Altered patterns of dynamic functional connectivity of brain networks in deficit and non-deficit schizophrenia.

This study aims to investigate the altered patterns of dynamic functional network connectivity (dFNC) between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS), and further explore the associations with cognitive impairments. 70 DS, 91 NDS, and 120 matched healthy controls (HCs) were enrolled. The independent component analysis was used to segment the whole brain. The fMRI brain atlas was used to identify functional networks, and the dynamic functional connectivity (FC) of each network was detected. Correlation analysis was used to explore the associations between altered dFNC and cognitive functions. Four dynamic states were identified. Compared to NDS, DS showed increased FC between sensorimotor network and default mode network in state 1 and decreased FC within auditory network in state 4. Additionally, DS had a longer mean dwell time of state 2 and a shorter one in state 3 compared to NDS. Correlation analysis showed that fraction time and mean dwell time of states were correlated with cognitive impairments in DS. This study demonstrates the distinctive altered patterns of dFNC between DS and NDS patients. The associations with impaired cognition provide specific neuroimaging evidence for the pathogenesis of DS.

Systemic inflammatory biomarkers in Schizophrenia are changed by ECT administration and related to the treatment efficacy.

Immune inflammation has long been implicated in the pathogenesis of schizophrenia. Despite as a rapid and effective physical therapy, the role of immune inflammation in electroconvulsive therapy (ECT) for schizophrenia remains elusive. The neutrophils to lymphocytes (NLR), platelets to monocytes (PLR) and monocytes to lymphocytes (MLR) are inexpensive and accessible biomarkers of systemic inflammation. In this study, 70 schizophrenia patients and 70 age- and sex-matched healthy controls were recruited. The systemic inflammatory biomarkers were measured before and after ECT. Our results indicated schizophrenia had significantly higher peripheral NLR, PLR and MLR compared to health controls at baseline, while lymphocytes did not differ. After 6 ECT, the psychiatric symptoms were significantly improved, as demonstrated by the Positive and Negative Syndrome Scale (PANSS). However, there was a decline in cognitive function scores, as indicated by the Mini-Mental State Examination (MMSE). Notably, the neutrophils and NLR were significantly reduced following ECT. Although lymphocytes remained unchanged following ECT, responders had significantly higher lymphocytes compared to non-responders. Moreover, the linear regression analyses revealed that higher lymphocytes served as a predictor of larger improvement in positive symptom following ECT. Overall, our findings further highlighted the presence of systemic inflammation in schizophrenia patients, and that ECT may exert a therapeutic effect in part by attenuating systemic inflammation. Further research may therefore lead to new treatment strategies for schizophrenia targeting the immune system.

Two new sesquiterpenoid glycoside compounds from the calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Two new sesquiterpenoid glycosides, 8α (H)-eudesmane-1,3,11 (13)-triene-2-one -12-O-ß-D-glucopyranoside (1) and dmetelisproside B (2), together with ten known compounds (3-12) were isolated from calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF). Their structures were unambiguously elucidated through HR-ESI-MS, UV, IR, and NMR spectral data. Compounds 1, 10, and 12 exhibited DPPH scavenging ability with IC50 values of 33.69 ± 6.65, 6.29 ± 0.06, and 25.66 ± 3.06 µM, respectively. Additionally, 10 and 12 demonstrated weak α-glucosidase inhibition activity with IC50 values of 250.9 ± 6.60 and 347.6 ± 2.48 µM, respectively.

High Stretch Associated with Mechanical Ventilation Promotes Piezo1-Mediated Migration of Airway Smooth Muscle Cells.

Ventilator-induced lung injury (VILI) during mechanical ventilation (MV) has been attributed to airway remodeling involving increased airway smooth muscle cells (ASMCs), but the underlying mechanism is not fully understood. Thus, we aimed to investigate whether MV-associated high stretch (>10% strain) could modulate mechanosensitive Piezo1 expression and thereby alter cell migration of ASMCs as a potential pathway to increased ASMCs in VILI. C57BL/6 mice and ASMCs were subjected to MV at high tidal volume (VT, 18 mL/kg, 3 h) and high stretch (13% strain, 0.5 Hz, 72 h), respectively. Subsequently, the mice or cells were evaluated for Piezo1 and integrin mRNA expression by immunohistochemical staining and quantitative PCR (qPCR), and cell migration and adhesion by transwell and cell adhesion assays. Cells were either treated or not with Piezo1 siRNA, Piezo1-eGFP, Piezo1 knockin, Y27632, or blebbistatin to regulate Piezo1 mRNA expression or inhibit Rho-associated kinase (ROCK) signaling prior to migration or adhesion assessment. We found that expression of Piezo1 in in situ lung tissue, mRNA expression of Piezo1 and integrin αVß1 and cell adhesion of ASMCs isolated from mice with MV were all reduced but the cell migration of primary ASMCs (pASMCs) isolated from mice with MV was greatly enhanced. Similarly, cell line mouse ASMCs (mASMCs) cultured in vitro with high stretch showed that mRNA expression of Piezo1 and integrin αVß1 and cell adhesion were all reduced but cell migration was greatly enhanced. Interestingly, such effects of MV or high stretch on ASMCs could be either induced or abolished/reversed by down/up-regulation of Piezo1 mRNA expression and inhibition of ROCK signaling. High stretch associated with MV appears to be a mechanical modulator of Piezo1 mRNA expression and can, thus, promote cell migration of ASMCs during therapeutic MV. This may be a novel mechanism of detrimental airway remodeling associated with MV, and, therefore, a potential intervention target to treat VILI.

Genetic mechanisms of COVID-19 and its association with smoking and alcohol consumption.

We aimed to investigate the genetic mechanisms associated with coronavirus disease of 2019 (COVID-19) outcomes in the host and to evaluate the possible associations between smoking and drinking behavior and three COVID-19 outcomes: severe COVID-19, hospitalized COVID-19 and COVID-19 infection. We described the genomic loci and risk genes associated with the COVID-19 outcomes, followed by functional analyses of the risk genes. Then, a summary data-based Mendelian randomization (SMR) analysis, and a transcriptome-wide association study (TWAS) were performed for the severe COVID-19 dataset. A two-sample Mendelian randomization (MR) analysis was used to evaluate the causal associations between various measures of smoking and alcohol consumption and the COVID-19 outcomes. A total of 26 protein-coding genes, enriched in chemokine binding, cytokine binding and senescence-related functions, were associated with either severe COVID-19 or hospitalized COVID-19. The SMR and the TWAS analyses highlighted functional implications of some GWAS hits and identified seven novel genes for severe COVID-19, including CCR5, CCR5AS, IL10RB, TAC4, RMI1 and TNFSF15, some of which are targets of approved or experimental drugs. According to our studies, increasing consumption of cigarettes per day by 1 standard deviation is related to a 2.3-fold increase in susceptibility to severe COVID-19 and a 1.6-fold increase in COVID-19-induced hospitalization. Contrarily, no significant links were found between alcohol consumption or binary smoking status and COVID-19 outcomes. Our study revealed some novel COVID-19 related genes and suggested that genetic liability to smoking may quantitatively contribute to an increased risk for a severe course of COVID-19.

The association between inflammation and kynurenine pathway metabolites in electroconvulsive therapy for schizophrenia: Implications for clinical efficacy.

The kynurenine pathway (KP) of tryptophan has been implicated in the pathogenesis of schizophrenia and its interaction with the immune system has been suggested to play a role. In this study, 28 schizophrenia patients and 25 healthy controls were recruited and divided into different inflammatory subgroups using a two-step recursive clustering analysis. Cytokine gene expression and plasma KP metabolites were measured before, during and after treatment. Our findings indicated that schizophrenia patients had lower levels of Tryptophan (TRP), N-formylkynurenine (NFK), xanthinic acid (XA), quinolinic acid (QA), kynurenic acid (KYNA), KYNA/KYN and QA/KYNA, but higher levels of IL-18 mRNA, KYN/TRP compared to healthy controls (all p < 0.05). After electroconvulsive therapy (ECT), patients with low inflammation achieved better clinical improvement (PANSS scores) compared to those with high inflammation (F = 5.672, P = 0.025), especially in negative symptoms (F = 6.382, P = 0.018, η2 = 0.197). While IL-18 mRNA (F = 32.910, P < 0.0001) was significantly decreased following ECT, the KYN/TRP (F = 3.455, p = 0.047) and KYNA/TRP (F = 4.264, P = 0.026) only significantly decreased in patients with low inflammation. Correlation analyses revealed that baseline IL-18 gene expression significantly correlated with pre- (r = 0.537, p = 0.008) and post-KYNA/TRP (r = 0.443, p = 0.034), post-KYN/TRP (r = 0.510, p = 0.013), and post-negative symptoms (r = 0.525, p = 0.010). Moreover, baseline TRP (r = -0.438, p = 0.037) and XA (r = -0.516, p = 0.012) were negatively correlated with baseline PANSS, while post-KYN (r = -0.475, p = 0.022), 2-AA (r = -0.447, p = 0.032) and KYN/TRP (r = -0.566, p = 0.005) were negatively correlated with Montreal Cognitive Assessment (MoCA) following ECT. Overall, these findings suggested that the association between inflammation and kynurenine pathway plays an essential role in mechanism of ECT for schizophrenia and that the regulation of ECT on KP is influenced by inflammatory characteristics, which may relate to clinical efficacy in schizophrenia.

Rumination mediates the relationship between childhood trauma and depressive symptoms in schizophrenia patients.

Rumination and childhood trauma are related to depressive symptoms in clinical and non-clinical individuals. This is the first study aimed to test the mediating effect of rumination on the relationship between childhood trauma and depressive symptoms in schizophrenia patients. A total of 313 schizophrenia patients were recruited in the present study. The 17-item Hamilton Depression Rating Scale (HAMD-17) was adopted to evaluate depressive symptoms, the short-form Childhood Trauma Questionnaire (CTQ-SF) and the 10-item Ruminative response scale (RRS-10) were utilized to assess the childhood trauma and rumination in patients, respectively. Our results showed that 168 schizophrenia patients (53.67%) had comorbid depressive symptoms. These patients with depressive symptoms had higher levels of childhood trauma [both CTQ-SF total scores and emotional abuse (EA), emotional neglect (EN), physical neglect (PN) subscale scores] and rumination (both RRS-10 total scores and brooding, reflection subscale scores) compared to patients without depressive symptoms. The stepwise logistic regression analysis identified that EN (OR 1.196, P = 0.003), PN (OR 1.1294, P < 0.001), brooding (OR 1.291, P < 0.001) and reflection (OR 1.481, P < 0.001) could independently predict the depressive symptoms in schizophrenia patients. Moreover, RRS-10 and its subscale scores could mediate the relationship between depressive symptoms and childhood trauma, especially EA, EN and PN in schizophrenia. Our preliminary findings suggest that the rigorous assessment and psychosocial interventions of rumination are important to alleviate the influence of childhood trauma on depressive symptoms in schizophrenia patients.

Antipsychotic-induced gastrointestinal hypomotility and the alteration in gut microbiota in patients with schizophrenia.

AIM: Gut microbiota play an important role in the pathogenesis of gut hypomotility and are critical for the production of the intestinal immune system and the maintenance of the intestinal homeostasis. Patients with psychotic disorders are at a high risk of antipsychotic-induced constipation. However, the mechanisms might be more than neurotransmission properties of antipsychotics. METHODS: We recruited a total of 45 patients with constipation according to Rome IV criteria and objective test for colonic motility and the other 45 gender- and age-matching patients without constipation and investigated their differences in composition of gut microbiota. The demographic and serum metabolic indices were collected. The subjective constipation assessment scale (CAS) and the Bristol stool classification (BSS) were also used to evaluate the degree of constipation in both groups. The fecal samples were analysed using the 16S rRNA gene sequencing. RESULTS: The constipation group had a significantly increased alpha diversity in Observed species, Chao 1, and ACE as compared to the non-constipation group. At the phylum levels, the relative abundances of Bacteroidetes and Fusobacteria decreased significantly, while those of Firmicutes, Verrucomicrobia, and Synergistetes increased significantly in the constipation group. At the genus level, the relative abundances of Christensenella and Desulfovibrio were higher in the constipation group. The α-diversity indices of gut microbiota were correlated positively with the levels of serum total bile acid and correlated negatively with BSS scores. The BSS scores were positively correlated with the relative abundance of Bacteroidetes but negatively correlated with the relative abundance of Firmicutes. PICRUSt analysis revealed the potential metabolic pathways of lipopolysaccharide, vitamin B6, riboflavin, pyruvate, and propionate functions. CONCLUSIONS: The alternation of the gut microbiota in schizophrenia patients with antipsychotic-induced constipation indicates antipsychotic agents might affect gastrointestinal motility via varying microbiome-related metabolites, and the specific bacteria, such as Synergistetes which might act as an anti-inflammatory factor in the healthy human gut, related to colonic transit motility seem inconsistent to the findings from previous literature in gastroenterology. However, the causal effects are still unknown. Our study provides a new possibility to understand the mechanisms of antipsychotic-induced constipation.

Altered intrinsic default mode network functional connectivity in patients with remitted geriatric depression and amnestic mild cognitive impairment.

OBJECTIVES: Patients with geriatric depression exhibit a spectrum of symptoms ranging from mild to severe cognitive impairment which could potentially lead to the development of Alzheimer's disease (AD). The aim of the study is to assess the alterations of the default mode network (DMN) in remitted geriatric depression (RGD) patients and whether it could serve as an underlying neuropathological mechanism associated with the risk of progression of AD. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 154 participants, comprising 66 RGD subjects (which included 27 patients with comorbid amnestic mild cognitive impairment [aMCI] and 39 without aMCI [RGD]), 45 aMCI subjects without a history of depression (aMCI), and 43 matched healthy comparisons (HC), were recruited. MEASUREMENTS: All participants completed neuropsychological tests and underwent resting-state functional magnetic resonance imaging (fMRI). Posterior cingulate cortex (PCC)-seeded DMN functional connectivity (FC) along with cognitive function were compared among the four groups, and correlation analyses were conducted. RESULTS: In contrast to HC, RGD, aMCI, and RGD-aMCI subjects showed significant impairment across all domains of cognitive functions except for attention. Furthermore, compared with HC, there was a similar and significant decrease in PCC-seed FC in the bilateral medial superior frontal gyrus (M-SFG) in the RGD, aMCI, and RGD-aMCI groups. CONCLUSIONS: The aberrations in rsFC of the DMN were associated with cognitive deficits in RGD patients and might potentially reflect an underlying neuropathological mechanism for the increased risk of developing AD. Therefore, altered connectivity in the DMN could serve as a potential neural marker for the conversion of geriatric depression to AD.

Preparation of an isorhamnetin phospholipid complex for improving solubility and anti-hyperuricemia activity.

To improve the solubility and anti-hyperuricemia activity of the insoluble natural flavonoid isorhamnetin (ISO), an isorhamnetin phospholipid complex (ISO-PC) was prepared. ISO-PC was prepared through solvent evaporation and its prescription process was optimized. The formation of ISO-PC was verified via multiple characterization methods. Parameters such as drug loading, solubility, octanol-water partition coefficient, stability, and in vivo anti-hyperuricemia activity of ISO-PC were investigated. The complexation efficiency of ISO-PC was 95.1% ± 0.56%. The characterization results confirmed that ISO-PC was bound by intermolecular interactions between ISO and phospholipids. Compared with ISO, the solubility of ISO-PC in water and 1-octanol increased by 122 and 16.5 times, respectively. In addition, the octanol-water partition coefficient decreased to 1.08. Pharmacodynamic studies have reported that ISO-PC has a more significant effect on reducing serum uric acid levels and renal protection. In conclusion, the findings of this study suggested that ISO-PC could be used as a promising formulation to improve the solubility and the anti-hyperuricemia activity of ISO.

Preparation and Evaluation of Novel Supersaturated Solid Dispersion of Magnolol : Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability.

This article aimed to design a new type of supersaturated solid dispersion (NS-SD) loaded with Magnolol (Mag) to raise the oral bioavailability in rats. In the light of the solubility parameters, phase solubility experiments, inhibition precipitation experiment, and in vitro release experiment, Plasdone-630 (PS-630) was selected as the optimum carrier. In addition, Mag-NS-SD was prepared by adding Monoglyceride (MG) and Lecithin High Potency (LHP) into the Mag-S-SD (Mag:PS-630 = 1:3), so as to reduce the dosage of carrier and improve the release rate. Using central composite design of response surface method, the prescription was further optimized. As the optimized condition was Mag:PS-630: MG: LHP = 1:3:0.8:0.266, the drug release rate was the fastest. Besides, after 45 min, the release rate was nearly 100%. The constructed Mag-S-SD and Mag-NS-SD were characterized by powder X-ray diffraction and infrared absorption spectrum. The XRD patterns of Mag-S-SD and Mag-NS-SD indicated that all APIs were amorphous. The IR spectra of Mag-S-SD and Mag-NS-SD demonstrated the existence of hydrogen bonding in the systems. Furthermore, in vivo pharmacokinetic study in rats revealed that compared with Mag and Mag-S-SD, Mag-NS-SD significantly increased the bioavailability (the relative bioavailability was 213.69% and 142.37%, separately). In this study, Mag-NS-SD was successfully prepared, which could improve the oral bioavailability and may increase the clinical application.

Causal influences of neuroticism on mental health and cardiovascular disease.

We investigated the relationship between neuroticism and 16 mental and 18 physical traits using summary results of genome-wide association studies for these traits. LD score regression was used to investigate genetic correlations between neuroticism and the 34 health outcomes. Mendelian randomization was performed to investigate mutual causal relationships between neuroticism and the 34 health outcomes. Neuroticism genetically correlates with a majority of health-related traits and confers causal effects on 12 mental traits (major depressive disorder (MDD), insomnia, subjective well-being (SWB, negatively), schizophrenia, attention-deficit/hyperactivity disorder, alcohol dependence, loneliness, anorexia nervosa, anxiety disorder, bipolar disorder, obsessive-compulsive disorder, and psychiatric disorders) and two physical diseases (cardiovascular disease and hypertensive disease). Conversely, MDD, SWB, and insomnia have a causal effect on neuroticism. We highlighted key genes contributing to the causal associations between neuroticism and MDD, including RBFOX1, RERE, SOX5, and TCF4, and those contributing to the causal associations between neuroticism and cardiovascular diseases, including MAD1L1, ARNTL, RERE, and SOX6. The present study indicates that genetic variation mediates the causal influences of neuroticism on mental health and cardiovascular diseases.

BioNorm: deep learning-based event normalization for the curation of reaction databases.

MOTIVATION: A biochemical reaction, bio-event, depicts the relationships between participating entities. Current text mining research has been focusing on identifying bio-events from scientific literature. However, rare efforts have been dedicated to normalize bio-events extracted from scientific literature with the entries in the curated reaction databases, which could disambiguate the events and further support interconnecting events into biologically meaningful and complete networks. RESULTS: In this paper, we propose BioNorm, a novel method of normalizing bio-events extracted from scientific literature to entries in the bio-molecular reaction database, e.g. IntAct. BioNorm considers event normalization as a paraphrase identification problem. It represents an entry as a natural language statement by combining multiple types of information contained in it. Then, it predicts the semantic similarity between the natural language statement and the statements mentioning events in scientific literature using a long short-term memory recurrent neural network (LSTM). An event will be normalized to the entry if the two statements are paraphrase. To the best of our knowledge, this is the first attempt of event normalization in the biomedical text mining. The experiments have been conducted using the molecular interaction data from IntAct. The results demonstrate that the method could achieve F-score of 0.87 in normalizing event-containing statements. AVAILABILITY AND IMPLEMENTATION: The source code is available at the gitlab repository https://gitlab.com/BioAI/leen and BioASQvec Plus is available on figshare https://figshare.com/s/45896c31d10c3f6d857a.

Eye movement characteristics in male patients with deficit and non-deficit schizophrenia and their relationships with psychiatric symptoms and cognitive function.

BACKGROUND: The cognitive impairment pattern of deficit schizophrenia (DS) is centered on an impaired attention function. Previous studies have suggested that the exploratory eye movement (EEM) tests reflect attention deficits in patients with schizophrenia. However, no study has investigated the characteristics of eye movement in DS in the Chinese Han population. This study aimed to investigate the pattern of eye movement characteristics in DS patients and to examine whether eye movement characteristic is associated with serious negative symptoms and cognitive decline in this schizophrenia subtype. METHODS: A total of 86 male patients [37 DS and 49 non-deficit schizophrenia (NDS)] and 80 healthy controls (HC) participated in this study. Clinical symptoms were assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). Cognitive function was assessed using the Mattis Dementia Rating Scale (MDRS-2). Eye movement data of subjects were collected using an eye movement tracking analyzer. RESULTS: There were significant differences in the overall eye movement data and cognitive test scores among the three groups (all P < 0.001). Both DS and NDS schizophrenia subgroups showed more severe eye movement and cognitive impairment compared with the control group. The number of eye fixations (NEF), total of eye scanning length (TESL), and cognitive function in DS patients were significantly lower than those in NDS patients. The discriminant analysis (D score) was higher than that of the control group (P < 0.001). In the DS group, the inattention factor of SANS was negatively correlated with the attention factor (r = - 0.545, P = 0.001) and structure factor of cognitive (r = - 0.389, P = 0.023), the affective flattening factor of SANS was negatively correlated with TESL (r = - 0.353, P = 0.041) and initiation/retention factor of cognitive (r = - 0.376,P = 0.028). TESL was found to positively correlate with the MDRS-2 total score (r = 0.427, P = 0.012), attention factor (r = 0.354, P = 0.040), and memory factor (r = 0.349, P = 0.043) in the DS group, whereas the mean of eye scanning length (MESL) positively correlated with cognitive impairments in the NDS group. The negative symptoms showed no significant correlation with cognition in the NDS group. CONCLUSIONS: Total of eye scanning length may be a characteristic eye movement symptom in DS patients, which is associated with serious negative symptoms and cognitive impairment in this schizophrenia subtype.

Anhedonia difference between major depressive disorder and bipolar disorder II.

OBJECTIVE: This study aims to explore the difference in anhedonia between Major Depressive Disorder (MDD) and Bipolar Disorder II (BD-II), and attempt to distinguish the two diseases through Snaith-Hamilton Pleasure Scale (SHAPS). METHODS: A total of 164 drug-free depressive patients (98 MDD patients, 66 BD-II patients) completed the investigation. 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA) and SHAPS were assessed in all participants. RESULTS: Our results showed that BD-II patients had higher SHAPS scores than MDD patients. The stepwise logistic regression analysis further revealed that SHAPS score, drinking habit, and extroversion as influencing factors for the identification of BD-II. The ROC curve analysis indicated that SHAPS could differentiate BD-II from MDD patients (AUC = 0.655, P = 0.001, 95% CI = 0.568 to 0.742), with the best screening cutoff at 26, and the corresponding sensitivity and specificity was 0.788 and 0.520, respectively. CONCLUSION: Our results suggest that BD-II patients had more severe anhedonia compared to MDD patients, and the difference in anhedonia may help clinicians preliminary identify BD patients from MDD patients. The preliminary findings are worthly of further exploration.

Development and evaluation of puerarin-loaded controlled release nanostructured lipid carries by central composite design.

The present work was aimed at developing optimized puerarin-loaded nanostructured lipid carrier (PA-NLC) on base of phospholipid complex. The puerarin phospholipid complex (PA-PC) was prepared by a solvent evaporation method and the formulation was confirmed according to the encapsulation efficiency (EE%). The hepatoprotective effect of PA-NLC on BRL 3A cell stimulated by ethanol was carried out using MTT assay, and cell imaging was done using an inverted phase contrast tissue culture microscope. The NLCs were produced by nanoemulsion method using glyceryl monostearate (GMS), olive oil, and Poloxamer 188 as the solid, liquid lipids, and surfactant. A single factor analysis determined the optimal ratio of solid lipid to liquid lipid. A three-factor, five-level central composite design (CCD) was used to predict response variables and construct 3D-response contour plots. The independent variables, which were the concentrations of PA-PC, total lipid, and surfactant affected particle size, surface charge of the nanoparticles, and the EE. An optimized NLC composition consisted of 31.25% PA-PC, 46.87% GMS, 9.38% olive oil, and 18.75% Poloxamer 188. The NLC had an average particle size of 159 ± 1.1 nm, zeta potential of -28.3 mV, EE% of 92.16%, and drug loading (DL%) of 5.75%. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) studies showed that the formation of NLC was accompanied by changes in crystallinity and intermolecular interaction. The PA-NLC system showed an enhanced therapeutic effect on alcohol-induced cell injury of BRL-3A.

Bio-semantic relation extraction with attention-based external knowledge reinforcement.

BACKGROUND: Semantic resources such as knowledge bases contains high-quality-structured knowledge and therefore require significant effort from domain experts. Using the resources to reinforce the information retrieval from the unstructured text may further exploit the potentials of such unstructured text resources and their curated knowledge. RESULTS: The paper proposes a novel method that uses a deep neural network model adopting the prior knowledge to improve performance in the automated extraction of biological semantic relations from the scientific literature. The model is based on a recurrent neural network combining the attention mechanism with the semantic resources, i.e., UniProt and BioModels. Our method is evaluated on the BioNLP and BioCreative corpus, a set of manually annotated biological text. The experiments demonstrate that the method outperforms the current state-of-the-art models, and the structured semantic information could improve the result of bio-text-mining. CONCLUSION: The experiment results show that our approach can effectively make use of the external prior knowledge information and improve the performance in the protein-protein interaction extraction task. The method should be able to be generalized for other types of data, although it is validated on biomedical texts.

Bacteriological profiles and drug susceptibility of Streptococcus isolated from conjunctival sac of healthy children.

BACKGROUND: To investigate bacterial flora and antibiotics susceptibility of Streptococcus pneumoniae isolated from the conjunctival sac of heathy children. METHODS: Bacteria were isolated from the secretions of conjunctival sac of healthy children between 2015 and 2018. Antimicrobial susceptibility of isolated S. pneumoniae strains were determined using microbroth dilution method. RESULTS: The sac secretions were collected from a total of 6440 children. 1409 samples presented bacterial growth, accounting for 21.8% of the samples. Among the 22 bacterial species isolated, 528 samples presented Gram-positive Staphylococcus spp. growth, accounting for 37.4% of the isolates, followed by Corynebacterium spp., counting for 30% of the isolates and Streptococcus pneumoniae, counting for 21.4% of the isolates. Antibiotics susceptibility tests showed that the majority of S. pneumoniae isolates were sensitive to most antibiotics tested. However, 72.8 and 81.2% of the isolates were resistant to erythromycin and tetracycline, respectively, and over 10% of them were resistant to gentamicin, tobramycin and rifampicin. CONCLUSIONS: The bacterial flora of healthy children is mainly consisted of Gram-positive bacteria belonging to Corynebacterium spp. and Streptococcus spp.; most of S. pneumoniae isolates were sensitive to antibiotics except erythromycin and tetracycline.

Prevalence, Sociodemographic, and Clinical Correlates of Older Chinese Patients With Deficit Schizophrenia.

OBJECTIVE: No study has investigated the frequency and risk factors for deficit schizophrenia (DS) in Chinese Han population. We investigated the prevalence of DS among community-dwelling older Chinese patients with schizophrenia and examined the sociodemographic and clinical correlates of DS in this population. METHODS: A total of 326 community-dwelling older patients with schizophrenia were recruited in this cross-sectional study. Deficit schizophrenia was confirmed using the Chinese version of the Schedule for the Deficit Syndrome. Data pertaining to sociodemographic and clinical characteristics were collected. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The prevalence of DS in the study population was 26.7% (31.2% among male patients and 21.6% among female patients with schizophrenia). Patients with DS had significantly higher current smoking rate, hospitalizations, PANSS negative score, PANSS total score, and had earlier age at onset than patients with non-deficit schizophrenia (N-DS). The N-DS patients had higher PANSS positive scores and a greater proportion of married patients. Multiple logistic regression analysis indicated that negative PANSS score (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04-1.16, P < .001), male sex (OR = 1.71, 95% CI = 1.53-1.91, P = .037), age at onset (OR = 0.88, 95% CI = 0.82-0.94, P = .035), and current smoking (OR = 1.37, 95% CI = 1.15-1.63, P = .041) were independently associated with DS. CONCLUSION: Deficit schizophrenia is relatively common among older community-dwelling Chinese patients with schizophrenia. High negative symptom scores, male sex, early onset, and smoking were independent correlates for DS.

Serum BDNF and GDNF in Chinese male patients with deficit schizophrenia and their relationships with neurocognitive dysfunction.

BACKGROUND: To measure the serum levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) in deficit schizophrenia (DS), in order to examine the association between these two neurotrophic factors (NFs) and cognitive performance. METHODS: A total of 109 male patients [51 DS and 58 non-deficit schizophrenia (NDS)] with schizophrenia and 40 sex and age matched healthy controls (HC) participated in this study. Processing speed, attention, executive function, and working memory of all subjects were assessed by means of a battery of classical neuropsychological tests. Serum BDNF and GDNF levels were measured simultaneously using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: There were significant differences in the overall cognitive test scores between three groups (all p < 0.001). Serum BDNF levels were significantly lower in patients (DS and NDS) than in HC (p < 0.001). Furthermore, BDNF levels were lower in the DS compared to the NDS group, although not significantly. However, there was no difference in the GDNF levels between patients (DS and NDS) and HC. GDNF levels were positively correlated with scores of Stroop words only (r = 0.311, p = 0.033), Stroop colors only (r = 0.356, p = 0.014) and Stroop interference (r = 0.348, p = 0.016) in DS group. CONCLUSION: Serum BDNF may be an unsuitable biomarker for DS, despite a significant decrease in schizophrenia patients. The different neurocognitive performance between the DS and NDS patients indicates that DS may be a separate clinical entity of schizophrenia. Finally, higher serum GDNF levels are associated with better cognitive performance in DS patients, indicating a possible neuroprotective function in DS.