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1.
Transl Pediatr ; 13(4): 575-583, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38715673

Background: The use of extracorporeal membrane oxygenation (ECMO) technology has significantly decreased mortality rates associated with neonatal pulmonary hypertension and respiratory failure. Prone positioning ventilation (PPV) is a commonly used technique in critically ill infants, designed to improve thoracic pressure gradients, re-expand dorsal lung segments, and increase oxygenation in approximately 70-80% of patients suffering from acute respiratory distress syndrome. This study aimed to evaluate the effects of PPV on pulmonary function in neonates undergoing venous-arterial extracorporeal membrane oxygenation (VA-ECMO). Methods: We conducted a retrospective analysis of clinical data from 17 neonates who received ECMO support in our institution, divided into two groups based on ventilation strategy: ECMO with PPV (ECMO-PPV, n=8) and ECMO with supine positioning ventilation (ECMO-SPV, n=9). Parameters such as the P/F ratio [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2)], oxygenation index (OI), respiratory system compliance (Crs), and airway resistance (RAW) were collected and analyzed at baseline, and at 1, 2, and 3 days post-ECMO initiation. In the ECMO-PPV group, these parameters were also assessed 3 days pre-treatment and 2 hours post-treatment initiation. Results: Initial comparisons between ECMO-PPV and ECMO-SPV groups showed no significant difference in PaO2/FiO2, OI, Crs, or RAW. Throughout the ECMO treatment, both groups demonstrated gradual improvements in PaO2/FiO2 and Crs, and reductions in OI and RAW. Notably, by day 3, the ECMO-PPV group exhibited significant improvements in Crs and RAW compared to the ECMO-SPV group (P<0.05). Specifically, in the ECMO-PPV group, Crs significantly increased and RAW decreased after 2 hours of initiating PPV, with these changes becoming statistically significant by day 3 (Crs P=0.03, RAW P=0.03). No severe PPV-related complications were noted. Conclusions: PPV during neonatal ECMO may improve respiratory compliance and reduce RAW, potentially aiding lung recovery. Our findings suggest PPV as a viable strategy for neonates under ECMO support.

2.
BMC Genomics ; 25(1): 454, 2024 May 08.
Article En | MEDLINE | ID: mdl-38720264

BACKGROUND: In response to seasonal cold and food shortage, the Xizang plateau frogs, Nanorana parkeri (Anura: Dicroglossidae), enter a reversible hypometabolic state where heart rate and oxygen consumption in skeletal muscle are strongly suppressed. However, the effect of winter hibernation on gene expression and metabolic profiling in these two tissues remains unknown. In the present study, we conducted transcriptomic and metabolomic analyses of heart and skeletal muscle from summer- and winter-collected N. parkeri to explore mechanisms involved in seasonal hibernation. RESULTS: We identified 2407 differentially expressed genes (DEGs) in heart and 2938 DEGs in skeletal muscle. Enrichment analysis showed that shared DEGs in both tissues were enriched mainly in translation and metabolic processes. Of these, the expression of genes functionally categorized as "response to stress", "defense mechanisms", or "muscle contraction" were particularly associated with hibernation. Metabolomic analysis identified 24 and 22 differentially expressed metabolites (DEMs) in myocardium and skeletal muscle, respectively. In particular, pathway analysis showed that DEMs in myocardium were involved in the pentose phosphate pathway, glycerolipid metabolism, pyruvate metabolism, citrate cycle (TCA cycle), and glycolysis/gluconeogenesis. By contrast, DEMs in skeletal muscle were mainly involved in amino acid metabolism. CONCLUSIONS: In summary, natural adaptations of myocardium and skeletal muscle in hibernating N. parkeri involved transcriptional alterations in translation, stress response, protective mechanisms, and muscle contraction processes as well as metabolic remodeling. This study provides new insights into the transcriptional and metabolic adjustments that aid winter survival of high-altitude frogs N. parkeri.


Anura , Hibernation , Metabolomics , Muscle, Skeletal , Animals , Hibernation/genetics , Hibernation/physiology , Muscle, Skeletal/metabolism , Anura/genetics , Anura/metabolism , Anura/physiology , Myocardium/metabolism , Transcriptome , Gene Expression Profiling , Seasons , Metabolome , Tibet
3.
Diagn Microbiol Infect Dis ; 109(4): 116374, 2024 May 23.
Article En | MEDLINE | ID: mdl-38805857

Whipple's disease is a chronic systemic infectious disease that mainly affects the gastrointestinal tract. In some cases, Tropheryma whipplei can cause infection at the implant site or even throughout the body. In this study, we collected alveolar lavage fluid samples from patients with Tropheryma whipplei from 2020 to 2022, and retrospectively analyzed the clinical data of Tropheryma whipplei positive patients. Patient's past history, clinical manifestations, laboratory examinations, chest CT findings, treatment, and prognosis were recorded. 16 BALFs (70/1725, 4.0 %) from 16 patients were positive for Tropheryma whipplei. 8 patients were male with an average age of 50 years. The main clinical symptoms of patients included fever (9/16), cough (7/16), dyspnea (7/16), and expectoration (5/16), but neurological symptoms and arthralgia were rare. Cardiovascular and cerebrovascular diseases were the most common comorbidity (n=8). The main laboratory characteristics of the patient are red blood cell count, hemoglobin, total protein and albumin below normal levels (11/16), and/or creatinine above normal levels(14/16). Most chest computed tomography mainly show focal or patchy heterogeneous infection (n=5) and pleural effusion (n=8). Among the 6 samples, Tropheryma whipplei was the sole agent, and Klebsiella pneumoniae was the most common detected other pathogens. Metagenomic next-generation sequencing technology has improved the detection rate and attention of Tropheryma whipplei. Further research is needed to distinguish whether Tropheryma whipplei present in respiratory samples is a pathogen or an innocent bystander.

4.
Heliyon ; 10(10): e31311, 2024 May 30.
Article En | MEDLINE | ID: mdl-38807889

Backfat thickness (BT) and intramuscular fat (IMF) content are closely appertained to meat production and quality in pig production. Deposition in subcutaneous adipose (SA) and IMF concerns different genes and regulatory mechanisms. And larger studies with rigorous design should be carried to explore the molecular regulation of fat deposition in different tissues. The purpose of this study is to gain a better understanding of the molecular mechanisms underlying differences in fat deposition among different tissues and identify tissue-specific genes involved in regulating fat deposition. The SA-associated datasets (GSE122349 and GSE145956) and IMF-associated datasets (GSE165613 and GSE207279) were downloaded from the Gene Expression Omnibus (GEO) as the BT and IMF group, respectively. Subsequently, the Robust Rank Aggregation (RRA) algorithm identified 27 down- and 29 up-regulated differentially expressed genes (DEGs) in the BT group. Based on bioinformatics and three machine learning algorithms, four SA deposition-related potential biomarkers, namely ACLY, FASN, ME1, and ARVCF were selected. FASN was evaluated as the most valuable biomarker for the SA mechanism. The 18 down- and 34 up-regulated DEGs in the IMF group were identified, and ACTA2 and HMGCL were screened as the IMF deposition-related candidate core genes, especially the ACTA2 may play the critical role in IMF deposition regulation. Moreover, based on the constructed ceRNA network, we postulated that the role of predicted ceRNA interaction network of XIST, NEAT1/miR-15a-5p, miR-16-5p, miR-424-5p, miR-497-5p/FASN were vital in the SA metabolism, XIST, NEAT1/miR-27a/b-3p, 181a/c-5p/ACTA2 might contribute to the regulation to IMF metabolism, which all gave suggestions in molecular mechanism for regulation of fat deposition. These findings may facilitate advancements in porcine quality at the genetic and molecular levels and assist with human obesity-associated diseases.

5.
Sci Adv ; 10(18): eadm8275, 2024 May 03.
Article En | MEDLINE | ID: mdl-38691607

Flaviviruses encode a conserved, membrane-associated nonstructural protein 1 (NS1) with replication and immune evasion functions. The current knowledge of secreted NS1 (sNS1) oligomers is based on several low-resolution structures, thus hindering the development of drugs and vaccines against flaviviruses. Here, we revealed that recombinant sNS1 from flaviviruses exists in a dynamic equilibrium of dimer-tetramer-hexamer states. Two DENV4 hexameric NS1 structures and several tetrameric NS1 structures from multiple flaviviruses were solved at atomic resolution by cryo-EM. The stacking of the tetrameric NS1 and hexameric NS1 is facilitated by the hydrophobic ß-roll and connector domains. Additionally, a triacylglycerol molecule located within the central cavity may play a role in stabilizing the hexamer. Based on differentiated interactions between the dimeric NS1, two distinct hexamer models (head-to-head and side-to-side hexamer) and the step-by-step assembly mechanisms of NS1 dimer into hexamer were proposed. We believe that our study sheds light on the understanding of the NS1 oligomerization and contributes to NS1-based therapies.


Cryoelectron Microscopy , Flavivirus , Models, Molecular , Protein Multimerization , Viral Nonstructural Proteins , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/metabolism , Flavivirus/metabolism , Flavivirus/chemistry , Protein Conformation
6.
Asian J Androl ; 2024 May 14.
Article En | MEDLINE | ID: mdl-38748861

ABSTRACT: Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%-46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: -2.70; 95% CI: -3.94--1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.

7.
Technol Health Care ; 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38759060

BACKGROUND: A growing body of evidence has shown that activating spinal cord glial cells (typically astrocytes and microglial cells) is closely related to hyperpathia and persistent pain. OBJECTIVE: To investigate the expression of GFAP and CR3/CD11b in cornu dorsale medullae spinalis of rats with nonbacterial prostatitis, to explore the therapeutic efficacy and action mechanism of intrathecal injection of BNP alleviating chronic neuropathic pain. METHODS: Eighteen male SPF SD rats were randomly divided into sham operation control group, nonbacterial prostatitis group (NBP) and intrathecal injection BNP group, the NBP model was established by intraprostatic injection of CFA, and the spinal cord of L6-S1 segment was extracted seven days after intrathecal injection of BNP; The expression of GFAP and CR3/CD11b in dorsal horn of spinal cord were detected by immunofluorescence and Western blot. RESULTS: The cumulative optical density values of GFAP and CR3/CD11b immunofluorescence assay in the NBP group were higher than those in the sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.01); The expression of GFAP and CR3/CD11b in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.01). Western blot results showed that the expression of GFAP and CR3/CD11B in NBP group were higher than those in sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.05). The expression of GFAP and CR3/CD11B in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.05). CONCLUSION: Intrathecal injection of BNP can down-regulate the expressions of GFAP and CR3/CD11b in L6-S1 spinal cord of NBP rat model and to further inhibit chronic pain caused by NBP.

8.
Cardiovasc Diabetol ; 23(1): 172, 2024 May 16.
Article En | MEDLINE | ID: mdl-38755609

BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.


Acute Coronary Syndrome , Biomarkers , Blood Glucose , Coronary Artery Disease , Insulin Resistance , Percutaneous Coronary Intervention , Humans , Acute Coronary Syndrome/blood , Acute Coronary Syndrome/mortality , Acute Coronary Syndrome/therapy , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Male , Female , Middle Aged , Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Risk Assessment , Risk Factors , Treatment Outcome , Blood Glucose/metabolism , Time Factors , Biomarkers/blood , Coronary Artery Disease/blood , Coronary Artery Disease/therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/diagnosis , Triglycerides/blood , Retrospective Studies , Predictive Value of Tests
9.
Animals (Basel) ; 14(10)2024 May 11.
Article En | MEDLINE | ID: mdl-38791658

The functional adaptation and underlying molecular mechanisms of hemoglobins (Hbs) have primarily concentrated on mammals and birds, with few reports on reptiles. This study aimed to investigate the convergent and species-specific high-altitude adaptation mechanisms of Hbs in two Eremias lizards from the Qinghai-Tibet Plateau. The Hbs of high-altitude E. argus and E. multiocellata were characterized by significantly high overall and intrinsic Hb-O2 affinity compared to their low-altitude populations. Despite the similarly low Cl- sensitivities, the Hbs of high-altitude E. argus exhibited higher ATP sensitivity and ATP-dependent Bohr effects than that of E. multiocellata, which could facilitate O2 unloading in respiring tissues. Eremias lizards Hbs exhibited similarly low temperature sensitivities and relatively high Bohr effects at lower temperatures, which could help to stably deliver and release O2 to cold extremities at low temperatures. The oxygenation properties of Hbs in high-altitude populations might be attributed to varying ratios of ß2/ß1 globin and substitutions on the ß2-type globin. Notably, the Asn12Ala in lowland E. argus could cause localized destabilization of the E-helix in the tetrameric Hb by elimination of hydrogen bonds, thereby resulting in its lowest O2 affinity. This study provides a valuable reference for the high-altitude adaptation mechanisms of hemoglobins in reptiles.

10.
J Funct Biomater ; 15(5)2024 May 17.
Article En | MEDLINE | ID: mdl-38786646

Biodegradable vascular stents (BVS) are deemed as great potential alternatives for overcoming the inherent limitations of permanent metallic stents in the treatment of coronary artery diseases. The current study aimed to comprehensively compare the mechanical behaviors of four poly(lactic acid) (PLA) BVS designs with varying geometries via numerical methods and to clarify the optimal BVS selection. Four PLA BVS (i.e., Absorb, DESolve, Igaki-Tamai, and Fantom) were first constructed. A degradation model was refined by simply including the fatigue effect induced by pulsatile blood pressures, and an explicit solver was employed to simulate the crimping and degradation behaviors of the four PLA BVS. The degradation dynamics here were characterized by four indices. The results indicated that the stent designs affected crimping and degradation behaviors. Compared to the other three stents, the DESolve stent had the greatest radial stiffness in the crimping simulation and the best diameter maintenance ability despite its faster degradation; moreover, the stent was considered to perform better according to a pilot scoring system. The current work provides a theoretical method for studying and understanding the degradation dynamics of the PLA BVS, and it could be helpful for the design of next-generation BVS.

11.
ACS Chem Neurosci ; 15(10): 2070-2079, 2024 May 15.
Article En | MEDLINE | ID: mdl-38691676

PDZ domains are modular domains that conventionally bind to C terminal or internal motifs of target proteins to control cellular functions through the regulation of protein complex assemblies. Almost all reported structures of PDZ-target protein complexes rely on fragments or peptides as target proteins. No intact target protein complexed with PDZ was structurally characterized. In this study, we used NMR spectroscopy and other biochemistry and biophysics tools to uncover insights into structural coupling between the PDZ domain of protein interacting with C-kinase 1 (PICK1) and α7 nicotinic acetylcholine receptors (α7 nAChR). Notably, the intracellular domains of both α7 nAChR and PICK1 PDZ exhibit a high degree of plasticity in their coupling. Specifically, the MA helix of α7 nAChR interacts with residues lining the canonical binding site of the PICK1 PDZ, while flexible loops also engage in protein-protein interactions. Both hydrophobic and electrostatic interactions mediate the coupling. Overall, the resulting structure of the α7 nAChR-PICK1 complex reveals an unconventional PDZ binding mode, significantly expanding the repertoire of functionally important PDZ interactions.


Carrier Proteins , PDZ Domains , Protein Binding , alpha7 Nicotinic Acetylcholine Receptor , alpha7 Nicotinic Acetylcholine Receptor/metabolism , Carrier Proteins/metabolism , Protein Binding/physiology , Humans , Nuclear Proteins/metabolism , Nuclear Proteins/chemistry , Binding Sites/physiology
15.
Nat Neurosci ; 2024 May 20.
Article En | MEDLINE | ID: mdl-38769152

Ancestral differences in genomic variation affect the regulation of gene expression; however, most gene expression studies have been limited to European ancestry samples or adjusted to identify ancestry-independent associations. Here, we instead examined the impact of genetic ancestry on gene expression and DNA methylation in the postmortem brain tissue of admixed Black American neurotypical individuals to identify ancestry-dependent and ancestry-independent contributions. Ancestry-associated differentially expressed genes (DEGs), transcripts and gene networks, while notably not implicating neurons, are enriched for genes related to the immune response and vascular tissue and explain up to 26% of heritability for ischemic stroke, 27% of heritability for Parkinson disease and 30% of heritability for Alzheimer's disease. Ancestry-associated DEGs also show general enrichment for the heritability of diverse immune-related traits but depletion for psychiatric-related traits. We also compared Black and non-Hispanic white Americans, confirming most ancestry-associated DEGs. Our results delineate the extent to which genetic ancestry affects differences in gene expression in the human brain and the implications for brain illness risk.

16.
J Environ Manage ; 360: 121156, 2024 May 13.
Article En | MEDLINE | ID: mdl-38744211

With continuous mine exploitation, regional ecosystems have been damaged, resulting in a decline in the carbon sink capacity of mining areas. There is a global shortage of effective soil ecological restoration techniques for mining areas, especially for vanadium (V) and titanium (Ti) magnetite tailings, and the impact of phytoremediation techniques on the soil carbon cycle remains unclear. Therefore, this study aimed to explore the effects of long-term Pongamia pinnata remediation on soil organic carbon transformation of V-Ti magnetite tailing to reveal the bacterial community driving mechanism. In this study, it was found that four soil active organic carbon components (ROC, POC, DOC, and MBC) and three carbon transformation related enzymes (S-CL, S-SC, and S-PPO) in vanadium titanium magnetite tailings significantly (P < 0.05) increased with P. pinnata remediation. The abundance of carbon transformation functional genes such as carbon degradation, carbon fixation, and methane oxidation were also significantly (P < 0.05) enriched. The network nodes, links, and modularity of the microbial community, carbon components, and carbon transformation genes were enhanced, indicating stronger connections among the soil microbes, carbon components, and carbon transformation functional genes. Structural equation model (SEM) analysis revealed that the bacterial communities indirectly affected the soil organic carbon fraction and enzyme activity to regulate the soil total organic carbon after P. pinnata remediation. The soil active organic carbon fraction and free light fraction carbon also directly regulated the soil carbon and nitrogen ratio by directly affecting the soil total organic carbon content. These results provide a theoretical reference for the use of phytoremediation to drive soil carbon transformation for carbon sequestration enhancement through the remediation of degraded ecosystems in mining areas.

17.
Infect Drug Resist ; 17: 1439-1445, 2024.
Article En | MEDLINE | ID: mdl-38628241

Background: The HACEK group comprises Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, are Gram-negative bacteria that are slow-growing and fastidious. These organisms are common causes of culture-negative endocarditis. However, brain abscesses caused by Haemophilus aphrophilus and E. corrodens have been rarely reported. The case we describe, which was promptly identified and successfully treated, will be meaningful for the diagnosis and treatment of such infectious diseases. Case Presentation: Herein, we report a case of brain abscess in a young man who was infected with Haemophilus aphrophilus and E. corrodens. The patient was admitted to the hospital with sudden onset of vomiting, coma, and fever. Magnetic resonance imaging (MRI) of the brain and cerebrospinal fluid cell counts suggested cerebral abscess, he underwent drainage of the abscess and empirical antimicrobial therapy of meropenem (2 g every 8 hours) and linezolid (0.6 g every 12 hours) for more than 10 days without significant improvement. Metagenomic next-generation sequencing (mNGS) of drainage fluid and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) detection for isolated bacteria from samples suggested the presence of H. aphrophilus and E. corrodens. After 7 weeks of ceftriaxone (2 g every 12 hours) and meropenem (2 g every 8 hours) intravenously, the patient was discharged with a normal temperature and brain MRI showed improvement of the lesion. Conclusion: Similar cases reported in previous studies were always associated with bacterial blood dissemination after dental surgery or myocarditis; however, the patient in our case had no any associated risk factors. As far as we know, this is the only case of central nervous system infection caused by H. aphrophilus and E. corrodens that has utilized combined mNGS and MALDI-TOF MS in the diagnosis.

18.
Neurosci Lett ; 831: 137790, 2024 May 14.
Article En | MEDLINE | ID: mdl-38670522

OBJECTIVE: To explore degree centrality (DC) abnormalities in ischemic stroke patients and determine whether these abnormalities have potential value in understanding the pathological mechanisms of ischemic stroke patients. METHODS: Sixteen ischemic stroke patients and 22 healthy controls (HCs) underwent resting state functional magnetic resonance imaging (rs-fMRI) scanning, and the resulting data were subjected to DC analysis. Then we conducted a correlation analysis between DC values and neuropsychological test scores, including Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). Finally, extracted the abnormal DC values of brain regions and defined them as features for support vector machine (SVM) analysis. RESULTS: Compared with HCs, ischemic stroke patients showed increased DC in the bilateral supplementary motor area, and median cingulate and paracingulate gyri and decreased DC in the left postcentral gyrus, right calcarine fissure and surrounding cortex, lingual gyrus, and orbital parts of the right superior frontal gyrus and bilateral cuneus. Correlation analyses revealed that DC values in the right lingual gyrus, calcarine fissure and surrounding cortex, and orbital parts of the right superior frontal gyrus were positively correlated with the MMSE scores. The SVM classification of the DC values achieved an area under the curve (AUC) of 0.93, an accuracy of 89.47%. CONCLUSION: Our research results indicate that ischemic stroke patients exhibit abnormalities in the global connectivity mechanisms and patterns of the brain network. These abnormal changes may provide neuroimaging evidence for stroke-related motor, visual, and cognitive impairments, contribute to a deeper comprehension of the underlying pathophysiological mechanisms implicated in ischemic stroke.


Brain , Ischemic Stroke , Magnetic Resonance Imaging , Humans , Male , Magnetic Resonance Imaging/methods , Female , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/physiopathology , Middle Aged , Brain/diagnostic imaging , Brain/physiopathology , Aged , Support Vector Machine , Rest , Brain Mapping/methods , Biomarkers
19.
Nat Commun ; 15(1): 3342, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38688917

The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia.


Corpus Striatum , Dopamine , Schizophrenia , Humans , Dopamine/metabolism , Dopamine/biosynthesis , Schizophrenia/genetics , Schizophrenia/metabolism , Male , Female , Corpus Striatum/metabolism , Adult , Caudate Nucleus/metabolism , Signal Transduction , Middle Aged , Hippocampus/metabolism , Multifactorial Inheritance , Genetic Predisposition to Disease , Dorsolateral Prefrontal Cortex/metabolism , Reward
20.
BMC Cardiovasc Disord ; 24(1): 233, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38689231

OBJECTIVE: This study aimed to examine the changes in absolute value and decline rate of early serum cardiac troponin T (cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in neonates who received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) support therapy within the first week of life. METHODS: We retrospectively collected clinical data and laboratory test results of 18 neonates who underwent V-A ECMO support within one week of birth, from July 2021 to June 2023, using the electronic medical record system. These patients were categorized into survival and death groups. Comparative analyses of the absolute values and decline rates of cTnT and NT-proBNP were made between the groups at baseline, and at 24, 48, and 72 h post-ECMO initiation. RESULTS: Out of the 18 neonates, 12 survived (survival rate: 66.7%), while 6 succumbed. The survival group exhibited significantly lower absolute values of cTnT and NT-proBNP than the death group, and their decline rates were significantly higher. Notably, all neonates without an early decline in cTnT and NT-proBNP levels were in the death group. CONCLUSION: The early changes in the absolute value and decline rate of serum cTnT and NT-proBNP in neonates undergoing V-A ECMO may serve as predictors of their prognosis.


Biomarkers , Extracorporeal Membrane Oxygenation , Natriuretic Peptide, Brain , Peptide Fragments , Troponin T , Humans , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/mortality , Natriuretic Peptide, Brain/blood , Troponin T/blood , Infant, Newborn , Peptide Fragments/blood , Retrospective Studies , Male , Female , Biomarkers/blood , Time Factors , Treatment Outcome , Predictive Value of Tests , Risk Factors
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