Safety and efficacy of GLP-1 and glucagon receptor dual agonist for the treatment of type 2 diabetes and obesity: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This study aimed to investigate the effects of randomized, placebo-controlled trials involving the GLP-1 and glucagon receptor dual agonists, mazdutide, and cotadutide, on glycaemic control and body weight changes in individuals with type 2 diabetes mellitus (T2DM), obesity, or both. METHODS: We conducted searches in Medline, PubMed, Scopus, the Cochrane database, and Web of Science up to March 5, 2024. The primary outcomes assessed were changes in HbA1c level and percentage changes in body weight from baseline (CFB). RESULTS: Eleven studies and four unpublished trials were included. The pooled meta-analysis revealed a significant reduction in HbA1c (MD = -0.63%; 95% CI = [-0.82, -0.44]; P < 0.00001), fasting plasma glucose (MD = -1.71 mmol/L; 95% CI = [-2.31, -1.10]; P < 0.00001), and percentage change in body weight (MD = -4.16%; 95% CI = [-5.41, -2.92]; P < 0.00001). Safety analysis revealed no significant change in serious adverse events (OR = 1.03; 95% CI = [0.61, 1.75]; P = 0.91), but there were significantly higher odds of treatment-emergent adverse events (OR = 2.52; 95% CI = [1.92, 3.30]; P < 0.00001) and vomiting (OR = 6.05; 95% CI = [3.52, 10.40]; P < 0.00001). CONCLUSION: These results suggest that mazdutide and cotadutide are effective for glycaemic control and weight reduction in individuals with T2DM, obesity, or both.

Unveiling the potential of breast MRI: a game changer for BI-RADS 4A microcalcifications.

PURPOSE: To assess the diagnostic performance of breast MRI for BI-RADS 4A microcalcifications on mammography and propose a potential clinical pathway to avoid unnecessary biopsies. METHODS: Bibliometrics analysis of breast MRI and BI-RADS 4 was provided. A retrospective analysis was conducted on 139 women and 142 cases of BI-RADS 4A microcalcifications on mammography from Fudan University Shanghai Cancer Center. The mammographic BI-RADS level and the MRI reports were compared with the final pathological diagnosis. RESULTS: Much attention has been given to breast MRI and BI-RADS 4 in the literature. However, studies on BI-RADS 4A are limited. Pathological results showed 117 cases (82.4%) were benign lesions, malignant cases of 25 (17.6%) in our study. The positive predictive values (PPV), specificity, sensitivity and negative predictive values (NPV) of MRI were 44.2% (23/52), 75.2% (88/117), 92.0% (23/25), and 97.8% (88/90), respectively. Therefore, 75.2% (88/117) of biopsies for benign lesions could potentially be avoided. There were 2.2% (2/90) malignant lesions missed. Logistic regression indicated that patients who are postmenopausal (HR = 2.655, p = 0.012), have a history of breast cancer (family history) (HR = 2.833, p = 0.029), and exhibit clustered microcalcifications (HR = 2.179, p = 0.046) are more likely to have a higher MRI BI-RADS level. CONCLUSIONS: Breast MRI has the potential to improve the diagnosis of BI-RADS 4A microcalcifications on mammography. We propose a potential clinical pathway that patients with BI-RADS 4A on mammography who are premenopausal, have no personal history of breast cancer (family history) or have non-clustered distribution of calcifications can undergo MRI to avoid unnecessary biopsies.

Characteristics of Volatile Organic Compounds Emitted from Airport Sources and Their Effects on Ozone Production.

In recent years, commercial air transport has increased considerably. However, the compositions and source profiles of volatile organic compounds (VOCs) emitted from aircraft are still not clear. In this study, the characteristics of VOCs (including oxygenated VOCs (OVOCs)) emitted from airport sources were measured at Shenzhen Bao'an International Airport. The results showed that the compositions and proportions of VOC species showed significant differences as the aircraft operating state changed. OVOCs were the dominant species and accounted for 63.17%, 58.44%, and 51.60% of the total VOC mass concentration during the taxiing, approach, and take-off stages. Propionaldehyde and acetone were the main OVOCs, and dichloromethane and 1,2-dichloroethane were the main halohydrocarbons. Propane had the highest proportion among all alkanes, while toluene and benzene were the predominant aromatic hydrocarbons. Compared with the source profiles of VOCs from construction machinery, the proportions of halogenated hydrocarbons and alkanes emitted from aircraft were significantly higher, as were those of propionaldehyde and acetone. OVOCs were still the dominant VOC species in aircraft emissions, and their calculated ozone formation potential (OFP) was much higher than that of other VOC species at all stages of aircraft operations. Acetone, propionaldehyde, formaldehyde, acetaldehyde, and ethylene were the greatest contributors to ozone production. This study comprehensively measured the distribution characteristics of VOCs, and its results will aid in the construction of a source profile inventory of VOCs emitted from aircraft sources in real atmospheric environments.

A metagenomic catalog of the early-life human gut virome.

Early-life human gut microbiome is a pivotal driver of gut homeostasis and infant health. However, the viral component (known as "virome") remains mostly unexplored. Here, we establish the Early-Life Gut Virome (ELGV), a catalog of 160,478 non-redundant DNA and RNA viral sequences from 8130 gut virus-like particles (VLPs) enriched or bulk metagenomes in the first three years of life. By clustering, 82,141 viral species are identified, 68.3% of which are absent in existing databases built mainly from adults, and 64 and 8 viral species based on VLPs-enriched and bulk metagenomes, respectively, exhibit potentials as biomarkers to distinguish infants from adults. With the largest longitudinal population of infants profiled by either VLPs-enriched or bulk metagenomic sequencing, we track the inherent instability and temporal development of the early-life human gut virome, and identify differential viruses associated with multiple clinical factors. The mother-infant shared virome and interactions between gut virome and bacteriome early in life are further expanded. Together, the ELGV catalog provides the most comprehensive and complete metagenomic blueprint of the early-life human gut virome, facilitating the discovery of pediatric disease-virome associations in future.

Glymphatic system impairment in Alzheimer's disease: associations with perivascular space volume and cognitive function.

OBJECTIVES: To investigate glymphatic function in Alzheimer's disease (AD) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and to explore the associations between DTI-ALPS index and perivascular space (PVS) volume, as well as between DTI-ALPS index and cognitive function. METHODS: Thirty patients with PET-CT-confirmed AD (15 AD dementia; 15 mild cognitive impairment due to AD) and 26 age- and sex-matched cognitively normal controls (NCs) were included in this study. All participants underwent neurological MRI and cognitive assessments. Bilateral DTI-ALPS indices were calculated. PVS volume fractions were quantitatively measured at three locations: basal ganglia (BG), centrum semiovale, and lateral ventricle body level. DTI-ALPS index and PVS volume fractions were compared among three groups; correlations among the DTI-ALPS index, PVS volume fraction, and cognitive scales were analyzed. RESULTS: Patients with AD dementia showed a significantly lower DTI-ALPS index in the whole brain (p = 0.009) and in the left hemisphere (p = 0.012) compared with NCs. The BG-PVS volume fraction in patients with AD was significantly larger than the fraction in NCs (p = 0.045); it was also negatively correlated with the DTI-ALPS index (r = - 0.433, p = 0.021). Lower DTI-ALPS index was correlated with worse performance in the Boston Naming Test (ß = 0.515, p = 0.008), Trail Making Test A (ß = - 0.391, p = 0.048), and Digit Span Test (ß = 0.408, p = 0.038). CONCLUSIONS: The lower DTI-ALPS index was found in patients with AD dementia, which may suggest impaired glymphatic system function. DTI-ALPS index was correlated with BG-PVS enlargement and worse cognitive performance in certain cognitive domains. CLINICAL RELEVANCE STATEMENT: Diffusion tensor image analysis along the perivascular space index may be applied as a useful indicator to evaluate the glymphatic system function. The impaired glymphatic system in patients with Alzheimer's disease (AD) dementia may provide a new perspective for understanding the pathophysiology of AD. KEY POINTS: • Patients with Alzheimer's disease dementia displayed a lower diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, possibly indicating glymphatic impairment. • A lower DTI-ALPS index was associated with the enlargement of perivascular space and cognitive impairment. • DTI-ALPS index could be a promising biomarker of the glymphatic system in Alzheimer's disease dementia.

Evaluation of Safety and Efficacy of Amniotic Mesenchymal Stem Cells for POI in Animals.

The efficacy of human amniotic mesenchymal stem cell (hAMSC) ovarian injection in improving ovarian function in primary ovarian insufficiency (POI) patients has been shown in some reports. However, the safety and efficacy of hAMSC vein injection remains unclear. In this study, we evaluated the safety and efficacy of hAMSC intravenous injection in cynomolgus macaques and SD rats and provided evidence for clinical trials. The hAMSCs were transplanted three times in SD rats at low, medium, and high doses. The animal behavior and biochemical and biophysical parameters were routinely monitored on a 2-month period posttransplantation, and histopathologic examinations were also performed. Experiments on the acute toxicity, allergy test, and hemolysis test showed that hAMSCs possess good biocompatibility. Our results showed that the maximum tolerated dose of hAMSCs in SD rats was 4.0 × 107 cells/kg. The maximum safe dose with three injections of hAMSCs in SD rats was 5.0 × 106 cells/kg. In addition, the results demonstrated that hAMSCs may restore POI rat ovarian function after two injections of 2.5 × 106 cells/kg or 5.0 × 106 cells/kg, which improved the disturbed estrous cycle, hormone levels, and ovarian lesions induced by pZP3. In conclusion, the preclinical results suggested that the transplantation of hAMSCs may be safe and efficacious for SD rats at doses of 5.0 × 106 cells/kg and lower.

Atorvastatin Promotes Pro/anti-inflammatory Phenotypic Transformation of Microglia via Wnt/ß-catenin Pathway in Hypoxic-Ischemic Neonatal Rats.

Inflammatory reaction plays a key role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonates. Microglia are resident innate immune cells in the central nervous system and are profoundly involved in neuroinflammation. Studies have revealed that atorvastatin exerts a neuroprotective effect by regulating neuroinflammation in adult animal models of brain stroke and traumatic brain injury, but its role regarding damage to the developing brain remains unclear. This study aimed to clarify the effect and mechanism of atorvastatin on the regulation of microglia function in neonatal hypoxic-ischemic brain damage (HIBD). The oxygen glucose deprivation (OGD) of microglia and neonatal rat HIBD model was established. Atorvastatin, recombinant sclerostin protein (SOST), and XAV939 (degradation of ß-catenin) were administered to OGD microglia and HIBD rats. The pathological changes of brain tissue, cerebral infarction volume, learning and memory ability of rats, pro-inflammatory (CD16+/Iba1+) and anti-inflammatory (CD206+/Iba1+) microglia markers, inflammation-related indicators (Inos, Tnfα, Il6, Arg1, Tgfb, and Mrc1), and Wnt/ß-catenin signaling molecules were examined. Atorvastatin reduced OGD-induced pro-inflammatory microglia and pro-inflammatory factors, while increasing anti-inflammatory microglia and anti-inflammatory factors. In vivo, atorvastatin attenuated hypoxia-ischemia (HI)-induced neuroinflammation and brain damage. Mechanistically, atorvastatin decreased SOST expression and activated the Wnt/ß-catenin signaling pathway, and the administration of recombinant SOST protein or XAV939 inhibited Wnt/ß-catenin signaling and attenuated the anti-inflammatory effect of atorvastatin. Atorvastatin promotes the pro/anti-inflammatory phenotypic transformation of microglia via the Wnt/ß-catenin pathway in HI neonatal rats. Atorvastatin may be developed as a potent agent for the treatment of HIE in neonates.

PACAP-Sirtuin3 alleviates cognitive impairment through autophagy in Alzheimer's disease.

BACKGROUND: Autophagy is vital in the pathogenesis of neurodegeneration. Thus far, no studies have specifically investigated the relationship between pituitary adenylate cyclase-activating polypeptide (PACAP) and autophagy, particularly in the context of Alzheimer's disease (AD). This study used in vitro and in vivo models, along with clinical samples, to explore interactions between PACAP and autophagy in AD. METHODS: AD model mice were administered 6 µl of 0.1 mg/ml PACAP liquid intranasally for 4 weeks, then subjected to behavioral analyses to assess the benefits of PACAP treatment. The underlying mechanisms of PACAP-induced effects were investigated by methods including real-time quantitative polymerase chain reaction, RNA sequencing, immunofluorescence, and western blotting. Exosomes were extracted from human serum and subjected to enzyme-linked immunosorbent assays to examine autophagy pathways. The clinical and therapeutic implications of PACAP and autophagy were extensively investigated throughout the experiment. RESULTS: Impaired autophagy was a critical step in amyloid ß (Aß) and Tau deposition; PACAP enhanced autophagy and attenuated cognitive impairment. RNA sequencing revealed three pathways that may be involved in AD progression: PI3K-AKT, mTOR, and AMPK. In vivo and in vitro studies showed that sirtuin3 knockdown diminished the ability of PACAP to restore normal autophagy function, resulting in phagocytosis dysregulation and the accumulation of pTau, Tau, and Aß. Additionally, the autophagic biomarker MAP1LC3 demonstrated a positive association with PACAP in human serum. CONCLUSIONS: PACAP reverses AD-induced cognitive impairment through autophagy, using sirtuin3 as a key mediator. MAP1LC3 has a positive relationship with PACAP in humans. These findings provide insights regarding potential uses of intranasal PACAP and sirtuin3 agonists in AD treatment. TRIAL REGISTRATION: NCT04320368.

The mechanism of acrolein exposure inhibited the release of neutrophil extracellular traps: By reducing respiratory burst and Raf/MEK/ERK pathway and promote cell apoptosis.

Acrolein (AC) is a highly toxic volatile substance in the environment, and studies have found that excessive AC had a toxic effect on the immune system. Neutrophils are the first line of defense against pathogen invasion. The release of neutrophil extracellular traps (NETs) is a protective mechanism for neutrophils, and its release is affected by environmental pollutants. However, the effect of AC on NETs release and its mechanism remains unclear. In this study, chicken peripheral blood neutrophils were pretreated with 20 µM AC and treated with 5 µM Phorbol 12-myristate 13-acetate (PMA) to stimulate the release of NETs. The results showed that AC exposure significantly inhibited the release of NETs induced by PMA, respiratory burst, and the expression levels of phospho-rapidly accelerated fibrosarcoma (p-Raf), phospho-mitogen-activated extracellular signal-regulated kinase (p-MEK) and phospho-extracellular regulated protein kinases (p-ERK). In addition, AC exposure significantly inhibited the expression of B-cell lymphoma-2 (Bcl-2) and promoted the expression of apoptotic factors Bcl2-Associated X (Bax), cytochrome c (Cyt C), cysteinyl aspartate specific proteinase 9 (Casp 9) and cysteinyl aspartate specific proteinase 3 (Casp 3). Further inhibition of neutrophil apoptosis significantly improved the release of NETs. The above results indicated that AC exposure led to a decrease in the formation of NETs, which is caused by excessive AC-induced neutrophil apoptosis. Our study clarified the immune toxicity mechanism of AC on chickens, which is of great significance and reference value for protecting the ecological environment and poultry health.

2D Bi2MoO6/Zn3V2O8 heterojunction photocatalyst for efficient photocatalytic reduction of CO2 to CO and CH4.

Two-dimensional (2D) "face-to-face" heterojunctions promote interfacial charge transfer and separation in composite photocatalysts. Here, we report an efficient 2D/2D step-scheme (S-scheme) photocatalyst composed of Bi2MoO6/Zn3V2O8 (BMO/ZVO), which has been designed and prepared via the self-assembly of BMO and ZVO nanoflakes. The heterojunction with an optimized composition of 30% BMO/ZVO showed extended light absorption capacity and enhanced separation efficiency of photogenerated carriers. Density functional theory (DFT) calculation on work function and charge density revealed the presence of a built-in electric field at the interface region, which should facilitate the separation of photogenerated electron-hole pairs. This work showed that it is essential to select two photocatalysts with interlaced band arrangement and to fine-tune the heterojunction interface for the preparation of S-scheme heterojunctions to achieve high photocatalytic efficiency.

The RNA m6A modification might participate in microglial activation during hypoxic-ischemic brain damage in neonatal mice.

BACKGROUND: The RNA m6A modification has been implicated in multiple neurological diseases as well as macrophage activation. However, whether it regulates microglial activation during hypoxic-ischemic brain damage (HIBD) in neonates remains unknown. Here, we aim to examine whether the m6A modification is involved in modulating microglial activation during HIBD. We employed an oxygen and glucose deprivation microglial model for in vitro studies and a neonatal mouse model of HIBD. The brain tissue was subjected to RNA-seq to screen for significant changes in the mRNA m6A regulator. Thereafter, we performed validation and bioinformatics analysis of the major m6A regulators. RESULTS: RNA-seq analysis revealed that, among 141 m6A regulators, 31 exhibited significant differential expression (FC (abs) ≥ 2) in HIBD mice. We then subjected the major m6A regulators Mettl3, Mettl14, Fto, Alkbh5, Ythdf1, and Ythdf2 to further validation, and the results showed that all were significantly downregulated in vitro and in vivo. GO analysis reveals that regulators are mainly involved in the regulation of cellular and metabolic processes. The KEGG results indicate the involvement of the signal transduction pathway. CONCLUSIONS: Our findings demonstrate that m6A modification of mRNA plays a crucial role in the regulation of microglial activation in HIBD, with m6A-associated regulators acting as key modulators of microglial activation.

Melatonin alleviates 3,3',4,4',5-pentachlorobenzene induced colon injury by relieving oxidative stress.

3,3',4,4',5-pentachlorobiphenyl (PCB126) is widely distributed, non-degradable and bioaccumulative, which can affect the function of tissues and organs of the living organisms. Melatonin (MT) is a sort of indole neurohormone that is mainly secreted by the pineal gland. Numerous studies have shown that MT can alleviate intestinal injury through various mechanisms such as antioxidant, anti-inflammatory, and anti-apoptosis. For the above reasons, the aim of this study is to explore the mechanism of intestinal injury in mice after exposure to PCB126 as well as the antagonistic effect of MT. Mice were respectively fed PCB126 (0.326 mg/kg) and/or MT (10 mg/kg) in vivo. In vitro, colonic epithelial cells (MCEC) were treated with PCB126 (150 µM) and/or MT (2 mM). We found that the microscopic structure of colon tissue was impaired after exposure to PCB126. The levels of oxidative stress, the protein and mRNA levels of expression of inflammatory related factors were significantly increased and the expression levels of intestinal tight junction protein were decreased. Notably, MT can promote Nrf2/HO-1 expression level and reduce the colonic injury caused by PCB126. Further in vitro treatment with reactive oxygen species inhibitors (NAC) showed that it significantly alleviated PCB126-induced in MCEC cell damage. In summary, the above results suggested that MT alleviates PCB126-induced colon inflammation by inhibiting the overproduction of reactive oxygen species (ROS) and up-regulating the expression level of intestinal tight junction protein. Our results contribute to the further comprehension of the intestinal toxicity effects of PCB126 and the significant role of MT in preserving the mechanisms of intestinal injury.

Single-cell immune profiling reveals broad anti-inflammation response in bipolar disorder patients with quetiapine and valproate treatment.

Bipolar disorder (BD) is a common mental disorder characterized by manic and depressive episodes. Mood disorders have been associated with immune dysfunction. The combination of quetiapine and valproate has shown positive effects in treating BD, but the impact on immune dynamics remains less understood. Using single-cell RNA sequencing, we observed that B cells exhibited downregulation of inflammation-related genes, while pro-inflammatory mast and eosinophil cells decreased following treatment. Ribosomal peptide production genes were found to be reduced in both B and T cells after treatment. Additionally, our findings suggest that the combined therapy effectively alleviates inflammation by reducing myloid-mediated immune signaling pathways. This study provides valuable insights into the immune atlas and uncovers a potential mechanism for immune disorder alleviation in patients with BD treated with quetiapine and valproate.

Blood-based biomarkers for Alzheimer's disease: a multicenter-based cross-sectional and longitudinal study in China.

Discrepancies in diagnostic biomarkers for Alzheimer's Disease (AD) may arise from racial disparities, risk factors, or lifestyle differences. Moreover, there has been a lack of systematic and multicenter studies to evaluate baselines of the AD biomarkers in Chinese populations. Thus, there is an urgent need for research to investigate the effectiveness of blood biomarkers for AD, specifically in the Chinese Han population, using a multicenter approach. In the present multicenter-based cross-sectional and longitudinal study, we evaluated 817 blood samples from 6 different clinical centers. We measured plasma amyloid beta (Aß)-40, Aß42, phosphorylated tau 181 (pTau), total tau (tTau), serum neurofilament light (NFL), and glial fibrillary acidic protein (GFAP). Additionally, 18F-florbetapir positron electron tomography and magnetic resonance imaging were also performed. A combination of the APOE genotype with plasma pTau and serum GFAP demonstrated exceptional performance in distinguishing Aß status. Furthermore, baseline GFAP levels exhibited a strong association with cognitive decline over time and brain atrophy, with higher GFAP levels predicting a faster rate of neurodegeneration. In summary, these results validate the practicality of blood biomarkers in the Chinese Han population, encompassing various regions within China. Additionally, they emphasize the potential of pTau and GFAP as non-invasive methods for detecting and screening AD at an early stage.

Photochemically induced thalamus infarction impairs cognition in a mouse model.

BACKGROUND: Small subcortical infarcts account for up to 25% of ischaemic strokes. Thalamus is one of the subcortical structures that commonly manifest with lacunar infarcts on MRI of the brain. Studies have shown that thalamus infarction is associated with cognitive decline. However, due to the lack of proper animal models, little is known about the mechanism. We aimed to establish a focal thalamus infarction model, characterise the infarct lesion and assess functional effects. METHODS: Male C57BL/6J mice were anaesthetised, and Rose Bengal dye was injected through the tail vein. The right thalamus was illuminated with green laser light by stereotactic implantation of optic fibre. Characteristics of the infarct and lesion evolution were evaluated by histological analysis and 7T MRI at various times. The cognitive and neurological functions were assessed by behavioural tests. Retrograde tracing was performed to analyse neural connections. RESULTS: An ischaemic lesion with small vessel occlusion was observed in the thalamus. It became a small circumscribed infarct with reactive astrocytes accumulated in the infarct periphery on day 21. The mice with thalamic infarction demonstrated impaired learning and memory without significant neurological deficits. Retrogradely labelled neurons in the retrosplenial granular cortex were reduced. CONCLUSION: This study established a mouse model of thalamic lacunar infarction that exhibits cognitive impairment. Neural connection dysfunctions may play a potential role in post-stroke cognitive impairment. This model helps to clarify the pathophysiology of post-stroke cognitive impairment and to develop potential therapies.

The comparison of efficacy and safety evaluation of vacuum-assisted Elite 10-G system and the traditional BARD 14-G core needle in breast diagnosis: an open-label, parallel, randomized controlled trial.

BACKGROUND: Vacuum-assisted biopsy (VAB) and core needle biopsy (CNB) are both widely used methods in diagnosing breast lesions. We aimed to determine whether the Elite 10-gauge VAB achieves higher accuracy than the BARD spring-actuated 14-gauge CNB. MATERIALS AND METHODS: This was a phase 3, open-label, parallel, randomized controlled trial (NCT04612439). In total, 1470 patients with ultrasound (US)-visible breast lesions requiring breast biopsy were enrolled from April to July 2021 and randomized at a 1 : 1 ratio to undergo VAB or CNB. All patients underwent surgical excision after needle biopsy. The primary outcome was accuracy, defined as the proportion of patients who had a consistent qualitative diagnosis between the biopsy and surgical pathology results. The underestimation rate, false-negative rate and safety evaluations were the secondary endpoints. RESULTS: A total of 730 and 732 patients were evaluable for endpoints in the VAB and CNB groups, respectively. The accuracy of VAB surpassed that of CNB in the whole population (94.8 vs. 91.1%, P =0.009). The overall malignant underestimation rate was significantly lower in the VAB group than in the CNB group (21.4 vs. 30.9%, P =0.035). Additionally, significantly more false-negative events were noted in the CNB group (4.9 vs. 7.8%, P =0.037). In patients who presented with accompanying calcification, the accuracy of VAB surpassed that of CNB (93.2 vs. 88.3%, P =0.022). The potential superiority of VAB was indicated in patients with heterogeneous echo on US. CONCLUSIONS: In general, the 10-G VAB procedure is a reasonable alternative to the 14-G CNB procedure with higher accuracy. We recommend the use of VAB for lesions with accompanying calcification or heterogeneous echo on US.

Association of Income with Post-Stroke Cognition and the Underlying Neuroanatomical Mechanism.

OBJECTIVE: To investigate the association between income and post-stroke cognition at 3 months, and the underlying neuroanatomical mechanism. METHODS: Patients with first-ever ischemic stroke were enrolled and analyzed. Baseline information on income and neuroimaging measurements with predictive values for post-stroke cognitive impairment (PSCI) were collected within 7 days of the admission. Three months after the index stroke, all participants underwent a detailed neuropsychological test battery. The associations between income and PSCI and between income and brain structural measurements were investigated. RESULTS: A total of 294 patients were recruited for this study. Lower income was independently associated with poor cognitive performance on Stroop tests, Clinical Dementia Rating, Boston Naming Test, and Verbal Fluency Test. Regarding neuroimaging parameters, lower income was associated with a lower total brain volume (TBV)/total intracranial volume (TICV) ratio (p = 0.004). CONCLUSIONS: Lower income is associated with an increased chance of post-stroke cognitive decline, particularly in executive function and language domains. Since global brain atrophy (measured by TBV/TICV ratio) is a strong predictor for PSCI, its correlation with income may help explain the neuroanatomical mechanism between income and post-stroke cognition.

Vascular-water-exchange MRI (VEXI) enables the detection of subtle AXR alterations in Alzheimer's disease without MRI contrast agent, which may relate to BBB integrity.

Blood-brain barrier (BBB) impairment is an important pathophysiological process in Alzheimer's disease (AD) and a potential biomarker for early diagnosis of AD. However, most current neuroimaging methods assessing BBB function need the injection of exogenous contrast agents (or tracers), which limits the application of these methods in a large population. In this study, we aim to explore the feasibility of vascular water exchange MRI (VEXI), a diffusion-MRI-based method proposed to assess the BBB permeability to water molecules without using a contrast agent, in the detection of the BBB breakdown in AD. We tested VEXI on a 3T MRI scanner on three groups: AD patients (AD group), mild cognitive impairment (MCI) patients due to AD (MCI group), and the age-matched normal cognition subjects (NC group). Interestingly, we find that the apparent water exchange across the BBB (AXRBBB) measured by VEXI shows higher values in MCI compared with NC, and this higher AXRBBB happens specifically in the hippocampus. This increase in AXRBBB value gets larger and extends to more brain regions (medial orbital frontal cortex and thalamus) from MCI group to the AD group. Furthermore, we find that the AXRBBB values of these three regions is correlated significantly with the impairment of respective cognitive domains independent of age, sex and education. These results suggest VEXI is a promising method to assess the BBB breakdown in AD.

Activin A rescues preterm brain injury through a novel Noggin/BMP4/Id2 signaling pathway.

Activin A (Act A) has been reported to promote oligodendrocyte progenitor cell (OPC) differentiation in vitro and improve neurological outcomes in adult mice. However, the roles and mechanisms of action of Act A in preterm brain injury are unknown. In the present study, P5 rats were subjected to hypoxia­ischemia to establish a neonatal white matter injury (WMI) model and Act A was injected via the lateral ventricle. Pathological characteristics, OPC differentiation, myelination, and neurological performance were analyzed. Further, the involvement of the Noggin/BMP4/Id2 signaling pathway in the roles of Act A in WMI was explored. Act A attenuated pathological damage, promoted OPC differentiation, enhanced myelin sheath and myelinated axon formation, and improved neurological performance of WMI rats. Moreover, Act A enhanced noggin expression, which, in turn, inhibited the expression of bone morphogenetic protein 4 (BMP4) and inhibitor of DNA binding 2 (Id2). Furthermore, upregulation of Id2 completely abolished the rescue effects of Act A in WMI rats. In conclusion, the present findings suggested that Act A rescues preterm brain injury via targeting a novel Noggin/BMP4/Id2 signaling pathway.

Vascular dementia has the highest hospitalisation rate in China: a nationwide hospital information system study.

BACKGROUND: Although vascular dementia (VaD) is not uncommon in the hospital, most studies on VaD are community based. This study on VaD is the first to use a national hospital information system (HIS) in China. METHODS: This study was a hospital population-based cohort study, and data were acquired from the Hospital Quality Monitoring System, a Chinese national database that covers 1531 tertiary hospitals in China. The medical records in the HIS included demographic information, diagnoses, procedures, expenses, etc. VaD was diagnosed by hospital attending physicians and identified by the International Classification of Diseases (ICD) 10 code (F01.0-F01.9). RESULTS: 1259 (82.23%) tertiary hospitals were included in this study, and 274 230 hospitalisation records of 123 700 VaD patients from 2016 to 2018 were identified for analysis. VaD (51.27%) was the most common type of dementia in hospitalised patients. The age-adjusted and sex-adjusted hospital incidence of VaD was estimated to be 2.97 per 100 000 person-years (95% CI 2.92 to 3.02). The mean age of VaD patients admitted to hospitals was 74.13±10.88, with more male (61.0%) patients. The main comorbidities were hypertension (67.2%), heart disease (63.6%) and cerebral infarction (55.5%). The mortality rate of VaD in hospital was 28.91‰ (95% CI 28.0 to 29.9) between 2016 and 2018. The top 1 cause of death due to VaD was pneumonia and other respiratory disorders. CONCLUSIONS: VaD is the most common form of dementia in hospitalised patients. It casts huge burdens on affected patients and their caregivers. Vascular risk factors are prevalent in VaD patients. Reducing these factors is essential to improve patient care. The leading causes of death by VaD are pneumonia and other respiratory disorders. Hospital care and the management of respiratory illness are critical for VaD care in the hospital.