Identification of Biomarkers Related to M2 Macrophage Infiltration in Alzheimer's Disease.

Many studies have demonstrated that neuroinflammation contributes to the onset and development of Alzheimer's disease (AD). The infiltration of immune cells in the brain was observed in AD. The purpose of the present study was to verify potential mechanisms and screen out biomarkers related to immune infiltration in AD. We collected the expression profiling datasets of AD patients and healthy donors from the NCBI's Gene Expression Omnibus (GEO) database. We confirmed that immune-related mechanisms were involved in AD using differentially expressed genes analysis and functional enrichment analysis. We then found that M2 macrophage infiltration was most positively correlated with AD according to the CIBERSORT algorithm and a weighted gene co-expression network analysis (WGCNA). TLR2, FCGR2A, ITGB2, NCKAP1L and CYBA were identified as hub genes correlated with M2 macrophage infiltration in AD. Furthermore, the expression levels of these hub genes were positively correlated with Aß42 and ß-secretase activity. A diagnostic model of these hub genes was constructed, which showed a high area under the curve (AUC) value in both the derivation and validation cohorts. Overall, our work further expanded our understanding of the immunological mechanisms of AD and provided new insights into therapeutic strategies in AD.

The differential effects of isoflurane and sevoflurane on neonatal mice.

Previous research has shown that exposure to volatile anesthetics can induce acute neuroinflammation and neuroapoptopsis in neonatal rodents and that these events can lead to cognitive dysfunction at later stages. Isoflurane and sevoflurane are two of the most popular anesthetics used in the field of pediatrics. However, the relative impact of these two anesthetics on the developing brain at distinct time points after the induction of anesthesia has not been compared. In the present study, we exposed 7-day-old mice to clinically equivalent doses of isoflurane (1.5%) and sevoflurane (2.5%) for 4 h and then investigated consequential changes in the brains of these mice at six different time points. We analyzed the levels of proteins that are directly related to neuroapoptosis, neuroinflammation, synaptic function, and memory, in the brains of neonatal mice. Exposure of neonatal mice to isoflurane and sevoflurane resulted in acute neuronal apoptosis. Our analysis observed significant levels of neuroinflammation and changes in the expression levels of proteins associated with both synaptic transmission and memory in mice from the isoflurane group but not the sevoflurane group. Our results therefore indicate that isoflurane and sevoflurane induce differential effects in the brains of neonatal mice.

Evaluation of the Mini-Mental State Examination and the Montreal Cognitive Assessment for Predicting Post-stroke Cognitive Impairment During the Acute Phase in Chinese Minor Stroke Patients.

Objective: To assess the value of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) during acute phase in predicting post-stroke cognitive impairment (PSCI) at 3-6 months. Methods: We prospectively recruited 229 patients who had suffered their first-ever ischemic stroke. PSCI was determined in 104 of these patients by a comprehensive neuropsychological battery performed at 3-6 months. Receiver operating characteristic (ROC) curve analysis was then performed to compare the discriminatory ability of the MMSE and MoCA. Also, we applied a decision tree generated by the classification and regression tree methodology. Results: In total, 66 patients had PSCI when evaluated 3-6 months after the onset of minor stroke. Logistic regression analysis revealed that education, body mass index (BMI), and baseline MoCA scores were independently associated with PSCI. ROC curve analysis showed that the ability to predict PSCI was similar when compared between baseline MoCA scores [area under curve (AUC), 0.821; 95% confidence interval (CI), 0.743-0.898] and baseline MMSE scores (AUC, 0.809; 95% CI, 0.725-0.892, P = 0.75). Both MMSE and MoCA exhibited similar predictive values at their optimal cut-off points (MMSE ≤27; sensitivity, 0.682; specificity, 0.816; MoCA ≤21; sensitivity, 0.636; specificity, 0.895). Classification and regression tree-derived analysis yielded an AUC of 0.823 (sensitivity, 0.803; specificity, 0.842). Conclusion: When applied within 2 weeks of stroke, the MMSE and MoCA are both useful and have similar predictive value for PSCI 3-6 months after the onset of minor stroke.

TLR4 Targeting as a Promising Therapeutic Strategy for Alzheimer Disease Treatment.

Alzheimer disease (AD) is a devastating neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta and formation of intracellular neurofibrillary tangles. Microglia activation and neuroinflammation play important roles in the pathogenesis of AD; Toll-like receptor 4 (TLR4)-a key component of the innate immune system-in microglia is also thought to be involved based on the observed association between TLR gene polymorphisms and AD risk. TLR4 has been shown to exert both detrimental and beneficial effects on AD-related pathologies. In preclinical models, experimental manipulations targeting TLR4 were shown to improve learning and memory, which was related to inhibition of pro-inflammatory cytokine release and reduction of oxidative stress. In this review, we summarize the key evidence supporting TLR4 as a promising therapeutic target in AD treatment.

Altered Expression Profile of Phosphatidylinositols in Erythrocytes of Alzheimer's Disease and Amnestic Mild Cognitive Impairment Patients.

BACKGROUND: Studies have demonstrated that the levels of phospholipids, including phosphatidylinositols (PIs), were decreased in Alzheimer's disease (AD) brain, presenting as a potential biomarker for AD. The plasma phospholipids levels have also been discovered to predict the conversion of cognitively normal elderly adults to amnestic mild cognitive impairment (aMCI) or demented patients. OBJECTIVE: To investigate the expression profile of PIs in erythrocytes of AD and aMCI patients, which would serve as a blood-based method to distinguish AD and aMCI patients from normal controls (NC). METHODS: In this study, we used anion-exchange high-performance liquid chromatography to analyze PIs alterations in erythrocytes from a total of 86 prospectively recruited subjects (including 24 NC, 21 aMCI patients, and 41 AD patients). RESULTS: We found that the levels of PI40 : 4, PI3/5P, and PI(3,4)P2 in aMCI patients, and the levels of PI4P, PI(3,4)P2, and PI3/5P in AD patients were significantly decreased compared to NC. The changed expression profile of PIs could effectively discriminate AD and aMCI patients from NC (AUC = 0.964, 0.938, respectively). CONCLUSION: The altered expression profile of erythrocytes PIs might be a potential blood-based biomarker for AD and aMCI. This alteration of PIs probably reflected the impaired deformability and oxygen-carrying capacity of erythrocytes in AD and aMCI patients.

Holmium Laser Enucleation of the Prostate: Modified Two-Lobe Technique versus Traditional Three-Lobe Technique-A Randomized Study.

BACKGROUND: Holmium laser enucleation of the prostate (HoLEP) is considered the standard endoscopic treatment of benign prostatic hyperplasia (BPH), but traditional HoLEP surgery will cause some postoperative complications. This study was attempted to evaluate the safety and efficacy of modified two-lobe technique versus traditional three-lobe technique of HoLEP focusing mainly on incidences of retrograde ejaculation (RE) and urinary incontinence (UI). METHODS: From March 2014 to February 2017, 191 men with BPH were randomly assigned to two groups: 97 underwent modified two-lobe technique; 94 underwent traditional three-lobe technique. All patients were followed up for 12 months. Primary outcomes were incidences of RE and UI, and secondary outcomes were international prostate symptom score (IPSS), quality of life (QOL), maximal urine flowing rate (MFR), and residual urine among the studied patients. RESULTS: Compared with the traditional technique, patients in the modified group had a statistically significant decrease in frequency of UI (1.03% vs 8.51%, p=0.036) and RE in the 6th month (33.33% vs 63.64%, p=0.030) and 12th month (13.33% vs 50%, p=0.034) and a significant increase in ejaculatory volume in the 6th month (p=0.050) and 12th month (p=0.003). Besides, the modified HoLEP was more beneficial to patients according to the change of QoL score at 1 month (p=0.002), 3 months (p=0.004), 6 months (p=0.026), and 12 months (p=0.015). CONCLUSIONS: The modified two-lobe technology of HoLEP reduced the incidence of RE and UI, which improved the quality of life of the patients after surgery compared to the traditional three-lobe technology. This trial is registered with ChiCTR1800018553.

Early-Onset Parkinson's Disease Caused by PLA2G6 Compound Heterozygous Mutation, a Case Report and Literature Review.

PLA2G6 has been certified as a causative gene in patients with autosomal recessive early-onset Parkinson's disease (EOPD). We reported an EOPD case caused by PLA2G6 gene mutation, and performed neurological examination, genetic analysis, and multimodal neuroimaging to describe this phenotype. A compound heterozygous mutation c.991G>T/c.1472+1G>A was detected in this patient. Heterozygous for the c.991G>T and c.1472+1G>A were separately detected in his parents. Pathogenicity of these two mutations were predicted according to the American college of medical genetics and genomics (ACMG) guideline. MRI assessment showed absence of bilateral "swallow tail sign" and cerebellar atrophy in this patient, while no obvious difference in brain iron accumulation between PLA2G6 mutant PD patient and healthy controls. Cerebellar abnormalities may be a marker for diagnosis and evaluation of PLA2G6 mutation Parkinsonism. However, the iron accumulation in PD may not be the result of PLA2G6 mutation.

Tumor Enucleation vs. Partial Nephrectomy for T1 Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

Purpose: Tumor enucleation (TE) and partial nephrectomy (PN) have both become main treatment strategies for T1 renal cell carcinoma (RCC), despite the discrepancy between their safety margin. We performed a meta-analysis on all the relevant trials in order to compare the clinical efficacy and safety of TE with those of PN for RCC treatment. Methods: In this meta-analysis, randomized controlled trials or retrospective studies were included if they compared TE and PN therapy in patients with localized renal cancer. The main outcomes extracted were perioperative data and post-operative outcomes. Subgroups for analyses were undertaken according to tumor size and duration of follow up. Data were pooled using the generic variance method with a fixed or random effects model and expressed as mean differences or odds ratios with 95% CI. Results: A total of 13 studies containing 1,792 patients undergoing TE and 3,068 undergoing PN were identified. Our study showed that the patients received TE had significantly shorter operative time (MD = -28.46, 95% CI = -42.09, -14.83, P < 0.0001), less hospital day (MD = -0.68, 95% CI = -1.04, -0.31, P = 0.0003), less estimate blood loss (MD = -59.90, 95% CI = -93.23, -26.58, P = 0.0004) and smaller change in estimated glomerular filtration rate (fixed effect: MD = 4.66, 95% CI = 1.67, 7.66, P = 0.002), fewer complications (fixed effect: OR = 0.65, 95% CI = 0.50, 0.85, P = 0.001) compared with those received PN. However, there were no significant differences in terms of warm ischemic time, positive margin rates, recurrence rates and survival rates between the two groups. All the subgroup analyses presented consistent results with the overall analyses. Conclusions: Our findings suggested that TE is not only less-traumatizing and beneficial for recovery, but also better for renal function protection. Moreover, it did not show the evidence of an increase relapse rate or mortality rate when compared with PN.

Non-Hodgkin Lymphoma With Longitudinally Extensive Transverse Myelopathy as the Initial Symptom: A Case Report.

Identifying lymphoma as the cause of neurological disease is diagnostically challenging when the clinical manifestations are atypical. We report an unusual case of a previously healthy immunocompetent 67-years-old man presenting with acute onset of symptoms of myelopathy and mild personality changes. Magnetic resonance imaging (MRI) revealed multifocal periventricular lesions and longitudinally extensive transverse myelitis (LETM). He had very good response to corticosteroids and was in remission for over 6 months. Repeat MRI showed an unexpected mass lesion in the brain which was later confirmed by brain biopsy as diffuse large B cell lymphoma. Subsequent FDG-PET/CT revealed systemic disease with lymphonodal and testicular manifestations (Stage IV disease). It is therefore important to consider lymphoma as a differential diagnosis in patients with LETM and demyelinating lesions in the brain.

Microbiota-gut-brain axis and toll-like receptors in Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disease which involves both the periphery and central nervous system (CNS). It has been recently recognized that gut microbiota interacts with the gut and brain (microbiota-gut-brain axis), contributing to the pathogenesis of neurodegenerative diseases, such as AD. Dysbiosis of gut microbiota can induce increased intestinal permeability and systemic inflammation, which may lead to the development of AD pathologies and cognitive impairment via the neural, immune, endocrine, and metabolic pathways. Toll-like receptors (TLRs) play an important role in the innate immune system via recognizing microbes-derived pathogens and initiating the inflammatory process. TLRs have also been found in the brain, especially in the microglia, and have been indicated in the development of AD. In this review, we summarized the relationship between microbiota-gut-brain axis and AD, as well as the complex role of TLRs in AD. Intervention of the gut microbiota or modulation of TLRs properly might emerge as promising preventive and therapeutic strategies for AD.

Reducing postoperative morbidity of mini-invasive percutaneous nephrolithotomy: Would it help if blood vessels are left unharmed during puncture? A CONSORT-prospective randomized trial.

BACKGROUND: The aim of this study was to provide a randomized controlled trial comparing single B-mode ultrasound guidance and color doppler ultrasound guidance in minimally invasive percutaneous nephrolithotomy. METHODS: Three hundred patients with renal calculus were prospectively randomly assigned into 2 groups. In group 1 (150 patients), minimally invasive percutaneous nephrolithotomy (m-PCNL) were managed with single B-mode ultrasound guidance; In group 2 (150 patients), m-PCNL were managed with color Doppler ultrasound guidance and a needle bracket in order to guide placement at a target location beneath the skin. The characteristics of patients, operation, complications and prognosis, including body temperature, urine culture, and hematologic tests after the operation were recorded and compared. RESULTS: Our vessel-sparing technique showed a statistically significant decrease in hemoglobin drop, postoperative procalcitonin values, the frequency of postoperative fever, systemic inflammatory response syndrome, and urosepsis (P < .05). CONCLUSION: Using color Doppler ultrasound in real time and a needle bracket to detect and avoid main renal blood vessels decreased incidences of hemorrhagic complications and postoperative infection.

Genetic Analysis of PICK1 Gene in Alzheimer's Disease: A Study for Finding a New Gene Target.

Background: Alzheimer's disease (AD) is a neurodegenerative disease with no effective treatment. Researchers have focused on exploring biomarkers for its early diagnosis, especially on finding a new gene target. Recent studies have shown that protein interacting with C-kinase-1(PICK1) is related to AD through regulating hippocampal synaptic plasticity. PICK1 gene polymorphisms have been identified in psychological and other related disorders. Methods: This study included 133 sporadic AD patients and 173 healthy controls. All coding exons and intron-exon boundaries of the PICK1 gene were amplified by polymerase chain reaction (PCR), which were subsequently sequenced and analyzed. Results: This is the first genetic association study to investigate the association between PICK1 gene and AD risk in Chinese Han population. Seven single nucleotide polymorphisms (SNPs) were found in our research (rs397780637, rs713729, rs2076369, rs58230476, rs7289911, rs149474436; and rs146770324 for patient M1659 only). Frequencies of the T allele (p = 0.002; OR, 0.083; 95%CI, 0.011-0.634) and TT/TC genotypes (p = 0.001) of rs149474436 were lower in AD patients than in the controls. The GG homozygotes of rs397780637 were found to be associated with an increased risk of AD (p = 0.018) in APOEε4 allele carriers, while the frequency of the T allele of rs149474436 was significantly lower among AD patients in APOEε4 non-carriers (p = 0.005). Conclusions: Our results suggest that PICK1 gene SNPs are associated with AD susceptibility in East Asian population, T allele of rs149474436 may play as a protective factor while the rs397780637 GG homozygotes may be associated with an increased risk of AD. Further studies should be considered in a larger cohort of patients with diverse demographics.