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Objective: To estimate the direct economic burden of tuberculous meningitis (TBM) in China for the first time. Methods: Patients who were first diagnosed with TBM from December 2015 to December 2018 in Western China Hospital were enrolled. We retrospectively collected data on demographic and clinical features, resource utilization, costs, and long‐term outcomes. The patients were followed up for 15–53 months. We performed a cost‐of‐illness study and analyzed the cost contributors with a generalized linear model. Results: In total, the cases of 154 TBM patients (95 males, 59 females, aged 14–82 years) were reviewed. The average total direct cost per person was USD (United States dollars) 9,484 (range 1,822–67,285), with a mean direct medical cost of USD 8,901 (range 1,189–67,049). The average inpatient cost and drug cost after discharge were USD 6,837 (range 845–52,921) and USD 1,967 (range 0–60,423), respectively. The mean direct nonmedical cost was USD 583 (range 33–3,817), which accounted for 6.2% of the total direct cost. The average length of stay (LOS) in hospital was 25.0 days (range 6–152). A total of 117 of the patients (76.0%) had good outcomes (mRS = 0–2). There was no significant difference in the costs, LOS, or outcomes between rural and urban patients. Contributors to total direct cost were definite TBM, fever, coma, seizures, multidrug resistance, hydrocephalus, and poor long‐term outcome. Conclusions: Although the accessibility of medical resources in remote and rural regions has significantly improved in China, the cost of TBM imposes a catastrophic burden on patients. [ABSTRACT FROM AUTHOR]

The versatility of multicolor imaging of human tissues based on staining with perylene monoimide–mannose conjugates PMI-Man and co-staining with PMI-Man and eosin (P&E) was investigated for human cancer and normal tissues. Staining with PMI-Man or co-staining with PMI-Man and eosin showed a perfect histological morphology both in confocal fluorescence microscopy and light microscopy. This approach provided a universal colorful staining method for cancer tissues and normal tissues. [ABSTRACT FROM AUTHOR]

Antimonene is a recently discovered two-dimensional semiconductor with high carrier mobility, suitable bandgap, and strong spin–orbit coupling, which is of great interest for future electronic, optoelectronic, and spintronics device applications. However, as the basic properties of materials, the electronic structure of antimonene is not fully understood. In this work, the whole and anisotropic electronic structures of antimonene modulated by a horizontal crystal field have been studied in detail by angle-resolved photoemission spectroscopy. The valence band of antimonene for semiconductor properties is characterized by a three-dimensional anisotropic "M"-shape with hexagonal deformation in (E, kx, ky) space. Moreover, the surface state of antimonene for metallic properties is characterized by an upward conelike structure with a stronger warping effect. The anisotropic electronic structure of antimonene is systematically depicted along the high symmetric direction and constant energy contours. [ABSTRACT FROM AUTHOR]

The diagnosis and treatment of cancer of unknown primary site (CUP) present with difficulties and produce a poor prognosis. The current study presents the case of a patient with CUP in the mandibular region was treated with docetaxel and lobaplatin chemotherapy, and vascular embolization of the tumor. The tumor size was markedly reduced and the patient's quality of life improved following radiotherapy. The present case report is accompanied by a discussion of the literature to contextualize the treatment regimen for patients with CUP. These findings will support current treatment practices, inform oncologists and benefit patients with cancer. [ABSTRACT FROM AUTHOR]

Both cocrystal and nanocrystal technologies have been widely used in the pharmaceutical development for poorly soluble drugs. However, the synergistic effects due to the integration of these two technologies have not been well investigated. The aim of this study is to develop a nano-sized cocrystal of phenazopyridine (PAP) with phthalimide (PI) to enhance the release rate and oral bioavailability of PAP. A PAP–PI nano-cocrystal with particle diameter of 21.4 ± 0.1 nm was successfully prepared via a sonochemical approach and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. An in vitro release study revealed a significant release rate enhancement for PAP–PI nano-cocrystal as compared to PAP–PI cocrystal and PAP hydrochloride salt. Further, a comparative oral bioavailability study in rats indicated significant improvement in C max and oral bioavailability (AUC 0 − ∞ ) by 1.39- and 2.44-fold, respectively. This study demonstrated that this novel nano-cocrystal technology can be a new promising option to improve release rate and absorption of poorly soluble compounds in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis) is the most common type of immune-mediated encephalitis. This study aimed to assess the incidence and mortality of anti-NMDAR encephalitis in intensive care unit (ICU) to evaluate the clinical manifestations, laboratory findings, managements and outcomes, and to compare these characteristics with patients with non-anti-NMDAR encephalitis admitted to ICU. Patients admitted to the neurological ICU with suspected encephalitis were included between January 1, 2012 and July 31, 2015. Cerebrospinal fluid (CSF) of enrolled patients was screened for anti-NMDAR antibodies using a cell-based assay. 72 critically ill patients with encephalitis of uncertain etiology were investigated, and 16 patients were positive for anti-NMDAR antibodies in CSF. Compared to patients with non-anti-NMDAR encephalitis, patients with anti-NMDAR encephalitis were younger, more likely to present with the psychiatric symptoms, dyskinesia, and autonomic dysfunction, and had longer ICU stays. The abnormal movements were so difficult to control that complicated the management. The outcome was favorable in ten patients 1 year after the disease onset, and the mortality was as high as 25 % overall. The incidence of anti-NMDAR encephalitis is high among critically ill patients with encephalitis of uncertain etiology. Controlling dyskinesia proved to be a challenge. Persistent dysautonomias were additional difficult to manage confounders. Same points being highlighted in this study may aid clinicians in the management of patients with anti-NMDAR encephalitis in intensive care practice. [ABSTRACT FROM AUTHOR]

A para-selective C¢H amidation of simple arenes with nitriles has been developed. By increasing the amount of arenes, a further meta-selective C¢H arylation of the produced amides occurred. Both steric and electronic effects are utilized to control the selectivity, resulting in only para-selective amidation products. The readily available nitriles as amidation reagents instead of amides makes the synthesis of N-arylamides more accessible. [ABSTRACT FROM AUTHOR]

Abstract: Tetramethylenedisulfotetramine (TETS), a neurotoxic rodenticide banned in China, has repeatedly been shown to kill healthy people. We report a series of nine people with TETS intoxication presenting with Convulsive Status Epilepticus (CSE) as the initial manifestation. Median duration of CSE after admission was 6h. All had normal neuro-imaging but inter-ictal EEG showed bilateral epileptic waves. Despite aggressive anti-convulsive treatment, attempts at reducing TETS levels and supportive therapy, outcomes were poor. Multiple organ dysfunction syndrome (MODS) occurred in six people, of whom three died. TETS exposure should be part of the differential diagnosis in people presenting with unexplained SE in rural China, particularly if this occurs in family clusters. Over 14,000 cases of TETS intoxication occurred in China between 1 January 1991 and 31 December 2010, and 932 of these died. Cases were widely distributed throughout the country, occurring primarily in rural areas. CSE seems to be a frequent symptom of severe intoxication. There is, however, still a lack of information about the hazards of TETS and it is imperative that both the public and physicians are made aware of its risks and complications. [Copyright &y& Elsevier]

Summary: Background: There has been a long-standing suspicion that an association exists between mesial temporal lobe epilepsy (MTLE) and the herpes virus. Evidence for HHV-6B involvement has been reported. However, no investigation has been performed in China. Methods: We used nested PCR and immunohistochemistry to detect viral DNA of human herpes virus (HHV)-6B, HHV-6A, herpes simplex virus (HSV)-1 and HSV-2 in resected brain tissues from patients with MTLE and control. A principal transcription factor, NF-κB, that is associated with the inflammatory response was also investigated by real-time PCR, western blotting and immunohistochemistry. Results: HHV-6B DNA was detected in hippocampal samples from 9 out of 32 (28.1%) patients with MTLE and in 1 of 12 (8.3%) control samples. Immunoreactivity for HHV-6B was consistently present in MTLE patients positive for HHV-6 detected by PCR. Significant staining for HHV-6B antigen was distributed mainly around or in the nucleus of cells that morphologically resembled astrocytes and microglia. HHV-6B positivity was related to febrile convulsion history of patients with MTLE. The expression of NF-κB was up-regulated and distributed in the nucleus of glial cells in MTLE patients positive for HHV-6B. Conclusion: This study was first to find HHV-6B in MTLE patients from West China and demonstrate a possible association between HHV-6B positivity and activation of NF-κB. The detailed role of HHV-6B and its association with NF-κB in the development of chronic MTLE requires further investigation. [ABSTRACT FROM AUTHOR]

Abstract: Glutamate receptor 5 (GluR5) plays a role as an excitatory regulator of synaptic transmission and plasticity; however, its exact role in the pathological mechanism underlying epilepsy is not fully known. We investigated GluR5 expression in resected brain tissues from humans with temporal lobe epilepsy (TLE) and from a macaque model of Coriaria lactone-induced TLE. GluR5 was upregulated in the hippocampus, but not in the temporal neocortex, of patients with TLE compared to the control group. In contrast, GluR5 expression in the hippocampus of macaques treated with Coriaria lactone was not upregulated compared to the control. In addition, mossy fiber sprouting in the hippocampus of TLE patients was correlated with GluR5 upregulation, whereas mossy fiber sprouting was not observed in the macaque model lacking GluR5 upregulation, suggesting that GluR5 function is mainly associated with mossy fiber sprouting. [Copyright &y& Elsevier]

Aim: To evaluate the efficacy and safety of 3,000 mg daily levetiracetam (LEV; Keppra) as an adjunctive therapy for Chinese patients with refractory partial seizures. Methods: This randomized, placebo-controlled trial consisted of an 8-week baseline period followed by a 4-week titration interval and a 12-week maintenance period, and concluded with a 4-week medication withdrawal period or entered an open-label study. LEV was compared with placebo. Results: The 50% responder rate (the proportion of patients with a minimum of 50% reduction in partial seizure frequency) occurred in 46.4% of the LEV group, compared with 39.3% of the placebo group (p = 0.590). The median of the absolute weekly frequency reduction from baseline of partial seizures was 0.66 per week for LEV versus 0.48 per week for placebo (p = 0.187). The most common treatment-emergent adverse events, mostly mild to moderate in severity, were somnolence, dizziness and agitation. Conclusion: In this study, adjunctive therapy with LEV 3,000 mg daily was well tolerated but not as effective as expected in controlling partial seizures in this study population. Considering the lower mean weight of this study population, we suggest the dosage of LEV 3,000 mg daily may contribute to the results. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in the temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures. [Copyright &y& Elsevier]

We report the epitaxial growth of monolayer copper arsenide (CuAs) with a honeycomb lattice on Cu(111) by molecular beam epitaxy (MBE). Scanning tunneling microscopy (STM), low energy electron diffraction (LEED), x-ray photoelectron spectroscopy (XPS), and density functional theory (DFT) verify the superlattice of monolayer CuAs on Cu(111) substrate. Angle-resolved photoemission spectroscopy (ARPES) measurements together with DFT calculations demonstrate the electronic band structures of monolayer CuAs and reveal its metallic nature. Further calculations show that charge transfer from Cu(111) substrate to monolayer CuAs lifts the Fermi level and tunes the band structure of the monolayer CuAs. This high-quality epitaxial monolayer CuAs with potential tunable band gap holds promise on the applications in nano-electronic devices. [ABSTRACT FROM AUTHOR]

A new general de novo synthesis of pharmaceutically important α-aryl β-perfluoroalkyl ketones has been disclosed. Compared with trifluoromethylation-initiated radical 1,2-aryl migration of α,α-diaryl allylic alcohols, this protocol employs a new strategy of biomimetic carbene catalysis to assemble alkene, aldehyde and perfluoroalkyl reagents, providing access to products with excellent flexibility of the aryl unit and perfluoroalkyl group. This method also demonstrates excellent functional group compatibility, including some Grignard reagent sensitive groups. [ABSTRACT FROM AUTHOR]

In the presence of 1.5 equiv. [ABSTRACT FROM AUTHOR]

• HHV-6B triggers immune modulatory factors in MTLE. • Increased IL-1a, IL-2 and IL-7 mRNA levels are associated with early antigen expression. • IL-1a and IL-7 may be taken as indirect biomarker of HHV-6B infection in CSF. • Co-localization of HHV-6B antigen with astrocytes and oligodendrocytes. Background: Human herpes virus-6B (HHV-6B) was suggested as an important etiologic factor of mesial temporal lobe epilepsy, while the mechanism is still unknown. Here, we aimed to analyze antigens representing latent, early and late HHV-6B infection and the association with inflammatory cytokines in brain tissue and cerebral spinal fluid (CSF) from MTLE patients with HHV-6B-positivity. Methods: Nested polymerase chain reaction (nPCR), real-time PCR, immunohistochemistry (IHC) and suspension bead array for cytokines were performed. Results : Nested polymerase chain reaction (nPCR) in brain tissue revealed HHV-6B DNA in 19 of 49 MTLE patients (39%) and 1 of 19 controls (5%) (P < 0.001), but not in CSF. ICH showed HHV-6B early antigen (P41) positivity in 3 patients (6%), late antigen (gp116/54/64) positivity in 5 patients (10%), latent antigen (U94) positivity in 8 patients (16%), and multiple antigen (early and late or/and latent) positivity in 9 patients (18%). None of these HHV-6B related proteins were found positive in control brain tissue. PCR revealed significant up-regulation of IL-1a, IL-2 and IL-7 mRNA levels in the brain tissue from MTLE patients expressing early antigens compared to those expressing late, latent, multiple antigens, negative antigens and the controls. Suspension bead array of the CSF confirmed significant up-regulation of IL-1a and IL-7 protein expression from MTLE patients expressing early antigens compared to the other groups. Conclusions: Our finding suggests HHV-6B is a common etiologic agent of MTLE. Different virus life cycle may play an important modifying role in inflammatory biology that warrants further investigation. Though virus DNA is difficult detected in CSF, up-regulation of IL-1a and IL-7 in CSF indicates the two cytokines may be taken as indirect biomarker of HHV-6B infection. [ABSTRACT FROM AUTHOR]

Development of novel biomarker and achievement of simple, sensitive, rapid and economical detection of cancer in clinic have become more urgent and indispensable. In this paper, a light-activated sensor, PMI-B , was developed. The selective sensing of BAs both in solution and in the PA membrane was achieved, especially for spermine. PMI-B exhibited selective sensing of BAs by a synergistic mechanism based on an autoacting photocatalytic mechanism and a pH-controlled deprotonation mechanism. Furthermore, the detection of cancer based on PMI-B with twenty-six human urine samples was investigated by UV–vis and fluorescence spectra. The ratio differences of A 741 / A 561 and A 741 / A 491 can effectively be used to classify breast cancer and other female cancer and lesion patients. Compared with the established tumor markers, the specificity of the A 741 / A 516 value (the raw median value = 0.27) for PMI-B with various human urine samples was a potential malignant tumor marker for breast cancer patients. [Display omitted] • A light-activated sensor (PMI-B) for selective sensing of biogenic amines both in solution and in the PA membrane was developed. • A synergistic mechanism based on an autoacting photocatalytic mechanism and a pH-controlled deprotonation mechanism was found. • The early diagnosis of breast cancer was studied both in a solution state and in a paper-based PA membrane. • The ratio difference of A 741 / A 561 can effectively be used to classify breast cancer and other female cancer and lesion patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential detection rate of anti-thyroid antibodies' (ATAbs) positivity, thyroid dysfunctions, and autoimmune thyroid diseases (AITDs) in autoimmune encephalitis (AE) and to analyze whether thyroid autoimmunity/dysfunction can affect the clinical course of AE.Methods: Two hundred twenty-one AE patients and 229 age- and sex-matched controls were included in this study. We measured the levels of ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) and thyroid hormones in all the individuals. In addition, the association of thyroid autoimmunity/dysfunctions with functional outcomes of AE was identified by using logistic regression and Kaplan-Meier analyses.Results: The prevalence of TPOAb-positive and TgAb-positive was significantly higher in AE patients (16.3% and 16.7%, respectively) as compared with controls (9.6% and 7.4%, respectively; P = 0.034 and P = 0.002, respectively). In addition, the free triiodothyronine (fT3) level was significantly lower in AE patients as compared to the controls (P < 0.001). However, the frequency of AITDs (Hashimoto's thyroiditis and Graves' disease) did not significantly differ between AE patients and control subjects. Importantly, low fT3 was found to be associated with poor functional outcomes at the 3-month follow-up in AE. Adjustment of potential confounders did not change the association. However, the presence of ATAbs did not significantly alert the disease course of AE.Conclusions: ATAbs-positive and/or AITD patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary. [ABSTRACT FROM AUTHOR]

Curcumin, a principle bioactive component of Curcuma longa L, is well known for its anti-hyperlipidemia effect. However, no holistic metabolic information of curcumin on hyperlipidemia models has been revealed, which may provide us an insight into the underlying mechanism. In the present work, NMR and MS based metabolomics was conducted to investigate the intervention effect of curcumin on hyperlipidemia mice induced by high-fat diet (HFD) feeding for 12 weeks. The HFD induced animals were orally administered with curcumin (40, 80 mg/kg) or lovastatin (30 mg/kg, positive control) once a day during the inducing period. Serum biochemistry assay of TC, TG, LDL-c, and HDL-c was conducted and proved that treatment of curcumin or lovastatin can significantly improve the lipid profiles. Subsequently, metabolomics analysis was carried out for urine samples. Orthogonal Partial Least Squares-Discriminant analysis (OPLS-DA) was employed to investigate the anti-hyperlipidemia effect of curcumin and to detect related potential biomarkers. Totally, 35 biomarkers were identified, including 31 by NMR and nine by MS (five by both). It turned out that curcumin treatment can partially recover the metabolism disorders induced by HFD, with the following metabolic pathways involved: TCA cycle, glycolysis and gluconeogenesis, synthesis of ketone bodies and cholesterol, ketogenesis of branched chain amino acid, choline metabolism, and fatty acid metabolism. Besides, NMR and MS based metabolomics proved to be powerful tools in investigating pharmacodynamics effect of natural products and underlying mechanisms. [ABSTRACT FROM AUTHOR]

Summary: Purpose: This study aimed to explore the most appropriate antiepileptic drug strategies after successful epilepsy surgery. Methods: A total of 131 refractory epilepsy patients who underwent epilepsy surgery from January 2005 to December 2008 in the Department of Neurosurgery, West China Hospital, were retrospectively reviewed. Patients were divided into three groups (monotherapy, duotherapy, and polytherapy) according to drug combinations used immediately after epilepsy surgery. Seizure outcomes were followed up for more than 2 years. Engel classification was used to evaluate seizure outcomes. Results: The mean postoperative follow-up period was 3.7±1.0 years. Preoperative baseline data among the three groups were comparable. Seizure recurrence rate in monotherapy was obviously higher than in other groups (34.1% vs. 15.1%, 7.1%) at 6-month follow-up, which showed a statistically significant difference (p =0.02). Seizure outcomes for 2 years were assessed using Engel classification. In the duotherapy group, the rate of Engel class I was definitely higher than in the other two groups (69.9% vs. 47.7%, 57.1%, p =0.02). Seizure relapse rates at the 2-year follow-up, after planned reduction or withdrawal, were 46.4% for monotherapy, 16.9% for duotherapy, and 25.0% for polytherapy (p =0.01). Conclusions: Monotherapy may be not sufficient enough to control seizures completely. It appears to have a higher risk for seizure relapse when considering drug reduction. It suggests that duotherapy may be more effective and safer than monotherapy. Even after successful epilepsy surgery, duotherapy seems preferable to monotherapy or polytherapy for control of residual seizures. [Copyright &y& Elsevier]

Abstract: Neuronal circuit remodeling is the most critical pathological characteristic closely associated with the initiation and maintenance of epilepsy; however, the exact mechanisms of neuronal remodeling need further elucidation. Neuronal Wiskott–Aldrich syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton that causes actin polymerization and thus neurite extension. Our previous research demonstrated that the upstream regulator of N-WASP, cell division cycle 42 GTP-binding protein (Cdc42), is significantly upregulated in the brains of patients with intractable epilepsy (IE). In addition, cDNA microarray analysis has shown that gene expression of N-WASP is notably enhanced in the epileptic brain, suggesting a possible role for N-WASP in epileptogenesis. Here, we investigated the expression of N-WASP and its downstream effector, actin-related protein 2/3 (Arp2/3), at the protein level in the temporal lobe of IE patient brains to explore its possible role in the genesis of IE. Forty surgical samples from brains of patients with IE and 20 control brain tissues were obtained for this study. The expression of N-WASP in the anterior temporal neocortex was detected using immunohistochemistry, immunofluorescence and western blotting; Arp2/3 expression was detected by western blotting. Compared with controls, N-WASP expression in brains of IE patients was significantly higher; similarly, Arp2/3 level was markedly increased in the IE patient group. These results suggest that increased expression of N-WASP in the human brain may be associated with human IE. [Copyright &y& Elsevier]

A mannose-modified perylene monoimide derivative PMI-Man was developed, which shows highly selective binding to double-stranded DNA molecules, potent live/dead cell imaging, and histological imaging via both confocal and light microscopies. This approach can be used to develop a universal colorful staining method for human tissues for both confocal and light microscopies. [ABSTRACT FROM AUTHOR]

Objective: To comprehensively describe the pathological features of neurons in patients with ovarian teratomas and paraneoplastic anti-NMDAR encephalitis (anti-NMDARE), emphasizing on NMDA-receptor expression and infiltrating lymphocytes. Methods: A retrospective study was performed in a large series of 159 patients from the West China Hospital. We retrospectively identified 12 patients with paraneoplastic anti-NMDARE (11 case with ovarian teratomas and 1 case with mixed germ cell tumor), which were compared to 35 patients with teratomas and no encephalitis and to 147 patients with anti-NMDARE and no evidence for tumors. Patient history and outcome were reviewed from the clinical charts and compared between all three groups. Histopathological examination, including double-immunofluorescence of NMDAR subunits and IgG was performed in all teratoma tissues. Magnetic Luminex Assay Human Premixed Multi-Analyte Kit was performed to investigate cytokines profile of CSF. Results: Patients with paraneoplastic anti-NMDARE had a more severe clinical presentation, i.e. they required more mechanical ventilation and intensive care (p < 0.001). Though immunotherapy was initiated earlier in this group, repeated intravenous immunoglobulin administration (IVIG) was more common (p = 0.002) and with higher cerebrospinal fluid (CSF) antibody titres (p = 0.004). Following tumor resection, the outcome did not differ between groups. A peculiar population of floating-frog like dysplastic neurons were observed only in teratomas of patients with paraneoplastic anti-NMDARE, co-expressing NR1, NR2A, NR2B subunits and IgG. Also, CD20 positive B-cells were more common in anti-NMDARE teratomas. In CSF of paraneoplastic anti-NMDARE patients, TNF-α, IL-10 and GM-CSF concentrations were higher than in negative symptom control and VEGF-A and IL-1a were lower than in anti-NMDARE patients (0.25 < p < 0.05). Conclusions: Patients with teratomas and paraneoplastic anti-NMDARE revealed a cellular population of dysplastic neurons co-expressing NMDAR subunits, which were the potential source of autoantigens triggering anti-NMDARE. Some inflammatory cytokines may be involved in pathogenesis of paraneoplastic anti-NMDARE. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT) and its analogues show potent antitumour activity. However, poor water solubility and severe side effects have restricted their applications in clinical practice. In this paper, a novel self‐assembly based on camptothecin and carbamoylmannose conjugates (CPT‐Man) was constructed. The self‐assembly increased the water solubility of camptothecin to 0.64 mg/ml and antitumour activity. Moreover, CPT‐Man could induce obvious cancer cell apoptosis. This work provides a new approach for exploring carbohydrate‐modified antitumour properties by self‐assembled CPT drugs. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) materials are playing more and more important roles in both basic sciences and industrial applications. For 2D materials, strain could tune the properties and enlarge applications. Since the growth of 2D materials on substrates is often accompanied by strain, the interaction between 2D materials and substrates is worthy of careful attention. Here we demonstrate the fabrication of strained monolayer silver arsenide (AgAs) on Ag(111) by molecular beam epitaxy, which shows one-dimensional stripe structures arising from uniaxial strain. The atomic geometric structure and electronic band structure are investigated by low energy electron diffraction, scanning tunneling microscopy, x-ray photoelectron spectroscopy, angle-resolved photoemission spectroscopy and first-principle calculations. Monolayer AgAs synthesized on Ag(111) provides a platform to study the physical properties of strained 2D materials. [ABSTRACT FROM AUTHOR]

Polymorphisms in arsenic (+ 3 oxidation state) methyltransferase (AS3MT) have been shown to be related to interindividual variations in arsenic metabolism and to influence adverse health effects in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (As2O3). The occurrence of hyperleukocytosis with As2O3 treatment seriously affects the early survival rate of APL patients, but no definite explanation for such a complication has been clearly established. To clarify the causes of this situation, AS3MT polymorphisms 14215 (rs3740390), 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) and profiles of plasma arsenic metabolites were evaluated in a group of 54 newly diagnosed APL patients treated with single-agent As2O3. High-performance liquid chromatography–hydride generation-atomic fluorescence spectrometry (HPLC–HG-AFS) was used to determine the concentrations of plasma arsenic metabolites. Plasma arsenic methylation metabolism capacity was evaluated by the percentage of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), primary methylation index (PMI, MMA/iAs), and secondary methylation index (SMI, DMA/MMA). The results showed that APL patients who developed hyperleukocytosis had a higher plasma iAs%, but a lower MMA% and PMI than those who did not develop hyperleukocytosis during As2O3 treatment. In addition, patients with the AS3MT 14215 (rs3740390) CC genotype had significantly higher plasma iAs% and incidence of hyperleukocytosis, but lower PMI than patients with the CT + TT genotype. Conversely, we did not observe statistically significant associations between the occurrence of hyperleukocytosis and AS3MT 14458 (rs11191439), 27215 (rs11191446), and 35991 (rs10748835) polymorphisms in our study subjects. These results indicated that AS3MT 14215 (rs3740390) might be used as an indicator for predicting the occurrence of hyperleukocytosis in APL patients treated with As2O3. [ABSTRACT FROM AUTHOR]

Purpose This study aimed to summarize the clinical characteristics and outcome of late-onset anti- N -methyl- d -aspartate receptor (anti-NMDAR) encephalitis in China. Method All cases of people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and April 2017 were retrospectively reviewed. The demographics, clinical characteristics, and outcome of those patients (age ≥ 45 years old) were summarized. Comparisons were conducted between older (≥ 45 years old) and younger (18–44 years old) adults. Result Eighteen (12%) of 151 people were ≥ 45 years old, 9 of whom (50%) were female. Psychiatric symptoms were the most common clinical manifestations of older adults and presented in all individuals. At the last follow-up, 14 (78%) of them had a good outcome (modified Rankin Scale: 0–2) and one (6%) died. Compared with 121 younger adults, older adults had a higher proportion of presenting memory deficit as the initial symptom (17% vs. 2%, p = 0.023), longer interval from onset to admission (30 vs. 13 days, p = 0.013), and longer interval from onset to diagnosis (42.5 vs. 24 days, p = 0.045). No older adults' condition was accompanied with teratoma compared with 75% of younger adults with tumor (p = 0.032). And older adults had a tendency to have a lower rate of positive NMDAR antibody (Ab) in serum (28% vs. 52%, p = 0.053). Conclusion Delayed admission and diagnosis are more common in older adults than in younger adults. A comprehensive consideration of all symptoms and early screening of NMDAR Ab, especially in cerebrospinal fluid, is necessary and beneficial to differential diagnosis. [ABSTRACT FROM AUTHOR]

Background and objective Allergy is a potential outcome of dysregulated immune system. Previous studies have shown the association of allergy and autoimmune diseases, however, there is few study to investigate the relationship between allergy and anti- N -methyl- d -aspartate receptor (anti-NMDAR) encephalitis. Thus, we investigate the rate of allergy in patients with anti-NMDAR encephalitis and analyze the risk factors. Method The rate of allergy was investigated in patients with anti-NMDAR encephalitis and was compared with patients with virus encephalitis. The clinical cutaneous characters were described in details. All patients with anti-NMDAR encephalitis were divided into allergic and nonallergic group. Clinical factors were compared in the two groups, and logistic regression model was also used to analyze possible risk factors of allergy. Results Patients with anti-NMDAR encephalitis had a higher rate of allergy than those with viral encephalitis (22.1% vs 9.2%, odds ratio (OR) = 3.23, confidence interval (CI) = 1.40–7.42, P = 0.006). In patients with anti-NMDAR encephalitis, allergic patients exhibited longer days in hospital (30 days vs 22 days, P = 0.005) and higher occurrence of decreased consciousness (81.5% vs 58.9%, P = 0.031), higher rate of complications (77.8% vs 57.9%, P = 0.046) and abnormal electroencephalography (EEG) (100% vs 78.6%, P = 0.021) than patients without allergy. Cerebrospinal fluid (CSF) antibody titers of allergic patients during the disease course were also higher than nonallergic patients (P = 0.004). However, further logistic regression analysis did not reveal independent predictors of allergy. Conclusions Patients with anti-NMDAR encephalitis show higher allergic rate than those with virus encephalitis. Patients with allergy show higher CSF antibody titers and greater illness severity. However, the final outcome of anti-NMDAR encephalitis was not influenced. [ABSTRACT FROM AUTHOR]

We aimed to assess suicidality risk amongst people who had had anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis. All people with a definitive diagnosis of anti-NMDAR encephalitis in West China Hospital between June 2012 and February 2017 were identified and their notes were retrospectively reviewed. Demographic and clinical characteristics and risk predictors for suicidality were summarized; those with suicidality were compared to those without. 17 of 133 people (13%) presented with suicidality symptoms: 7 (5%) with suicidal ideation; 8 (6%) who attempted suicide; and 2 (1.5%) who completed suicide. Median age was 27 (16-78) years, most were female [13 (76%)]. Compared with those with no suicidality, psychiatric symptoms as the initial symptoms were more frequent in those who reported suicidality ( p = 0.039); insomnia, aggression, mania, depression and delusion were also more common ( p < 0.05). The use of antidepressants ( p < 0.001) and recurrence of encephalitis ( p = 0.020) were higher in people with suicidality than in those without. Other characteristics were not significantly different in those who had suicidality and those who did not. Suicidality is a common and potentially lethal risk for people with anti-NMDAR encephalitis. Those presenting with psychiatric symptoms as the initial symptom and with insomnia, aggression, mania, depression and delusion should be carefully screened for suicidality. Closely monitoring people who have been treated with antidepressants is necessary. [ABSTRACT FROM AUTHOR]

Gliomas, especially low-grade gliomas, are highly epileptogenic brain tumors. Histopathological information is valuable in evaluating the diagnosis and/or biologic behavior of various gliomas. Here we explored the clinical data and histopathological predictors of the occurrence of epilepsy in patients with gliomas. A retrospective study examined 310 consecutive patients who had undergone surgical treatment for gliomas in our institution from January 2013 to January 2015. Clinical data and pathological examination results were analyzed. Literatures regarding the predictors and etiology of glioma associated epileptic seizures in the period of 1995–2015 were also reviewed. A total of 234 (75.5%) astrocytic tumors and 76 (24.5%) oligodendrial tumors were included. At diagnosis, 33.6% of patients had epileptic seizures. Multivariate analysis revealed cortex involvement (OR = 7.991, 95%CI = 1.599–39.926), lower World Health Organization grade (OR = 3.584, 95%CI = 1.032–12.346) and topoisomerase II (TopoII) positivity (OR = 0.943, 95%CI = 0.903–0.982) were strong predictors for preoperative epileptic seizures. Gender, disease course, tumor classification, location or volume did not significantly affect epileptic seizure occurrence. Forty-three publications involved glioma-associated epilepsy were found in PubMed online database and key data were extracted and summarized. The present studies on glioma-related epilepsy are relatively limited and inconsistent. Low-grade gliomas, cortex involvement and TopoII positivity were independent predictors of a history of epileptic seizures at diagnosis. Further studies to examine the underlying mechanism of topoisomerase II as well as other molecules in epilepsy occurrence in brain gliomas are needed in the future. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy is one of the most common clinical neurological disorders. One of the major pathological findings in temporal lobe epilepsy is hippocampal sclerosis, characterized by massive neuronal loss and severe gliosis. The epileptogenesis process of temporal lobe epilepsy usually starts with initial precipitating insults, followed by neurodegeneration, abnormal hippocampus circuitry reorganization, and the formation of hypersynchronicity. Experimental and clinical evidence strongly suggests that dysfunctional neurogenesis is involved in the epileptogenesis. Recent data demonstrate that neurogenesis is induced by acute seizures or precipitating insults, whereas the capacity of neuronal recruitment and proliferation substantially decreases in the chronic phase of epilepsy. Participation of the Wnt/β-catenin signaling pathway in neurogenesis reveals its importance in epileptogenesis; its dysfunction contributes to the structural and functional abnormality of temporal lobe epilepsy, while rescuing this pathway exerts neuroprotective effects. Here, we summarize data supporting the involvement of Wnt/β-catenin signaling in the epileptogenesis of temporal lobe epilepsy. We also propose that the Wnt/β-catenin signaling pathway may serve as a promising therapeutic target for temporal lobe epilepsy treatment. [ABSTRACT FROM AUTHOR]

Purpose To investigate the antiepileptic and protective effects of intravenous levetiracetam (iv LEV) in the rhesus monkey model of acute status epilepticus (SE). Methods Thirty minutes before intraperitoneal induction of SE by Coriaria lactone (CL), rhesus monkeys were treated with LEV (15 or 150 mg/kg) delivered intravenously as a single bolus. CL dose and epileptic behavior were recorded. Electroencephalography (EEG) was performed before and during the experiment. All rhesus monkeys were killed after 1-month video monitoring and processed for pathological investigation of neuronal injury, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, and glial fibrillary acidic protein (GFAP) staining. Results No animal exhibited spontaneous seizures during 1-month video monitoring. Development of acute SE was significantly inhibited in the group given 150 mg/kg LEV, compared with controls and the 15 mg/kg LEV group. Delayed latency, reduction of SE duration, decreased cumulative time of tonic convulsions, slight severity of SE, and a high CL induction dose were observed in the high LEV dose group (p < 0.05). The EEG showed less frequent epileptic discharges in the group administered with 150 mg/kg LEV. Hematoxylin and eosin (H&E) staining, ultrastructural examination, TUNEL and GFAP staining revealed serious damage, including neuron loss, swollen mitochondrion, and strong positivity for TUNEL in the hippocampus and thalamus of controls, whereas moderate damage in the group administered with 15 mg/kg LEV, and very mild damage in the 150 mg/kg LEV group. Gliosis was found in the hippocampus of controls, not in the LEV groups and normal rhesus monkey. Conclusion The study supports the antiepileptic and protective effect of pretreatment with intravenous LEV in rhesus monkey model with SE. [ABSTRACT FROM AUTHOR]

• An all covariates-based association model was built to explain the risk of CAD. • The model incorporated both a gene-score and 8 lifestyle/clinical risk factors. • The gene-score was derived from ALDH2 , ADCY3 and BCMO1 polymorphisms. • The findings may provide implications for CAD pathogenesis in Chinese Han population. To investigate associations of genetic and environmental factors with coronary artery disease (CAD), we collected medical reports, lifestyle details, and blood samples of 2113 individuals, and then used the polymerase chain reaction (PCR)-ligase detection reaction (LDR) to genotype the targeted 102 SNPs. We adopted elastic net algorithm to build an association model that considered simultaneously genetic and lifestyle/clinical factors associated with CAD in Chinese Han population. In this study, we developed an all covariates-based model to explain the risk of CAD, which incorporated 8 lifestyle/clinical factors and a gene-score variable calculated from 3 significant SNPs (rs671, rs6751537 and rs11641677), attaining an area under the curve (AUC) value of 0.71. It was found that, in terms of genetic variants, the AA genotype of rs671 in the additive (adjusted odds ratio (OR) = 2.51, p = 0.008) and recessive (adjusted OR = 2.12, p = 0.021) models, the GG genotype of rs6751537 in the additive (adjusted OR = 3.36, p = 0.001) and recessive (adjusted OR = 3.47, p = 0.001) models were associated with increased risk of CAD, while GG genotype of rs11641677 in additive model (adjusted OR = 0.39, p = 0.044) was associated with decreased risk of CAD. In terms of lifestyle/clinical factors, the history of hypertension (unadjusted OR = 2.37, p < 0.001) and dyslipidemia (unadjusted OR = 1.82, p = 0.007), age (unadjusted OR = 1.07, p < 0.001) and waist circumference (unadjusted OR = 1.02, p = 0.05) would significantly increase the risk of CAD, while height (unadjusted OR = 0.97, p = 0.006) and regular intake of chicken (unadjusted OR = 0.78, p = 0.008) reduced the risk of CAD. A significant interaction was found between rs671 and dyslipidemia (the relative excess risk due to interaction (RERI) = 3.36, p = 0.05). In this study, we constructed an association model and identified a set of SNPs and lifestyle/clinical risk factors of CAD in Chinese Han population. By considering both genetic and non-genetic risk factors, the built model may provide implications for CAD pathogenesis and clues for screening tool development in Chinese Han population. [ABSTRACT FROM AUTHOR]

The aim of this qualitative study was to explore the challenges that patients with epilepsy (PWEs) face and the opportunities or areas where changes in nursing care may improve epilepsy care in western China. Semi-structured interviews with open-ended questions based on a review of the literature were conducted at the epilepsy center of a tertiary hospital in western China. A total of 18 PWEs, 18 caregivers and 11 neurology nurses were interviewed by using purposive sampling. The data were transcribed verbatim, and a content analysis was used to conduct the framework analysis. Three key themes were identified, namely, the impact of epilepsy, barriers to epilepsy management, and measures in nursing care for improving epilepsy care. Psychological stress, the side effects of drugs and accidental injury related to seizures were reported to be the main negative impacts on patients. Limited knowledge about epilepsy, poor adherence to therapy, and a lack of effective communication between patients and medical staff were the major barriers to epilepsy management. Strengthening health education, assessing the frequency and type of seizures, screening for psychological disorders and mental intervention, and maintaining continuity of care were identified as crucial measures for nurses to improve epilepsy care. This study highlights the challenges among PWEs and opportunities for improving the quality of epilepsy care in western China. Limited knowledge and poor drug adherence are the main barriers to epilepsy management, which might be improved by more health education and continuing care provided by nurses. Assessing seizures, screening for psychological disorders and providing appropriate psychological care would help improve epilepsy care • Psychological stress, side effects of drugs and injury were the main negative impacts of epilepsy. • Limited knowledge, poor compliance, and insufficient communication were the major barriers to epilepsy management. • Health education, seizure assessment, screening for psychological disorders, and continuity of care can help epilepsy care. [ABSTRACT FROM AUTHOR]

Abstract: We investigated laminin β1 expression in the hippocampi of patients with intractable epilepsy and explored the role of laminin β1 in the pathogenesis of this condition. Fluorescence quantitative PCR, immunofluorescence, immunohistochemistry and Western blotting were used to measure laminin β1 expression in surgically removed hippocampi of patients with intractable epilepsy, and the results were compared with control hippocampi. Fluorescence quantitative PCR showed increased expression of laminin β1 mRNA in patient hippocampi compared with control tissues. Immunohistochemical staining demonstrated that laminin β1 protein expression was significantly increased in patient hippocampi, and immunofluorescence microscopy showed accumulation of laminin β1 in the cell membrane and cytoplasm of patient hippocampi. These findings were confirmed by Western blotting of protein preparations from patient hippocampi. Elevated expression of laminin β1 mRNA and protein in the hippocampus suggests that laminin β1 may play a role in the development of epileptic seizures in patients with intractable epilepsy. [Copyright &y& Elsevier]

Abstract: TDAG51 (T cell death-associated gene 51) is an apoptosis-associated protein. Our aim was to investigate TDAG51 expression in the anterior temporal neocortex of patients with intractable epilepsy (IE), and then to discuss the possible role of TDAG51 in IE. Tissue samples from the anterior temporal neocortex of 33 patients who had surgery for IE were used to detect TDAG51 expression by immunohistochemistry, immunofluorescence, and Western blotting. We compared these tissues with nine histologically normal anterior temporal lobes from intracranial hypertension patients who had decompression procedures. TDAG51 was mainly expressed in the cytoplasm of neurons and glial cells. TDAG51 in IE was significantly higher than that in the controls. These findings were consistently observed using Western blotting, immunofluorescence, and immunohistochemistry techniques. TDAG51 in patients with IE was significantly higher when compared with levels in the controls. This finding suggests TDAG51 is consistent with a possible role of this gene in the evolution of the pathology in IE. [Copyright &y& Elsevier]

Heat Shock Protein BAP1 (heat shock 27-kDa-associated protein 1, HSPBAP1) inhibits the function of heat shock protein 27, which has a neuroprotective effect during experimentally induced epileptic neuropathology. In our study, fluorescence quantitative polymerase chain reaction, immunohistochemistry, immunofluorescence, western blot were used to test the levels of HSPBAP1 mRNA and protein in surgical samples of the anterior temporal neocortex of patients with intractable epilepsy (IE) and normal controls samples. HSPBAP1 mRNA was abnormally expressed in the anterior temporal neocortex of patients with IE. Moreover, HSPBAP1 was found extensively in the cytoplasm of neurons and glial cells in all epilepsy specimens. Western blot showed a clear immunoreactive band of HSPBAP1 in IE specimens whereas it was absent in control specimens. The expression of HSPBAP1 mRNA and protein in the anterior temporal neocortex from patients with IE may play a role in the development of epileptic seizures in patients with cell loss in this brain region. Additional studies will be required to elucidate the mechanism by which HSPBAP1 affects brain function in IE. Synapse 61:741-747, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the expression of PSD-93 mRNA and NR2B mRNA in the brain tissue from the patients with epilepsy so as to explore the possible mechanisms of the pathogenesis of the epilepsy. Methods: Fifty-six patients with epilepsy were divided into intractable epilepsy (IE) and non-intractable epilepsy (NIE) groups. cDNA microarrays prepared from the brain tissues obtained from these two groups were scanned and comparison to those from the non-epileptogenic control (C) was made. Expression level of PSD-93mRNA and NR2BmRNA were examined by reverse transcription polymerase chain reaction (GAPDH gene, internal control). Expression ratio (target gene/GAPDH) was used to evaluate each gene relative expression level. Results: The cDNA microarray analysis showed that the expression of PSD-93 mRNA related to the function of NMDAR-NO signal transduction pathway was significantly higher in epilepsy patients than those in the controlled group. The results of RT-PCR were consistent with those of the cDNA microarrays. The relative expression ratio of PSD-93 in patients with non-epileptogenic control, NIE, and IE was 0.159, 0.368, and 0.341, respectively. Correspondingly, that of NR2B was 0.198, 0.738, and 0.903, respectively. The expressions of PSD-93 and NR2B in the NIE and IE were significantly higher than those of control, respectively (P <0.05). However, there was no significantly difference the expression of PSD-93 between NIE and IE. (P >0.05), neither do that of NR2B (P >0.05). Conclusions: The upregulated expressions of PSD-93 mRNA and NR2BmRNA may be involved in the pathogenesis of epilepsy. [Copyright &y& Elsevier]

This study aimed to investigate the impact of timing interval to start AED withdraw (TIW) after surgery on the seizure outcome in non-neoplastic drug resistant epilepsy (DRE). TIW were divided into three groups (respectively,<1 year, 1-<2 years, and ≥2 years). The seizure outcome at the different time points after starting AED withdrawal were compared among three groups. Other factors that related to seizure recurrence and TIW were included into the multiple analysis to investigate the predictors of seizure-free. Altogether, 205 patients were involved in the study. 102 individuals (50%) had seizure recurrence and 127 (62%) had seizure-free at the final follow up. 115 of them have attempted AED reduction and had not seizure recurrence before AED reduction. The rate of seizure-free had no significant difference among people with different TIW. Multiple analysis indicated that temporal surgery is a favorable predictor of seizure-free at the first year after starting AED withdrawal, and preoperative secondary generalized seizures is an unfavorable predictor of seizure-free at the final follow up. In patients with non-neoplastic DRE, TIW is not the mainly influence factor on seizure outcome, however, preoperative secondary generalized seizures and extra-temporal surgery are negatively associated with seizure-free. [ABSTRACT FROM AUTHOR]

The article presents chemical equations on article "Copper-Catalyzed Amidation of Arylboronic Acids with Nitriles." by and others, published in the "Synlett" in 2016.