Background:Neuropsychiatric disorders are highly prevalent, significantly impacting patients' Quality of Life. Probiotics can modulate the balance of gut flora, ameliorating neuropsychiatric disorders and ultimately reducing Oxidative Stress (OS) and inflammatory responses. Herein, we aimed to determine the associations of probiotics, prebiotics, synbiotics, and yogurt supplements with Oxidative Balance Scores (OBS) and all-cause and cardiovascular mortalities in neuropsychiatric disorders. Methods:This study utilized the National Health and Nutrition Examination Survey (NHANES) 2007-2018 data, with 13,857 participants included in the final analysis. Probiotics supplements intakes, OBS values, depression, sleep disturbances, and cognitive function were assessed based on questionnaires and laboratory data. Logistic regression, mediation effects analysis, and COX regression modeling were employed to explore these supplements' associations with OBS values in relation to mortality linked to depression, sleep disorders, and cognitive dysfunction. Results:The intake of probiotics was positively correlated with OBS, indicating that the subjects who took probiotic supplements had healthier dietary habits and lifestyles. Mediation analysis revealed that probiotics could improve depressive symptoms (mediation effect = 28.03%, p = 0.024) and cognitive function (mediation effects = 9.26%, 14.64%, and 18.63%, respectively; p < 0.05) by reducing inflammatory responses. Furthermore, probiotic intake correlated negatively with all-cause mortality at the levels of depression, sleep disorders, and cognitive functioning [Hazard Ratio (HR) = 0.874, 0.906, and 0.810, respectively] and cardiovascular mortality related to depression and cognitive dysfunction (HR = 0.963 and 0.403, respectively). Conclusion:Probiotics, prebiotics, synbiotics, and yogurt supplements may reduce inflammatory responses and OS, potentially alleviating neuropsychiatric disorders and improving patients' Survival Rates.

Objectives Insulin resistance has been an established risk factor for cognitive impairment. Patients with moderate to severe obstructive sleep apnea (OSA) are at an increased risk of insulin resistance. However, the correlation between insulin resistance and cognitive impairment in OSA has not yet been confirmed. This study aims to investigate the relationship between brain insulin resistance and mild cognitive impairment (MCI) in patients with OSA. Methods A total of 284 participants with complete clinical data were evaluated at baseline. Brain insulin resistance was assessed using phosphorylated insulin receptor substrate-1 (phospho-IRS-1) and IRS-1 phosphorylation at serine site 312 (pS312-IRS-1) from neuron-derived exosomes isolated by co-immunoprecipitation, while peripheral insulin resistance was evaluated using the triglyceride-glucose (TyG) index. Follow-up measurements of phospho-IRS-1 and pS312-IRS-1 were obtained in 23 patients after weight loss and in 23 patients after continuous positive airway pressure (CPAP) therapy. Results Higher TyG index, phospho-IRS-1, and pS312-IRS-1 levels were associated with an increased risk of cognitive impairment in OSA. Poor cognitive performance correlated with higher phospho-IRS-1 and pS312-IRS-1 levels but not the TyG index. Exploratory mediation models suggested that phospho-IRS-1 and pS312-IRS-1 may partly account for the association between hypoxia and cognitive impairment in OSA, with mediated proportions ranging from 79.64% to 252.03%. Areas under the receiver-operating characteristic curve for insulin resistance-associated proteins ranged from 0.775 to 0.914. Weight loss reduced the phospho-IRS-1 and pS312-IRS-1 levels, while CPAP therapy did not significantly change the phospho-IRS-1 or pS312-IRS-1 levels. Conclusions This study provides evidence of brain insulin resistance in OSA, which has an essential effect on intermittent hypoxia-mediated cognitive impairment. Insulin sensitivity is improved with weight reduction but not CPAP therapy. Brain insulin resistance represents a potential target for early intervention in OSA.

BACKGROUND:Cerebral microbleeds (CMBs) have been found to promote Alzheimer's disease (AD) progression. Hypertension (HTN) is one of the major etiological factors for CMBs and an important risk factor for AD. However, the association between HTN-related CMBs and AD pathology remains undetermined. This study aims to identify the relationship between HTN-related CMBs and amyloid-β 42 (Aβ42) and β-site amyloid precursor protein cleaving enzyme 1 (BACE-1) levels in plasma astrocyte-derived exosomes (ADEs). METHODS:In total, 88 HTN participants including 30 with deep/infratentorial (D/I) CMBs, 30 with mixed CMBs, and 28 without CMBs were analyzed. Susceptibility-weighted imaging was performed to assess the location, presence, and number of CMBs. ELISA kits for BACE-1 and Aβ42 were employed to evaluate the levels of astrocyte-derived exosomal proteins. RESULTS:The results indicated that plasma ADE levels of Aβ42 were reduced in the HTN + D/I CMBs and HTN + Mixed CMBs groups relative to the HTN-CMBs group. Furthermore, the plasma ADE levels of Aβ42 were significantly associated with CMBs in patients with HTN. However, no significant differences were found in the plasma ADE levels of BACE-1 among the HTN + D/I CMBs, HTN + Mixed CMBs, and HTN-CMBs groups. CONCLUSIONS:The study revealed that reduced plasma ADE levels of Aβ42 were significantly associated with CMBs in HTN patients. This finding suggests a potential link between HTN-related CMBs and AD-related amyloid-β pathology, offering novel insights into the mechanisms by which HTN-related CMBs promote AD progression.

BackgroundCoronavirus disease 2019 (COVID-19) may induce cognitive impairment, insomnia, anxiety, and depression through secondary inflammatory reaction. Remote ischemic conditioning (RIC), a promisingly noninvasive intervention, can modulate the inflammatory reaction in target organs and offer organ protection.MethodsThis randomized, placebo-controlled, double-blinded trial recruited 65 patients with COVID-19-related insomnia to investigate whether RIC can improve neuropsychiatric symptoms in COVID-19 patients. Participants were evaluated for neuropsychiatric symptoms including cognition (Beijing version of the Montreal Cognitive Assessment (MoCA)), sleep (Pittsburgh Sleep Quality Index (PSQI), 14-item Fatigue Scale (FS-14) and Epworth Sleepiness Scale (ESS)), anxiety (Hamilton Anxiety Scale (HAMA)) and depression (Hamilton Depression Scale (HAMD-17)). Serum neuronal-derived exosomes (NDEs) complement proteins and mitochondria proteins were extracted and quantified.ResultsMoCA score was significantly ameliorated in the RIC group and the PSQI, FS-14, ESS, HAMA and HAMD-17 scores were remarkably decreased in the RIC group at 3 months (P < 0.001 for MoCA, PSQI, FS-14, and ESS; P = 0.003 for HAMA; P = 0.005 for HAMD-17). The interaction effect of time-by group was also different (P < 0.001 for MoCA, PSQI, FS-14, and ESS; P = 0.003 for HAMA). Furthermore, the PSQI, FS-14, ESS, HAMA, and HAMD-17 scores were statistically decreased in the RIC group at three months after the end of RIC treatment (P < 0.001 for MoCA, PSQI, FS-14, and ESS; P = 0.03 for HAMA; P = 0.027 for HAMD-17).ConclusionsOur study suggested that RIC may be a potential adjuvant therapy for neuropsychiatric symptoms after COVID-19.Clinical trial registrationhttp://www.chictr.org.cn/, identifier ChiCTR2300071190.

Obstructive sleep apnea is characterized by recurrent intermittent hypoxia (IH), which contributes to neuroinflammation and neurological dysfunction. Microglia are pivotal regulators of inflammatory responses in the central nervous system, but the molecular mechanisms underlying IH-induced microglial activation remain unclear. This study aimed to identify key genes mediating this phenomenon and to elucidate their functional significance. An IH model was established in BV2 cells, with inflammation assessed via western blot for cyclooxygenase-2 (COX2) /inducible nitric oxide synthase (iNOS) and ELISA for Interleukin-6 (IL-6) /Tumour necrosis factor-alpha (TNF-α). RNA sequencing was performed to profile transcriptional changes induced by IH. Differential expression analysis, functional enrichment analysis, protein interaction network analysis, transcription factor prediction, and machine learning-based screening were integrated to identify candidate key genes. Pharmacological modulation of Nr1d1 was then performed to evaluate its role in IH-induced inflammation. IH significantly increased COX2, iNOS, IL-6 and TNF-α levels in BV2 cells. Transcriptomics showed distinct profiles between control and IH groups. Enrichment analyses linked IH-related genes to immune regulation, stress responses, and metabolic pathways. Network analysis highlighted a circadian gene cluster as a prominent component of the IH-responsive transcriptional network. Integrated network and machine learning analyses further identified Nr1d1 as a key candidate. Pharmacological experiments showed that inhibition of Nr1d1 attenuated IH-induced inflammatory responses. IH induces pronounced inflammatory activation and transcriptional reprogramming in BV2 cells. Nr1d1 may represent a circadian-associated candidate regulator involved in IH-induced microglial inflammatory activation.

The association of Obstructive Sleep Apnea (OSA) with cognitive deficits is increasingly recognized. In non-demented OSA patients, this research explored the associations among sleep architecture instability, intermittent hypoxia, and cognitive impairment, along with the potential mediating role of IL-6 and core Alzheimer’s disease biomarkers. A total of 370 participants reporting snoring were enrolled and compledted both polysomnography and cognitive assessment. Ultimately, 299 met inclusion criteria. Sleep stage durations and transitions were extracted from hypnograms using a custom program. Blood samples were collected at 7:00 AM for biochemical assays.Neuronal-derived exosomes (NDEs) were immunocaptured for the quantification of total tau (T-tau), amyloid-β (Aβ42), and phosphorylated tau (P-T181-tau) via ELISA. Mediation analysis was employed to evaluate whether inflammatory and Alzheimer’s biomarkers mediate the link between sleep disruption and cognitive performance. A comparative analysis showed significant differences in OSA patients with mild cognitive impairment, including increased sleep fragmentation, ODI, IL-6 levels, and more N1-to-wake transitions compared to controls and OSA patients without MCI. Spearman correlations revealed negative associations between cognitive scores and both N1-to-wake duration and ODI, as well as IL-6. Linear regression showed N1-to-wake duration was positively correlated with IL-6, while ODI correlated with Aβ42 and IL-6. Mediation analyses indicated IL-6 and P-T181-tau served as a partial mediator in impact of intermittent hypoxia on cognition. Sleep instability, along with elevated levels of IL-6, serves as a strong predictor for cognitive impairment observed in OSA. Furthermore, IL-6 and phosphorylated T181-tau in NDEs play a mediating role in the cognitive dysfunction that arises due to intermittent hypoxia.

ObjectiveThe objective of this study is to explore whether metagenomic next-generation sequencing (mNGS) and Epithelial Neutrophil Activating Peptide-78 (ENA-78) assays in the amniotic fluid (AF) of patients with preterm labor (PTL) could be employed for diagnosing intra-amniotic infection/inflammation (IAI/I) and predict the outcomes of emergency cerclage in women with cervical insufficiency(CI).MethodsAF samples from 40 patients were subjected to PTL were subjected to mNGS and microbial culture to diagnose intra-amniotic infection known as microbial invasion of the amniotic cavity (MIAC); ELISA was used to analyze ENA-78 levels for prediction of intra-amniotic inflammation (IAI). Pregnancy outcomes were compared, the predictive performance of mNGS and ENA-78 were assessed to evaluate the efficacy of emergency cervical cerclage.ResultsThe diagnosis rate of MIAC was higher with mNGS (17.5%) compared to microbial culture (2.5%). AF ENA-78 levels were significantly higher in IAI patients than in non-IAI/I patients. ENA-78 demonstrated certain accuracy in identifying IAI, with sensitivity and specificity of 73.3% and 100%, respectively. Compared with non-IAI/I patients, patients with MIAC or IAI exhibited poor pregnancy outcomes after cervical cerclage.ConclusionsmNGS and ENA-78 assays are valuable means for assessing the state of infection/inflammation in the amniotic cavity and predicting the outcomes of emergency cerclage.

BackgroundPrimary long-segment occlusion of the inferior vena cava (IVC) is a rare condition with diverse clinical presentations. The optimal management approach for this condition remains uncertain, warranting further investigation into endovascular treatment methods.MethodsA retrospective study conducted at Qilu Hospital of Shandong University from 2012 to 2018 assessed 16 patients with primary long-segment IVC occlusion. Patients underwent comprehensive imaging evaluations and received endovascular interventions such as angioplasty, stent placement, and online blood flow restoration. Additionally, a literature review was performed to analyze current practices in managing IVC occlusion.ResultsEndovascular treatment was completed in all patients, with favorable primary and secondary patency rates during follow-up. Clinical symptoms significantly improved post-treatment, and the majority of patients achieved IVC patency without major complications. The study showcased the efficacy of angioplasty and stent placement in managing primary IVC occlusion.ConclusionEndovascular therapy is a safe and effective approach for tackling long-segment IVC occlusion, leading to improved patient outcomes. Long-term anticoagulant prophylaxis is advised to mitigate the risk of venous thrombosis in these patients. This study contributes valuable insights for guiding clinical practice in treating primary IVC occlusion.

Thyroid hormones (THs) dysfunctions have been demonstrated to be associated with the risk of developing different types of cancers. The role of THs in regulating hepatocellular carcinoma (HCC) progression is still controversial. We demonstrated that T3 can inhibit HCC progression by enhancing the expression of THRSP. Mechanistically, T3 can activate tumor suppressor LKB1/AMPK/Raptor signaling as well as oncogenic PI3K/Akt signaling in HCC. Interestingly, T3-induced THRSP can augment the activation of LKB1/AMPK/Raptor signaling, yet inhibit T3-induced PI3K/Akt signaling activation, thereby preventing mTOR-induced nuclear translocation of HIF-1α, and ultimately suppressing ENO2-induced glycolysis and HCC progression. More importantly, the exogenous T3 enhances the antitumor effect of multikinase inhibitor lenvatinib in vitro and in vivo by regulating glycolysis. Our findings reveal the role and mechanism of THs in HCC progression and glucose metabolism and provide new potential therapeutic strategies for HCC treatment and drug resistance reversal.

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.

Importance Previous studies revealed limited effectiveness of neuroprotective agents in treating acute ischemic stroke (AIS). Tongxinluo, developed from traditional Chinese medicines, has been recognized as a novel neuroprotective agent with anti-inflammatory properties that stabilize vulnerable plaques in animal models and patients with myocardial infarction. Objective To assess the efficacy and safety of Tongxinluo in patients with acute ischemic stroke (AIS). Design, Setting, and Participants This multicenter, open-label, double-blind, randomized clinical trial included 2007 patients with AIS and a National Institutes of Health Stroke Scale score between 4 and 22 at admission. The trial was conducted at 50 hospitals in China from March 1, 2014, to October 31, 2016. Data were analyzed from November 14, 2016, to November 16, 2017. Interventions Eligible patients were randomized within 72 hours of symptom onset to the Tongxinluo group or the control group. Participants received 4 oral capsules of Tongxinluo or placebo, 3 times a day for 90 days. Other treatment was administrated according to guidelines. Main Outcomes and Measure The primary outcome was a favorable functional outcome at day 90 after randomization, defined as a modified Rankin Scale (mRS) score of 0 to 1 (on a scale of 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]). All statistical analyses were performed in a modified intention-to-treat population, defined as all patients who underwent randomization, were given any treatment, and underwent any posttreatment assessment. Results Among 2007 patients with AIS who were randomized, 1946 (96.5%) were included in the modified intention-to-treat analysis (973 in the Tongxinluo group and 973 in the control group, with mean [SD] age of 60.5 [9.2] years and 1342 [69.0%] male). Patients in the Tongxinluo group had a significantly higher proportion of favorable functional outcomes at day 90 compared with those in the control group (mRS score of 0-1, 640 [65.8%] vs 575 [59.1%]; odds ratio, 1.33 [95% CI, 1.11-1.60]; P = .002). The prespecified subgroup analyses indicated that, among all subgroups, additional Tongxinluo treatment had similar outcomes. Conclusions and Relevance Among patients with ischemic stroke within 72 hours after symptom onset, those additionally receiving Tongxinluo were more likely to have a favorable functional outcome, compared with a placebo group. Further research in patients with thrombolysis and endovascular treatment are needed to explore these outcomes. Trial registration ClinicalTrials.gov Identifier: NCT01919671

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 (beta: 0.505, SE: 0.048, P < 0.001), MOTS-c (beta: 0.580, SE: 0.001, P < 0.001), and NRGN (beta: 0.585, SE: 0.553, P < 0.001). The relationship between sleep parameters (mean SaO(2) 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.

The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B‑related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.

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

Background The presence of sudden onset to maximal deficit (SOTMD) in patients with acute basilar artery occlusion often results in more severe outcomes. However, the effect of endovascular therapy on SOTMD and whether the outcome is affected by onset‐to‐puncture time remain unclear. Methods and Results This retrospective analysis was conducted using data from the prospective BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study Registry). Consecutive patients with basilar artery occlusion receiving endovascular therapy were dichotomized into SOTMD and non‐SOTMD cohorts. The primary outcomes included a favorable outcome (modified Rankin scale 0–3), recanalization, and mortality at 90 days. The outcomes of patients with SOTMD were analyzed using multivariable logistic regression. In the multivariate analysis, a favorable outcome was similar between the two cohorts (odds ratio [OR], 0.88 [95% CI, 0.58–1.34]; P=0.5), although the mortality of patients with SOTMD was higher than that of patients with non‐SOTMD (OR, 1.67 [95% CI, 1.14–2.44]; P=0.008). The probability of mortality increased from 40.0% at 1 hour to 70.0% at 6 hours in the SOTMD cohort, and favorable outcomes of patients with non‐SOTMD declined from 38.0% at 1 hour to 18.0% at 8 hours. Conclusions No significant difference was observed in favorable outcomes between the SOTMD and non‐SOTMD groups, although mortality was higher in the SOTMD cohort. The patients with SOTMD had a stronger time dependence for endovascular therapy in terms of mortality, while the time dependency regarding favorable outcome in the NSOTMD group was even higher. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800014759.

Background: The complement system plays a crucial role in cognitive impairment. The aim of this study is to investigate the correlation between the complement proteins levels in serum astrocyte-derived exosomes (ADEs) and mild cognitive impairment (MCI) in type 1 diabetes mellitus (T1DM) patients.Methods: In this cross-sectional study, the patients with immune-mediated T1DM were enrolled. Healthy subjects matched for age and sex with T1DM patients were selected as controls. The cognitive function was evaluated by a Beijing version of the Montreal Cognitive Assessment (MoCA) questionnaire. The complement proteins including C5b-9, C3b and Factor B in serum ADEs were measured by ELISA kits.Results: This study recruited 55 subjects immune-mediated T1DM patients without dementia, including 31 T1DM patients with MCI, 24 T1DM patients without MCI. 33 healthy subjects were enrolled as controls. The results showed higher complement proteins including C5b-9, C3b and Factor B levels in ADEs from T1DM patients with MCI than those in the controls (P < 0.001, P < 0.001, P = 0.006) and T1DM patients without MCI (P = 0.02, P = 0.02, P = 0.03). The C5b-9 levels in ADEs were independently associated with MCI in T1DM patients (OR: 1.20, 95% CI: 1.00-1.44, P = 0.04). The C5b-9 levels in ADEs were significantly correlated with global cognitive scores (& beta; = -0.360, P<0.001) and visuo-executive (& beta; = -0.132, P<0.001), language (& beta; = -0.036, P = 0.026) and delayed recall score (& beta; = -0.090, P = 0.007). There was no correlation between the C5b-9 levels in ADEs and the fasting glucose, HbA1c, fasting c-peptide and GAD65 antibody in T1DM patients. Furthermore, the C5b-9, C3b and Factor B levels in ADEs exhibited a fair combined diagnostic value for MCI, with an area under the curve of 0.76 (95% CI: 0.63-0.88, P = 0.001).Conclusion: The elevated C5b-9 levels in ADEs were significantly associated with the MCI in T1DM patients. The C5b-9 in ADEs may be used as a marker of MCI in T1DM patients.

STUDY OBJECTIVES:The relationship between autonomic nervous system dysfunction measured by heart rate variability (HRV) and cognitive impairment in obstructive sleep apnea (OSA) patients is complex and still not well understood. We aimed to analyze the role of complement activation, Alzheimer's disease (AD) biomarkers, and white matter hyperintensity (WMH) in modulating the association of HRV with cognitive performance.METHODS:There were 199 subjects without dementia, including 42 healthy controls, 80 OSA patients with mild cognitive impairment (MCI), and 77 OSA patients without cognitive impairment. All participants who completed polysomnography, cognition, WMH volume, and 5-min HRV analysis were recorded during wakefulness and sleep periods. Neuron-derived exosome and astrocyte-derived exosome proteins were measured by ELISA kits.RESULTS:The OSA with MCI group were associated with a lower mean of standard deviations of R-R intervals for 5-min intervals (SDANN index) during wakefulness, standard deviation of the R-R interval (SDNN) during sleep stage and percentage of adjacent R-R intervals differing by more than 50 ms (PNN50) in each stage compared with OSA without MCI. The influence of HRV on cognition was partially mediated by complement activation (C5b-9 mediated a maximum of 51.21%), AD biomarkers, and WMH.CONCLUSIONS:Lower SDANN index and PNN50 during wakefulness and SDNN and PNN50 during sleep periods were found in OSA patients with MCI, suggesting potential vulnerability to autonomic and parasympathetic dysfunction. Complement activation, AD biomarkers, and WMH might partially mediate and interact with the influence of HRV on cognitive impairment in OSA patients.CLINICAL TRIAL REGISTRATION:ChiCTR1900021544.

PURPOSE Brucella aneurysms are very rare but life-threatening, and a standard treatment approach has yet to be established. The current study aimed to assess the safety and efficacy of endovascular treatment for Brucella aneurysms. MATERIALS AND METHODS The clinical data of 15 Brucella aortic-iliac aneurysm patients who underwent endovascular repair at 2 hospitals from January 2012 to December 2021 were retrospectively collected and analyzed. RESULTS Fifteen patients (12 men and 3 women) with a mean age of 59.3 years were included. Fourteen patients (93.3%) had a history of exposure to animals (cattle and sheep). All patients had aortic or iliac pseudoaneurysms, 9 abdominal aortic aneurysms (AAAs), 4 iliac aneurysms, and 2 AAA combined with iliac aneurysms. Endovascular aneurysm repair (EVAR) was performed in all patients without conversion to open surgery. Six cases were treated for emergency surgery due to aneurysm rupture. The immediate technique success rate was 100%, with no postoperative death. Two cases had the iliac artery ruptured again after operation because of lack of antibiotic treatment and was given endovascular treatment again. Once brucellosis is diagnosed, antibiotic treatment with doxycycline and rifampicin was initiated for all the patients until 6 months after operation. All patients survived over a median follow-up period of 45 months. Follow-up computed tomography angiography showed that all stent grafts remained patent, with no endoleak. CONCLUSION EVAR combined with antibiotics treatment is feasible, safe, and effective for Brucella aneurysms and represents a promising treatment option for these Brucella aneurysms. CLINICAL IMPACT Brucella aneurysms are very rare but life-threatening, and a standard treatment approach has yet to be established. The traditional operation management strategy is surgical resection and debridement of the infected aneurysm and the surrounding tissues. However, open surgical management in these patients causes severe trauma with high surgical risks and mortality (13.3%-40%). We tried to treat Brucella aneurysms with endovascular therapy, and the technique success and survival rate of the operation reached 100%. EVAR combined with antibiotics treatment is feasible, safe, and effective for Brucella aneurysms and represents a promising treatment option for some mycotic aneurysms.

An association between neuroinflammation and cognitive decline has been established. The complement system regulates neuroinflammation. Dysregulation, impairment, or inadvertent activation of complement components contribute to preclinical Alzheimer’s disease. The astrocyte-derived exosome (ADE) complement proteins, including C3b and C5b-9, may be predictive biomarkers of mild cognitive impairment conversion to Alzheimer’s disease dementia. We hypothesized that complement proteins might be involved in cognitive impairment during obstructive sleep apnea (OSA). The aim of our study was to explore the correlation between the complement system and mild cognitive impairment (MCI) in patients with OSA. All participants with subjective snoring complaints from the Sleep Medicine Center underwent polysomnography. OSA was defined as apnea-hypopnea index ≥ 5 events/h. MCI was defined as the Montreal Cognitive Assessment < 26 and met the criteria: (1) a subjective cognitive impairment; (2) an objective impairment in 1 or more cognitive domains; (3) complex instrumental daily abilities can be slightly impaired but independent daily living abilities are maintained; and (4) no dementia. The ADEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of complement proteins, including C3b, C5b-9, and CD55. The participants who received continuous positive airway pressure were followed up and their complement protein levels were reassessed after 1 year of treatment. A total of 212 participants (66.98 https://www.chictr.org.cn/ ; Identifier: ChiCTR1900021544.