The clinic-based predictive modeling for prognosis of patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system that can cause significant morbidity and mortality. Although several prognostic factors have been identified, their clinical efficacy and use in combination to predict outcomes in immunocompetent patients with CM are not clear. Therefore, we aimed to determine the utility of those prognostic factors alone or in combination in predicting outcomes of immunocompetent patients with CM. METHODS: The demographic and clinical data of patients with CM were collected and analyzed. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1-4) outcome groups. Prognostic model was created and receiver-operating characteristic curve analyses were conducted. RESULTS: A total of 156 patients were included in our study. Patients with higher age at onset (p = 0.021), ventriculoperitoneal shunt placement (p = 0.010), Glasgow Coma Scale (GCS) score of less than 15(p< 0.001), lower CSF glucose concentration (p = 0.037) and immunocompromised condition (p = 0.002) tended to have worse outcomes. Logistic regression analysis was used to create a combined score which had a higher AUC (0.815) than those factors used alone for predicting outcome. CONCLUSIONS: Our study shows that a prediction model based on clinical characteristics had satisfactory accuracy in prognostic prediction. Early recognition of CM patients at risk of poor prognosis using this model would be helpful in providing timely management and therapy to improve outcomes and to identify individuals who warrant early follow-up and intervention.

Silencing miR-20a-5p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa-RhoA-mediated synaptic plasticity.

Epileptogenesis is a potential process. Mossy fibre sprouting (MFS) and synaptic plasticity promote epileptogenesis. Overexpression of repulsive guidance molecule a (RGMa) prevents epileptogenesis by inhibiting MFS. However, other aspects underlying the RGMa regulatory process of epileptogenesis have not been elucidated. We studied whether RGMa could be modulated by microRNAs and regulated RhoA in epileptogenesis. Using microRNA databases, we selected four miRNAs as potential candidates. We further experimentally confirmed miR-20a-5p as a RGMa upstream regulator. Then, in vitro, by manipulating miR-20a-5p and RGMa, we investigated the regulatory relationship between miR-20a-5p, RGMa and RhoA, and the effects of this pathway on neuronal morphology. Finally, in the epilepsy animal model, we determined whether the miR-20a-5p-RGMa-RhoA pathway influenced MFS and synaptic plasticity and then modified epileptogenesis. Our results showed that miR-20a-5p regulated RGMa and that RGMa regulated RhoA in vitro. Furthermore, in primary hippocampal neurons, the miR-20a-5p-RGMa-RhoA pathway regulated axonal growth and neuronal branching; in the PTZ-induced epilepsy model, silencing miR-20a-5p prevented epileptogenesis through RGMa-RhoA-mediated synaptic plasticity but did not change MFS. Overall, we concluded that silencing miR-20a-5p inhibits axonal growth and neuronal branching and prevents epileptogenesis through RGMa-RhoA-mediated synaptic plasticity in the PTZ-induced epilepsy model, thereby providing a possible strategy to prevent epileptogenesis.

MicroRNAs and target genes in epileptogenesis.

Epilepsy is a chronic brain dysfunction. Current antiepileptic medicines cannot prevent epileptogenesis. Increasing data have shown that microRNAs (miRNAs) are selectively altered within the epileptic hippocampi of experimental models and human tissues, and these alterations affect the genes that control epileptogenesis. Furthermore, manipulation of miRNAs in animal models can modify epileptogenesis. As a result, miRNAs have been proposed as promising targets for treating epilepsy. We searched PubMed using the terms "microRNAs/miRNAs AND epilepsy", "microRNAs/miRNAs AND epileptogenesis", and "microRNAs/miRNAs AND seizure". We selected the articles in which the relationship between miRNAs and target gene(s) was validated and manipulation of miRNAs in in vivo epilepsy models modified epileptogenesis during the chronic phase via gene regulation. A total of 13 miRNAs were found in the present review. Based on the current analysis of miRNAs and their target gene(s), each miRNA has limitations as a potential epilepsy target. Importantly, miR-211 or miR-128 transgenic mice displayed seizures. These findings highlight new developments for epileptogenesis prevention. Developing novel strategies to modify epileptogenesis will be effective in curing epilepsy patients. This article provides an overview of the clinical application of miRNAs as novel targets for epilepsy.

Impaired consciousness and decreased glucose concentration of CSF as prognostic factors in immunocompetent patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) is the most common fungal infection of the central nervous system and has high morbidity and mortality. Almost studies about prognostic factors have largely focused on the immunocompromised population rather than immunocompetent patients. So that we sought to conduct a retrospective study to determine prognostic factors which predict the outcomes in immunocompetent patients with CM. METHODS: We retrospectively collected and analyzed the demographic and clinical data of 76 apparently immunocompetent patients with cryptococcal meningitis from January 2003 to June 2019 in China. The clinical outcome was graded by the Glasgow outcome scale (GOS) at discharge, and patients were divided into good (score of 5) and unfavorable (score of 1-4) outcome groups, potential prognostic factors were analyzed. RESULTS: Non-parametric test confirmed that unfavorable outcome was associated with lower glucose level of CSF(P = 0.001), and Pearson's χ2 analysis confirmed that unfavorable outcome was associated with opening pressure of CSF(>300mmH20, P = 0.038), impaired consciousness (P = 0.001), hydrocephalus(P = 0.045), and Shunt surgery (P = 0.045), and then multiple logistic regression analysis confirmed that impaired consciousness(P = 0.015) and lower glucose concentration of CSF(P = 0.012) increased the likelihood of unfavorable outcome in CM patients. CONCLUSION: Impaired consciousness and decreased glucose concentration of CSF were independently prognostic factors which predict the unsatisfactory outcome in immunocompetent patients with CM.

Spectrum of clinical features and neuroimaging findings in acute cerebral infarction patients with unusual ipsilateral motor impairment- a series of 22 cases.

BACKGROUND: Cerebral infarction occurs when the arteries to brain are obstructed, and motor impairment contralateral to responsible lesion is commonly recognized. Few studies have profiled the characteristics of cases with ipsilateral motor impairment. We sought to characterize clinical features of patients with motor dysfunction caused by ipsilateral ischemic stroke. METHODS: We retrieved and analyzed the medical data for patients with ipsilateral cerebral infarction. Patients were regarded as having ipsilateral cerebral infarction if motor impairment is ipsilateral to recent stroke lesions. RESULTS: Only 22 patients with unusual ipsilateral cerebral infarction were included in this study. Ipsilateral limb paralysis was observed in all cases, and one case showed central facioplegia. Majority of patients with limb paralysis (90.9%, 20/22) presented with mild muscle strength deficits (MRC grading of 4 or more). Most of the patients (72.7%, 16/22) had a past history of stroke, and previous strokes were contralateral to the side of the recent stroke in 14 out of 16 patients (87.5%). No history of stroke or cerebral injury was identified in seven patients. With aspect of MRI findings, recent infarct lesions of all cases were located along the corticospinal tract. CONCLUSIONS: History of stroke plays an important role in the pathogenesis of ipsilateral motor impairment, and cortical reorganization in the unaffected hemisphere may contribute to the compensation of motor function after stroke. Besides that, some cases with first stroke may be due to impairment of ipsilateral uncrossed corticospinal fibers.

Successful treatment of reflex epilepsy with praxis induction by stimulus avoidance only.

PURPOSE: Reflex epilepsy is a type of epilepsy with seizures that are consistently triggered by a specific stimulus. Zipai is a Chinese ancient card game which has been popular in Southern China for hundreds of years. We sought to report and characterize clinical features of patients with reflex epilepsy evoked by playing Zipai. METHODS: We collected and analyzed clinical data of patients with Zipai-induced epilepsy. Patients were regarded as having Zipai-induced epilepsy if they suffered at least two seizure attack during the course of playing Zipai. Prolonged electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were applied to all patients. All patients were advised to avoid watching and playing Zipai games in daily life, instead of using antiepileptic drugs. The seizure outcome was assessed during outpatient visits and by telephone contact. RESULTS: Five patients were included in this study. No spontaneous seizures occurred in all five patients. No patients had experienced myoclonic and coexistent absences with generalized tonic-clonic seizures (GTCS). All patients had normal MRI and prolonged EEG findings. All patients were advised to avoid the Zipai game, and became seizure-free without medication during the follow-up period (mean 5.4 years, range 3.5-7 years). CONCLUSION: Zipai-induced epilepsy may be an unreported subtype form of reflex epilepsy with praxis induction. Nonpharmacological conservative treatment plays a significant role in the treatment of reflex epilepsy.

IL-35 Is Involved in the Pathogenesis of Guillain-Barré Syndrome Through Its Influence on the Function of CD4+ T Cells.

CD4+ T cells and many cytokines play critical roles in the pathogenesis of Guillain-Barré Syndrome (GBS), an immune-mediated inflammatory disease. However, the role of IL-35, a novel member of the IL-12 cytokine family, in this kind of disease has not yet been elucidated. In this study, we investigated the functional changes of CD4+ T cells from GBS patients with IL-35 treatment in vitro. This study involved 21 GBS patients and an equal number of healthy controls (HCs). The results indicated that the average concentration of IL-35 in the plasma of GBS patients was lower than that of healthy controls (HCs). Increased levels of STAT1, STAT3 and STAT4 proteins and T-bet, ROR γt, IFN-γ and IL-17A mRNA were observed in CD4+ T cells from GBS patients. In contrast, the levels of STAT5 and STAT6 proteins and GATA3, Foxp3, IL-4 and TGF-ß1 mRNAs were decreased in GBS patients in comparison with those of HCs. In addition, treatment of CD4+ T cells from GBS patients with IL-35 upregulated IL-35, STAT5 and STAT6 protein and T-bet, GATA3, Foxp3, IFN-γ, IL-4, IL-17A and TGF-ß1 mRNA while inhibited levels of STAT3 and STAT4 protein and RORγt and IL-17A mRNA. These results indicate that IL-35 might play a potential role in GBS pathogenesis. Further studies are required in order to evaluate its role in GBS.

Roles of Rho guanine nucleotide triphosphatases in hippocampal mossy fiber sprouting in the pentylenetetrazole kindling model.

BACKGROUND: One unique feature of chronic human and experimental epilepsy is hippocampal dentate granule cell axon (mossy fiber) sprouting which creates an aberrant positive-feedback circuit that may be epileptogenic. However, the mechanism underlying this process remains unclear. Rho guanine nucleotide triphosphatases (RhoGTP ases) Rac1 and RhoA are important regulators of axon growth and synaptic plasticity and can be blocked by treatment with fasudil. We hypothesized that Rac1 and RhoA are involved in aberrant mossy fiber sprouting (MFS). METHODS: A temporal lobe epilepsy model was established by intraperitoneal pentylenetetrazole (PTZ) injection for animals in PTZ group, and fasudil was injected 30 minutes prior to PTZ injection for animals in PTZ + Fas group. The expression of Rac1 and RhoA in the rat hippocampus was tested at different time points by immunohistochemistry, Western blot and quantitative real-time PCR. Mossy fiber sprouting in the hippocampus was evaluated by Timm staining. RESULTS: Rac1 and RhoA were significantly up-regulated in the PTZ group, and as predicted, the degree of aberrant MFS was correspondingly increased. However, the expression of Rac1 and RhoA was not inhibited in the PTZ + Fas group, and the epileptiform activity, EEG and aberrant MFS were not suppressed following PTZ + Fas treatment. CONCLUSIONS: RhoGTPases play a role in MFS but fasudil is not sufficient to inhibit RhoGTPases and MFS in the PTZ kindling model.

Expression of SOCSs and TLRs in the hippocampus of pentylenetetrazole kindling model.

BACKGROUND: Epilepsy is one of the most common neurological disorders, and approximately one-third of patients with epilepsy are resistant to anti-epileptic drugs (AEDs). Recent emerging evidence has demonstrated the roles of innate immunity and the associated inflammatory processes in epilepsy. Toll-like receptors (TLRs) are a type of pattern-recognition receptor that promote innate immune defense. The SOCS proteins as negative-feedback regulators in cytokine signaling are involved in the regulation of TLR-mediated immune responses. However, few studies investigating the role of TLRs and SOCSs in epilepsy have been reported. METHODS: To explore the role of innate immunity in the mechanism of epilepsy, the pentylenetetrazole (PTZ) kindling rat model was established using intraperitoneal injection of PTZ. The expression levels of TLR2, TLR4, and STAT molecules in rat hippocampi were analyzed using qRT-PCR and western blotting techniques. The expression levels of SOCS-1 and SOCS-3 in rat hippocampi were analyzed using qRT-PCR. RESULTS: Our data demonstrated that both the mRNA and protein expression of TLR2 and TLR4 were significantly upregulated in the rat hippocampus with PTZ injection, which was accompanied by an inhibition of SOCS-1 and SOCS-3 and an upregulation of STAT3. CONCLUSIONS: Our study suggested that SOCSs and TLRs contribute to the development of epilepsy which may lead to therapeutic interventions that limit epileptogenesis.

Serotonergic neurotransmission mediated cognitive dysfunction in two mouse models of sepsis-associated encephalopathy.

BACKGROUND: Patients with sepsis-associated encephalopathy (SAE) often exhibit cognitive impairments. Despite this, the underlying mechanisms of SAE remain largely unexplored. Here, we explored the role of serotonergic neurotransmission in cognitive dysfunction of two mouse models of SAE. METHODS: The mouse models of SAE were established by injection of lipopolysaccharide (LPS, 10 mg/kg, intraperitoneal) and cecal ligation puncture (CLP) respectively. Barnes maze, new object recognition test and open field test were used to evaluate the effects of fluoxetine (selective serotonin reuptake inhibitor) and cyproheptadine (nonselective 5-HT2 receptor antagonist) on cognition and motor activity of mice. Additionally, WAY100635 (5-HT1A receptor antagonist) was co-administered with fluoxetine to explore the mechanism underlying effect of fluoxetine on cognitive impairments of SAE. Enzyme-linked immunosorbent assay (ELISA) was performed to determine 5-HT levels in hippocampus, brainstem and frontal lobe of experimental groups. RESULTS: Both LPS-induced sepsis and CLP induced sepsis resulted in a notable learning deficit. Fluoxetine ameliorated, while cyproheptadine aggravated, cognitive impairment in two classic mouse models of SAE. The cognition-enhancing effect of fluoxetine is reversed by WAY100635. Decreased 5-HT levels in hippocampus, brainstem and frontal lobe were observed in LPS septic model and CLP septic model. Notably, both fluoxetine and cyproheptadine significantly increased 5-HT levels in those brain regions in LPS septic model. Additionally, fluoxetine significantly increased 5-HT levels in frontal lobe of CLP septic model. CONCLUSIONS: Our study demonstrated that serotonergic neurotransmission plays a significant role in mechanisms underlying cognitive impairment in SAE. These findings contribute to identification of novel targets to prevent and arrest cognitive impairment in SAE.

MicroRNA-based therapy: a new dimension in epilepsy treatment.

Epilepsy is a brain disorder, which is characterized by a predisposition to generate seizures that are associated with neurobiological, psychological cognitive and linguistic problems. Current treatments of epilepsy remain difficult, and antiepileptic drugs fail for some patients. Expressions of different microRNAs (miRNAs) in different brain regions are implicated in epileptogenic activity. MiRNAs are important regulators of seizure-induced neuronal death. The activation of inflammatory pathways is involved in reactive astrocytes and cells of the microglia in human temporal lobe epilepsy (TLE). MiRNAs are regulators of the innate immune response in the modulation of astrocyte-mediated inflammation. These miRNAs can possibly be used as a novel therapeutic target in the treatment of TLE. Targeting miRNA in epilepsy supports it as a feasible strategy for the treatment of epilepsy. But this powerful technique has received less attention as a potential therapeutic strategy. This is mainly because of the lack of well-defined targets in epilepsy. This review focuses on the role of miRNA in epilepsy, and recent advances in miRNA targeted epileptic therapies.

The Residual Risks Associated with Atherothrombosis of Recurrent Ischemic Stroke (IS) After Non-cardiogenic IS.

Recurrent ischemic stroke (IS) is one of the leading causes of disability and death worldwide. Patients with recurrent IS, in comparison with survivors of the initial non-cardiogenic IS, have more serious neurological deficit and longer hospital stay with heavier family and socio-economic burden. Therefore, recurrent IS is a major challenge that we urgently need to address. The recurrence rate of non-cardiogenic IS is not zero and even shows an increasing trend over a long period of time, despite receiving evidence-based management in accordance with guideline, indicating that patients suffering from non-cardiogenic IS and who are receiving optimal management remain at considerable residual risks (RRs) responsible for the recurrence of cerebrovascular events. In addition to low-density lipoprotein cholesterol (LDL-C) and platelets, some new non-traditional parameters such as high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], peripheral circulating platelet-derived microvesicles, white blood cells-platelet complexes, NODlike receptor protein 3 (NLRP3) inflammasome, monomeric C-reactive protein, neutrophils and their products (neutrophil extracellular traps, NETs), may also be potential sources of RRs for recurrent IS. On the basis of the three pillars of secondary stroke prevention, namely, blood pressure reduction, lipid-lowering and antiplatelet therapy, the reduction in RRs may provide additional protection against recurrent IS. With this background, the identification and quantification of RRs associated with disease heterogeneity and individualized treatment strategies based on risk stratification are favorable in the mitigation of the huge stroke burden people unceasingly face.

Silencing of dentate gyrus inhibits mossy fiber sprouting and prevents epileptogenesis through NDR2 kinase in pentylenetetrazole kindling rat model of TLE.

Epileptogenesis is a potential process. Mossy fiber sprouting (MFS) contributes to epileptogenesis. Silencing of the dentate gyrus (DG) suppressed spontaneous seizures model of epilepsy and hyperactivity of granule cells resulted in MFS in vitro. However, the role of DG's excitability in epileptogenesis have not yet been well explored, and underlying mechanisms has not been elucidated. Using chemical genetics, we studied whether MFS and epileptogenesis could be modulated by silencing of DG in the PTZ kindling rat model of epilepsy. MFS and protein expression was measured by Timm staining, Western blotting, and Immunofluorescence. Previous studies demonstrated that MFS and epileptogenesis could be modulated by a regulator of axonal growth (e.g. RGMa, PTEN). NDR2 kinase regulate neuronal polarity and prevents the formation of supernumerary axons in the hippocampus. We experimentally confirmed chemogenetic inhibition in DG resulted in decreased MFS and NDR2 expression, and alleviated epileptogenesis. Furthermore, our results showed that injection of AVV vector expressing NDR2 into DG induced upregulation of NDR2 in the hippocampus, and over expression of NDR2 in the hippocampus promote MFS and block protective effect of chemogenetic silencing of DG on epileptogenesis. Overall, we concluded that silencing of DG inhibits MFS and prevents epileptogenesis through NDR2 in the hippocampus in the PTZ kindling rat model of TLE, thereby providing a possible strategy to prevent epileptogenesis.

No genetic causal association between dental caries and Alzheimer's disease: a bidirectional two-sample Mendelian randomization analysis.

Background: An increasing number of observational studies have suggested an association between dental caries and Alzheimer's disease (AD). The association between dental caries and Alzheimer's disease may be mediated by confounders or reverse causality. In this study, we conducted bidirectional two-sample Mendelian randomization (MR) to estimate the bidirectional causality between dental caries and AD. Materials and Methods: Genome-wide association study (GWAS) summary statistics of dental caries were extracted from a published meta-analysis which included a total of 487,823 participants. GWAS datasets of AD and AD onset age were obtained from the FinnGen bank. A bidirectional two-sample analysis was performed to explore the causality between dental caries and AD. Results: For the dental caries-AD causality estimation, there was no significant association between dental caries and AD, neither with the AD GWASs from the FinnGen database (OR: 1.041, p = 0.874) nor with those from the International Genomics of Alzheimer's Project (OR: 1.162, p = 0.409). In addition, the genetic susceptibility to dental caries was not related to the onset age of AD. No causality existed between dental caries and early-onset AD (OR: 0.515, p = 0.302) or late-onset AD (OR: 1.329, p = 0.347). For the AD-dental caries relationship, no causality was detected by the IVW method (OR: 1.000, p = 0.717). Findings from other MR methods were consistent. The pleiotropy test and sensitivity analysis confirmed the validity of these MR results. Conclusions: In this bidirectional MR study, robust evidence to support a bidirectional causal effect between dental caries and AD from the GWAS results within large-scale European-descent populations was absent. Having dental caries would not alter the onset age of AD.

Establishment and verification of a nomogram model for predicting the risk of post-stroke depression.

Objective: The purpose of this study was to establish a nomogram predictive model of clinical risk factors for post-stroke depression (PSD). Patients and Methods: We used the data of 202 stroke patients collected from Xuanwu Hospital from October 2018 to September 2020 as training data to develop a predictive model. Nineteen clinical factors were selected to evaluate their risk. Minimum absolute contraction and selection operator (LASSO, least absolute shrinkage and selection operator) regression were used to select the best patient attributes, and seven predictive factors with predictive ability were selected, and then multi-factor logistic regression analysis was carried out to determine six predictive factors and establish a nomogram prediction model. The C-index, calibration chart, and decision curve analyses were used to evaluate the predictive ability, accuracy, and clinical practicability of the prediction model. We then used the data of 156 stroke patients collected by Xiangya Hospital from June 2019 to September 2020 for external verification. Results: The selected predictors including work style, number of children, time from onset to hospitalization, history of hyperlipidemia, stroke area, and the National Institutes of Health Stroke Scale (NIHSS) score. The model showed good prediction ability and a C index of 0.773 (95% confidence interval: [0.696-0.850]). It reached a high C-index value of 0.71 in bootstrap verification, and its C index was observed to be as high as 0.702 (95% confidence interval: [0.616-0.788]) in external verification. Decision curve analyses further showed that the nomogram of post-stroke depression has high clinical usefulness when the threshold probability was 6%. Conclusion: This novel nomogram, which combines patients' work style, number of children, time from onset to hospitalization, history of hyperlipidemia, stroke area, and NIHSS score, can help clinicians to assess the risk of depression in patients with acute stroke much earlier in the timeline of the disease, and to implement early intervention treatment so as to reduce the incidence of PSD.

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

Background: The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association. Methods: According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1ß, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay. Results: Fifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014). Conclusions: Our findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

Associations of vitamin D-related single nucleotide polymorphisms with post-stroke depression among ischemic stroke population.

Objective: To investigate the relationship between single nucleotide polymorphisms (SNPs) related to vitamin D (VitD) metabolism and post-stroke depression (PSD) in patients with ischemic stroke. Methods: A total of 210 patients with ischemic stroke were enrolled at the Department of Neurology in Xiangya Hospital, Central South University, from July 2019 to August 2021. SNPs in the VitD metabolic pathway (VDR, CYP2R1, CYP24A1, and CYP27B1) were genotyped using the SNPscan™ multiplex SNP typing kit. Demographic and clinical data were collected using a standardized questionnaire. Multiple genetic models including dominant, recessive, and over-dominant models were utilized to analyze the associations between SNPs and PSD. Results: In the dominant, recessive, and over-dominant models, no significant association was observed between the selected SNPs in the CYP24A1 and CYP2R1 genes and PSD. However, univariate and multivariate logistic regression analysis revealed that the CYP27B1 rs10877012 G/G genotype was associated with a decreased risk of PSD (OR: 0.41, 95% CI: 0.18-0.92, p = 0.030 and OR: 0.42, 95% CI: 0.18-0.98, p = 0.040, respectively). Furthermore, haplotype association analysis indicated that rs11568820-rs1544410-rs2228570-rs7975232-rs731236 CCGAA haplotype in the VDR gene was associated with a reduced risk of PSD (OR: 0.14, 95% CI: 0.03-0.65, p = 0.010), whereas no significant association was observed between haplotypes in the CYP2R1 and CYP24A1 genes and PSD. Conclusion: Our findings suggest that the polymorphisms of VitD metabolic pathway genes VDR and CYP27B1 may be associated with PSD in patients with ischemic stroke.

Expression of Toll-like receptors 2, 4 and 9 in patients with Guillain-Barré syndrome.

OBJECTIVE: A myriad of transcription factors and inflammatory cytokines have been described to participate in the pathogenesis of Guillain-Barré syndrome (GBS). However, the innate immunity components--Toll-like receptors (TLRs)--have never been explored in this disease. We therefore investigated the expression of TLR2, 4 and 9 in the peripheral circulation of GBS patients as well as healthy controls. METHODS: Twenty-one GBS patients and 21 healthy donors participated in this study. Peripheral blood mononuclear cells were used for mRNA and protein analysis of TLR-related molecules. Also, peripheral blood mononuclear cells from different subjects were incubated with different TLR agonists and the subsequent IFN-γ secretion was determined. RESULTS: Expression of TLR2, 4 and 9 as well as their related signaling molecules were higher in GBS patients compared to healthy controls. Disability scores of GBS patients had a strong positive correlation with the high levels of expression of TLR2, 4 and 9. CONCLUSIONS: The TLR signaling pathway may be involved in the pathogenesis of GBS.