Polystyrene microplastics (PS-MPs) are common microplastics that pose significant health hazards to humans. Due to multifunctionality in the gut system, MP-associated damage and mechanisms require further exploration. This study was undertaken with the objective of elucidating the impact of PS-MP exposure on colonic inflammation in rats, and to explore its potential mechanisms. Forty-eight specific-pathogen-free Wistar male rats were administered 0, 0.5, 5, and 50 mg/kg/d of PS-MPs for 90 days, after which intestinal flora distribution, inflammatory factor levels in the colon, and TLR4/NF-kappa B/COX-2 gene levels were examined. To clarify whether PS-MPs directly infiltrate intestinal epithelial cells and induce cytotoxicity, human intestinal epithelial cells (HIECs) were exposed to a range of PS-MP concentrations (0 similar to 100 mu g/mL) for 48 h, and CCK-8 assays were conducted to assess the cell survival rates. In the colon tissue of rats exposed to PS-MP, goblet cells decreased, muscular layer arrangements were disordered, and disrupted and discontinuous crypt structures appeared in colon tissue, while high numbers of inflammatory cells infiltrated the colonic mucosa and submucosa. PS-MPs could accumulate in HIECs, and cell survival rates were decreased. In the colons of rats exposed to PS-MPs, the levels of Interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were found to be elevated. Additionally, the mRNA and protein levels of TLR4/MyD88 in the colons of PS-MP-exposed rats exhibited a significant increase. Furthermore, the TLR4/NF-kappa B/COX-2 signaling pathway in rat colons was activated after MP exposure. When the TLR4/NF-kappa B/COX-2 signaling pathway was inhibited, the significant increases in IL-6 and TNF-alpha levels caused by PS-MPs were significantly reversed. PS-MP exposure also altered intestinal flora abundance in rats. Compared with the control group, the proportion of Firmicutes, Proteobacteria and Actinobacteria in PS-MPs exposed group was increased. In contrast, the proportion of Bacteroidetes and Verrucomicrobia decreased. Taken together, our results suggest that PS-MP could exert adverse effects on the gastrointestinal health of rats. Pro-inflammatory cytokine (IL-6, IL-1 beta and TNF-alpha) levels increased, and the TLR4/NF-kappa B/COX-2 signaling pathway was triggered. Thus, flora changes and increased intestinal inflammation may interact with each other.

Mono-(2-ethylhexyl) phthalate (MEHP) can accumulate in the liver and then lead to hepatic steatosis, while the underlying mechanism remains unclear. Inflammation plays an important role in the disorder of hepatic lipid metabolism. This study aims to clarify the role of the inflammatory response mediated by formyl peptide receptor 2 (FPR2) in steatosis of L02 cells exposed to MEHP. L02 cells were exposed to MEHP of different concentrations and different time. A steatosis model of L02 cells was induced with oleic acid and the cells were exposed to MEHP simultaneously. In addition, L02 cells were incubated with FPR2 antagonist and then exposed to MEHP. Lipid accumulation was determined by oil red O staining and extraction assay. The indicators related to lipid metabolism and inflammatory response were measured with appropriate kits. The relative expression levels of FPR2 and its ligand were determined by Western blot, and the interaction of them was detected by co-immunoprecipitation. As a result, MEHP exposure could promote the occurrence and progression of steatosis and the secretion of chemokines and inflammatory factors in L02 cells. MEHP could also affect the expression and activation of FPR2 and the secretion of FPR2 ligands. In addition, the promotion effect of MEHP on the secretion of total cholesterol and interleukin 1β in L02 cells could be significantly inhibited by the FPR2 antagonist. We concluded that FPR2 might affect the promotion effect of MEHP on steatosis of L02 cells by mediating inflammatory response.

OBJECTIVE:To identify an optimal lifestyle profile to protect against memory loss in older individuals. DESIGN:Population based, prospective cohort study. SETTING:Participants from areas representative of the north, south, and west of China. PARTICIPANTS:Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009. MAIN OUTCOME MEASURES:Participants were followed up until death, discontinuation, or 26 December 2019. Six healthy lifestyle factors were assessed: a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items), regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week), active social contact (≥twice per week), active cognitive activity (≥twice per week), never or previously smoked, and never drinking alcohol. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor. Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample. RESULTS:29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10 year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52). CONCLUSION:A healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline. TRIAL REGISTRATION:ClinicalTrials.gov NCT03653156.

IntroductionN-methyl-D-aspartate receptor (NMDAR) is one of the main receptor of the excitatory neurotransmitter glutamate in the brain, which is the key determinant of the excitatory/inhibitory balance of neural network. GluN2A/GRIN2A is one of the subunits of NMDAR and plays an important role in epilepsy. Approximately 78% of patients with GluN2A/Grin2a mutations have epilepsy, and the underlying mechanism of this association is not well characterized.MethodsWe constructed a mouse model of hyperthermic seizure, and conducted in vitro and in vivo electrophysiological and behavioral studies to clarify the pathogenic characteristics and mechanism of GluN2A/GRIN2A-V685G mutation. In addition, the drug efavirenz (EFV), which is used to treat HIV infection, was administrated to mutant animals to assess whether it can restore the loss of function.ResultsMutant mice showed no significant change in the mRNA or protein expressions of NMDAR compared with wild type (WT) mice. Mice with GluN2A/GRIN2A-V685G mutation exhibited shorter latency to seizure, increased frequency of seizure-like events, decreased peak current and current area of NMDAR excitatory postsynaptic current, and decreased event frequency of micro-inhibitory postsynaptic current, compared to WT mice. They also exhibited decreased threshold, increased amplitude, increased input resistance, and increased root number of action potential. EFV administration reversed these changes. The loss-of-function (LoF) mutation of NMDAR changed the excitatory/inhibitory balance of neural network, rendering animal more prone to seizures.DiscussionEFV was indicated to hold its potential in the treatment of inherited epilepsy.

APOE ε4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention. This is the first study to validate GWAS-based predictive models for evaluating the risk of AD onset in a large Chinese population. The clinical application of these models will be beneficial for individuals harbouring these risk variants.

Background China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). Methods For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. Findings Overall age-adjusted and sex-adjusted prevalence was estimated to be 60% (95% CI 58-63) for dementia, 39% (38-41) for Alzheimer's disease, 16% (15-17) for vascular dementia, and 05% (05-06) for other dementias. We estimated that 1507 million (95% CI 1453-1562) people aged 60 years or older in China have dementia: 983 million (939-1029) with Alzheimer's disease, 392 million (364-422) with vascular dementia, and 132 million (116-150) with other dementias. Overall MCI prevalence was estimated to be 155% (152-159), representing 3877 million (3795-3962) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 269 [95% CI 243-298] to 660 [524-832]; MCI: from 189 [177-200] to 470 [377-587]); female sex (dementia: 143 [131-156]; MCI: 151 [143-159]); parental history of dementia (dementia: 720 [568-912]; MCI:191 [148-246]); rural residence (dementia:116 [106-127]; MCI:145 [138-154]); fewer years of education (dementia: from 117 [106-129] to 155 [138-173]; MCI: from 148 [139-158] to 348 [325-373]); being widowed, divorced, or living alone (dementia: from 259 [230-290] to 266 [229-310]; MCI: from 158 [144-173] to 174 [156-195]); smoking (dementia: 185 [167-204]; MCI: 127 [119-136]), hypertension (dementia: 186 [170-203]; MCI: 162 [154-171] for MCI), hyperlipidaemia (dementia: 187 [171-205]; MCI: 129 [121-137]), diabetes (dementia: 214 [196-234]; MCI: 144 [135-153]), heart disease (dementia: 198 [173-226]; MCI: 117 [106-130]), and cerebrovascular disease (dementia: 544 [495-597]; MCI: 149 [136-162]). Nine of these risk factors are modifiable. Interpretation Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system.

RATIONALE:Anti-GQ1b antibody syndrome refers to a distinct variant of Guillain- Barré syndrome. Involvement of the optic nerve in anti-GQ1b antibody syndrome is extremely rare. PATIENT CONCERNS:Here, we report a case of anti-GQ1b antibody syndrome presenting with visual deterioration as the initial symptom. A 73-year-old man presented with a 5-day history of bilateral blurred vision and ptosis. He had a previous history of diarrhea starting 10 days before admission. Physical examination showed visual deterioration, ophthalmoplegia, and peripheral facial paralysis. Testing of both serum and cerebrospinal fluid was positive for anti-GQ1b immunoglobulin G antibodies and negative for anti-aquaporin 4antibodies. DIAGNOSIS:Anti-GQ1b antibody syndrome. INTERVENTIONS:The patient was treated with intravenous methylprednisolone and human immunoglobulin. OUTCOMES:After a 20-day follow-up, the patient's condition took a favorable turn. LESSONS:This case reminds us that anti-GQ1b antibody syndrome should be suspected in patients with visual deterioration and preceding infection.

INTRODUCTION:The genetic risk effects of apolipoprotein E (APOE) on familial Alzheimer's disease (FAD) with or without gene mutations, sporadic AD (SAD), and normal controls (NC) remain unclear in the Chinese population.METHODS:In total, 15 119 subjects, including 311 FAD patients without PSEN1, PSEN2, APP, TREM2, and SORL1 pathogenic mutations (FAD [unknown]); 126 FAD patients with PSENs/APP mutations (FAD [PSENs/APP]); 7234 SAD patients; and 7448 NC were enrolled. The risk effects of APOE ε4 were analyzed across groups.RESULTS:The prevalence of the APOE ε4 genotype in FAD (unknown), FAD (PSENs/APP), SAD, and NC groups was 56.27%, 26.19%, 36.23%, and 19.54%, respectively. Further, the APOE ε4 positive genotype had predictive power for FAD (unknown) risk (odds ratio: 4.51, 95% confidence interval: 3.57-5.45, P < .001).DISCUSSION:APOE ε4 positive genotype may cause familial aggregation, and the investigation of multiple interventions targeting APOE pathological function to reduce the risk for this disease warrants attention.

Acute ischemic stroke is a devastating disease with very limited therapeutics. Growing appreciation of dysregulated autophagy contributes to the progression of brain ischemic injury, making it to be an appealing intervention target. In terms of its well-characterized consequences, the signal molecules required for autophagy activation are rather poorly defined. Here, we found the induction of chloride channel-3 (ClC-3) directly activated autophagy, which played an important role in limiting cerebral ischemia/reperfusion (I/R) injury. Further mechanism exploration discovered that the up-regulation of ClC-3 was critical for the interaction of Beclin1 and Vps34. After ClC-3 knockdown using adeno-associated virus vectors in vivo, the autophagy activation was partially inhibited through disrupting the formation of Beclin1 and Vps34 complex. Consistent with these observations, ClC-3 knockdown could also significantly aggravated cerebral I/R injury through suppressing autophagy in vivo, which further confirmed the neuroprotective roles of ClC-3. Collectively, we provided an novel evidence for ClC-3 serving as a crucial regulator of autophagy; and our results indicated that the induction of ClC-3 may serve as a self-protective mechanism against cerebral I/R injury.

Objective: Atorvastatin and aspirin have been used in treating different forms of epilepsy. However, their effect on post-stroke epilepsy (PSE) still needs to be validated by large-scale clinical studies. In addition, their impact on the use of the antiepileptic drug levetiracetam for post-stroke epilepsy remains to be explored. Thus, the aim of this study was to further evaluate the effect of atorvastatin and aspirin on PSE and their effect on the usage of the antiepileptic drug levetiracetam in PSE patients. Methods: Patients, aged 65 to 85 years, with newly diagnosed post-ischemic stroke epilepsy from August 30, 2014 to August 30, 2018 were included in the study, with the exclusion of those with coexisting conditions. Results: Initially, 1321 patients were included, and 780 remained in the study at the 1-year follow-up. During the study, atorvastatin treatment with or without aspirin reduced the number of clinical epileptic episodes in PSE patients. It also reduced the dosage of levetiracetam and achieved better control of epilepsy compared to levetiracetam mono-treatment. Aspirin co-treatment with levetiracetam did not result in a significant improvement. However, the combination of aspirin with atorvastatin significantly reduced the number of seizures compared to atorvastatin treatment alone. Conclusion: Atorvastatin and aspirin co-treatment with levetiracetam can reduce epilepsy in PSE patients and reduce the dosage of levetiracetam required for effective control of PSE.

自发性低颅压(spontaneous intracranial hypotension,SIH)又称自发性低脑脊液容量(pontaneous cerebrospinal fluid hypovolemia,SCFH) 是一种少见的神经系统疾患.虽然其典型的临床特点是体位性头痛,在临床上的漏诊和误诊率仍较高.由于国内很多神经诊疗中心一直沿用陈旧的诊疗观念,有些明确诊断的患者得不到规范的治疗.低颅压的病理基础是硬脊膜脑脊液瘘,文献报道瘘口以胸腰段脊柱多发,而颈段特别是高位颈段相对罕见.本文报道 1 例轻微外伤后高颈段脑脊液瘘导致 SIH 的患者.通过文献复习,对其致病机制、 诊断手段和治疗方法进行梳理.

The long non-coding RNA, urothelial carcinoma associated 1 (UCA1) has been demonstrated to play important roles in various types of cancers. This study investigated the functional role of UCA1 in glioma and explored the underlying molecular mechanisms. UCA1 was found to be highly up-regulated in glioma cells, and knock-down of UCA1 inhibited cell growth, invasion and migration, and also induced apoptosis in glioma cells. On the other hand, overexpression of UCA1 promoted cell proliferation, cell invasion and migration in glioma cells. Knock-down of UCA1 suppressed the activity of Wnt/β-catenin signaling, and treatment with lithium chloride restored the inhibitory effect of UCA1 knock-down on cell invasion and migration. More importantly, the aberrant expression of UCA1 was associated with chemo-resistance to cisplatin and temozolomide in glioma cells via interacting with Wnt/β-catenin signaling. In vivo studies showed that overexpression of UCA1 promoted the in vivo tumor growth of U87 cells in the nude mice. Clinically, UCA1 was found to be up-regulated in glioma tissues and higher expression level of UCA1 was correlated with poor survival in patients with glioma. Taken together, our results showed that UCA1 had a functional role in the regulation of glioma cell growth, invasion and migration, and chemo-resistance possibly via Wnt/β-catenin signaling pathway.

Post-stroke depression often seriously affects the prognosis and quality of life of patients and many clinical trials had shown that Chai Hu Shu Gan San combined with selective serotonin reuptake inhibitors (SSRIs) had good efficacy and minor side effects. We aimed to conduct this meta-analysis to evaluate the efficacy and safety of Chai Hu Shu Gan San as an adjuvant drug for SSRI in treating post-stroke depression. We searched PubMed, EMBASE, Cochrane Library, Wanfang, China Biology Medicine disc (CBM), Chongqing VIP, and CNKI (China National Knowledge Infrastructure) from their date of foundation to December 15, 2018. Literature screening, data extraction and quality assessment were conducted by two authors independently. The data synthesis and analysis were performed by using Review Manager (RevMan) 5.3 software and sensitivity analysis was conducted to assess the robustness of the results. Finally, a total of 22 articles were included. The meta-analysis confirmed the advantages of the combination of SSRI and Chai Hu Shu Gan San, mainly from four aspects: the Hamilton Depression (HAMD) scale score (MD=3.66; 95% DI=2.33-4.98; p<0.001), the Modified Edinburgh Scandinavian Stroke Scale (MESSS) score (MD=4.87; 95% CI=2.32-7.43; p<0.001), the efficacy rate (OR=3.50; 95% CI=2.61-4.69; p<0.001) and the incidence of adverse reactions (OR=0.28; 95% CI=0.17-0.46; p<0.001). No significant publication bias was observed, and sensitivity analysis suggested a good stability of the results. According to the present evidence, we concluded that Chai Hu Shu Gan San in combination with SSRI may be effective and safe in the treatment of post-stroke depression.

INTRODUCTION:Neuronal-derived exosomal Aβ42, T-tau, and P-T181-tau have been demonstrated to be biomarkers of Alzheimer's disease (AD). However, no study has assessed the association of Aβ42, T-tau, and P-T181-tau between exosomes and CSF.METHODS:This was a multicenter study with two-stage design. The subjects included 28 AD patients, 25 aMCI patients, and 29 controls in the discovery stage; the results of which were confirmed in the validation stage (73 AD, 71 aMCI, and 72 controls).RESULTS:The exosomal concentrations of Aβ42, T-tau, and P-T181-tau in AD group were higher than those in aMCI and control groups (all P < .001). The level of each exosomal biomarker was highly correlated with that in CSF.DISCUSSION:This study verified the agreement between CSF and blood exosomal biomarkers and confirmed that exosomal Aβ42, T-tau, and P-T181-tau have the same capacity as those in CSF for the diagnosis of AD and aMCI.

The aim of this study is to investigate the effects of long‐chain noncoding RNA plasmacytoma variant translocation 1 (PVT1) on the activation of astrocytes and the expression of brain‐derived neurotrophic factor (BDNF) in hippocampus tissues of epileptic rats. The epilepsy rat model was induced by intraperitoneal injection of lithium chloride–pilocarpine. Successfully modeled rats were grouped, and their spatial learning and memory, neuronal loss, number of TdT‐mediated dUTP nick labeling (TUNEL)‐positive cells, and the expression of cleaved‐caspase‐3, pro‐caspase‐3, Bax, Bcl‐2, GFAP, BDNF, tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), IL‐6, axin, and cyclin D1 in hippocampus tissues were evaluated. Increased expression of PVT1 was found in hippocampus tissues of epileptic rats. Silencing of PVT1 improved spatial learning and memory, decreased neuronal loss, decreased the number of TUNEL‐positive cell, decreased the expression of cleaved‐caspase‐3 and Bax while increased pro‐caspase‐3 and Bcl‐2 expression, decreased the expression of GFAP, increased the expression of BDNF, decreased the expression of TNF‐α, IL‐1β, and IL‐6, and decreased the expression of axin and cyclin D1 in hippocampus tissues in epileptic rats. Our study provides evidence that the inhibition of PVT1 may decrease the loss of neurons, inhibit the activation of astrocytes, and increase the expression of BDNF in hippocampus by downregulating the Wnt signaling pathway.

OBJECTIVE: Cerebral small vessel diseases (CSVDs) are common causes of cognitive impairments and mood disorders. In recent years, event-related potential P300 has received increasing attention as a biomarker of cognitive impairments or mood disorders. Previous studies on P300 mainly focused on anxiety, depression or cognitive impairments, and few results have been reported on P300 in CSVD patients. The present study aimed to explore the relationship between neuropsychological test scores and P300 in patients with CSVDs. METHODS: The clinical data of 52 patients with CSVDs admitted to the Neurology ward of the First Hospital of Jilin University from June 2016 to October 2017 were collected. All patients who met the inclusion criteria were assessed by both cognitive tests and mood scales within 1 week after enrollment, followed by measurement of P300. Accordingly, patients were assigned to the following four groups: cognitive impairment, non-cognitive impairment, mood disorder, and non-mood disorder.The amplitude and latency values of P300 were measured from the Pz, Fz, Fpz, C3, C4 and Cz electrode sites. In addition, correlations of P300 responses and neuropsychological test scores were analyzed. RESULTS: Significant differences were found in the P300 latency values between the cognitive impairment group and non-cognitive impairment group (P<0.05). P300 latency values were more significantly prolonged in the mood disorder group at the Fz, C3 and Cz electrode sites than in the non-mood disorder group. Positive correlations were found between Hamilton Depression Scale scores and C3, Fz and Cz latencies. Females tended to have a statistically higher risk of emotional impairment than did males (p<0.05). CONCLUSION: P300 latency values can be used as a objective indicator of cognitive impairments and mood disorders in CSVD patients.

China has the largest population of patients with dementia in the world, imposing a heavy burden on the public and health care systems. More than 100 epidemiological studies on dementia have been done in China, but the estimates of the prevalence and incidence remain inconsistent because of the use of different sampling methods. Despite improved access to health services, inadequate diagnosis and management for dementia is still common, particularly in rural areas. The Chinese Government issued a new policy to increase care facilities for citizens older than 65 years, but most patients with dementia still receive care at home. Western medicines for dementia symptoms are widely used in China, but many patients choose Chinese medicines even though they have little evidence supporting efficacy. The number of clinical trials of Chinese and western medicines has substantially increased as a result of progress in research on new antidementia drugs but international multicentre studies are few in number. Efforts are needed to establish a national system of dementia care enhance training in dementia for health professionals, and develop global collaborations to prevent and cure this disease.

In this report, we describe a woman patient who presented with general fatigue and gradual weakness of the limbs. Her husband was diagnosed with syphilis. We performed a serological examination for syphilis and muscle biopsy. Her serological examination was TPPA (treponema pallidum particle agglutination assay)-positive and RPR (rapid plasma reagin)-positive with a titer of 1:16. Muscle biopsy showed abnormal lipid accumulation in myofibers. The genetic test revealed homozygous mutation at c. 770A > G (p.Y257C) of the ETFDH (electron transferring-flavoprotein dehydrogenase) gene. We conclude that this woman was infected with syphilis from her husband, and because she was a c.770A > G ETFDH mutant, multiple acyl-CoA dehydrogenase deficiency (MADD) was triggered.