Unraveling the Role of RNA-Binding Proteins, with a Focus on RPS5, in the Malignant Progression of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) represents a major global health concern, demanding a thorough understanding of its molecular mechanisms for effective therapeutic strategies. RNA-binding proteins (RBPs) play critical roles in post-transcriptional gene regulation, with their dysregulation increasingly recognized as a hallmark of various cancers. However, the specific contributions of RBPs to HCC pathogenesis and prevention remain incompletely understood. In this study, we systematically conducted an examination of the expression profiles and clinical relevance of RBPs in 556 clinical samples from well-established cohorts. Through comprehensive analyses, a subset of RBPs exhibiting significant overexpression in HCC was identified, establishing a noteworthy correlation between their aberrant expression and HCC progression. Furthermore, 40S ribosomal protein S5 (RPS5), a ribosomal protein, emerged as a potential key contributor in HCC progression. Rigorous analyses established a correlation between elevated RPS5 expression and advanced clinicopathological features, suggesting its potential as a prognostic biomarker. Experiments further confirmed the impact of RPS5 on pivotal cellular processes implicated in cancer progression, including cell proliferation and metastasis. Further mechanistic studies unveiled the potential of RPS5 to activate the cell cycle by binding to key molecules involved in the pathway, thereby promoting the malignant progression of HCC. Additionally, our analysis of the etiology behind RPS5 overexpression in HCC posited it as an outcome of transcriptional regulation by the transcription factors Nuclear Respiratory Factor 1 (NRF1) and MYC-associated zinc finger protein (MAZ). In conclusion, our study contributes to the growing evidence elucidating the intricate involvement of RBPs, exemplified by RPS5, in the malignant progression of HCC. The integration of genomic, transcriptomic, and functional analyses provides a comprehensive understanding of the regulatory mechanisms associated with RPS5 in HCC. This comprehensive analysis not only advances our knowledge of the molecular drivers behind HCC but also highlights the potential therapeutic relevance of targeting RBPs and their regulatory network for the development of more effective treatment strategies.

Near-IR Electrochromic Film with High Optical Contrast and Stability Prepared by Oxidative Electropolymerization of Triphenylamine Modified Terpyridine Platinum(II) Chloride.

Terpyridine (TPY) platinum(II) chloride with a triphenylamine (TPA) group was successfully synthesized. The strong intramolecular Donor(TPA)-Acceptor(TPY) interaction induced the low-energy absorption band, mixing the spin-allowed singlet dπ(Pt)→π*(TPY) metal-to-ligand charge transfer (MLCT) with the chloride ligand-to-metal charge transfer (LMCT) and chloride ligand-to-ligand (TPY) charge transfer (LLCT) transitions, to bathochromically shift to λmax = 449 nm with significant enhancement and broadening effects. Using the cyclic voltammetry method, its oxidative electropolymerization (EP) films on working Pt disk and ITO electrodes were produced with tunable thickness and diffusion controlled redox behavior, which were characterized by the SEM, EDS, FT-IR, and AC impedance methods. Upon applying +1.4 V voltage, the sandwich-type electrochromic device (ECD) with ca. 290 nm thickness of the EP film exhibits a distinct color transformation from red (CIE coordinates: L = 50.75, a = 18.58, b = 5.69) to dark blue (CIE coordinates: L = 45.65, a = -1.35, b = -12.49). Good electrochromic (EC) parameters, such as a large optical contrast (ΔT%) of 78%, quick coloration and bleaching response times of 2.9 s and 1.1 s, high coloration and bleaching efficiencies of 278.0 and 390.5 C-1·cm2, and good cycling stability (maintains 70% of the initial ΔT% value after 3200 voltage switching cycles), were obtained.

Liver Parenchyma Transection-First Approach for Laparoscopic Left Hemihepatectomy: A Propensity Score Matching Analysis.

BACKGROUND: Laparoscopic major liver resection, such as laparoscopic left hemihepatectomy (LLH), is still perceived as a complicated procedure due to technical difficulties and slow learning curve. The study introduced an optimized procedure using the liver parenchyma transection-first approach and investigated its advantages on surgical outcomes by comparison with the conventional hilar dissection approach for LLH. METHODS: Between January 2015 and May 2019, 96 patients who underwent laparoscopic left hemihepatectomy for hepatocellular carcinoma (HCC) were enrolled in the study. Among these, 41 patients underwent the liver parenchyma transection-first approach (LP-first group) and the other 55 underwent the conventional hilar dissection approach (conventional group). A 1:1 propensity score matching (PSM) was performed to compare the perioperative and long-term oncological outcomes of the two groups. RESULTS: After 1:1 PSM, 37 patients in each group were selected for further analysis. The LP-first group was associated with shorter median operative time (210 vs 235 min, P = 0.035) and less blood loss (200 vs 300 mL, P = 0.410). In addition, no statistical differences were found in overall complications between the two groups (8.1% vs 24.3%, P = 0.058). There were no significant differences between the two groups in terms of 1-year and 3-year disease-free survival (DFS, P = 0.608) and overall survival (OS, P = 0.414). CONCLUSION: The prior liver parenchyma approach for LLH is safe and reproducible in selected patients, which showed improved perioperative outcomes and comparable long-term oncological outcomes compared with the conventional approach.

Root resorptions associated with canine retraction treatment.

INTRODUCTION: The hypothesis of this study was that multiple factors are dominant in causing external apical root resorption (EARR). The objective of this investigation was to better understand the clinical factors that may lead to EARR. METHODS: Maxillary cone-beam computed tomography scans of 18 subjects who were treated with bilateral canine retractions during orthodontics were used to calculate EARR. The subjects were treated using well-calibrated segmental T-loops for delivering a 124-cN retraction force and the moment-to-force ratio suitable for moving the canine under either translation or controlled tipping. The subjects' age, sex, treatment duration, and genotype were collected. RESULTS: Six subjects of the 18 showed definite EARR, meaning that load was not the only causing factor. All 5 subjects with the genotype identified had GG genotype of IL-1ß rs11143634, indicating that people with this genotype may be at high risk. Longer treatment duration, female sex, and older age may also contribute to EARR, although the findings were not statistically significant. CONCLUSIONS: EARR appears to be related to multiple factors. The orthodontic load and the genotype should be the focuses for future studies.

Targeting PTEN in ischemic stroke: From molecular mechanisms to therapeutic potentials.

Ischemic stroke remains a leading cause of mortality and disability worldwide, driven by complex pathophysiological mechanisms, including excitotoxicity, oxidative stress, apoptosis, and neuroinflammation. PTEN (Phosphatase and tensin homolog deleted on chromosome 10) plays a crucial role in these processes, influencing key signaling pathways such as PI3K/Akt and mTOR. This review aims to explore PTEN's multifaceted functions in ischemic stroke, examining its interactions with non-coding RNAs, involvement in mitophagy and immune suppression, and overall impact on cellular homeostasis. We will investigate various therapeutic strategies targeting PTEN, including synthetic drugs, natural products, and exosome-based therapies enriched with specific miRNAs. Additionally, we will assess the potential of non-pharmaceutical interventions such as electroacupuncture, exercise, transcranial direct current stimulation (tDCS), and therapeutic hypothermia in modulating PTEN activity to enhance cererbroprotection and functional recovery. By elucidating these aspects, this review aims to inspire and motivate the audience in their research and clinical practice, highlighting PTEN as a promising therapeutic target and paving the way for developing effective treatments for ischemic stroke.

Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice.

BACKGROUND: The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain ß-amyloid (Aß) deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear. OBJECTIVES: This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. METHODS: Female APP/PS1 mice at 8 wk of age were administered either 50mg/kg Pb-acetate (PbAc) (i.e., 27mg Pb/kg) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immunostaining. In addition, Aß perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed in vivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice. RESULTS: APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to Aß40, higher Aß40/Aß42 ratios, strikingly lower Aß40 levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure. DISCUSSION: Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384.

Demyelination and impaired oligodendrogenesis in the corpus callosum following lead exposure.

The corpus callosum is an oligodendrocyte-enriched brain region, replenished by newborn oligodendrocytes from oligodendrocyte progenitor cells (OPCs) in subventricular zone (SVZ). Lead (Pb) exposure has been associated with multiple sclerosis, a disease characterized by the loss of oligodendrocytes. This study aimed to investigate the effects of Pb exposure on oligodendrogenesis in SVZ and myelination in the corpus callosum. Adult female mice were used for a disproportionately higher prevalence of multiple sclerosis in females. Acute Pb exposure (one ip-injection of 27 mg Pb/kg as PbAc2 24 hr before sampling) caused mild Pb accumulation in the corpus callosum. Ex vivo assay using isolated SVZ tissues collected from acute Pb-exposed brains showed a diminished oligodendrogenesis in SVZ-derived neurospheres compared with controls. In vivo subchronic Pb exposure (13.5 mg Pb/kg by daily oral gavage 4 wk) revealed significantly decreased newborn BrdU+/MBP+ oligodendrocytes in the corpus callosum, suggesting demyelination. Mechanistic investigations indicated decreased Rictor in SVZ OPCs, defective self-defense pathways, and reactive gliosis in the corpus callosum. Given the interwined pathologies between multiple sclerosis and Alzheimer's disease, the effect of Pb on myelination was evaluated in AD-modeled APP/PS1 mice. Myelin MRI on mice following chronic exposure (1,000 ppm Pb in drinking water as PbAc2 for 20 wk) revealed a profound demyelination in the corpus callosum compared with controls. Immunostaining of the choroid plexus showed diminished signaling molecule (Klotho, OTX2) expressions in Pb-treated animals. These observations suggest that Pb caused demyelination in the corpus callosum, likely by disrupting oligodendrogenesis from SVZ OPCs. Pb-induced demyelination represents a crucial pathogenic pathway in Pb neurotoxicity, including multiple sclerosis.

RNA-binding protein RPS7 promotes hepatocellular carcinoma progression via LOXL2-dependent activation of ITGB1/FAK/SRC signaling.

BACKGROUND: Metastasis is one of the leading cause contributes to treatment failure and poor prognosis of hepatocellular carcinoma (HCC) patients. The underlying mechanism of HCC metastasis remains to be determined. Although several RNA binding proteins (RBPs) have been found to participate in tumorigenesis and progression of liver cancer, the role of RBPs in HCC patients with extrahepatic metastases is poorly understood. METHODS: By performing RNA-seq of primary HCC tissues (including HCC with extrahepatic metastasis and those did not develop metastasis), we identified a set of HCC metastasis-associated RBPs candidates. Among which, ribosomal protein S7 (RPS7) was found to be remarkably increased in HCC tissues and be strongly related to HCC poor survival. Overexpression or CRISPR-Cas9-mediated knockout were applied to investigate the role of RPS7 on the metastasis-associated phenotypes of HCC cells. RNA sequencing, RIP, RNA-pull down, dual luciferase reporter assay, nascent RNA capture assay, and RNA decay and so on, were applied to reveal the underlying mechanism of RPS7 induced HCC metastasis. RESULTS: Gain- and loss- of function analyses revealed that RPS7 promoted HCC cells adhesion, migration and invasion capabilities, as well as lung metastasis. Mechanistically, we uncovered that lysyl oxidase-like 2 (LOXL2) was a critical downstream target of RPS7. RPS7 could stabilize LOXL2 mRNA by binding to AUUUA motifs in the 3155-3375 region of the 3'UTR of LOXL2 mRNA, thus increased LOXL2 expression via elevating LOXL2 mRNA abundance. Further research revealed that LOXL2 could accelerate focal adhesion formation through maintaining the protein stability of ITGB1 and activating ITGB1-mediated FAK/SRC signaling pathway, and thereby contribute to the pro-metastasis effect of RPS7. CONCLUSIONS: Taken together, our data reveal a novel function of RPS7 in HCC metastasis, also reveal the critical roles of the RPS7/LOXL2/ITGB1 axis in HCC metastasis and shed new light on the exploration of molecular drugs against HCC.

Human anti-prion antibodies block prion peptide fibril formation and neurotoxicity.

Prion diseases are a group of rare, fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrP(C)) into a self-replicating and proteinase K-resistant conformer, termed scrapie PrP (PrP(Sc)). Aggregates of PrP(Sc) deposited around neurons lead to neuropathological alterations. Currently, there is no effective treatment for these fatal illnesses; thus, the development of an effective therapy is a priority. PrP peptide-based ELISA assay methods were developed for detection and immunoaffinity chromatography capture was developed for purification of naturally occurring PrP peptide autoantibodies present in human CSF, individual donor serum, and commercial preparations of pooled intravenous immunoglobulin (IVIg). The ratio of anti-PrP autoantibodies (PrP-AA) to total IgG was ∼1:1200. The binding epitope of purified PrP-AA was mapped to an N-terminal region comprising the PrP amino acid sequence KTNMK. Purified PrP-AA potently blocked fibril formation by a toxic 21-amino acid fragment of the PrP peptide containing the amino acid alanine to valine substitution corresponding to position 117 of the full-length peptide (A117V). Furthermore, PrP-AA attenuated the neurotoxicity of PrP(A117V) and wild-type peptides in rat cerebellar granule neuron (CGN) cultures. In contrast, IgG preparations depleted of PrP-AA had little effect on PrP fibril formation or PrP neurotoxicity. The specificity of PrP-AA was demonstrated by immunoprecipitating PrP protein in brain tissues of transgenic mice expressing the human PrP(A117V) epitope and Sc237 hamster. Based on these intriguing findings, it is suggested that human PrP-AA may be useful for interfering with the pathogenic effects of pathogenic prion proteins and, thereby has the potential to be an effective means for preventing or attenuating human prion disease progression.

High affinity of ß-amyloid proteins to cerebral capillaries: implications in chronic lead exposure-induced neurotoxicity in rats.

Lead (Pb) is a known environmental risk factor in the etiology of Alzheimer's disease (AD). The existing reports suggest that Pb exposure increases beta-amyloid (Aß) levels in brain tissues and cerebrospinal fluid (CSF) and facilitates the formation of amyloid plaques, which is a pathological hallmark for AD. Pb exposure has long been associated with cerebral vasculature injury. Yet it remained unclear if Pb exposure caused excessive Ab buildup in cerebral vasculature, which may damage the blood-brain barrier and cause abnormal Ab accumulation. This study was designed to investigate the impact of chronic Pb exposure on Aß accumulation in cerebral capillary and the expression of low-density lipoprotein receptor protein-1 (LRP1), a critical Aß transporter, in brain capillary and parenchyma. Sprague-Dawley rats received daily oral gavage at doses of 0, 14 (low-dose), and 27 (high-dose) mg Pb/kg as Pb acetate, 5 d/wk, for 4 or 8 wks. At the end of Pb exposure, a solution containing Aß40 was infused into the brain via the cannulated internal carotid artery. Data by ELISA showed a strikingly high affinity of Ab to cerebral vasculature, which was approximately 7-14 times higher than that to the parenchymal fractions collected from control brains. Pb exposure further aggravated the Aß accumulation in cerebral vasculature in a dose-dependent manner. Western blot analyses revealed that Pb exposure decreased LRP1 expression in cortical capillaries and hippocampal parenchyma. Immunohistochemistry (IHC) studies further revealed a disrupted distribution of LRP1 alongside hippocampal vasculature accompanied with a decreased expression in hippocampal neurons by Pb exposure. Taken together, the current study demonstrated that the cerebral vasculature naturally possessed a high affinity to Aß present in circulating blood. Pb exposure significantly increased Aß accumulation in cerebral vasculature; such an increased Aß accumulation was due partly to the diminished expression of LRP1 in response to Pb in tested brain regions. Perceivably, Pb-facilitated Ab aggravation in cerebral vasculature may contribute to Pb-associated amyloid alterations.

Pb Induces MCP-1 in the Choroid Plexus.

Lead (Pb) is an environmental element that has been implicated in the development of dementia and Alzheimer's disease (AD). Additionally, innate immune activation contributes to AD pathophysiology. However, the mechanisms involved remain poorly understood. The choroid plexus (CP) is not only the site of cerebrospinal fluid (CSF) production, but also an important location for communication between the circulation and the CSF. In this study, we investigated the involvement of the CP during Pb exposure by evaluating the expression of the monocyte chemoattractant protein-1 (MCP-1). MCP-1 is highly expressed in the CP compared to other CNS tissues. MCP-1 regulates macrophage infiltration and is upregulated in AD brains. Our study revealed that Pb exposure stimulated MCP-1 expression, along with a significantly increased macrophage infiltration into the CP. By using cultured Z310 rat CP cells, Pb exposure stimulated MCP-1 expression in a dose-related fashion and markedly activated both NF-κB and p38 MAP kinase. Interestingly, both SB 203580, a p38 inhibitor, and BAY 11-7082, an NF-κB p65 inhibitor, significantly blocked Pb-induced MCP-1 expression. However, SB203580 did not directly inhibit NF-κB p65 phosphorylation. In conclusion, Pb exposure stimulates MCP-1 expression via the p38 and NF-κB p65 pathways along with macrophage infiltration into the CP.

Distribution of Pb and Se in mouse brain following subchronic Pb exposure by using synchrotron X-ray fluorescence.

Lead (Pb) is a well-known neurotoxicant and environmental hazard. Recent experimental evidence has linked Pb exposure with neurological deterioration leading to neurodegenerative diseases, such as Alzheimer's disease. To understand brain regional distribution of Pb and its interaction with other metal ions, we used synchrotron micro-x-ray fluorescence technique (µ-XRF) to map the metal distribution pattern and to quantify metal concentrations in mouse brains. Lead-exposed mice received oral gavage of Pb acetate once daily for 4 weeks; the control mice received sodium acetate. Brain tissues were cut into slices and subjected for analysis. Synchrotron µ-XRF scans were run on the PETRA III P06 beamline (DESY). Coarse scans of the entire brain were performed to locate the cortex and hippocampus, after which scans with higher resolution were run in these areas. The results showed that: a) the total Pb intensity in Pb-exposed brain slices was significantly higher than in control brain; b) Pb typically deposited in localized particles of <10 um2 in both the Pb-exposed and control brain slices, with more of these particles in Pb-exposed samples; c) selenium (Se) was significantly correlated with Pb in these particles in the cortex and hippocampus/corpus callosum regions in the Pb-exposed samples, and the molar ratio of the Se and Pb in these particles is close to 1:1. These results indicated that Se may play a crucial role in Pb-induced neurotoxicity. Our findings call for further studies to investigate the relationship between Pb exposure and possible Se detoxification responses, and the implication in the etiology of Alzheimer's disease.

Case report: A case of severe acute hepatitis of unknown origin.

According to analyses of etiology, clinical features, diagnostic methods, and treatment strategies by summarizing a case of unexplained acute hepatitis recently experienced, we are aiming to provide some information to enrich the clinical experience in diagnosis and treatment of severe acute hepatitis of unknown etiology in young children. A boy, aged 10 years and 6 months old, was admitted to the hospital due to acute abdominal pain, jaundice, and exceptionally high levels of ALT and AST. A range of measures, including patient history, physical examination, and routine laboratory testing, were performed. Furthermore, strategies such as trio-based next-generation sequencing (Trio-NGS) and liver biopsy, as well as metagenomic NGS (mNGS) of blood and liver samples were also performed. In summary, this case was an acute severe non-A-E hepatitis that is a probable case with hepatitis of unknown origin. Immunohistochemical analysis showed an immune injury in liver tissues. Torque teno virus (TTV) sequences were detected by mNGS assay. As for treatment strategies, in addition to general treatment, this patient also underwent plasmapheresis and methylprednisolone treatment due to disease deterioration. The patient's liver function was improved afterward and discharged after one month of treatment. Taken together, this work reported the clinical feature and treatment of severe acute hepatitis with non-A-E hepatitis in detail. The potential mechanism of liver damage might be due to an immune attack in which TTV might play a role as a co-factor.

Association of clusterin gene polymorphisms with late-onset Alzheimer's disease.

BACKGROUND/AIMS: Some studies have implicated the role of apolipoprotein J [clusterin (CLU), apoJ] in the pathogenesis of Alzheimer's disease (AD). In this study, we investigated the polymorphisms rs11136000 and rs9331888 within CLU in late-onset sporadic AD (LOAD) patients and nondemented subjects. METHODS: LOAD patients and control subjects were analyzed. Genotyping of rs11136000 and rs9331888 was performed using standard PCR following different restriction endonuclease digestion. RESULTS: Although there were no significant differences in genotype frequencies of these two polymorphisms, the haplotype CG was associated with a statistically significantly increased LOAD risk. CONCLUSION: The rs11136000 and rs9331888 polymorphisms of the CLU gene are associated with LOAD.

Minocycline, but not doxycycline attenuates NMDA-induced [Ca2+]i and excitotoxicity.

Minocycline and doxycycline, two semisynthetic second-generation tetracyclines, are reported to provide neuroprotection against brain injury and glutamate-induced neurotoxicity in neuronal cultures. Doxycycline has been postulated as the potential ideal candidate for further therapeutic development as it has fewer adverse effects than minocycline. In this study, we determined whether minocycline and doxycycline could similarly protect neurons against excitotoxic insults. We treated cultured rat cortical neurons and cerebellar granule neurons (CGN) with excitotoxic concentrations of NMDA or glutamate in the presence or absence of minocycline or doxycycline. Intracellular Ca concentration ([Ca]i) was also measured using a Fluorescent Light Imaging Plate Reader (FLIPR; Molecular Devices) with the calcium sensitive dye Fluo-3 AM. We found that minocycline and tetracycline markedly protected neurons against NMDA- and glutamate-induced neuronal death. In contrast, the structurally related tetracycline, doxycycline, was ineffective at concentrations up to 100 µM. Furthermore, minocycline, but not doxycycline, also significantly attenuated NMDA- or glutamate-induced [Ca]i in both cortical neurons and CGN. Our results suggest that minocycline but not doxycycline is able to directly block NMDA- or glutamate-induced excitotoxicity in neurons most likely by inhibiting NMDA- and glutamate-induced [Ca]i. This finding may contribute to our understanding of the molecular mechanisms underlying doxycycline- and minocycline-induced neuroprotection.

A Nomogram Model for Predicting the Response to Transcatheter Arterial Embolization in Patients With Symptomatic Hepatic Hemangioma.

Background: Transcatheter arterial embolization (TAE) is regarded as an effective treatment for patients with symptomatic hepatic hemangioma. However, few studies have evaluated the efficacy of TAE alone for treating hepatic hemangioma. The aim of this study was to identify the factors that influence the response to TAE and formulate a quantitative nomogram to optimize the individualized management of hepatic hemangioma. Methods: We retrospectively studied 276 patients treated with TAE for hepatic hemangioma at our center from January 2011 to December 2019. The full cohort was randomly divided into training and validation cohorts. After assessing the potential predictive factors for the efficacy of TAE in the training cohort, a nomogram model was established and evaluated by discrimination and calibration. Results: During follow-up, the symptom relief rate was 100%. The tumor blood supply (p < 0.001), tumor number (p = 0.004), and tumor size (p = 0.006) were identified as significant predictors of the failure of tumor shrinkage in response to TAE. The nomogram model showed favorable discrimination and calibration, with a C-index of 0.775 (95% CI, 0.705-0.845) in the training cohort, which was further confirmed in the validation cohort (C-index 0.768; 95% CI, 0.680-0.856). The side effects of TAE were relatively minor and included mainly abdominal pain, nausea, vomiting, fever, and the presence of elevated hepatic transaminases. Conclusion: TAE is a safe and effective treatment for symptomatic hepatic hemangioma. The established nomogram performed well for the estimation of the effect of TAE in patients with hepatic hemangioma and can facilitate the selection of patients who would benefit most from the treatment.

Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity.

Unconjugated bilirubin, the end product of heme catabolism and antioxidant, induced brain damage in human neonates is a well-recognized clinical syndrome. However, the cellular and molecular mechanisms underlying bilirubin neurotoxicity remain unclear. To characterize the sequence of events leading to bilirubin-induced neurotoxicity, we investigated whether bilirubin-induced glial activation was involved in bilirubin neurotoxicity by exposing co-cultured rat glial cells and cerebellar granule neurons (CGN) to bilirubin. We found that bilirubin could markedly induce the expression of TNF-α and iNOS in glial cells, and even at low concentrations, the co-culture of glial cells with neurons significantly enhances neurotoxicity of bilirubin. Pretreatment of the co-cultured cells with minocycline protected CGN from glia-mediated bilirubin neurotoxicity and inhibited overexpression of TNF-α and iNOS in glia. Furthermore, we found that high doses of bilirubin were able to induce glial injury, and minocycline attenuated bilirubin-induced glial cell death. Our data suggest that glial cells play an important role in brain damage caused by bilirubin, and minocycline blocks bilirubin-induced encephalopathy possibly by directly and indirectly inhibiting neuronal death pathways.

Efficacy and safety of apatinib combined with transarterial chemoembolization (TACE) in treating patients with recurrent hepatocellular carcinoma.

BACKGROUND: Apatinib, a vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, has shown promising therapeutic effect for hepatocellular carcinoma (HCC). This prospective clinical study was implemented to evaluate the efficacy and safety of apatinib combined with transarterial chemoembolization (TACE) versus TACE alone in treating patients with recurrent HCC after hepatectomy. METHODS: Eligible patients with postoperative recurrent HCC from January 2018 to January 2020 were enrolled at the Xinqiao Hospital of Army Medical University. Patients were randomized 1:1 into TACE plus apatinib group or TACE-alone group. The clinical information of patients was collected, and the patients were followed up until untreatable progression or the end of the study. Adverse events (AEs), overall survival (OS) and progression-free survival (PFS) between the two groups were evaluated. In addition, the objective response rate (ORR) and the disease control rate (DCR) were determined according to the modified Response Evaluation Criteria In Solid Tumors (mRECIST). Among those indexes, PFS was the primary endpoint. RESULTS: This study enrolled 80 patients with recurrent HCC, and the demographics and primary tumor characteristics were balanced between the two groups. However, TACE plus apatinib treatment could significantly improve the median PFS of patients when compared with the TACE-alone group (17.2 vs. 12.5 months, P=0.041). The 1- and 2-year overall survival (OS) rates showed a tendency of improving in the TACE plus apatinib group, but not significantly (95.0% vs. 85.0%, and 90.0% vs. 75.0%; both P>0.05). Furthermore, the TACE plus apatinib treatment did significantly increase the short-term ORR and DCR when compared with the TACE-alone group (all P<0.05). And no unexpected toxicity or procedure-related mortality was occurred during this study. CONCLUSIONS: The combination treatment of apatinib and TACE might be safe and of potential benefit on patients with intrahepatic recurrent HCC.

Evaluation of chronic lead effects in the blood brain barrier system by DCE-CT.

BACKGROUND: Lead (Pb) is an environmental factor has been suspected of contributing to the dementia including Alzheimer's disease (AD). Our previous studies have shown that Pb exposure at the subtoxic dose increased brain levels of beta-amyloid (Aß) and amyloid plaques, a pathological hallmark for AD, in amyloid precursor protein (APP) transgenic mice, and is hypothesized to inhibit Aß clearance in the blood- cerebrospinal fluid (CSF) barrier. However, it remains unclear how different levels of Pb affect Aß clearance in the whole blood-brain barrier system. This study was designed to investigate whether chronic exposure of Pb affected the permeability of the blood-brain barrier system by using the Dynamic Contrast-Enhanced Computerized Tomography (DCE-CT) method. METHODS: DEC-CT was used to investigate whether chronic exposure of toxic Pb affected the permeability of the real-time blood brain barrier system. RESULTS: Data showed that Pb exposure increased permeability surface area product, and also significantly induced brain perfusion. However, Pb exposure did not alter extracellular volumes or fractional blood volumes of mouse brain. CONCLUSION: Our data suggest that Pb exposure at subtoxic and toxic levels directly targets the brain vasculature and damages the blood brain barrier system.