Impact of early cognitive impairment on outcome trajectory in patients with intracerebral hemorrhage.

OBJECTIVE: To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short-term recovery trajectories among ICH patients with early cognitive impairment. METHODS: We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini-mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. RESULTS: Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1-year increase, 1.037; 95% confidence interval [CI], 1.003-1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1-point increase, 1.146; 95% CI, 1.065-1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810-12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133-0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503-12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). INTERPRETATION: Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short-term functional recovery.

DNA methylation-activated full-length EMX1 facilitates metastasis through EMX1-EGFR-ERK axis in hepatocellular carcinoma.

Altered DNA methylation is a crucial epigenetic event in hepatocellular carcinoma (HCC) development and progression. Through methylation-transcriptomic analysis, we identified a set of sixty potential DNA methylation-based epidriver genes. In this set of genes, we focused on the hypermethylation of EMX1, which is frequently observed in hepatobiliary tumors. Despite of its frequent occurrence, the function of EMX1 remains largely unknown. By utilizing bisulfite-next-generation sequencing, we have detected EMX1 DNA hypermethylation on the gene body, which is positively correlated with EMX1 mRNA expression. Further analysis revealed that EMX1 mRNA terminal exon splicing in HCC generated two protein isoforms: EMX1 full length (EMX1-FL) and alternative terminal exon splicing isoform (EMX1-X1). Cellular functional assays demonstrated that gain-of-function EMX1-FL, but not EMX1-X1, induced HCC cells migration and invasion while silencing EMX1-FL inhibited HCC cells motility. This result was further validated by in vivo tumor metastasis models. Mechanistically, EMX1-FL bound to EGFR promoter, promoting EGFR transcription and activating EGFR-ERK signaling to trigger tumor metastasis. Therefore, EGFR may be a potential therapeutic target for EMX1-high expression HCC. Our work illuminated the crucial role of gene body hypermethylation-activated EMX1-FL in promoting tumorigenesis and metastasis in HCC. These findings pave the way for targeting the EMX1-EGFR axis in HCC tumorigenicity and metastasis.

Gender differences in clinical characteristics of patients with non-cystic fibrosis bronchiectasis in different age groups in northern China.

INTRODUCTION: Patient gender has clinical and prognostic implications in non-cystic fibrosis bronchiectasis, yet the potential effect of gender on clinical characteristics of patients with non-cystic fibrosis bronchiectasis is still unclear. OBJECTIVES: This study aimed to investigate the gender differences in clinical characteristics of patients with bronchiectasis in different age groups in northern China. METHODS: A total of 777 patients diagnosed with bronchiectasis were retrospectively included in Beijing Chaoyang Hospital and divided into two groups by gender: the male group and the female group. Each group was then subdivided into two according to their age (≤65 and >65 years). Gender differences in clinical characteristics were compared in all patients with bronchiectasis in the two age groups, respectively. RESULTS: A total of 777 bronchiectasis patients were included. Of these patients, the prevalence of female non-smokers was substantially higher than that of male non-smokers (94.0% vs. 36.8%). There were gender differences in etiology of bronchiectasis, with more post-measles and connective tissue disease in females (p = 0.006 and 0.002 separately) and more chronic obstructive pulmonary disease (COPD) in males (p < 0.001). The male group had a significantly higher C-reactive protein (CRP) on admission (p = 0.03). Female patients showed a higher forced expiratory volume in 1 s as percentage of predicted volume (FEV1%pred) and forced vital capacity rate of 1 s (FEV1/FVC) (p < 0.001), lower partial pressure of carbon dioxide (PaCO2 ) (p = 0.04) and hospital costs (p = 0.02) than males, and a higher prevalence of infection with Pseudomonas aeruginosa in >65-year-old group (p = 0.019). CONCLUSIONS: There were many differences between male and female patients in smoking status, etiology, lung function, blood gas analysis, and hospital costs in all patients or different age groups.

Altered resting-state network connectivity patterns for predicting attentional function in deaf individuals: An EEG study.

Multiple aspects of brain development are influenced by early sensory loss such as deafness. Despite growing evidence of changes in attentional functions for prelingual profoundly deaf, the brain mechanisms underlying these attentional changes remain unclear. This study investigated the relationships between differential attention and the resting-state brain network difference in deaf individuals from the perspective of brain network connectivity. We recruited 36 deaf individuals and 34 healthy controls (HC). We recorded each participant's resting-state electroencephalogram (EEG) and the event-related potential (ERP) data from the Attention Network Test (ANT). The coherence (COH) method and graph theory were used to build brain networks and analyze network connectivity. First, the ERPs of analysis in task states were investigated. Then, we correlated the topological properties of the network functional connectivity with the ERPs. The results revealed a significant correlation between frontal-occipital connection in the resting state and the amplitude of alert N1 amplitude in the alpha band. Specifically, clustering coefficients and global and local efficiency correlate negatively with alert N1 amplitude, whereas the characteristic path length positively correlates with alert N1 amplitude. In addition, deaf individuals exhibited weaker frontal-occipital connections compared to the HC group. In executive control, the deaf group had longer reaction times and larger P3 amplitudes. However, the orienting function did not significantly differ from the HC group. Finally, the alert N1 amplitude in the ANT task for deaf individuals was predicted using a multiple linear regression model based on resting-state EEG network properties. Our results suggest that deafness affects the performance of alerting and executive control while orienting functions develop similarly to hearing individuals. Furthermore, weakened frontal-occipital connections in the deaf brain are a fundamental cause of altered alerting functions in the deaf. These results reveal important effects of brain networks on attentional function from the perspective of brain connections and provide potential physiological biomarkers to predicting attention.

Dual regulation of lipid droplet-triacylglycerol metabolism and ERG9 expression for improved ß-carotene production in Saccharomyces cerevisiae.

BACKGROUND: The limitation of storage space, product cytotoxicity and the competition for precursor are the major challenges for efficiently overproducing carotenoid in engineered non-carotenogenic microorganisms. In this work, to improve ß-carotene accumulation in Saccharomyces cerevisiae, a strategy that simultaneous increases cell storage capability and strengthens metabolic flux to carotenoid pathway was developed using exogenous oleic acid (OA) combined with metabolic engineering approaches. RESULTS: The direct separation of lipid droplets (LDs), quantitative analysis and genes disruption trial indicated that LDs are major storage locations of ß-carotene in S. cerevisiae. However, due to the competition for precursor between ß-carotene and LDs-triacylglycerol biosynthesis, enlarging storage space by engineering LDs related genes has minor promotion on ß-carotene accumulation. Adding 2 mM OA significantly improved LDs-triacylglycerol metabolism and resulted in 36.4% increase in ß-carotene content. The transcriptome analysis was adopted to mine OA-repressible promoters and IZH1 promoter was used to replace native ERG9 promoter to dynamically down-regulate ERG9 expression, which diverted the metabolic flux to ß-carotene pathway and achieved additional 31.7% increase in ß-carotene content without adversely affecting cell growth. By inducing an extra constitutive ß-carotene synthesis pathway for further conversion precursor farnesol to ß-carotene, the final strain produced 11.4 mg/g DCW and 142 mg/L of ß-carotene, which is 107.3% and 49.5% increase respectively over the parent strain. CONCLUSIONS: This strategy can be applied in the overproduction of other heterogeneous FPP-derived hydrophobic compounds with similar synthesis and storage mechanisms in S. cerevisiae.

Research progress of the paraventricular thalamus in the regulation of sleep-wake and emotional behaviors.

The paraventricular thalamus (PVT) is a major component of the midline structure of the thalamus. It is one of the nonspecific nuclei of the thalamus, which plays a great role in the regulation of cortical arousal. PVT, an important node in the central nervous system, sends widespread outputs to many brain regions and also accepts plentiful inputs from many brain regions to modulate diverse functions, including sleep-wake state, attention, memory, and pain. Recently, with the increasing prevalence of sleep disorders and mood disorders, people pay great attention to PVT, which was implicated in arousal and emotional behaviors. Therefore, the main purpose of this review is to illustrate the characteristic of PVT to provide a reference for future research.

Oxygen Metabolism-induced Stress Response Underlies Heart-brain Interaction Governing Human Consciousness-breaking and Attention.

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions.

Toripalimab Combined With Hepatic Arterial Infusion Chemotherapy Versus Lenvatinib for Advanced Hepatocellular Carcinoma.

Purpose: Immunotherapy combined with chemotherapy have synergistic effects in multiple malignancies. We aimed to compare the efficacy and safety of toripalimab plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin versus lenvatinib in advanced hepatocellular carcinoma (HCC). Materials and Methods: We conducted this retrospective study at 3 hospitals in China and eligible patients were 18 years or older and had a primary diagnosis of unresectable HCC with macroscopic vascular invasion and/or extrahepatic spread. These patients were treated with toripalimab plus HAIC or lenvatinib monotherapy. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were overall survival (OS), disease control rate per response evaluation criteria in solid tumors (RECIST) 1.1, and objective response rate (ORR) per RECIST 1.1. The results were compared by Student's test or the chi-square test, and the survival curves were calculated by the Kaplan-Meier method, and propensity-score matching (PSM) was used to reduce bias. Results: A total of 118 patients were recruited for this study: 53 in the TorHAIC group and 65 in the lenvatinib group. We found that the TorHAIC group showed a longer PFS (9.3 [95% CI, 7.81-10.8] vs 4.8 months [95% CI, 3.31-6.29]; hazard ratio [HR] = 0.57, 95% CI, 0.38-0.85; p = .006), a longer OS (17.13 [95% CI, 13.99-20.27] vs 10.1 months [95% CI, 8.14-12.06]; HR = 0.5, 95% CI, 0.31 - 0.81; p = .005), a higher disease control rate (86.8% vs 69.2%, p = .002) and a higher ORR (47.2% vs 9.2%, p < .001) by RECIST criteria than the lenvatinib group. Both toripalimab plus HAIC and lenvatinib had acceptable safety profiles. No treatment-related deaths occurred in this study. In the propensity score-matched cohorts (47 pairs), the outcomes in the TorHAIC group were also better than those in the lenvatinib group (p < .05). Conclusion: Toripalimab plus HAIC was tolerable and effective in advanced HCC and the result needs to be confirmed in the phase III trial.

Construction of a single nucleotide variant score-related gene-based prognostic model in hepatocellular carcinoma: analysis of multi-independent databases and validation in vitro.

BACKGROUND: The accumulation of single nucleotide variants (SNVs) and the emergence of neoantigens can affect tumour proliferation and the immune microenvironment. However, the SNV-related immune microenvironment characteristics and key genes involved in hepatocellular carcinoma (HCC) are still unclear. We aimed to evaluate differences in the SNV-related immune microenvironment, construct a prognostic model and validate the key genes in vitro. METHODS: The categories of samples were defined by the expression of SNV score-related genes to evaluate the differences in mutational features, immune environment and prognosis. The survival model was constructed with survival-associated genes and verified in two independent test datasets. RCAN2, the key gene screened out for biofunction, was validated in vitro. RESULTS: IC2, among the three integrated clusters (IC1, IC2, IC3) classified by the 82 SNV score-related genes, was distinct from the rest in SNV score and immune cell infiltration, showing a better prognosis. Seven prognostic markers, HTRA3, GGT5, RCAN2, LGALS3, CXCL1, CLEC3B, and CTHRC1, were screened to construct a prognostic model. The survival model distinguished high-risk patients with poor prognoses in three independent datasets (log-rank P < 0.0001, 0.011, and 0.0068, respectively) with acceptable sensitivity and specificity. RCAN2 was inversely correlated with NK cell infiltration, and knockdown of RCAN2 promoted proliferation in HCC. CONCLUSIONS: This study revealed the characteristics of the HCC SNV-associated subgroup and screened seven latent markers for their accuracy of prognosis. Additionally, RCAN2 was preliminarily proven to influence proliferation in HCC and it had a close relationship with NK cell infiltration in vitro. With the capability to predict HCC outcomes, the model constructed with seven key differentially expressed genes offers new insights into individual therapy.

A Conjugative MDR pMG1-Like Plasmid Carrying the lsa(E) Gene of Enterococcus faecium With Potential Transmission to Staphylococcus aureus.

lsa(E) is a pleuromutilin, lincosamide, and streptogramin A (PLSA phenotype) resistance gene that was first described in S. aureus and was thought to have been transferred from Enterococcus sp. This study aimed to elucidate the prevalence of the lsa(E) gene among E. faecium isolates at a tertiary teaching hospital and to evaluate the transferability of the lsa(E) gene from E. faecium to S. aureus in vitro. A total of 96 E. faecium strains isolated from one hospital in Beijing in 2013 were analysed for quinupristin-dalfopristin (QDA) resistance genes, and multilocus sequence typing (MLST) was performed. The transferability of QDA resistance between ten E. faecium strains and four S. aureus strains was determined by filter mating. Genome sequencing of the transconjugant was performed. A total of 46 E. faecium isolates (46/96, 47.92%) tested positive for lsa(E), while two isolates (2/96, 2.08%) tested positive for lsa(A). Thirty-six lsa(E)-positive strains (36/46, 78.3%) belonged to ST78. Among 40 mating tests, lsa(E) was successfully transferred through one conjugation at a frequency of 1.125 × 10-7 transconjugants per donor. The QDA resistance of the transconjugant N7435-R3645 was expressed at a higher level (MIC = 16 mg/L) than that of the parent S. aureus strain (MIC = 0.38 mg/L). Next-generation sequencing (NGS) analysis of the transconjugant N7435-R3645 showed that the complete sequence of the lsa(E)-carrying plasmid pN7435-R3645 had a size of 92,396 bp and a G + C content of 33% (accession no. MT022086). The genetic map of pN7435-R3645 had high nucleotide similarity and shared the main open reading frame (ORF) features with two plasmids: E. faecium pMG1 (AB206333.1) and E. faecium LS170308 (CP025078.1). The rep gene of pN7435-R3645 showed 100% identity with that of pMG1, although it did not belong to the rep1-19 family but instead a unique rep family. Multiple antibiotic resistance genes, including lsa(E), aadE and lnu(B), erm(B), ant6-Ia, and lnu(B), were present on the plasmid. In conclusion, an lsa(E)-carrying plasmid that can be transferred by conjugation from E. faecium to S. aureus in vitro was identified. This multidrug resistance (MDR) pMG1-like plasmid may act as a vector in the dissemination of antimicrobial resistance among species.

Hepatic Arterial Infusion Chemotherapy of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Sorafenib as Initial Treatment for Advanced Hepatocellular Carcinoma.

PURPOSE: Our previous study showed that hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) plus sorafenib provided a significant survival benefit over sorafenib for advanced hepatocellular carcinoma. However, it is unclear whether the survival benefit should be attributed to the synergism between HAIC and sorafenib or just HAIC alone. We aim to compare HAIC using FOLFOX plus sorafenib with HAIC alone in patients with advanced hepatocellular carcinoma. MATERIALS AND METHODS: This was a retrospective study including 225 eligible patients treated with HAIC using FOLFOX (HAIC alone group, n=126, oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil bolus 400 mg/m² and 2400 mg/m² for 46 hours, every 3 weeks) alone or HAIC plus sorafenib (soraHAIC group, n=99, sorafenib 400 mg twice daily). Survival curves were calculated by the Kaplan-Meier method, and propensity-score matching was used to reduce bias. RESULTS: The soraHAIC group showed a longer overall survival (12.9 [95% CI, 10.4-15.4] vs. 10.5 [95% CI, 9.5-11.5] months, HR=0.71 [95% CI, 0.53-0.96]; P=0.025), a better progression free survival (7.0 [95% CI, 5.3-8.8] vs. 5.3 [95% CI, 3.5-7.1] months, HR=0.76 [95% CI, 0.58-0.99]; P=0.046), and a higher disease control rate (RECIST 1.1: 74.8% vs. 61.1%, P=0.030) than the HAIC alone group. In multivariate analysis, soraHAIC was an independent favor factor for survival. In terms of the grade 3/4 adverse event, hand-foot skin reaction was more frequent in the soraHAIC group than the HAIC alone group. In the propensity-score matched cohorts (93 pairs), the overall survival, the progression free survival and disease control rates in the soraHAIC group were also better than those in the HAIC group (P<0.05). CONCLUSION: HAIC plus sorafenib may improve overall survival and progression free survival compared with HAIC alone as initial treatment for advanced hepatocellular carcinoma.

[Effect of single hyperbaric oxygen treatment on attention networks in young migrants in Tibet].

Many studies have shown that high-altitude exposure could significantly influence human cognition, and the approaches which could enhance the human cognition in high-altitude hypoxia environment attract great attention. In the present study, we recruited a total of 60 subjects who had been migrated to Tibet University as adults for more than one year. These participants were randomly divided into the experimental group and the control group. The participants in the experimental group were instructed to complete a hyperbaric oxygen treatment, and those in the control group just completed a wait condition. By using the attention network test (ANT), the changes of the attention function before and after a single session of hyperbaric oxygen treatment were explored. The results showed that single hyperbaric oxygen treatment significantly improved the orienting function of attention, with an obvious post-intervention effect, but not the alerting and conflict function of attention. We also found a strong association between alerting function and conflict function after the end of intervention, suggesting the change of the overall performance of attention function. The present findings might suggest that the improvement of attention function by a single session of hyperbaric oxygen intervention is derived from the increase of general cognitive resources, rather than the transfer of cognitive resources within the attention system.

The mental health of Chinese women with polycystic ovary syndrome is related to sleep disorders, not disease status.

BACKGROUND: Mental health disorders are highly prevalent in polycystic ovary syndrome (PCOS) cases. The etiology for anxiety/depression in women with PCOS still remains unclear, due to conflicting results. AIM: To examine whether an association exists between the mental health of Chinese women with PCOS and various indicators such as their disease characteristics, biochemistry results and sleep status. METHODS: During July 2018 and January 2020, our study included a total of 433 women diagnosed with PCOS at Chongqing Hospital of Traditional Chinese Medicine. Sleep-related variables were evaluated by the Pittsburgh Sleep Quality Index (PSQI), anxiety and depression values were quantified by the Hospital Anxiety and Depression Scale (HADS), and biochemistry results were collected from the medical records of the patients. RESULTS: 26.6% patients resulted as positive anxiety and 23.6% as positive depression. We found significant associations between anxiety/depression status and sleep conditions of PCOS patients. More specifically, anxiety significantly associated with sleep quality OR (95%CI) = 1.611 (1.147-2.261), sleep disturbance 2.326 (1.468-3.685) and daytime dysfunction 1.457 (1.122-1.891). Similarly, depression significantly associated with sleep quality 1.467 (1.043-2.063), sleep disturbance 1.624 (1.030-2.561) and daytime dysfunction 1.406 (1.077-1.836). There was no association detected between mental health and disease characteristics, as well as reproductive and metabolic indicators in PCOS. LIMITATION: Cross-sectional nature of the data prevents causal associations, selection bias of a hospital-based population. CONCLUSIONS: Sleep-related disorders might be involved in the etiology and development of the anxiety/depression observed in PCOS cases. We propose that management of sleep disorders should be an integral part of the disease management of women with PCOS.

Engineering endogenous ABC transporter with improving ATP supply and membrane flexibility enhances the secretion of ß-carotene in Saccharomyces cerevisiae.

BACKGROUND: Product toxicity is one of the bottlenecks for microbial production of biofuels, and transporter-mediated biofuel secretion offers a promising strategy to solve this problem. As a robust microbial host for industrial-scale production of biofuels, Saccharomyces cerevisiae contains a powerful transport system to export a wide range of toxic compounds to sustain survival. The aim of this study is to improve the secretion and production of the hydrophobic product (ß-carotene) by harnessing endogenous ABC transporters combined with physiological engineering in S. cerevisiae. RESULTS: Substrate inducibility is a prominent characteristic of most endogenous transporters. Through comparative proteomic analysis and transcriptional confirmation, we identified five potential ABC transporters (Pdr5p, Pdr10p, Snq2p, Yor1p, and Yol075cp) for ß-carotene efflux. The accumulation of ß-carotene also affects cell physiology in various aspects, including energy metabolism, mitochondrial translation, lipid metabolism, ergosterol biosynthetic process, and cell wall synthesis. Here, we adopted an inducible GAL promoter to overexpress candidate transporters and enhanced the secretion and intracellular production of ß-carotene, in which Snq2p showed the best performance (a 4.04-fold and a 1.33-fold increase compared with its parental strain YBX-01, respectively). To further promote efflux capacity, two strategies of increasing ATP supply and improving membrane fluidity were following adopted. A 5.80-fold increase of ß-carotene secretion and a 1.71-fold increase of the intracellular ß-carotene production were consequently achieved in the engineered strain YBX-20 compared with the parental strain YBX-01. CONCLUSIONS: Overall, our results showcase that engineering endogenous plasma membrane ABC transporters is a promising approach for hydrophobic product efflux in S. cerevisiae. We also highlight the importance of improving cell physiology to enhance the efficiency of ABC transporters, especially energy status and cell membrane properties.

Do higher-class individuals feel more entitled? The role of system-justifying belief.

Sense of entitlement can be defined as a pervasive sense that one deserves more and is entitled to more than others. Two studies examined the relationship between social class and sense of entitlement and how this relationship is moderated by system-justifying belief (SJB) in China. In Study 1, we conducted a survey among adults (N = 669) with results showing that social class was positively correlated with sense of entitlement for those endorsing SJB, but negatively correlated with sense of entitlement for those opposing SJB. In Study 2, we conducted an experiment among undergraduates (N = 128) with both social class and SJB being primed and the results replicated the pattern: the positive effect of primed higher social class on pay entitlement existed only for those primed with high SJB, and was dampened for those primed with low SJB. Therefore, higher-class individuals do not necessarily feel more entitled, and SJB may play an important role in shaping their sense of entitlement.

Serum cystatin C levels are negatively correlated with post-stroke cognitive dysfunction.

Stroke is the leading cause of death and long-term disability worldwide, and cognitive impairment and dementia are major complications of ischemic stroke. Cystatin C (CysC) has been found to be a neuroprotective factor in animal studies. However, the relationship between CysC levels and cognitive dysfunction in previous studies has revealed different results. This prospective observational study investigated the correlation between serum CysC levels and post-stroke cognitive dysfunction at 3 months. Data from 638 patients were obtained from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE) at 3 months after stroke. According to the MMSE score, 308 patients (52.9%) had post-stroke cognitive dysfunction. After adjusting for potential confounding factors, the odds ratio (95% CI) of post-stroke cognitive dysfunction for the highest quartile of serum CysC levels was 0.54 (0.30-0.98), compared with the lowest quartile. The correlation between serum CysC and cognitive dysfunction was modified by renal function status. We observed a negative linear dose-response correlation between CysC and cognitive dysfunction in patients with normal renal function (Plinearity = 0.044), but not in those with abnormal renal function. Elevated serum CysC levels were correlated with a low risk of 3-month cognitive dysfunction in patients with acute ischemic stroke, especially in those with normal renal function. The current results suggest that CysC is a protective factor for post-stroke cognitive dysfunction, and could be used to treat post-stroke cognitive dysfunction. The CATIS study was approved by the Institutional Review Boards at Soochow University from China (approval No. 2012-02) on December 30, 2012, and was registered at ClinicalTrials.gov (identifier No. NCT01840072) on April 25, 2013.

[Comparative observation of acupoint thread-embedding and acupuncture therapy of Shugan Tiaoshen for insomnia of liver depression and qi stagnation].

OBJECTIVE: To compare the effect of Shugan Tiaoshen (soothing the liver and regulating mind) acupoint thread-embedding therapy and Shugan Tiaoshen acupuncture therapy for insomnia of liver depression and qi stagnation. METHODS: A total of 68 patients with insomnia of liver depression and qi stagnation were randomly divided into an acupoint embedding group (34 cases) and an acupuncture group (34 cases). Two groups were respectively treated with acupoint thread-embedding and acupuncture at Baihui (GV 20), Shenmen (HT 7), Neiguan (PC 6), Taichong (LR 3), Ganshu (BL 18) and Xinshu (BL 15). The treatment in the acupoint embedding group was given once a week, and in the acupuncture group was given once every other day for 6 weeks. The Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS), self-rating depression scale (SDS), TCM syndrome scores before and after treatment and medical expenses were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: After treatment, the PSQI total scores, each sub-item score and SAS and SDS scores of the two groups were lower than those before treatment (P<0.05); the sleep quality, time during fall asleep, sleep time, sleep efficiency, daytime dysfunction scores and PSQI total score in the acupoint embedding group after treatment were lower than those in the acupuncture group (P<0.05). After treatment, except for constipation and yellowish urine, the sub-item scores and total scores of TCM syndromes in the two groups were lower than those before treatment (P<0.05); the sleep disturbance score of the acupoint embedding group was lower than that of the acupuncture group (P<0.05). The medical expenses in the acupoint embedding group was lower than that in the acupuncture group (P<0.05). The total effective rate of the acupoint embedding group was 85.3% (29/34), and the acupuncture group was 82.4% (28/34), there was no significant difference between the two groups (P>0.05). CONCLUSION: Shugan Tiaoshen acupoint thread-embedding therapy and Shugan Tiaoshen acupuncture therapy both have significant curative effect on insomnia of liver depression and qi stagnation, but acupoint thread-embedding therapy is better than acupuncture therapy in improving sleep quality and reducing medical expenses.

Association between IDH1/2 mutations and brain glioma grade.

Isocitrate dehydrogenase 1/2 (IDH)1/2 mutations are frequently detected in glioma. The aim of the present study was to investigate the association between IDH1/2 mutations and glioma grades. The current study was retrospective and used samples from 206 patients with brain glioma and 9 patients with spinal cord glioma as a control. Patients were diagnosed and graded according to the World Health Organization classification of tumors of the central nervous system. The association of patient age with glioma grade was evaluated, and IDH1/2 mutations were also examined and analyzed in different grades. On average, brain glioma grade tended to increase with increasing patient age; patients with grade IV (primary) gliomas had a significantly higher mean age than those with grades I and II (P<0.05), and patients with grade II glioma had a significantly lower mean age than those with grade III (P<0.05). The majority of brain gliomas with mutations in IDH1/2 in grade II, II-III and III occurred in adults, rather than adolescents. IDH1/2 mutations occurred most frequently in grade II, II-III and III gliomas, and these mutation frequencies differed significantly between brain glioma grades (P<0.001). In summary, mutations in IDH1/2 were associated with grade II, II-III and III brain gliomas, and possibly with the progression of brain glioma from grade II to grade III.

Quantitative analysis of chloramphenicol, thiamphenicol, florfenicol and florfenicol amine in eggs via liquid chromatography-electrospray ionization tandem mass spectrometry.

A widely applicable method involving liquid chromatography-electrospray ionization tandem triple quadrupole mass spectrometry (LC-ESI/MS/MS) was developed for the simultaneous determination of chloramphenicol, thiamphenicol, florfenicol, and florfenicol amine in eggs. Samples were extracted with ethyl acetate-acetonitrile-ammonium hydroxide (49:49:2, v/v) and defatted with hexane saturated with acetonitrile. The analysis was carried out on a mass spectrometer via an electrospray interface operated in the positive and negative ionization modes using deuterated chloramphenicol-d5 as the internal standard. The limits of detection and limits of quantification were 0.04-0.5 µg/kg and 0.1-1.5 µg/kg in eggs, respectively. The average recoveries of the four analytes from egg samples were 90.84-108.23%, with relative standard deviations of less than 9.61%. The corresponding intra-day and inter-day variations were found to be less than 8.11% and 11.30%, respectively. Finally, the new approach was successfully applied to the quantitative determination of these analytes in 50 commercial eggs from local supermarkets.