Electroencephalographic slowdowns during sleep are associated with cognitive impairment in patients who have obstructive sleep apnea but no dementia.

OBJECTIVES: To research the relationship between quantitative electroencephalogram (qEEG) and impaired cognitive function patients who have obstructive sleep apnea (OSA) but no dementia. METHODS: Subjects who complained of snoring between March 2020 and April 2021 in the Sleep Medicine Center of Weihai Municipal Hospital were included. All subjects underwent overnight in-laboratory polysomnography (PSG) and were assessed using a neuropsychological scale. Standard fast fourier transform (FFT) was used to obtain the electroencephalogram (EEG) power spectral density curve, and to calculate the delta, theta, alpha, and beta relative power and the ratio between slow and fast frequencies. Binary logistic regression was used to assess the risk factors for cognitive impairment in patients who had OSA but no dementia. Correlation analysis was performed to determine the relationship between qEEG and cognitive impairment. RESULTS: A total of 175 participants without dementia who met the inclusion criteria were included in this study. There were 137 patients with OSA, including 76 with mild cognitive impairment (OSA + MCI), 61 without mild cognitive impairment (OSA-MCI), and 38 participants without OSA (non-OSA). The relative theta power in the frontal lobe in stage 2 of non-rapid eye movement sleep (NREM 2) in OSA + MCI was higher than that in OSA-MCI (P = 0.038) and non-OSA (P = 0.018). Pearson correlation analysis showed that the relative theta power in the frontal lobe in NREM 2 was negatively correlated with Mini-Mental State Examination (MMSE) scores, Montreal Cognitive Assessment (MoCA) Beijing version scores, and MoCA subdomains scores (visual executive function, naming, attention, language, abstraction, delayed recall and orientation) outside language. CONCLUSIONS: In patients who had OSA but no dementia, the EEG slower frequency power increased. The relative theta power in the frontal lobe in NREM 2 was associated with MCI of patients with OSA. These results suggest that the slowing of theta activity may be one of the neurophysiological changes in the early stage of cognitive impairment in patients with OSA.

Graphery: interactive tutorials for biological network algorithms.

Networks have been an excellent framework for modeling complex biological information, but the methodological details of network-based tools are often described for a technical audience. We have developed Graphery, an interactive tutorial webserver that illustrates foundational graph concepts frequently used in network-based methods. Each tutorial describes a graph concept along with executable Python code that can be interactively run on a graph. Users navigate each tutorial using their choice of real-world biological networks that highlight the diverse applications of network algorithms. Graphery also allows users to modify the code within each tutorial or write new programs, which all can be executed without requiring an account. Graphery accepts ideas for new tutorials and datasets that will be shaped by both computational and biological researchers, growing into a community-contributed learning platform. Graphery is available at https://graphery.reedcompbio.org/.

A case of hypophysis with HIV negative cryptococcal meningitis. / 垂体功能减退症伴HIV阴性的隐球菌性脑膜炎1例.

The clinical mortality of cryptococcal meningitis (CM) is high. There is no report of hypopituitarism associated with HIV negative CM so far. The patients with hypopituitarism complicated with CM are easy to be misdiagnosed and mistreated. A patient with hypopituitarism and HIV negative CM was admitted to Weihai Municipal Hospital on August 27, 2021. The patient was treated for 18 years after craniopharyngioma with headache for more than 2 months, nausea and vomiting for 4 days. MRI showed abnormal enhancement of the right basal ganglia, edema of surrounding tissue, and multiple striated enhancement of the bilateral cerebellar hemisphere. The smear of cerebrospinal fluid showed a large number of fungi and Cryptococcus. Culture of cerebrospinal fluid showed positive in Cryptococcus. The patient's HIV and syphilis antibodies were negative. The condition of the patient was improved after active antifungal therapy. The clinician should make a definite diagnosis and give early treatment as soon as possible.

Genome-wide dissection of hybridization for fiber quality- and yield-related traits in upland cotton.

An evaluation of combining ability can facilitate the selection of suitable parents and superior F1 hybrids for hybrid cotton breeding, although the molecular genetic basis of combining ability has not been fully characterized. In the present study, 282 female parents were crossed with four male parents in accordance with the North Carolina II mating scheme to generate 1128 hybrids. The parental lines were genotyped based on restriction site-associated DNA sequencing and 306 814 filtered single nucleotide polymorphisms were used for genome-wide association analysis involving the phenotypes, general combining ability (GCA) values, and specific combining ability values of eight fiber quality- and yield-related traits. The main results were: (i) all parents could be clustered into five subgroups based on population structure analyses and the GCA performance of the female parents had significant differences between subgroups; (ii) 20 accessions with a top 5% GCA value for more than one trait were identified as elite parents for hybrid cotton breeding; (iii) 120 significant single nucleotide polymorphisms, clustered into 66 quantitative trait loci, such as the previously reported Gh_A07G1769 and GhHOX3 genes, were found to be significantly associated with GCA; and (iv) identified quantitative trait loci for GCA had a cumulative effect on GCA of the accessions. Overall, our results suggest that pyramiding the favorable loci for GCA may improve the efficiency of hybrid cotton breeding.

Effects of orthostatic hypotension on cognition in type 2 diabetes mellitus.

OBJECTIVE: To evaluate the effect of a decrease in blood pressure (BP) fulfilling the diagnostic criteria for orthostatic hypotension (OH) on performance in each domain of cognitive function in patients with type 2 diabetes mellitus using a cross-sectional and within-group design. METHODS: Subjects were individuals without dementia and with type 2 diabetes mellitus, including 107 individuals without OH and 94 with OH (DMOH); 95 control participants were also included. BP was assessed in both the supine and standing positions. A detailed neuropsychological assessment was made in each posture for all subjects. RESULTS: There were statistically significant differences between the patients without OH and the DMOH group with regard to some cognitive measures while supine. Standing posture exacerbated and broadened cognitive deficits in the DMOH group for all measures in the different domains of cognition including executive functioning, memory, visuospatial skills, information processing speed, and attention. When group-specific supine scores were used as baseline anchors, both the patients without OH and the DMOH group showed cognitive changes when transitioning from a supine to a standing, upright position, with the DMOH group exhibiting a wider range of neuropsychological deficits in memory, visuospatial skills, executive function, and sustained attention, as well as significant changes in information processing speed. INTERPRETATION: These data demonstrate that type 2 diabetes mellitus patients with OH had transient, posture-mediated cognitive deficits in excess of those found in diabetes mellitus without OH. Understanding the effects of OH on cognition due to autonomic failure is important, particularly as clinical assessments and neuroimaging collect data only in the seated or supine positions. ANN NEUROL 2019;86:754-761.

LBX2-AS1 up-regulated by NFIC boosts cell proliferation, migration and invasion in gastric cancer through targeting miR-491-5p/ZNF703.

BACKGROUND: The crucial role of long non-coding RNAs (lncRNAs) has been certified in human cancers. The lncRNAs with abnormal expressions could act as tumor inhibitors or oncogenes in the advancement of tumors. LBX2-AS1 was once reported to accelerate esophageal squamous cell carcinoma. Nonetheless, its function in gastric cancer (GC) remained a riddle. METHODS: RT-qPCR was used to examine the expression of NFIC/LBX2-AS1/miR-491-5p/ZNF703 in GC cell lines. The functions of LBX2-AS1 in GC were appraised by colony formation, EdU, flow cytometry analysis, transwell and wound healing assays. Luciferase reporter, ChIP and RNA pull down assays were utilized to evaluate the interactions among genes. RESULTS: LBX2-AS1 was up-regulated in GC cell lines. Knockdown of LBX2-AS1 repressed the proliferative, migratory, and invasive abilities of GC cells. Moreover, LBX2-AS1 was transcriptionally activated by NFIC. And LBX2-AS1 could bind with miR-491-5p. Besides, miR-491-5p depletion or ZNF703 upregulation could counteract the repressing effects of LBX2-AS1 silence on GC progression. CONCLUSION: In a word, LBX2-AS1 up-regulated by NFIC promoted GC progression via targeting miR-491-5p/ZNF703, implying LBX2-AS1 was an underlying treatment target for GC patients.

Association between lumbar disc herniation and facet joint osteoarthritis.

BACKGROUND: This study was performed to investigate the association between lumbar disc herniation (LDH) and facet joint osteoarthritis (FJOA) using magnetic resonance imaging (MRI). METHODS: Between March 2012 and September 2018, a total of 441 segments from 394 patients with LDH were included in the study. LDH was classified according to the Michigan State University (MSU) classification, in which the degree of LDH is divided into 3 levels (expressed as 1, 2, and 3) and the location of LDH is divided into 4 zones (described as A, AB, B, and C). Bilateral FJOA was graded from 0 to 3 using the criteria introduced by Weishaupt et al., and bilateral facet orientations were measured on axial MRI slices. A mixed-effects ordinal logistic regression model was utilized to determine the potential factors that may be associated with FJOA, including sex, age, body mass index (BMI), segment, facet orientation and tropism, and the degree and location of LDH. RESULTS: In general, the prevalence of FJOA (grade ≥ 2) was 66.2% in LDH segments. For both the left and right sides, the degree of LDH was associated with the severity of FJOA (p < 0.01). Age and BMI were also associated with the severity of left and right FJOA (p = 0.002 and p < 0.001 for age, p < 0.001 and p = 0.003 for BMI, respectively), while segment, facet orientation, and facet tropism were not (p > 0.05 for all). Notably, MSU-B LDH was associated with greater odds of having more severe FJOA on the herniation side (left: p < 0.001, odds ratio (OR) = 2.714, 95% confidence interval (CI) = 1.583~4.650; right: p = 0.003, OR = 2.615, 95% CI = 1.405~4.870). However, other locations of LDH were not associated with the severity of FJOA (p > 0.05 for all). CONCLUSIONS: Both the degree of LDH and MSU-B LDH are associated with the severity of FJOA. The association between LDH and FJOA highlights the complexity of the etiology of FJOA.

Analysis and improvement of the three-column spinal theory.

BACKGROUND: Denis and Ferguson et al.'s three-column spinal theory has been widely accepted and applied. However, this three-column theory was proposed based solely on observation and experience without thorough documented data and analysis. The aim of this study was to analyze and improve Denis and Ferguson et al.'s three-column spinal theory to propose a novel three-column concept in epidemiology, morphology and biomechanics. METHODS: A retrospective analysis of the computed tomography imaging data of patients with a diagnosis of T11-L5 vertebral fractures was conducted between February 2010 and December 2018. Three-dimensional (3D) distribution maps of fracture lines of all subjects were obtained based on 3D mapping techniques. In addition, a 25-year-old health male volunteer was recruited for the vertebral finite element force analysis. RESULTS: The present study enrolled 459 patients (age: 48 ± 11.42 years), containing a total of 521 fractured vertebrae. The fracture lines peaked in the upper and the outer third sections of the vertebra, starting from the anterior part of the vertebral pedicles in 3-D maps. Regarding flexion and extension of the spine, the last third of the vertebral body in front of the spinal canal was one main stress center in the finite element analysis. The stress on the vertebral body was greater in front of the pedicles in the lateral bending. CONCLUSION: The study reveals that the posterior one-third of the vertebral body in front of the spinal canal and the posterior one-third of the vertebral body in front of the pedicle are very different in terms of fracture characteristics and risks to spinal canal (3D maps and stress distributing graphs), therefore, they should be classified as different columns. We provide strong evidence that Su's three-column theory complies with the characteristics of vertebral physiological structure, vertebral fracture, and vertebral biomechanics.

Integration of conventional and advanced molecular tools to track footprints of heterosis in cotton.

BACKGROUND: Heterosis, a multigenic complex trait extrapolated as sum total of many phenotypic features, is widely utilized phenomenon in agricultural crops for about a century. It is mainly focused on establishing vigorous cultivars with the fact that its deployment in crops necessitates the perspective of genomic impressions on prior selection for metric traits. In spite of extensive investigations, the actual mysterious genetic basis of heterosis is yet to unravel. Contemporary crop breeding is aimed at enhanced crop production overcoming former achievements. Leading cotton improvement programs remained handicapped to attain significant accomplishments. RESULTS: In mentioned context, a comprehensive project was designed involving a large collection of cotton accessions including 284 lines, 5 testers along with their respective F1 hybrids derived from Line × Tester mating design were evaluated under 10 diverse environments. Heterosis, GCA and SCA were estimated from morphological and fiber quality traits by L × T analysis. For the exploration of elite marker alleles related to heterosis and to provide the material carrying such multiple alleles the mentioned three dependent variables along with trait phenotype values were executed for association study aided by microsatellites in mixed linear model based on population structure and linkage disequilibrium analysis. Highly significant 46 microsatellites were discovered in association with the fiber and yield related traits under study. It was observed that two-thirds of the highly significant associated microsatellites related to fiber quality were distributed on D sub-genome, including some with pleiotropic effect. Newly discovered 32 hQTLs related to fiber quality traits are one of prominent findings from current study. A set of 96 exclusively favorable alleles were discovered and C tester (A971Bt) posited a major contributor of these alleles primarily associated with fiber quality. CONCLUSIONS: Hence, to uncover hidden facts lying within heterosis phenomenon, discovery of additional hQTLs is required to improve fibre quality. To grab prominent improvement in influenced fiber quality and yield traits, we suggest the A971 Bt cotton cultivar as fundamental element in advance breeding programs as a parent of choice.

The cost of Alzheimer's disease in China and re-estimation of costs worldwide.

INTRODUCTION: The socioeconomic costs of Alzheimer's disease (AD) in China and its impact on global economic burden remain uncertain. METHODS: We collected data from 3098 patients with AD in 81 representative centers across China and estimated AD costs for individual patient and total patients in China in 2015. Based on this data, we re-estimated the worldwide costs of AD. RESULTS: The annual socioeconomic cost per patient was US $19,144.36, and total costs were US $167.74 billion in 2015. The annual total costs are predicted to reach US $507.49 billion in 2030 and US $1.89 trillion in 2050. Based on our results, the global estimates of costs for dementia were US $957.56 billion in 2015, and will be US $2.54 trillion in 2030, and US $9.12 trillion in 2050, much more than the predictions by the World Alzheimer Report 2015. DISCUSSION: China bears a heavy burden of AD costs, which greatly change the estimates of AD cost worldwide.

Association mapping analysis of fiber yield and quality traits in Upland cotton (Gossypium hirsutum L.).

Fiber yield and quality are the most important traits for Upland cotton (Gossypium hirsutum L.). Identifying high yield and good fiber quality genes are the prime concern of researchers in cotton breeding. Association mapping offers an alternative and powerful method for detecting those complex agronomic traits. In this study, 198 simple sequence repeats (SSRs) were used to screen markers associated with fiber yield and quality traits with 302 elite Upland cotton accessions that were evaluated in 12 locations representing the Yellow River and Yangtze River cotton growing regions of China. Three subpopulations were found after the estimation of population structure. The pair-wise kinship values varied from 0 to 0.867. Only 1.59% of the total marker locus pairs showed significant linkage disequilibrium (LD, p < 0.001). The genome-wide LD decayed within the genetic distance of ~30 to 32 cM at r 2 = 0.1, and decreased to ~1 to 2 cM at r 2 = 0.2, indicating the potential for association mapping. Analysis based on a mixed linear model detected 57 significant (p < 0.01) marker-trait associations, including seven associations for fiber length, ten for fiber micronaire, nine for fiber strength, eight for fiber elongation, five for fiber uniformity index, five for fiber uniformity ratio, six for boll weight and seven for lint percent, for a total of 35 SSR markers, of which 11 markers were associated with more than one trait. Among marker-trait associations, 24 associations coincided with the previously reported quantitative trait loci (QTLs), the remainder were newly identified QTLs/genes. The QTLs identified in this study will potentially facilitate improvement of fiber yield and quality in the future cotton molecular breeding programs.

Association between platelet function and recurrent ischemic vascular events after TIA and minor stroke
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Platelet activation and aggregation play an important role in the pathological and physiological processes of recurrent ischemic vascular events in stroke patients. The purpose of this study is to determine the association between platelet function measured in the acute period and recurrent ischemic vascular events in patients with transient ischemic attack (TIA) or minor stroke. A total of 417 patients who were within the 24-hour period of clopidogrel-aspirin therapy after onset of a minor stroke or high-risk transient ischemic attack according to the Clopidogrel in High-risk patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial were included in this study. The platelet aggregation ratio was detected using a method of continuous platelet counting; patients underwent CYP2C19 genotyping, and the baseline data were recorded. The patients underwent a 6-month follow-up period during which the recurrent ischemic vascular events were observed. Logistic regression analysis was performed to obtain the risk factors for recurrent ischemic vascular events. The number of patients with recurrent ischemic events who had an arachidonic acid-induced maximum platelet aggregation ratio (MAR-AA) (aspirin 100 mg) (31.85 ± 12.86 vs. 26.71 ± 12.44, p = 0.007) and adenosine diphosphate-induced maximum platelet aggregation ratio (MAR-ADP) after the administration of 75 mg clopidogrel for 12 ± 2 days (65.82 ± 10.72 vs. 53.10 ± 12.98, p < 0.001) was significantly higher compared with the no ischemic vascular event group. Multivariate logistic regression analyses showed that being a carrier of the CYP2C19 loss-of-function (LOF) allele (OR = 2.308, 95% CI: 1.087 ~ 4.901, p = 0.029) as well as the MAR-AA (aspirin 100 mg) (OR = 1.028, 95% CI: 1.006  ~  1.052, p = 0.014) and MAR-ADP after the administration of 75 mg clopidogrel (OR = 1.067, 95% CI: 1.037 ~ 1.095, p < 0.001) were risk factors for ischemic vascular events. The MAR-ADP after the administration of 75 mg clopidogrel was significantly higher in patients who were carriers of the CYP2C19 (LOF) allele compared with non-carriers (57.53 ± 13.32 vs. 50.86 ± 12.55, p < 0.001), and no significant differences between the CYP2C19 LOF allele carriers and non-carriers in the MAR-ADP were detected after the administration of 300 mg clopidogrel (37.18 ± 11.36 vs. 35.86 ± 12.49, p = 0.264). Being a carrier of the CYP2C19 LOF allele has a significant influence on clopidogrel response. Platelet function is closely related to recurrent ischemic vascular events in acute minor stroke or TIA patients.
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Ischemic Stroke in Young Adults of Northern China: Characteristics and Risk Factors for Recurrence.

BACKGROUND: Young adults accounted for 10-14% of ischemic stroke patients. The risk factors may differ in this population from elder patients. In addition, the factors associated with stroke recurrence in this population have not been well investigated. OBJECTIVE: The study aimed to investigate the characteristics and risk factors associated with recurrence of ischemic stroke in young adults. METHODS: Clinical data of 1,395 patients of age 18-45 years who were treated between 2008 and 2014 in 3 centers located in northern China was reviewed. The first onset of stroke was taken as the initial events and recurrent stroke as the end point events. The end point events, age, gender, duration after first onset of stroke, history of disease, National Institutes of Health Stroke Scale (NIHSS) score at admission, Trial of Org 10172 in Acute Stroke Treatment classifications of the cause of stroke and adherence to medication were recorded. These factors were analyzed and compared between recurrence and non-recurrence group. Information about recurrent stroke was collected through clinical (readmission to hospital with ischemic stroke) or telephone follow-up survey. Logistic regression was used to analyze the risk factors of recurrence. RESULTS: The most common causes of stroke were large vessel atherosclerosis and small vessel occlusion, followed by cardioembolism. NIHSS score at admission (OR 1.088; 95% CI 1.028-1.152; p = 0.004) were associated with recurrence. CONCLUSIONS: Vascular disease, especially premature atherosclerosis, is the major risk factor for ischemic stroke in the young adult population of northern China. Timely screening of the cause of stroke with severe NIHSS score needs further attention.

Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients.

BACKGROUND: The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. SUBJECTS AND METHODS: Data from 176 PD patients participating in the collaborative PD study between June 2010 and June 2014 were collected; the Chinese edition of the Montreal Cognitive Assessment (MoCA) score was used to evaluate the cognitive function of patients, and falls were recorded. PD patients with cognitive dysfunction were randomly administered either a placebo or Rivastigmine. The cognitive function changes and difference in fall incidence were compared between the 2 groups. RESULTS: The average number of falls per person in PD patients without cognitive impairment dysfunction was significantly lower than that in patients in the PD mild cognitive impairment (PD-MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001, respectively), and the incidence of falls was significantly lower than that in patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively). Compared to the PD-MCI group, the incidence of falls of patients in the PDD group (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were significantly increased (p < 0.01). After taking the placebo or Rivastigmine for 12 months, the MoCA scores of patients in the Rivastigmine treatment group were significantly higher than those of the control group (p = 0.002). The number of falls per person and the incidence of falls of patients in Rivastigmine treatment group were significantly lower than those in the placebo group (p < 0.01). CONCLUSION: This study suggests that the degree of cognitive impairment is closely associated with the incidence of falls, and the cholinesterase inhibitor Rivastigmine can delay the deterioration of cognitive function and lower the incidence of falls in PD patients.

The effect of creatine and coenzyme q10 combination therapy on mild cognitive impairment in Parkinson's disease.

BACKGROUND: To investigate the effect of creatine and coenzyme Q10 (CoQ10) combination therapy on mild cognitive impairment (MCI) in Parkinson's disease (PD; PD-MCI) and its influences on plasma phospholipid (PL) levels in PD-MCI. METHODS: The demographic data of 75 PD-MCI patients who enrolled in this collaborative PD study were collected. These patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) III and the Montreal Cognitive Assessment (MoCA). These 75 PD-MCI patients were randomly treated with creatine monohydrate 5 g b.i.d. and CoQ10 100 mg t.i.d. orally or placebo. MoCA evaluation and PL level measurements were performed after 12 and 18 months of treatment. RESULTS: After 12 and 18 months of treatment, the differences in the MoCA scores of the combination therapy and control groups were statistically significant (p < 0.05 at 12 months and p < 0.01 at 18 months), and the plasma PL levels of the combination therapy group were significantly lower than those of the control group (p < 0.01 at 12 months and p < 0.001 at 18 months). CONCLUSIONS: Combination therapy with creatine and CoQ10 could delay the decline of cognitive function in PD-MCI patients and could lower their plasma PL levels; therefore, this combination therapy may have a neuroprotective function.

Mechanisms of immune injury and heterogeneity of bone marrow hematopoietic cells island in patients with auto-immuno-related hematocytopenia.

Because of environmental pollution more and more people are suffered with auto-immuno-related hematocytopenia (AIRH). Serum IL-12, IL-17, and IFN-γ levels were detected by ELISA and lymphocyte subsets were analyzed by flow cytometry. Peroxidase (POX) and HLA-DR of immune cells were detected by cytochemical and immunochemical staining. Cells expressing anti-human IgG, FcγR II, MR, and other molecules in HI were detected by immunofluorescence. Serum IL-12, IL-17, and IFN-γ levels of patients were significantly higher than control group. Lymphocyte subsets of patients showed that the percentages of CD19+ B cells and CD3+ CD8+ T cell in peripheral blood were both significantly elevated. HI were mainly classified into three types, in these three types of hematopoietic cells island, peroxidase, and HLA-DR expression varied. Hematopoietic cells with pathological changes expressed anti-human IgG. The immunocytes with different levels of immunomolecules adhered captured and devoured abnormal hematopoietic cells. Immune cells expressed IL-12, IL-17A, and IL-17RA, leading to inflammatory injury of hematopoietic cells. HI destroys cells which connect auto-antibodies. Immune cells in HI express a variety of immune molecules, promote cell immune responses, and amplify the inflammatory reaction by ADCC effect or phagocytosis. These ultimately destruct directly and damage indirectly hematopoietic cells.

Glucose Fluctuation Inhibits Nrf2 Signaling Pathway in Hippocampal Tissues and Exacerbates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats.

Background: This research investigated whether glucose fluctuation (GF) can exacerbate cognitive impairment in streptozotocin-induced diabetic rats and explored the related mechanism. Methods: After 4 weeks of feeding with diets containing high fats plus sugar, the rat model of diabetes mellitus (DM) was established by intraperitoneal injection of streptozotocin (STZ). Then, GF was triggered by means of alternating satiety and starvation for 24 h. The weight, blood glucose level, and water intake of the rats were recorded. The Morris water maze (MWM) test was carried out to appraise the cognitive function at the end of week 12. Moreover, the morphological structure of hippocampal neurons was viewed through HE and Nissl staining, and transmission electron microscopy (TEM) was performed for ultrastructure observation. The protein expression levels of Nrf2, HO-1, NQO-1, Bax, Bcl-2, and Caspase-3 in the hippocampal tissues of rats were measured via Western blotting, and the mRNA expressions of Nrf2, HO-1, and NQO-1 were examined using qRT-PCR. Finally, Western blotting and immunohistochemistry were conducted to detect BDNF levels. Results: It was manifested that GF not only aggravated the impairment of spatial memory in rats with STZ-induced type 2 DM but also stimulated the loss, shrinkage, and apoptosis of hippocampal neurons. Regarding the expressions in murine hippocampal tissues, GF depressed Nrf2, HO-1, NQO-1, Bcl-2, and BDNF but boosted Caspase-3 and Bax. Conclusions: GF aggravates cognitive impairment by inhibiting the Nrf2 signaling pathway and inducing oxidative stress and apoptosis in the hippocampal tissues.

Mitochondrial dysfunction is associated with cognitive impairment in adults with OSA without dementia.

STUDY OBJECTIVES: Increased reactive oxygen species associated with loss of mitochondrial function affect synaptic activity, which is an important mechanism underlying cognitive decline. This study assesses the role of mitochondrial proteins in neuron-derived exosomes (NDEs) on cognitive impairment in patients with obstructive sleep apnea (OSA) without dementia. METHODS: Analyses were conducted in 268 study participants with complete polysomnography data, cognitive tests, and important clinical data available. NDEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of mitochondrial proteins, i.e., humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), and synaptic protein, i.e., neurogranin (NRGN). A mediation analysis of the relationship between sleep parameters and cognition was performed using humanin, MOTS-c, and NRGN values as a mediating factor. Twenty-two patients with moderate to severe OSA who received CPAP therapy were followed up, and humanin, MOTS-c and NRGN levels were reassessed after 1 year of treatment. RESULTS: All participants were divided into the OSA + MCI group (n = 91), OSA-MCI group (n = 89), MCI group (MCI without OSA) (n = 38) and control group (normal cognitive state without OSA) (n = 50). The mean CD63-normalized NDE levels of humanin, MOTS-c, and NRGN in the OSA + MCI group were higher than those in the OSA-MCI and control groups. The NDE levels of humanin, MOTS-c, and NRGN in the MCI group were lower than those in controls. The odds of cognitive impairment in patients with OSA were higher with higher NDE levels of humanin, MOTS-c, and NRGN (odds ratio (OR): 2.100, 95 % confidence interval (CI): 1.646-2.679, P < 0.001; OR: 5.453, 95 % CI: 3.112-9.556, P < 0.001; OR: 3.115, 95 % CI: 2.163-4.484, P < 0.001). The impaired cognitive performance was associated with higher NDE levels of humanin (ß: 0.505, SE: 0.048, P < 0.001), MOTS-c (ß: 0.580, SE: 0.001, P < 0.001), and NRGN (ß: 0.585, SE: 0.553, P < 0.001). The relationship between sleep parameters (mean SaO2 and T90) and MoCA scores was mediated by the NDE levels of humanin, MOTS-c, and NRGN with the proportion of mediation varying from 35.33 % to 149.07 %. Receiver operating characteristic curve revealed an area under the curve of 0.905 for humanin, 0.873 for MOTS-c, and 0.934 for NRGN to predict MCI in OSA patients without dementia. Increased humanin, MOTS-c, and NRGN levels significantly decreased after CPAP treatment. CONCLUSIONS: Mitochondrial dysfunction is implicated in cognitive impairment in OSA patients without dementia, and mainly mediates the association between intermittent hypoxia and cognitive impairment in adults with OSA without dementia. Mitochondrial dysfunction can be partially reversible by CPAP treatment. Mitochondrial proteins can be used as markers of cognitive impairment in patients with OSA.

Complement Proteins in Serum Astrocyte-Derived Exosomes Are Associated with Poststroke Cognitive Impairment in Type 2 Diabetes Mellitus Patients.

Background: The complement system plays crucial roles in cognitive impairment and acute ischemic stroke (AIS). High levels of complement proteins in plasma astrocyte-derived exosomes (ADEs) were proven to be associated with Alzheimer's disease. We aimed to investigate the relationship of complement proteins in serum ADEs with poststroke cognitive impairment in type 2 diabetes mellitus (T2DM) patients. Methods: This study analyzed 197 T2DM patients who suffered AIS. The Beijing version of the Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Complement proteins in serum ADEs were quantified using ELISA kits. Results: Mediation analyses showed that C5b-9 and C3b in serum ADEs partially mediate the impact of obstructive sleep apnea (OSA), depression, small vessel disease (SVD), and infarct volume on cognitive function at the acute phase of AIS in T2DM patients. After adjusting for age, sex, time, and interaction between time and complement proteins in serum ADEs, the mixed linear regression showed that C3b and complement protein Factor B in serum ADEs were associated with MoCA scores at three-, six-, and twelve-months after AIS in T2DM patients. Conclusions: Our study suggested that the impact of OSA, depression, SVD, and infarct volume on cognitive impairment in the acute stage of AIS may partially mediate through the complement proteins in serum ADEs. Additionally, the complement proteins in serum ADEs at the acute phase of AIS associated with MoCA scores at three-, six-, twelve months after AIS in T2DM patients.REGISTRATION: URL: http://www.chictr.org.cn/,ChiCTR1900021544.

Orthostatic Hypotension Promotes the Progression From Mild Cognitive Impairment to Dementia in Type 2 Diabetes Mellitus.

CONTEXT: In type 2 diabetes mellitus (T2DM), orthostatic hypotension (OH) is associated with cognition, but the mechanisms governing the link between OH and cognition are still unclear. OBJECTIVE: We sought to analyze Alzheimer's disease (AD) biomarkers and the part of complement proteins in modulating the association of OH with cognitive impairment and examine whether OH could accelerate the clinical progression of mild cognitive impairment (MCI) to dementia in T2DM. METHODS: We recruited patients with T2DM with MCI and collected general healthy information and blood samples. Complement proteins of astrocyte-derived exosomes were isolated and AD biomarkers of neuronal cell-derived exosomes isolated were quantified by enzyme-linked immunosorbent assay. Cognitive assessments were performed at patient enrollment and follow-up. RESULTS: Mediation analysis showed that the influence of OH on cognition in T2DM was partly mediated by baseline AD biomarkers and complement proteins. Cox proportional-hazards regression proved the OH group had a higher risk of developing dementia compared to the T2DM without OH group. CONCLUSION: In T2DM with MCI patients, AD biomarkers and complement proteins mediate the effects of OH on cognitive impairment and OH may be a risk factor of progression from MCI to dementia in T2DM.