RESUMEN
Face perception is a complex process that involves highly specialized procedures and mechanisms. Investigating into face perception can help us better understand how the brain processes fine-grained, multidimensional information. This research aimed to delve deeply into how different dimensions of facial information are represented in specific brain regions or through inter-regional connections via an implicit face recognition task. To capture the representation of various facial information in the brain, we employed support vector machine decoding, functional connectivity, and model-based representational similarity analysis on fMRI data, resulting in the identification of three crucial findings. Firstly, despite the implicit nature of the task, emotions were still represented in the brain, contrasting with all other facial information. Secondly, the connection between the medial amygdala and the parahippocampal gyrus was found to be essential for the representation of facial emotion in implicit tasks. Thirdly, in implicit tasks, arousal representation occurred in the parahippocampal gyrus, while valence depended on the connection between the primary visual cortex and the parahippocampal gyrus. In conclusion, these findings dissociate the neural mechanisms of emotional valence and arousal, revealing the precise spatial patterns of multidimensional information processing in faces.
Asunto(s)
Emociones , Imagen por Resonancia Magnética , Humanos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Giro Parahipocampal/diagnóstico por imagen , Expresión FacialRESUMEN
On the basis of variable-temperature single-crystal X-ray diffraction, variable-temperature/frequency dielectric analysis, variable-temperature solid-state nuclear magnetic resonance spectroscopy, and molecular dynamics simulations, here we present a new model of crystalline supramolecular rotor (i-PrNHMe2)[CdBr3], where a conformationally flexible near-spherical (i-PrNHMe2)+ cation functions as a rotator and a rod-like anionic coordination polymer {[CdBr3]-}∞ acts as the stator, and the adhesion of them is realized by charge-assisted hydrogen bonds.
RESUMEN
OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Spastic paraplegia type 5A (SPG5A). METHODS: A pedigree suspected for Hereditary spastic paraplegia (HSP) at Henan Children's Hospital on August 15 2022 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples were collected from members of the pedigree. Following extraction of genomic DNA, trio-WGS was carried out, and candidate variant was verified by Sanger sequencing. RESULTS: The child, a 1-year-old boy, had presented with microcephaly, hairy face and dorsal side of distal extremities and trunk, intellectual and motor development delay, increased muscle tone of lower limbs, hyperreflexes of bilateral knee tendons, and positive pathological signs. His parents and sister both had normal phenotypes. Trio-WGS revealed that the child has harbored a homozygous c.1250G>A (p.Arg417His) variant of the CYP7B1 gene, for which his mother was heterozygous, the father and sister were of the wild type. The variant was determined to have originated from maternal uniparental disomy (UPD). The result of Sanger sequencing was in keeping with the that of trio-WGS. SPG5A due to maternal UPD of chromosome 8 was unreported previously. CONCLUSION: The child was diagnosed with SPG5A, a complex type of HSP, for which the homozygous c.1250G>A variant of the CYP7B1 gene derived from maternal UPD may be accountable.
Asunto(s)
Paraplejía Espástica Hereditaria , Humanos , Lactante , Masculino , China , Mutación , Paraplejía/genética , Linaje , Fenotipo , Paraplejía Espástica Hereditaria/genéticaRESUMEN
BACKGROUND: A blunted hypothalamic-pituitary-adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated. METHODS: Seventy-seven participants (17-22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17-22 years old, 24 women). RESULTS: Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response. CONCLUSIONS: This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.
Asunto(s)
Hidrocortisona , Resiliencia Psicológica , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Hidrocortisona/análisis , Sistema Hipotálamo-Hipofisario , Habituación Psicofisiológica/fisiología , Estrés Psicológico/psicología , Sistema Hipófiso-Suprarrenal , Saliva/químicaRESUMEN
Research over the last 10 years suggests that the brain's reward system plays a crucial role in stress resilience. Notably, reward processing includes both an anticipatory (cue-triggered "wanting") phase and a consummatory ("liking") phase. However, previous studies manipulated rewards via direct reward administration, which makes it difficult to isolate the buffering effect of anticipating the reward stimulus. In the current study, we designed a paradigm to manipulate participants into generating reward anticipation or not and investigated whether reward anticipation can buffer psychological, neuroendocrine, and cardiovascular responses to psychosocial stress. A sample of 78 healthy young adults underwent the Trier Social Stress Test or placebo-Trier Social Stress Test after a reward anticipation task. Results showed that reward anticipation relieved subjective stress feelings, as well as the overall cortisol secretion and the increased heart rate induced by psychosocial stress. Taken together, these findings expanded our understanding of the role the reward system plays in stress resilience, and the possible psychological mechanism of the buffering effect for future stress study was also discussed.HIGHLIGHTSReward processing includes both an anticipatory and consummatory phasesThe buffering effect of anticipating the reward stimulus requires elucidationWe examined if said anticipation buffers varied responses to psychosocial stressReward anticipation relieved subjective stress, cortisol secretion, and heart rateWe clarified the role of the reward system in stress resilience.
Asunto(s)
Anticipación Psicológica , Estrés Psicológico , Anticipación Psicológica/fisiología , Emociones , Humanos , Sistemas Neurosecretores , Recompensa , Adulto JovenAsunto(s)
Leucemia Promielocítica Aguda , Cromosomas Humanos Par 17/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo C , Humanos , Leucemia Promielocítica Aguda/genética , Proteínas de Fusión Oncogénica/genética , Receptores de Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico/genética , Translocación GenéticaRESUMEN
Stress resilience has been largely regarded as a process in which individuals actively cope with and recover from stress. Over the past decade, the emergence of large-scale brain networks has provided a new perspective for the study of the neural mechanisms of stress. However, the role of inter-network functional-connectivity (FC) and its temporal fluctuations in stress resilience is still unclear. To bridge this knowledge gap, seventy-seven participants (age, 17-22 years, 37 women) were recruited for a ScanSTRESS brain imaging study. A static perspective was initially adopted, using changes in FC that obtained from stress vs. control condition during the entire stress induction phase as a static indicator. Further, changes in FC between different stress runs were analyzed as an index of temporal dynamics. Stress resilience was gauged using salivary cortisol levels, while trait resilience was measured via behavioral-activation-system (BAS) sensitivity. Results found that, for the static index, enhanced FC between the salience-network (SN), default-mode-network (DMN) and limbic-network (LBN) during acute stress could negatively signal stress resilience. For the temporal dynamics index, FC among the dorsal-attention-network (DAN), central-executive-network (CEN) and visual-network (VN) decreased significantly during repeated stress induction. Moreover, the decline of FC positively signaled stress resilience, and this relationship only exist in people with high BAS. The current research elucidates the intricate neural underpinnings of stress resilience, offering insights into the adaptive mechanisms underlying effective stress responses.
Asunto(s)
Encéfalo , Hidrocortisona , Imagen por Resonancia Magnética , Red Nerviosa , Resiliencia Psicológica , Estrés Psicológico , Humanos , Femenino , Adulto Joven , Masculino , Estrés Psicológico/fisiopatología , Estrés Psicológico/metabolismo , Adolescente , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiología , Hidrocortisona/metabolismo , Mapeo Encefálico , Vías Nerviosas/fisiología , Vías Nerviosas/diagnóstico por imagen , Saliva/metabolismoRESUMEN
Background: Individuals with subclinical depression are prone to major depression and experience emotional responses and attentional biases to negative stimuli. Method: In a randomized controlled study (N = 42) using functional magnetic resonance imaging (fMRI), we examined the neurocognitive mechanisms behind mindfulness-based cognitive therapy (MBCT) combining loving-kindness meditation (LKM) on a group with subclinical depression compared with the relaxation group across emotional face n-back (EFNBACK) tasks and resting state. We also collected behavioral and self-reported data to confirm neurocognitive results. Results: During EFNBACK, the MBCT+LKM group showed greater activation in the left lingual gyrus and right inferior lateral occipital cortex. During rest, the MBCT+LKM group demonstrated increased connectivity of the anterior cingulate cortex and right inferior lateral occipital cortex, right anterior insula and left precentral gyrus. From amplitude of low frequency fluctuation (ALFF) data, activity in brain regions associated with cognitive control decreased and activity in brain regions associated with sensorimotor increased. Conclusion: These results suggest that MBCT+LKM alleviate depression for subclinical individuals through improving executive function when they face negative stimuli.
RESUMEN
Personal self-esteem (PSE) has been well recognized as a buffer against stress; however, the effects of other types of self-esteem, such as relational self-esteem (RSE) and collective self-esteem (CSE), on stress have not been adequately explored. This study investigated the roles of PSE, RSE, and CSE in reducing stress response. The Rosenberg, Relational, and Collective Self-Esteem Scales were adopted to assess PSE, RSE, and CSE, respectively. Participants underwent an acute social stress paradigm, and their acute stress response was assessed using subjective stress reports and salivary cortisol levels. Chronic stress level was estimated using the Perceived Stress Scale and hair cortisol concentration. The results showed that PSE was negatively correlated with salivary cortisol response during acute social stress; however, no significant associations were found between any type of self-esteem and subjective stress reports. For chronic stress, all types of self-esteem were negatively associated with perceived stress level, but not with hair cortisol concentration. Further hierarchical regression analyses suggested that only PSE negatively predicted acute salivary cortisol response and perceived stress level. Overall, the findings suggest the essential role of PSE in predicting acute salivary cortisol responses and perceived stress.
Asunto(s)
Cabello , Hidrocortisona , Saliva , Autoimagen , Estrés Psicológico , Humanos , Hidrocortisona/metabolismo , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Saliva/química , Saliva/metabolismo , Masculino , Femenino , Adulto Joven , Adulto , Cabello/química , Adolescente , Relaciones InterpersonalesRESUMEN
Photodynamic therapy has been regarded as a noninvasive treatment for cancer with spatiotemporal control over drug activation. Bis-terpyridyl Ru(II) complexes exhibit a promising achiral structure but suffer from low photoreactivity due to deviation from the ideal octahedral geometry. Herein, we introduce the donor-acceptor-donor motif to construct a dinuclear bis-terpyridyl Ru(II) complex (Ru2). Ru2 exhibits superior light absorption properties compared with mononuclear complex Ru1. Importantly, upon 595 nm light excitation, Ru2 shows promising synergetic type I/II photosensitization and photocatalytic activity, while Ru1 is inactive. Anticancer mechanistic studies reflect that Ru2 induces intracellular redox imbalance and affects the biosynthetic and metabolic processes, leading to cell apoptosis. Overall, this work provides a simple strategy to rouse the PDT efficiency of bis-terpyridyl Ru(II) complexes.
Asunto(s)
Antineoplásicos , Complejos de Coordinación , Fotoquimioterapia , Fármacos Fotosensibilizantes , Rutenio , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Rutenio/química , Rutenio/farmacología , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/síntesis química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Relación Estructura-ActividadRESUMEN
BACKGROUND: Gallbladder adenoma represents a precancerous lesion of gallbladder cancer. However, distinguishing it from cholesteryl polyps of the gallbladder before surgery is challenging. Thus, we aimed to comprehensively explore various risk factors contributing to the formation of gallbladder adenoma to facilitate an informed diagnosis and treatment by clinicians. METHODS: We conducted a retrospective analysis of patients who had undergone cholecystectomy at the Affiliated Hospital of Qingdao University between January 2015 and December 2022. Following postoperative pathological examination, patients were categorized into cholesterol polyp and adenoma groups. We analyzed their baseline characteristics, ultrasound imaging variables, and biochemical data using logistic, lasso, and stepwise regression. Subsequently, we constructed a preoperative prediction model based on the independent risk factors. RESULTS: Regression analysis of 520 gallbladder polyps and 288 gallbladder adenomas in the model group revealed that age, gallbladder wall thickness, polyp size, echogenicity, pedunculation, and adenosine deaminase (ADA) levels were independent predictors of gallbladder adenoma, all with P < 0.05. Using these indicators, we established a regression equation: Logistic (P) = -5.615 + 0.018 ∗ age - 4.64 ∗ gallbladder wall thickness + 1.811 ∗ polyp size + 2.855 ∗ polyp echo + 0.97∗ pedunculation + 0.092 ∗ ADA. The resulting area under the curve (AUC) value was 0.894 (95 % CI: 0.872-0.917, P < 0.01), with a sensitivity of 89.20 %, specificity of 79.40 %, and overall accuracy of 84.41 % for adenoma detection. CONCLUSION: Age, polyp size, gallbladder wall thickness, polyp echogenicity, pedunculation, and ADA levels emerge as independent risk factors for gallbladder adenoma.
Asunto(s)
Adenoma , Enfermedades de la Vesícula Biliar , Neoplasias de la Vesícula Biliar , Pólipos , Humanos , Preescolar , Estudios Retrospectivos , Neoplasias de la Vesícula Biliar/diagnóstico por imagen , Neoplasias de la Vesícula Biliar/cirugía , Enfermedades de la Vesícula Biliar/diagnóstico por imagen , Enfermedades de la Vesícula Biliar/cirugía , Ultrasonografía/métodos , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Pólipos/diagnóstico por imagen , Pólipos/cirugíaRESUMEN
BACKGROUND: Previous research regarding the effects of sleep quality and quantity on the acute stress response has yielded inconsistent findings. This may be attributed to various factors, including composite sleep components (i.e., means and daily variations) and mixed cortisol stress response (i.e., reactivity and recovery). Thus, this study aimed to separate the effects of means and daily variations of sleep on the reactivity and recovery of cortisol responses to psychological challenges. METHODS: In study 1, we recruited 41 healthy participants (24 women; age range, 18-23 years), monitored their sleep during seven consecutive days via wrist actigraphy and sleep diaries, and adopted the Trier Social Stress Test (TSST) paradigm to induce acute stress. Study 2 consisted of a validation experiment using the ScanSTRESS paradigm, which included 77 additional healthy individuals (35 women; age range, 18-26 years). Similarly to the TSST, the ScanSTRESS induces acute stress using uncontrollability and social evaluation. In both studies, saliva samples from the participants were collected before, during, and after the acute stress task. RESULTS: Using residual dynamic structural equation modeling, both study 1 and study 2 demonstrated that higher means of objective sleep efficiency, and longer means of objective sleep duration were related to greater cortisol recovery. In addition, fewer daily variations in objective sleep duration were associated with greater cortisol recovery. However, there was no correlation between sleep variables and cortisol reactivity, except for the daily variations in objective sleep duration in study 2. No correlation was observed between subjective sleep and cortisol response to stress. CONCLUSIONS: The present study separated two features of multi-day sleep patterns and two components of cortisol stress response, providing a more comprehensive picture of the effect of sleep on the stress-induced salivary cortisol response, and contributing to the future development of targeted interventions for stress-related disorders.
Asunto(s)
Hidrocortisona , Sistema Hipotálamo-Hipofisario , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Hidrocortisona/análisis , Estrés Psicológico/psicología , Saliva/química , SueñoRESUMEN
Empirical evidence indicates that high interdependent self-construal (InterSC) is correlated with exaggerated acute stress responses; however, the underlying neural correlates remain unclear. Considering the regulatory effect of the prefrontal cortex and limbic system on the acute stress response, the primary aim of this study was to investigate the role of the orbitofrontal cortex (OFC) and hippocampus (HIP) in the relationship between InterSC and acute stress responses. Forty-eight healthy college students underwent a modified version of the Montreal imaging stress task (MIST), while brain activity was recorded using functional magnetic resonance imaging (fMRI). Participants' saliva samples and subjective stress feelings were collected before, during, and after the MIST. Additionally, participants' self-construal was measured using questionnaires. Results revealed that InterSC was positively correlated with the activation of OFC, which, in turn, was associated with higher subjective stress feelings. A higher InterSC was also significantly associated with an enhanced salivary cortisol response in those with lower HIP activity. Furthermore, the HIP moderated the indirect effect of InterSC on subjective stress feelings by moderating the effect of InterSC on neural activity in the OFC. This indicated the mediation of the OFC was stronger in those with higher neural activity in the HIP than in those with lower activity in the HIP. In summary, the current study proposed an important role of the OFC-HIP regions in the relationship between InterSC and acute stress responses, making contribution to broadening the field of personality and stress and deepening our understanding of individual differences in acute stress responses.
Asunto(s)
Sistema Límbico , Corteza Prefrontal , Humanos , Corteza Prefrontal/diagnóstico por imagen , Emociones , Hipocampo/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Previous studies revealed that high long-term hypothalamic-pituitaryadrenal (HPA) axis activity measured by the hair cortisol concentrations predicts lower acute stress cortisol response and reported the influences of hair cortisol on brain activity during acute stress exposure. However, considering that long-term HPA axis activity has a close relationship with the brain's resting-state functional connectivity (RSFC), the current study aimed to explore the role of RSFC between limbic and salience network in this relationship. Seventy-seven healthy participants underwent resting-state imaging scans before performing the acute ScanSTRESS task. Saliva samples were collected to assess the levels of acute stress salivary cortisol. Hair samples were also collected, and the corticosteroid concentration extracted from these samples were used as a biomarker of long-term HPA axis activity. High hair cortisone (HairE) levels predicted lower acute stress cortisol response. Moreover, high HairE levels were significantly correlated with enhanced RSFC between limbic and salience networks, while RSFC was negatively associated with acute stress cortisol response. Importantly, the RSFC between left insula and left parahippocampus mediated the association between HairE and acute cortisol stress response. Taken together, this study uncovers the important role of RSFC between salience and limbic networks in the long-term relationship between HairE and acute cortisol response and contributes to a deeper understanding of the individual differences in acute stress response.
Asunto(s)
Cortisona , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisario , Sistema Hipófiso-Suprarrenal , Cabello/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Background: HLA-DR+ T cell, accounting for 1.2%-5.8% of peripheral lymphocyte, is a type of activated T lymphocyte. This retrospective study aimed to evaluate the prognostic value of HLA-DR+ T cell for progression-free survival (PFS) and overall survival (OS) in hepatocellular carcinoma (HCC) patients after curative surgery. Patients and Methods. Clinicopathological data of 192 patients who underwent curative resection for hepatocellular carcinoma in the affiliated hospital of Qingdao University between January 2013 and December 2021 were collected and analyzed. Statistical tests used in this study were the chi-square test and Fisher's exact test. The prognostic value of the HLA-DR+ T cell ratio was analyzed using univariate and multivariate Cox regression analyses. The Kaplan-Meier curves were drawn by the R programming language. Results: HCC patients were divided into high (≥5.8%) and low (<5.8%) HLADR+ T cell ratio groups. Cox regression analysis indicated that a high HLA-DR+ T cell ratio was positively related to the PFS in HCC patients (P=0.003) and AFP-positive (≥20 ng/ml) HCC patients (P=0.020). HCC patients and AFP-positive HCC patients in the high HLA-DR+ T cell ratio group were prone to have a higher T cell ratio, a higher CD8+T cell ratio, and a lower B cell ratio than the low HLA-DR+ T cell ratio group. However, the HLA-DR+ T cell ratio was not a statistically significant predictor for OS in HCC patients (P=0.57) as well as PFS (P=0.088) and OS (P=0.63) in AFP-negative HCC patients. Conclusions: This study confirmed that the HLA-DR+ T cell ratio was a significant predictor of PFS in HCC patients and AFP-positive HCC patients after curative surgery. This association may have guiding significance for the follow-up work of HCC patients after surgery.
RESUMEN
OBJECTIVE: To investigate the expression of CK19 in HBV-related hepatocellular carcinoma (HCC) tissues in patients with low serum AFP concentration and the relationship between them and the recurrence and prognosis of HCC after R0 radical hepatectomy. METHODS: The expressions of CK19 and Ki67 in HCC tissues of 235 cases were examined using tissue microarray and two-step methods of PV-6000 immunohistochemistry. The expression of CK19 mRNA in 20 frozen HCC specimens was examined by RT-PCR. The correlation between gene expressions and tumor recurrence and prognosis was analyzed. RESULTS: Among the 235 HBV-related HCC patients after R0 radical hepatectomy, the median disease-free survival (DFS) was 31.2 months in the patients with serum AFP < 400 µg/L and 13.8 months in the patients with serum AFP ≥ 400 µg/L (P = 0.041), the overall survival (OS) was 84.0 and 58.6 months in the two subgroups (P = 0.125), and the tumor recurrence within one year was in 43 cases (27%) and 37 cases (49.3%), respectively, (P = 0.001). The DFS was 11.6 months in the CK19-positive cases and 27.0 months in the CK19-negative cases (P > 0.05). The OS was significantly lower in the CK19-positive cases than that in the CK19-negative cases (P = 0.023). Both DFS and OS in the CK19-positive cases with AFP < 400 µg/L were significantly lower than those in the CK19-negative cases with AFP < 400 µg/L (both P < 0.05). The CK19 expression was significantly correlated with histological differentiation (P = 0.023), number of tumor foci (P = 0.044), vascular tumor embolism (P = 0.005), regional lymph node metastasis (P = 0.023), and 1-year recurrence (P = 0.006). Among the patients with AFP < 400 µg/L, the 1-year recurrence was 53% in the CK19-positive cases and 23% in the CK19-negative cases (P < 0.001), the median DFS was 11.3 months in CK19-positive cases and 34.0 months in CK19-negative cases (P = 0.010), and the median OS was 19.5 months in the CK19-positive cases, significantly lower than 84.0 months in the CK19-negative cases (P = 0.001). Cox regression analysis showed that CK19-positive expression was an independent factor affecting early HCC recurrence and prognosis. CONCLUSION: In HBV-related HCC patients after radical hepatectomy with AFP < 400 µg/L, positive expression of CK19 indicates a higher proliferation and invasiveness of HCC, and is an important factor of early recurrence and poor prognosis.
Asunto(s)
Carcinoma Hepatocelular , Virus de la Hepatitis B , Queratina-19/metabolismo , Neoplasias Hepáticas , alfa-Fetoproteínas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/virología , Supervivencia sin Enfermedad , Femenino , Hepatectomía/métodos , Humanos , Queratina-19/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/virología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , ARN Mensajero/metabolismo , Tasa de Supervivencia , Adulto JovenRESUMEN
Objective: The aim of this study was to determine how gemcitabine, oxaliplatin combination, and apatinib affect immune function and SIL-2R and sicAM-1 levels in patients with gallbladder cancer. Methods: Retrospective analysis of 116 patients with gallbladder cancer treated at our institution between February 2019 and February 2021. The patients were randomly divided into control and study groups, with 58 patients in each group. The study group received the combination of apatinib and the control group received gemcitabine and oxaliplatin. Immune function, serum tumor markers, short-term efficacy, survival measures, and incidence of adverse events were monitored and compared between the two groups. Results: CD3+, CD4+, CD4+/CD8+, and NK levels were significantly higher in both groups after treatment, while CD8+ levels were significantly lower; levels of sicAM-1, sicAM-1 (VEGF), and CEA were greatly reduced in both groups after treatment; there were significant differences between the study and control groups in terms of rr46.55% and DCR84.48%; at one year after treatment, the survival rate in the study group increased from 67.24% in the control group to 79.31%, with an increase in both PFs and 0S. Compared with the control group, the incidence of hypertension and myelosuppression, neutropenia, proteinuria, and hand-foot syndrome were lower in the study group (P < 0.05). All differences were statistically significant. Conclusion: In the treatment of gallbladder cancer, the use of gemcitabine and oxaliplatin combined with apatinib can effectively control the progression of patients' disease.
Asunto(s)
Neoplasias de la Vesícula Biliar , Desoxicitidina/análogos & derivados , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Humanos , Inmunidad , Oxaliplatino/efectos adversos , Piridinas , Estudios Retrospectivos , GemcitabinaRESUMEN
OBJECTIVES: Since the publication of the third edition, the WHO classification of tumors of hematopoietic and lymphoid disorders has introduced the disease entity of 'myeloid/lymphoid neoplasms with eosinophilia and PDGFRB rearrangement', in which the most common chromosomal abnormality is t(5;12) (q32;p13.2), and this abnormality generates the ETV6::PDGFRB fusion gene. However, there have been patients with hematologic features and chromosomal abnormalities that are extremely similar to those carrying ETV6::PDGFRB fusion. These rare disorders harbor ETV6::ACSL6 fusion, and only sporadic cases have been reported at present. METHODS: We report a patient with chronic eosinophilic leukemia (CEL) carrying chromosome translocation t(5;12)(q32;p13.2), and we present the clinical features. In addition, we conducted a literature review to collect all reported cases and summarized the genetic and clinical profiling as well as the treatments and outcomes. RESULT: In addition to our patient, a total of 19 cases have been previously reported, including 6 variants of ETV6::ACSL6 and 3 reciprocals. We identified a novel variant of the ETV6::ACSL6 transcript in our patient, and the breakpoint was flanked by exon 2 of ETV6 and exon 2 of ACSL6. The cellular morphology features consisted of myeloproliferative neoplasm (MPN); myelodysplastic/myeloproliferative neoplasm (MDS/MPN), specifically CEL; and acute myelocytic leukemia (AML). The treatments and outcomes varied greatly depending on the type of disease, although tyrosine kinase inhibitors (TKIs) were not effective. CONCLUSION: In contrast to neoplasms with ETV6::PDGFRB fusion, myeloid neoplasms with ETV6::ACSL6 fusion have unique characteristics.
Asunto(s)
Síndrome Hipereosinofílico , Leucemia Mieloide Aguda , Trastornos Mieloproliferativos , Aberraciones Cromosómicas , Fusión Génica , Humanos , Leucemia , Leucemia Mieloide Aguda/genética , Trastornos Mieloproliferativos/genética , Trastornos Mieloproliferativos/patología , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/genéticaRESUMEN
In the previous 10 years, researchers have suggested a critical role for the brain reward system in stress resilience. However, no study has provided an empirical link between activity in the mesostriatal reward regions during stress and the recovery of cortisol stress response. Moreover, although reward sensitivity as a trait has been demonstrated to promote stress resilience, it remains unclear whether it modulates the brain reward system in stress resilience and how this effect is achieved by the inherent neuroendocrine system. To investigate these uncertainties, 70 young adults were recruited to participate in a ScanSTRESS task, and their brain imaging data and saliva samples (for cortisol assay) were collected during the task. In addition, we assessed reward sensitivity, cortisol awakening response, and intrinsic functional connectivity of the brain in all the participants. We found that left putamen activation during stress exposure positively predicted cortisol recovery. In addition, reward sensitivity was positively linked with activation of the left putamen, and this relationship was serially mediated by the cortisol awakening response and right hippocampus-left inferior frontal gyrus intrinsic connectivity. These findings suggest that reward sensitivity modulates reward pathways in stress resilience through the interplay of the diurnal stress response system and network of the hippocampus-prefrontal circuitry. Summarily, the current study built a model to highlight the dynamic and multifaceted interaction between pertinent allostatic factors in the reward-resilience pathway and uncovered new insight into the resilience function of the mesostriatal reward system during stress.
RESUMEN
Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and a star medication used to treat non-small-cell lung carcinomas (NSCLCs). It has caused broad public concern that osimertinib has relatively low stability in plasma. We explored why osimertinib and its primary metabolites AZ-5104 and AZ-7550 are unstable in rat plasma. Our results suggested that it is the main reason inducing their unstable phenomenon that the Michael addition reaction was putatively produced between the Michael acceptor of osimertinib and the cysteine in the plasma matrix. Consequently, we identified a method to stabilize osimertinib and its metabolite contents in plasma. The assay was observed to enhance the stability of osimertinib, AZ-5104, and AZ-7550 significantly. The validated method was subsequently applied to perform the pharmacokinetic study for osimertinib in rats with the newly established, elegant, and optimized ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) strategy. The assay was assessed for accuracy, precision, matrix effects, recovery, and stability. This study can help understand the pharmacological effects of osimertinib and promote a solution for the similar problem of other Michael acceptor-contained third-generation EGFR-TKI.