Effect of quality nursing intervention on wound healing in patients with burns: A meta-analysis.

This meta-analysis aimed to explore the effects of quality nursing intervention on wound healing in patients with burns. A computerised search was conducted for randomised controlled trials (RCTs) on the effect of quality nursing intervention on wound healing in patients with burns in the PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from the date of database inception to November 2023. Two researchers independently screened the literature, extracted data and performed quality assessment based on the inclusion and exclusion criteria. Stata 17.0 software was used for the data analysis. Twenty-nine RCTs involving 2637 patients with burns were included. The meta-analysis revealed that compared with conventional nursing, the implementation of quality nursing intervention in patients with burns significantly shortened the wound healing time (standardised mean difference [SMD] = -2.93, 95% confidence interval [CI]: -3.44 to -2.42, p < 0.001). The incidence of wound infections (odds ratio [OR] = 0.14, 95% CI: 0.07-0.27, p < 0.001) and complications (OR = 0.16, 95% CI: 0.11-0.23, p < 0.001) was also reduced significantly. This meta-analysis shows that applying quality nursing interventions in patients with burns can significantly shorten the wound healing time and reduce the incidence of wound infection and complications, thus promoting early patient recovery.

A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV.

Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.

Catalpol Prevents Glomerular Angiogenesis Induced by Advanced Glycation End Products via Inhibiting Galectin-3.

OBJECTIVE: The main characteristics of diabetic nephropathy (DN) at the early stage are abnormal angiogenesis of glomerular endothelial cells (GECs) and macrophage infiltration. Galectin-3 plays a pivotal role in the pathogenesis of DN via binding with its ligand, advanced glycation end products (AGEs). Catalpol, an iridoid glucoside extracted from Rehmannia glutinosa, has been found to ameliorate vascular inflammation, reduce endothelial permeability, and protect against endothelial damage in diabetic milieu. However, little is known about whether catalpol could exert an anti-angiogenesis and anti-inflammation effect induced by AGEs. METHODS: Mouse GECs (mGECs) and RAW 264.7 macrophages were treated with different concentrations of AGEs (0, 50, 100, 200 and 400 µg/mL) for different time (0, 6, 12, 24 and 48 h) to determine the optimal concentration of AGEs and treatment time. Cells were treated with catalpol (10 µmol/L), GB1107 (1 µmol/L, galectin-3 inhibitor), PX-478 (50 µmol/L, HIF-1α inhibitor), adenovirus-green fluorescent protein (Ad-GFP) [3×107 plaque-forming unit (PFU)/mL] or Ad-galectin-3-GFP (2×108 PFU/mL), which was followed by incubation with 50 µg/mL AGEs. The levels of galectin-3, vascular endothelial growth factor A (VEGFA) and pro-angiogenic factors angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), tunica interna endothelial cell kinase-2 (Tie-2) were detected by enzymelinked immunosorbent assay (ELISA). Cell counting kit-8 (CCK-8) assay was used to evaluate the proliferation of these cells. The expression levels of galectin-3, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, and hypoxia-inducible factor-1α (HIF-1α) in mGECs and those of galectin-3 and HIF-1α in RAW 264.7 macrophages were detected by Western blotting and immunofluorescence (IF) staining. The rat DN model was established. Catalpol (100 mg/kg) or GB1107 (10 mg/kg) was administered intragastrically once a day for 12 weeks. Ad-galectin-3-GFP (6×107 PFU/mL, 0.5 mL) or Ad-GFP (6×106 PFU/mL, 0.5 mL) was injected into the tail vein of rats 48 h before the sacrifice of the animals. The expression of galectin-3, VEGFR1, VEGFR2, and HIF-1α in renal cortices was analyzed by Western blotting. The expression of galectin-3, F4/80 (a macrophage biomarker), and CD34 (an endothelium biomarker) in renal cortices was detected by IF staining, and collagen accumulation by Masson staining. RESULTS: The expression levels of galectin-3 and VEGFA were significantly higher in mGECs and RAW 264.7 macrophages treated with 50 µg/mL AGEs for 48 h than those in untreated cells. Catalpol and GB1107 could block the AGEs-induced proliferation of mGECs and RAW 264.7 macrophages. Over-expression of galectin-3 was found to reduce the inhibitory effect of catalpol on the proliferation of cells. Catalpol could significantly decrease the levels of Ang-1, Ang-2 and Tie-2 released by AGEs-treated mGECs, which could be reversed by over-expression of galectin-3. Catalpol could significantly inhibit AGEs-induced expression of galectin-3, HIF-1α, VEGFR1, and VEGFR2 in mGECs. The inhibitory effect of catalpol on galectin-3 in AGEs-treated mGECs was impaired by PX-478. Moreover, catalpol attenuated the AGEs-activated HIF-1α/galectin-3 pathway in RAW 264.7 macrophages, which was weakened by PX-478. Additionally, catalpol significantly inhibited the expression of galectin-3, macrophage infiltration, collagen accumulation, and angiogenesis in the kidney of diabetic rats. Over-expression of galectin-3 could antagonize these inhibitory effects of catalpol. CONCLUSION: Catalpol prevented the angiogenesis of mGECs and macrophage proliferation via inhibiting galectin-3. It could prevent the progression of diabetes-induced renal damage.

Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants.

Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers against the ancestral strain. Notably, it provides protection against infection with prototype and B.1.351 strains in mice. These results provide a proof of principle for the development of multivalent vaccines against pandemic and potential pre-emergent SARS-CoV-2 variants.

Oleanolic acid combined with olaparib enhances radiosensitization in triple negative breast cancer and hypoxia imaging with 18F-FETNIM micro PET/CT.

The heterogeneity of triple negative breast cancer (TNBC) results in the worst prognosis among breast cancer types, making its treatment strategy very challenging. A recent study showed that oleanolic acid (OA) has a radiosensitizing effect on tumor cells, but it does not show a good clinical effect when used alone in radiotherapy. The cytotoxicity of radiotherapy can be enhanced by modulating DNA repair, so new treatment options are being investigated to inhibit DNA repair pathways and sensitize tumors to radiation. Radiation induces DNA double-strand breaks (DSBs), and inhibition of Poly (ADP-Ribose) polymerase (PARP) can prevent the repair of these lesions. Hence, we evaluated the radiosensitization and the underlying mechanism of combination treatment with OA and olaparib in TNBC. Meanwhile, tumor hypoxia was monitored with 18F-Fluoroerythronitroimidazole (FETNIM) positron emission tomography/computed tomography (PET/CT) during radiosensitization therapy. Here, we found that OA and olaparib in combination with radiotherapy significantly inhibited cell proliferation compared with other groups. The results were observed using colony formation assays [sensitization enhancement ratios (SER) 1.16-1.65]. In vivo, tumor growth was significantly delayed in transplanted tumors receiving irradiation (IR) with OA and olaparib. 18F-FETNIM PET/CT can be utilized for tumor hypoxia monitoring and radiosensitization response evaluation. In conclusion, these results suggest that the combination of OA and olaparib with IR enhances the inhibition of MDA-MB-231 in cell culture and in mice, providing a potentially novel combination for the effective treatment of TNBC patients.

Vesicular Stomatitis Virus-Based Epstein-Barr Virus Vaccines Elicit Strong Protective Immune Responses.

Epstein-Barr virus (EBV), the first identified human tumor virus, is etiologically associated with various kinds of malignant and benign diseases, accounting for 265,000 cancer incident cases and 164,000 cancer deaths in 2017. EBV prophylactic vaccine development has been gp350 centered for several decades. However, clinical studies show that gp350-centered vaccines fail to prevent EBV infection. Advances in the EBV infection mechanisms shed light on gB and gHgL, the two key components of the infection apparatus. In this study, for the first time, we utilized recombinant vesicular stomatitis virus (VSV) to display EBV gB (VSV-ΔG-gB/gB-G) or gHgL (VSV-ΔG-gHgL). In vitro studies confirmed successful virion production and glycoprotein presentation on the virion surface. In mouse models, VSV-ΔG-gB/gB-G or VSV-ΔG-gHgL elicited potent humoral responses. Neutralizing antibodies elicited by VSV-ΔG-gB/gB-G were prone to prevent B cell infection, while those elicited by VSV-ΔG-gHgL were prone to prevent epithelial cell infection. Combinatorial vaccination yields an additive effect. The ratio of endpoint neutralizing antibody titers to the endpoint total IgG titers immunized with VSV-ΔG-gHgL was approximately 1. The ratio of IgG1/IgG2a after VSV-ΔG-gB/gB-G immunization was approximately 1 in a dose-dependent, adjuvant-independent manner. Taken together, VSV-based EBV vaccines can elicit a high ratio of epithelial and B lymphocyte neutralizing antibodies, implying their unique potential as EBV prophylactic vaccine candidates. IMPORTANCE Epstein-Barr virus (EBV), one of the most common human viruses and the first identified human oncogenic virus, accounted for 265,000 cancer incident cases and 164,000 cancer deaths in 2017 as well as millions of nonmalignant disease cases. So far, no prophylactic vaccine is available to prevent EBV infection. In this study, for the first time, we reported the VSV-based EBV vaccines presenting two key components of the EBV infection apparatus, gB and gHgL. We confirmed potent antigen-specific antibody generation; these antibodies prevented EBV from infecting epithelial cells and B cells, and the IgG1/IgG2a ratio indicated balanced humoral-cellular responses. Taken together, we suggest VSV-based EBV vaccines are potent prophylactic candidates for clinical studies and help eradicate numerous EBV-associated malignant and benign diseases.

Parallel profiling of antigenicity alteration and immune escape of SARS-CoV-2 Omicron and other variants.

SARS-CoV-2 variants have evolved a variety of critical mutations, leading to antigenicity changes and immune escape. The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance to current antibody therapies and vaccines. Here, we profiled the mutations of Omicron and other various circulating SARS-CoV-2 variants in parallel by computational interface analysis and in vitro experimental assays. We identified critical mutations that lead to antigenicity changes and diminished neutralization efficiency of a panel of 14 antibodies due to diverse molecular mechanisms influencing the antigen-antibody interaction. Our study identified that Omicron exhibited extraordinary potency in immune escape compared to the other variants of concern, and explores the application of computational interface analysis in SARS-CoV-2 mutation surveillance and demonstrates its potential for the early identification of concerning variants, providing preliminary guidance for neutralizing antibody therapy.

Eslicarbazepine acetate add-on therapy for drug-resistant focal epilepsy.

BACKGROUND: This is an update of a review first published in 2011, and last updated in 2017. Most people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant focal epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS: For this update, we searched the following databases on 10 September 2020: Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid). CRS Web includes randomized or quasi-randomized, controlled trials from Specialized Registers of Cochrane Review Groups including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov and the WHO ICTRP. There were no language restrictions. We reviewed the reference lists of retrieved studies and contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo-controlled double-blind add-on trials of ESL in people with drug-resistant focal epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models. MAIN RESULTS: We included seven trials (2185 participants, aged 2 to 77 years), which were at low or unclear risk of bias apart from a high risk of attrition bias; all studies were funded by the pharmaceutical company, BIAL. The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.57 (95% confidence interval (CI) 1.34 to 1.83). For adults, the RR was 1.71 (95% CI 1.42 to 2.05; 5 studies, 1799 participants; moderate-certainty evidence); for children aged six to 18 years, the RR was 1.35 (95% CI 0.98 to 1.87; 2 studies, 322 participants; moderate-certainty evidence). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was associated with seizure freedom (RR 3.16, 95% CI 1.73 to 5.78; 6 studies, 1922 participants; moderate-certainty evidence). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.72, 95% CI 1.66 to 4.46; 7 studies, 2185 participants; moderate-certainty evidence), but not for any reason (RR 1.25, 95% CI 0.93 to 1.70; 7 studies, 2185 participants; moderate-certainty evidence). The following adverse effects were associated with ESL: dizziness (RR 2.77, 99% CI 1.85 to 4.15); nausea (RR 2.55, 99% CI 1.39 to 4.67); somnolence (RR 1.75, 99% CI 1.18 to 2.61); diplopia (RR 4.07, 99% CI 1.86 to 8.89); and vomiting (RR 2.37, 99% CI 1.19 to 4.74). Overall, the certainty of the evidence was moderate due to a high discontinuation rate in studies of adults. AUTHORS' CONCLUSIONS: ESL reduces seizure frequency when used as an add-on treatment for adults with drug-resistant focal epilepsy. The trials included in this review were of short-term duration. In addition, this update found that ESL may reduce seizure frequency in children from 6 to 18 years of age; however the results are inconclusive.

Loganin alleviates macrophage infiltration and activation by inhibiting the MCP-1/CCR2 axis in diabetic nephropathy.

BACKGROUND/AIMS: The theory of inflammation is one of the important theories in the pathogenesis of diabetic nephropathy (DN). We herein aimed to explore whether loganin affected macrophage infiltration and activation upon diabetic nephropathy (DN) by a spontaneous DN mice and a co-culture system of glomerular mesangial cells (GMCs) and macrophage cells (RAW264.7) which was induced by advanced glycation end products (AGEs). METHODS AND KEY FINDINGS: Loganin showed remarkable capacity on protecting renal from damage by mitigating diabetic symptoms, improving the histomorphology of the kidney, decreasing the expression of extracellular matrix such as FN, COL-IV and TGF-ß, reversing the production of IL-12 and IL-10 and decreasing the number of infiltrating macrophages in the kidney. Moreover, loganin showed markedly effects by suppressing iNOS and CD16/32 expressions (M1 markers), increasing Arg-1 and CD206 expressions (M2 markers), which were the phenotypic transformation of macrophage. These effects may be attributed to the inhibition of the receptor for AGEs (RAGE) /monocyte chemotactic protein-1 (MCP-1)/CC chemokine receptor 2 (CCR2) signaling pathway, with significantly down-regulated expressions of RAGE, MCP-1 and CCR2 by loganin. Loganin further decreased MCP-1 secretion when RAGE was silenced, which means other target was involved in regulating the MCP-1 expression. While loganin combinated with the inhibitor of CCR2 exerted stronger anti-inhibition effects of iNOS expression, suggesting that CCR2 was the target of loganin in regulating the activation of macrophages. SIGNIFICANCE: Loganin could ameliorate DN kidney damage by inhibiting macrophage infiltration and activation via the MCP-1/CCR2 signaling pathway in DN.

Comparatively Evaluating the Role of Herb Pairs Containing Angelicae Sinensis Radix in Xin-Sheng-Hua Granule by Withdrawal Analysis.

The present study aims to investigate the roles of herb pairs containing Angelicae Sinensis Radix (Danggui) in Xin-Sheng-Hua Granule (XSHG) on hemolytic and aplastic anemia (HAA) mice. HAA model mice were induced by acetyl phenylhydrazine and cyclophosphamide; then the samples of XSHG and its decomposed recipes (DY, DC, DT, DH, DJ, and DZ) were orally administrated to these mice. Indicators of peripheral blood routine, organ index, and ATPase activities were tested. Moreover, the main effective components in these samples were also analyzed by UHPLC-TQ-MS/MS. Clear separation between the control and model groups from score plot of principal component analysis (PCA) was easily seen, indicating that HAA model was successfully conducted. Afterwards, relative distance calculation method between dose groups and control group from PCA score plot was adopted to evaluate the integrated effects of hematinic function of different samples. And the orders of hematinic effects were as follows: XHSG > DJ > DT > DZ > DH > DC > DY. Further analysis of these samples by UHPLC-TQ-MS/MS revealed that XSHG underwent complicated changes when herb pairs containing Danggui were excluded from XSHG, respectively. Compared with XSHG, the vast majority of active compounds in sample DY (formula minus herb pair Danggui-Yimucao) decreased significantly, which could partly explain why herb pair Danggui-Yimucao made great contribution to XSHG. These findings showed that withdrawal analysis method is a valuable tool to analyze the impacts of herb pairs containing Danggui on XSHG, which could lay foundation to reveal the compatibility rules of this formula.

Comparison of the performance of two depression rating scales in patients with epilepsy in southern China.

OBJECTIVE: The aim of this study was to evaluate and compare the performance of the Chinese version of the Neurological Disorder Depression Inventory for Epilepsy (CNDDI-E) with that of the depression subscale of the Hospital Anxiety and Depression Scale (C-HADS-D) as screening tools for depression in the same patients with epilepsy (PWE). METHODS: A total of 213 consecutive PWE were evaluated. Receiver operating characteristic (ROC) analysis was performed using the C-NDDI-E and C-HADS-D as predictors and the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI) as the gold standard. RESULTS: The area under the curve (AUC) for the C-NDDI-E was 0.870, and the optimal cutoff score was >11 (sensitivity 85.71%, specificity 79.78%); for the C-HADS-D, the AUC was 0.804, and the optimal cutoff score was >5 (sensitivity 85.71%, specificity 62.36%). The AUC for the C-NDDI-E was larger than the AUC for the C-HADS-D, but the comparison of the AUCs revealed no significant differences (P = 0.1444). CONCLUSION: Our findings indicate that the C-NDDI-E and C-HADS-D have high validity and support the use of these screening tools for depression in PWE. Moreover, the C-NDDI-E is a better screening scale for diagnosing depression than the C-HADS-D according to the results of this study.

Synergistic protection of tetramethylpyrazine phosphate and borneol on brain microvascular endothelium cells injured by hypoxia.

The combination of tetramethylpyrazine phosphate (TMPP) and borneol (BO) protects against cerebral ischemia. However, the mechanism for their synergistic effect is unclear. In this study, an oxygen-glucose deprivation (OGD) injured brain model was induced in microvascular endothelium cells (BMECs). TMPP and BO concentrations were optimized according to an MTT assay. Cells were divided into five groups: control, model, TMPP, BO, and TMPP+BO. Subsequently, oxidative stress was evaluated based on the levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS). Intracellular calcium ([Ca2+]i) was detected using a laser confocal microscope. Cellular apoptosis was examined via Hoechst 33342 staining, flow cytometry, and expression of p53, B-cell lymphoma 2 (BCL-2), BCL-2-like protein 4 (BAX), and caspase-3 mRNA. Angiogenesis was evaluated based on expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), fibroblast growth factor receptor 1 (FGFR1), Vascular endothelial growth factor receptor 1 (VEGFR1), and VEGFR2. Results showed that 5.0 µM TMPP and 0.5 µM BO were optimal. Monotherapy significantly enhanced CAT, BCL-2, and VEGF, and also reduced [Ca2+]i, apoptosis, and BAX. TMPP increased SOD, GSH-Px, and bFGF, and reduced MDA, ROS, p53, and caspase-3 levels. BO reduced VEGFR1 expression. TMPP+BO combination exhibited synergistic effects in decreasing apoptosis, and modulating expression of BCL-2, BAX, and VEGFR1. These results indicate that protection of OGD-injured BMECs by TMPP+BO combination involves anti-oxidation, apoptosis inhibition, and angiogenesis. Moreover, their synergistic mechanism was mainly related to the regulation of apoptosis and angiogenesis.

Reliability and validity of the Chinese version of the Patient Health Questionnaire 9 (C-PHQ-9) in patients with epilepsy.

OBJECTIVE: The aim of this study was to evaluate the clinical reliability and validity of the Chinese version of the Patient Health Questionnaire 9 (C-PHQ-9) in patients with epilepsy. METHODS: A total of 213 consecutive adult patients with epilepsy were evaluated. Receiver operating characteristic (ROC) analysis was performed using C-PHQ-9 and Chinese version of Patient Health Questionnaire 2 (C-PHQ-2) as predictors and the Mini International Neuropsychiatric Interview Plus Version 5.0.0 as the gold standard. RESULTS: The C-PHQ-9 was easily understood and quickly finished by the patients. According to the gold standard, the prevalence of current major depressive disorder in this population was 16.4%. Cronbach's α coefficient for the C-PHQ-9 was 0.860. The ROC analysis showed an area under the curve (AUC) of 0.888 (95% confidence interval [CI] = 0.838-0.927). At a cutoff score of >6, the C-PHQ-9 had a sensitivity of 82.86%, a specificity of 84.27%, a positive predictive value of 50.9%, and a negative predictive value of 96.2%. The C-PHQ-2 at a cutoff score of >1 resulted in the greatest balance of sensitivity and specificity (77.14% and 75.28%, respectively). CONCLUSION: Our findings support a high reliability and validity for the C-PHQ-9 as a screening tool for the detection of current major depression in Chinese patients with epilepsy.

Analysis of risk factors for antiepileptic drug-induced adverse psychotropic effects in Chinese outpatients with epilepsy.

Antiepileptic drugs (AEDs) have adverse psychotropic effects (APEs). To explore the risk factors for AED-induced APEs, we compared Chinese outpatients with epilepsy with and without AED-induced APEs. We reviewed the medical data of outpatients with epilepsy enrolled in the Epilepsy Long-term Follow Up Registry Study (ELFURS) between January 1, 2003 and December 31, 2015. Data on demographics, comorbidities, variables related to epilepsy, AED use, and APEs were collected. APEs were determined by experienced epileptologists based on the definition of "adverse drug reaction (ADR)" proposed by the World Health Organization (WHO) in 1972, and the causality relationship between APEs and suspected medications was assessed based on the WHO-UMC scale. APEs included effects on memory, sleep, behavior, mood, psychotic symptoms, and others in this study. We divided the study population into patients with and without AED-induced APEs and then compared the differences between the two groups using univariate and multivariate methods. A total of 3074 eligible patients were included in this study (1001 patients with AED-induced APEs and 2073 patients without AED-induced APEs). Of all APEs, the effects on memory and sleep were most pronounced. The results show that the female sex (odds ratio [OR] 1.242, 95% confidence interval [CI] 1.055-1.463), psychotic disorder comorbidities (OR 1.815, 95% CI 1.159-2.841), polytherapy with AEDs (OR 1.400, 95% CI 1.061-1.847), and the duration of epilepsy (OR 1.010, 95% CI 1.000-1.020) are significant nondrug risk factors for AED-induced APEs. Recognizing risk factors for APEs may help determine optimal treatment strategies for epilepsy.

Simvastatin prevents and ameliorates depressive behaviors via neuroinflammatory regulation in mice.

BACKGROUND: Statins play a beneficial role in the treatment of coronary artery disease and are widely prescribed to prevent hypercholesterolemia. Previous studies have demonstrated that statins also have anti-inflammatory and immunomodulatory properties, and these are being explored for potential benefits in depression. However, the role of statins in the treatment of depression has not been well examined. METHODS: We investigated the effects of simvastatin on depressive behaviors and neuroinflammation in lipopolysaccharide (LPS) and chronic mild stress (CMS) induced depression model in mice. Sucrose preference test (SPT), forced swimming test (FST), novelty-suppressed feeding test (NSFT) were used to detect the depressive behaviors. The microglial activation was detected by immunohistochemistry analysis and the pro-inflammatory cytokines expressions including IL-1ß, TNF-α and IL-6 were examined by Western blot analysis. RESULTS: Our data indicated that oral administration of simvastatin at 20 mg/kg significantly prevented and ameliorated depressive behaviors reflected by better performance in the SPT, FST and NSFT. Moreover, simvastatin markedly prevented and ameliorated LPS and CMS-induced neuroinflammation, as shown by the suppressed activation of microglia in hippocampus and decreased hippocampal pro-inflammatory cytokines expressions including IL-1ß, TNF-α, IL-6, which might be mediated via the inhibition of NF-κB pathway, as shown by the decreased nuclear NF-κB p65 expression. LIMITATIONS: The interpretation of the evidence of a positive treatment effect of simvastatin on the depressive manifestations, multifaceted etiology of depression, and confirmation of this finding from animal models to humans is needed. CONCLUSION: These results suggest that simvastatin has the potential to be employed as a therapy for depression associated with neuroinflammation.

Garcin syndrome caused by parotid gland adenoid cystic carcinoma: A case report.

RATIONALE: Garcin syndrome is characterized by the gradual involvement, and ultimately, unilateral paralysis of at least 7 and sometimes all cranial nerves, without intracranial hypertension or any long tract signs. PATIENT CONCERNS: We report the case of a 59-year-old woman who presented with Garcin syndrome, which gradually progressed over a period of 2 years. DIAGNOSIS: A left parotid gland biopsy revealed parotid gland adenoid cystic carcinoma (PGACC) with perineural invasion of a peripheral nerve bundle and lymph node metastasis. INTERVENTIONS: The patient was treated 3 times with local-field palliative radiotherapy. OUTCOMES: She died after several months. LESSONS: To the best of our knowledge, this is the first report of PGACC presenting as Garcin syndrome. PGACC is a rare tumor with a high propensity for perineural spread, and it should be considered as a possible cause of Garcin syndrome.

Eslicarbazepine acetate add-on for drug-resistant partial epilepsy.

BACKGROUND: This is an updated version of the Cochrane Review published in the Cochrane Library 2011, Issue 12.The majority of people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant partial epilepsy. SEARCH METHODS: The searches for the original review were run in November 2011. Subsequently, we searched the Cochrane Epilepsy Group Specialized Register (6 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11) and MEDLINE (1946 to 6 December 2016). There were no language restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo controlled double-blind add-on trials of ESL in people with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects, and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models. MAIN RESULTS: We included five trials (1799 participants) rated at low risk of bias; all studies were funded by BIAL. The overall risk ratio (RR) with 95% confidence interval (CI) for 50% or greater reduction in seizure frequency was 1.71 (95% CI 1.42 to 2.05). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was significantly associated with seizure freedom (RR 2.90, 95% CI 1.49 to 5.68). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.66, 95% CI 1.42 to 4.96) but not for any reason (RR 1.19, 95% CI 0.86 to 1.64). The following adverse effects were significantly associated with ESL: dizziness (RR 2.81, 99% CI 1.86 to 4.27); nausea (RR 2.61, 99% CI 1.36 to 5.01); diplopia (RR 4.14, 99% CI 1.74 to 9.84); somnolence (RR 1.71, 99% CI 1.11 to 2.63) and vomiting (RR 3.30, 99% CI 1.34 to 8.13). Overall the quality of the evidence was rated as moderate to high. AUTHORS' CONCLUSIONS: ESL reduces seizure frequency when used as an add-on treatment for people with drug-resistant partial epilepsy. The trials included in this review were of short-term duration and focused on adults. One new trial has been included in this update, but the conclusions are unchanged.

Food-advanced glycation end products aggravate the diabetic vascular complications via modulating the AGEs/RAGE pathway.

The aim of this study was to investigate the effects of high-advanced glycation end products (AGEs) diet on diabetic vascular complications. The Streptozocin (STZ)-induced diabetic mice were fed with high-AGEs diet. Diabetic characteristics, indicators of renal and cardiovascular functions, and pathohistology of pancreas, heart and renal were evaluated. AGEs/RAGE/ROS pathway parameters were determined. During the experiments, the diabetic mice exhibited typical characteristics including weight loss, polydipsia, polyphagia, polyuria, high-blood glucose, and low-serum insulin levels. However, high-AGEs diet effectively aggravated these diabetic characteristics. It also increased the 24-h urine protein levels, serum levels of urea nitrogen, creatinine, c-reactive protein (CRP), low density lipoprotein (LDL), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the diabetic mice. High-AGEs diet deteriorated the histology of pancreas, heart, and kidneys, and caused structural alterations of endothelial cells, mesangial cells and podocytes in renal cortex. Eventually, high-AGEs diet contributed to the high-AGE levels in serum and kidneys, high-levels of reactive oxygen species (ROS) and low-levels of superoxide dismutase (SOD) in serum, heart, and kidneys. It also upregulated RAGE mRNA and protein expression in heart and kidneys. Our results showed that high-AGEs diet deteriorated vascular complications in the diabetic mice. The activation of AGEs/RAGE/ROS pathway may be involved in the pathogenesis of vascular complications in diabetes.

Risk of seizure relapse after antiepileptic drug withdrawal in adult patients with focal epilepsy.

OBJECTIVE: The objective of this study was to estimate the risk of a seizure relapse and the high-risk period of recurrence after antiepileptic drug (AED) withdrawal and to determine the predictive factors for a seizure relapse in adult patients with focal epilepsy who were seizure-free for more than 2years. METHODS: Using the Wenzhou Epilepsy Follow-Up Registry Database, 200 adult patients with focal epilepsy were recruited, who were undergoing follow-up, met the inclusion criteria of this study, were seizure-free for more than 2years, began withdrawing between June 2003 and June 2014, and were followed up prospectively for at least 1year or until a seizure relapse. The risk of recurrence and the time to seizure relapse were analyzed by the Kaplan-Meier method, and the predictive factors were identified by the Cox proportional hazard regression model. RESULT: A total of 99 patients had an unprovoked relapse during the follow-up period. The relapse rate was 49.5%, and each year, the recurrence probability of 12, 24, 36, 48, 60, 72, and 84months after AED withdrawal was 24.0%, 20.4%, 8.3%, 2.7%, 4.6%, 0.97%, and 0.98%, respectively. The two independent risk factors for recurrence after withdrawal in adult patients with focal epilepsy were a longer duration of active epilepsy and a shorter seizure-free period before withdrawal. CONCLUSION: The high-risk period of a seizure relapse in adult patients with focal epilepsy is the first 2years after withdrawal, and beyond 5years after withdrawal, seizures rarely relapse (relapse rate<1%). A seizure-free period for less than 4years before withdrawal is a predictive factor of risk for seizure recurrence after AED withdrawal in adult patients with focal epilepsy.

[Comparatively evaluating effect contribution of promoting blood circulation of herb pairs containing Angelicae Sinensis Radix on Xin-Sheng-Hua granule by withdrawal analysis].

Xin-Sheng-Hua granule (XSHG) is a popular remedy commonly used in clinic for the treatment of lochiostasis after delivery. To comparatively investigate the roles of herb pairs containing Angelicae Sinensis Radix (Danggui) upon the formula by evaluating the blood coagulation and hemorheology function in acute blood stasis rats, acute blood stasis rat model was established by ice water bath and subcutaneous injection of adrenaline. And the blood stasis mice were administrated intragastrically with different samples of the formula minus herb pairs containing Danggui and the whole formula (XSHG, SHD, DY, DC, DT, DH, DJ and DZ). The whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and haematocrit (HCT) were applied to evaluate the effects of the formula minus herb pairs containing Danggui on hemorheology of blood stasis rats. The thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT), and plasma fibrinogen (FIB) were used to observe the effects of the formula minus herb pairs containing Danggui on blood coagulation function of blood stasis rats. Additionally, the maximum aggregation induced by adenosine diphosphate (ADP) was tested to observe the effect of different samples on platelet aggregation index of blood stasis rats.Afterwards, multi-attribute comprehensive index methods and principal component analysis were both applied to comprehensively assess the total effects of the formula minus herb pairs containing Danggui on promoting blood circulation and dissipating blood stasis. Compared with normal group, the hemorheological parameters and coagulation indexes of model group had statistical differences (P<0.01). Compared with model group, different samples (XSHG, SHD, DY, DC, DT, DH, DJ and DZ) could improve the blood hemorheology indexes, coagulation parameters and platelet aggregation in acute blood stasis rats. According to multi-attribute comprehensive index methods and the principal component analysis, the effects of promoting blood circulation by removing blood stasis became poor when excluding herb pairs containing Danggui from the formula, the sample DY and DC had the weakest effect of activating blood circulation and dissipating blood stasis, and the effect of sample DY was slightly poorer than DC. The orders of contribution of herb pairs containing Danggui on the formula were Danggui-Yimucao>Danggui-Chuanxiong>Danggui-Honghua>Danggui-Zhigancao>Danggui-Taoren>Danggui-Jiangtan. In conclusion, various herb pairs containing Danggui played different roles on the effects of improving the abnormality of hemorheology and coagulation function. And the herb pairs Danggui-Yimucao were particularly important for the formula, which was consistent with the characteristics of XSHG and the traditional effect of Yimucao. Moreover, it could lay foundation to further reveal the compatibility mechanism of XSHG.