INTRODUCTION AND OBJECTIVES:Tenofovir alafenamide (TAF) and entecavir (ETV) are both considered renal-friendly nucleoside/nucleotide analogs (NAs). However, the difference between ETV and TAF in terms of renal function remains unclear. This study aims to compare the renal safety profiles of two antiviral medications directly and evaluate the impact of switching from ETV to TAF treatment on renal function in chronic hepatitis B (CHB) patients with low estimated glomerular filtration rates (eGFR). PATIENTS AND METHODS:A total of 179 CHB patients who received TAF (n = 84) or ETV (n = 95) between 2019 and 2023 were included in the study. Changes in eGFR levels between two treatment groups from baseline to 72 weeks were compared to measure the influence of these NAs on renal function. RESULTS:At baseline, 84 patients were included in each treatment group after a 1:1 propensity score matching process. At week 48, a notable different changes in eGFR were observed between the two groups. Gender, baseline eGFR, and medication (TAF/ETV) were significantly correlated with eGFR abnormalities. Furthermore, eGFR abnormalities at week 48 led to the transition of 6 patients in the ETV group to TAF. eGFR significantly increased (83.60 ± 5.45 vs. 93.39 ± 9.88 mL/min/1.73 m2; p = 0.031) and serum creatinine significantly decreased (81.47 ± 11.36 vs. 74.9 ± 10.67 μmol/L; p = 0.046) from week 48 to 60. At week 48, the incidence of low-level viremia (LLV) was 19.0 % in the ETV group and 16.7 % in the TAF group, respectively (p > 0.05). Pairwise comparisons revealed no significant difference in the percentage of LLV between the ETV continued group and the TAF continued group at week 48, 60, and 72. Additionally, there was also no significant difference in the proportion of LLV between the ETV + TAF combination group and the TAF + ETV combination group at week 48, 60, and 72. CONCLUSIONS:There was a substantial difference in eGFR between ETV and TAF treatments at week 48. Gender, baseline eGFR, and medication (TAF/ETV) were all remarkably positive indicators of eGFR abnormalities. In patients receiving ETV, an early switch to TAF may result in the reversal of early-stage renal damage.

OBJECTIVE:This review aims to summarize existing evidence on the adverse pregnancy outcomes and seizure control effects of using lamotrigine (LTG) monotherapy in pregnancy women with epilepsy (WWE) during pregnancy. METHODS:A comprehensive search was conducted in various databases including Cochrane, Web of Science, CBM, PubMed, Embase, CNKI, and Pregnancy Registration Center databases to identify relevant studies. The search was concluded up to January 2024. Studies comparing LTG with other antiseizure medications (ASMs) for treating epilepsy in pregnant women were included, with no language or regional restrictions. RESULTS:A total of 19 studies were included for analysis, with 16 studies reporting adverse pregnancy outcomes and 6 studies reporting seizure control outcomes. Meta-analysis showed that compared to monotherapy with carbamazepine (CBZ), sodium valproate (VPA), and levetiracetam (LEV), LTG monotherapy had a slightly weaker ability to control seizures during pregnancy, with ORs and 95 %CIs of 0.65 (0.57-0.75; CBZ), 0.50 (0.32-0.79; VPA), and 0.55 (0.36-0.84; LEV). Regarding adverse pregnancy outcomes, the occurrence rate of LTG monotherapy was significantly lower than that of CBZ, VPA, phenytoin (PHT), and phenobarbital (PHB), with ORs and 95 %CIs ranging from 0.30 (0.25-0.35; VPA) to 0.68 (0.56-0.81; CBZ). CONCLUSION:Based on meta-analysis, LTG and LEV appear to be preferred medications for controlling seizures during pregnancy. This review provides further support for the use of LTG monotherapy in pregnant WWE, building upon existing evidence for clinical practitioners.

The biomimetic nanoparticles (NPs) possessing abilities of tumor targeting and multimodal therapy show great potential for efficient combat of colon cancer. Herein, we developed a multifunctional biomimetic nanoplatform (Fe3O4@PDA@CaCO3-ICG@CM) based on CaCO3-modified magnetic polydopamine (PDA) loaded with indocyanine green (ICG), which was encapsulated by a mouse lymphoma cell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte function-associated antigen 1, LFA-1; transforming growth factor-beta receptor, TGF-beta R; programmed cell death protein 1, PD-1; and factor related apoptosis ligand, FasL). Under magnetic attraction and LFA-1/PD-1-mediated endocytosis, Fe3O4@PDA@CaCO3-ICG@CM efficiently targeted CT26 colon tumor cells. The released calcium ion (Ca2+) from the NPs triggered by acidic tumor microenvironment, the enhanced photothermal effect contributed by the combination of PDA and ICG, and FasL's direct killing effect together induced tumor cells apoptosis. Moreover, the apoptosis of CT26 cells induced immunogenic cell death (ICD) to promote the maturation of dendritic cells (DCs) to activate CD4(+)/CD8(+) T cells, thereby fighting against tumor cells, which could further be boosted by programmed death-ligand 1 (PD-L1) blockage and transforming growth factor-beta (TGF-beta) scavenging by Fe3O4@PDA@CaCO3-ICG@CM. As a result, in vivo satisfactory therapeutic effect was observed for CT26 tumor bearing-mice treated with Fe3O4@PDA@CaCO3-ICG@CM under laser irradiation and magnetic attraction, which could eradicate primary tumors and restrain distant tumors through dual tumor targeting-assisted multimodal therapy and eliciting adaptive antitumor immune response, generating the immune memory for inhibiting tumor metastasis and recurrence. Taken together, the multifunctional biomimetic nanoplatform exhibits superior antitumor effects, providing an insightful strategy for the field of nanomaterial-based treatment of cancer.

Lead (Pb), mercury (Hg), and cadmium (Cd) are prevalent and persistent environmental contaminants, causing detrimental effects on millions of individuals worldwide. Our previous research demonstrated that early-life exposure to low-level Pb, Hg, and Cd mixtures may lead to cognitive impairments. However, the association and interaction among low levels of Pb, Hg, or Cd exposure remains unclear. In this study, a two-level full factorial design (5.481, 0.036, and 2.132 mg/L for Pb, Hg, and Cd respectively) was conducted to assess the interplay among maternal Pb, Hg, and Cd exposure on offspring cognition. Following exposure during pregnancy and lactation, a competitive absorption among Pb, Hg, and Cd was observed. Maternal exposure to each metal alone resulted in higher blood and brain concentrations of Pb, Hg, and Cd in offspring compared to co-exposure at equivalent levels. However, behavioral experiments conducted in the Morris water maze and novel object recognition test revealed maternal Pb, Hg, and Cd exposure synergistically impaired offspring's spatial cognition and recognition memory. Importantly, this dysfunction persisted into middle age even without exposure after adulthood. Moreover, the open field test and elevated plus maze indicated maternal low-level Pb, Hg, and Cd co-exposure triggered risk-taking behavior in weaning offspring, with a significant main effect for Pb exposure. No long-lasting effect on risk-taking behavior was detected in middle-aged offspring. Further investigation into molecular mechanisms showed that the dysregulation of corticosterone reaction and immune response might be the potential mechanism underlying Pb, Hg, and Cd co-exposure-induced cognitive impairments. Our study highlights the synergistic and long-lasting effects of multiple heavy metal exposures,underscoring the urgency to prevent exposure to metal mixtures among children and women of childbearing age.

Background Previous research has revealed that patients with major depressive disorder (MDD) have negative biases in various aspects of information processing, and these biases are mainly manifested in recognizing facial expressions. However, the link between this emotional cognitive inhibition and neural activation mechanisms in cortical brain regions remains poorly understood. Therefore, this study employed functional near-infrared spectroscopy (fNIRS) to explore the potential impaired regions and neural mechanisms associated with facial emotion cognition in MDD patients. Methods 37 MDD patients and 34 healthy controls (HC) were recruited to participate in three sets of cognitive tasks for emotion recognition, and the cortical activation in the brain was synchronously recorded using multi-channel fNIRS. Results During tasks requiring the motions identification of sad versus happy emotional states, MDD patients exhibit altered activation in both the left frontopolar cortex (FPC) and the right dorsolateral prefrontal cortex (DLPFC). Notably, the FPC demonstrates a higher level of internal coherence and broader correlation with other cortical areas. Moreover, MDD patients showed lower accuracy in distinguishing emotional cues associated with sadness versus those associated with neutral and happy emotions. Limitations The study had a relatively small sample size, and it specifically examined only three prevalent facial expressions. Conclusion Facial expression recognition in MDD patients is characterized by negative cognitive interpretation of expressions, which are associated with various cortical altered activations. Neuroimaging further suggests that the cognitive inhibition of emotion signal recognition in everyday interpersonal interactions in MDD patients may primarily be influenced by activation in the left FPC.

AbstractAggressive nature of colon cancer and current imprecise therapeutic scenarios simulate the development of precise and effective treatment strategies. To achieve this, a tumor environment‐activated photosensitized biomimetic nanoplatform (PEG2000‐SiNcTI‐Ph/CpG‐ZIF‐8@CM) is fabricated by encapsulating metal‐organic framework loaded with developed photosensitizer PEG2000‐SiNcTI‐Ph and immunoadjuvant CpG oligodeoxynucleotide within fusion cell membrane expressing programmed death protein 1 (PD‐1) and cluster of differentiation 47 (CD47). By stumbling across, systematic evaluation, and deciphering with quantum chemical calculations, a unique attribute of tumor environment (low pH plus high concentrations of adenosine 5′‐triphosphate (ATP))‐activated photodynamic effect sensitized by long‐wavelength photons is validated for PEG2000‐SiNcTI‐Ph/CpG‐ZIF‐8@CM, advancing the precision of cancer therapy. Moreover, PEG2000‐SiNcTI‐Ph/CpG‐ZIF‐8@CM evades immune surveillance to target CT26 colon tumors in mice mediated by CD47/signal regulatory proteins α (SIRPα) interaction and PD‐1/programmed death ligand 1 (PD‐L1) interaction, respectively. Tumor environment‐activated photodynamic therapy realized by PEG2000‐SiNcTI‐Ph/CpG‐ZIF‐8@CM induces immunogenic cell death (ICD) to elicit anti‐tumor immune response, which is empowered by enhanced dendritic cells (DC) uptake of CpG and PD‐L1 blockade contributed by the nanoplatform. The photodynamic immunotherapy efficiently combats primary and distant CT26 tumors, and additionally generates immune memory to inhibit tumor recurrence and metastasis. The nanoplatform developed here provides insights for the development of precise cancer therapeutic strategies.

The heavy metals lead (Pb), cadmium (Cd), and mercury (Hg) that cause neurocognitive impairment have been extensively studied. These elements typically do not exist alone in the environment; they are often found with other heavy metals and can enter the body through various routes, thereby impacting health. Our previous research showed that low Pb, Cd, and Hg levels cause neurobehavioral impairments in weaning and adult rats. However, little is known about the biomarkers and mechanisms underlying Pb, Cd, and Hg mixture-induced neurological impairments. A combined analysis of metabolomic and proteomic data may reveal heavy metal-induced alterations in metabolic and protein profiles, thereby improving our understanding of the molecular mechanisms underlying heavy metal-induced neurological impairments. Therefore, brain tissue and serum samples were collected from rats exposed to a Pb, Cd, and Hg mixture for proteomic and metabolomic analyses, respectively. The analysis revealed 363 differential proteins in the brain and 206 metabolites in serum uniquely altered in the Pb, Cd, and Hg mixture exposure group, compared to those of the control group. The main metabolic impacted pathways were unsaturated fatty acids biosynthesis, linoleic acid metabolism, phenylalanine metabolism, and tryptophan metabolism. We further identified that the levels of arachidonic acid (C20:4 n-3) and, adrenic acid (C22:4 n-3) were elevated and that kynurenic acid (KA) and quinolinic acid (QA) levels and the KA/QA ratio, were decreased in the group exposed to the Pb, Cd, and Hg mixture. A joint analysis of the proteome and metabolome showed that significantly altered proteins such as LPCAT3, SLC7A11, ASCL4, and KYAT1 may participate in the neurological impairments induced by the heavy metal mixture. Overall, we hypothesize that the dysregulation of ferroptosis and kynurenine pathways is associated with neurological damage due to chronic exposure to a heavy metal mixture.

BackgroundObsessive–compulsive disorder (OCD) is one of the top ten disabling diseases seriously affecting the health of population. Recently, studies on this disease significantly increased. However, only a few bibliometric analyses concerning this area have been reported. In this study, we used bibliometrics and visualization tools to examine the current state, hot topics and future trends in OCD research.MethodsScientific publications regarding OCD were retrieved from the Web of Science Core Collection (WoSCC) database. The features of OCD research were further analyzed using VOSviewer.ResultsA total of 24,552 publications and 65,296 authors in the field of OCD were retrieved from 2000 to 2022, showing an overall upward trend in publications over the past 22 years. One hundred and thirteen countries around the world had participated in the research. Among these countries, the developed countries such as the United States, England, and Canada were the crucial productive nations in this subject. As for institutions, the Harvard University, the University of London, and the University of California system were the leading institutions. Authors including Storch EA, Mataix-Cols D, and Stein DJ were the prolific authors. 1,949 journals are contributing to the OCD field, of which the top three are Biological Psychiatry (831 articles), European Neuropsychopharmacology (776 articles) and Psychiatric Research (648 articles). Research hotspots of OCD included pathogenesis, epidemiology, comorbidities, clinical features, and evaluation methods. COVID-19, mental health, functional connectivity, and genome-wide association were emerging trends in the field of OCD.ConclusionThis study integrates the bibliometric information on the current research status and emerging trends in OCD from a macro perspective. The findings can provide valuable insights into further research on OCD.

Lead (Pb), cadmium (Cd), and mercury (Hg) are environmentally toxic heavy metals that can be simultaneously detected at low levels in the blood of the general population. Although our previous studies have demonstrated neurodevelopmental toxicity upon co-exposure to these heavy metals at these low levels, the precise mechanisms remain largely unknown. Dendritic spines are the structural foundation of memory and undergo significant dynamic changes during development. This study focused on the dynamics of dendritic spines during brain development following Pb, Cd, and Hg co-exposure-induced memory impairment. First, the dynamic characteristics of dendritic spines in the prefrontal cortex were observed throughout the life cycle of normal rats. We observed that dendritic spines increased rapidly from birth to their peak value at weaning, followed by significant pruning and a decrease during adolescence. Dendritic spines tended to be stable until their loss in old age. Subsequently, a rat model of low-dose Pb, Cd, and Hg co-exposure from embryo to adolescence was established. The results showed that exposure to low doses of heavy metals equivalent to those detected in the blood of the general population impaired spatial memory and altered the dynamics of dendritic spine pruning from weaning to adolescence. Proteomic analysis of brain and blood samples suggested that differentially expressed proteins upon heavy metal exposure were enriched in dendritic spine-related cytoskeletal regulation and axon guidance signaling pathways and that cofilin was enriched in both of these pathways. Further experiments confirmed that heavy metal exposure altered actin cytoskeleton dynamics and disturbed the dendritic spine pruning-related LIM domain kinase 1-cofilin pathway in the rat prefrontal cortex. Our findings demonstrate that low-dose Pb, Cd, and Hg co-exposure may promote memory impairment by perturbing dendritic spine dynamics through dendritic spine pruning-related signaling pathways.

Purpose:To explore the alterations in both local and remote brain connectivity in patients with thyroid-associated ophthalmopathy (TAO) and to investigate whether the alterations of local neural function could be used to distinguish patients with TAO from healthy controls (HCs) using support vector machine (SVM) classifier.Materials and Methods:In total, 21 patients with TAO and 21 well-matched HCs were enrolled in our study and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We employed regional homogeneity (ReHo) algorithm to evaluate local neural function and selected significantly altered brain regions as seed areas for subsequent study of the remote functional connectivity (FC). Moreover, we chose the observed alterations in the ReHo analysis as classification features to differentiate patients with TAO from HCs through SVM classification method.Results:Compared with the HCs, TAO patients showed significantly lower ReHo values in the right middle occipital gyrus (MOG) and right angular (ANG). In contrast, TAO patients displayed higher ReHo values in the left hippocampus (Hipp). We further found TAO patients exhibited decreased FC between the left and right Hipp, right MOG and left cerebellum (CER), right ANG and left rectus, right superior temporal pole gyrus (PSTG) (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). The alterations in local neural function exhibited an accuracy of 78.57% and area under curve of 0.81 for distinguishing the patients from HCs.Conclusion:We mainly found the results that patients with TAO showed significantly dysfunctional local and remote brain functional connectivity in several brain regions associated with visual and cognitive functions. The ReHo variability has potential value in differentiating patients with TAO from HCs. These findings may provide novel insights into the neurological mechanisms underlying visual and cognitive disorders in patients with TAO.

BACKGROUND:Effective treatment methods for rheumatoid arthritis (RA) are still lacking. Previous studies have shown that icariin exerts a significant therapeutic effect on RA; however, the molecular mechanism requires further analysis.METHODS:qRT-PCR and western blot were performed to examine the gene or protein levels, respecctively. The proinflammatory cytokine levels were determined utilizing ELISA and western blot assays. Cell proliferation and apoptosis were quantified using CCK-8, EdU and flow cytometry assays, respectively. A RA mouse model was established to observe histopathological changes.RESULTS:Both icariin treatment and TRIB1 overexpression inhibited proliferation and inflammatory responses but promoted the apoptosis of TNF-α-treated RA-FLSs. Icariin treatment increased TRIB1 expression by promoting Nrf2 expression, thus blocking TLR2/NF-κB signalling. In addition, functional rescue experiments suggested that TRIB1 knockdown strikingly restrained the biological effects of icariin on TNF-α-treated RA-FLSs. Moreover, in vivo experimental results revealed that icariin restored inflammation and deterioration in RA mice by upregulating TRIB1.CONCLUSIONS:Based on these results, icariin repressed TNF-α-induced inflammatory responses and survival in RA-FLSs by regulating the TRIB1/TLR2/NF-kB pathway, implying that icariin may be a promising candidate drug for RA treatment.