that they were eliminated faster than expected in humans. Various perfluoroalkyl substances were detected in human hair, and their compositions were similar to those in human serum, suggesting that hair is a good non-invasive indicator for long-term exposure to legacy long-chain perfluoroalkyl carboxylic acids and HFPOs. This study provided valuable information about the human exposure to legacy PFOA and HFPOs in highly impacted areas near point sources and necessitates studies on the toxicokinetics of HFPOs.

Occurrence and sources of per- and polyfluoroalkyl substances in the ice-melting lakes of Larsemann Hills, East Antarctica.

The contamination and sources of per- and polyfluoroalkyl substances (PFASs) in the Antarctic continent have not been systematically investigated. In this study, 21 PFASs including some new emerging one, were measured in the surface waters collected from 21 ice-melting lakes next to the research stations in Larsemann Hills, East Antarctica (EA). All the PFASs had a median concentration lower than 26.7 pg/L, representing the background levels in EA. The contamination of PFASs in EA was generally lower than in West Antarctica (WA), which might be due to the less on-site human activities in EA than in WA. In the ice-melting lakes, perfluorooctane acid (PFOA) was predominant, and its concentrations in several lakes close to the research stations in EA could be up to 458 pg/L. For the first time, an emerging substitute of perfluorooctane sulfate (PFOS), 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFESA), was detected in several of the samples. Source apportionment methods including isomer profiling were applied, and the results collectively indicated that the PFASs in the melting lakes in EA were mainly derived from airborne input, but local discharge might also contribute to PFOA in some lakes. The results of this study supplied information about the sources of PFASs in Antarctica, and suggested that caution should be taken in future to control the local discharge due to increasing human activities in EA.

Mechanisms for tissue-specific accumulation and phase I/II transformation of 6:2 fluorotelomer phosphate diester in earthworm (M. guillelmi).

Polyfluoroalkyl phosphate esters (PAPs) are high production volume surfactants used in the food contact paper and packaging industries. They are prone to partition to soil due to their strong hydrophobicity and may biotransform into recalcitrant perfluoroalkyl carboxylic acids (PFCAs); little is known about their fate and behaviors in terrestrial organisms. Here, geophagous earthworms (M. guillelmi) were exposed to 6:2 fluorotelomer phosphate diester (6:2 diPAP)-contaminated soil to examine tissue-specific accumulation and biotransformation. 6:2 diPAP quickly accumulated in M. guillelmi with the highest biota-soil-accumulation factor (BSAF) in the gut, followed by the organs, skin, and body fluid. The total amount of 6:2 diPAP accumulated in the skin was the highest due to its high mass content. These results indicated that skin absorption and gut processes were two major pathways for earthworms to accumulate 6:2 diPAP from soil. In vitro desorption experiments indicated that the gut digestion fluid greatly promoted the desorption of 6:2 diPAP from the soil and enhanced its bioavailability. Degradation of 6:2 diPAP in the soil was stimulated when the earthworm appeared. In contrast to the soil, a more extensive transformation occurred in the earthworm. Perfluorohexanoic acid (PFHxA) was the primary phase Ⅰ product, followed by perfluoropentyl propanoic acid (FPePA), perfluoropentanoic acid (PFPeA), 2-perfluorohexyl ethanoic acid (FHEA), and perfluoroheptanoic acid (PFHpA), which confirmed the occurrence of α- and ß-oxidation in earthworms. For the first time, a new phase II product, namely, a 6:2 fluorotelomer alcohol sulfate conjugate, was identified in earthworms at unexpectedly high levels, which might be the primary way earthworms eliminate 6:2 diPAP. Both in vivo and in vitro experiments suggested that 6:2 diPAP experienced faster and more extensive biotransformation in the gut than in the organs. This work sheds light on the bioaccumulation and biotransformation of 6:2 diPAP in terrestrial invertebrates, providing strong evidence of indirect sources of PFCAs in the environment.

Legacy and emerging per- and poly-fluoroalkyl substances in surface seawater from northwestern Pacific to Southern Ocean: Evidences of current and historical release.

Knowledge on distribution of per- and poly-fluoroalkyl substances (PFASs) in open oceans is limited. By taking part in the 32nd Chinese Antarctic Research Expedition, 41 surface seawater samples were collected in the northwestern Pacific Ocean (NW-PO), eastern Indian Ocean (E-IO) and Southern Ocean (SO), and 23 PFASs comprised of legacy perfluoroalkyl carboxylic acids, perfluoroalkyl sulfonate acids and some new emerging homologs such as 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) were measured. The concentrations of the total PFASs decreased in the order of NW-PO>E-IO>SO. Perfluorooctanoic acid (PFOA) was the most dominant, followed by perfluorooctane sulfonate (PFOS). The PFOA concentration declined exponentially with the offshore distance, while such trend was not obvious for PFOS and other legacy PFASs, suggesting that PFOA was mainly derived from the ongoing land-based emissions, while PFOS was mainly from historical residues. 6:2 Cl-PFESA was identified (<11.1-170 pg/L) in the oceanic waters with relatively high level at the sites near Australia. Multiple receptor models indicated that PFASs in the SO were mainly contributed by atmosphere input, while those in the NW-PO and E-IO were originated from land sources. Isomeric profiles of PFOA showed that telomere-based source became more outstanding than electrochemical fluorinated production in recent years.

First report on the sources, vertical distribution and human health risks of legacy and novel per- and polyfluoroalkyl substances in groundwater from the Loess Plateau, China.

In this study, legacy and novel per and polyfluoroalkyl substances (PFASs) were measured in groundwater samples collected from the Loess Plateau of China to understand their occurrence, sources and health risks. The total concentration of PFASs ranged from 2.78 to 115 ng/L, with perfluorooctanoic acid (PFOA) as the dominant compound. Many emerging PFASs, including 6:2 fluorotelomer sulfonates (FTS), 6:2 chlorinated polyfluorinated ether sulfonic acid (Cl-PFESAs), ammonium 4,8-dioxa-3H-perfluorononanoate (ADONA), and hexafluoropropylene oxide (HFPO) homologues were frequently detected in 96.7-100% of the samples. Multiple source apportionment analyses indicated that the PFASs in the groundwater mainly originated from industrial activities, but in rural areas, agricultural activities also contributed. The total oxidizable precursor (TOP) assay indicated that there were substantial unknown precursors of perfluoroalkyl acids (PFAAs) in the groundwater samples. The total concentration of PFASs decreased with the well depth, while the PFAA-precursors displayed contrasting vertical profile trends, which might be due to the suppressed microbial transformation in the groundwater. The potential human health risk caused by PFAS exposure via drinking groundwater in the Loess Plateau was low, except for one site that was close to the industry bases.

Effects of atorvastatin and aspirin on post-stroke epilepsy and usage of levetiracetam.

OBJECTIVE: Atorvastatin and aspirin have been used in treating different forms of epilepsy. However, their effect on post-stroke epilepsy (PSE) still needs to be validated by large-scale clinical studies. In addition, their impact on the use of the antiepileptic drug levetiracetam for post-stroke epilepsy remains to be explored. Thus, the aim of this study was to further evaluate the effect of atorvastatin and aspirin on PSE and their effect on the usage of the antiepileptic drug levetiracetam in PSE patients. METHODS: Patients, aged 65 to 85 years, with newly diagnosed post-ischemic stroke epilepsy from August 30, 2014 to August 30, 2018 were included in the study, with the exclusion of those with coexisting conditions. RESULTS: Initially, 1321 patients were included, and 780 remained in the study at the 1-year follow-up. During the study, atorvastatin treatment with or without aspirin reduced the number of clinical epileptic episodes in PSE patients. It also reduced the dosage of levetiracetam and achieved better control of epilepsy compared to levetiracetam mono-treatment. Aspirin co-treatment with levetiracetam did not result in a significant improvement. However, the combination of aspirin with atorvastatin significantly reduced the number of seizures compared to atorvastatin treatment alone. CONCLUSION: Atorvastatin and aspirin co-treatment with levetiracetam can reduce epilepsy in PSE patients and reduce the dosage of levetiracetam required for effective control of PSE.

Predicting tumor recurrence using metabolic indices of 18F-FDG PET/CT prior to orthotopic liver transplantationfor hepatocellular carcinoma.

The present study analyzed the ability of metabolic burden indices from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to predict tumor recurrence following orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). Seven major metabolic indices were measured by 18F-FDG PET/CT in 93 patients with HCC, prior to OLT. The Mann-Whitney U test was then used to predict the association of metabolic indices, including the maximum standardized uptake value (SUVmax), tumor-to-mediastinum SUV ratio, tumor-to-normal-liver SUV ratio, SUV normalized to lean body mass metabolic tumor volume (MTV), total lesion glycolysis (TLG) and uptake-volume product (UVP), with the recurrence risk. The Deauville-like scoring system was used to quantify the recurrence risk. Univariate and multivariable Cox regression models were performed to determine survival rate. The results showed that Deauville-like score (PET-negative vs. -positive), MTV (cutoff value, 13.36), TLG (cutoff value, 62.21) and UVP (cutoff value, 66.60) had high prediction performance for tumor recurrence (P<0.05). TLG had the highest receiver operating characteristics area under the curve of 0.725. Among the clinical factors, high level of α-fetoprotein (AFP, ≥144 ng/ml), Milan criteria, tumor number (>3), involvement of both right and left lobes, and tumor size (>5 cm) were found to be significant predictors of tumor recurrence. Patients in the low metabolic group had longer recurrence-free survival (RFS) times compared with those in the high metabolic group, regardless of whether they met the Milan criteria or not. AFP, uptake-volume product according the SUV mean of mediastinum (UVP-M), Milan criteria, lymph node metastasis, and the number of tumors were significant prognostic factors for RFS (P<0.05) in both univariate and multivariate survival analyses. Additionally, the MVI was a significant prognostic factor based on univariate survival analyses. Overall, the present study demonstrated the metabolic burden indices measured by PET/CT, Deauville-like score, MTV, TLG and UVP as significant prognostic factors in patients with HCC following OLT. The combination of metabolic indices measured by PET/CT and the existing criteria, such as the Milan criteria, may play an important role in evaluating the suitability of OLT in specific patients.

Potential sources and sediment-pore water partitioning behaviors of emerging per/polyfluoroalkyl substances in the South Yellow Sea.

Emerging per/polyfluoroalkyl substances (PFASs) have received great concerns, but there are few data in the coastal environment, which play an essential role in their global transport. In this study, surface water and sediment samples were collected in the South Yellow Sea close to Jiangsu Province China, and 26 legacy as well as emerging PFASs were investigated. Perfluorooctanoic acid (PFOA) and perfluorobutane sulfonate (PFBS) were predominant in the coastal water of the South Yellow Sea with a relatively higher level than other coastal regions in the world. PFBS and 6:2 fuorotelomer sulfonic acid (6:2 FTSA) were two major alternatives of perfluorooctane sulfonate (PFOS) which were used in textile surface treatment and fire-fighting foams, respectively. Multiple receptor models identified that fluoropolymer manufacture, textile and food packages were three major sources of PFASs in the South Yellow Sea. The partitioning behaviors of PFASs between sediment and pore water in the marine environment were compared, and the partitioning coefficients of hexafluoropropylene oxide trimer acid (HFPO-TA) and 6:2 chlorinated polyfluorinated ether sulfonic acid (6:2 F-53B) were reported for the first time, which exhibited stronger partition in sediment than their predecessors. The results provide important hints to understand the environmental transport of PFASs in the marine environment.

Occurrence and source apportionment of novel and legacy poly/perfluoroalkyl substances in Hai River basin in China using receptor models and isomeric fingerprints.

A variety of fluorinated alternatives are being manufactured and applied as a consequence of stringent regulations on legacy poly/perfluoroalkyl substances (PFASs). In this study, 26 emerging and legacy PFASs were measured in the surface water (including dissolved phase and suspended particulate matter) and sediments taken from Hai River basin, China. The total concentrations of PFASs (∑PFASs) ranged from 1.74 to 172 ng/L, with perfluorooctanonate (PFOA) as the dominant compound (15.2% of the ∑PFASs, median value). Emerging PFASs, such as dimer acid of hexafluoropropylene oxide dimer acid (HFPO-DA) and trimer acid (HFPO-TA), were widely detected in the water samples. Specifically, chlorinated polyfluorinated ether sulfonate (F-53B) was observed to be predominant in some sediment samples. A receptor model, Unmix, was introduced to identify the sources of PFASs in the surface water, and the results indicated that fire-fighting foam/fluoropolymer processing aids (36.6%) were the dominant source. The field-based sediment-water (organic carbon normalized) coefficients, Koc, were correlated to the carbon chain lengths of the PFASs. A technique coupling one-way analysis of variance with chemical mass balance model was developed to trace the manufacturing sources of PFOA. Electrochemical fluorination (ECF) was the major PFOA manufacturing source with considerable contribution by telomerization. For the first time, the isomers of perfluorooctane sulfonamide (PFOSA) were quantified in the environmental samples. The lower proportion of branched (br-) PFOSA isomers and higher percentage of br-perfluorooctane sulfonate (PFOS) isomers in the water samples relative to their corresponding commercial products, provided more direct evidences that br-PFOSA isomers were biotransformed more easily than n-PFOSA, explaining the observed enrichment of br-PFOS in the aquatic environment.

Losmapimod Protected Epileptic Rats From Hippocampal Neuron Damage Through Inhibition of the MAPK Pathway.

Objective: This research aimed to validate the therapeutic effect of losmapimod and explore the underlying mechanism in its treatment of epilepsy. Methods: A rat model of epilepsy was constructed with an injection of pilocarpine. Microarray analysis was performed to screen aberrantly expressed mRNAs and activated signaling pathways between epileptic rats and normal controls. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was used to identify cell apoptosis. Hippocampal cytoarchitecture was visualized with Nissl staining. The secretion of inflammatory factors as well as the marker proteins in the mitogen-activated protein kinase (MAPK) pathway were detected by Western blot. A Morris water maze navigation test evaluated the rats' cognitive functions. Results: Activation of the MAPK signaling pathway was observed in epilepsy rats. A decrease in the MAPK phosphorylation level by application of losmapimod protected against epilepsy by reducing neuron loss. Losmapimod effectively improved memory, reduced the frequency of seizures, protected the neuron from damage, and limited the apoptosis of neurons in epilepsy rats. Conclusion: The application of losmapimod could partly reverse the development of epilepsy.