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BACKGROUND: Impaired gamma band oscillation, specifically 40-Hz auditory steady state response (ASSR) has been robustly found in schizophrenia, while there is relatively little evidence characterizing the ASSR before full-blown psychosis. OBJECTIVE: To characterize gamma-band ASSR in populations at clinical high-risk for psychosis (CHR). METHODS: One hundred and seven CHR subjects and sixty-five healthy control (HC) subjects were included and completed clinical assessments, the ASSR paradigm of electroencephalography (EEG) and cognitive assessments. Both indices of event-related spectrum perturbation (ERSP) and intertrial coherence (ITC) in response to 20-Hz, 30-Hz and 40-Hz click sounds were respectively qualified and compared between these two groups, as well as the relationship to clinical psychopathology and cognitive function was assessed. RESULTS: At 40-Hz click sounds, ERSP in HC group (1.042⯱â¯0.047) was statistical significantly increased than that in CHR group (0.873⯱â¯0.036) (pâ¯=â¯0.005)ï¼at 30-Hz, ERSP in HC group (0.536⯱â¯0.024) was increased than that in CHR group (0.483⯱â¯0.019), but the difference was trend statistical significance (pâ¯=â¯0.083)ï¼at 20-Hz, ERSP in HC group (0.452⯱â¯0.017) was not different significantly from CHR group (0.418⯱â¯0.013) (pâ¯=â¯0.104). ERSP of the HC group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of the three ERSP showed statistical significance (30-Hz vs. 40-Hz: pâ¯<â¯0.001; 20-Hz vs. 40-Hz: pâ¯<â¯0.001ï¼20-Hz vs. 30-Hz: pâ¯=â¯0.003). Similarly, ERSP of the CHR group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of these three ERSP showed statistical significance (30-Hz vs. 40-Hz: pâ¯<â¯0.001; 20-Hz vs. 40-Hz: pâ¯<â¯0.001ï¼20-Hz vs. 30-Hz: pâ¯=â¯0.002). A statistically significant small positive correlation of 40-Hz ERSP with signal processing speed score was observed in the HC group (ρâ¯=â¯0.27, pâ¯=â¯0.029). A statistically significant small negative correlation of 40-Hz ERSP with visual learning score was observed in the CHR group (ρâ¯=â¯-0.22, pâ¯=â¯0.023). CONCLUSION: Impaired 40-Hz but undamaged hierarchical organization mode of auditory steady state presented in the CHR populations. Abnormal 40â¯Hz ASSR for CHR might be associated with cognitive functions, such as information processing speed and visual memory.
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BACKGROUND AND HYPOTHESIS: Psychiatric comorbidities suggest that symptoms overlap across different diagnoses; the transdiagnostic network approach is valuable for studying psychopathology. Childhood trauma is a common transdiagnostic risk factor for psychiatric disorders, but the complex relationship between childhood trauma and psychopathology has seldom been investigated using a large cross-sectional transdiagnostic sample. STUDY DESIGN: This study recruited 869 patients with different diagnoses, including 418 schizophrenia, 215 bipolar disorder, and 236 major depressive disorder. Participants completed psychiatric interviews and self-report questionnaires. We constructed dimension- and item-level Least Absolute Shrinkage and Selection Operator-based (LASSO) networks to explore the relationship between childhood trauma, psychopathology, and duration of illness. Moreover, we constructed directed acyclic graphs (DAGs) to tentatively clarify the potential directions of associations among these variables. Network Comparison Tests (NCTs) were conducted for different diagnostic groups and gender-stratified groups. STUDY RESULTS: The transdiagnostic LASSO networks showed that different types of childhood trauma exerted distinct impacts on various psychopathological dimensions. Emotional abuse was linked to depressive symptoms, physical abuse to excited symptoms, sexual abuse to positive and disorganized symptoms, emotional neglect to depressive symptoms and motivation and pleasure (MAP) deficits factor of negative symptoms, and physical neglect to MAP factor. The DAG findings generally concurred with the LASSO network. The NCT showed comparable networks. CONCLUSIONS: Our findings suggest that childhood trauma is significantly associated with the development of psychopathology across different diagnostic groups. The affective pathway model suggests that early identification and tailored interventions would be needed for people with a history of childhood trauma.
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BACKGROUND: Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children. METHOD: We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children's Hospital. Clinical characteristics, pathogens and management were analyzed. RESULTS: We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p < 0.001), single abscess (p = 0.042), unilateral involvement (p = 0.039), and small size of the abscess (p = 0.008). Twenty-four patients (42.1%) had extrahepatic organ involvement. Pathogens were identified in 17 patients (29.8%), the most common pathogens were Klebsiella pneumoniae and Staphylococcus aureus. The positive rate of metagenomic next-generation sequencing (mNGS) was 87.5% (7/8). On multivariable analysis, the extrahepatic organ involved (p = 0.029) and hepatomegaly (p = 0.025) were two independent factors associated with poor outcomes. CONCLUSIONS: PLA is usually seen in children with predisposing factors. Malignant hematology and primary immunodeficiency disease were the most common underlying diseases. Extrahepatic organ involvement and hepatomegaly are associated with poor prognosis. Increased use of mNGS could be beneficial for identifying pathogens.
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Absceso Piógeno Hepático , Humanos , Absceso Piógeno Hepático/microbiología , Absceso Piógeno Hepático/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Niño , Lactante , Beijing/epidemiología , Adolescente , Klebsiella pneumoniae/aislamiento & purificación , Antibacterianos/uso terapéutico , Factores de Riesgo , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
Antimicrobial blue light (aBL) is utilized as a new approach to inhibit the growth of Staphylococcus aureus (S. aureus). Mediated by the endogenous chromophore, aBL possesses the similar photokilling property with aPDI (antimicrobial photodynamic inactivation), however, their mechanistic discrepancies in triggering the death of staphylococcal cells are not yet understood. Here, we describe the use of a 460-nm-LED to curb the viability of S. aureus. According to the results, the bacterial survival was sharply decreased when blue light was applied, reaching a maximum of 4.11 ± 0.04 log10 units. Moreover, the membrane integrity was damaged by aBL, causing the leakage of intracellular DNA. Transcriptomic analysis indicates the divergent gene expression upon either aBL or aPDI, with pathways such as transport, DNA repair, expression regulation and porphyrin massively affected by aBL. Among the commonly regulated genes, LrgA was underpinned on account of its involvement with biofilm formation and protein transport. By comparing the wildtype with the LrgA-overexpressing (LrgA+) strain, the survival rate, membrane penetration, surface structure and biofilm formation were, to a varying degree, improved for LrgA+, which may suggest that LrgA plays essential roles in modulating the responsiveness of S. aureus. Besides, LrgA may function through regulating the expression of autolysis-related systems. Finally, LrgA overexpression did not attenuate but aggravate the impairment induced by aPDI, showcasing a distinct responsive strategy from aBL. Taken together, this study unveils a unique molecular alteration for the aBL-mediated inactivation, providing the basis of utilizing blue light to reduce the harm brought by S. aureus.
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Proteínas Bacterianas , Biopelículas , Luz , Staphylococcus aureus , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/efectos de la radiación , Staphylococcus aureus/genética , Staphylococcus aureus/fisiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Biopelículas/efectos de los fármacos , Biopelículas/efectos de la radiación , Regulación Bacteriana de la Expresión Génica/efectos de la radiación , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Transcripción Genética/efectos de la radiación , Transcripción Genética/efectos de los fármacos , Viabilidad Microbiana/efectos de la radiación , Viabilidad Microbiana/efectos de los fármacos , Porfirinas/química , Porfirinas/farmacología , Luz AzulRESUMEN
Background: Chronic respiratory disease is an important public health problem in the United States and globally. Diet, an important part of a healthy lifestyle, is also relevant to chronic respiratory health. We aimed to explore the relationship between overall dietary quality and the risk of chronic respiratory disease (CRD), include chronic bronchitis (CB), emphysema and asthma. Method: A total of 4,499 United States adults were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2017-2018. Diet quality was assessed using 2 day, 24 h dietary recall data and quantified as the Healthy Diet Index (HEI)-2020 score. Binary logistic regression models, restricted cubic splines (RCS) and generalized additive modeling (GAM), the weighted quartile sum (WQS) and qgcom models were used to assess the relationship between HEI-2020 scores and risk of CB, emphysema and asthma. Results: High HEI-2020 scores are associated with low risk of chronic respiratory disease (CB: 0.98, 0.97-0.99; emphysema: 0.98, 0.97-0.99; asthma: 0.98, 0.97-0.99) and consistent results across different dietary variable categorization (Tertile: CB: 0.58, 0.42-0.81; asthma: 0.51, 0.35-0.74; Quartile: CB: 0.57, 0.34-0.97; asthma: 0.56, 0.36-0.86) and different weighting models. Negative dose-response relationship between dietary quality and risk of chronic respiratory disease also shown in RCS and GAM models. The WQS and qgcom models also showed a healthy mixing effect of dietary components on respiratory disease, with high-quality proteins, vegetables, and fruits making the heaviest contributions. Conclusion: Higher HEI-2020 scores were associated with lower risk of CB, emphysema, and asthma. Following Dietary Guidelines for Americans 2020-2025 could support enhanced respiratory health.
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OBJECTIVE: High-risk human papillomavirus (HR-HPV) infection is the chief cause of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. The Erhuang suppository (EHS) is a traditional Chinese medicine (TCM) prepared from realgar (As2S2), Coptidis rhizoma, alumen, and borneolum syntheticum and has been used for antiviral and antitumor purposes. However, whether EHS can efficiently alleviate HR-HPV infection remains unclear. This study was conducted to evaluate the efficacy of EHS for the treatment of persistent HR-HPV infection in the uterine cervix. METHODS: In this study, we evaluated the therapeutic efficacy of EHS in a randomized controlled clinical trial with a 3-month follow-up. Totally, 70 patients with persistent HR-HPV infection were randomly assigned to receive intravaginal administration of EHS or placebo. HPV DNA, ThinPrep cytologic test (TCT), colposcopy, and safety evaluation were carried out after treatment. Microarray analysis was performed to compare transcriptome profiles before and after EHS treatment. A K14-HPV16 mouse model was generated to confirm the efficiency of EHS. RESULTS: After 3 months, 74.3% (26/35) of the patients in the treatment group were HPV negative, compared to 6.9% (2/29) in the placebo group. High-throughput microarrays revealed distinct transcriptome profiles after treatment. The differentially expressed genes were significantly enriched in complement activation, immune response, and apoptotic processes. The K14-HPV16 mouse model also validated the remarkable efficacy of EHS. CONCLUSION: This study demonstrated that EHS is effective against HR-HPV infection and cervical lesions. Additionally, no obvious systemic toxicity was observed in patients during the trial. The superior efficacy and safety of EHS demonstrated its considerable value as a potential cost-effective drug for the treatment of HPV infection and HPV-related cervical diseases.
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Persicae Semen (Taoren), the seed of mature peaches consumed as both food and medicine, is native to the temperate regions of China, distributed in the provinces of North and East China, and currently cultivated worldwide. The primary components of Persicae Semen include volatile oil, protein, amino acids, amygdalin, and prunasin, all of which have pharmacological properties, such as anti-inflammatory, antioxidant, and immune regulatory effects, and are clinically used in the treatment of gynecological, cardiovascular, cerebrovascular, orthopedic, and digestive system diseases. This review provides a comprehensive perspective on the resource status, ethnopharmacology, phytochemistry, pharmacology, and toxicology, as well as the trend of Persicae Semen patent, global distribution, and clinical applications. This review will help facilitate the development and utilization of Persicae Semen in clinical settings.
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BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.
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Iron homeostasis is of critical importance to living organisms. Drosophila melanogaster has emerged as an excellent model to study iron homeostasis, while the regulatory mechanism of iron metabolism remains poorly understood. Herein, we accidently found that knockdown of juvenile hormone (JH) acid methyltransferase (Jhamt) specifically in the fat body, a key rate-limiting enzyme for JH synthesis, led to iron accumulation locally, resulting in serious loss and dysfunction of fat body. Jhamt knockdown-induced phenotypes were mitigated by iron deprivation, antioxidant and Ferrostatin-1, a well-known inhibitor of ferroptosis, suggesting ferroptosis was involved in Jhamt knockdown-induced defects in the fat body. Further study demonstrated that upregulation of Tsf1 and Malvolio (Mvl, homolog of mammalian DMT1), two iron importers, accounted for Jhamt knockdown-induced iron accumulation and dysfunction of the fat body. Mechanistically, Kr-h1, a key transcription factor of JH, acts downstream of Jhamt inhibiting Tsf1 and Mvl transcriptionally. In summary, the findings indicated that fat body-derived Jhamt is required for the development of Drosophila by maintaining iron homeostasis in the fat body, providing unique insight into the regulatory mechanisms of iron metabolism in Drosophila.
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Proteínas de Drosophila , Drosophila melanogaster , Cuerpo Adiposo , Homeostasis , Hierro , Metiltransferasas , Animales , Drosophila melanogaster/metabolismo , Hierro/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Cuerpo Adiposo/metabolismo , Metiltransferasas/metabolismo , Metiltransferasas/genética , Hormonas Juveniles/metabolismo , Ferroptosis/fisiología , Factores de Transcripción de Tipo KruppelRESUMEN
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is crucial for neuronal survival and may be implicated in the pathophysiological process of depression. This study aimed to prospectively investigate the association between serum BDNF and post-stroke depression (PSD) at 3 months in a multicenter cohort study. METHODS: A total of 611 ischemic stroke patients with serum BDNF measurements from the China Antihypertensive Trial in Acute Ischemic Stroke were included in this analysis. We used the 24-item Hamilton Depression Rating Scale to assess depression status at 3 months after ischemic stroke, and PSD was defined as a score of ≥8. RESULTS: Baseline serum BDNF was inversely associated with the risk of depression after ischemic stroke. The multivariable-adjusted odds ratio of PSD for the highest tertile of BDNF was 0.53 (95 % confidence interval, 0.34-0.82; P for trend = 0.004) compared with the lowest tertile. Multivariable-adjusted spline regression model also showed a linear does-response association between serum BDNF levels and PSD at 3 months (P for linearity = 0.006). In addition, adding serum BDNF to conventional risk factors significantly improved the risk reclassification of PSD (net reclassification improvement: 16.98 %, P = 0.039; integrated discrimination index: 0.93 %, P = 0.026). LIMITATIONS: All patients in this study were Chinese, so our findings should be applied to other populations cautiously. CONCLUSIONS: Higher serum BDNF levels at baseline were significantly associated with a decreased risk of PSD at 3 months, suggesting that BDNF might be a valuable predictive biomarker and potential therapeutic target for PSD among ischemic stroke patients.
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Factor Neurotrófico Derivado del Encéfalo , Depresión , Accidente Cerebrovascular Isquémico , Humanos , Factor Neurotrófico Derivado del Encéfalo/sangre , Femenino , Masculino , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/complicaciones , Persona de Mediana Edad , Anciano , China , Depresión/sangre , Estudios Prospectivos , Factores de Riesgo , Biomarcadores/sangreRESUMEN
BACKGROUND: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited. PURPOSE: To gain a better understanding about GAS meningitis. METHODS: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized. RESULTS: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%. CONCLUSIONS: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death.
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Meningitis Bacterianas , Infecciones Estreptocócicas , Streptococcus pyogenes , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Antibacterianos/uso terapéutico , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Bacterianas/microbiología , Meningitis Bacterianas/mortalidad , Factores de Riesgo , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/mortalidadRESUMEN
BACKGROUND: Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. METHODS: We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. RESULTS: High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). CONCLUSIONS: Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention.
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Encéfalo , Cognición , Demencia , Análisis de la Aleatorización Mendeliana , Juegos de Video , Humanos , Demencia/epidemiología , Demencia/genética , Masculino , Femenino , Encéfalo/patología , Cognición/fisiología , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Imagen por Resonancia Magnética , Reino Unido/epidemiología , IncidenciaRESUMEN
Inspired by the charge-governed protein channels located in the cell membrane, a series of polyether ether ketone-based polymers with side chains containing ionically cross-linkable quaternary ammonium groups and acidic groups have been designed and synthesized to prepare monovalent cation-selective membranes (MCEMs). Three acidic groups (sulfonic acid, carboxylic acid, and phenolic hydroxyl) with different acid dissociation constant (pKa) were selected to form the ionic cross-linking structure with quaternary ammonium groups in the membranes. The ionic cross-linking induced the nanophase separation and constructed ionic channels, which resulted in excellent mechanical performance and high cation fluxes. Interesting, the cation flux of membranes increased as the ionization of acidic groups increase, but the selectivity of MCEMs did not follow the same trend, which was mainly dependent on the affinity between the functional groups and the cations. Carboxyl group-containing MCEMs exhibited the best selectivity (9.01 for Li+/Mg2+), which was higher than that of the commercial monovalent cation-selective CIMS membrane. Therefore, it is possible to prepare stable MCEMs through a simple process using ionically cross-linkable polymers, and tuning acidic groups in the membranes provided an attractive approach to improving the cation flux and selectivity of MCEMs.
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Disulfidptosis is a novel form of cell death that is distinguishable from established programmed cell death pathways such as apoptosis, pyroptosis, autophagy, ferroptosis, and oxeiptosis. This process is characterized by the rapid depletion of nicotinamide adenine dinucleotide phosphate (NADPH) in cells and high expression of solute carrier family 7 member 11 (SLC7A11) during glucose starvation, resulting in abnormal cystine accumulation, which subsequently induces andabnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. This review aimed to summarize the underlying mechanisms, influencing factors, comparisons with traditional cell death pathways, associations with related diseases, application prospects, and future research directions related to disulfidptosis.
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OBJECTIVE: To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. METHODS: An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. RESULTS: The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p < 0.001). There were 28 (93.3%), 2 (6.7%), 0, and 0 patients in the study group and 16 (53.3%), 7 (23.3%), 5 (16.7%), and 2 (6.7%) in the control group (p < 0.001) who had grade 0, 1, 2, and 3 perfusion impairment, respectively. Additionally, there were 27 (90%), 3 (10%), and 0 patients in the study group and 19 (63.3%), 10 (33.3%), and 1 (3.3%) in the control group who had grade 0, 1, and 2 endometrial dehydration (p = 0.01). The ablation rates achieved in the study and control groups were 93.3 ± 17% (range: 69.2-139.6%) and 99.7 ± 15.7% (range: 71.5-129.8%), and they were not significantly different (p = 0.14). No significant difference was found in the intra-ablation discomfort. CONCLUSION: Intrauterine chilled saline can effectively reduce endometrial impairment after PMWA treatment for adenomyosis. CRITICAL RELEVANCE STATEMENT: This trial demonstrated that the instillation of intrauterine chilled saline reduced endometrial impairment on MRI during PMWA of adenomyosis. This approach allows more precise and safe ablation in clinical practice. KEY POINTS: Endometrial impairment occurs in the PMWA treatment of adenomyosis. Intrauterine chilled saline can reduce endometrial impairment during PMWA for adenomyosis. An intrauterine catheter is a practical endometrial protecting method during thermal ablation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100053582. Registered 24 November 2021, www.chictr.org.cn/showproj.html?proj=141090 .
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Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1-nitropyrene (1-NP), a key component of motor vehicle exhaust, on autism-like behaviors in a mouse model. Three-chamber test finds that prenatal 1-NP exposure causes autism-like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1-NP-exposed weaning pups. Immunofluorescence finds that prenatal 1-NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1-NP exposure retards tangential migration of GAD67-positive interneurons and downregulates interneuron migration-related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1-NP exposure reduces hydroxymethylation of interneuron migration-related genes through inhibiting ten-eleven translocation (TET) activity in fetal forebrain. Supplement with alpha-ketoglutarate (α-KG), a cofactor of TET enzyme, reverses 1-NP-induced hypohydroxymethylation at specific sites of interneuron migration-related genes. Moreover, α-KG supplement alleviates 1-NP-induced migration retardation of interneurons in fetal forebrain. Finally, maternal α-KG supplement improves 1-NP-induced autism-like behaviors in weaning offspring. In conclusion, prenatal 1-NP exposure causes autism-like behavior partially by altering DNA hydroxymethylation of interneuron migration-related genes in developing brain.
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Encéfalo , Modelos Animales de Enfermedad , Efectos Tardíos de la Exposición Prenatal , Animales , Ratones , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/genética , Femenino , Embarazo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Trastorno Autístico/genética , Trastorno Autístico/inducido químicamente , Trastorno Autístico/metabolismo , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Conducta Animal/efectos de los fármacos , Masculino , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/inducido químicamente , Trastorno del Espectro Autista/metabolismo , Pirenos/toxicidad , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Pulmonary hypertension (PH) is a key complication in interstitial lung disease (ILD), with recent therapeutic advances. RESEARCH QUESTION: What are the diagnostic evaluation, epidemiologic features, associated factors, prognostic significance, and outcome measures in interventional trials for PH in patients with ILD in the current literature? STUDY DESIGN AND METHODS: Ovid MEDLINE, Embase, and CENTRAL databases were searched for original research evaluating PH in participants with ILD of any cause. The definition of PH was based on the investigators' criteria. RESULTS: Three hundred two studies were included, with varying diagnostic evaluations used to define PH. Commonly used diagnostic tests were right heart catheterization (RHC; 56%) and transthoracic echocardiography (TTE; 50%). The pooled prevalence for PH in general populations with ILD was 36% (95% CI, 30%-42%) using RHC and 34% (95% CI, 29%-38%) using TTE. Lower diffusion capacity of the lungs for carbon monoxide, worse oxygenation status, reduced exercise capacity, increased pulmonary artery to aorta ratio and pulmonary artery diameter, and elevated serum brain natriuretic peptide consistently were associated with the presence of PH in at least 60% of reported studies. The presence of PH was associated with increased symptom burden and worse prognosis. Outcome measures in interventional trials of PH in ILD focused on changes in pulmonary vascular hemodynamics and 6-min walk distance. INTERPRETATION: PH is a common complication in ILD with significant health impacts. A standardized definition with prospective evaluation of risk-stratified assessments for PH using identified associated risk factors is warranted. Our findings provide an evidence base for validation as surrogate end points in future PH interventional trials in ILD. TRIAL REGISTRY: International Prospective Register of Systematic Reviews; No.: CRD42021255394; URL: https://www.crd.york.ac.uk/prospero/.
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BRAFV600E-mutant metastatic colorectal cancer represents a distinct molecular phenotype known for its aggressive biological behavior, resistance to standard therapies, and poor survival rates. Improved understanding of the biology of the BRAF oncogene has led to the development of targeted therapies that have paved the way for a paradigm shift in managing this disease. However, despite significant recent advancements, responses to targeted therapies are short-lived, and several challenges remain. In this review, we discuss how progress in treating BRAFV600E-mutant metastatic colorectal cancer has been made through a better understanding of its unique biological and clinical features. We provide an overview of the evidence to support current treatment approaches and discuss critical areas of need and future research strategies that hold the potential to refine clinical practice further. We also discuss some challenging aspects of managing this disease, particularly the complexity of acquired resistance mechanisms that develop under the selective pressure of targeted therapies and rational strategies being investigated to overcome them.
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BACKGROUND: Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris. METHODS: This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8â :â 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts. RESULTS: A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively. CONCLUSION: Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris.