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1.
Neuroimage ; 290: 120578, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38499051

RESUMO

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.


Assuntos
Emoções , Imageamento por Ressonância Magnética , Humanos , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Giro Para-Hipocampal/diagnóstico por imagem , Expressão Facial
2.
Phys Chem Chem Phys ; 26(5): 3974-3980, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38221866

RESUMO

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.

3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(4): 437-442, 2024 Apr 10.
Artigo em Zh | MEDLINE | ID: mdl-38565509

RESUMO

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.


Assuntos
Paraplegia Espástica Hereditária , Humanos , Lactente , Masculino , China , Mutação , Paraplegia/genética , Linhagem , Fenótipo , Paraplegia Espástica Hereditária/genética
4.
Psychol Med ; 53(16): 7735-7745, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37309913

RESUMO

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.


Assuntos
Hidrocortisona , Resiliência Psicológica , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Hidrocortisona/análise , Sistema Hipotálamo-Hipofisário , Habituação Psicofisiológica/fisiologia , Estresse Psicológico/psicologia , Sistema Hipófise-Suprarrenal , Saliva/química
5.
Stress ; 24(6): 805-813, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33970772

RESUMO

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.


Assuntos
Antecipação Psicológica , Estresse Psicológico , Antecipação Psicológica/fisiologia , Emoções , Humanos , Sistemas Neurossecretores , Recompensa , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-38362823

RESUMO

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.

8.
Neuroscience ; 551: 132-142, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38763226

RESUMO

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.

9.
Int J Clin Health Psychol ; 24(2): 100459, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660392

RESUMO

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.

10.
Eur J Surg Oncol ; 50(2): 107930, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159390

RESUMO

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.


Assuntos
Adenoma , Doenças da Vesícula Biliar , Neoplasias da Vesícula Biliar , Pólipos , Humanos , Pré-Escolar , Estudos Retrospectivos , Neoplasias da Vesícula Biliar/diagnóstico por imagem , Neoplasias da Vesícula Biliar/cirurgia , Doenças da Vesícula Biliar/diagnóstico por imagem , Doenças da Vesícula Biliar/cirurgia , Ultrassonografia/métodos , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Pólipos/diagnóstico por imagem , Pólipos/cirurgia
11.
Psychoneuroendocrinology ; 151: 106059, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36812860

RESUMO

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.


Assuntos
Hidrocortisona , Sistema Hipotálamo-Hipofisário , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Hidrocortisona/análise , Estresse Psicológico/psicologia , Saliva/química , Sono
12.
Neuropsychologia ; 188: 108620, 2023 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-37315890

RESUMO

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.


Assuntos
Sistema Límbico , Córtex Pré-Frontal , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Emoções , Hipocampo/diagnóstico por imagem , Imageamento por Ressonância Magnética
13.
Neuroscience ; 517: 61-69, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36924986

RESUMO

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.


Assuntos
Cortisona , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Cabelo/diagnóstico por imagem , Imageamento por Ressonância Magnética
14.
J Oncol ; 2023: 1875153, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873738

RESUMO

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.

15.
Zhonghua Zhong Liu Za Zhi ; 34(10): 753-8, 2012 Oct.
Artigo em Zh | MEDLINE | ID: mdl-23291069

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Vírus da Hepatite B , Queratina-19/metabolismo , Neoplasias Hepáticas , alfa-Fetoproteínas/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/virologia , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Queratina-19/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , RNA Mensageiro/metabolismo , Taxa de Sobrevida , Adulto Jovem
16.
Comput Intell Neurosci ; 2022: 4959840, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059420

RESUMO

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.


Assuntos
Neoplasias da Vesícula Biliar , Desoxicitidina/análogos & derivados , Neoplasias da Vesícula Biliar/tratamento farmacológico , Humanos , Imunidade , Oxaliplatina/efeitos adversos , Piridinas , Estudos Retrospectivos , Gencitabina
17.
Hematology ; 27(1): 1010-1018, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36069745

RESUMO

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.


Assuntos
Síndrome Hipereosinofílica , Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Aberrações Cromossômicas , Fusão Gênica , Humanos , Leucemia , Leucemia Mieloide Aguda/genética , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Receptor beta de Fator de Crescimento Derivado de Plaquetas/genética
18.
Front Pharmacol ; 13: 928983, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935836

RESUMO

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.

19.
Neurobiol Stress ; 20: 100485, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36132434

RESUMO

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.

20.
Front Pharmacol ; 13: 827668, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35264960

RESUMO

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4'-teterahydroxystilbene-2-O-ß-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-ß-D-glucoside (EG), and physcion-8-O-ß-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.

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