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BACKGROUND: Thalamic abnormalities in schizophrenia are recognized, alongside cognitive deficits. However, the current findings about these abnormalities during the prodromal period remain relatively few and inconsistent. This study applied multimodal methods to explore the alterations in thalamic function and structure and their relationship with cognitive function in first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, aiming to affirm the thalamus's role in schizophrenia development and cognitive deficits. METHODS: 75 FES patients, 60 UHR individuals, and 60 healthy controls (HC) were recruited. Among the three groups, gray matter volume (GMV) and functional connectivity (FC) were evaluated to reflect the structural and functional abnormalities in the thalamus. Pearson correlation was used to calculate the association between these abnormalities and cognitive impairments. RESULTS: No significant difference in GMV of the thalamus was found among the abovementioned three groups. Compared with HC individuals, FES patients had decreased thalamocortical FC mostly in the thalamocortical triple network, including the default mode network (DMN), salience network (SN), and executive control network (ECN). UHR individuals had similar but milder dysconnectivity as the FES group. Furthermore, FC between the left thalamus and right putamen was significantly correlated with execution speed and attention in the FES group. CONCLUSIONS: Our findings revealed decreased thalamocortical FC associated with cognitive deficits in FES and UHR subjects. This improves our understanding of the functional alterations in thalamus in prodromal stage of schizophrenia and the related factors of the cognitive impairment of the disease. TRIAL REGISTRATION: ClinicalTrials.govNCT03965598; https://clinicaltrials.gov/ct2/show/NCT03965598.
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Brain structural abnormality has been observed in the prodromal and early stages of schizophrenia, but the mechanism behind it is not clear. In this study, to explore the association between cortical abnormalities, metabolite levels, inflammation levels and clinical symptoms of schizophrenia, 51 drug-naive first-episode schizophrenia (FES) patients, 51 ultra-high risk for psychosis (UHR), and 51 healthy controls (HC) were recruited. We estimated gray matter volume (GMV), cortical thickness (CT), concentrations of different metabolites, and inflammatory marks among four groups (UHR converted to psychosis [UHR-C], UHR unconverted to psychosis [UHR-NC], FES, HC). UHR-C group had more CT in the right lateral occipital cortex and the right medial orbito-frontal cortex (rMOF), while a significant reduction in CT of the right fusiform cortex was observed in FES group. UHR-C group had significantly higher concentration of IL-6, while IL-17 could significantly predict CT of the right fusiform and IL-4 and IL-17 were significant predictors of CT in the rMOF. To conclude, it is reasonable to speculate that the increased CT in UHR-C group is related to the inflammatory response, and may participate in some compensatory mechanism, but might become exhaustive with the progress of the disease due to potential neurotoxic effects.
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Corteza Cerebral , Imagen por Resonancia Magnética , Esquizofrenia , Humanos , Esquizofrenia/patología , Esquizofrenia/diagnóstico por imagen , Masculino , Femenino , Adulto Joven , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Adulto , Sustancia Gris/patología , Sustancia Gris/diagnóstico por imagen , AdolescenteRESUMEN
Hydraulic fracturing generates fractures in a coal seam, which has been extensively used in coal mining and disaster management. To study the influences of water injection pressure and time on the propagation of hydraulic fracture, we conducted true triaxial hydraulic fracturing experiments under acoustic emission monitoring. Five briquette specimens were prepared by molding the mixture of coal powder, cement, river sand, and distilled water under 60 MPa to simulate the properties of coal seam. True triaxial loading was used to simulate the in situ stress environment of the coal seam. Hydraulic fracturing experiments on the test specimens were conducted under different water injection pressures and times. The following conclusions have been drawn. At the fixed injection time, increasing water injection pressure promotes the propagation of hydraulic fracture and the migration of water in the coal seam after the fractures are connected. The number of fractures increases from 3 to 8 as the water injected pressure increased from 3 to 9 MPa. Under the constant water injection pressure, the increase in longitudinal wave velocity in the test specimen decreases with the prolongation of water injection time. When the water reaches the action boundary of the water injection pressure, the water stops moving. At this moment, the water injection time has no effect on the longitudinal wave velocity anymore. The fracturing influence range can be increased by increasing the water injection pressure to produce a fracture network of a large radius with many fractures. Appropriately prolonging hydraulic fracturing time can ensure that the fracturing fluid fully moistens the coal seam and thus effectively reduces dust pollution.
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BACKGROUND: The effect of childhood trauma on Internet gaming disorder remains unclear. In this study, we examined this association in Chinese students and explored the possible associated roles of psychological resilience and depression. METHODS: In total, 8,579 students from Hunan Province, China, provided information regarding their sociodemographic factors, history of childhood trauma, any symptoms of depression, psychological resilience, and characteristics of Internet gaming disorder for this cross-sectional study. The impact of childhood trauma on Internet gaming disorder, as well as the extent to which it was mediated by depression and moderated by psychological resilience was evaluated. RESULTS: The influence of childhood trauma on Internet gaming disorder was partially mediated by depression (B = 0.07, 95% CI [0.04, 0.05], p < 0.001), with psychological resilience acting as a mitigating factor (B = -0.002, 95% CI [13.74, 21.72], p < 0.001). Psychological resilience also moderated the association between childhood trauma and depression (B = - 0.003, 95% CI [22.17, 28.10], p < 0.001). Our moderated mediation model elucidated psychosocial mechanisms, revealing the underlying link between childhood trauma and Internet gaming disorder. It also demonstrated the partial mediating role of depression and modulating role of psychological resilience among Chinese students. CONCLUSIONS: Education and interventions, along with effective social support, should be provided to enhance students' psychological resilience and prevent childhood trauma and depression.
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Experiencias Adversas de la Infancia , Depresión , Trastorno de Adicción a Internet , Análisis de Mediación , Resiliencia Psicológica , Humanos , Masculino , Trastorno de Adicción a Internet/psicología , Femenino , China , Estudios Transversales , Depresión/psicología , Experiencias Adversas de la Infancia/psicología , Adulto Joven , Adolescente , Adulto , Juegos de Video/psicología , Estudiantes/psicologíaRESUMEN
OBJECTIVE: Patients with psychotic diseases have been reported to exhibit abnormalities in their olfactory discrimination. These alterations have also been identified in people at high genetic or clinical risk for psychosis, suggesting olfactory discrimination dysfunction may be a potential risk factor for developing psychosis. Thus, the purpose of our study is to explore the difference in olfactory discrimination ability in the prosal stage and early stage of psychosis and to explore the potential risk factor of developed psychosis. METHODS: We compared olfactory identification and cognitive function in 89 ultra-high-risk (UHR) individuals, 103 individuals with Drug-naïve first-episode schizophrenia (FES), 81 genetic high-risk (GHR) individuals, and 97 healthy controls (HC). Additionally, we compared olfactory identification and cognitive function between two groups; UHR individuals who later transitioned to psychosis (UHR-T; n = 33) and those who did not transition (UHR-NT; n = 42)). Furthermore, we analyzed the correlations between olfactory discrimination ability and cognitive function and symptoms and compared the olfactory function between men and women. RESULTS: Patients with first-episode schizophrenia (FES) and those at ultra-high risk (UHR) for psychosis exhibited more significant deficits in olfactory identification than healthy controls (HC), while no differences in olfactory identification dysfunction were observed between the genetic high risk (GHR) and HC groups. Notably, individuals in the UHR group who later developed psyhchosis displayed a steeper marked decline in their baseline olfactory identification ability than that of those in the UHR group who did not develop psychosis. Cognitive dysfunction is widely observed in both the FES and UHR groups, with a distinct correlation identified between olfactory discrimination function and cognitive performance. Finally, overall, women exhibit significantly superior olfactory function than men. CONCLUSION: In conclusion, these findings suggest that impairment of olfactory identification exists in the early stage of psychosis. Olfactory identification dysfunction may therefore be a potential marker of predicting the transition to schizophrenia.
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Trastornos del Olfato , Trastornos Psicóticos , Humanos , Masculino , Femenino , Trastornos Psicóticos/complicaciones , Adulto Joven , Adulto , Esquizofrenia/fisiopatología , Esquizofrenia/complicaciones , Discriminación en Psicología/fisiología , Factores de Riesgo , Adolescente , Percepción Olfatoria/fisiología , Olfato/fisiologíaRESUMEN
Based on the matching of the database of China Industry Business Performance and China Customs Trade from 2000 to 2013, this paper constructs the digital product import index, and adopts the method of panel data modeling to systematically investigate the impact and mechanism of digital product import on the domestic value-added rate of Chinese enterprises' export from the theoretical and empirical aspects. The research finds that the import of digital products significantly promotes the improvement of the domestic value-added rate of enterprises' export, and the core conclusion is still valid after considering the endogeneity of variables, changing the measurement index and estimation method. The mechanism test finds that the import of digital products improves the domestic value-added rate of enterprises' export through two channels: cost markup and relative price. In addition, the heterogeneity test finds that the import of digital products has a stronger effect on the improvement of the domestic value-added rate of enterprises' export in non-export enterprises, pure general trading enterprises, foreign-funded enterprises, labor-intensive enterprises and enterprises in the eastern region.
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OBJECTIVES: To investigate the effect of subacute exposure of Di (2-ethylhexyl) phthalate (DEHP) on endometrial decidualization in mice. METHODS: CD1 mice were orally administrated with 300 mg·kgï¼1·dï¼1 (low-dose group), 1000 mg·kgï¼1·dï¼1 (medium-dose group), or 3000 mg·kgï¼1·dï¼1 DEHP (1/10 LD50, high-dose group) for 28 days, respectively. The early natural pregnancy model and artificially induced decidualization model were established, and the uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization, respectively. The effects of subacute exposure to DEHP on the decidualization of mice were detected by HE staining, Masson staining, TUNEL staining, and Western blotting, respectively. A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg-1·d-1 DEHP, and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation. RESULTS: Compared with the control group, the conception rate was significantly lower in the high-dose DEHP subacute exposure group. HE staining showed that, compared with the control group, the decidual stromal cells in the low- and medium-dose exposure groups were disorganized, the nuclei of the cells were irregular, the cytoplasmic staining was uneven, and the number of polymorphonuclear cells was significantly reduced. Masson staining showed that compared with the control group, the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed, more abundant and more disorderly. TUNEL staining showed increased apoptosis in the decidua area compared to the control group. Western blotting showed that the expression of BMP2, a marker molecule for endometrial decidualization, was significantly reduced. The abortion rate and embryo resorption rate were significantly higher, and the number of embryos, uterine wet weight, uterine area and placenta wet weight were significantly lower in mice exposed to 300 mg·kgï¼1·dï¼1 DEHP than in control mice stimulated by mifepristone abortifacient drug. CONCLUSIONS: Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnant outcomes in mice.
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The objective of this meta-analysis is to delineate the association between H. pylori CagA serological status and the prevalence of gastric precancerous lesions (GPL). We searched peer-reviewed articles up to October 2023. The extraction of data from the included studies was carried out as well as the quality assessment. Pooled effect sizes were calculated using a random effect model. Thirteen studies met the inclusion criteria, comprising 2728 patients with GPL and 17â 612 controls. The aggregate odds ratio (OR) for the association between serum CagA and GPL was 2.74 (95% CIâ =â 2.25-3.32; P â =â 0.00; I 2 â =â 60.4%), irrespective of H. pylori infection status. Within the H. pylori -infected cohort, the OR was 2.25 (95% CIâ =â 1.99-2.56; P â =â 0.00; I 2 â =â 0.0%). Conversely, among the non-infected individuals, the OR was 1.63 (95% CIâ =â 1.04-2.54; P â =â 0.038; I 2 â =â 0.0%). Heterogeneity was explored using subgroup and meta-regression analyses, indicating that the variability between studies likely stemmed from differences in disease classification. Our results demonstrated robustness and negligible publication bias. The meta-analysis underscores a more pronounced association between H. pylori CagA seropositivity and the risk of developing GPL than between seronegativity and the same risk, irrespective of H. pylori infection status at the time. Additionally, the strength of the association was heightened in the presence of an active H. pylori infection. The implications of these findings advocate for the utility of CagA serostatus as a potential biomarker for screening GPL.
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Antígenos Bacterianos , Proteínas Bacterianas , Infecciones por Helicobacter , Helicobacter pylori , Lesiones Precancerosas , Neoplasias Gástricas , Humanos , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/sangre , Helicobacter pylori/inmunología , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Proteínas Bacterianas/inmunología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/sangre , Neoplasias Gástricas/inmunología , Lesiones Precancerosas/microbiología , Lesiones Precancerosas/sangre , Factores de Riesgo , PrevalenciaRESUMEN
Background: Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis. Objectives: This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs. Design: A retrospective study. Methods: A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators. Results: A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma (n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection (p < 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups (p < 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876-1.000), 0.892 (95% CI, 0.656-0.934), and 0.786 (95% CI, 0.491-0.937) at 1-, 2-, and 5-year follow-up, respectively. Conclusion: The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.
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BACKGROUND: Pancreatic cancer (PC) is usually detected in the advanced stages. Liquid biopsy has become a revolutionary strategy for cancer diagnosis and prognosis prediction. This study aims to investigate the diagnostic and prognostic value of circulating exosomal glypican-1 (GPC-1) in PC. METHODS: We systematically searched relevant studies. For diagnostic accuracy, pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated. Regarding prognostic value, hazard ratios (HRs) and 95% CIs for overall survival (OS) were summarized by using a random-effects model. RESULTS: We found 8 studies that examined the diagnostic value of circulating exosomal GPC-1 in PC, and 3 studies that investigated its prognostic value. Pooled sensitivity and specificity were 0.88 (95% CI, 0.65-0.97) and 0.86 (95% CI, 0.72-0.94). The AUC was 0.93 (95% CI, 0.90-0.95). Prognostic analysis showed that higher levels of circulating exosomal GPC-1 were associated with poorer OS in PC patients, and the combined HR for OS was 4.59 (random-effects model, 95% CI = 1.17-18.03, P = .022). The results of both studies were robust and neither had publication bias. CONCLUSION: Circulating exosomal GPC-1 may be used as a diagnostic and prognostic biomarker for PC. However, this result needs to be validated by further research using a larger sample size.
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Background: DHEA is a steroid hormone produced by the gonads, adrenal cortex, brain, and gastrointestinal tract. While the anti-obesity, anti-atherosclerosis, anti-cancer, and memory-enhancing effects of DHEA have been substantiated through cell experiments, animal studies, and human trials, the precise mechanisms underlying these effects remain unclear. Altered mitochondrial dynamics can lead to mitochondrial dysfunction, which is closely related to many human diseases, especially cancer and aging. This study was to investigate whether DHEA inhibits lung adenocarcinoma through the mitochondrial pathway and its molecular mechanism. Methods: Through animal experiments and cell experiments, the effect of DHEA on tumor inhibition was determined. The correlation between FASTKD2 expression and DHEA was analyzed by Western blot, Reverse transcription-quantitative PCR, Immunohistochemistry, and TCGA database. Results: In this study, DHEA supplementation in the diet can inhibit the tumor size of mice, and the effect of adding DHEA one week before the experiment is the best. DHEA limits the glycolysis process by inhibiting G6PDH activity, increases the accumulation of reactive oxygen species, and initiates apoptosis in the mitochondrial pathway of cancer cells. Conclusion: DHEA suppresses mitochondrial fission and promotes mitochondrial fusion by downregulating the expression of FASTKD2, thereby inhibiting tumor growth and prolonging the overall survival of lung adenocarcinoma patients, which also provides a new target for the prevention and treatment of lung adenocarcinoma.
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PURPOSE: The purpose of this study was to explore the expression and potential mechanism of hsa_circ_0005397 in hepatocellular carcinoma progression. METHODS: Quantitative reverse transcription-polymerase chain reaction(qRT-PCR) was used to measure the expression level of hsa_circ_0005397 and EIF4A3 from paired HCC tissues and cell lines. Western Blot (WB) and immunohistochemistry (IHC) were used to verify the protein level of EIF4A3. The specificity of primers was confirmed by agarose gel electrophoresis. Receiver Operating Characteristic (ROC) Curve was drawn to analyze diagnostic value. Actinomycin D and nuclear and cytoplasmic extraction assays were utilized to evaluate the characteristics of hsa_circ_0005397. Cell Counting kit-8 (CCK-8) and colony formation assays were performed to detect cell proliferation. Flow cytometry analysis was used to detect the cell cycle. Transwell assay was performed to determine migration and invasion ability. RNA-binding proteins (RBPs) of hsa_circ_0005397 in HCC were explored using bioinformatics websites. The relationship between hsa_circ_0005397 and Eukaryotic Translation Initiation Factor 4A3 (EIF4A3) was verified by RNA Binding Protein Immunoprecipitation (RIP) assays, correlation and rescue experiments. RESULTS: In this study, hsa_circ_0005397 was found to be significantly upregulated in HCC, and the good diagnostic sensitivity and specificity shown a potential diagnostic capability. Upregulated expression of hsa_circ_0005397 was significantly related to tumor size and stage. Hsa_circ_0005397 was circular structure which more stable than liner mRNA, and mostly distributed in the cytoplasm. Upregulation of hsa_circ_0005397 generally resulted in stronger proliferative ability, clonality, and metastatic potency of HCC cells; its downregulation yielded the opposite results. EIF4A3 is an RNA-binding protein of hsa_circ_0005397, which overexpressed in paired HCC tissues and cell lines. In addition, expression of hsa_circ_0005397 decreased equally when EIF4A3 was depleted. RIP assays and correlation assay estimated that EIF4A3 could interacted with hsa_circ_0005397. Knockdown of EIF4A3 could reverse hsa_circ_0005397 function in HCC progression. CONCLUSIONS: Hsa_circ_0005397 promotes progression of hepatocellular carcinoma through EIF4A3. These research findings may provide novel clinical value for hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , ARN Circular/genética , ARN Circular/metabolismo , Regulación hacia Abajo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismo , ARN Helicasas DEAD-box/genéticaRESUMEN
The nonclassical ten-pi-electron 5,5-fused thieno[3,4-c]thiadiazole (TTD) unit is an excellent building block for constructing sub-silicon-band gap organic semiconductors. However, no small molecule acceptor (SMA) materials based on TTD have been reported despite the fact that high-sensitivity near-infrared organic photodetectors (OPDs) are generally achieved by using SMAs. In this work, we report a TTD-based narrow band gap (0.95 eV) SMA material TTD(DTC-2FIC)2 with strong near-infrared absorption. Employing PTB7-Th as a donor, OPDs based on TTD(DTC-2FIC)2 exhibit an optimized responsivity of 0.095 (±0.007) A W-1 at 1100 nm and sustain a decent responsivity of 0.074 (±0.008) A W-1 at 1200 nm. Moreover, a good specific detectivity over 1 × 1011 Jones is achieved at a wavelength of 1200 nm. Detailed characterizations imply that the performance of TTD(DTC-2FIC)2-based OPDs may be substantially improved by choosing lower-mixing donors with shallower energy levels. This work demonstrates that SMAs incorporating TTD as the core unit hold promise for constructing high-sensitivity sub-silicon-band gap OPDs.
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OBJECTIVE: To investigate the treatment plan and prognosis of children with ocular dyskinesia and hemifacial spasm secondary to pontine tumours adjacent to the fourth ventricle. METHODS: In this retrospective study, the clinical information of 10 consecutively collected children with ocular dyskinesia and hemifacial spasm secondary to pontine tumours adjacent to the fourth ventricle was analyzed. All 10 children underwent pontine tumour resection through a trans-cerebellomedullary fissure approach; 4 children underwent preoperative diffusion tensor imaging scans to determine the relationship between the tumour and facial nerve nucleus, and the other 6 children underwent intraoperative deep electroencephalography (EEG) tumour monitoring, in which the tumour electrical discharge activity of the tumour was recorded. A voxel distribution map was established to describe the distribution of the tumour location, and patient prognosis was evaluated through clinical and imaging follow-up. RESULTS: All 10 children achieved total tumour resection; 9 tumours were pathologically suggested to be ganglioglioma (WHO grade I), and 1 was a hamartoma. The symptoms of the original ocular dyskinesia and hemifacial spasm disappeared immediately after the operation. The children were followed up for 4-75 months, and none of the symptoms recurred; four cases with preoperative diffusion tensor imaging showed that the tumour was close to the facial nerve. Four in six intraoperative electrophysiological monitoring showed that the tumour had electrical discharge behaviour, and the tumour distribution map indicates a high density of tumour presence in the facial nerve nucleus and the nucleus of the abducens nerve. CONCLUSIONS: In paediatric patients, the facial symptoms are related to the location and abnormal electrical discharge of the tumour. There is no significant correlation between ocular dyskinesia and the location of the tumour. Conventional antiepileptic therapy for this disease is ineffective, and early surgical intervention for total tumour resection can achieve a clinical curative effect.
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Espasmo Hemifacial , Humanos , Femenino , Masculino , Espasmo Hemifacial/etiología , Espasmo Hemifacial/cirugía , Niño , Preescolar , Estudios Retrospectivos , Neoplasias del Tronco Encefálico/complicaciones , Neoplasias del Tronco Encefálico/cirugía , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Cuarto Ventrículo/cirugía , Cuarto Ventrículo/diagnóstico por imagen , Lactante , Trastornos de la Motilidad Ocular/etiología , Trastornos de la Motilidad Ocular/cirugía , AdolescenteRESUMEN
A subgroup of patients with schizophrenia is believed to have aberrant excess of glutamate in the frontal cortex; this subgroup is thought to show poor response to first-line antipsychotic treatments that focus on dopamine blockade. If we can identify this subgroup early in the course of illness, we can reduce the repeated use of first-line antipsychotics and potentially stratify first-episode patients to intervene early with second-line treatments such as clozapine. The use of proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate and Glx (glutamate plus glutamine) may provide a means for such a stratification. We must first establish if there is robust evidence linking elevations in anterior cingulate cortex (ACC) glutamate metabolites to poor response, and determine if the use of antipsychotics worsens the glutamatergic excess in eventual nonresponders. In this study, we estimated glutamate levels at baseline in 42 drug-naive patients with schizophrenia. We then treated them all with risperidone at a standard dose range of 2-6 mg/day and followed them up for 3 months to categorize their response status. We expected to see baseline "hyperglutamatergia" in nonresponders, and expected this to worsen over time at the follow-up. In line with our predictions, nonresponders had higher glutamate than responders, but patients as a group did not differ in glutamate and Glx from the healthy control (HC) group before treatment-onset (F1,79 = 3.20, p = 0.046, partial η2 = 0.075). Glutamatergic metabolites did not change significantly over time in both nonresponders and responders over the 3 months of antipsychotic exposure (F1,31 = 1.26, p = 0.270, partial η2 = 0.039). We conclude that the use of antipsychotics without prior knowledge of later response delays symptom relief in a subgroup of first-episode patients, but does not worsen the glutamatergic excess seen at the baseline. Given the current practice of nonstratified use of antipsychotics, longer-time follow-up MRS studies are required to see if improvement in symptoms accompanies a dynamic shift in glutamate profile.
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Antipsicóticos , Trastornos Psicóticos , Esquizofrenia , Humanos , Antipsicóticos/uso terapéutico , Antipsicóticos/farmacología , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/metabolismo , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/tratamiento farmacológico , Trastornos Psicóticos/metabolismo , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Ácido Glutámico/metabolismo , Espectroscopía de Protones por Resonancia Magnética/métodos , Glutamina/metabolismoRESUMEN
Objective To explore the prevalence rate and related factors of urban and rural residents with hyperuricemia (HUA). Methods A total of 360 subjects in physical examination department of Sanliusan Hospital from January 2020 to January 2023 were selected and divided into urban residents and rural residents according to their permanent residence addresses, and the demographic information, living habits and underlying diseases were collected. Fasting blood glucose (FBG), serum uric acid (SUA), body mass index (BMI) and triglyceride (TG) were measured. The risk factors of HUA were analyzed by logistics regression analysis. Results The incidence rates of HUA in urban and rural residents were 12.18% and 12.88%. There were statistically significant differences in education level, occupation, BMI, sleep time, alcohol drinking, FBG and TG between urban and rural residents (all P24 kg/m2, alcohol drinking and chronic kidney disease were independent risk factors for HUA occurrence among urban residents (all P<0.05). Chronic kidney disease, FBG≥7.0 mmol/L and TG≥2.3 mmol/L were independent risk factors for hyperuricemia occurrence among rural residents (all P<0.05). Conclusion Rural residents should strengthen health education and blood glucose and lipid control, and urban residents should pay more attention to reasonable exercise, control alcohol consumption and reduce HUA occurrence.
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Objective To study the therapeutic effect of Xuefu Zhuyu Capsule combined with sacubitril valsartan on dilated cardiomyopathy.Methods A total of 70 patients with dilated cardiomyopathy who were hospitalized in the Hospital from January to December 2020 were selected as the research objects and random-ly divided into control group and experimental group,with 35 cases in each group.The control group was only treated with sacubitril valsartan,and the experimental group was treated with Xuefu Zhuyu Capsule combined with sacubitril valsartan.According to the patient's blood pressure and renal function,sacubitril valsartan was titrated from a small dose to the maximum dose.Xuefu Zhuyu Capsule was uesd 2.4 g each time,twice a day,and the treatment time was three months.The symptoms of heart failure,glycosylated hemoglobin(HbA1c),low density lipoprotein(LDL),total cholesterol(TC),triglyceride(TG),ALT,AST,N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular end-systolic diameter(LVEDd),left ventricular end-dias-tolic diameter(LVEDs),ejection fraction(EF)and the incidence of arrhythmia were observed in the two groups after treatment.Results After treatment,the level of NT-proBNP in the experimental group was sig-nificantly lower than that in the control group(P<0.05).There was no significant difference in LDL,TC,TG,LVEDd,LVEDs and EF between the two groups(P>0.05).The incidence of atrial tachycardia and ven-tricular premature beat in the experimental group was higher than that in the control group(P<0.05).Con-clusion Xuefu Zhuyu Capsule combined with sacubitril valsartan can significantly improve the symptoms of patients with heart failure and reduce the level of NT-proBNP,but it may increase the proportion of patients with atrial tachycardia and ventricular premature beats.
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Objective:To investigate the clinical characteristics and prognosis of CpG island methylator phenotype (CIMP+ ) colon cancer, and the significance of CIMP status in the diagnosis and prognosis prediction in defective mismatch repair (dMMR) colon cancer.Methods:The keywords "colorectal cancer" "patient" and "CpG Island Methylator Phenotype" were used to search the Gene Expression Omnibus (GEO) database, and the GSE39582 was obtained, which included the clinical data of 585 patients with colorectal cancer and the sequencing data of the whole transcriptome of the tumor tissues. After excluding 72 cases with missing CIMP values, 513 cases were included for further analysis, including 278 males and 235 females, with a mean age of (67±13) years. According to the CIMP status, they were divided into CIMP+ group ( n=93) and CIMP-group ( n=420), then compare the differences in clinical characteristics, the Kaplan-Meier survival curves were plotted to compare the overall survival and disease-free survival; 71 dMMR cases were divided into CIMP+ group ( n=43) and CIMP-group ( n=28), and the K-M curves were plotted to analyze the differences in overall survival (OS) and disease free survival (DFS). Comparisons between groups were performed by t-test, χ2 test or Mann-Whitney U nonparametric test, and the difference in survival curves was tested by Long-rank test. Results:Patients in the CIMP+ group were significantly older than those in the CIMP-group [(70.84±12.60) years vs (66.21±13.08) years, t=3.18, P=0.002]. Right colon tumors originating from the CIMP+ molecular pathway were 9.3 times more likely to be CIMP+ than those of the left colon cancers ( OR=9.3, 95% CI: 5.2-17.9). BRAF mutant colon cancer originating from CIMP+ was 215.2 times more common than BRAF wild-type colon cancer originating with CIMP+ ( OR=215.2, 95% CI: 53.2-1906.7); and patients with dMMR colon cancer originated 12.8 times more common than patients with pMMR ( OR=12.8, 95% CI: 7.0-23.9). The difference between the CIMP+ and CIMP-groups was not statistically significant in terms of overall survival and disease-free survival ( P=0.590, 0.220). In the dMMR colon cancer subgroup, CIMP status did not correlate with patients′ overall survival and disease-free survival ( P>0.05). Conclusions:CIMP+ colon cancer patients were mostly of advanced age, with tumors originating from the right colon, mostly combined with BRAF gene mutations, and manifested as mismatch repair-deficient colon cancers. CIMP status had no correlation with TNM stage and survival of colon cancers patients. There was no significant difference in the survival between dMMR colon cancers caused by CIMP+ and those caused by MMR gene mutations.
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Objective:To establish the animal model of cervicofacial venous malformations(VMs)by surgical reconstruction of exter-nal jugular vein in sheep.Methods:The external jugular veins of 5 sheep were dissected,and the position,course,branch and exter-nal diameter were observed and measured.The models of VMs with draining and returning veins were constructed by suturing or constric-ting the proximal part of main trunk and ligating or constricting the distal part of the jugular or branch veins.The animal model was eval-uated by Doppler ultrasound,gross observation and histological observation at the 4th week after surgery.Results:The external jugular veins of sheep is in the lateral side of bilateral neck,and the main trunk is formed by the maxillary vein and lingual facial vein.The ex-ternal diameter ranges from 6 to 12 mm,with an average external diameter of 9.3 mm.Immediately after the external jugular vein was sutured and narrowed at the proximal part of the main vein,the distal part of the vein branch was ligated or narrowed,the blood flow speed slowed down and the veins in the model area bulged.4 weeks after surgery,gross observation showed that most veins narrowed and thrombosis was formed in part of the venous lumen.The central region of some specimens was dilated,and the peripheral collateral veins were dilated in some models.Doppler ultrasonography showed that the lumens of most veins were dilated and the returning veins and the inflow veins were narrowed.Colored blood flow was seen in the lumen.Histological observation showed that the structure of vein endothelium and wall was close to the normal vein,and the vein vessel wall of some specimens was thickened.Conclusion:The VMs model estab-lished by external jugular vein of sheep basically meets the re-quirements and is expected to be used in the therapeutic meth-odology research of cervicofacial VMs.
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BACKGROUND:Multiple clinical observational studies have suggested a close relationship of serum trace elements and nutrients with osteonecrosis,but it remains unclear whether there is a genetic causal effect between serum trace elements and nutrients on osteonecrosis. OBJECTIVE:To investigate the causal effects of serum trace elements and nutrients on osteonecrosis using the Mendelian randomization approach. METHODS:The exposure factors of serum trace elements and vitamins with mononucleotide polymorphisms were obtained from the published UK Biobank database and publicly available databases of genome-wide association studies.The outcome event of osteonecrosis was derived from the FinnGen Biobank database.Mendelian randomization methods were employed to explore the causal relationship between seven trace elements and three nutrients with osteonecrosis.Causal inference was conducted using inverse variance weighting,MR-Egger,and weighted median methods.F-statistic was calculated to ensure the robustness of instrumental variables.Cochran's Q test and leave-one-out method were used for heterogeneity testing.MR-Egger regression and MR-PRESSO were employed for horizontal pleiotropy testing.PhenoScanner database was utilized to remove mononucleotide polymorphisms with horizontal pleiotropy to ensure the reliability of the results. RESULTS AND CONCLUSION:Causal relationships were found between serum selenium,phosphate,vitamin C,vitamin E,and osteonecrosis through Mendelian randomization analysis.Serum selenium,vitamin C,and vitamin E were found to have a protective effect on osteonecrosis,while excessive intake of phosphate increased the risk of osteonecrosis.No heterogeneity or horizontal pleiotropy was observed during the study,and Mendelian randomization statistical power(Power value>80%)indicated the reliability of the aforementioned four results.These findings have important clinical implications for the development of targeted preventive and therapeutic measures for osteonecrosis.